U.S. patent application number 11/326844 was filed with the patent office on 2006-06-08 for n-halamine vinyl compounds and their polymeric biocides.
This patent application is currently assigned to Regents of the University of California. Invention is credited to Gang Sun, YuYu Sun.
Application Number | 20060120991 11/326844 |
Document ID | / |
Family ID | 24133786 |
Filed Date | 2006-06-08 |
United States Patent
Application |
20060120991 |
Kind Code |
A1 |
Sun; Gang ; et al. |
June 8, 2006 |
N-halamine vinyl compounds and their polymeric biocides
Abstract
The present invention provides heterocyclic vinylic compounds
that can be used to form biocidal polymers. The polymers thus
generated can be used alone or can be grafted onto textiles,
fabrics and polymers. The polymers are readily converted to
N-halamine structures on exposure to a halogen source such as
commercially available chlorine bleach. The N-halamine derivatives
exhibit potent antibacterial properties against microorganisms and
these properties are durable and regenerable.
Inventors: |
Sun; Gang; (Davis, CA)
; Sun; YuYu; (Austin, TX) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER
EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Assignee: |
Regents of the University of
California
Oakland
CA
|
Family ID: |
24133786 |
Appl. No.: |
11/326844 |
Filed: |
January 6, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10431029 |
May 6, 2003 |
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11326844 |
Jan 6, 2006 |
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09535348 |
Mar 24, 2000 |
6768009 |
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10431029 |
May 6, 2003 |
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Current U.S.
Class: |
424/78.3 ;
525/283 |
Current CPC
Class: |
C08F 26/06 20130101;
A61K 31/77 20130101; C08F 253/00 20130101; C08L 51/04 20130101;
C09J 151/04 20130101; C09J 151/003 20130101; C08F 271/02 20130101;
C08L 2666/02 20130101; C08F 291/00 20130101; C08F 251/02 20130101;
C09J 151/02 20130101; C09J 151/08 20130101; C07D 233/74 20130101;
C08L 51/02 20130101; C07D 235/02 20130101; C07D 251/34 20130101;
C08F 289/00 20130101; A01N 59/00 20130101; C08L 51/08 20130101;
C08L 51/003 20130101; C08F 8/30 20130101; A01N 43/50 20130101; C08F
265/04 20130101; C08L 51/003 20130101; C08L 2666/02 20130101; C08L
51/02 20130101; C08L 2666/02 20130101; C08L 51/04 20130101; C08L
2666/02 20130101; C08L 51/08 20130101; C08L 2666/02 20130101; C09J
151/003 20130101; C08L 2666/02 20130101; C09J 151/02 20130101; C08L
2666/02 20130101; C09J 151/04 20130101; C08L 2666/02 20130101; C09J
151/08 20130101; C08L 2666/02 20130101 |
Class at
Publication: |
424/078.3 ;
525/283 |
International
Class: |
A61K 31/77 20060101
A61K031/77; C08F 271/02 20060101 C08F271/02 |
Claims
1. A polymer comprising a mixture of monomeric units having the
formulae: ##STR12## wherein: A is a member selected from the group
consisting of NH, N--R.sup.8 and CR.sup.1R.sup.2, wherein R.sup.8
is a halogen; R.sup.1 and R.sup.2, are each independently selected
from the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.1
and R.sup.2 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Q is a member selected from the group consisting
of C(O), NH, N--R.sup.9 and CR.sup.3R.sup.4, wherein R.sup.9 is a
halogen; R.sup.3 and R.sup.4, are each independently selected from
the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.3
and R.sup.4 and the carbon to which they are bound, join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring. X is a member selected from the group consisting
of C(O)--NR.sup.10 and CR.sup.6R.sup.7, wherein R.sup.10 is a
member selected from the group consisting of hydrogen, halogen,
optionally substituted (C.sub.2-C.sub.6)alkenyl and optionally
substituted (C.sub.1-C.sub.6)alkyl; R.sup.6 and R.sup.7, are each
independently selected from the group consisting of optionally
substituted (C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.6
and R.sup.7 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Z is a member selected from the group consisting
of optionally substituted (C.sub.1-C.sub.3)alkylene, C(O), or a
single bond; R.sup.11 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl; R.sup.12 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl; R.sup.13 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl; R.sup.14 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl; and n and y are each independently an integer from 1
to 250 inclusive.
2. The polymer of claim 1, wherein: A is NH and Z is CH.sub.2.
3. The polymer of claim 1, wherein: A is CR.sup.1R.sup.2, wherein
R.sup.1 and R.sup.2, are each optionally substituted
(C.sub.1-C.sub.6)alkyl.
4. The polymer of claim 3, wherein: R.sup.1 and R.sup.2, are each
(C.sub.1-C.sub.3)alkyl.
5. The polymer of claim 1, wherein: A is CR.sup.1R.sup.2, and
wherein R.sup.1 and R.sup.2 and the carbon to which they are bound
join to form an optionally substituted carbocyclic or optionally
substituted heterocyclic ring.
6. The polymer of claim 5, wherein: R.sup.1 and R.sup.2 and the
carbon to which they are bound join to form an optionally
substituted carbocyclic ring.
7. The polymer of claim 1, wherein: Q is C(O).
8. The polymer of claim 1, wherein: Q is NH.
9. The polymer of claim 1, wherein: Q is CR.sup.3R.sup.4, wherein
R.sup.3 and R.sup.4, are each optionally substituted
(C.sub.1-C.sub.6)alkyl.
10. The polymer of claim 1, wherein: X is CR.sup.6R.sup.7, wherein
R.sup.6 and R.sup.7, are each optionally substituted
(C.sub.1-C.sub.6)alkyl.
11. The polymer of claim 1, wherein: X is C(O)NH.
12. The polymer of claim 1, wherein said polymer is a film.
13. A textile material comprising a polymer of claim 1.
14. A method for making a polymer, said method comprising: admixing
a compound having the formula: ##STR13## wherein: A is a member
selected from the group consisting of NH, N--R.sup.8 and
CR.sup.1R.sup.2, wherein R.sup.8 is a halogen; R.sup.1 and R.sup.2,
are each independently selected from the group consisting of
optionally substituted (C.sub.1-C.sub.6)alkyl, optionally
substituted (C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.1
and R.sup.2 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Q is a member selected from the group consisting
of C(O), NH, N--R.sup.9 and CR.sup.3R.sup.4, wherein R.sup.9 is a
halogen; R.sup.3 and R.sup.4, are each independently selected from
the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.3
and R.sup.4 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; X is a member selected from the group consisting
of C(O), C(O)--NR.sup.5 and CR.sup.6R.sup.7, wherein R.sup.5 is a
member selected from the group consisting of hydrogen, halogen,
optionally substituted (C.sub.2-C.sub.6)alkenyl and optionally
substituted (C.sub.1-C.sub.6)alkyl; R.sup.6 and R.sup.7, are each
independently selected from the group consisting of optionally
substituted (C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.6
and R.sup.7 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; and Z is a member selected from the group
consisting of optionally substituted (C.sub.1-C.sub.3)alkylene,
C(O), or a single bond, with a vinyl monomer in a reaction mixture
thereby making said polymer.
15. The method of claim 14, wherein said vinyl monomer is a member
selected from the group consisting of an acrylic monomer, a
monofunctional vinyl monomer, a polyfunctional vinyl monomer and
mixtures thereof.
16. The method of claim 14, wherein said reaction mixture further
comprises a free radical initiator.
17. The method of claim 14, wherein said vinyl monomer is selected
from the group consisting of acrylonitrile, methacrylate, vinyl
acetate and mixtures thereof.
18. The method of claim 14, further comprising treating said
polymer with a halogenated aqueous solution.
19. A polymer comprising a monomeric unit having the formula:
##STR14## wherein: A is a member selected from the group consisting
of NH, N--R.sup.8 and CR.sup.1R.sup.2, wherein R.sup.8 is a
halogen; R.sup.1 and R.sup.2, are each independently selected from
the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.1
and R.sup.2 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Q is a member selected from the group consisting
of C(O), NH, N--R.sup.9 and CR.sup.3R.sup.4, wherein R.sup.9 is a
halogen; R.sup.3 and R.sup.4, are each independently selected from
the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.3
and R.sup.4 and the carbon to which they are bound, join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring. X is a member selected from the group consisting
of C(O)--NR.sup.10 and CR.sup.6R.sup.7, wherein R.sup.10 is a
member selected from the group consisting of hydrogen, halogen,
optionally substituted (C.sub.2-C.sub.6)alkenyl and optionally
substituted (C.sub.1-C.sub.6)alkyl; R.sup.6 and R.sup.7, are each
independently selected from the group consisting of optionally
substituted (C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.6
and R.sup.7 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Z is a member selected from the group consisting
of optionally substituted (C.sub.1-C.sub.3)alkylene, C(O), or a
single bond; and n is an integer from 1 to 250 inclusive.
20. A method for making a polyethylene derivative antimicrobial
polymer comprising: polymerizing a mixture comprising: (a) an
ethylene derivative of the formula:
R.sup.11R.sup.12C.dbd.CR.sup.13R.sup.14 and (b) a compound of the
formula: ##STR15## to produce a polyethylene derivative
antimicrobial polymer, wherein A is a member selected from the
group consisting of NH, N--R and CR.sup.1R.sup.2, wherein R.sup.8
is a halogen; R.sup.1 and R.sup.2, are each independently selected
from the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.1
and R.sup.2 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Q is a member selected from the group consisting
of C(O), NH, N--R.sup.9 and CR.sup.3R.sup.4, wherein R.sup.9 is a
halogen; R.sup.3 and R.sup.4, are each independently selected from
the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.3
and R.sup.4 and the carbon to which they are bound, join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring. X is a member selected from the group consisting
of C(O)--NR.sup.10 and CR.sup.6R.sup.7, wherein R.sup.10 is a
member selected from the group consisting of hydrogen, halogen,
optionally substituted (C.sub.2-C.sub.6)alkenyl and optionally
substituted (C.sub.1-C.sub.6)alkyl; R.sup.6 and R.sup.7, are each
independently selected from the group consisting of optionally
substituted (C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.6
and R.sup.7 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Z is a member selected from the group consisting
of optionally substituted (C.sub.1-C.sub.3)alkylene, C(O), or a
single bond; R.sup.11 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl; R.sup.12 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl; R.sup.13 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl; R.sup.14 is a member selected from the group
consisting of hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C6)alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl;
and n and y are each independently an integer from 1 to 250
inclusive.
21. A method for making an antimicrobial polymer, said method
comprising: contacting a polymer with a compound of the formula:
##STR16## under conditions sufficient to covalently attach the
compound of Formula I to the polymer to produce an antimicrobial
polymer, wherein A is a member selected from the group consisting
of NH, N--R.sup.8 and CR.sup.1R.sup.2, wherein R.sup.8 is a
halogen; R.sup.1 and R.sup.2, are each independently selected from
the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.1
and R.sup.2 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; Q is a member selected from the group consisting
of C(O), NH, N--R.sup.9 and CR.sup.3R.sup.4, wherein R.sup.9 is a
halogen; R.sup.3 and R.sup.4, are each independently selected from
the group consisting of optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.3
and R.sup.4 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; X is a member selected from the group consisting
of C(O), C(O)--NR.sup.5 and CR.sup.6R.sup.7, wherein R.sup.5 is a
member selected from the group consisting of hydrogen, halogen,
optionally substituted (C.sub.2-C.sub.6)alkenyl and optionally
substituted (C.sub.1-C.sub.6)alkyl; R.sup.6and R.sup.7, are each
independently selected from the group consisting of optionally
substituted (C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl; or, R.sup.6
and R.sup.7 and the carbon to which they are bound join to form an
optionally substituted carbocyclic or optionally substituted
heterocyclic ring; and Z is a member selected from the group
consisting of optionally substituted (C.sub.1-C.sub.3)alkylene,
C(O), or a single bond.
22. The method of claim 21, wherein the polymer comprises an
unsaturated carbon-carbon bond such that the compound of formula I
is covalently attached to the polymer via a carbon-carbon
linkage.
23. The method of claim 22, wherein the carbon-carbon linkage is
formed via free-radical reaction.
Description
FIELD OF THE INVENTION
[0001] This invention relates to heterocyclic vinylic amines
reagents useful for the preparation of biocidal polymers. The
biocidal polymers are useful for generating medical and
hygienic-use textiles.
BACKGROUND OF THE INVENTION
[0002] Contamination of polymeric materials by microorganisms such
as pathogenic bacteria, odor-generating bacteria, molds, fungi and
viruses is of great concern in the medical industry, the food and
restaurant industries, as well as in consumer products. Survival of
microorganisms on polymeric materials and transfer of these
microorganisms between patients and health care workers (HCWs) has
been demonstrated, and it is widely accepted that hospital gowns,
patient drapes, carpeting and bedding materials, etc., can be
elements in cross-infections. (see, Lidwell, O. M. et al., J. Appl.
Bact. 37:649 (1974)); Rubbo, S. D. and Saunders, J., J. Hyg. Camb.,
61:507 (1963); Ransjo, U., J. Hyg. Camb., 82:369 (1979); and
Hambraeus, A., J. Hyg. Camb., 71:799 (1973)). Medical gowns and
uniforms currently in use provide barriers for HCWs, but have
proven to be ineffectual in studies by numerous researchers. (see,
for example, Beck, W. C. and Collette, T. S., Am. J. Surg., 83:125
(1952); Smith, J. W. and Nichols, R. L. Arch. Surg., 126:756
(1991); Lovitt, S. A. et al., Am. J. Infect. Control, 20:185
(1992); Quebbeman, E. J. et al., Annal. Surg., 214:614 (1991);
Granzow, J. W. et al., Am. J. Infect. Control, 26:85 (1998)).
[0003] The occurrence of contaminated cleaning cloths in domestic
applications has also been investigated. Results from several
different studies indicate that more than half of the investigated
dish cloths and cleaning cloths were contaminated by one or more of
the following organisms: Escherichia coli, Staphylococcus aureus,
Streptococcus faecalis and Clostridium perfringens (see, Scott, E.
et al., J. Hyg. Camb., 89:279 (1982); Tebutt, C. M., J. Hyg. Camb.,
97:81 (1986); and Scott, E. et al., J. Appl. Bact., 68:271 (1990)).
Further studies show that wiping hard surfaces with contaminated
cloths can result in contamination of hands, equipment and other
surfaces. (see, Mackintosh, C. A. and Hoffman, P. N. J. Hyg. Camb.,
92:345 (1984)).
[0004] These findings suggest that biocidal properties should be an
effective feature of medical and related healthcare and
hygienic-use textiles. In general, hygenic-use textiles are made of
synthetic polymers, and polymeric biocides have been reviewed by
several researchers recently. (see, Vigo, T. L. (R. B. Seymour and
R. S. Porter, Eds.), Manmade Fibers: Their Origin and Development,
Elsevier Appl. Sci., p. 214 (1992); Vigo, T. L. (Gebelein, C. and
Carraher, C., Eds.), Biotechnology and Bioactive Polymers, Plenum
Press, p. 225 (1994); Worley, S. D. and Sun, G., Trends Polym.
Sci., 11:364 (1996)).
[0005] Among the currently investigated biocidal materials,
N-halamines have been shown to provide almost instant and total
kill of a wide range of microorganisms. (see, Worley, S. D. et al.,
Trends Polym. Sci., 11:364 (1996)). There are many advantages
associated with using N-halamine structures. First, they are stable
in long-term use and storage over a wide temperature range. Second,
they are regenerable when activity is lost due to normal use
patterns. (see, Sun, G. et al., Polymer, 37:3753 (1996); Worley, S.
D. et al., The Polymeric Materials Encyclopedia, 1, A-B, p. 550
(1996); Sun, G. et al. Water Res. Bull., 1996, 32:793 (1996)). More
recently, N-halamine materials have been incorporated into
cellulose-containing fabrics. (see, Bickert, J. R. et al.,
International Conference on Safety & Protective fabric '98,
1998, p 1; Sun, G. et al., Textile Chem. Colorist, 6:26 (1998);
Sun, G. et al., Textile Chem. Colorist, 31:21 (1999)). Results
indicate that as little as 1% (wt) add-on of halamine structures
provides powerful biocidal efficacy (6-7 log reduction) against the
most common pathogens, at a contact time of two minutes.
[0006] U.S. Pat. No. 5,882,357, issued to Sun et al., on Mar. 16,
1999, discloses durable and regenerable microbiocidal textiles and
methods for preparing the same. The microbiocidal textiles are
prepared using a wet finishing process to covalently attach a
heterocyclic N-halamine to a cellulose-based material or other
polymeric material. The biocidal activity of the textiles can be
regenerated by washing with a halogenated solution. In addition,
U.S. Pat. No. 6,020,491, issued to Wonley et al., on Feb. 1, 2000,
discloses cyclic amine monomers and polymers that are used to form
biocidal N-halamine polymers. The polymers are useful as
disinfectants for potable water, swimming pools, hot tubs,
industrial water systems, cooling towers, air-conditioning systems,
and the like.
[0007] In spite of the advances in the prior art, there remains a
need for new monomeric units useful for generating polymers having
microbiocidal activity. Polymers that can be used to generate
microbiocidal fabrics, rubbers, plastics, paints, coatings, and
articles are also needed. The present invention fulfills these and
other needs.
SUMMARY OF THE INVENTION
[0008] In certain embodiments, the present invention provides
heterocyclic vinylic amines that can be readily polymerized with
most acrylic, substituted-acrylic and vinyl monomers. The polymers
thus generated exhibit biocidal efficacy after exposure to a
halogen source, such as chlorine bleach. Moreover, their
antibacterial properties are durable and regenerable. As such, the
present invention provides a compound having the formula
##STR1##
[0009] In Formula I, A is a functional group including, but not
limited to, NH, N--R.sup.8 and CR.sup.1R.sup.2, wherein R.sup.8 is
a halogen. R.sup.1 and R.sup.2, in Formula I are each a functional
group including, but not limited to, optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl.
[0010] In an alternative embodiment, R.sup.1 and R.sup.2 and the
carbon to which they are bound, join to form an optionally
substituted carbocyclic or optionally substituted heterocyclic
ring.
[0011] In Formula I, Q is a functional group including, but not
limited to, C(O), NH, N--R.sup.9 and CR.sup.3R.sup.4, wherein
R.sup.9 is a halogen. R.sup.3 and R.sup.4, in Formula I are each a
functional group including, but not limited to, optionally
substituted (C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl.
[0012] In an alternative embodiment, R.sup.3 and R.sup.4 and the
carbon to which they are bound, join to form an optionally
substituted carbocyclic or optionally substituted heterocyclic
ring.
[0013] In Formula I, X is a functional group including, but not
limited to, C(O)--NR.sup.5 and CR.sup.6R.sup.7, wherein R.sup.5 is
a functional group including, but not limited to, hydrogen,
halogen, optionally substituted (C.sub.2-C.sub.6)alkenyl and
optionally substituted (C.sub.1-C.sub.6)alkyl. R.sup.6 and R.sup.7,
in Formula I, are each a functional group including, but not
limited to, optionally substituted (C.sub.1-C.sub.6)alkyl,
optionally substituted (C.sub.2-C.sub.6)alkenyl, optionally
substituted (C.sub.2-C.sub.6)alkynyl, optionally substituted
cycloalkyl, optionally substituted (C.sub.1-C.sub.6)alkoxy,
optionally substituted aryl and optionally substituted
heteroaryl;
[0014] In an alternative embodiment, R.sup.6 and R.sup.7 and the
carbon to which they are bound, join to form an optionally
substituted carbocyclic or optionally substituted heterocyclic
ring.
[0015] Z, in Formula I, is a functional group including, but not
limited to, optionally substituted (C.sub.1-C.sub.3)alkylene, C(O),
or a single bond. When Z is a single bond, a vinyl group is bonded
directly to the ring nitrogen.
[0016] In another embodiment, the present invention provides a
polymer comprising a mixture of monomeric units having the formulae
##STR2##
[0017] In Formula II, A is a functional group including, but not
limited to, NH, N--R.sup.8 and CR.sup.1R.sup.2, wherein R.sup.8 is
a halogen. R.sup.1 and R.sup.2, in Formula II, are each a
functional group including, but not limited to, optionally
substituted (C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C6)alkoxy, optionally substituted
aryl and optionally substituted heteroaryl.
[0018] In an alternative embodiment, R.sup.1 and R.sup.2 and the
carbon to which they are bound, join to form an optionally
substituted carbocyclic or optionally substituted heterocyclic
ring.
[0019] In Formula II, Q is a functional group including, but not
limited to, C(O), NH, N--R.sup.9 and CR.sup.3R.sup.4, wherein
R.sup.9 is a halogen.
[0020] R.sup.3 and R.sup.4, in Formula II are each a functional
group including, but not limited to, R.sup.3 and R.sup.4,
optionally substituted (C.sub.2-C.sub.6)alkyl, optionally
substituted (C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl.
[0021] In an alternative embodiment, R.sup.3 and R.sup.4 and the
carbon to which they are bound, join to form an optionally
substituted carbocyclic or optionally substituted heterocyclic
ring.
[0022] In Formula II, X is a functional group including, but not
limited to, C(O)--NR.sup.10 and CR.sup.6R.sup.7, wherein R.sup.10
is a functional group including, but not limited to, hydrogen,
halogen, optionally substituted (C.sub.2-C.sub.6)alkenyl and
optionally substituted (C.sub.1-C.sub.6)alkyl.
[0023] R.sup.6 and R.sup.7, in Formula II, are each a functional
group including, but not limited to, optionally substituted
(C.sub.1-C.sub.6)alkyl, optionally substituted
(C.sub.2-C.sub.6)alkenyl, optionally substituted
(C.sub.2-C.sub.6)alkynyl, optionally substituted cycloalkyl,
optionally substituted (C.sub.1-C.sub.6)alkoxy, optionally
substituted aryl and optionally substituted heteroaryl.
[0024] In an alternative embodiment, R.sup.6 and R.sup.7 and the
carbon to which they are bound, join to form an optionally
substituted carbocyclic or optionally substituted heterocyclic
ring.
[0025] Z, in Formula I, is a functional group including, but not
limited to, optionally substituted (C.sub.1-C.sub.3)alkylene, C(O),
or a single bond.
[0026] R.sup.11 in Formula II, is a functional group including, but
not limited to, hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl.
[0027] R.sup.12 in Formula II, is a functional group including, but
not limited to, hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl.
[0028] R.sup.13 in Formula II, is a functional group including, but
not limited to, hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, amido, aldehydo, aryl and
heterocyclyl.
[0029] R.sup.14 in Formula II, is a functional group including, but
not limited to, hydrogen, halogen, hydroxyl, cyano,
(C.sub.1-C.sub.6)alkyl, (C.sub.2-C.sub.6)alkenyl,
(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarbonyl,
(C.sub.1-C.sub.6)alkylcarboxyl, aldehydo, amido, aryl and
heterocyclyl. The index "x" is an integer from 1 to 250 inclusive.
The index "y" is an integer from 1 to 250 inclusive.
[0030] In yet another embodiment,-the present invention provides a
polymer comprising a polymeric unit of the formula: ##STR3##
wherein A, Q, X, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.6,
R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13,
R.sup.14, "n" and "y" have been defined above. In this embodiment.
The polymer comprises a least one unit having a dimmer wherein "n"
is 1 and "y" is 1.
[0031] In still yet another embodiment, the present invention
provides a method for making a polymer, comprising: admixing a
compound having the formula ##STR4## wherein A, Q, X Z, R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and
R.sup.9 have been defined above, with a with a vinyl monomer in a
reaction mixture thereby making a polymer.
[0032] In another embodiment, the present invention provides a
method for chemically modifying a polymer, comprising: admixing the
polymer in a reaction mixture with a compound having the formula he
formula ##STR5## wherein A, Q, X, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 have been
defined above, with a vinyl monomer in a reaction mixture thereby
chemically modifying the polymer.
[0033] In certain aspects, a hydantoin-containing monomer such as
3-allyl-5,5-dimethylhydantoin, are grafted onto a polymer such
cotton cellulose, in the presence of a monomeric unit such as
acrylonitrile. Thereafter, the hydantoin units in the grafted
copolymers are readily converted to N-halamine structures on
exposure to a halogenated material (e.g., chlorine bleach). The
N-halamine derivatives of the corresponding grafted samples exhibit
potent antibacterial properties against microorganisms e.g.,
Escherichia coli. Moreover, these antibacterial properties are
durable and regenerable.
[0034] These and other features and advantages will become more
apparent when read with the accompanying figures and detailed
description that follows.
DEFINITIONS
[0035] As used herein "ADMH" means
3-allyl-5,5-dimethylhydantoin.
[0036] As used herein "AIBN" means 2,2'-azobisisobutyronitrile.
[0037] As used herein "AN" means acrylonitrile.
[0038] As used herein "BADD" means
7,8-benzo-1,3-diazasprio[4.5]decane-2,4-dione.
[0039] As used herein "BADDD" means
7,8-benzo-3-allyl-1,3-diazasprio[4. 5]decane-2,4-dione.
[0040] As used herein "DMH" means 5,5-dimethylhydantoin.
[0041] As used herein "MMA" means methyl methacrylate.
[0042] As used herein "PPS" means potassium persulfate.
[0043] As used herein "VAC" means vinyl acetate.
[0044] As used herein, the term "alkyl" denotes branched or
unbranched hydrocarbon chains, preferably having about 1 to about 8
carbons, such as, methyl, ethyl, n-propyl, iso-propyl, n-butyl,
sec-butyl, iso-butyl, tert-butyl, octa-decyl and 2-methylpentyl.
These groups can be optionally substituted with one or more
functional groups which are attached commonly to such chains, such
as, hydroxyl, bromo, fluoro, chloro, iodo, mercapto or thio, cyano,
alkylthio, heterocyclyl, aryl, heteroaryl, carboxyl, carbalkoyl,
alkyl, alkenyl, nitro, amino, alkoxyl, amido, and the like to form
alkyl groups such as trifluoro methyl, 3-hydroxyhexyl,
2-carboxypropyl, 2-fluoroethyl, carboxymethyl, cyanobutyl and the
like.
[0045] The term "alkylene" refers to a divalent alkyl group as
defined above, such as methylene (--CH.sub.2--), propylene
(--CH.sub.2CH.sub.2CH.sub.2--), chloroethylene (--CHClCH.sub.2--),
2-thiobutene --CH.sub.2CH(SH)CH.sub.2CH.sub.2,
1-bromo-3-hydroxyl-4-methylpentene
(--CHBrCH.sub.2CH(OH)CH(CH.sub.3)CH.sub.2--), and the like.
[0046] The term "alkenyl" denotes branched or unbranched
hydrocarbon chains containing one or more carbon-carbon double
bonds.
[0047] The term "alkynyl" refers to branched or unbranched
hydrocarbon chains containing one or more carbon-carbon triple
bonds.
[0048] The term "aryl" denotes a chain of carbon atoms which form
at least one aromatic ring having preferably between about 6-14
carbon atoms, such as phenyl, naphthyl, and the like, and which may
be substituted with one or more functional groups which are
attached commonly to such chains, such as hydroxyl, bromo, fluoro,
chloro, iodo, mercapto or thio, cyano, cyanoamido, alkylthio,
heterocycle, aryl, heteroaryl, carboxyl, carbalkoyl, alkyl,
alkenyl, nitro, amino, alkoxyl, amido, and the like to form aryl
groups such as biphenyl, iodobiphenyl, methoxybiphenyl, anthryl,
bromophenyl, iodophenyl, chlorophenyl, hydroxyphenyl,
methoxyphenyl, formylphenyl, acetylphenyl,
trifluoromethylthiophenyl, trifluoromethoxyphenyl, alkylthiophenyl,
trialkylammoniumphenyl, amidophenyl, thiazolylphenyl,
oxazolylphenyl, imidazolylphenyl, imidazolylmethylphenyl, and the
like.
[0049] The term "alkoxy" denotes --OR--, wherein R is alkyl.
[0050] The term "amido" denotes an amide linkage: --C(O)NHR
(wherein R is hydrogen or alkyl).
[0051] The term "amino" denotes an amine linkage: --NR--, wherein R
is hydrogen or alkyl.
[0052] The term "carboxyl" denotes --C(O)O--, and the term
"carbonyl" denotes --C(O)--.
[0053] The term "alkylcarbonyl" denote an alkyl group as defined
above substituted with a C(O) group, for example, CH.sub.3C(O)--,
CH.sub.3CH.sub.2C(O)--, etc.
[0054] The term "alkylcarboxyl" denote an alkyl group as defined
above substituted with a C(O)O group, for example, CH.sub.3C(O)O--,
CH.sub.3CH.sub.2C(O)O--, etc.
[0055] The term "carbocycle" means a cyclic hydrocarbon chain
having about 5 to about 8 ring carbons such as cyclopentyl,
cylcohexyl, etc. These groups can be optionally substituted with
one or more functional groups as defined under "alkyl" above.
[0056] The term "halogen" includes chlorine, fluorine, bromine,
iodine and mixtures thereof.
[0057] The term "heterocycle" means a straight chain or ring system
that may contain from zero to four heteroatoms selected from N, O,
and S, wherein the nitrogen and sulfur atoms are optionally
oxidized, and the nitrogen atom(s) are optionally quaternized.
Non-limiting examples of heterocycle groups include 1-pyrrolyl,
2-pyrrolyl, 3-pyrrolyl, .sup.3-pyrazolyl, 2-imidazolyl,
4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl,
2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl,
5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl,
3-furyl, 2-thienyl, etc. These groups can be optionally substituted
with one or more functional groups as defined under "alkyl"
above.
[0058] The terms "antimicrobial," "microbicidal," or "biocidal" as
used herein, refer to the ability to kill at least some types of
microorganisms, or to inhibit the growth or reproduction of at
least some types of microorganisms. The polymers prepared in
accordance with the present invention have microbicidal activity
(antimicrobial) against a broad spectrum of pathogenic
microorganisms. For example, if the polymer is grafted to a
textile, the textiles have microbicidal activity against
representative gram-positive (such as Staphylococcus aureus) and
gram-negative bacteria (such as Escherichia coli). Moreover, the
microbicidal activity of such textiles is readily regenerable.
BRIEF DESCRIPTION OF THE DRAWINGS
[0059] FIG. 1 illustrates a representative synthesis scheme for
compounds of the present invention.
[0060] FIG. 2 illustrates a FT-IR spectrum FT-IR spectra of PAN and
ADMH physical mixtures of different ADMH/PAN weight ratio in the
range of 1725 to 2325 cm.sup.-1.
[0061] FIG. 3 illustrates a representative method of determining
copolymerization of the present invention.
[0062] FIG. 4 illustrates a representative embodiment of varying
free-radical initiator on polymerization yields of the present
invention. Effect of ACN concentration on: .tangle-solidup.
percentage graft, and .box-solid. C.sub.ADMH (Total monomer
concentration: 5 wt %; ADMH molar fraction: 20 mol %; T=45.degree.
C. and t=180 min).
[0063] FIG. 5 illustrates an effect of mole fraction in the monomer
mixture on graft copolymerization of the present invention. Effect
of ADMH mole fraction in the monomer mixtures on: .tangle-solidup.
percentage graft, and .box-solid. C.sub.ADMH (Total monomer
concentration: 5 wt %; ACN concentration: 0.06 mol/L, T=45.degree.
C. and t=180 min).
[0064] FIG. 6 illustrates an effect of monomer concentration on
graft copolymerization of the present invention. Effect of total
monomer concentration on: .tangle-solidup. percentage graft, and
.box-solid. C.sub.ADMH (ADMH molar fraction: 20 mol %; ACN
concentration: 0.06 mol/L, T=45.degree. C. and t=180 min).
[0065] FIG. 7 illustrates an effect of reaction temperature on
graft copolymerization of the present invention. Effect of reaction
temperature on: .tangle-solidup. percentage graft, and .box-solid.
C.sub.ADMH (Total monomer concentration: 5 wt %; ADMH molar
fraction: 20 mol %; ACN concentration: 0.06 mol/L, and t=180
min).
[0066] FIG. 8 illustrates an effect of reaction time on graft
copolymerization of the present invention. Effect of reaction time
on: .tangle-solidup. percentage graft, and .box-solid. C.sub.ADMH
(Total monomer concentration: 5 wt %; ADMH molar fraction: 20 mol
%; ACN concentration: 0.06 mol/L, and T=45.degree. C.).
[0067] FIG. 9 illustrates a FT-IR spectrum of an embodiment of the
present invention.
DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
[0068] In one embodiment, the present invention provides
heterocyclic vinylic compounds that can be used to form
microbiocidal polymers. In other aspects, the polymers thus made
can be grafted onto textiles, fabrics and polymers. The polymers
are readily converted to N-halamine structures on exposure to a
halogen source such as commercially available chlorine bleach. The
N-halamine derivatives of the corresponding grafted samples exhibit
potent antibacterial properties against microorganisms such as
Escherichia coli, and these properties are durable and
regenerable.
[0069] As such, in certain aspects, the present invention provides
a compound having the formula ##STR6## wherein A, Q, X, Z, R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and
R.sup.9 have been defined above. With reference to FIG. 1 an
illustrative example of the synthesis of a compound of Formula I is
set forth. FIG. 1 is merely an example that should not limit the
scope of the claims herein. One of ordinary skill in the art will
recognize many other variations, alternatives, and modifications.
As shown therein, to a solution of DMH in water containing KOH was
added allyl bromide in methanol. The solution was stirred at
elevated temperature. Thereafter, the solution was cooled and dried
under reduced pressure at room temperature to produce a compound of
Formula I.
[0070] Suitable heterocyclic amine reagents useful in the synthesis
reaction illustrated in FIG. 1, include, but are not limited to,
6,6-dimethyl-1,3,5-triazine-2,4-dione,
4,4,5,5-tetramethyl-1,3-imidazolidin-2-one, and
5,5-dimethylhydantoin, and mixtures thereof. Compounds of Formula I
wherein Z is CH.sub.2 that generates a heterocyclic allylic amine
are preferred. Certain preferred compounds of Formula I are set
forth in Table 1. TABLE-US-00001 TABLE 1 ##STR7## Compound A Q X Z
1 NH CR.sup.3R.sup.4 C(O) CH.sub.2 R.sup.3 is CH.sub.3 R.sup.4 is
4- methylbenzyl 2 NH CR.sup.3R.sup.4 C(O) CH.sub.2 R.sup.3 and
R.sup.4 join to form cyclopentyl 3 NH C(O) CR.sup.6R.sup.7 CH.sub.2
R.sup.6 is CH.sub.3 R.sup.7 is CH.sub.3 4 NH CR.sup.3R.sup.4
CR.sup.6R.sup.7 CH.sub.2 R.sup.3 is CH.sub.3 R.sup.6 is CH.sub.3
R.sup.4 is CH.sub.3 R.sup.7 is CH.sub.3 5 NH C(O) NH C(O) CH.sub.2
6 CR.sup.1R.sup.2 NH C(O) CH.sub.2 R.sup.1 is CH.sub.3 R.sup.2 is
CH.sub.3 7 Substituted NH C(O) CH.sub.2 Cyclohexyl 8 NH C(O)
C(O)--N-allyl CH.sub.2
[0071] Once generated, the compounds of Formula I are used to
generate polymers such as copolymers. Unlike other reported vinylic
monomers, in which the copolymerization with other monomers is
sluggish, the compounds of Formula I, such as ADMH and BADDD, can
be copolymerized with most acrylic, substituted-acrylic and vinyl
monomers. The reaction proceeds smoothly under ordinary conditions
with a very satisfactory conversion. In certain aspects, about 5
mole % to about 100 mole % of compounds of Formula I can be
copolymerized with other monomers, more preferably about 5 mole %
to about 50 mole %.
[0072] In certain aspects, the compounds of Formula I alone, or
together, can be polymerized with at least one other existing vinyl
monomer, with or without the addition of free radical initiators,
in bulk, aqueous solution or suspension, organic solvents, or
emulsions. The resultant polymers can thereafter be used as
plastics, rubbers, polymeric materials, paints, surface coatings,
adhesives, etc, in the form of bulk, films/membranes, powder,
solutions, gels, etc.
[0073] As such, in another embodiment, the present invention
provides a polymer comprising a mixture of monomer units having the
formula ##STR8## wherein A, Q, X Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.4, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11,
R.sup.12, R.sup.13, R.sup.14 "n" and "y" have been defined above.
In this embodiment, a compound of Formula I and a vinyl monomer,
such as an acrylic monomer, a monofunctional vinyl monomer, a
polyfunctional vinyl monomer and mixtures thereof, are reacted
together to form copolymers. Examples of such vinyl monomers
include, but are not limited to, acrylonitrile, styrene,
acrylamide, methacrylamide, methyl methacrylate, ethylene,
propylene, butylenes, butadienes and other alkenes and dienes. The
copolymers thus formed have a least one dimmeric unit wherein "n"
is 1 and "y" is 1.
[0074] In certain embodiments, each of end groups in the polymers
are hydrogen. The polymers of the present invention comprise at
least one dimmeric unit of Formula II, wherein n is 1 and y is 1.
In certain aspects, the units of Formula II are grafted onto
existing polymers. The polymers comprise varying amounts of units
of "n" and "y", i.e., the number of"n" and "y" units can be random.
For example, the polymer can comprise about 10 "n" units followed
by about 20 "y" units or visa versa. All combinations and
variations of "n" and "y" are encompassed and contemplated by the
present invention.
[0075] In certain aspects, the present invention provides a polymer
comprising a polymeric unit having the formula:
[0076] In yet another embodiment, the present invention provides a
polymer comprising a polymeric unit of the formula: ##STR9##
wherein A, Q, X, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.6,
R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13,
R.sup.14, "n" and "y" have been defined above. In this embodiment.
The polymer comprises a least one unit having a dimmer wherein "n"
is 1 and "y" is 1.
[0077] As merely as an example, that should not limit the scope of
the claims herein, copolymerization of compounds of Formula I
wherein Z is CH.sub.2 e.g., ADMH or BADDD, will be illustrated. One
of ordinary skill in the art will recognize many other variations,
alternatives, and modifications. In certain aspects, the ease of
copolymerization is attributable to the an imide structure
generated during polymerization. Surprisingly, the polymerization
reaction of the present invention proceeds without termination of
the growing polymer chain or termination of the kinetic chain as in
prior art systems. (see, Schildknecht, C. E., Allyl Compounds and
Their Polymers, John Wiley & Sons, New York, 1973, p 30;
Shigetomi, Y., et al., J. Polym. Sci., part A, Polym. Chem.,
28:3317 (1990)). Without being bound by any particular theory, it
is believed that the strong electron-withdrawing ability of the
imide group lowers the electron density of the allylic carbon, and
thus, the termination steps involving the abstraction of the
allylic hydrogen in allyl copolymerizations is retarded. As a
result, degradative chain transfer decreases, and satisfactory
copolymerization takes place.
[0078] Although it is possible to prepare homopolymers of the
compounds of Formula I employing the methods described herein,
"autoinhibition" of allylic structures may occur. However,
homopolymers comprising "n" unit polymers are an aspect of the
present invention. Once formed, the allylic radical is very stable,
with the result that degradative chain transfer competes
exceptionally well with normal propagation, and the polymer chains
are terminated after the addition of only a few monomer units (see,
Bartlett, P. D. et al., J. Am. Chem. Soc., 75:91 (1953);
Schildknecht, C. E., Allyl Compounds and Their Polymers, John Wiley
& Sons, New York, 1973, p 30.)). This characteristic is not
necessarily a disadvantage. For example, less homopolymerization
ensures an excellent yield in the monomer synthesis process
described above, as well as good storage stability and a prolonged
shelf-life.
[0079] Once formed, the polymers can be made biocidal by reacting
the corresponding unhalogenated polymers, with a halogen source.
Suitable halogenating agents such as calcium hypochlorite, sodium
hypochlorite (e.g., CLOROX.RTM.), N-chlorosuccinimide,
N-bromosuccinimide, sodium dichloroisocyanurate,
trichloroisocyanuric acid, tertiary butyl hypochlorite,
N-chloroacetamide, N-chloramines, N-bromamines, etc., can be
used.
[0080] The halogenation of the unhalogenated polymers can be
accomplished in aqueous media or in mixtures of water with common
inert organic solvents such as methylene chloride, chloroform, and
carbon tetrachloride, or in inert organic solvents themselves, at
room temperature. Those of skill in the art will know of other
solvents or solvent mixtures suitable for use in the present
invention. In certain instances, the unhalogenated polymers can be
a previously-utilized cyclic N-halamine polymer that needs to be
regenerated due to inactivation of the N-halamine moieties. As used
herein, "halogenating" or "halogenated" polymers refers to
partially as well as fully halogenated. Preferred halogens are
chlorine and bromine.
[0081] Once formed, it is possible to determine copolymer contents
from the FT-IR spectra of the polymers (see, for example, Nyquist,
R. A., Appl. Spectrosc., 41, 797 (1987); Liu, M. X. et al., Appl.
Spectrosc., 50:349 (1996)). With reference to FIG. 2, the FT-IR
spectra of PAN and ADMH physical mixture films cast from DMF
solution are shown in the range of 1725 to 2330 cm.sup.-1. With an
increase in ADMH content, the intensity of the 1770 cm.sup.-1 band
also increases, while that of the 2243 cm.sup.-1 band
decreases.
[0082] FIG. 3 shows the plot of A.sub.1770/A.sub.2243 vs.
W.sub.ADMH/W.sub.AN, wherein A.sub.1770 and A.sub.2243 represents
the area of the 1770, 2243 cm.sup.-1 bands, and W.sub.ADMH,
W.sub.AN, the weight of ADMH and AN in the physical mixtures,
respectively. A linear relationship is obtained and the slope is
determined to be 0.74. Thus, the weight content of ADMH units in an
"An-co-ADMH" copolymer is calculated to be 3.4%. Similarly, the
hydantoin contents of other copolymers were obtained, as shown in
Table 2. In the copolymers, the hydantoin structure contents are
all below 5% wt (the original monomer ratio), and the BADDD
contents are usually lower than ADMH, except in the case
of"MMA-co-BADDD", where bulk copolymerization was employed.
[0083] In certain other embodiments, the present invention provides
a method for making a polymer, comprising:
[0084] admixing a compound having the formula ##STR10## wherein A,
Q, X, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, R.sup.8, and R.sup.9 have been defined above, with a with
a vinyl monomer in a reaction mixture thereby making the polymer.
Vinyl monomers suitable for use in the present invention include,
but are not limited to, an acrylic monomer, a monofunctional vinyl
monomer, a polyfunctional vinyl monomer and mixtures thereof The
polymerization reaction proceeds with a compound of Formula I and
at least one other existing vinyl monomer, optionally in the
presence of a free radical initiator. The reaction can take place
in bulk, an aqueous solution or a suspension, or an organic
solvent, or emulsion.
[0085] In another embodiment, the present invention provides a
method for chemically modifying a polymer, comprising: admixing the
polymer in a reaction mixture with a compound having the formula
##STR11## wherein A, Q, X, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4,
R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 have been defined
above, with a with a vinyl monomer in a reaction mixture thereby
chemically modifying the polymer. As used herein "chemical
modification" includes grafting the monomers alone or as a
copolymer onto existing natural or synthetic polymers in the
presence of at least one other existing vinyl monomer. The
polymerization and chemical modification reactions can be initiated
by thermal or radiation method, or the combinations thereof,
optionally in the presence of initiators. The resultant grafted
polymers can be used as plastics, rubbers, polymeric materials,
paints, surface coatings, adhesives, etc., in the form of bulk,
films/membranes, powder, solutions, gels, etc.
[0086] For example, a hydantoin-containing monomer such as
3-allyl-5,5-dimethylhydantoin (ADMH), is grafted onto a textile in
the presence of a vinyl monomeric unit such as acrylonitrile (AN).
In this aspect, a compound of Formula I in the grafted copolymers
are readily converted to N-halamine structures on exposure to a
halogenated material, such as commercially available chlorine
bleach. The exposure to a halogenated source generates a
N-halamine, and these structures are biocidal. Advantageously,
compounds of Formula I can readily be grafted onto other polymers
such as fabrics, in the presence of mono or polyfunctional acrylic
and vinyl monomers.
[0087] Various polymers can be chemically modified using the
methods of the present invention. Polymers suitable for use in the
present invention include, but are not limited to, a plastic, a
rubber, a textile material, a paint, a surface coating, an
adhesives, cellulose, a polyester, wood pulp, paper and a
polyester/cellulose blend. The polymeric materials suitable for the
present invention include, but are not limited to, naturally
occurring fibers from plants, such as cellulose, cotton, linin,
hemp, jute and ramie. They include polymers from animals, based
upon proteins and include, but are not limited to, wool, mohair,
vicuna and silk. Textiles also include manufactured fibers based
upon natural organic polymers such as, rayon, lyocell, acetate,
triacetate and azlon. Textiles suitable for use in the present
invention include synthetic organic polymers which include, but are
not limited to, acrylic, aramid, nylon, olefin, polyester, spandex,
vinyon, vinyl and graphite. Textiles also include inorganic
substances such as glass, metallic and ceramic.
[0088] Various textiles are preferred to practice the invention.
These include, but are not limited to, a fiber, a yarn or a natural
or synthetic fabric. Various fabrics include, but are not limited
to, a nylon fabric, a polyester, an acrylic fabric, NOMEX.RTM., a
triacetate, an acetate, a cotton, a wool and mixtures thereof NOMEX
is made of an aromatic polyamide material and is available from
DuPont (Wilmington, Del.). NOMEX is used in fire fighting
equipment.
[0089] The polymeric plastics suitable for the present invention
include thermoplastic or thermosetting resins. The thermoplastics
include, but are not limited to, polyethylene, polypropylene,
polystyrene, and polyvinylchloride. Thermoplastics also include,
polyamideimide, polyethersulfone, polyarylsulfone, polyetherimide,
polyarylate, polysulfone, polycarbonate and polystyrene. Additional
thermoplastics include, but are not limited to, polyetherketone,
polyetheretherketone, polytetrafluoroethylene, nylon-6,6,
nylon-6,12, nylon-11, nylon-12, acetal resin, polypropylene, and
high and low density polyethylene.
[0090] The polymerization and chemical modification reactions can
proceed by various polymerization techniques well known by those of
skill in the art. For example, a free radical initiation method, a
photoinitiated method or thermal initiated method are all suitable
methods. For example, one can dissolve a compound of Formula I in
absolute ethanol or other suitable solvent and react this solution,
at the boiling point for the solvent, with azobisisobutyronitrile
(AIBN) under nitrogen atmosphere to produce the unhalogenated
polymer.
[0091] Alternatively, the compounds of Formula I can be
copolymerized with a vinyl monomers by a free radical initiation
method, such as by dissolving all desired monomers in
N,N-dimethylacetamide or other suitable solvent and adding, under
nitrogen atmosphere, azobisisobutyronitrile, and allowing the
mixture to react, at the boiling point temperature for the solvent,
under nitrogen atmosphere to produce the copolymer. For example,
other monomer types that can be copolymerized with a compound of
Formula I can include acrylonitrile, styrene, methacrylamide,
methyl-methacrylate, ethylene, propylene, butylenes, butadienes and
other alkenes and dienes. The resulting unhalogenated polymers or
copolymers can then be halogenated, such as with free chlorine and
bromine sources, as described herein. Additionally, the compound of
Formula I can be halogenated and thereafter polymerized.
[0092] Various parameters of the polymerization and chemical
modifications were examined to optimize the reactions. These
parameters, such as concentration of radical initiator, will be
illustrated with a specific example. However, this is merely an
example that should not limit the scope of the claims herein. One
of ordinary skill in the art will recognize many other variations,
alternatives, and modifications. In certain instances, the
concentration of free radical initiator can have an effect on the
polymerization reaction. For example, with reference to FIG. 4, the
effect of varying the concentration of ACN on the percentage graft
yield and C.sub.ADMH is presented. (C.sub.ADMH is the mole content
of the ADMH unit in the grafted polymer). As shown therein, the
percentage of graft obtained and C.sub.ADMH increase and thereafter
decrease after an optimum value of 0.06 mol/L. Without being bound
by any particular theory, it is believed that as the concentration
of ACN increases, a large number of cotton macroradicals form,
thereby increasing the graft yield and C.sub.ADMH. However, when
the concentration of ACN is higher than 0.06 mol/L, further
increase in initiator concentration may bring about the following
effects: (1) abundant free radicals, as well as PAN homopolymer
and/or AN/ADMH copolymer macroradicals are formed in the solution
that might terminate the growing chain; (2) the free radicals
formed on the main chain of cotton cellulose might be oxidized and
thus terminate the reactive sites; and (3) the graft
copolymerization, homopolymerization of AN, and the
copolymerization of ADMH/AN in such a system is a matter
"competition", which depends on the direct attack of free radicals
to cotton or to monomers. In certain instances, the net result is a
higher concentration of initiator results in the production of more
free radicals, and thus more homopolymer/copolymer macroradicals,
thereby reducing the graft yield, as well as the ADMH unit content
in the grafted samples.
[0093] In certain instances, the concentration of the compound of
Formula I has an effect on the polymerization reaction. For
example, the graft copolymerization of ADMH/AN monomer mixtures
onto cotton was investigated by varying the ADMH molar fraction in
the mixtures. In certain instances, the data shows that with
increased ADMH content in the monomer mixtures, graft yield
decreases. For example, grafting AN alone onto cotton results in a
graft yield of 63.8 wt %; however, keeping other conditions
constant, when the molar ratio of ADMH in the mixtures is 50%, the
graft yield is 3.2 wt % (see, FIG. 5). When the molar content of
ADMH was higher than 50%, the monomer mixtures acted as pure ADMH,
i.e., extended periods of grafting (12 h) resulted in a graft yield
of about 1 wt %. Thus, in certain instances, the presence of ADMH
reduces the graft yield of the AN component, which can also be
explained by the "autoinhibition" effect of the allylic structure
in ADMH. However, "AN" enhances the ADMH graft yield to a
considerable extent, showing positive synergism.
[0094] In other aspects, the ADMH molar content in the monomer
mixtures influences the value of C.sub.ADMH. In certain instances,
this value increases with the increase of ADMH molar content up to
20 % and then decreases with further increases in the ADMH content,
as shown in FIG. 5. Without being bound by any particular theory,
this "increase-decrease" trend may be explained by an "equilibrium"
between graft yield and .phi..sub.ADMH. Increasing the ADMH molar
content, causes the total graft yield to decrease, while the
content of the ADMH units in the grafted copolymers (.phi.ADMH)
increases. Thus, at a certain ADMH molar content (about 20%), a
maximum value of C.sub.ADMH can be observed. For C.sub.ADMH, the
synergistic effect was at its highest when an AN/ADMH mixture
containing 20 mol % ADMH was used.
[0095] FIG. 6 shows the influence of the monomer mixture
concentration on graft copolymerization. In certain instances, by
increasing the total monomer concentrations, the graft yield and
C.sub.ADMH gradually increase. In this heterogeneous reaction
system, the graft copolymerization largely depends on the diffusion
of monomers to cotton samples. As monomer concentrations go up,
more and more monomers can reach reactive sites on cotton
molecules. Furthermore, increasing monomer concentrations may
increase the amount of PAN homopolymer and/or AN/ADMH copolymer in
the solution, and consequently, this will result in increased
viscosity. This effect hinders termination, particularly through
the coupling of growing polymer chains. So, the graft yield and
C.sub.ADMH increase.
[0096] It should be noted that at higher than 5 wt % total monomer
concentration, this trend is not very significant. For example,
from 5 wt % to 20 wt %, the monomer concentration increases 4
times, but the graft yield only increases 1.4 times, and
C.sub.ADMH, about 2 times.
[0097] In other aspects, the effect of temperature on graft
copolymerization was investigated over the range of 20-70.degree.
C. With reference to FIG. 7, in certain instances, the percentage
graft increases with the increase of temperature. In case of
C.sub.ADMH, it first increases with the increase of temperature up
to 45.degree. C., and beyond this limit it decreases.
[0098] Without being bound by any particular theory, it is believed
that the "increase-decrease" trend of C.sub.ADMH is most likely due
to the influence of temperature on .phi..sub.ADMH: it was found
that .phi..sub.ADMH increases with the increase in temperature up
to 45.degree. C.; and after this, further increases in temperature
decreased .phi..sub.ADMH. Consequently, at higher than 45.degree.
C., although the percentage graft increases, C.sub.ADMH, decreases.
Without being bound by any particular theory, these findings may
suggest that compared with ADMH, polymerization of AN is favored at
higher-temperatures. Moreover, at higher temperatures (higher than
45.degree. C.), some PAN homopolymer, instead of AN/ADMH copolymer,
may be grafted onto cotton fibers.
[0099] In certain aspects, reaction time influences graft
copolymerization. For example, with reference to FIG. 8 with longer
reaction time, both percentage graft and C.sub.ADMH increase, but
to different degree. For example, from 30 to 300 min, the
percentage graft increases only 1.7 times, but for C.sub.ADMH, the
increase is 4.3 times. This means that with longer reaction times,
.phi..sub.ADMH and C.sub.ADMH increase more quickly than the
percentage graft. The reactivity of AN is higher than that of ADMH,
and thus, AN preferentially enters the copolymer. As a result,
there is a drift in the co-monomer composition toward ADMH as the
reaction time is extended, and the percentage graft increases more
slowly than C.sub.ADMH.
[0100] Numerous applications for the biocidal polymers of the
present invention exist. For instance, the biocidal polymers can
provide biocidal protective clothing to personnel in the medical
area as well as in the related healthcare and hygiene area. The
regenerable and reusable biocidal materials can replace currently
used disposable, nonwoven fabrics as medical textiles, thereby
significantly reducing hospital maintenance costs and disposal
fees. The microbicidal properties of the polymers of the present
invention can be advantageously used for women's wear, underwear,
socks, and other hygienic purposes. In addition, the microbicidal
properties can be imparted to carpeting materials to create
odor-free and germ-free carpets. Moreover, all germ-free
environments, such as required in biotechnology and pharmaceutical
industry, would benefit from the use of the microbicidal textiles
of the present invention to prevent any contamination from air,
liquid, and solid media.
[0101] The biocidal polymer are effective against all
microorganisms. Such microorganisms include, for example, bacteria,
protozoa, fungi, viruses and algae. Moreover, the biocidal polymers
described herein can be employed in a variety of disinfecting
applications, such as water purification. They will be of
importance in controlling microbiological contamination or growth
of undesirable organisms in the medical and food industries. In
addition, they can be used as preservatives and preventatives
against microbiological contamination in paints, coatings, and on
surfaces.
EXAMPLES
[0102] The following examples are offered to illustrate, but not to
limit the claimed invention.
[0103] a) Materials
[0104] Bleached desized cotton print cloth # 400 (Testfabrics Inc.)
was used throughout this study. 5,5-dimethylhydantoin (DMH,
Aldrich), ammonium cerium (IV) nitrate (Acros, ACN) and allyl
bromide (Acros) were used without further purification. AN (Acros)
was distilled twice before use.
7,8-Benzo-1,3-diazaspiro[4.5]decane-2,4-dione (BDDD, Aldrich) and
allyl bromide (Acros) were used without further purification. AN,
VAC, and MMA were distilled twice under reduced pressure.
2,2'-Azobisisobutyronitrile (AIBN) and potassium persulfate (PPS)
was recrystallized from EtOH and distilled water, respectively.
[0105] b) Instruments
[0106] FT-IR spectra were taken on a Nicolet Magana IR-560
spectrometer using KBr pellets. The samples were made to be thin
enough to ensure that the Beer--Lambert law was fulfilled.
.sup.1H-NMR spectra were recorded on a GE NMR QD-300 spectrometer.
The DSC study of the samples was performed using a Shimadzu DSC-50
instrument at a heating rate of 20.degree. C./min under N.sub.2
atmosphere.
Example 1
[0107] This example illustrates the synthesis of ADMH and
BADDD.
[0108] With reference FIG. 1, a solution of 6.4 g (0.05 mole) of
DMH in 25 mL H.sub.2O containing 2.8 g (0.05 mole) of KOH was
combined with a solution of 4.4 mL (0.05 mole) allyl bromide in 10
mL of methanol. The solution was stirred at 60.degree. C. for 2 h,
cooled, and dried under reduced pressure at room temperature. The
solid was recrystallized from petroleum ether, yielding, 7.7 g
(92%) of ADMH; m.p., 74-75.degree. C. .sup.1H-NMR (DMSO-d6,
.delta.): 1.29(6H, s, CH.sub.3), 3.94(2H, d, N-CH.sub.2),
4.99-5.12(1H, m, .dbd.CH), 5.73-5.86(2H, m, .dbd.CH.sub.2),
8.33(1H, s, NH).
[0109] BADDD was prepared in a similar fashion and recrystallized
from isopropyl alcohol, with a yield of 68% and m.p., 160-161
.degree. C. .sup.1H-NMR (DMSO-d.sub.6, .delta.): 1.83-2.08(2H, m,
CH.sub.2), 2.77-2.96(2H, m, CH.sub.2), 3.08-3.34(2H, m, CH.sub.2)
3.98-3.99(2H, d, N--CH.sub.2), 5.04-5.14(1H, m, .dbd.CH),
5.76-5.89(2H, m, .dbd.CH.sub.2), 7.14(4H, m, benzene ring),
8.69(1H, s, NH):
[0110] Both ADMH and BADDD showed significant differences from
their corresponding parent chemicals in FT-IR and .sup.1H-NMR
spectra. FIG. 9 shows the FT-IR spectra of DMH, ADMH, BDDD and
BADDD. It can be seen clearly that unlike DMH which shows two
absorption bands in the region of 3000-3500 cm.sup.-1, ADMH has
only one band in this region. Furthermore, the C.dbd.O stretching
band shifts from 1727 cm.sup.-1 in DMH to 1710 cm.sup.-1 in ADMH.
Similar changes from BDDD to BADDD can also be found in their FT-IR
spectra. With regard to the NMR spectra, ADMH shows characteristic
peaks at 3.94(2H d, N--CH.sub.2), 4.99-5.12(1H, m, .dbd.CH), and
5.73-5.86(2H, m, .dbd.CH.sub.2), indicative of the allylic
structure. Furthermore, DMH shows two peaks in the region of
7.8.about.11.0, corresponding to the N-1 and N-3 protons,
respectively (see, Ware, E. et al., Chem. Rev., 46:403 (1950)), but
in the NMR spectrum of ADMH, only one band around 8.5 is observed.
Similar changes in the NMR spectra from BDDD to BADDD can also be
detected. All these findings suggest typical N-3 substitutions of
hydantoins.
Example 2
[0111] This example illustrates the synthesis of copolymers using
ADMH and BADDD.
[0112] Synthesis conditions for the copolymers are summarized in
Table 2. About 5 wt % of the two hydantoin-containing monomers was
copolymerized with other 10 monomers separately, in order to obtain
desired antimicrobial properties without causing deterioration of
the original properties of the polymers. AN, MMA and VAC
homopolymers were also synthesized using the same conditions as the
corresponding copolymers. TABLE-US-00002 TABLE 2 Synthesis
Conditions and Some Properties of the Copolymers AN-co- AN-co-
MMA-co- MMA-co- VAC-co- VAC- ADMH BADDD ADMH BADDD ADMH BADDD M1
ADMH BADDD ADMH BADDD ADMH BADDD M2 AN AN MMA MMA VAC VAC M1/M2
(wt) 1/19 1/19 1/19 1/19 1/19 1/19 Initiator (M) PPS AIBN PPS AIBN
AIBN AIBN Solvent H.sub.2O DMF H.sub.2O None H.sub.2O/CH.sub.3OH
H.sub.2O/CH.sub.3OH Temp. (.degree. C.) 75 72 75 80 68 68 Time (h)
1.5 2.0 1.0 0.5 4.5 5.0 Conversion 38% 63% 22% 46% 54% 42% [.eta.]
(dl/g) 1.344* 1.864* 0.446** 0.412** 0.776** 0.623** .sup.+W.sub.M1
(wt %) 3.4 3.1 2.2 4.1 1.8 1.2 *Measured in DMF at 25.degree. C.
**Measured in acetone at 25.degree. C. .sup.+W.sub.M1: ADMH or
BADDD. Weight fraction in the copolymers.
[0113] The FT-IR spectrum of PAN shows absorption bands at 2243,
1454, 1248 and 1073 cm.sup.-1, which are attributed to the v(CN),
.delta.(CH.sub.2), .gamma..sub.w(CH), and v+(0), respectively, in
agreement with the literature data (see, Liang, C. Y., et al., J.
Polym. Sci., 31:513 (1958)). In the spectrum of AN-co-ADMH, besides
the characteristic bands of PAN, two bands centered at 1770 at 1710
cm.sup.-1, assigned to the amide and imide band of the hydantoin
structure respectively, can also be observed. All other copolymers
also show these characteristic bands of the hydantoin
structures.
[0114] The copolymers were characterized by .sup.1H-NMR studies.
The NMR spectrum of AN-co-ADMH at the copolymerization ratio of
1/6(W.sub.ADMH/W.sub.AN) shows characteristic peaks of ADMH at 1.29
(CH.sub.3) and 8.5(NH, weak). Furthermore, there are no peaks in
the region of 4.99-5.12 and 5.73-5.86, indicating the sample is a
polymer, not a mixture of monomers.
[0115] The DSC results of PAN, AN-co-ADMH and AN-co-BADDD show a
striking feature in the appearance of a sharp endotherm peak at
280.degree. C. in that of AN-co-BADDD, indicating the melting point
of the polymer. It has been widely accepted that PAN has a
"semi-crystalline" structure and because of the strong
dipole-dipole interaction between CN groups, instead of the melting
point, one can only observe the decomposition of the polymer in
ordinary thermal studies The existence of a T.sub.m in AN-co-BADDD
is very likely, due to the large side groups of BADDD, i.e., not
all of the AN units can pack favorably. Consequently, "physical
cross-linking" due to dipole-dipole interactions between CN groups
is actually diluted, resulting in a detectable T.sub.m. In case of
AN-co-ADMH, although the ADMH content is higher than that of BADDD
in AN-co-BADDD, the side groups of ADMH are much smaller, and
little difference between the DSC curves of AN-co-ADMH and PAN can
be observed.
Example 3
[0116] This example illustrates the antibacterial assessment of
copolymers synthesized in Example 2.
[0117] The antibacterial properties of VAC-co-ADMH and VAC-co-BADDD
were explored. Polymer films were cast from acetone solution. The
films (about 0.5 mm thick) were cut into small pieces (about 2
cm.sup.2), and then treated with 20 mL 1% CLOROX regular bleach at
40.degree. C. for 1.5 h, then thoroughly washed with distilled
water, and dried under reduced pressure to remove free chlorine. 10
.mu.l of an aqueous solution containing 10.sup.5-10.sup.6 colony
forming units (CFU)/mL of Escherichia coli were placed onto the
surface of the film. The film was then "sandwiched" using an
identical film. After different contact times, the entire
"sandwich" was placed into 10 mL of 0.03% sodium thiosulfate
aqueous solution. The resultant solution was then vigorously shaken
for 5 min. An aliquot of the solution was then serially diluted,
and 100 .mu.L of each dilution was plated onto a nutrient agar
plate. The same procedure was also applied to the un-halogenated
samples as controls. Bacterial colonies on the agar plates were
counted after incubation at 37.degree. C. for 48 h.
[0118] To study the durability of the antibacterial properties of
the films, samples were immersed in 500 mL of distilled water at
45.degree. C. for 60 min, and air dried at room temperature for 24
h. After each wash, the antibacterial properties of the treated
samples were examined by the same method mentioned above.
[0119] In certain instances, powdered samples were used to study
their antibacterial properties. One gram of the powder was treated
with 20 mL CLOROX regular bleach (sodium hypochlorite 5.25%) at
40.degree. C. for 1.5 h, washed thoroughly with distilled water,
and then dried under reduced pressure to remove free chlorine. The
antibacterial properties of the halogenated copolymers were tested
according to a modified method reported previously. (see, Worley,
S. D. et al., The Polymeric Materials Encyclopedia, 1, A-B, p. 550
(1996)). 10 mL of an aqueous solution containing 10.sup.5-10.sup.6
CFU/mL of Escherichia coli passed through a column containing about
1 cm length of the corresponding sample powders, using gravity
feed. The effluent was collected and the diluted solutions were
plated onto nutrient agar plates. Same procedure was also applied
to un-halogenated samples as controls. Bacterial colonies on the
agar plates were counted after incubation at 37.degree. C. for 24
h.
Example 4
[0120] This example further illustrates the antibacterial
assessment of copolymers synthesized in Example 2.
[0121] After treatment with CLOROX regular bleach, the amide groups
of the copolymers are readily transformed into N-halamine
structures as demonstrated in the FT-IR spectra of AN-co-ADMH and
VAC-co-ADMH before and after bleach treatment, respectively. Before
treatment, both of the two samples show a band at 1770 cm.sup.-1,
attributed to the amide structures of the hydantoin rings. After
treatment, the 1770 cm.sup.-1 band disappears, instead, a new band
centered at 1784 cm.sup.-1 can be detected. The 14 cm.sup.-1
difference between the treated and untreated samples strongly
suggests that the hydantoin structures are transformed into
N-halamine structures. The N-halamine structures in all of the
copolymers are very stable. After being immersed in distilled water
for 2 months, the FT-IR spectra were re-recorded and no difference
could be observed between the water treated and untreated
N-halamines. After treatment with 0.1 mol/L sodium thiosulfate
aqueous solution at 60.degree. C. for 2 h, the N-halamine
structures are converted to hydantoins, the 1784 cm.sup.-1 bands
changing back to 1770 cm.sup.-1. However, after another bleach
treatment, the 1770 cm.sup.-1 band can be converted into 1784
cm.sup.-1 again. The same "1784.fwdarw.1770.fwdarw.1784" cycle has
been repeated 10 times, each time with the same result. Thus, the
N-halamine structures possess durability and regenerability.
Example 5
[0122] This example illustrates the biocidal efficacy, durablility
and regenerability of the halogenated polymers by using the
bacterium Escherichia coli.
[0123] The halogenated polymers were tested for biocidal efficacy
by using the bacterium Escherichia coli. Samples in the form of
films or powders were employed. The results are shown in Table 3.
It can be clearly seen that all the halogenated copolymers
demonstrate total kill against Escherichia coli at a flow rate of
0.2-0.6 mL/min for the powdered samples, and a contact time of less
than 30 min for the film samples. No significant differences can be
noticed in the antibacterial properties between different
copolymers, indicating that the N-halamine structure in the
halogenated copolymers provide the antibacterial activities.
TABLE-US-00003 TABLE 3 Antibacterial Properties of the Copolymers
Against E. Coli AN-co- AN-co- MMA-co- MMA-co- VAC-co- VAC-co- ADMH
BADDD ADMH BADDD ADMH BADDD Form of samples powder powder powder
powder film film E. Coli concentration 10.sup.6 10.sup.6 10.sup.5
10.sup.6 10.sup.6 10.sup.5 (CFU/mL) Flow speed for total 0.4 0.6
0.5 0.2 X X kill (mL/min)* Contact time for total X X X X 15 25
kill (min)** *For powdered samples. **For film samples. * and **
Flow rate or contact time shown here are minimum conditions
necessary for total kill of E. Coli.
[0124] The durability of the antibacterial properties of the
copolymers was also studied. For all of the samples, after storage
at 25.degree. C. and 65% Relative Humidity for 3 months,
antibacterial properties are essentially unchanged. VAC-co-ADMH
films were also washed with distilled water, and after each wash,
the antibacterial property was retested. Results are shown in Table
4. After different wash periods, the contact time necessary for a
total kill of E. coli becomes longer and longer, indicating the
decrease of antibacterial properties. On the other hand, the FT-IR
spectra of the washed samples still show bands centered at 1784
cm.sup.-1, and no bands at 1770 cm.sup.-1 can be detected,
suggesting that the N-halamine structure remains almost unchanged
upon washing. TABLE-US-00004 TABLE 4 Relationship Between Wash
Times(N) and Contact Time(T) Necessary for a total kill of E. Coli
by VAC-co-ADMH Film (E. Coli concentration: 10.sup.5-10.sup.6
CFU/mL) N 0 3 5 10 15 T (min) 15 15 20 45 60
[0125] These findings are very likely due to the structure of the
films. It has been pointed out that N-halamines kill microorganisms
upon contact and films, unlike fibers and powders, have small
surface areas. Upon washing, the N-halamines structures in the
surface parts can be converted into hydantoins, but those in the
bulk are unchanged. Because the surface provides the antibacterial
properties, the antibacterial properties decrease. However, after
re-bleaching, the sample can provide a total kill at a contact time
of 15 min again. And after 20 cycles of this "bleach.fwdarw.wash 10
times.fwdarw.re-bleach", the antibacterial properties of the sample
are essentially unchanged, indicating that they are
regenerable.
Example 6
[0126] This example illustrates the graft copolymerization
procedure.
[0127] About 1 g of cotton was immersed in 30 mL of distilled water
containing a known amount of ACN. The initiator was allowed to
interact with cotton for 30 min and the ADMH/AN mixture of known
composition was added to the solution. The solution was stirred for
a certain period of time at a known temperature. After the graft
copolymerization, the cotton sample was taken out and extracted 3
times with 100 mL of hot DMF at 60.degree. C. for 2 h to remove any
un-grafted polymers. The cotton sample was then washed with large
excess of distilled water, dried at 60.degree. C. for 24 h, and
stored in a desiccator for 72 h to reach constant weight.
Measurements
[0128] Percentage graft was calculated from the relation: %
Grafting=(W.sub.2-W.sub.1)/W.sub.1.times.100 Where W.sub.1 and
W.sub.2 are the weights of the original and the grafted cotton,
respectively.
[0129] ADMH unit content in the grafted samples was calculated
according to:
C.sub.ADMH=6.0.times.10.sup.-3.times.(W.sub.2-W.sub.1).times..phi..s-
ub.ADMH/W.sub.1
[0130] Where C.sub.ADMH is the mole content of the ADMH unit in the
grafted cotton, 6.0.times.10.sup.-3 is the reciprocal of the
molecular weight of the ADMH unit in the grafted copolymers, and
.phi..sub.ADMH is the weight fraction of ADMH unit in the grafted
copolymers.
[0131] In a FT-IR spectra of cotton and an ADMH/AN grafted cotton,
the 2243 cm.sup.-1 band is attributed to v(CN) and the 1707 and
1770 cm.sup.-1 bands can be assigned to the imide and amide
structure, respectively. This is clear indication that ADMH/AN
mixtures can be grafted onto cotton cellulose.
[0132] The fractional weight of the compound of Formula I such as
ADMH, in the grafted copolymer can be calculated from the
corresponding FT-IR spectra. For instance, in the FT-IR spectra of
ADMH/polyacrylonitrile (PAN) physical mixtures, with increases in
ADMH content, the intensity of the 1770 cm.sup.-1 band increases,
while that of the 2243 cm.sup.-1 band decreases. In the plot of
A.sub.1770/A.sub.2243 VS. W.sub.ADMH/W.sub.AN (A.sub.1770 and
A.sub.2243 represented the area of the 1770, 2243 cm.sup.-1 band,
and W.sub.ADMH and W.sub.AN, the weight of ADMH and PAN in the
physical mixtures, respectively), a linear relationship is obtained
and the slope can be determined to be 0.74. Consequently,
.phi..sub.ADMH, the weight content of the ADMH units in the grafted
copolymers, could be calculated from Equation:
.phi.ADMH=0.74.times.A.sub.1770/(0.74.times.A.sub.1770+A.sub.2243)
[0133] It should be kept in mind that because the graft
copolymerization process is complicated, the graft copolymer is not
well defined. Thus, this value (.phi..sub.ADMH is the weight
fraction of ADMH unit in the grafted copolymers.) is an "average"
value. Nevertheless, this parameter works well in exploring the
influence of reaction conditions on ADMH content, and this is very
important in determining the antibacterial properties of the
grafted samples, as can be seen in the next section.
Example 7
[0134] This example illustrates grafting polyesters with
monomers.
[0135] About 1 g of poly(ethylene terephthalate) (PET) fabric was
immersed in 30 mL of distilled water containing a known amount
(0.625-15% conc. of two in solution) of ADMH (90-50%) and
triallyl-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (10-50%, as
co-linker). The solution was heated to a known temperature
(65-100.degree. C.). A known amount of benzoyl peroxide (BPO)
(0.125-1.5%) dissolved in an organic solvent (acetic acid, or
acetone, or ethanol) was then added. Under constant stirring, the
solution was kept at that temperature for a certain period of time
(30 minutes to 3 hours). After the graft copolymerization, the PET
sample was taken out and extracted 3 times with 100 mL of hot
acetone at 60.degree. C. for 2 h to remove any un-grafted polymers.
The PET sample was then washed with large excess of distilled
water, dried at 60.degree. C. for 24 h, and stored in a desiccator
for 72 h to reach constant weight. Yields were 2-30%,
controllable.
Example 8
[0136] This example illustrates the antibacterial properties of the
halogenated copolymers.
[0137] To transform hydantoin groups into N-halamine structures,
the grafted cotton samples were bleached according to a method
reported previously. (see, Sun, G. and Xu, X. Textile Chem.
Colorist, 6:26 (1998).) Antibacterial properties of the bleached
samples were evaluated against Escherichia coli according to AATCC
Test Method 100. Durability and regeneration of the biocidal
properties were tested with machine washing following AATCC Test
Method 124. AATCC standard reference detergent WOB was used in all
machine washing tests.
[0138] After treatment with CLOROX bleach, the amide groups of the
grafted copolymers can be readily transformed into N-halamine
structures. Before bleach treatment, the grafted sample shows a
band at 1770 cm.sup.-1 in the FT-IR spectrum attributed to the
amide group of the hydantoin rings. After treatment, the 1770
cm.sup.-1 band disappears, instead, a new band centered at 1782
cm.sup.-1 can be detected. The 12 cm.sup.-1 difference between the
treated and untreated sample strongly suggests that the hydantoin
structure has been transformed into N-halamine structures.
[0139] The stability of the N-halamine structure was also studied
by using machine washing following AATCC Test Method 124. It was
found that the N-halamine structures in the grafted cotton samples
were stable up to 10 washes. After 15 washes, the N-halamine
structure had been converted back to hydantoin, the 1782 cm.sup.-1
bands changed back to 1770 cm.sup.-1 However, after another bleach
treatment, the 1770 cm.sup.-1 band converted into 1782 cm.sup.-1
again. The same "1782.fwdarw.1770.fwdarw.1782" cycle have been
repeated 10 times, each with the same result.
[0140] The halogenated graft samples were tested for biocidal
efficacy by using the bacterium Escherichia coli at a concentration
of 10.sup.6.about.10.sup.7 CFU/mL, following AATCC Test Method 100.
The results are shown in Table 5. With the increasing of ADMH unit
content in the grafted samples, the minimum contact time for a
total kill of 10.sup.6.about.10.sup.7 CFU/mL E. coli decreased.
(Note the difference between sample 1 and sample 4), strongly
indicating that it is the N-halamine structures in the grafted
samples that provide the antibacterial properties. TABLE-US-00005
TABLE 5 Antibacterial Properties of Some Halogenated Grafted
Samples Against E. Coli* Sample Contact Time No. Graft % C.sub.ADMH
(mol/g) Wash Times** (min)*** 1 15.2 3.4 .times. 10.sup.-2 0 20 2
15.2 3.4 .times. 10.sup.-2 10 30 3 15.2 3.4 .times. 10.sup.-2 20
180 4 26.4 9.0 .times. 10.sup.-2 0 10 5 26.4 9.0 .times. 10.sup.2
20 60 *Antibacterial properties were tested according to AATCC Test
Methods 100. E Coli concentration: 10.sup.6.about.10.sup.7 CFU/mL.
**Machine washing, following AATCC Test Methods 124, AATCC standard
reference detergent WOB was used in all of the machine washing
tests. ***Minimum contact time for a total kill.
[0141] The durability of the antibacterial properties of the
grafted samples has studied. After 10 washes, the contact time
necessary for a total kill of E. coli was relatively unchanged,
indicating the stability of the N-halamine structures. However,
further washes converted the N-halamine structures to hydantoins
and the minimum contact time for a total kill gone up as the
antibacterial properties decreased (see Table I, sample 2, 3, and
5). However, after re-bleaching, the sample again provided total
kill at a contact time of less than 30 min. And after 10 these
"bleach wash 10 times.fwdarw.re-bleach" cycles, the antibacterial
properties of the samples were unchanged, indicating the
antibacterial properties were regenerable.
[0142] It is understood that the examples and embodiments described
herein are for illustrative purposes only and that various
modifications or changes in light thereof will be suggested to
persons skilled in the art and are to be included within the spirit
and purview of this application and scope of the appended claims.
All publications, patents, and patent applications cited herein are
hereby incorporated by reference in their entirety for all
purposes.
* * * * *