U.S. patent application number 10/235370 was filed with the patent office on 2003-04-03 for surface active n-halamine compounds.
This patent application is currently assigned to Auburn University. Invention is credited to Eknoian, Michael W., Li, Yanjun, Worley, Shelby D..
Application Number | 20030064051 10/235370 |
Document ID | / |
Family ID | 26937801 |
Filed Date | 2003-04-03 |
United States Patent
Application |
20030064051 |
Kind Code |
A1 |
Worley, Shelby D. ; et
al. |
April 3, 2003 |
Surface active N-halamine compounds
Abstract
N-halamine biocidal materials and coatings are provided.
Monomeric oxazolidinones or hydantoins are homopolymerized or
copolymerized with other monomers so as to produce materials or
coatings, which upon exposure to solutions of chlorine or bromine
become biocidal. The biocidal materials and coatings are effective
at inactivating microorganisms upon surface contact and are
regenerable following loss of efficacy upon further exposure to
solutions of chlorine or bromine. Surfaces which could be treated
with the materials and coatings include, but are not limited to:
glass, plastic, metals, fibers, and wood for use in pool and tank
liners, food wrappers, catheters, paints, tiles, shower walls,
fabrics, sterile bandages, pipes, medical and dental coatings,
preservatives, and the like.
Inventors: |
Worley, Shelby D.; (Auburn,
AL) ; Eknoian, Michael W.; (Warren, NJ) ; Li,
Yanjun; (Auburn, AL) |
Correspondence
Address: |
CHRISTENSEN, O'CONNOR, JOHNSON, KINDNESS, PLLC
1420 FIFTH AVENUE
SUITE 2800
SEATTLE
WA
98101-2347
US
|
Assignee: |
Auburn University
|
Family ID: |
26937801 |
Appl. No.: |
10/235370 |
Filed: |
September 3, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10235370 |
Sep 3, 2002 |
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09710090 |
Nov 10, 2000 |
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6469177 |
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09710090 |
Nov 10, 2000 |
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09246217 |
Feb 8, 1999 |
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6162452 |
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09246217 |
Feb 8, 1999 |
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08987698 |
Dec 9, 1997 |
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5902818 |
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Current U.S.
Class: |
424/78.22 ;
525/203 |
Current CPC
Class: |
A01N 43/76 20130101;
A01N 2300/00 20130101; C07D 233/22 20130101; C07D 263/20 20130101;
C07D 263/26 20130101; C07D 263/24 20130101; A01N 59/00 20130101;
A01N 43/76 20130101 |
Class at
Publication: |
424/78.22 ;
525/203 |
International
Class: |
A61K 031/785; C08L
039/04 |
Claims
The embodiments of the invention in which an exclusive property or
privilege is claimed are defined as follows:
1. A method of using a monomer having structure I for producing a
biocide that is biocidal upon halogenation with chlorine or
bromine, comprising the step of: 10preparing a precursor compound
from the monomer through homopolymerization, copolymerization or
grafting, wherein in STRUCTURE I, X is hydrogen; R.sub.1 is
hydroxyl, C.sub.2-C.sub.4 alkyl, benzyl, alkyl-substituted benzyl,
phenyl, or alkyl-substituted phenyl; and R.sub.2, R.sub.3, and
R.sub.4 are independently hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
substituted benzyl, phenyl, or substituted phenyl.
2. The method of claim 1, wherein R.sub.1 is ethyl, and R.sub.2,
R.sub.3, and R.sub.4 are independently hydrogen, or C.sub.1-C.sub.2
alkyl.
3. The method of claim 2 wherein the monomer is
4-acryloxymethyl-4-ethyl-2- -oxazolidinone.
4. The method of claim 1 further comprising the step of
halogenating the compound with chlorine or bromine.
5. The method of claim 4, wherein the step of halogenating the
compound is carried out in situ by adding a solution of a
stoichiometric amount of chlorine or bromine.
6. The method of claim 1, wherein the biocide is a coating capable
of being applied or adhered to a substrate.
7. A method of using a monomer having structure 1 as a biocide,
comprising the step of: STRUCTURE I: 11inactivating a microorganism
selected from the group consisting of bacteria, fungi, molds,
protozoa, viruses, and algae, wherein in STRUCTURE I, X is
hydrogen; R.sub.1 is hydroxyl, C.sub.2-C.sub.4 alkyl, benzyl,
alkyl-substituted benzyl, phenyl, or alkyl-substituted phenyl; and
R.sub.2, R.sub.3, and R.sub.4 are independently hydrogen,
C.sub.1-C.sub.4 alkyl, benzyl, substituted benzyl, phenyl, or
substituted phenyl.
8. A monomer having structure IV: 12wherein X is hydrogen,
chlorine, or bromine; R.sub.1 and R.sub.2 are independently
hydrogen, C.sub.1-C.sub.4 alkyl, benzyl, alkyl-substituted benzyl,
phenyl, or alkyl-substituted phenyl; and R.sub.3, R.sub.4, and
R.sub.5 are independently hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
alkyl-substituted benzyl, phenyl, or alkyl-substituted phenyl.
9. The monomer of claim 8, wherein R.sub.1 and R.sub.2 are methyl;
and R.sub.3, R.sub.4, and R.sub.5 are independently hydrogen or
methyl.
10. The monomer of claim 9, wherein the monomer is
3-(acryloxymethyl)-5,5-- dimethylhydantoin.
11. A method of using a monomer having structure IV for producing a
biocide, comprising the steps of: 13preparing a precursor compound
from the monomer through homopolymerization, copolymerization or
grafting, wherein in STRUCTURE IV, X is hydrogen, chlorine, or
bromine; R.sub.1 and R.sub.2 are independently hydrogen,
C.sub.1-C.sub.4 alkyl, benzyl, alkyl-substituted benzyl, phenyl, or
alkyl-substituted phenyl; and R.sub.3, R.sub.4, and R.sub.5 are
independently hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
alkyl-substituted benzyl, phenyl, or alkyl-substituted phenyl; and
halogentating the compound with chlorine or bromine.
12. The method of claim 11, wherein the halogenated compound is the
homopolymer
poly-1-chloro-3-(acryloxymethyl)-5,5-dimethylhydantoin.
13. The method of claim 11, wherein the halogenated compound is the
homopolymer
poly-1-bromo-3-(acryloxymethyl)-5,5-dimethylhydantoin.
14. The method of claim 11, wherein the halogenated compound is the
copolymer
poly-acrylonitrile-co-1-chloro-3-(acryloxymethyl)-5,5-dimethylh-
ydantoin.
15. The method of claim 11, wherein the halogenated compound is the
copolymer
poly-acrylonitrile-co-1-bromo-3-(acryloxymethyl)-5,5-dimethylhy-
dantoin.
16. The method of claim 11, wherein the halogenated compound is the
copolymer poly-methyl
methacrylate-co-1-chloro-3-(acryloxymethyl)-5,5-dim-
ethylhydantoin.
17. The method of claim 11, wherein the halogenated compound is the
copolymer poly-methyl
methacrylate-co-1-bromo-3-(acryloxymethyl)-5,5-dime-
thylhydantoin.
18. The method of claim 11, wherein the halogenated compound is the
copolymer poly-vinyl
acetate-co-1-chloro-3-(acryloxymethyl)-5,5-dimethylh- ydantoin.
19. The method of claim 11, wherein the halogenated compound is the
copolymer poly-vinyl
acetate-co-1-bromo-3-(acryloxymethyl)-5,5-dimethylhy- dantoin.
20. The method of claim 11, wherein the halogenated compound is the
copolymer poly-ethyl
acrylate-co-styrene-co-1-chloro-3-(acryloxymethyl)-5-
,5-dimethylhydantoin.
21. The method of claim 11, wherein the halogenated compound is the
copolymer poly-ethyl
acrylate-co-styrene-co-1-bromo-3-(acryloxymethyl)-5,-
5-dimethylhydantoin.
22. The method of claim 11, wherein the halogenated compound is the
copolymer poly-vinyl acetate-co-methyl
methacrylate-co-1-chloro-3-(acrylo-
xymethyl)-5,5-dimethylhydantoin.
23. The method of claim 11, wherein the halogenated compound is the
copolymer poly-vinyl acetate-co-methyl
methacrylate-co-1-bromo-3(-acrylox-
ymethyl)-5,5-dimethylhydantoin.
24. The method of claim 11, wherein the halogenated compound is the
copolymer poly-vinyl acetate-co-butyl
acrylate-co-1-chloro-3-(acryloxymet-
hyl)-5,5-dimethylhydantoin.
25. The method of claim 11, wherein the halogenated compound is the
copolymer poly-vinyl acetate-co-butyl
acrylate-co-1-bromo-3-(acryloxymeth- yl)-5,5-dimethylhydantoin.
26. The method of claim 11, wherein the halogenated compound is the
grafted copolymer
poly-acrylonitrile-g-1-chloro-3-(acryloxymethyl)-5,5-di-
methylhydantoin.
27. The method of claim 11, wherein the halogenated compound is the
grafted copolymer
poly-acrylonitrile-g-1-bromo-3-(acryloxymethyl)-5,5-dim-
ethylhydantoin.
28. The method of claim 11, wherein the halogenated compound is the
grafted copolymer poly-vinyl
alcohol-g-1-chloro-3-(acryloxymethyl)-5,5-di- methylhydantoin.
29. The method of claim 11, wherein the halogenated compound is the
grafted copolymer poly-vinyl
alcohol-g-1-bromo-3-(acryloxymethyl)-5,5-dim- ethylhydantoin.
30. The method of claim 11, wherein the halogenated compound is the
grafted copolymer
cellulose-g-1-chloro-3-(acryloxymethyl)-5,5-dimethylhyd-
antoin.
31. The method of claim 11, wherein the halogenated compound is the
grafted copolymer
cellulose-g-1-bromo-3-(acryloxymethyl)-5,5-dimethylhyda- ntoin.
32. The method of claim 11, further comprising the step of:
introducing a diisocyanate in the presence of a tertiary amine to
form a thermoset compound.
33. The method of claim 32, wherein the diisocyanate is
4,4'-methylenebis(phenyl isocyanate) or 1,6-diisocyanatohexane.
34. The method of claim 32, wherein the tertiary amine is dimethyl
benzyl amine.
35. The method of claim 32, wherein the thermoset compound is the
copolymer poly-methyl
methacrylate-co-1-chloro-3-(acryloxymethyl)-5,5-dim-
ethylhydantoin-co-hydroxyethyl acrylate.
36. The method of claim 32, wherein the thermoset compound is the
copolymer poly-methyl
methacrylate-co-1-bromo-3-(acryloxymethyl)-5,5-dime-
thylhydantoin-co-hydroxyethyl acrylate.
37. The method of claim 32, wherein the thermoset compound is the
copolymer poly-methyl
methacrylate-co-1-chloro-3-(acryloxymethyl)-5,5-dim-
ethylhydantoin-co-acrylic acid.
38. The method of claim 32, wherein the thermoset compound is the
copolymer poly-methyl
methacrylate-co-1-bromo-3-(acryloxymethyl)-5,5-dime-
thylhydantoin-co-acrylic acid.
39. The method of claim 11, wherein the step of halogenating the
compound is carried out in situ by adding a solution of a
stoichiometric amount of chlorine or bromine.
40. The method of claim 11, wherein the biocide is a coating
capable of being applied or adhered to a substrate.
41. A method of using a monomer having structure IV as a biocide,
comprising the step of: 14inactivating a microorganism selected
from the group consisting of bacteria, fungi, molds, protozoa,
viruses, and algae, wherein in STRUCTURE IV, X is hydrogen,
chlorine, or bromine: R.sub.1 and R.sub.2 are independently
hydrogen, C.sub.1-C.sub.4 alkyl, benzyl, alkyl-substituted benzyl,
phenyl, or alkyl-substituted phenyl; and R.sub.3, R.sub.4, and
R.sub.5 are independently hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
alkyl-substituted benzyl, phenyl, or alkyl-substituted phenyl.
42. A method of using a chemical unit having structure III for
producing a monomer of a biocide, comprising the step of:
15condensing the unit with a diisocyanate or low molecular weight
polyurethane in the presence of a catalytic amount of a tertiary
amine to form the monomer, wherein in STRUCTURE III, R.sub.1 and
R.sub.2 are independently hydrogen, hydroxyl, C.sub.1-C.sub.4
alkyl, benzyl, substituted benzyl, phenyl or substituted
phenyl.
43. A method of using a monomer of
4,4-dihydroxymethyl-2-oxazolidinone to produce a biocide,
comprising the steps of: polymerizing the monomer with a
diisocyanate or low molecular weight polyurethane in the presence
of a catalytic amount of a tertiary amine to form a precursor
compound, and halogenating the compound with chlorine or
bromine.
44. The method of claim 43, wherein the diisocyanate is
1,6-diisocyanatohexane.
45. The method of claim 43, wherein the tertiary amine is dimethyl
benzyl amine.
46. The method of claim 43, wherein the diol is 1,4-butanediol.
47. The method of claim 43, wherein the step of halogenating the
compound is carried out in situ by adding a solution of a
stoichiometric amount of chlorine or bromine.
48. The method of claim 43, wherein the biocide is a polyurethane
surface coating.
49. A method of using a monomer of
4,4-dihydroxymethyl-2-oxazolidinone as a biocide, comprising the
step of: inactivating a microorganism selected from the group
consisting of bacteria, fungi, molds, protozoa, viruses, and
algae.
50. A biocidal article, comprising: a film or material made from a
monomer of structure I 16wherein X is hydrogen; R.sub.1 is
hydroxyl, C.sub.2-C.sub.4 alkyl, benzyl, alkyl-substituted benzyl,
phenyl, or alkyl-substituted phenyl; and R.sub.2, R.sub.3, and
R.sub.4 are independently hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
substituted benzyl, phenyl, or substituted phenyl, and wherein the
film or material is coated onto a substrate and treated with a
halogen.
51. The article of claim 50, wherein the substrate is selected from
the group consisting of glass, wood, metal, plastic, concrete, and
fibers.
52. A biocidal article, comprising: a film or material made from a
monomer of structure IV. 17wherein X is hydrogen, chlorine, or
bromine; R.sub.1 and R.sub.2 are independently hydrogen,
C.sub.1-C.sub.4 alkyl, benzyl, alkyl-substituted benzyl, phenyl, or
alkyl-substituted phenyl; and R.sub.3, R.sub.4 and R.sub.5 are
independently hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
alkyl-substituted benzyl, phenyl, or alkyl-substituted phenyl, and
wherein the film or material is coated onto a substrate and treated
with a halogen.
53. The article of claim 52, wherein the substrate is selected from
the group consisting of glass, wood, metal, plastic, concrete, and
fibers.
54. A biocidal article, comprising: a film or material made from a
monomer of structure III. 18wherein R.sub.1 and R.sub.2 are
independently hydrogen, hydroxyl, C.sub.1-C.sub.4 alkyl, benzyl,
substituted benzyl, phenyl, or substituted phenyl, and wherein the
film or material is coated onto a substrate and treated with a
halogen.
55. The article of claim 54 wherein the substrate is selected from
the group consisting of glass, wood, metal, plastic, concrete, and
fibers.
56. A biocidal article, comprising: a film or material made from a
monomer of 4,4-dihydroxymethyl-2-oxazolidinone, wherein the film or
material is coated onto a substrate and treated with a halogen.
57. The article of claim 56, wherein the substrate is selected from
the group consisting of glass, wood, metal, plastic, concrete, and
fibers.
Description
RELATED APPLICATIONS
[0001] This application is a continuation in part of U.S. patent
application Ser. No. 09/246,217, filed Feb. 8, 1999, now pending
which in turn is a Divisional of U.S. patent application Ser. No.
09/987,698, filed on Dec. 9, 1997, now U.S. Pat. No. 5,902,818.
FIELD OF THE INVENTION
[0002] The following invention relates to disinfectant compounds
that act as biocides to an array of microorganisms. The biocides
are comprised of cyclic N-halamines that are biocidal when they
come in contact with hallogen-sensitive organisms for a specific
contact time. This is achieved by coating the N-halamine on a
substrate; such as, but not limited to: glass, metal, wood,
plastic, concrete, and fabric.
BACKGROUND OF THE INVENTION
[0003] Current surface contact biocides for the use of producing a
sterile environment such as for medical tables, surgical equipment,
fabric materials, gloves, catheter tubing, piping, industrial and
commercial surfaces, swimming pools, floors, can and bottle liners,
food production equipment and liners, and various medical and
dental applications do not exist or are severely limited in their
biocidal abilities. Most commonly used water-soluble disinfectants
which contain free halogen have severely limited lifetimes, produce
adverse reactions to their environment, and produce toxic
by-products. Disinfectants which do not contain free halogen, such
as quaternary ammonium and phenolic compounds, are only effective
towards specific organisms, are water soluble, and can cause skin
and eye irritation. Commercially employed hydantoins, cyanurates,
oxazolidinones (Kaminski et al., U.S. Pat. Nos. 4,000,293 and
3,931,213), imidazolidinones (Worley et al., U.S. Pat. Nos.
4,681,948; 4,767,542; 5,057,612; 5,126,057), and polymeric
N-halamines (Worley et al., U.S. Pat. Nos. 5,490,983 and 5,670,646)
are much more stable than free halogen, ozone, and chlorine
dioxide, and are more versatile than phenolic and quaternary
ammonium compounds.
[0004] Currently only a few disinfectant surfaces have been
prepared, most of which focus on quaternary ammonium compounds
(quats) anchored on polymer backbones (Hazziza-Laskar et al., J.
Appl. Polym. Sci., 50:651 (1993); Nurdin et al., J. Appl. Polym.
Sci., 50:663 (1993); Nurdin et al., J. Appl. Polym. Sci., 50:671
(1993); Hazziza-Laskar et al., J. Appl. Polym. Sci., 58:77 (1995))
which are then cast as films. Although these films are biocidal,
their limitations are that they need long contact times to kill the
organisms, the surface cannot be reactivated once the biocidal
activity is lost, the films are relatively expensive to make, and
the films are partially water soluble. Other types of surface
active disinfectants are polymeric phosphonium materials (Kanazawa
et al., J. Polym. Sci., Part A: Polym. Chem., 31:1467 (1993); J.
Appl. Polym. Sci., 52:641 (1994)), modified polyesters, polyethers
and benzimidiazoles (Oh et al., J. Appl. Polym. Sci., 52:583
(1994); J. Appl. Polym. Sci., 54:859 (1994); Cho et al., J.
Macromol. Sci., Pure Appl. Chem., A32:479 (1995)) which are
resistant to several types of microorganisms, but the biocidal
moiety cannot be regenerated once exhausted, the films are costly
to make, and they can be water soluble.
[0005] Therefore, there is a need for a surface active biocide that
is inexpensive to manufacture, can regenerate its biocidal
activity, is water insoluble when necessary, can kill a broad
spectrum of microorganisms, does not affect its environment
unfavorably, and requires relatively short contact times to
inactivate microorganisms when necessary. There is also a need for
the contact biocide to be applied to numerous substrates such as
glass, wood, metal, fibrous materials, and concrete to maximize the
applications for its use.
SUMMARY OF THE INVENTION
[0006] The present invention relates to a monomer and its
corresponding polymers and copolymers comprising a cyclic
N-halamine unit, wherein the cyclic N-halamine unit comprises: a
5-membered ring wherein 3 members of the ring are carbon, 1 member
of the ring is a nitrogen heteroatom, and 1 member of the ring is
oxygen heteroatom; wherein one carbon member comprises a carbonyl
group; wherein one non-carbonyl carbon member is attached to an
acryloxymethyl linkage which is substituted with moieties R.sub.2,
R.sub.3, and R.sub.4, which moieties are selected from the group
consisting of hydrogen, C.sub.1-C.sub.4 alkyl, benzyl, substituted
benzyl, phenyl and substituted phenyl; wherein said non-carbonyl
carbon member is also joined to a moiety R.sub.1 selected from the
group consisting of hydroxyl, C.sub.1-C.sub.4 alkyl, benzyl,
substituted benzyl, phenyl and substituted phenyl; and wherein the
nitrogen heteroatom is joined to a moiety X selected from the group
consisting of chlorine, bromine or hydrogen. The general structure
for one embodiment of the monomer is shown below. 1
[0007] wherein X is chlorine, bromine or hydrogen; R.sub.1 is
selected from the group consisting of hydroxyl, C.sub.1-C.sub.4
alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl;
R.sub.2, R.sub.3 and R.sub.4 are each independently selected from
the group consisting of hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
substituted benzyl, phenyl and substituted phenyl. A method of
using the monomer of structure I for producing a biocidal material
or coating through halogenation with chlorine or bromine is also
disclosed. The biocidal material can be applied as a coating or
film onto a plurality of substrates useful for their disinfectant
properties. The biocidal properties can be regenerated by renewed
halogenation in chlorine or bromine solutions.
[0008] The present invention also relates to biocidal polymers
comprising a cyclic N-halamine unit linked at a carbon atom to a
second N-halamine unit via acryloxymethyl linkage wherein each
N-halamine unit comprises a 5 membered ring, wherein 3 members of
the ring are carbon, 1 member of the ring is nitrogen heteroatom,
and 1 member of the ring is oxygen heteroatom; wherein 1 carbon
member comprises a carbonyl group; wherein 1 non-carbonyl carbon
member is linked to the second N-halamine unit via acryloxymethyl
linkage, which linkage is substituted with moieties R.sub.2,
R.sub.3 and R.sub.4 each of which are independently selected from
the group consisting of hydrogen, C.sub.1-C.sub.4 alkyl, phenyl,
substituted phenyl, benzyl, substituted benzyl; wherein said
non-carbonyl carbon member is also joined to an R.sub.1 substituent
selected from the group consisting of hydroxyl, C.sub.1-C.sub.4
alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl; and
wherein the nitrogen heteroatom is joined to a moiety X selected
from the group consisting of chlorine and bromine.
[0009] The invention also relates to biocidal copolymers comprising
a cyclic N-halamine monomeric unit linked at a carbon atom by an
acryloxymethyl linkage to a second monomeric unit, wherein the
second monomeric unit is any polymerizable olefin, e.g., acrylic
acid, vinyl acetate, vinyl chloride, styrene, acrylonitrile,
propylene, or ethylene; wherein the N-halamine monomeric unit
comprises a 5 membered ring, wherein 3 members of the ring are
carbon, 1 member of the ring is nitrogen heteroatom, and 1 member
of the ring is oxygen heteroatom; wherein 1 carbon member comprises
a carbonyl group; wherein 1 non-carbonyl carbon member is linked to
the second monomeric unit via acryloxymethyl linkage, which linkage
is substituted with moieties R.sub.2, R.sub.3 and R.sub.4 each of
which are independently selected from the group consisting of
hydrogen, C.sub.1-C.sub.4 alkyl, phenyl, substituted phenyl, benzyl
and substituted benzyl; wherein said non-carbonyl carbon member is
also joined to an R.sub.1 substituent selected from the group
consisting of hydroxyl, C.sub.1-C.sub.4 alkyl, phenyl, substituted
phenyl, benzyl and substituted benzyl; and wherein the nitrogen
heteroatom is joined to a moiety X selected from the group
consisting of chlorine and bromine.
[0010] The invention also relates to biocidal grafted copolymers
comprising a cyclic N-halamine unit linked at a carbon atom by an
acryloxymethyl linkage to a polymer backbone wherein the polymer
backbone is any commercial polymer, e.g., poly-vinyl chloride,
poly-acrylonitrile, poly-vinyl acetate, poly-vinyl alcohol,
poly-styrene, cellulose, and cellulose blends with polyester,
rayon, spandex, and poly-urethanes; wherein the N-halamine unit
comprises a 5 membered ring, wherein 3 members of the ring are
carbon, 1 member of the ring is nitrogen heteroatom, and 1 member
of the ring is oxygen heteroatom; wherein 1 carbon member comprises
a carbonyl group; wherein 1 non-carbonyl carbon member is linked to
the polymer via acryloxymethyl linkage, which linkage is
substituted with moieties R.sub.2, R.sub.3 and R.sub.4 each of
which are independently selected from the group consisting of
hydrogen, C.sub.1-C.sub.4 alkyl, phenyl, substituted phenyl, benzyl
and substituted benzyl; wherein said non-carbonyl carbon member is
also joined to a substituent R.sub.1 selected from the group
consisting of hydroxyl, C.sub.1-C.sub.4 alkyl, phenyl, substituted
phenyl, benzyl and substituted benzyl; and wherein the nitrogen
heteroatom is joined to a moiety X selected from the group
consisting of chlorine and bromine.
[0011] The present invention further relates to another monomer and
its corresponding polymers and copolymers, the monomer comprising a
cyclic N-halamine unit, wherein the cyclic N-halamine unit
comprises: a 5-membered ring wherein 3 members of the ring are
carbon, 2 members of the ring are nitrogen heteroatoms; wherein two
carbon members each comprise a carbonyl group; wherein one nitrogen
heteroatom is attached to an acryloxymethyl linkage which is
substituted with moieties R.sub.3, R.sub.4, and R.sub.5, which
moieties are selected from the group consisting of hydrogen,
C.sub.1-C.sub.4 alkyl, benzyl, substituted benzyl, phenyl and
substituted phenyl; wherein the remaining non-carbonyl carbon
member is also joined to moieties R.sub.1 and R.sub.2 selected from
the group consisting of hydrogen, hydroxyl, C.sub.1-C.sub.4 alkyl,
benzyl, substituted benzyl, phenyl and substituted phenyl; and
wherein the remaining nitrogen heteroatom is joined to a moiety X
selected from the group consisting of chlorine, bromine or
hydrogen. The general structure for one embodiment of the monomer
is shown as structure IV below. 2
[0012] A method of using the monomer of structure IV for producing
a biocidal material or coating through halogenation with chlorine
or bromine is also disclosed. The biocidal material can be applied
as a coating or film onto a plurality of substrates useful for
their disinfectant properties. The biocidal properties can be
regenerated by renewed halogenation in chlorine or bromine
solutions.
[0013] The present invention further relates to a chemical unit
useful to produce monomers and corresponding polymers and
copolymers which are used to produce biocides, the unit comprising
a cyclic N-halamine unit, wherein the cyclic N-halamine unit
comprises: a 5-membered ring wherein 3 members of the ring are
carbon, and 2 members of the ring are nitrogen heteroatoms; wherein
two carbon members each comprise a carbonyl group; one nitrogen
heteroatom is attached to a hydroxymethyl group and the remaining
is attached to a hydrogen and the remaining non-carbonyl carbon
member is joined to moieties R.sub.1 and R.sub.2 selected from the
group consisting of hydrogen, hydroxyl, C.sub.1-C.sub.4 alkyl,
benzyl, substituted benzyl, phenyl and substituted phenyl. The
general structure for one embodiment of the unit is shown as
structure III below. 3
[0014] A method of using the unit of structure III for producing
monomers by condensation of the unit with a diisocyanate or
polyurethane in the presence of a tertiary amine, wherein the
monomers are useful in producing biocidal materials and coatings by
polymerization, and followed by halogenation with chlorine or
bromine, is also disclosed. The biocidal material can be applied as
a coating or film onto a plurality of substrates useful for their
disinfectant properties. The biocidal properties can be regenerated
by renewed halogenation with chlorine or bromine solutions.
[0015] The present invention further relates to another monomer and
its corresponding polymers and copolymers, the monomer comprising a
cyclic N-halamine unit, wherein the cyclic N-halamine unit
comprises: a 5-membered ring wherein 3 members of the ring are
carbon, and 1 member of the ring is nitrogen heteroatom, and the
remaining member of the ring is oxygen heteroatom; wherein one
carbon member comprises a carbonyl group; the nitrogen heteroatom
is attached to a hydrogen and one of the remaining carbons is
attached to 2 hydroxymethyl groups. The general structure for one
embodiment of the monomer is shown as structure V below. 4
[0016] A method of using the monomer of structure V for producing a
biocidal material or coating by polymerization with a diisocyanate
or polyurethane in the presence of a tertiary amine, followed by
halogenation with chlorine or bromine is also disclosed. In one
actual embodiment, a diol can be included in the polymerization
step. The biocidal material can be applied as a coating or film
onto a plurality of substrates useful for their disinfectant
properties. The biocidal properties can be regenerated by renewed
halogenation in chlorine or bromine solutions.
[0017] The invention further relates to a method for disinfecting a
habitat for halogen-sensitive microorganisms comprising contacting
the habitat with a N-halamine monomer, polymer, copolymer or
grafted copolymer as described above.
[0018] The present invention provides an improved compound and
method of using the same for disinfecting a habitat for
halogen-sensitive microorganisms, and further provides novel
N-halamine biocidal compounds in surface coatings for disinfection
of halogen-sensitive organisms.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0019] The present invention may be understood more readily by
reference to the following detailed description of specific
embodiments and the Examples and Figures included therein.
[0020] As used herein, "precursor" or "intermediate" compound can
mean a single chemical unit, or its derivatives, a monomer, or its
derivatives, or any chain of units, derivatives, and monomers which
have been polymerized, co-polymerized, or grafted with each other
or with units, derivatives, or monomers.
[0021] As used herein, "cyclic N-halamine unit" refers to a
heterocyclic, monocyclic compound wherein the ring members comprise
at least carbon, nitrogen, and oxygen provided there is at least
one nitrogen heteroatom; wherein at least one halogen, preferably
chlorine or bromine, is bonded to a nitrogen heteroatom; and
wherein at least one carbon ring member can comprise a carbonyl
group. The presence of the halogen renders it biocidal. The term
"cyclic amine unit" refers to a heterocyclic, monocyclic compound
wherein the ring members comprise at least carbon, nitrogen, and
oxygen provided there is at least one nitrogen heteroatom; wherein
hydrogen is bonded to a nitrogen heteroatom; and wherein at least
one carbon ring member can comprise a carbonyl group. Methods
described herein for preparing polymers using cyclic N-halamine
monomers can readily be performed with cyclic amine monomers.
[0022] Herein, "polymer" and "copolymer" are at times used
interchangeably. The use of one or the other term is not meant to
be limiting except where indicated by the context.
[0023] As used herein, the term "a polymer comprising a cyclic
amine or N-halamine unit joined by a linkage to a second cyclic
amine or N-halamine unit" is not meant to be limiting as to the
number of cyclic amine or N-halamine units in a polymer. A
"polymer" can comprise two or more cyclic amine or N-halamine
units, and the number of units in any given polymer can vary
according to the use intended for the polymer. For example, the
polymer can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40,
50, 75, 100, 150, 200, 250, 500, 1000, and so forth, units.
[0024] Additionally, a "polymer comprising a cyclic amine unit
joined by a linkage to a second cyclic amine unit" or a "biocidal
polymer comprising a cyclic N-halamine unit joined by a linkage to
a second cyclic N-halamine unit" can further comprise additional,
other monomer types, which can be designated monomer "M" or monomer
"O," for example, for convenience (i.e., a copolymer). Each cyclic
amine or N-halamine unit in the polymer can be identical or they
can vary. A polymer/copolymer can comprise, for example, one, two,
three, four, five, ten or more different monomers. The monomers can
be arranged in random arrangement or in block arrangement. A
"biocidal polymer" of this invention can comprise one or more
biocidal cyclic N-halamine units, i.e., halogenated cyclic amine
units.
[0025] As used herein, a "biocidal N-halamine copolymer comprising
N-halamine unit joined by an acryloxymethyl linkage to a second
monomeric unit" is not meant to be limiting as to the number of
cyclic N-halamine units in a polymer, nor is it meant to suggest
that each cyclic N-halamine unit is linked to a different monomeric
unit. It refers to a copolymerization of the cyclic amine with one
or more different monomeric units in a controlled or random array
in the polymer. A "copolymer" can comprise two or more cyclic
N-halamine units, and one or more different monomeric units and the
number of units in any given copolymer can vary according to the
use of the copolymer.
[0026] The copolymer can be prepared in bulk, solution, emulsion,
or suspension depending on the application desired. A "bulk"
copolymerization can comprise cyclic amine monomer and at least one
other monomer wherein the polymerization occurs in the absence of
solvent. A "solution" copolymerization can comprise cyclic amine
monomer and at least one other monomer wherein the polymerization
occurs in a solvent, either organic or inorganic. An "emulsion"
copolymerization can comprise cyclic amine monomer and at least one
other monomer wherein the polymerization occurs where water is the
solvent along with a surfactant. A "suspension" copolymerization
can comprise cyclic amine monomer and at least one other monomer
wherein the polymerization occurs where water is the solvent. Each
cyclic N-halamine unit and monomeric unit in the copolymer can be
identical. A "latex" is any polymer that is emulsified in water via
surfactant or any other emulsifying agent. An example of the
nomenclature used throughout for all copolymerizations goes as
follows:
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone-
.
[0027] As used herein, a "biocidal N-halamine grafted copolymer
comprising a N-halamine unit joined by an acryloxymethyl linkage to
a polymer backbone" is not meant to be limiting as to the number of
cyclic N-halamine units in a polymer, nor is it meant to suggest
that each cyclic N-halamine unit is directly linked to the polymer
backbone. It refers to chemically grafting two or more cyclic amine
units on to a pre-existing polymeric backbone in a specific or
random arrangement. A "grafted copolymer" can comprise a polymer
backbone wherein the. polymer is comprised of one or more monomeric
units which can be polymeric cyclic N-halamines. A grafting
reaction can occur in solution or bulk. Each cyclic N-halamine unit
and polymeric backbone in the grafted copolymer can be identical,
they can be repeat motifs of two or more units, or they can be a
random arrangement of two or more different units. An example of
the nomenclature used throughout for all grafting reactions is as
follows:
poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazo-
lidinone.
[0028] As used herein, a "habitat for halogen-sensitive
microorganisms" is any substance in which or on which such
organisms are capable of survival for a predetermined and
undesirable period of time.
[0029] Cyclic organic N-halamine compounds having two alkyl
substituent groups substituted on the ring carbons adjacent to the
N--Cl and N--Br moieties exhibit long-term stability in aqueous
solution and release little or no free halogen, while providing
adequate disinfection efficacy. Additionally, because polymeric
molecules can be constructed to have low solubility in water, an
insoluble cyclic N-halamine polymer containing similar cyclic
N-halamine structural groups is an ideal polymeric biocide.
[0030] A strategy for incorporating cyclic N-halamine structural
groups into polymers is: an existing cyclic amine or amide such as
those described by Worley in U.S. Pat. Nos. 4,681,948; 4,767,542;
5,057,612; 5,126,057 is functionalized with a polymerizable moiety
such as a vinyl group and then polymerized and halogenated. The
insoluble cyclic N-halamine polymers inactivate microorganisms once
applied to a substrate upon contact, release minimal amounts of
free halogen and other leachable impurities, and can be prepared or
regenerated by applying diluted solutions of free halogen to the
coated substrate containing the cyclic amine or amide.
[0031] A second strategy for incorporating cyclic N-halamine
structural groups into polymers is to modify an existing polymer by
linking a biocidal moiety to it as in Worley U.S. Pat. No.
5,490,983. The former strategy is more preferable in the current
embodiment.
[0032] The novel N-halamine biocidal polymers described herein
contain heterocyclic units which have stable N--Cl or N--Br
chemical bonds necessary for biocidal action. The heterocyclic
N-halamine units can comprise 5 membered rings, wherein at least
one heteroatom is nitrogen and at least one heteroatom is oxygen,
and which can have one carbonyl group. A carbon atom of these
heterocyclic moieties can be joined by a linkage to an additional
heterocyclic N-halamine unit by one of many possible linkages which
attach to each N-halamine unit at a single non-carbonyl carbon
atom, such as by a lower alkyl, i.e., a three to eleven carbon
chain that can be branched when greater than three carbons, or a
phenyl-lower alkyl-phenyl i.e., two phenyl groups joined by a three
to eleven carbon chain that can be branched when greater than three
carbons wherein one phenyl attaches to a cyclic N-halamine unit and
the other phenyl attaches to a neighboring cyclic N-halamine
unit.
[0033] Specifically, compounds can include biocidal monomers
comprising a cyclic N-halamine unit wherein the cyclic N-halamine
unit comprises: a 5-membered ring, wherein at least 3 members of
the ring are carbon, 1 member of the ring is nitrogen heteroatom,
and 1 member is oxygen heteroatom; wherein 1 carbon member
comprises a carbonyl group; wherein one non-carbonyl carbon member
is attached to an acryloxymethyl linkage which is substituted with
moieties R.sub.2, R.sub.3, and R.sub.4, which moieties are selected
from the group consisting of hydrogen, C.sub.1-C.sub.4 alkyl,
benzyl, substituted benzyl, phenyl and substituted phenyl; wherein
said non-carbonyl carbon member is also joined to a moiety R.sub.1
selected from the group consisting of hydroxyl, C.sub.1-C.sub.4
alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl;
and wherein the nitrogen heteroatom is joined to a moiety X
selected from the group consisting of chlorine and bromine.
[0034] Thus the present invention provides a monomer and its
corresponding polymers and copolymers comprising a cyclic
N-halamine unit, wherein the cyclic N-halamine unit comprises: a
5-membered ring wherein 3 members of the ring are carbon, 1 member
of the ring is a nitrogen heteroatom, and 1 member of the ring is
oxygen heteroatom; wherein 1 carbon member comprises a carbonyl
group; wherein one non-carbonyl carbon member is attached to an
acryloxymethyl linkage which is substituted with moieties R.sub.2,
R.sub.3, and R.sub.4, which moieties are selected from the group
consisting of hydrogen, C.sub.1-C.sub.4 alkyl, benzyl, substituted
benzyl, phenyl and substituted phenyl; wherein said non-carbonyl
linkage carbon member is also joined to a moiety R.sub.1 selected
from the group consisting of hydroxyl, C.sub.1-C.sub.4 alkyl,
benzyl, substituted benzyl, phenyl and substituted phenyl; and
wherein the nitrogen heteroatom is joined to a moiety X selected
from the group consisting of chlorine, bromine or hydrogen. A
general structure for one embodiment of the monomer is shown below.
5
[0035] wherein X is chlorine, bromine or hydrogen; R.sub.1 is
selected from the group consisting of hydroxyl, C.sub.1-C.sub.4
alkyl, benzyl, substituted benzyl, phenyl and substituted phenyl;
R.sub.2, R.sub.3 and R.sub.4 are each independently selected from
the group consisting of hydrogen, C.sub.1-C.sub.4 alkyl, benzyl,
substituted benzyl, phenyl and substituted phenyl. The monomer is
biocidal when X is chlorine or bromine.
[0036] Compounds also include biocidal polymers comprising a cyclic
N-halamine unit linked at a carbon atom by acryloxymethyl linkage
to a second cyclic N-halamine unit, wherein each cyclic N-halamine
unit is a 5-membered ring, wherein 3 members of the ring are
carbon, and 1 member of the ring is nitrogen heteroatom; wherein 1
member of the ring is oxygen heteroatom; wherein 1 carbon member
comprises a carbonyl group; wherein 1 non-carbonyl carbon member is
attached to an acryloxymethyl linkage which is substituted with
moieties R.sub.2, R.sub.3, and R.sub.4, which moieties are selected
from the group consisting of hydrogen, C.sub.1-C.sub.4 alkyl,
benzyl, substituted benzyl, phenyl and substituted phenyl; wherein
said non-carbonyl linkage carbon member is also joined to a moiety
R.sub.1 selected from the group consisting of hydroxyl,
C.sub.1-C.sub.4 alkyl, benzyl, substituted benzyl, phenyl and
substituted phenyl; and wherein the nitrogen heteroatom is joined
to a moiety X selected from the group consisting of chlorine,
bromine or hydrogen.
[0037] Compounds also include biocidal copolymers comprising one or
more cyclic N-halamine units linked at a carbon atom by
acryloxymethyl linkage to a second monomeric unit, wherein the
second monomeric unit can be any polymerizable olefin.
[0038] Compounds also include biocidal grafted copolymers
comprising one or more cyclic N-halamine units linked at a carbon
atom by acryloxymethyl linkage to a pre-existing polymer backbone,
wherein the polymeric backbone can be any commercial polymer.
[0039] Examples of the aforementioned polymers, copolymers and
grafted copolymers include, but are not limited to, polymers,
copolymers and grafted copolymers comprising one or more cyclic
amine and N-halamine monomers represented by the repeating unit
graphic formula illustrated below. 6
[0040] wherein X is selected from the group consisting of hydrogen,
chlorine, and bromine but when X is hydrogen, no biocidal activity
is imparted; wherein R.sub.1 is selected from the group consisting
of hydroxyl, C.sub.1-C.sub.4 alkyl, benzyl, substituted benzyl,
phenyl, substituted phenyl, and any combination thereof; and
wherein R.sub.2, R.sub.3, and R.sub.4 are each independently
selected from the group consisting of hydrogen, C.sub.1-C.sub.4
alkyl, benzyl, substituted benzyl, phenyl, and substituted
phenyl.
[0041] The alkyl substituents representing R.sub.1, R.sub.2,
R.sub.3, and R.sub.4 or those attached to phenyl or benzyl may
contain from 1 to 4 carbon atoms, including methyl, ethyl, propyl,
isopropyl, n-butyl, isobutyl, secondary butyl, and tertiary butyl.
As shown by the graphic formulae, the linkages between two cyclic
N-halamine units can be a "lower alkyl" defined as a hydrocarbon
chain, branched or unbranched, having three carbon atoms. For
example, a structure II polymer may contain a three carbon linkage,
wherein R.sub.1 is methyl, and R.sub.2, R.sub.3, and R.sub.4 are
hydrogen.
[0042] Examples of the aforementioned compounds for each structure
type include, but are not limited to: structure I:
3-chloro-4-(acryloxymethyl)- -4-ethyl-2-oxazolidinone;
3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidino- ne; structure II:
poly-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone- ;
poly-3-bromo-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone;
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone-
;
poly-acrylonitrile-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone-
; poly-acrylic
acid-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone- ;
poly-styrene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone;
poly-vinyl
acetate-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone- ;
poly-vinyl
chloride-co-3-chloro-4-(acryloxy-methyl)-4-ethyl-2-oxazolidin- one;
poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidin-
one; poly-vinyl
chloride-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidi- none;
poly-styrene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone;
poly-vinyl
acetate-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone;
poly-vinyl
alcohol-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone.
[0043] By substitution of other named substituents for R.sub.1,
R.sub.2, R.sub.3, and R.sub.4, e.g., propyl, phenyl, etc., for one
or more of the derivatives above named, other correspondingly named
N-halo derivatives may be formed.
[0044] The polymeric N-halamine biocidal compounds of the present
invention can be prepared by reacting the corresponding
unhalogenated polymers, herein referred to as "precursor cyclic
amines" or "cyclic amines," with a source of chlorine or bromine.
While chlorine gas or liquid bromine may be utilized, other milder
halogenating agents such as, but not limited to, calcium
hypochlorite, sodium hypochlorite, N-chlorosuccinimide,
N-bromosuccinimide, sodium dichloroisocyanurate,
trichloroisocyanuric acid, tertiary butyl hypochlorite,
N-chloroacetamide, N-chloramines, N-bromamines, etc., can also be
employed. Halogenation of the unhalogenated compounds can be
accomplished in aqueous media, in mixtures of water with common
inert organic solvents such as methylene chloride, chloroform, and
carbon tetrachloride, in inert organic solvents themselves, or with
no solvent present, at room temperature. The precursor cyclic
amines can be a previously utilized cyclic N-halamine that has
become ineffective at killing microorganisms due to inactivation of
the N--Cl or N--Br moieties. The above-described halogenations can
be performed in situ, if desired.
[0045] The unhalogenated precursor cyclic amines described in this
invention can be prepared from existing inexpensive commercial
grade starting materials. In the case of the structure represented
above by structure I, commercial grade
2-amino-2-alkyl-1,3-propanediols can be reacted with dialkyl
carbonates in the presence of sodium methoxide or sodium ethoxide
as a catalyst in common solvents in a cyclization reaction to
produce the 4-alkyl-4-hydroxymethyl-2-oxazolidinone, followed by
reaction with acryloyl chloride, or substituted acryloyl chlorides
in common solvents such as chloroform, methylene chloride, benzene,
toluene, acetone, etc., to produce the
4-(acryloxymethyl)-4-alkyl-2-oxazolidinone. Those who are skilled
in the art know that the 4-alkyl-4-hydroxymethyl-2-- oxazolidinone
could be prepared by other synthetic strategies. For the structures
represented by structure II, the compounds encompassing those in
structure I are homopolymerized in the presence of an organic
soluble initiator, such as, but not limited to,
1,1'-azobis(cyclohexanecarbonitri- le),
2,2'-azobisisobutyronitrile, substituted
2,2'-azobisisobutyronitrile, benzoyl peroxide, substituted benzoyl
peroxide, etc., or a water soluble initiator, such as, but not
limited to, hydrogen peroxide, ammonium persulfate, sodium
persulfate, potassium persulfate, etc., in the presence of a
surfactant, such as, but not limited to, sodium laurel sulfate,
ammonium laurel sulfate, etc., when water is used as the solvent,
and in common solvents such as, chloroform, methylene chloride,
carbon tetrachloride, dimethylformamide, etc. For
copolymerizations, the compounds encompassing those in structure
I-type are copolymerized with various monomers, such as, but not
limited to, acrylonitrile, acrylic acid, ethylene, propylene,
styrene, vinyl acetate, vinyl chloride, etc., in the presence of an
initiator as mentioned above, in solvents as mentioned above, and
with a surfactant as mentioned above. For grafting reactions, the
compounds encompassing structure I-type are grafted on to polymeric
backbones, such as, but not limited to, poly-acrylonitrile,
poly-acrylic acid, poly-styrene, poly-vinyl acetate, poly-vinyl
alcohol, poly-vinyl chloride, etc., in the presence of an initiator
as mentioned above, with the addition of a surfactant as mentioned
above. The polymeric backbone is in latex form, which means it is
emulsified in water prior to the grafting reaction either with
surfactants for water soluble polymers, i.e., poly-vinyl alcohol,
poly-acrylic acid, etc., or for water insoluble polymers, i.e.,
poly-acrylonitrile, poly-vinyl chloride, poly-styrene, etc.; the
corresponding monomers, i.e., acrylonitrile, vinyl chloride,
styrene, etc., are polymerized in an emulsion prior to the grafting
reaction.
[0046] The present invention further provides a method for
disinfecting a habitat for halogen-sensitive microorganisms
comprising contacting the habitat with a biocidal amount of a
biocidal monomer as described herein. For example, the biocidal
monomer can be any of the following, used singly or in
combination:
[0047] 3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0048] 3-chloro-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
[0049]
3-chloro-4-(2'-methylacryloxymethyl)-4-ethyl-2-oxazolidinone,
[0050]
3-chloro-4-(3',3'-dimethylacryloxymethyl)-4-ethyl-2-oxazolidinone,
[0051] 3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0052] 3-bromo-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
[0053] 3-bromo-4-(2'-methylacryloxymethyl)-4-ethyl-2-oxazolidinone,
and
[0054]
3-bromo-4-(3',3'-dimethylacryloxymethyl)-4-ethyl-2-oxazolidinone.
[0055] The present invention further provides a method for
disinfecting a habitat for halogen-sensitive microorganisms
comprising contacting the habitat with a biocidal amount of a
biocidal polymer as described herein. For example, the biocidal
polymer can be any of the following, used singly or in
combination.
[0056]
poly-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0057]
poly-3-chloro-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
[0058]
poly-3-chloro-4-(2'-methylacryloxymethyl)-4-ethyl-2-oxazolidinone,
[0059]
poly-3-chloro-4-(3',3'-dimethylacryloxymethyl)-4-ethyl-2-oxazolidin-
one,
[0060]
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazoli-
dinone,
[0061]
poly-styrene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone-
,
[0062] poly-vinyl
acetate-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazoli-
dinone,
[0063] poly-vinyl
chloride-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazol-
idinone,
[0064]
poly-ethylene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinon-
e,
[0065]
poly-propylene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidino-
ne,
[0066]
poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolid-
inone,
[0067]
poly-styrene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0068] poly-vinyl
acetate-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolid-
inone,
[0069] poly-vinyl
alcohol-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolid-
inone,
[0070] poly-vinyl
chloride-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazoli-
dinone,
[0071]
poly-ethylene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone-
,
[0072]
poly-propylene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinon-
e,
cellulose-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0073] poly-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0074]
poly-3-bromo-4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone,
[0075]
poly-3-bromo-4-(2'-methylacryloxymethyl)-4-ethyl-2-oxazolidinone,
[0076]
poly-3-bromo-4-(3',3'-dimethylacryloxymethyl)-4-ethyl-2-oxazolidino-
ne,
[0077]
poly-acrylonitrile-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolid-
inone,
[0078]
poly-styrene-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0079] poly-vinyl
acetate-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolid-
inone,
[0080] poly-vinyl
chloride-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazoli-
dinone,
[0081]
poly-ethylene-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone-
,
[0082]
poly-propylene-co-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinon-
e,
[0083]
poly-acrylonitrile-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidi-
none,
[0084]
poly-styrene-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0085] poly-vinyl
acetate-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidi- none,
[0086] poly-vinyl
alcohol-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidi- none,
[0087] poly-vinyl
chloride-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolid-
inone,
[0088]
poly-ethylene-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone,
[0089]
poly-propylene-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone-
, and
cellulose-g-3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone.
[0090] The cyclic N-halamine biocidal compounds can be made soluble
or insoluble in water depending on the application desired. They
can be employed as disinfectants against undesirable microorganisms
in many habitats including surfaces of materials by treating the
material with a biocidally effective amount of polymer compound.
Water insoluble biocidal surfaces can include the following
applications: for example, oil and water based paints, catheters,
surgical tables, surgical instrumentation, medical tables and
desktops, medical instrumentation, dental tables and desktops,
dental instrumentation, swimming pool liners, fabric materials,
medical wrappings, piping, workbenches, counter tops, and the like.
Water soluble biocidal surfaces can include the following
applications, for example, oil and gas tank liners, preservatives,
can and bag liners, water based paints, and the like. As used
herein, a "surface" can include any surface upon which
halogen-sensitive microorganisms can dwell and to which a claimed
polymer can be bound, which can include surfaces of, for example,
textile fabric, metal, rubber, concrete, wood, glass, bandaging,
and plastic.
[0091] For surfaces, disinfection testing is best accomplished by
placing microbiologically contaminated water onto the polymer
coated substrate. The contact time will be measured, which is the
amount of time needed for the surface to kill a substantial amount
of the microorganism; depending on the application, the contact
times will vary. These polymeric biocides can be incorporated into
textile and solid surfaces which can serve as disinfectants or
biological preservatives.
[0092] Once a surface becomes ineffective at killing microorganisms
due to inactivation of the N--Cl or N--Br moieties, it can be
regenerated by wiping an aqueous solution of free halogen over it.
Additionally, the cyclic N-halamine biocide can be created or
regenerated in situ by adding a stoichiometric amount of free
halogen, either chlorine or bromine, to a precursor cyclic amine
contained in a material such as in paint, oil, textile fabric or
the like, or bound to a surface of a material such as wood, glass,
plastic polymer coating, textile fabric, metal, rubber, concrete,
cloth bandage, or the like.
[0093] All microorganisms on hard surfaces susceptible to
disinfection by free halogen, e.g., free chlorine, or combined
halogen, e.g., N-haloimidazolidinones, N-halohydantoins,
N-halooxazolidinones, N-haloisocyanurates, etc., will also be
susceptible to disinfection by the biocidal compounds of this
invention. Such microorganisms include, for example, bacteria,
protozoa, fungi, viruses, and algae.
[0094] The biocidal compounds described herein can be employed in a
variety of disinfecting applications. They will be of importance in
controlling microbiological contamination on surfaces, for medical
and dental applications, bandages, fabric materials, piping,
paints, swimming pools, catheters, and the like. For example, the
halogenated polymers will prevent the growth of undesirable
organisms, such as the bacteria genera Staphylococcus, Pseudomonas,
Salmonella, Shigella, Legionella, Methylobacterium, Klebsiella, and
Bacillus; the fungi genera Candida, Rhodoturula, and molds such as
mildew; the protozoa genera Giardia, Entamoeba, and
Cryptosporidium; the viruses poliovirus, rotavirus, HIV, and
herpesvirus; and the algae genera Anabaena, Oscillatoria, and
Chlorella; and other sources of biofouling on surfaces. They will
be of importance as preservatives and preventatives against
microbiological contamination in paints, coatings, and on surfaces.
They will be of particular importance to the medical field for use
in ointments, bandages, sterile surfaces, and the like, and for the
attachment to liners of containers used in the food processing
industry. They can be used in conjunction with textiles for sterile
applications, such as coatings or physical bonds to sheets or
bandages used for burn victims or on microbiological
decontamination suits.
[0095] The halogenated compounds described herein can be used in
diverse liquid and solid formulations such as powders, granular
materials, solutions, concentrates, emulsions, slurries, and in the
presence of diluents, extenders, fillers, conditioners, aqueous
solvent, organic solvents, plasticizers, pigments, and the like. Of
particular use can be their employment in formulations involving
wetting emulsifying, or dispersing agents such as sulfonates,
alcohols, or similar surface active materials. The compounds are
also compatible with buffering agents and other sources of
halogen.
[0096] A further embodiment of biocidal compounds made in
accordance with the invention uses monomers of:
[0097] 3-hydroxymethyl-5,5-dimethylhydantoin (Structure III,
wherein R.sub.1 and R.sub.2 are methyl), 7
[0098] 3-(acryloxymethyl)-5,5-dimethylhydantoin (Structure IV,
wherein R.sub.1 and R.sub.2 are methyl, and R.sub.3, R.sub.4, and
R.sub.5 are hydrogen) and, 8
[0099] 4,4-dihydroxymethyl-2-oxazolidinone (Structure V) 9
[0100] in synthesizing polymers, copolymers, and grafted copolymers
which can be coated onto surfaces and upon halogenation with free
chlorine or bromine, become biocidal. Of particular importance is
the use of these monomers in the preparation of the N-chlorinated
copolymers of 3-(acryloxymethyl)-5,5-dimethylhydantoin and methyl
methacrylate/2-hydroxyethyl acrylate or methyl methacrylate/acrylic
acid for biocidal thermosetting coatings, and in the preparation of
N-chlorinated copolymers of 4,4-dihydroxymethyl-2-oxazolidinone and
diisocyanates. The latter class of compounds is preferably used for
biocidal polyurethane coatings.
[0101] The present invention is more particularly described in the
following examples which are intended as illustrative only since
numerous modifications and variations therein will be apparent to
those skilled in the art.
EXAMPLES
Example 1
Preparation of 3-halo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone
(1a-Cl, la-Br)
[0102] To a one-neck round bottom flask were added 13.7 grams
(0.115 mole) 2-amino-2-ethyl-1,3-propanediol (Aldrich Chemical Co.,
Milwaukee, Wis.), 17.5 milliliters (0.144 mole) diethylcarbonate,
and 0.10 grams (0.0019 mole) sodium methoxide. The reagents were
heated to 110.degree. C. and refluxed with stirring for forty-eight
hours. The reflux condenser was then removed and replaced with a
distillation head. The ethanol was then removed by simple
distillation, and the thick residue was cooled to room temperature.
100 milliliters ethyl acetate was then added to the residue, and
the solution was vigorously stirred. Slowly a white solid formed.
The solid was vacuum filtered to give 13.34 grams (80% of yield
theoretically expected) 4-hydroxymethyl-4-ethyl-2-oxazolidinone as
a white powder. The product exhibited a melting point of
75-77.degree. C.; and the following spectral characteristics:
.sup.1H NMR (CDCl.sub.3) .delta. 0.91 (t, 3H J=7.5 Hz), 1.53-1.65
(m, 2H), 3.31 (s, 2H), 3.92 (d, 1H J=2.4 Hz), 4.13 (d, 1H J=2.4
Hz), 5.83 (s, 1H), 7.46 (s, 1H); .sup.13C NMR (CDCl.sub.3) .delta.
7.7, 28.2, 62.6, 66.2, 71.2, 160.8; IR (KBr) 3316, 3245, 2967, 1727
cm.sup.-1; MS m/z.145.
[0103] 3.10 grams (0.021 mole) of the
4-hydroxymethyl-4-ethyl-2-oxazolidin- one prepared as described
above, 2.0 grams (0.022 mole) acryloyl chloride, and 25 milliliters
chloroform were mixed in a one-neck round-bottom flask. The
heterogeneous solution was heated to reflux, with stirring, for six
hours, at which time all of the solid had dissolved. The solution
was cooled to room temperature, and the solvent was removed under
reduced pressure. 4.10 grams (98% of the yield theoretically
expected) 4-(acryloxymethyl)-4-ethyl-2-oxazolidinone (1 a) was
obtained as a yellow oil. The product exhibited the following
spectral data: .sup.1H NMR (CDCl.sub.3) .delta. 0.88 (t, 3H J=1.8
Hz), 1.53-1.66 (m, 2H), 3.99-4.18 (m, 4H), 5.83 (d, 1H J=2.4 Hz),
5.98-6.10 (m, 1H), 6.34-(d, 1H J=4.1 Hz), 7.24 (s, 1H); .sup.13C
NMR (CDCl.sub.3) .delta. 7.4, 28.4, 60.2, 67.2, 71.0, 127.6, 132.1,
159.7, 165.7; IR (NaCl) 3229, 3015, 2969, 1753 cm.sup.-1; MS m/z
199.
[0104] 1.0 gram (0.005 mole) of the
4-(acryloxymethyl)-4-ethyl-2-oxazolidi- none prepared as described
above, 1.1 grams (0.01 mole) tertiary butyl hypochlorite, and 5.0
milliliters methylene chloride were added to a one-neck round
bottom flask. The solution was stirred at room temperature for 30
minutes and the solvent removed under reduced pressure. 1.17 grams
(100% of the yield theoretically expected)
3-chloro-4-(acryloxymethyl)-4-- ethyl-2-oxazolidinone(1a-Cl) was
obtained as a clear oil. The product had the following spectral
data: .sup.1H NMR (CDCl.sub.3) .delta. 0.93 (t, 3H J=1.8 Hz),
1.54-1.78 (m, 2H), 4.10-4.23 (m, 4H), 5.84-(d, 1H J=2.4 Hz),
5.98-6.10 (m, 1H), 6.32 (d, 1H J=4.2 Hz); .sup.13C NMR (CDCl.sub.3)
.delta. 6.6, 24.7, 65.9, 67.7, 71.0, 127.2, 132.6, 159.6, 165.3; IR
(NaCl) 2969, 1783 cm.sup.-1; MS m/z 234. 1.0 gram (0.005 mol) of
the 4-(acryloxymethyl)-4-ethyl-2-oxazolidinone prepared as
described above, and 50 milliliters of a 0.1 normal sodium
hypobromite solution were stirred together at room temperature for
30 minutes in a sealed flask. The solution was then extracted with
three 50 milliliter portions of methylene chloride, and the organic
layer was washed with saturated sodium chloride solution and dried
over sodium sulfate. The solvent was removed under reduced pressure
to give 1.40 grams (100% of the yield theoretically expected)
3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazolidinon- e(1a-Br) as a
clear oil. The product exhibited the following spectral data:
.sup.1H NMR (CDCl.sub.3) .delta. 0.90 (t, 3H J=2.0 Hz), 1.58-1.81
(m, 2H), 4.15-4.27 (m, 4H), 5.80 (d, 1H J=2.3 Hz), 6.00-6.15 (m,
1H), 6.37 (d, 1H J=4.5 Hz); .sup.13C NMR (CDCl.sub.3) .delta. 7.6,
25.6, 64.9, 68.3, 71.7, 123.2, 136.6, 159.1, 165.5; IR (NaCl) 2970,
1775 cm.sup.-1; MS m/z 278.
Example 2
Preparation of 4-(crotonoxymethyl)-4-ethyl-2-oxazolidinone(1b)
[0105] 3.1 grams (0.021 mole)
4-ethyl-4-hydroxymethyl-2-oxazolidinone, prepared identically to
that discussed in example 1, 2.3 grams (0.022 mole) trans-crotonyl
chloride, and 25 milliliters chloroform were mixed in a one-necked
round-bottom flask. The procedure employed was identical to that
discussed in example 1. 4.20 grams (98% of the yield theoretically
expected) of pure product was obtained as a clear oil. The product
exhibited the following spectral data: .sup.1H NMR (CDC1.sup.3)
.delta. 0.90 (t, 3H J=1.8 Hz), 1.48-1.67 (m, 2H), 1.83 (d, 3H J=3.6
Hz), 3.97-4.19 (m, 4H), 5.79 (d, 1H J=3.6 Hz), 6.90-6.99 (m, 2H);
.sup.13C NMR (CDCl.sub.3) .delta. 7.3, 18.1, 28.3, 60.2, 66.7,
70.9, 121.7, 146.3, 159.6, 166.0; IR (NaCl) 3229, 3020, 2960, 1780
cm.sup.-1; MS m/z 213. This monomer can be chlorinated or
brominated by the same procedure as in example 1.
Example 3
Preparation of 4-(2'-methylacryloxymethyl)-4-ethyl-2-oxazolidinone
(1c)
[0106] 3.1 grams (0.021 mole)
4-ethyl-4-hydroxymethyl-2-oxazolidinone, prepared identically to
that discussed in example 1, 2.3 grams (0.022 mole)
2-methylacryloyl chloride, and 25 milliliters chloroform were mixed
in a one-necked round-bottom flask. The procedure employed was
identical to that discussed in example 1. 2.56 grams (60% the yield
theoretically expected) of pure product was obtained as a brown
oil. The product gave the following spectral data: .sup.1H NMR
(CDCl.sub.3) .delta. 0.92 (t, 3H J=1.8 Hz), 1.46-1.65 (m, 2H), 1.93
(s, 3H), 4.12-4.25 (m, 4H), 5.55 (s, 1H), 6.07 (s, 1H), 7.06 (s,
1H); .sup.13C NMR (CDCl.sub.3) .delta. 7.2, 18.0, 27.7, 60.2, 65.6,
70.8, 126.6, 135.4, 160.4, 166.8; IR (NaCl) 3230, 3010,-2960, 1740
cm.sup.-1, MS m/z 213. This monomer can be chlorinated or
brominated by the same procedure as in example 1.
Example 4
Preparation of
4-(3',3'-dimethylacryloxymethyl)-4-ethyl-2-oxazolidinone (1d)
[0107] 3.1 grams (0.021 mole)
4-ethyl-4-hydroxymethyl-2-oxazolidinone, prepared identically to
that discussed in example 1, 2.6 grams (0.022 mole)
3,3-dimethylacryloyl chloride, and 25 milliliters chloroform were
mixed in a one-necked round-bottom flask. The procedure employed
was identical to that discussed in example 4. 4.10 grams (90% of
the yield theoretically expected) of pure product was obtained as a
yellow oil. The product exhibited the following spectral data:
.sup.1H NMR (CDCl.sub.3) .delta. 0.98 (t, 3H J=1.2 Hz), 1.65-1.71
(m, 2H), 1.92 (s, 3H), 2.17 (s, 3H), 4.04-4.23 (m. 4H), 5.71 (s,
1H), 6.43 (s, 1H); .sup.13C NMR (CDCl.sub.3) .delta. 7.6, 20.6,
27.7, 28.7, 60.3, 66.1, 71.3, 115.2, 159.0, 159.5, 166.2; IR (NaCl)
3215, 3020, 2970, 1785 cm.sup.-1; MS m/z 227. This monomer can be
chlorinated or brominated by the same procedure as in example
1.
Example 5
Preparation of
poly-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone (2a)
[0108] 1.0 gram (0.005 mole)
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone, prepared identically to
that discussed in example 1, 0.01 grams (6.1.times.10.sup.-5 mole)
2,2'-azobisisobutyronitrile, and 10 milliliters anhydrous
N,N-dimethylformamide were added to a two-neck round-bottom flask.
The reagents were purged with nitrogen for fifteen minutes, and the
flask was sealed and heated to 70.degree. C. for ten hours with
stirring. The viscous solution was cooled to room temperature and
was drop-added into 200 milliliters water. The polymer immediately
precipitated out and was filtered and dried in a vacuum oven to
give 0.9 grams (90% of the yield theoretically expected) pure
product as an amorphous solid. The product,
poly-4-(acryloxymethyl)-4-ethyl-2-oxazolidi- none, exhibited the
following spectral data: .sup.13C NMR (CDCl.sub.3) .delta. 7.1,
27.6, 30.8, 35.7, 59.2, 60.9, 67.1, 69.8, 158.1, 162.3; IR (neat)
3400, 2937, 1757 cm.sup.-1.
[0109] 0.5 grams (0.0025 mole)
poly-4-(acryloxymethyl)-4-ethyl-2-oxazolidi- none, prepared
identically to that discussed above, 0.3 grams (0.0028 mole)
tertiary butyl hypochlorite, and 10 milliliters methylene chloride
were added to a one-neck round bottom flask. The reagents were
stirred vigorously for 30 minutes and the solvent removed under
reduced pressure. The residue was dried in a vacuum oven to give
0.58 grams (100% of the yield theoretically expected)
poly-3-chloro-4-(acryloxymethyl)-4-ethyl-2-- oxazolidinone (2a) as
an amorphous solid. The product exhibited the following spectral
data: .sup.13C NMR (CDC1.sup.3) .delta. 7.5, 26.6, 31.8, 35.7,
59.2, 60.3, 69.1, 70.0, 159.1, 160.3; IR (neat) 3400, 2937, 1780
cm.sup.-1. This polymer can be brominated by the same procedure as
employed in example 6.
Example 6
Preparation of
poly-acrylonitrile-co-3-halo-4-(acryloxymethyl)-4-ethyl-2-o-
xazolidinone (3a-C, 3a-Br)
[0110] 1.0 gram (0.005 mole)
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone, prepared identically to
that discussed in example 1, 2.7 grams (0.05 mole) acrylonitrile
(Aldrich Chemical Co. Milwaukee, Wis.), 0.02 grams
(1.2.times.10.sup.-6 mole) 2,2'-azobisisobutyronitrile, and 10
milliliters anhydrous N,N-dimethylformamide were placed in a
two-neck round-bottom flask. The reaction mixture was purged with
nitrogen for fifteen minutes and the flask sealed and heated to
70.degree. C. for 10 hours with stirring. The solution was cooled
to room temperature and the polymer precipitated in 200 milliliters
water. The polymer was filtered off, redissolved in
N,N-dimethylformamide, and reprecipitated two more times. The
resulting solid was filtered and dried in a vacuum oven to give 3.3
g (90% of the yield theoretically expected) pure product as a white
solid. The product,
poly-acrylonitrile-co-4-(acryloxymethyl)-4-ethy- l-2-oxazolidinone,
exhibited the following spectral data: .sup.13C NMR (DMSO-d.sub.6)
.delta. 7.17, 26.7, 27.4, 27.9, 30.6, 32.6, 35.7, 59.2, 67.7, 69.9,
116.6, 120.0, 120.3, 158.2, 162.3; IR (KBr) 3400, 2938, 2244, 1757
cm.sup.-1.
[0111] 1.0 gram of
poly-acrylonitrile-co-4-(acryloxymethyl)-4-ethyl-2-oxaz- olidinone,
prepared identically as that discussed above and 50 milliliters 2.0
normal sodium hydroxide were added to an Erlenmeyer flask. The
stirred, heterogeneous solution was cooled in an ice bath until the
temperature was 10.degree. C. Chlorine gas (Matheson Gas Co.,
Montgomeryville, Pa.) was bubbled into the solution slowly so the
temperature did not exceed 15.degree. C. Once the pH reached 7.0,
the chlorine gas flow was stopped, and the flask was sealed for
thirty minutes. The solution was allowed to come to room
temperature and was vacuum filtered. The resulting solid was washed
with 200 milliliters distilled water and was dried to give 1.0 gram
(90% of the yield theoretically expected)
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-
-4-ethyl-2-oxazolidinone (3a-Cl) as a white solid. The product
exhibited the following spectral data: IR (KBr) 2940, 2243, 1764
cm.sup.-1. Comparable results were obtained using compounds
1b-1d.
[0112] 1.0 gram of
poly-acrylonitrile-co-4-(acryloxymethyl)-4-ethyl-2-oxaz- olidinone,
prepared identically as that discussed above, and 50 milliliters
0.1 normal sodium hypobromite were stirred at room temperature for
30 minutes in a sealed flask. The solution was then filtered and
the solid washed with 200 milliliters distilled water and dried to
give 1.0 gram poly-acrylonitrile-co-3-bromo-4-(acryloxymethyl)-4-
-ethyl-2-oxazolidinone (3a-Br) as a pale yellow solid. The product
exhibited the following spectral data: IR (KBr) 2950, 2245, 1770
cm.sup.-1. Comparable results were obtained using compounds
1b-Id.
Example 7
Preparation of
poly-styrene-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazo-
lidinone (3b)
[0113] A copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-- oxazolidinone and styrene (Aldrich
Chemical Co., Milwaukee, Wis.) using the procedure employed which
was identical to that discussed in example 6. The yield of
poly-styrene-co-4-(acryloxymethyl)-4-ethyl-2-oxazolidinon- e was
90% of that theoretically expected. The product exhibited prominent
infrared bands in a KBr pellet at 2930 and 1754 cm.sup.-1.
[0114] Chlorination of the above sample in the manner analogous to
that discussed in example 6 produced
poly-styrene-co-3-chloro-4-(acryloxymethy-
l)-4-ethyl-2-oxazolidinone (3b) in 100% yield with prominent
infrared bands in a KBr pellet at 2927 and 1767 cm.sup.-1.
Comparable results were obtained with compounds 1b-Id, and the
bromination can be done in the manner described in example 6.
Example 8
Preparation of poly-vinyl
chloride-co-3-chloro-4-(acryloxymethyl)-4-ethyl-- 2-oxazolidinone
(3c)
[0115] A copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-- oxazolidinone and vinyl chloride
(Aldrich Chemical Co., Milwaukee, Wis.) using the procedure
employed which was identical to that discussed in example 6. The
yield of poly-vinyl chloride-co-4-(acryloxymethyl)-4-ethyl-
-2-oxazolidinone was 90% of that theoretically expected. The
product exhibited prominent infrared bands in a KBr pellet at 2920
and 1750 cm.sup.-1.
[0116] Chlorination of the above sample in the manner analogous to
that discussed in example 6 produced poly-vinyl
chloride-co-3-chloro-4-(acrylo- xymethyl)-4-ethyl-2-oxazolidinone
(3c) in 100% yield with prominent infrared bands in a KBr pellet at
2930 and 1770 cm.sup.-1. Comparable results were obtained with
compounds 1b-Id, and the bromination can be done in the manner
described in example 6.
Example 9
Preparation of
poly-acrylonitrile-co-4-(acryloxymethyl)-4-ethyl-2-oxazolid- inone
latex (3d)
[0117] 5.0 grams (0.025 mole)
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone, prepared identically to
that discussed in example 1, 10.0 grams (0.190 mole) acrylonitrile,
30.0 grams (1.67 mole) water, and 0.20 grams (6.94.times.10.sup.-4
mole) sodium lauryl sulfate were added to a three-necked
round-bottom flask equipped with a gas inlet and reflux condenser.
The solution was stirred and heated to 60.degree. C. and purged
with nitrogen for ten minutes. A solution of 0.025 grams
(9.26.times.10.sup.-5 mole) potassium persulfate and 1.0 milliliter
water was prepared and added in the reaction mixture after the
nitrogen purge was completed. The reaction was stirred for twelve
hours and then cooled to room temperature. Any precipitated polymer
was allowed to settle, and the latex was decanted off. The product
poly-acrylonitrile-co-4-(acryloxy- methyl)-4-ethyl-2-oxazolidinone
latex (3d) was produced in 95% yield with prominent infrared bands
in a KBr pellet at 2985, 2244, and 1750 cm.sup.-1. Comparable
results were obtained with compounds 1b-Id, and the bromination can
be done in the manner described in example 6.
Example 10
Preparation of poly-vinyl
chloride-co-4-(acryloxymethyl)-4-ethyl-2-oxazoli- dinone latex
(3e)
[0118] An emulsion copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone and vinyl chloride using
the procedure employed which was identical to that discussed in
example 9. The yield of poly-vinyl
chloride-co-4-(acryloxymethyl)-4-ethyl-2-oxazolid- inone latex (3e)
was 90% of that theoretically expected. The product exhibited
prominent infrared bands in a KBr pellet at 2980 and 1750
cm.sup.-1. Comparable results were obtained with compounds 1b-Id,
and the bromination can be done in the manner described in example
6.
Example 11
Preparation of
poly-styrene-co-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone latex
(3f)
[0119] An emulsion copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone and styrene using the
procedure employed which was identical to that discussed in example
9. The yield of
poly-styrene-co-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone latex
(3f) was 90% of that theoretically expected. The product exhibited
prominent infrared bands in a KBr pellet at 3050, 2985, and 1750
cm.sup.-1. Comparable results were obtained with compounds 1b-Id,
and the bromination can be done in the manner described in example
6.
Example 12
Preparation of poly-vinyl
acetate-co-4-(acryloxymethyl)-4-ethyl-2-oxazolid- inone latex (3
g)
[0120] An emulsion copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone and vinyl acetate
(Aldrich Chemical Co., Milwaukee, Wis.) using the procedure
employed which was identical to that discussed in example 9. The
yield of poly-vinyl
acetate-co-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone latex (3 g)
was 90% of that theoretically expected. The product exhibited
prominent infrared bands in a KBr pellet at 2985, 1772, and 1750
cm.sup.-1. Comparable results were obtained with compounds 1b-1d,
and the bromination can be done in the manner described in example
6.
Example 13
Preparation of
poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2--
oxazolidinone (4a)
[0121] 2.3 grams (0.013 mole)
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone, prepared identically to
that discussed in example 1, 10 grams poly-acrylonitrile latex
which was prepared from acrylonitrile using the method described by
Hayes, R. A., J. Polymer Sci., 11:531 (1967), and 20 grams (1.1
mole) water, were added to a 100 milliliters three-neck round
bottom flask. The reagents were purged with nitrogen for fifteen
minutes; the flask was then sealed and heated to 60.degree. C. with
stirring. Once the internal temperature reached 60.degree. C., 0.05
grams (1.9.times.10.sup.-4 mole) potassium persulfate, dissolved in
1.0 milliliters water, was added in to the reaction mixture. The
reaction mixture was heated and stirred for twelve hours, then
cooled to room temperature. The polymer was precipitated into 150
milliliters of a saturated sodium chloride solution to give a white
solid. The solid was collected by vacuum filtration and extracted
with 200 milliliters boiling 50/50 DMF/water. The resulting solid
was refiltered and re-extracted two more times to give 5.0 grams
poly-acrylonitrile-g-4-(acryloxymethyl)-4-et- hyl-2-oxazolidinone
in 75% yield with prominent infrared bands in a KBr pellet at 2965,
2240, and 1750 cm.sup.-1.
[0122] 2.0 grams of the poly-acrylonitrile grafted copolymer
product prepared as described above and 50 milliliters 2.0 normal
sodium hydroxide were placed in an Erlenmeyer flask in an ice bath
with stirring. The stirred mixture was maintained at a temperature
lower than 10.degree. C., while chlorine gas was bubbled in until
the pH reached 7.0, at which time the flask was sealed and stirred
for thirty minutes at room temperature. The solution was filtered,
washed with 200 milliliters water, and dried to give 2.0 grams
poly-acrylonitrile-g-3-chloro-4-(acryl-
oxymethyl)-4-ethyl-2-oxazolidinone (4a) in 100% yield with
prominent infrared bands in a KBr pellet at 2960, 2240, and 1768
cm.sup.-1. Comparable results were obtained with compounds 1b-id,
and the bromination can be done in the manner described in example
6.
Example 14
Preparation of
poly-styrene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazol-
idinone (4b)
[0123] A grafting copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone and poly-styrene using
the procedure employed which was identical to that discussed in
example 13. The yield of
poly-styrene-g-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone was 85%
of that theoretically expected, and the product exhibited prominent
infrared bands in a KBr pellet at 3015, 2980, and 1747
cm.sup.-1.
[0124] The poly-styrene grafted copolymer was then chlorinated in a
manner analogous to that discussed in example 13 and produced
poly-styrene-g-3-chloro-4-acryloxymethyl-4-ethyl-2-oxazolidinone
(4b) in 100% yield with prominent infrared bands in a KBr pellet at
3020, 2985, and 1765 cm.sup.-1. Comparable results were obtained
with compounds 1b-1d, and the bromination can be done in the manner
described in example 6.
Example 15
Preparation of poly-vinyl
alcohol-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-- oxazolidinone
(4c)
[0125] A grafting copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone and poly-vinyl alcohol
using the procedure employed which was identical to that discussed
in example 13. The yield of poly-vinyl
alcohol-g-4-(acryloxymethyl)-4-ethyl-2-oxazol- idinone was 95% of
that theoretically expected, and the product exhibited prominent
infrared bands in a KBr pellet at 3415, 2975, and 1757
cm.sup.-1.
[0126] The poly-vinyl alcohol grafted copolymer was then
chlorinated in a manner analogous to that discussed in example 13
and produced poly-vinyl
alcohol-g-3-chloro-4-acryloxymethyl-4-ethyl-2-oxazolidinone (4c) in
100% yield with prominent infrared bands in a KBr pellet at 3420,
2980, and 1760 cm.sup.-1. Comparable results were obtained with
compounds 1b-Id, and the bromination can be done in the manner
described in example 6.
Example 16
Preparation of poly-vinyl
acetate-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-- oxazolidinone
(4d)
[0127] A grafting copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone and poly-vinyl acetate
using the procedure employed which was identical to that discussed
in example 13. The yield of poly-vinyl
acetate-g-4-(acryloxymethyl)-4-ethyl-2-oxazol- idinone was 90% of
that theoretically expected, and the product exhibited prominent
infrared bands in a KBr pellet at 2980, 1750, and 1710
cm.sup.-1.
[0128] The poly-vinyl acetate grafted copolymer was then
chlorinated in a manner analogous to that discussed in example 13
produced poly-vinyl
acetate-g-3-chloro-4-acryloxymethyl-4-ethyl-2-oxazolidinone (4d) in
100% yield with prominent infrared bands in a KBr pellet at 2980,
1768, and 1710 cm.sup.-1. Comparable results were obtained with
compounds 1b-Id, and the bromination can be done in the manner
described in example 6.
Example 17
Preparation of poly-vinyl
chloride-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2- -oxazolidinone
(4e)
[0129] A grafting copolymerization was performed with
4-(acryloxymethyl)-4-ethyl-2-oxazolidinone and poly-vinyl chloride
using the procedure employed which was identical to that discussed
in example 13. The yield of poly-vinyl
chloride-g-4-(acryloxymethyl)-4-ethyl-2-oxazo- lidinone was 75% of
that theoretically expected, and the product exhibited prominent
infrared bands in a KBr pellet at 2975 and 1740 cm.sup.-1.
[0130] The poly-vinyl chloride grafted copolymer was then
chlorinated in a manner analogous to that discussed in example 13
produced poly-vinyl
chloride-g-3-chloro-4-acryloxymethyl-4-ethyl-2-oxazolidinone (4e)
in 100% yield with prominent infrared bands in a KBr pellet at 2970
and 1767 cm.sup.-1. Comparable results were obtained with compounds
1b-Id, and the bromination can be done in the manner described in
example 6.
Example 18
Preparation of
cellulose-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidi- none
(4f)
[0131] 1.0 gram cellulose and 50.0 milliliters 0.05 normal nitric
acid were placed in an Erlenmeyer flask and stirred for 30 minutes
at 30.degree. C. under nitrogen. 1.54 grams (0.008 mole)
4-(acryloxymethyl)-4-ethyl-4-hydroxymethyl-2-oxazolidinone,
prepared identically to that discussed in example 1, was added, and
the reaction was stirred for 15 minutes; then 0.11 grams
(2.0.times.10.sup.-4 mole) ceric ammonium nitrate was added to the
reaction. A continuous supply of purified nitrogen was maintained
throughout the reaction period of 30 minutes, at which time the
polymerization was complete and the cellulose filtered off. The
solid was washed with distilled water and acetone and dried in an
oven at 50.degree. C. to give cellulose-g-3-4-(acryloxymethyl-
)-4-ethyl-2-oxazolidinone in 100% yield.
[0132] The grafted cellulose, as described above, was chlorinated
by soaking it in a diluted sodium hypochlorite solution for 20
minutes, washed with synthetic chlorine-demand-free water, and
dried at room temperature overnight to produce,
cellulose-g-3-chloro-4-(acryloxymethyl)- -4-ethyl-2-oxazolidinone
(4f).
Example 19
Efficacies of the Poly N-halamine Compounds Against Staphylococcus
aureus
[0133] Solid samples of the poly N-halamine compounds described in
examples 6-18 were packed into glass Pasteur pipettes (5.75 inches
long, 0.25 inches inside diameter) at a length of 1.0 inch. The
samples were washed with pH 7.0 aqueous solution and then 10.sup.6
CFU per milliliter of Staphylococcus aureus (ATCC 6538) was added
to the pipette, and the inoculum was, allowed to pass through the
packed column using gravity feed in most cases. The particle size
for some of the polymer samples was sufficiently small that
compressed nitrogen was used to force the inoculum through the
column to enhance flow rates. The effluent from each sample was
collected, and 25 microliter aliquots were removed and plated on
nutrient agar. The remaining portions of the effluents were
recycled through the columns. This procedure was repeated 5-6 times
which allowed for an assessment of biocidal contact times. The
plated samples were incubated at 37.degree. C. for 48 hours and
then examined for viable growth. Control samples consisted of
plating aliquots of the bacterial suspension before passing the
bacteria through the biocidal polymer columns, or in some cases, of
passing the bacteria through columns containing unchlorinated
precursor polymer samples having similar particle sizes. In all
cases the two types of control experiments yielded plates which
contained confluent growth too numerous to count indicating that
the bacterial samples were viable and that the organisms were not
simply eliminated by filtration upon passing through the samples.
Results are tabulated in Table I.
[0134] The data in Table I demonstrate that all of the N-halamine
biocidal polymers tested were effective at inactivating S. aureus
over extended periods of time.
1TABLE I Biocidal Effects of the N-halamine Polymers Column Contact
Time for Length Age 6-log Inactivation Polymer.sup.a Mesh Size
(inches) (Days).sup.b of S. aureus (min) 3a-Cl >45 1.0 3
.ltoreq.2.28 3a-Cl >45 1.0 365 4.56-5.30 3a-Br >45 1.0 1
.ltoreq.1.30 3b 35-60 1.0 4 .ltoreq.1.35 3b 35-60 1.0 365 2.35-3.02
3c 35-60 1.0 2 .ltoreq.1.25 3c 35-60 1.0 365 1.96-2.35 4a 35-60 1.0
5 .ltoreq.2.65 4a 35-60 1.0 60 .ltoreq.3.56 4b 35-60 1.0 10
.ltoreq.1.25 4b 35-60 1.0 65 .ltoreq.1.30 4e 35-60 1.0 5
.ltoreq.1.05 4e 35-60 1.0 68 .ltoreq.1.25 .sup.a3a-Cl =
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-eth-
yl-2-oxazolidinone 3a-Br = poly-acrylonitrile-co-3-bromo-4-(acrylo-
xymethyl)-4-ethyl-2-oxazolidinone 3b = poly-styrene-co-3-chloro-4--
(acryloxymethyl)-4-ethyl-2-oxazolidinone 3c = poly-vinyl
chloride-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone 4a
=
poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidi-
none 4b = poly-styrene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxa-
zolidinone 4e = poly-vinyl chloride-g-3-chloro-4-(acryloxymethyl)--
4-ethyl-2-oxazolidinone .sup.bTime in days elapsing between sample
synthesis and biocidal test run with storage at room
temperature.
Example 20
Efficacies of N-Halamine Compounds Against Staphylococcus aureus in
Aqueous Solution
[0135] The bacterial efficacies of the compounds against S. aureus
(ATCC 6538) in chlorine-demand-free water were determine by using
techniques employed previously in extensive detail by Williams et
al., Appl. Environ. Microbial., 54:2583 (1987). Solutions
containing 10.sup.6 CFU final cell densities of bacteria were
prepared and treated with the various disinfectant compounds
described in examples 1-17 at either 5 or 10 milligrams/liter total
chlorine concentration which was previously determined by titration
using a stock solution with sodium thiosulfate. Aliquots were
removed at several predetermined times, and the active halogen was
quenched by sterile 0.02 normal sodium thiosulfate. Serial
dilutions were made into sterile saline, and three 25 microliter
aliquots of each dilution were applied to the dried surface of a
Petri dish containing nutrient agar. After incubation at 37.degree.
C. for 48 hours, the three replicates for each dilution were
counted and averaged. Control samples containing no disinfectant,
or in some cases, unchlorinated precursor compounds, were handled
in the same manner. In all cases the two types of control
experiments yielded plates which contained confluent growth too
numerous to count indicating that the bacterial samples were
viable. Inactivation of the organism was considered to be at least
99.9999% when no colonies were detected in the thiosulfate-quenched
aliquots.
[0136] The data in Table II demonstrate that all of the soluble
N-halamine biocidal compounds tested were effective at inactivating
S. aureus in less than 10 minutes.
2TABLE II Biocidal Effects of the N-Halamine Compounds Contact Time
for 6-log Inactivation Compound.sup.a pH Temperature (.degree.C.)
of S. aureus (min). 1a-Cl 7.0 22 <5 1a-Br 7.0 22 <5 2a 7.0 22
<5 3g 7.0 22 5-10 4c 7.0 22 5-10 4d 7.0 22 5-10 .sup.a1a-Cl =
3-chloro-4-(acryloxymethyl)-4-ethyl-2- -oxazolidinone 1a-Br =
3-bromo-4-(acryloxymethyl)-4-ethyl-2-oxazo- lidinone 2a =
poly-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolid- inone 3g =
poly-vinyl acetate-co-3-chloro-4-(acryloxymethyl)-4-et-
hyl-2-oxazolidinone latex 4c = poly-vinyl alcohol-g-3-chloro-4-(a-
cryloxymethyl)-4-ethyl-2-oxazolidinone 4d = poly-vinyl
acetate-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone
Example 21
Preparation of Surface Films and Coatings
[0137] Unchlorinated poly N-halamine compounds described in
examples 5-17 were cast into thin films on various surfaces and
then chlorinated to determine the biocidal efficacy of these
disinfectant surfaces. The general method for coating granular
polymeric materials on to various substrates is as follows. 1.0
gram of the unchlorinated polymer was dissolved in 50 milliliters
of an appropriate solvent and the solution filtered to remove any
undissolved polymer particles. The substrate to be coated was
washed, autoclaved, and dried at 100.degree. C. before the polymer
solution was added. Enough of the polymeric solution was added to
coat the surface of the substrate without running over the sides;
then the material with the polymer solution coating it was heated
in an oven set between 80-100.degree. C. until the solvent was
removed. In all cases, the coating was clear, tough, resistant to
abrasion, and had good adherence to the substrate. Once coated, the
surface was chlorinated with a diluted solution of sodium
hypochlorite (3000 ppm free chlorine) by soaking the surface in the
aqueous solution for 20 minutes. The surface was then removed,
washed with synthetic chlorine-demand-free water, and dried at room
temperature overnight to ensure all residual sodium hypochlorite
was removed.
[0138] For the case in which an emulsion or latex was used, the
emulsified solution was added directly to the substrate, prepared
in the same manner as described above, and heated to remove the
solvent, water, as well as coalesce the polymer particles to form
the coating. The chlorination of the coating was done in the same
manner as described above.
Example 22
Efficacies of Poly N-Halamine Surfaces Against Staphylococcus
aureus
[0139] The surfaces to be tested for biocidal activity against S.
aureus (ATCC 6538) were applied to a circular glass coverslip
measuring 12 millimeters in diameter. The surfaces were chlorinated
in the same manner as mentioned in example 21. 50 microliters of a
10.sup.6 CFU solution of S. aureus were placed on the surface, and
a 25 microliter aliquot was removed at a predetermined time, and
the active halogen was quenched by sterile 0.02 normal sodium
thiosulfate. The aliquot was then applied to the dried surface of a
Petri dish containing nutrient agar. After incubation at 37.degree.
C. for 48 hours, the bacteria were counted. Control samples
containing no disinfectant, or in some cases, unchlorinated
precursor surfaces, were handled in the same manner. In all cases
the two types of control experiments yielded plates which contained
confluent growth too numerous to count indicating that the
bacterial samples were viable. Inactivation of the organism was
considered to be at least 99.9999% when no colonies were detected
in the thiosulfate-quenched aliquots.
[0140] The data in Table III demonstrate that all of the N-halamine
biocidal compounds tested were effective at inactivating S. aureus
on a glass surface.
3TABLE III Biocidal Effects of the N-Halamine Surfaces Contact Time
for Chlorination 6-log Inactivation Compound.sup.a Time (min) Age
(Days).sup.b of S. aureus (min) 3d 20 5 10-20 3g 10 12 5-10 4c 20
60 5-10 4d 10 20 5-10 4e 30 3 30-60 .sup.a3d =
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethy-
l-2-oxazolidinone latex 3g = poly-vinyl acetate-co-3-chloro-4-(ac-
ryloxymethyl)-4-ethyl-2-oxazolidinone latex 4c = poly-vinyl
alcohol-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone 4d =
poly-vinyl
acetate-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinon- e 4e
= poly-vinyl chloride-g-3-chloro-4-(acryloxymethyl)-4-ethyl--
2-oxazolidinone .sup.bTime in days elapsing between sample
synthesis and biocidal test run with storage at room
temperature.
Example 23
Poly N-Halamine Zone of Inhibition Studies for Fabrics
[0141] Zone of inhibition studies were performed for fabric
materials coated with various poly N-halamines described in
examples 9-18 with the coating and chlorination protocol used in
example 21. The coated fabric samples were cut into 1-1.5 cm
squares prior to chlorination and dried thoroughly after
chlorination, and they were placed on a Tryptic Soy agar plate
which was inoculated with Staphylococcus aureus (ATCC 6538). The
plates were incubated for 24 hours at 37.degree. C. The zones of
inhibition were measured, and the results are tabulated in Table
IV. The bacteria were not able to colonize on the fabric samples,
and small zones of inhibition were produced around them.
4TABLE IV Zones of Inhibition of Poly N-Halamines Polymer.sup.a
Fabric Material.sup.b % Weight Increase Zone in mm.sup.c 3d
Printcloth 15.6 0.5 3d Cotton 20.3 1.0 3e Printcloth 25.1 0.1 3e
Cotton 30.3 0.2 3f Printcloth 30.1 0.5 3g Printcloth 23.2 0.5 4a
Printcloth 19.5 0.8 4a Cotton 26.2 1.2 4b Printcloth 13.5 0.3 4c
Printcloth 30.2 0.5 4c Cotton 36.1 1.0 4e Printcloth 15.7 0.1 4e
Cotton 20.6 0.1 .sup.a3d =
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone
latex 3e = poly-vinyl chloride-co-3-chloro-4-(acryloxymethyl)-4-e-
thyl-2-oxazolidinone latex 3f = poly-styrene-co-3-chloro-4-(acrylo-
xymethyl)-4-ethyl-2-oxazolidinone latex 3g = poly-vinyl
acetate-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone
latex 4a =
poly-acrylonitrile-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazol-
idinone 4b = poly-styrene-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2--
oxazolidinone 4c = poly-vinyl alcohol-g-3-chloro-4-(acryloxymethyl-
)-4-ethyl-2-oxazolidinone 4e = poly-vinyl chloride-g-3-chloro-4-(a-
cryloxymethyl)-4-ethyl-2-oxazolidinone .sup.bPrintcloth comprises a
54/46 cotton/polyester blend. .sup.cLength in mm from the edge of
the fabric to the viable bacteria.
Example 24
Efficacies of Poly N-Halamines on Fabric Against Salmonella
enteritidis
[0142] Fabric materials coated with various poly N-halamines
described in examples 9-18 containing the coating and chlorination
protocol used in example 21 were challenged with the bacterium
Salmonella enteritidis according to protocol #100 of the American
Association of Textile Chemists and Colorants (AATCC), slightly
modified to accommodate small sample size. In this test procedure,
each fabric sample was prepared as a disc of diameter 1.0
centimeter and challenged with 100 microliters of a suspension
containing 106 colony forming units (CFU) of the bacteria for a
contact time of 10 minutes at ambient temperature. Control samples
coated with unchlorinated polymers were similarly challenged. At
the end of the incubation period each sample was immersed in 10
milliliters of 0.02 normal sodium thiosulfate solution in a 50
milliliter test tube to quench chlorine biocidal action and was
agitated vigorously for 60 seconds. Aliquots of 100 microliters
were removed from the tubes, serially diluted in sterile water, and
plated in duplicate on 10 centimeter diameter Trypticase-Soy agar
plates for 24 hours at 37.degree. C. The numbers of colony forming
units of surviving bacteria present in the eluates were determined,
and compared to the total numbers detected in the eluates from the
corresponding challenged control samples, to establish the percent
reduction brought about by each of the chlorinated polymers. The
data are tabulated in Table V. The three polymer coatings tested
were clearly effective at significantly reducing the numbers of CFU
of Salmonella enteritidis over a 10 minute contact period.
5TABLE V Reduction of S. enteritidis Caused by Poly N-Halamines on
Fabric % Dry Weight % Reduction of Polymer.sup.a Fabric
Material.sup.b Gain on Fabric enteritidis in 10 min. 3d Printcloth
20.3 97.0 3g Printcloth 18.5 99.99 4c Printcloth 22.3 99.9 .sup.a3d
=
poly-acrylonitrile-co-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone
latex 3g = poly-vinyl acetate-co-3-chloro-4-(acryloxymethyl)-4-et-
hyl-2-oxazolidinone latex 4c = poly-vinyl alcohol-g-3-chloro-4-(ac-
ryloxymethyl)-4-ethyl-2-oxazolidinone .sup.bPrintcloth comprises a
54/46 cotton/polyester blend.
Example 25
Efficacies of Poly N-Halamine Coatings Against Pseudomonas
aeruginosa in Flowing Water
[0143] N-halamine polymers 3 g (poly-vinyl
acetate-co-3-chloro-4-(acryloxy- methyl)-4-ethyl-2-oxazolidinone
latex) and 4e (poly-vinyl
chloride-g-3-chloro-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone)
were coated onto the surfaces of pieces of polyurethane medical
catheters as substrates using procedures discussed in example 21.
Analogous unchlorinated samples were also prepared to be used as
controls. The samples which were approximately 2 to 3 square
millimeters in surface area and 150 micrometers thick were placed
in coarse mesh histological specimen bags in a 15 milliliter
chamber through which a suspension of Pseudomonas aeruginosa
(10.sup.5 CFU per milliliter) was flowed constantly at a rate of
approximately 200 milliliters per day for a total of three days.
Samples were removed at 24 hour intervals, fixed in 4%
glutaraldehyde for 2 hours, dehydrated by exposure to ethanol
rinses, coated with gold (20 nanometers) using a Sputter Coater
Model SC500, and subjected to analysis using a JEOL Scanning
Electron Microscope for comparison of the extent of adherence of
the Pseudomonas organisms to the test and control surfaces. At each
test period the bacteria were observed to be adherent in increasing
numbers to the control sample surfaces, so that by 72 hours there
was extensive slime formation over the entire surface as a
homogeneous layer. In contrast, no biofilm formation occurred on
the chlorinated test sample at any observation point. A few
colonies of Pseudomonas were adherent on the 4e surfaces after 72
hours, but the 3 g surface was almost entirely free of bacteria at
this sampling time. It may be concluded from these data that
surfaces treated with certain N-halamine polymers can effectively
inhibit biofilm formation by Pseudomonas aeruginosa (an important
biofilm-forming contaminant in aqueous flow systems in industry and
medicine) for up to 72 hours.
Example 26
Use of Grafted Copolymer 4c as a Preservative Biocide in
Emulsions
[0144] Samples of poly-vinyl
alcohol-g-4-(acryloxymethyl)-4-ethyl-2-oxazol- idinone which is the
precursor for the chlorinated copolymer 4c were tested for efficacy
at preventing biofouling in poly-vinyl alcohol, which is used as an
emulsifier in various emulsions, paints, and coatings. 5.0 grams of
a 10% aqueous poly-vinyl alcohol solution and 5.0 grams poly-vinyl
alcohol-g-4-(acryloxymethyl)-4-ethyl-2-oxazolidinone were spiked
with 0.5 milliliters of a diluted aqueous solution of sodium
hypochlorite and were loosely covered and allowed to stand at room
temperature. The samples were inspected periodically to determine
if any viable bacteria were apparent. It was found that after three
months the ungrafted poly-vinyl alcohol had severe biofouling,
while the grafted copolymer had none; in fact, the grafted
poly-vinyl alcohol showed no biofouling for up to six months at
which time the experiment was concluded. Therefore polymer 4c
should be effective as a preservative at low concentration for
emulsions which do not contain reducing agents such as bisulfites,
thiosulfates, etc.
Example 27
Preparation of 3-(acryloxymethyl)-5,5-dimethylhydantoin and its
1-chloro Derivative
[0145] To a three-neck round bottom flask equipped with a
condenser, an addition funnel and a gas inlet, were added 100
milliliters of chloroform, 15.8 grams (0.10 mole)
3-hydroxymethyl-5,5-dimethylhydantoin (TCI Co., recrystallized from
ethyl acetate), and 10.1 grams (0.101 mole) freshly distilled
triethylamine. To the mixture in an ice bath, 10.08 grams (0.101
mole) acryloyl chloride in 30 milliliters chloroform were added
dropwise while the reaction mixture was held under N.sub.2
atmosphere. After addition in about 30 minutes, the ice bath was
removed, and the mixture was stirred at room temperature for 3
hours. The solvent was removed under reduced pressure, and 100 ml
ethyl acetate were added to the residue with stirring. The white
solid was filtered off, and the ethyl acetate solution was washed
with 0.02 N HCl solution, 10% NaHCO.sub.3 solution, saturated NaCl
solution, and then dried over anhydrous Na.sub.2SO.sub.4. The
solvent was removed under reduced pressure to give 19.05 grams (90%
of the yield theoretically expected)
3-acryloxymethyl-5,5-dimethylhydantoin as a clear oil. The product
exhibited the following spectral data: .sup.1H NMR (DMSO-d.sub.6) *
1.31 (s, 6H), 5.43 (s, 2H), 5.95-6.41 (m, 3H), 8.61 (s, 1H);
.sup.13C NMR (DMSO-d.sub.6) * 24.5, 58.0, 61.6, 127.4, 132.9,
153.5, 164.4, 176.6; IR (NaCl) 3341, 2982, 1738, 1456, 1250, 1163
cm.sup.-1; MS m/z .sup.21.sup.2. 1.05 grams (0.005 mole) of
3-acryloxymethyl-5,5-dimethylhy- dantoin prepared as described
above, 1.10 grams (0.01 mole) tertiary butyl hypochlorite, and 10
milliliters methylene chloride were added to a round bottom flask
and sealed. The solution was stirred at room temperature for 30
minutes and the solvent removed under reduced pressure. 1.23 grams
(100% of that theoretically expected)
1-chloro-3-(acryloxymethyl)-5,5-dim- ethylhydantoin was obtained as
a yellow clear oil. The product had the following spectral data:
.sup.1H NMR (CDCl.sub.3) * 1.49 (s, 6H), 5.60 (s, 2H), 5.90-6.50
(m, 3H); .sup.13C NMR(CDCl.sub.2) * 24.7, 59.0, 61.7, 127.3, 132.2,
154.6, 164.8, 176.4; IR (NaCl) 3347, 2978, 1751, 1416, 1173
cm.sup.-1.
Example 28
Preparation of
3-(2'-methylacryloxymethyl)-5,5-dimethylhydantoin
[0146] 15.80 grams (0.10 mole)
3-hydroxymethyl-5,5-dimethylhydantoin, 100 milliliters of
chloroform, and 10.1 grams (0.101 mole) freshly distilled
triethylamine were mixed in a three-neck round bottom flask
equipped with a condenser, an addition funnel and a nitrogen inlet.
To the mixture in an ice bath, 11.50 grams (0.101 mole)
2-methylacryloyl chloride in 30 milliliters chloroform were added
dropwise while the reaction mixture was held under N.sub.2
atmosphere. After addition in about 30 minutes, the ice bath was
removed, and the mixture was stirred at room temperature for 3
hours. The solvent was removed under reduced pressure, and 100 ml
ethyl acetate were added to the residue with vigorous stirring. The
solid was filtered off, and the ethyl acetate solution was washed
with 0.02 N HCl solution, 10% NaHCO.sub.3 solution, saturated NaCl
solution, and then dried over anhydrous Na.sub.2SO.sub.4. The
solvent was removed under reduced pressure to give 20.52 grams (91%
of that theoretically expected) of pure product as a clear oil. The
product exhibited the following spectral data: .sup.1H NMR
(DMSO-d.sub.6) * 1.26 (s, 6H), 1.93 (s, 3H), 5.60 (s, 2H), 5.64 (s,
1H), 6.12 (s, 1H), 7.06 (s, 1H); .sup.13C NMR (DMSO-d.sub.6) *
17.7, 24.5, 56.2, 62.0, 126.8, 135.3, 153.7, 172.1, 176.7; IR
(NaCl) 3351, 2985, 1734, 1456, 1149 cm.sup.-1; MS m/z 226.
Example 29
Preparation of poly-3-(acryloxymethyl)-5,5-dimethylhydantoin
[0147] 2.12 grams (0.01 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin, as prepared in example
27, 0.01 gram (6.times.10.sup.-5 mole) 2,2'-azobisisobutyronitrile,
and 10 milliliters anhydrous N,N-dimethylformamide were placed in a
two-neck round bottom flask. The reaction mixture was purged with
nitrogen for 15 minutes, and the flask was sealed and heated to
60.degree. C. for 10 hours with stirring. The solution was cooled
to room temperature and the polymer precipitated in 250 milliliters
water. The polymer was filtered off, redissolved in
N,N-dimethylformamide, and reprecipitated in water two more times.
The resulting solid was filtered and dried in a vacuum oven to give
2.02 grams (95% of the yield theoretically expected) pure product
as a white solid. The product,
poly-3-(acryloxymethyl)-5,5-dimethylhydantoin, exhibited the
following spectral data: .sup.1H NMR (DMSO-d.sub.6) * 1.31, 2.22,
5.35, 8.40; .sup.13C NMR (DMSO-d.sub.6) * 24.4, 35.8, 56.1, 57.9,
61.2, 153.5, 172.5, 176.4; IR (KBr) 3341, 2982, 1738, 1456
cm.sup.-1.
Example 30
Preparation of
poly-acrylonitrile-co-1-halo-3-(acryloxymethyl)-5,5-dimethy-
lhydantoin (30-Cl, 30-Br)
[0148] 1.06 grams (0.005 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin, as prepared in example
27, 4.24 grams (0.08 mole) acrylonitrile, 0.03 grams
(1.83.times.10.sup.-4 mole) 2,2'-azobisisobutyronitrile, and 15
milliliters anhydrous N,N-dimethylformamide were placed in a
two-neck round bottom flask. The reaction mixture was purged with
nitrogen for 15 minutes, and the flask was sealed and heated to
65.degree. C. for 10 hours with stirring. The solution was cooled
to room temperature and the polymer precipitated in 250 milliliters
water. The polymer was filtered off, redissolved in
N,N-dimethylformamide, and reprecipitated in water two more times.
The resulting solid was filtered and dried in a vacuum oven to give
4.82 grams (90% of the yield theoretically expected) pure product
as a white solid. The product, poly-acrylonitrile-co-3-(acryloxym-
ethyl)-5,5-dimethylhydantoin, exhibited the following spectral
data: .sup.1H NMR (DMSO-d.sub.6) .delta.1.33, 2.09, 3.14, 3.35,
5.46, 8.60;
[0149] .sup.13C NMR (DMSO-d.sub.6) .delta. 14.1, 20.7, 25.1, 59.8,
63.8, 115.2, 122.0, 126.7, 149.9, 156.3, 164.2, 170.4, 176.9; IR
(KBr) 3377, 2938, 2243, 1777, 1732, 1456 cm.sup.-1. 1.0 gram
poly-acrylonitrile-co-3-- (acryloxymethyl)-5,5-dimethylhydantoin,
prepared as described above and 50 milliliters 1.0 normal sodium
hydroxide were added to an Erlenmeyer flask. The stirred,
heterogeneous mixture was cooled in an ice bath until the
temperature was 10.degree. C. Chlorine gas (Matheson Gas Co.,
Montgomeryville, Pa.) was bubbled into the solution slowly so that
the temperature did not exceed 15.degree. C. Once the pH of the
solution reached 7.0, the chlorine gas flow was stopped, and the
mixture was stirred for 30 more minutes. The mixture was allowed to
come to room temperature and was vacuum filtered. The resulting
solid was washed with 200 milliliters distilled water and was air
dried to give 1.0 gram
poly-acrylonitrile-co-1-chloro-3-(acryloxymethyl)-5,5-dimethylhydantoin
(30-Cl) as a white solid. The product exhibited the following
spectral data: IR (KBr) 2938, 2244, 1788, 1734, 1456 cm.sup.-1.
[0150] 1.0 gram
poly-acrylonitrile-co-3-(acryloxymethyl)-5,5-dimethylhydan- toin,
prepared as described above, and 50 milliliters 1.0 normal sodium
hypobromite were stirred at room temperature for 30 minutes in a
sealed flask. The solution was then filtered and the solid washed
with 200 milliliters distilled water and dried to give 1.0 gram
poly-acrylonitrile-co-1-bromo-3-(acryloxymethyl)-5,5-dimethylhydantoin
(30-Br) as a pale yellow solid. The product exhibited the following
spectral data: IR (KBr) 2937, 2244, 1786, 1733, 1456 cm.sup.-1.
Example 31
[0151] Preparation of Poly-methyl
methacrylate-co-1-chloro-3-(acryloxymeth- yl)-5,5-dimethylhydantoin
(31-Cl)
[0152] A copolymerization was performed with 1.0 gram
(4.7.times.10.sup.-3 mole) of
3-(acryloxymethyl)-5,5-dimethylhydantoin and 4.0 grams (0.04 mole)
of methyl methacrylate using the procedure employed which was
identical to that discussed in example 30. The yield of poly-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin was 92% of
that theoretically expected. The product exhibited prominent
infrared bands in a KBr pellet at 3446, 2952, 1734, 1456, 1149
cm.sup.-1.
[0153] Chlorination of the above sample in the manner analogous to
that discussed in example 30 produced poly-methyl
methacrylate-co-1-chloro-3-(- acryloxymethyl)-5,5-dimethylhydantoin
(5-Cl) in 100% yield with prominent infrared bands in a KBr pellet
at 2952, 1791, 1734, 1457, 1149 cm.sup.-1. The bromination can be
done in the same manner described in example 30.
Example 32
Preparation of poly-vinyl
acetate-co-3-(acryloxymethyl)-5,5-dimethylhydant- oin
[0154] A copolymerization was performed with 1.0 gram
(4.7.times.10.sup.-3 mole) of
3-(acryloxymethyl)-5,5-dimethylhydantoin and 4.0 grams (0.046 mole)
of vinyl acetate using the procedure employed which was identical
to that discussed in example 30. The yield of poly-vinyl
acetate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin was 86% of that
theoretically expected. The product exhibited prominent infrared
bands in a KBr pellet at 3355, 2980, 1740, 1240, 1022
cm.sup.-1.
Example 33
Preparation of
poly-acrylonitrile-co-3-(acryloxymethyl)-5,5-dimethylhydant- oin by
emulsion polymerization
[0155] 4.2 grams (0.02 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin, prepared identically to
that discussed in example 27, 10.0 grams (0.190 mole)
acrylonitrile, 30 milliliters deionized water, and 0.20 grams
(6.94.times.10.sup.-4 mole) sodium lauryl sulfate were added to a
three-neck round bottom flask equipped with a gas inlet and reflux
condenser. The solution was stirred and heated at 60.degree. C. and
purged with nitrogen for ten minutes. A solution of 0.025 grams
(9.26.times.10.sup.-5 mole) potassium persulfate and 1.0 milliliter
water was prepared and added in the reaction mixture after the
nitrogen purge was completed. The reaction was stirred for eight
hours and then cooled to room temperature. Any precipitated polymer
was allowed to settle, and the latex was decanted off. The polymer
can be isolated by pouring the latex into 150 milliliters of water,
then slowly adding salt with stirring to coagulate the emulsion.
The polymer was collected by filtration, washed with water, and
dried at room temperature. The product
poly-acrylonitrile-co-3-(acryloxymethyl)-5,5-dimethylhydantoin was
produced in 91% yield with infrared bands in a KBr pellet at 3375,
2938, 2243, 1732, 1456 cm.sup.-1.
Example 34
Preparation of poly-ethyl
acrylate-co-styrene-co-3-(acryloxymethyl)-5,5-di- methylhydantoin
latex
[0156] 4.2 grams (0.02 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin, prepared identically to
that discussed in example 27, 8.0 grams (0.08 mole) ethyl acrylate,
2.1 grams (0.02 mole) styrene, 30 milliliters deionized water, and
0.20 grams (6.94.times.10.sup.-4 mole) sodium lauryl sulfate were
added to a three-neck round bottom flask equipped with a gas inlet
and reflux condenser. The solution was stirred and heated at
60.degree. C. and purged with nitrogen for ten minutes. A solution
of 0.025 grams (9.26.times.10.sup.-5 mole) potassium persulfate and
1.0 milliliter water was prepared and added in the reaction mixture
after the nitrogen purge was completed. The reaction was stirred
for eight hours and then cooled to room temperature. Any
precipitated polymer was allowed to settle, and the latex was
decanted off. The polymer can be isolated by pouring the latex into
150 milliliters of water, then slowly adding salt with stirring to
coagulate the emulsion. The polymer was collected by filtration,
washed with water, and dried at room temperature. The product
poly-ethyl
acrylate-co-styrene-co-3-(acryloxymethyl)-5,5-dimethylhydantoi- n
was produced in 96% yield with infrared bands in a KBr pellet at
3380, 3058, 2924, 1773, 1738, 1453 cm.sup.-1.
Example 35
Preparation of poly-vinyl acetate-co-methyl
methacrylate-co-3-(acryloxymet- hyl)-5,5-dimethylhydantoin
latex
[0157] An emulsion copolymerization was performed with vinyl
acetate (8.6 grams, 0.10 mole) and methyl methacrylate (4.0 grams,
0.04 mole) and 3-(acryloxymethyl)-5,5-dimethylhydantoin (4.2 grams,
0.02 mole) using the procedure employed which was identical to that
discussed in example 34. The yield of poly-vinyl acetate-co-methyl
methacrylate-co-3-(acryloxymeth- yl)-5,5-dimethylhydantoin was 93%
of that theoretically expected. The product had infrared bands in a
KBr pellet at 3365, 2980, 1740, 1240 cm.sup.-1.
Example 36
Preparation of poly-vinyl acetate-co-butyl
acrylate-co-3-(acryloxymethyl)-- 5,5-dimethylhydantoin latex
[0158] An emulsion copolymerization was performed with vinyl
acetate (8.6 grams, 0.10 mole) and butyl acrylate (2.6 grams, 0.02
mole) and 3-(acryloxymethyl)-5,5-dimethylhydantoin (4.2 grams, 0.02
mole) using the procedure employed which was identical to that
discussed in example 34. The yield of poly-vinyl acetate-co-butyl
acrylate-co-3-(acryloxymethyl)-5- ,5-dimethylhydantoin was 91% of
that theoretically expected. The product had infrared bands in a
KBr pellet at 3370, 2975, 1734, 1457 cm.sup.-1.
Example 37
Preparation of
poly-acrylonitrile-g-3-(acryloxymethyl)-5,5-dimethylhydanto- in
[0159] 2.1 grams (0.01 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin, prepared identically to
that discussed in example 27, 10 grams poly-acrylonitrile latex
which was prepared from acrylonitrile using the method described by
Hayes, R. A., J. Polymer Sci. 11:531 (1967), and 20 milliliters of
water, were added to a three-neck round bottom flask. The reagents
were purged with nitrogen for fifteen minutes; the flask was then
sealed and heated to 60.degree. C. with stirring. Once the internal
temperature reached 60.degree. C., 0.05 grams (1.9.times.10.sup.-4
mole) sodium persulfate dissolved in 1.0 milliliter water was added
into the reaction mixture. The reaction mixture was heated and
stirred for twelve hours, then cooled to room temperature. The
solution was poured into 150 milliliters of a saturated sodium
chloride solution, and the solid was collected by filtration and
extracted with 200 milliliters boiling 50/50 DMF/water. The
resulting solid was refiltered and air dried to give 5.0 grams
product,
poly-acrylonitrile-g-3-(acryloxymethyl)-5,5-dimethylhydant- oin
which exhibited prominent infrared bands in a KBr pellet at 3377,
2938, 2243, 1730 cm.sup.-1.
Example 38
Preparation of poly-vinyl
alcohol-g-3-(acryloxymethyl)-5,5-dimethylhydanto- in
[0160] 5.0 grams poly-vinyl alcohol (molecular weight 85000-146000)
dissolved in 30 milliliters deionized water and 2.10 grams (0.01
mole) 3-(acryloxymethyl)-5,5-dimethylhydantoin, prepared
identically to that discussed in example 27, were added to a
three-neck round bottom flask. The mixture was purged with nitrogen
for fifteen minutes; the flask was then sealed and heated to
60.degree. C. with stirring. Once the internal temperature reached
60.degree. C., 0.05 grams (1.9.times.10.sup.-4 mole) sodium
persulfate dissolved in 1.0 milliliter water was added into the
reaction mixture. The reaction mixture was heated and stirred for
twelve hours to give poly-vinyl
alcohol-g-3-(acryloxymethyl)-5,5-dimethylhydanto- in latex.
Example 39
Preparation of
cellulose-g-3-(acryloxymethyl)-5,5-dimethylhydantoin
[0161] 1.00 gram cellulose and 50.0 milliliters 0.05 normal nitric
acid were placed in an Erlenmeyer flask and stirred for 30 minutes
at 30.degree. C. under nitrogen. 1.06 grams (0.005 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin, prepared identically to
that discussed in example 27, were added, and the mixture was
stirred for another 15 minutes; then 0.11 grams (2.0.times.10.sup.4
mole) ammonium ceric nitrate was added to the reaction. A
continuous supply of nitrogen was maintained throughout the
reaction time of 30 minutes, at which time the polymerization was
complete, and the product was filtered off. The solid was washed
with distilled water and then acetone and dried in an oven to give
1.09 grams of cellulose-g-3-(acryloxymethyl)-5,5-dimethylhyd-
antoin. The percentage add-on is 9%.
Example 40
Efficacies of the Poly N-halamine Compounds against Staphylococcus
aureus
[0162] Solid samples of the polymeric N-halamine compounds
described in examples 30 and 31 were packed into glass Pasteur
pipettes (5.75 inches long, 0.25 inches inside diameter) at a
length of 1.0 inch. The samples were washed with pH 7.0 aqueous
solution and then 10.sup.6 CFU per milliliter of Staphylococcus
aureus (ATCC 6538) were added to the pipette, and the inoculum was
allowed to pass through the packed column using gravity feed. The
effluent from each sample was collected, and a 25.0 .mu.L aliquot
was quenched with an equal volume of 0.02 N sodium thiosulfate. A
25.0 uL sample of the mixture was plated on nutrient agar. The bulk
bacteria solution was recycled through the columns. This procedure
was repeated typically 6 times which allowed for an assessment of
biocidal contact time. The plated samples were incubated at
37.degree. C. for 48 hours and then examined for viable growth.
Control samples consisted of plating aliquots of the bacterial
suspension before passing through the biocidal polymer columns, and
of passing the bacteria through columns containing unchlorinated
precursor polymer samples. In all cases the two types of control
experiments yielded plates which contained confluent growth too
numerous to count indicating that the bacterial samples were viable
and that the organisms were not simply eliminated by filtration
upon passing through the samples. Results are tabulated in Table
VI. They demonstrate that the materials were biocidal.
6TABLE VI Biocidal Effects of the N-halamine Polymers Contact time
Column for 6-log Length Inactivation of Polymers.sup.a Mesh Size
(Inches) Age (Days).sup.b S. aureus (min) 30-Cl 30-60 1.0 1 <0.9
30-Cl 30-60 1.0 60 1.5-2.3 30-Br 30-60 1.0 1 <0.9 31-Cl 30-60
1.0 1 1.0-1.3 31-Cl 30-60 1.0 60 1.8-2.4 .sup.a30-Cl =
poly-acrylonitrile-co-1-chloro-3-(acryloxymethyl)-5,5-dim-
ethylhydantoin 30-Br = poly-acrylonitrile-co-1-bromo-3-(acryloxyme-
thyl)-5,5-dimethylhydantoin 31-Cl = poly-methyl
methacrylate-co-1-chloro-3-(acryloxymethyl)-5,5-dimethylhydantoin
.sup.bTime in days elapsing between sample synthesis and biocidal
test run with storage at room temperature.
Example 41
Preparation of Films and Surface Coatings
[0163] Unchlorinated poly N-halamine compounds described in
examples 32-38 were cast into thin films on various surfaces and
then chlorinated so as to determine the biocidal efficacy of these
disinfectant surfaces. The general method of film forming is as
follows. 1 gram of the unchlorinated polymer was dissolved in about
10 milliliters of an appropriate solvent. The solution was added to
cover the pre-cleaned surface of substrate without running over the
sides. The solvent was evaporated in air, and the substrate was
heated in an oven until the solvent was completely removed and dry
coating resulted. In all cases, the coating was clear, tough,
resistant to abrasion, and had good adherence to the substrate.
Once coated, the surface was chlorinated with a diluted solution of
sodium hypochlorite (3000 ppm free chlorine) by soaking in the
aqueous solution for 1 hour. The surface was then removed, washed
with chlorine-demand-free water, and air dried at room temperature
to ensure all residual sodium hypochlorite was removed.
[0164] For the case in which an emulsion or latex was used, the
emulsified solution was added directly to the substrate and heated
in the oven to remove the solvent, water, as well as coalesce the
polymer particles to form the coating. The chlorination of the
coating was done in the same manner as described above.
Example 42
Efficacies of Poly N-halamine Surfaces Against Staphylococcus
aureus
[0165] The surfaces to be tested for biocidal activity against S.
aureus (ATCC 6538) were applied to a square microscope glass slide.
The surfaces were chlorinated in the same manner as mentioned in
example 41. 50 microliters of a 10.sup.6 CFU solution S. aureus
were placed on the surface, and a 25 microliters aliquot was
removed at a predetermined time, and the active halogen was
quenched by sterile 0.02 normal sodium thiosulfate. The mixture was
then applied to the dried surface of a Petri dish containing
nutrient agar. After incubation at 37.degree. C. for 48 hours, the
bacteria were counted. Control samples containing no disinfectant,
or in some cases, unchlorinated precursor surfaces, were handled in
the same manner. In all cases the two types of control experiments
yielded plates which contained confluent growth too numerous to
count indicating that the bacteria samples were viable.
[0166] The data in Table VII demonstrate that all of the N-halamine
biocidal polymers tested effectively deactivated S. aureus on a
glass substrate.
7TABLE VII Biocidal Effects of the N-halamine Surfaces the Number
of Chlorination Contact log Inactivation Polymer.sup.a Time (min)
Age (days).sup.b Time (min) of S. aureus 32 30 1 30 >4.1 33 30 1
30 >4.1 34 30 1 30 >4.1 35 30 1 30 >4.1 36 30 1 30 >4.1
37 30 1 30 >4.1 38 30 1 30 >4.1 .sup.a32 = poly-vinyl
acetate-co-3-(acryloxymethyl)-5,5-dimethylhydantoi- n 33 =
poly-acrylonitrile-co-3-(acryloxymethyl)-5,5-dimethylhydant- oin 34
= poly-ethyl acrylate-co-styrene-co-3-(acryloxymethyl)-5,5--
dimethylhydantoin latex 35 = poly-vinyl acetate-co-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin latex 36 =
poly-vinyl acetate-co-butyl
acrylate-co-3-(acryloxymethyl)-5,5-dimethyl- hydantoin latex 37 =
poly-acrylonitrile-g-1-chloro-3-(acryloxymeth-
yl)-5,5-dimethylhydantoin 38 = poly-vinyl alcohol-g-1-chloro-3-(ac-
ryloxymethyl)-5,5-dimethylhydantoin .sup.bTime in days elapsing
between sample synthesis and biocidal test run with storage at room
temperature.
Example 43
Zone of Inhibition Study of Sample 39
[0167] The sample 39,
cellulose-g-3-(acryloxymethyl)-5,5-dimethylhydantoin (1 cm.times.1
cm), was chlorinated by soaking in 2% NaOCl aqueous solution for
one hour, washed thoroughly with chlorine-demand-free water, and
then air dried. A piece of 1 cm square of this sample was placed on
a Tryptic Soy agar plate which was inoculated with Staphylococcus
aureus (ATCC 6538). The plate was incubated for 24 hours at
37.degree. C. The zone of inhibition was distinct, and it was
measured to be 1.2 mm from the edge of the sample to the viable
bacteria.
Example 44
Preparation of Thermosetting Coatings
[0168] A 250 mL three-neck flask was equipped with condenser,
dropping funnel, nitrogen inlet, and stirrer. It was flushed with
nitrogen, and 40 mL methyl ethyl ketone were added. A batch
containing 3.50 g (3.50.times.10.sup.-2 mole) methyl methacrylate,
1.72 g (1.48.times.10.sup.-2 mole) 2-hydroxyethyl acrylate, 6.64 g
(3.10.times.10.sup.-2 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin (prepared as described in
EXAMPLE 27), and 0.20 g (1.2.times.1O-3 mole)
2,2'-azobisisobutyronitrile was added to the dropping funnel. The
methyl ethyl ketone was brought to reflux under a light stream of
nitrogen, and the monomer-initiator batch was then added at a
constant rate over a period of 30 minutes. After the addition,
refluxing was continued for 3 hours. The solution was then allowed
to cool and weighed (44.14 g). A portion of the copolymer was
isolated by precipitation into ethanol, followed by filtration,
ethanol washing, and air drying. The copolymer, poly-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin-co-2-
-hydroxyethyl acrylate, exhibited the following spectra: .sup.1H
NMR (DMSO-d.sub.6) .delta. 0.74-0.99, 1.05, 1.31, 3.29-3.55, 4.36,
5.33, 8.49; .sup.13C NMR (DMSO-d.sub.6) .delta. 18.5, 24.4, 44.4,
51.6, 56.0, 57.9, 58.7, 61.1, 65.7, 153.4, 175.1, 176.3.
[0169] To a 10.0 g solution of the copolymer prepared as above,
0.42 g (1.678.times.10.sup.-3 mole) 4,4'-methylenebis(phenyl
isocyanate) and 0.10 g (7.41.times.10.sup.-4 mole)
dimethylbenzylamine were added. The mixture was stirred vigorously
for five minutes and then coated onto a glass slide. The sample was
allowed to dry in air and then heated in an oven at 90.degree. C.
for 2 hours. A clear, strong thermosetting coating resulted.
[0170] To a 10.0 g solution of the copolymer prepared as above,
0.28 g (1.678.times.10.sup.-3 mole) 1,6-diisocyanatohexane and 0.10
g (7.41.times.10.sup.-4 mole) dimethylbenzylamine were added. The
mixture was stirred vigorously for five minutes and then coated
onto a glass slide. The sample was allowed to dry in air and then
heated in an oven at 90.degree. C. for 2 hours. A clear, strong
thermosetting coating resulted from this treatment also.
[0171] As discussed above, a 250 mL three-neck flask was equipped
with condenser, dropping funnel, nitrogen inlet, and stirrer. It
was flushed with nitrogen, and 40 mL methyl ethyl ketone were
added. A batch containing 3.60 g (3.60.times.10.sup.-2 mole) methyl
methacrylate, 0.72 g (1.00.times.10.sup.-2 mole) acrylic acid, 6.12
g (2.89.times.10.sup.-2 mole)
3-(acryloxymethyl)-5,5-dimethylhydantoin, and 0.20 g
(1.2.times.10.sup.-3 mole) 2,2'-azobisisobutyronitrile was added to
the dropping funnel. The methyl ethyl ketone was brought to reflux
under a light stream of nitrogen, and the monomer-initiator batch
was then added at a constant rate over a period of 30 minutes.
After the addition, refluxing was continued for another 3 hours.
The solution was then allowed to cool and weighed (41.66 g). A
portion of the copolymer was isolated by precipitation into
ethanol, followed by filtration, ethanol washing, and air drying.
The copolymer, poly-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin-co-acrylic
acid, exhibited following spectra: .sup.1H NMR (DMSO-d.sub.6)
.delta. 0.74-1.05, 1.30, 1.58-2.20, 3.34-3.55, 4.36, 5.33, 8.51,
12.31; .sup.13C NMR (DMSO-d.sub.6) .delta. 7.7, 17.9, 18.5, 24.4,
44.3, 51.6, 56.1, 57.9, 61.1, 153.4, 175.8, 176.3.
[0172] To a 10.0 g solution of copolymer prepared as above, 0.30 g
(1.199.times.10.sup.-3 mole) 4,4'-methylenebis(phenyl isocyanate)
and 0.10 g (7.41.times.10.sup.-4 mole) dimethylbenzylamine were
added. The mixture was stirred vigorously for five minutes and then
coated onto a glass slide. The sample was allowed to dry in air and
then heated in an oven at 90.degree. C. for 2 hours. A clear,
strong thermosetting coating resulted.
[0173] To a 10.0 g solution of copolymer prepared as above, 0.20 g
(1.199.times.10.sup.-3 mole) 1,6-diisocyanatohexane and 0.10 g
(7.41.times.10.sup.-4 mole) dimethylbenzylamine were added. The
mixture was stirred vigorously for five minutes and then coated
onto a glass slide. The sample was allowed to dry in air and then
heated in an oven at 90.degree. C. for 2 hours. A clear, strong
thermosetting coating resulted.
[0174] All of the thermosetting coatings were activated for
biocidal testing by soaking the coated slides in 5% sodium
hypochlorite solution.
Example 45
Preparation of Polyurethane Materials
[0175] The monomer 4,4-dihydroxymethyl-2-oxazolidinone was
synthesized by a procedure similar to that reported by Horn, et al.
in U.S. Pat. No. 3,133,932, but with some modifications. To a 250
milliliter round-bottom flask were added 12.1 g (0.10 mole)
trishydroxymethylaminomethane, 6.0 g (0.10 mole) urea, and 50
milliliters N,N-dimethylformamide. The mixture was then refluxed at
160.degree. C. for 6 hours. The N,N-dimethylformamide solvent was
then removed by distillation, and 100 milliliters of ethyl acetate
were added to the residue with stirring. The solid product was
isolated by vacuum filtration and recrystallized from acetone. The
yield was 10.3 g (70%); the mp was 107-108.5.degree. C. 0.94 g
(5.48.times.10.sup.-3 mole) 1,6-diisocyanatohexane, 0.81 g
(5.48.times.10.sup.-3 mole) 4,4-dihydroxymethyl-2-oxazolidinone, 10
mL anhydrous N,N-dimethylformamide, and 0.20 g
(1.48.times.10.sup.-3 mole) N,N-dimethylbenzylamine were mixed in a
50 mL round-bottom flask. The mixture was heated in an oil bath at
90.degree. C. under reflux for 5 hours. After cooling to room
temperature, a portion of the solution was coated onto a glass
slide. The solvent was evaporated in air first and then in a vacuum
oven at 90.degree. C., and a clear, strong coating resulted. The
coating was activated for biocidal testing by soaking the slide in
5% sodium hypochlorite solution.
[0176] 0.735 g (5.0.times.10.sup.-3 mole)
4,4-dihydroxymethyl-2-oxazolidin- one, 1.714 g (1.0.times..sup.-2
mole) 1,6-diisocyanatohexane, 10 mL anhydrous
N,N-dimethylformamide, and 0.20 g (1.48.times.10.sup.-3 mole)
N,N-dimethylbenzylamine were mixed in a three-neck 50 mL round
bottom flask. The mixture was heated in an oil bath at 90.degree.
C. under reflux for 1 hour, and then 0.45 g (5.0.times.10.sup.-3
mole) 1,4-butanediol was added through an addition funnel. The
reaction was stirred for another 5 hours under reflux and then
cooled to room temperature. A portion of the solution was coated
onto a glass slide. The solvent was evaporated in air first and
then in a vacuum oven at 90.degree. C., and a clear, strong coating
resulted. The coating was activated by soaking in 5% sodium
hypochlorite solution.
Example 46
Efficacies of Poly N-halamine Coatings against Staphylococcus
aureus
[0177] The surface bactericidal tests were performed on the
theromosetting coatings and polyurethane coatings against S. aureus
in as discussed in Example 42. The results are tabulated in Table
VIII.
8TABLE VIII Biocidal Efficacies of the N-halamine Coatings
Chlorination Contact Log Reduction Coating.sup.a Time (min) Age
(days).sup.b Time (min) S. aureus 44a 30 1 30 3.7 44b 30 1 30 3.5
44c 30 1 30 2.0 44d 30 1 30 2.1 45a 60 1 60 >4.6 45b 60 1 60
>4.6 45a 60 7 60 >4.6 45b 60 7 60 >4.6 .sup.a44a =
Poly-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin-co-2-
-hydroxyethyl acrylate, crosslinked by reaction with
4,4'-methylenebis(phenyl isocyanate). 44b = Poly-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin-co-2-hydroxyethy-
l acrylate, crosslinked by reaction with 1,6-diisocyanatohexane.
44c = Poly-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoi-
n-co-acrylic acid, crosslinked by reaction with
4,4'-methylenebis(phenyl isocyanate). 44d = Poly-methyl
methacrylate-co-3-(acryloxymethyl)-
-5,5-dimethylhydantoin-co-acrylic acid, crosslinked by reaction
with 1,6-diisocyanatohexane. 45a = Polyurethane prepared from
4,4-dihydroxymethyl-2-oxazolidinone and 1,6-diisocyanatohexane. 45b
= Polyurethane prepared from 1,4-butanediol,
4,4-dihydroxymethyl-2-ox- azolidinone and 1,6-diisocyanatohexane.
.sup.bTime in days elapsing between sample synthesis and biocidal
test run with storage at room temperature.
[0178] As can be seen, the coatings were bactericidal against S.
Aureus.
Example 47
[0179] Efficacies of Poly N-halamine Coatings against E. coli The
surface bacterial tests were performed on the theromosetting
coatings and polyurethane coatings against E. coli using the
procedure discussed in Example 42. The results are tabulated in
Table IX.
9TABLE IX Biocidal Efficacies of the N-halamine Coatings
Chlorination Contact Log Reduction Coating.sup.a Time (min) Age
(days).sup.b Time (min) E. coli 44a 30 1 45 3.9 44c 30 1 45 1.5 45a
60 1 60 >4.7 45b 60 1 30 >4.8 .sup.a44a = Poly-methyl
methacrylate-co-3-(acryloxymethyl)-5,5-dimethylhydantoin-co-2-hydroxyethy-
l acrylate, crosslinked by reaction with 4,4'-methylenebis(phenyl
isocyanate). 44c = Poly-methyl methacrylate-co-3-(acryloxymethyl)-
-5,5-dimethylhydantoin-co-acrylic acid, crosslinked by reaction
with 4,4'-methylenebis(phenyl isocyanate). 45a = Polyurethane
prepared from 4,4-dihydroxymethyl-2-oxazolidinone and
1,6-diisocyanatohexane. 45b = Polyurethane prepared from
1,4-butanediol, 4,4-dihydroxymethyl-2-oxazolidinone and
1,6-diisocyanatohexane. .sup.bTime in days elapsing between sample
synthesis and biocidal test run with storage at room
temperature.
[0180] As can be seen, the coatings were bactericidal against E.
coli.
[0181] While the preferred embodiment of the invention has been
illustrated and described, it will be appreciated that various
changes can be made therein without departing from the spirit and
scope of the invention.
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