U.S. patent application number 10/035243 was filed with the patent office on 2002-09-12 for phthalocyanine analogs.
This patent application is currently assigned to QinetiQ. Invention is credited to Cook, Michael J..
Application Number | 20020128249 10/035243 |
Document ID | / |
Family ID | 10821284 |
Filed Date | 2002-09-12 |
United States Patent
Application |
20020128249 |
Kind Code |
A1 |
Cook, Michael J. |
September 12, 2002 |
Phthalocyanine analogs
Abstract
Disclosed are compounds of formula V 1 where M is a metal atom;
a metal compound; 2H whereby one H is bonded to each of the two
nitrogen atoms depicted as being bonded to M (positions 29 and 31
shown) R.sub.3 is H or methyl; R.sub.1 and R.sub.4 are
independently selected from: H, C.sub.1 to C.sub.4 alkyl, C.sub.2
to C.sub.4 alkenyl, methoxy, butoxy, propoxy, NH.sub.2,
NH--(C.sub.1 to C.sub.4 alkyl), N--(C.sub.1 to C.sub.4
alkyl).sub.2, S--(C.sub.1 to C.sub.4 alkyl); R.sub.8 to R.sub.25
are the same or different and are independently selected from:
C.sub.1 to C.sub.32 alkyl; C.sub.2 to C.sub.32 alkenyl; X--O--Y;
X-phenyl, X.sup.2COOX.sup.1, X.sup.2CONR.sup.1R.sup.11, H; halide;
where: X and X.sup.2 are independently selected from: a chemical
bond, --(CH.sub.2).sub.n-- where n is an integer from 1 to 32,
--(CH.sub.2).sub.a--CH.dbd.CH(CH.sub.2).sub- .b where a and b are
independently selected from integers 0-32 and a+b totals 32;
X.sup.1 and Y are independently selected from: C.sub.1 to C.sub.32
alkyl, C.sub.2 to C.sub.32 alkenyl, and H; R.sup.1 and R.sup.11 are
independently selected from: H; C.sub.1 to C.sub.32 alkyl, C.sub.2
to C.sub.32 alkenyl, --(CH.sub.2).sub.n--; with the proviso that at
least one of R.sub.8 to R.sub.25 is selected from: C.sub.1 to
C.sub.32 alkyl, C.sub.2 to C.sub.32 alkenyl, X--O--Y, X-phenyl,
X.sup.2COOX.sup.1, X.sup.2CONR.sup.1R.sup.11.
Inventors: |
Cook, Michael J.; (Norwich,
GB) |
Correspondence
Address: |
NIXON & VANDERHYE P.C.
8th Floor
1100 North Glebe Road
Arlington
VA
22201-4714
US
|
Assignee: |
QinetiQ
|
Family ID: |
10821284 |
Appl. No.: |
10/035243 |
Filed: |
January 4, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10035243 |
Jan 4, 2002 |
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09529673 |
Apr 18, 2000 |
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6384027 |
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Current U.S.
Class: |
514/185 ;
514/410; 540/124 |
Current CPC
Class: |
A61P 35/00 20180101;
B82Y 30/00 20130101; C09B 47/00 20130101; C07D 487/22 20130101;
A61P 43/00 20180101; C09K 19/3488 20130101; B82Y 10/00
20130101 |
Class at
Publication: |
514/185 ;
514/410; 540/124 |
International
Class: |
A61K 031/555; A61K
031/409; C09B 047/04 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 30, 1997 |
GB |
9722883.7 |
Oct 26, 1998 |
GB |
PCT/GB98/03185 |
Claims
1. A compound of Formula I (FIG. 1(b)) wherein: M is selected from:
a metal atom; a metal compound; 2H whereby one H is bonded to each
of the two nitrogen atoms depicted as being bonded to M (positions
29 and 31 shown) and wherein: one or more of the Q groups is
selected from: formula II (FIG. 1(c)) or formula III (FIG. 1(d)),
with the remaining Q groups each being formula IV (FIG. 1(e)):
wherein: R.sub.33 and R.sub.34 are independently selected from: H
or methyl R.sub.35 is selected from: H; C.sub.1 to C.sub.4 alkyl;
C.sub.2 to C.sub.4 alkenyl: methoxy: butoxy; propoxy; NH.sub.2;
NH--(C.sub.1 to C.sub.4 alkyl); N--(C.sub.1 to C.sub.4
alkyl).sub.2, S--(C.sub.1 to C.sub.4 alkyl), each R.sub.n and
R.sub.p group is independently selected from: C.sub.1 to C.sub.32
alkyl; C.sub.2 to C.sub.32 alkenyl; X--O--Y; X-phenyl
X.sup.2COOX.sup.1; X.sup.2CONR.sup.1R.sup.11; H; halide wherein: X
and X.sup.2 are independently selected from: a chemical bond;
--(CH.sub.2).sub.n-- wherein n is an integer from 1 to 32;
--(CH.sub.2).sub.a--CH.dbd.CH(CH.su- b.2).sub.b where a and b are
independently selected from integers 0-32 and a+b totals 32.
X.sup.1 and Y are independently selected from: C.sub.1 to C.sub.32
alkyl; C.sub.2 to C.sub.32 alkenyl; H R.sup.1 and R.sup.11 are
independently selected from: H; C.sub.1 to C.sub.32 alkyl; C.sub.2
to C.sub.32 alkenyl; --(CH.sub.2).sub.n--with the proviso that
where more than one Q is Formula II with the remaining Q group
being Formula IV, at least one group independently selected from:
R.sub.33, R.sub.34, R.sub.35, an R.sub.n group, an R.sub.p group,
is not H.
2. A compound as claimed in claim 1 having formula V (FIG. 1(f)),
Wherein: M is selected from: a metal atom, a metal compound: 2H
whereby one H is bonded to each of the two nitrogen atoms depicted
as being bonded to M (positions 29 and 31 shown) R.sub.3 is H or
methyl R.sub.1 and R.sub.4 are independently selected from: H;
C.sub.1 to C.sub.4 alkyl; C.sub.2 to C.sub.4 alkenyl; methoxy;
butoxy; propoxy; NH.sub.2; NH--(C.sub.1 to C.sub.4 alkyl);
N--(C.sub.1 to C.sub.4 alkyl).sub.2, S--(C.sub.1 to C.sub.4 alkyl),
R.sub.8 to R.sub.25 are the same or different and are independently
selected from: C.sub.1 to C.sub.32 alkyl; C.sub.2 to C.sub.32
alkenyl; X--O--Y; X-phenyl X.sup.2COOX.sup.1;
X.sup.2CONR.sup.1R.sup.11; H; halide and wherein X, X.sup.2,
X.sup.1, Y, R.sup.1 and R.sup.11 are as defined in claim 1.
3. A compound as claimed in claim 1 or claim 2 wherein all
non-peripheral R groups other than those attached to pyridyl nuclei
are selected from: H; alkyl containing up to 32; up to 20; between
4-14; or between 8-12 C atoms where 1 or more adjacent CH.sub.2
groups may be replaced by O or a double bond, and the remaining R
groups are all H.
4. A compound as claimed in claim 3 wherein all non-peripheral R
groups are H.
5. A compound as claimed in any one of the preceding claims wherein
all peripheral R groups other than those attached to pyridyl nuclei
are selected from: alkyl containing up to 32; up to 20; between
4-14; between 8-12 C atoms, and the remaining R groups are all
H.
6. A compound as claimed in any one of the preceding claims wherein
R.sub.33, R.sub.34, R.sub.1 and R.sub.3are H.
7. A compound as claimed in any one of the preceding claims wherein
R.sub.35 and R.sub.4 are electron donating groups independently
selected from: O-alkyl, NH.sub.2, NH-alkyl, N(alkyl).sub.2, alkyl,
S-alkyl.
8. A compound as claimed in any one of the preceding claims wherein
those the alkyl groups present within R groups are straight chain
alkyl.
9. A compound as claimed in any one of the preceding claims wherein
M is selected from: 2H; Ru, Ni, Pb, V, Pd, Co, Nb, Al, Sn, Zn, Cu,
Mg, Ca, In, Ga, Fe, Eu, Lu and Ge.
10. A compound as claimed in claim 9 wherein M is selected from:
2H; Zn; Cu; Co; Ru; and Ni.
11. A compound as claimed in claim 10 having formula VI (FIG. 1(g))
wherein M is selected from: 2H; Zn; Ni.
12. A compound as claimed in any one of the preceding claims which
has an absorption maximum in the near infra-red.
13. A compound as claimed in any one of the preceding claims which
is soluble.
14. A composition comprising a compound as claimed any one of the
preceding claims.
15. A pharmaceutical composition comprising a compound of any one
of claims 1 to 13 in admixture with a pharmaceutically acceptable
carrier.
16. A compound of any one of claims 1 to 13 for use in PDT.
17. A compound of any one of claims 1 to 13 for use in the
preparation of a medicament.
18. A compound as claimed in claim 16 or claim 17 wherein the PDT
or the medicament is for the treatment of a mammal having a tumour
susceptible to photodynamic treatment.
19. A method of treatment comprising the step of exposing a
compound as claimed in any one of claims 1 to 13 to laser
radiation.
20. Use of a compound of any one of claims 1 to 13 in an LC
device.
21. An LC device comprising two spaced walls each bearing electrode
structures and treated on at least one facing surface with an
alignment layer comprising a compound as claimed in any one of
claims 1 to 13.
22. An LC device as claimed in claim 21 which is an electro-optical
display device.
23. Use of a compound of any one of claims 1 to 13 in an optical
recording medium.
24. A method of storing or retrieving information comprising the
step of exposing a compound as claimed in any one of claims 1 to 13
to laser radiation.
25. An optical recording medium comprising a recording layer, said
layer comprising a compound as claimed in any one of claims 1 to
13.
26. An optical recording medium as claimed 25 wherein the compound
is present as a spin coated film.
27. An optical recording medium as claimed in claim 26 wherein the
compound is a near infra-red absorber.
28. Use of a compound of any one of claims 1 to 13 in a gas
sensor.
29. A method of detecting a gas in a sample comprising the step of
exposing a compound as claimed in any one of claims 1 to 13 to the
sample.
30. A gas sensor comprising a compound as claimed in any one of
claims 1 to 13.
31. A gas sensor as claimed in claim 30 wherein the compound is
present as a spin coated film.
32. An LB film comprising a compound as claimed in any one of
claims 1 to 13.
33. A molecular wire comprising a compound as claimed in any one
claims 1 to 13.
34. Use of a compound as claimed in any one of claims 1 to 13 in a
Photonic device.
35. A Photonic device comprising a compound as claimed in any one
of claims 1 to 13.
36. Use of a compound as claimed in claimed in any one of claims 1
to 13 in any one of the following: electrocatalysis;
photocatalysis; electric conduction; photoconductivity:
electrochromism; a photovoltaic cell; a battery.
37. Use of a compound as claimed in any one of claims 1 to 13 in
the production of a dimer.
38. A dimer or higher oligomer consisting of a compound as claimed
in any one claims 1 to 13.
39. A mixed dimer or higher oligomer comprising a compound as
claimed in any one and a further Pc or Pc derivative.
40. Use of a compound of any one of claims 1 to 13 in the
production of a polymer.
41. A polymer consisting of a compound as claimed in any one of
claims 1 to 13 in polymerised form.
42. An AzaPc essentially as described herein with reference to the
accompanying Examples and Figures.
43. A method of producing a compound as claimed in any one claims 1
to 13 essentially as described herein with reference to Example 1.
Description
[0001] The present invention relates to phthalocyanine analogs, in
particularly to azaphthalocyanines (pyridinoporphyrazines). It
further relates to compositions containing these compounds, and
methods of use of such compounds and compositions.
[0002] Phthalocyanine is shown in FIG. 1(a). The nomenclature for
the numbering of the Benzo portion is also included in the above
depiction. Generally substituents in the R2, 3, 9, 10, 16, 17, 23,
24 positions are referred to as peripheral groups and substituents
in the R1, 4, 8, 11, 15, 18, 22, 25 positions are referred to as
non-peripheral groups.
[0003] Often, phthalocyanine is abbreviated to Pc.
[0004] Pcs in condensed phases possess interesting optical
absorption signatures, semiconductivity and optoelectronic
properties which are often sensitive to molecular packing.
Normally, the planar molecules are prone to form co-facial or near
co-facial assemblies. These "Face-to-Face" structures include the
simple aggregates found in solution,.sup.2 the longer columnar
stacks in the liquid crystal phases of mesogenic derivatives..sup.3
and the classic "herring bone" columnar packing in the most common
polymorphs of the unsubstituted compounds..sup.4 Polymeric columnar
structures include the "shish-kebab" polymers formed when the
central metal atoms of neighbouring Pc units are covalently or
coordinatively linked via bridging atoms or molecules..sup.5
[0005] The unusual properties that Pcs and Pc analogs exhibit means
they have many applications.
[0006] UK Patent GB 2,229,190 B relates to certain novel
substituted phthalocyanines, methods for their preparation and to
certain uses thereof. For example the compounds described in GB
2,229,190 B are suitable for use in optical recording media. Kuder
in J. of Imaging Science, vol. 32, (1988). pp51-56 discusses how
phthalocyanine dyes may be used in laser addressed optical
recording media, in particular it sets out how active layers may be
deposited.
[0007] UK Patent Application 9317881.2 describes substituted
metallophthalocyanines and phthalocyanines as PDT agents.
[0008] Patent application WO 93/09124 describes the use of water
soluble salt or acid forms of transition metal phthalocyanines for
use in photodynamic therapy. In this patent application,
phthalocyanines containing second or third row transition metals
with a d6 low-spin electronic configuration are disclosed. The
compounds exemplified in patent application WO 93/09124 contain
Ru.
[0009] Phthalocyanine derivatives have also been used in Langmuir
Blodgett films as described in UK Patent 2,229,190 B.
[0010] The redox behaviour of phthalocyanines is also of interest.
Some uses which exploit the redox properties of phthalocyanines
include electrocatalysis, photocatalysis, photovoltaics, electric
conduction, photoconductivity and electrochromism. These uses
(amongst others) of phthalocyanines are discussed by A. B. P. Lever
in Chemtech, 17, pp506-510, 1987.
[0011] Certain pyridinoporphrazines (azaphthalocyanines, or
AzaPcs)have been prepared and reported in the literature. These
include tetrapyridino derivatives and bipyridino derivatives having
Cr, Co, Cu, Fe and Ni centres. Thus Linstead.sup.7 first
demonstrated the replacement of all four benzene rings of the Pc
nucleus by pyridine in his classic investigations in the 1930s,
obtaining a mixture of insoluble isomeric dyes from
3,4-dicyanopyridine. Subsequently, Shibamiya and coworkers prepared
unsubstituted inacrocycles containing combinations of both
benzenoid and pyridinoid rings..sup.8 The absorption spectra of
these compounds were described, although not with reference to any
particular applications.
[0012] It can thus be seen that the provision of novel Pc
derivatives (or uses for such derivatives) particularly those with
novel absorption signatures, would provide a contribution to the
art.
DISCLOSURE OF THE INVENTION
[0013] The present inventors have now produced and characterised
novel organic solvent-soluble AzaPcs in which a pyridinoid ring is
incorporated in or around the Pc nucleus. Such compounds provide,
inter alia, for the generation of "Edge-to-Face" assemblies via
metal-nitrogen coordination involving the pyridyl nitrogen atom of
one molecule and the metal ion of a second molecule.
[0014] Although Edge-to-Face assembles have been constructed
earlier using porphyrin derivatives,.sup.6 they have not as yet
been realised within the Pc series. Such compounds have unexpected
and industrially applicable properties in a variety of technical
fields as is described in further detail hereinafter.
[0015] Thus according to one aspect of the invention there is
disclosed an AzaPc of Formula I (FIG. 1(b)):
[0016] wherein:
[0017] M is selected from:
[0018] a metal atom; a metal compound, 2H whereby one H is bonded
to each of the two nitrogen atoms depicted as being bonded to M
(positions 29 and 31 shown)
[0019] and wherein:
[0020] one or more of the Q groups is selected from: formula II or
formula III, with the remaining Q groups each being formula IV:
[0021] wherein:
[0022] R.sub.33 and R.sub.34 are independently selected from: H or
methyl
[0023] R.sub.35 is selected from: H; C.sub.1 to C.sub.4 alkyl;
C.sub.2 to C.sub.4 alkenyl; methoxy; butoxy; propoxy; NH.sub.2;
NH--(C.sub.1 to C.sub.4 alkyl); N--(C.sub.1 to C.sub.4
alkyl).sub.2, S--(C.sub.1 to C.sub.4 alkyl).
[0024] each R.sub.n and R.sub.p group is independently selected
from: C.sub.1 to C.sub.32 alkyl: C.sub.2 to C.sub.32 alkenyl;
X--O--Y; X-phenyl
[0025] X.sup.2COOX.sup.1; X.sup.2CONR.sup.1R.sup.11; H; halide
[0026] wherein:
[0027] X and X.sup.2 are independently selected from: a chemical
bond, --(CH.sub.2).sub.n-- wherein n is an integer from 1 to 32;
--(CH.sub.2).sub.a--CH.dbd.CH(CH.sub.2).sub.b where a and b are
independently selected from integers 0-32 and a+b totals 32.
[0028] X.sup.1 and Y are independently selected from: C.sub.1 to
C.sub.32 alkyl; C.sub.2 to C.sub.32 alkenyl; H
[0029] R.sup.1 and R.sup.11 are independently selected from: H;
C.sub.1 to C.sub.32 alkyl; C.sub.2 to C.sub.32 alkenyl;
--(CH.sub.2).sub.n--
[0030] with the proviso that where more than one Q is Formula II
with the remaining Q group being Formula IV, at least one of the
R.sub.33, R.sub.34, R.sub.35, R.sub.n, or R.sub.p groups is not
H.
[0031] In a further, preferred aspect of the invention, there is
disclosed an AzaPc having formula V (FIG. 1(f)).
[0032] Wherein:
[0033] M is selected from:
[0034] a metal atom; a metal compound; 2H whereby one H is bonded
to each of the two nitrogen atoms depicted as being bonded to M
(positions 29 and 31 shown)
[0035] R.sub.3 is H or methyl
[0036] R.sub.1 and R.sub.4 are independently selected from: H;
C.sub.1 to C.sub.4 alkyl: C.sub.2 to C.sub.4 alkenyl; methoxy;
butoxy; propoxy; NH,; NH--(C.sub.1 to C.sub.4 alkyl); N--(C.sub.1
to C.sub.4 alkyl).sub.2, S--(C.sub.1 to C.sub.4 alkyl).
[0037] R.sub.8 to R.sub.25 are the same or different and are
independently selected from:
[0038] C.sub.1 to C.sub.32 alkyl; C.sub.2 to C.sub.32 alkenyl;
X--O--Y; X-phenyl X.sup.2COOX.sup.1; X.sup.2CONR.sup.1R.sup.11; H
halide
[0039] wherein:
[0040] X and X.sup.2 are independently selected from: a chemical
bond: --(CH.sub.2).sub.n-- wherein n is an integer from 1 to 32:
--(CH.sub.2).sub.a--CH.dbd.CH(CH.sub.2).sub.b where a and b are
independently selected from integers 0-32 and a+b totals 32.
[0041] X.sup.1 and Y are independently selected from: C.sub.1 to
C.sub.32 alkyl; C.sub.2 to C.sub.32 alkenyl; H
[0042] R.sup.1 and R.sup.11 are independently selected from: H;
C.sub.1 to C.sub.32 alkyl; C.sub.1 to C.sub.32 alkenyl;
--(CH.sub.2).sub.n--
[0043] Most preferably the compound has formula VI (as shown in
FIG. 1(g), wherein M=2H, Ni, Zn, Co, Cu, Pd, Ru or Al.
[0044] Referring to formula I, formula VI has one Q group of
formula II with the remaining Q groups each being formula IV,
R.sub.33, R.sub.34 and R.sub.35 are H; R.sub.n are C.sub.8 alkyl
and R.sub.p is H.
[0045] Preferred Compounds
[0046] Preferred compounds of the present invention are those
wherein any one or more of the following apply:
[0047] All non-peripheral R groups (e.g. R.sub.n in formula III and
IV) are H.
[0048] All R groups other than those attached to pyridyl nuclei are
alkyl containing up to 32 (preferably up to 20, more preferably
between 4-14 or between 8-12) C atoms where 1 or more adjacent
CH.sub.2 groups may be replaced by O or a double bond, and the
remaining R groups are all H.
[0049] All peripheral R groups other than those attached to pyridyl
nuclei are alkyl containing up to 32 (preferably up to 20, more
preferably between 4-14 or between 8-12) C atoms, and the remaining
R groups are all H.
[0050] The R groups attached to the or each pyridyl nucleus on the
C atoms adjacent the N (i.e. R.sub.33, R.sub.34, R.sub.1, R.sub.3
as appropriate) are H, thereby minimising steric hindrance in those
embodiments of the invention which form "edge-to-face" dimers or
higher oligomers.
[0051] The R group attached to the or each pyridyl nucleus which is
in the meta-position with respect to the N (i.e. R.sub.35 or
R.sub.4 as appropriate) is an electron donating group thereby
increasing the basicity of the N such as to enhance its properties
as a ligand.
[0052] Examples of this type of group include O-alkyl, NH.sub.2,
NH-alkyl, N(alkyl).sub.2, alkyl, S-alkyl.
[0053] In all cases the alkyl groups may be straight or branched
chain. Straight chain are preferred.
[0054] The compounds of the invention may be metal free or contain
a metal bound to a ligand (such compounds may have utility, inter
alia, in the manufacture of metal containing derivatives, for
instance as intermediates) or may contain a metal atom, preferably
a diamagnetic metal atom.
[0055] The metal atom may be present for example as the metal with
an oxidation state of +2 or it may be present with other ligands
(or anions) attached to it. These ligands (or anions) may serve the
purpose of altering the hydrophobicity of the molecule as a whole.
Examples of suitable anions include chloride, bromide or oxide.
Examples of suitable metals include Ru, Ni, Pb, V, Pd, Co, Nb, Al,
Sn, Zn, Cu, Mg, Ca, In, Ga, Fe, Eu, Lu and Ge. Preferably when M is
a metal or metal compound then the metal is, or the metal compound
contains Cu, Zn, Ru, Pb, V, Co, Eu, Lu, Al. Examples of suitable
metal compounds include V0 and TiO. Those which may preferentially
form "edge-to-face" dimers or higher oligomers under appropriate
conditions include Zn, Cu, Co, Ru, and Ni.
[0056] Applications
[0057] Methods of use of the compounds described above form further
aspects of the present invention. Some particular applications are
exemplified below:
[0058] PDT
[0059] In this application it is preferred that M in the compounds
of the present invention is diamagnetic e.g. a second or third row
transition metal with a d.sup.6 low-spin electronic configuration,
preferably Zn. Ru-containing compounds may also be
advantageous.
[0060] A number of Pc derivatives have previously been proposed as
potential photodynamic therapeutic (PDT) agents. The combination of
a sensitizer and electromagnetic radiation for the treatment of
cancer is commonly known as photodynamic therapy. In the
photodynamic therapy of cancer, dye compounds are administered to a
tumour-bearing subject. These dye substances may be taken up, to a
certain extent, by the tumour. Upon selective irradiation with an
appropriate light source the tumour tissue is destroyed via the dye
mediated photo-generation of species such as singlet oxygen or
other cytotoxic species such as free radicals, for example hydroxy
or superoxide. Most biological studies on Pc compounds related to
PDT have been conducted with water soluble sulfonated
metallo-phthalocyanines as described by I. Rosenthal, Photochem.
Photobiol. 53(6), 859-870, 1991. Methods for synthesizing these
compounds often results in mixtures of compounds containing a
variety of isomers and/or different degrees of sulfonation.
[0061] Ideally compounds for use as photosensitizers in PDT have
some or all of the following characteristics: solubility; high
quantum yield of reactive species; low toxicity; high absorption
coefficients, preferably in the red or near infra red of the
spectrum; selective accumulation in the tumour.
[0062] The reason why absorption in the red-region of the EM
spectrum is desirable is that red light shows greater penetration
than light of shorter wavelengths. Such sensitisers can be
irradiated e.g. with laser light, or from other non-laser sources
e.g. tungsten halogen light. The compounds of the present invention
are particularly advantageous in this regard because of their
spectral properties, their ability to form high concentrations of
dimers which fluoresce, and their solubility. Preferred compounds
have Zn, Ru or Al as their metal centre, since these have
previously been shown (in other PCs) to be effective generators of
singlet oxygen.
[0063] One aspect of the present invention provides a
pharmaceutical composition comprising a compound of the invention
(e.g Formula VI wherein M is Zn or Ru) in a mixture or in
association with a pharmaceutically acceptable carrier or
diluent.
[0064] Also embraced is use of such a compound in the preparation
of a medicament, preferably a medicament for treatment against
cancer, most preferably for the treatment of a mammal having a
tumour susceptible to photodynamic treatment.
[0065] In a further aspect, the invention also includes a method of
treatment of a mammal having a tumour susceptible to photodynamic
treatment wherein the mammal is administered an effective dose of a
compound of formula I or a pharmaceutically acceptable salt form
thereof and the tumour is subjected to suitable electromagnetic
radiation.
[0066] The compounds described by the present invention may be
induced to act as a photosensitizers by incident electromagnetic
radiation of a suitable wavelength. Preferably, the electromagnetic
radiation is somewhere in the range ultra-violet to infra-red, even
more preferably it is in the range visible to red to near
infra-red.
[0067] The pharmaceutical compositions may be formulated according
to well-known principles and may desirably be in the form of unit
dosages determined in accordance with conventional pharmacological
methods. The unit dosage forms may provide daily dosage of active
compound in a single dose or in a number of smaller doses. Dosage
ranges may be established using conventional pharmacological
methods and are expected to lie in the range 1 to 60 mg/kg of body
weight. Other active compounds may be used in the compositions or
administered separately, or supplemental therapy may be included in
a course of treatment for a patient. The pharmaceutical
compositions may desirably be in the form of solutions of
suspensions for injection or in forms for topical application
including application in for example the oral cavity. Application
in other cavities is also possible. Suitable carriers and diluents
are well known in the art and the compositions may include
excipients and other components to provide easier or more effective
administration.
[0068] Following administration to the patient, photodynamic
therapy may be carried out in a conventional manner, using light
sources and delivery systems that are known in the art, for
example, see Phys. Med. biol. (1986), 31, 4, 327-360.
[0069] Enhanced positioning of the compounds of formula I in
relation to treating tumours may be achieved. For example, the
compounds of the present invention may be combined with other
chemical moieties.
[0070] Thus a further aspect embraces compositions comprising such
compounds plus a targeting molecule (e.g. an antibody) which may be
part of a binding pair, the other member of the pair being located
or concentrated in the target site (e.g. an antigen associated with
a tumour). A particular compound could be combined, for example, by
chemical attachment, with an antibody tailored to attach itself to
the tumour site. Antibodies as prepared from cultured samples of
the tumour. Examples include P.L.A.P. (Placental Alkaline
Phosphatase), H.M.F.G. (Hunan Milk Fat Globulin), C.E.A. (Carcino
Embryonic Antibody), H.C.G. (Human Chorionic Gonadotrophin).
[0071] Other targeting molecules may include lectins, protein A,
nucleic acids (which bind complementary nucleic acids) etc.
[0072] Further possible uses of Pcs (as photosensitizers) include
use as anti-virals in blood-banks or insecticides.
[0073] LCDs
[0074] It is well known that some phthalocyanine compounds exhibit
liquid crystalline behaviour.
[0075] The majority of known liquid crystalline compounds have a
generally rod-shaped molecular structure and are often
characterised by nematic and/or smectic mesophases. There are,
however, a number of known compounds which are characterised by a
generally disc-like molecular structure. These compounds are termed
discotic compounds, which can be characterised by discotic nematic
or columnar mesophase(s).
[0076] Discotic compounds can be based on a number of "cores", e.g.
benzene, truxene, metallophthalocyanine, phthalocyanines and
triphenylene.
[0077] Certain compounds of the present invention e.g. Ni, Cu, Co
and 2H containing compounds, have been demonstrated to exhibit
columnar mesophases.
[0078] Guillon et al Mol. Cryst Liq. Cryst.; 1985, vol. 130.
pp223-229, discuss columnar mesophases from metallated and metal
free derivatives of phthalocyanine in which the phthalocyanine is
substituted on the benzene rings with various groups all of which
are attached to the phthalocyanine core via a CH.sub.2 unit.
[0079] Piechocki and Simon, New Journal of Chemistry, vol. 9, no 3,
1985, pp159-166, report the synthesis of octa-substituted
phthalocyanine derivatives forming discotic mesophases. The side
chains are linked to the phthalocyanine core via a CH.sub.2
unit.
[0080] Most liquid crystal compounds are known as thermotropic
liquid crystal compounds. Thermotropic liquid crystals exist in
dependence of the temperature in certain temperature intervals. In
some cases when different substances are mixed together with a
solvent the mixture can exhibit different phases not only as the
temperature is changed, but also as the concentration of the solute
is changed. When the liquid crystal phase is dependent on the
concentration of one component in another it is called a lyotropic
liquid crystal. The easiest way to make a lyotropic liquid crystal
mixture is to start with a molecule that possesses end groups with
different properties For example one end could show an affinity for
water and the other end tends to exclude water. Molecules which
possess both a hydrophilic group and a part which is a hydrophobic
group can display characteristics of both classes, therefore they
are called amphiphilic molecules.
[0081] Lyotropic liquid crystals have numerous potential
applications including detergents, the recovery of oil from porous
rocks and in the food industry, providing they are sufficiently
non-toxic, for example as food emulsifiers. There may also be
medical applications for lyotropic liquid crystal systems. For
example, amphiphilic materials could help to make drugs more
soluble in the blood.
[0082] For a review of phthalocyanine thermotropics, see Simon and
Bassoul in Phthalocyanines, Properties and Applications, Ed., C. C.
Leznoff and A. B. P. Lever, V.C.H. Publishers 1992, p227.
[0083] Liquid Crystal Devices
[0084] One aspect of the invention includes use of the compounds of
Formula I, and use of mixtures including Formula I, in a liquid
crystal device. Typically such devices include linear and
non-linear electrical, optical and electro-optical devices,
magneto-optical devices, and devices providing responses to stimuli
such as temperature changes and total or partial pressure changes.
The devices themselves form a further aspect of the present
invention.
[0085] A typical example of the use of a compound of Formula I in a
liquid crystal material and device embodying the present invention
will now be described with reference to FIG. 4. The liquid crystal
device consists of two transparent plates, 1 and 2, in this case
made from glass. These plates are coated on their internal face
with transparent conducting electrodes 3 and 4. An alignment layer
5, 6 is introduced onto the internal faces of the cell so that a
planar orientation of the molecules making up the liquid
crystalline material will be approximately parallel or at a small
angle to the glass plates 1 and 2. For some types of display the
plane of the molecules is approximately perpendicular to that of
the glass plates, and at each glass plate the alignment directions
are orthogonal. The electrodes 3, 4 may be formed into row and
column electrodes so that the intersections between each column and
row form an x, y matrix of addressable elements or pixels. A spacer
7 e.g. of polymethyl methacrylate separates the glass plates 1 and
2 to a suitable distance e.g. 2 microns. Liquid crystal material 8
is introduced between glass plates 1, 2 by filling the space in
between them. The spacer 7 is sealed with an adhesive 9 in a vacuum
using an existing technique. Polarisers 10, 11 are arranged in
front of and behind the cell. For some devices, only one or even no
polarisers are required.
[0086] The device may operate in a transmissive or reflective mode.
In the former, light passing through the device, e.g. from a
tungsten bulb, is selectively transmitted or blocked to form the
desired display. In the reflective mode a mirror (12) is placed
behind the second polariser 11 to reflect ambient light back
through the cell and two polarisers. By making the mirror partly
reflecting the device may be operated both in a transmissive and
reflective mode.
[0087] The alignment layers 5,6 have two functions one to align
contacting liquid crystal molecules in a preferred direction and
the other to give a tilt to these molecules--a so called surface
tilt--of a few degrees typically around 4E or 5E. The alignment
layers 5, 6 may be formed by placing a few drops of the polyimide
onto the cell wall and spinning the wall until a uniform thickness
is obtained. The polyimide is then cured by heating to a
predetermined temperature for a predetermined time followed by
unidirectional rubbing with a roller coated with a nylon cloth.
[0088] Laser Addressed Applications
[0089] Some phthalocyanines also absorb radiation in the far-red to
near infra-red regions of the electromagnetic spectrum. Compounds
which absorb strongly at wavelengths of laser light can in
principle be exploited as guest dyes dissolved in liquid
crystalline host materials in a laser addressed system.
[0090] Materials have been proposed for laser addressed
applications in which laser beams are used to scan across the
surface of the material or leave a written impression thereon. For
various reasons, many of these materials have consisted of organic
materials which are at least partially transparent in the visible
region. The technique relies upon localised absorption of laser
energy which causes localised heating and in turn alters the
optical properties of the otherwise transparent material in the
region of contact with the laser beam. Thus as the beam traverses
the material, a written impression of its path is left behind. One
of the most important of these applications is in laser addressed
optical storage devices, and in laser addressed projection displays
in which light is directed through a cell containing the material
and is projected onto a screen. Such devices have been described by
Khan Appl. Phys. Lett. Vol. 22, p 111, 1973; and by Harold and
Steele in Proceedings of Euro display 84, pages 29-31, September
1984, Paris, France. in which the material in the device was a
smectic liquid crystal material. Devices which use a liquid crystal
material as the optical storage medium are an important class of
such devices. The use of semiconductor lasers, especially
Ga.sub.xAl.sub.1-xAs lasers where x is from 0 to 1, and is
preferably 1, has proven popular in the above applications because
they can provide laser energy at a range of wavelengths in the near
infra-red which cannot be seen and thus cannot interfere with the
visual display, and yet can provide a useful source of
well-defined, intense heat energy. Gallium arsenide lasers provide
laser light at wavelengths of about 850 nm, and are useful for the
above applications. With increasing Al content (x<1), the laser
wavelength may be reduced down to about 750 nm.
[0091] One of the main problems associated with the use of the
above materials is that it has proved difficult to provide
materials which are transparent in the visible region and yet are
strong absorbers in either the UV or IR region, preferably in the
near-IR region. The use of dyes within these materials can provide
strong absorption at certain wavelengths, but few dyes are
transparent in the visible region and many are insoluble in the
type of materials used for laser addressed applications.
EP-A-0155780 discloses a group of metal and metal-free
phthalocyanines which have been used as infra-red absorbing dyes
for a number of applications. These phthalocyanines contain from 5
to 16 peripheral organic substituent groups that are linked to the
phthalocyanine through sulphur, selenium, tellurium, nitrogen or
oxygen atoms. However, very few of the groups disclosed absorb
infra-red radiation strongly at or near the wavelength of a gallium
arsenide laser (850 nm). This problem also applies to a further
group of infra-red absorbing phthalocyanines disclosed in
EP-A-0134518. This further group consists of naphthalocyanines
which are peripherally substituted with alkyl groups and centrally
substituted with a metal atom or a chloride, bromide or oxide
thereof. Materials Science II/1-2, 1976 pp 39-45 discloses the
synthesis of octamethoxyphthalocyanines but these are insoluble in
organic solvents and as such are unsuitable for acting as dyes in
liquid crystalline solvents for laser addressed systems. Various of
the compounds of the present invention are particularly suitable
for this application owing to their high solubility and the
retention of high absorbance at appropriate wavelengths even at
high concentrations. The absorption maxima may be controlled by
altering the central atom, or by use of additives (e.g. metal
salts) or other agents to (e.g. pyridine to decomplex ZnAzaPc).
[0092] Optical Recording Media
[0093] For corresponding reasons to those discussed above, the
compounds of the present invention will be suitable for use in
optical recording media. Typically the phthalocyanine will absorb
in the near-infrared. In order to make an optical recording media
using a near-infrared absorber, the near-infrared absorber may be
coated or vacuum-deposited onto a transparent substrate. European
patent application EP 0 337 209 A2 describes the processes by which
the above optical-recording media may be made. Further the
materials described in EP 0 337 209 A2 are useful in near-infrared
absorption filters and liquid crystal display devices, as are the
compounds described by the current invention. As described in EP 0
337 209 A2, display materials can be made by mixing a near-infrared
absorber of formula I with liquid crystal materials such as nematic
liquid crystals, smectic liquid crystals and cholesteric liquid
crystals. The compounds of the current invention may be
incorporated into liquid crystal panels wherein the near-infrared
absorber is incorporated with the liquid crystal and laser beam is
used to write an image. Mixtures of phthalocyanines of the current
invention may be mixed with liquid crystal materials in order to be
used in guest-host systems. GB 2,229,190 B describes the use of
phthalocyanines incorporated into liquid crystal materials and
their subsequent use in electro-optical devices.
[0094] The properties of spin coated films of compounds of the
present invention are discussed hereinafter. Such spin coated films
may be useful in the production of optical recording media, and
also in sensors.
[0095] Sensors
[0096] Films of Pcs of the prior art have been used for as the
active component in conductometric and optical based sensors. They
may also have utility as selective gas sensors (e.g. for N.sub.2),
as demonstrated by the alteration in spectral properties which
occurs in the presence of particular gasses e.g. HCl (see Figures
below).
[0097] Langmuir-Blodgett (LB) Films
[0098] The materials of the current invention may also be
incorporated in Langmuir-Blodgett (LB) films. LB films
incorporating phthalocyanines of the current invention may be laid
down by conventional and well known techniques, see R. H. Tredgold
in `Order in Thin Organic Films`, Cambridge University Press, p74,
1994 and references therein. Generally an LB film is prepared by
depositing a monolayer of a surface-active material onto a water
surface; this may be done using well established techniques. The
molecules of the surface active material align in the monolayer,
the hydrophilic ends remaining in the water, and the hydrophobic
end projecting out of the surface. By other known techniques this
monolayer may be transferred essentially intact onto the surface of
a solid substrate and further monolayers deposited on the layer on
the substrate to form a film, i.e. an LB film.
[0099] LB films including compounds of the current invention may be
used as optical or thermally addressable storage media.
[0100] Molecular Wires
[0101] The compounds of the current invention may also be used as
molecular wires, see R. J. M. Nolte et al, Angew, Chem. Int. Ed.
Eng., vol. 33, part 21, page 2173, 1994.
[0102] Photonic Devices
[0103] It is known that some phthalocyanines are excellent
generators of third order non-linear optical effects and thus show
promise for use in photonic devices including all-optical switches
and computers, see Bredas, Adant, Tackx Persoons and Pierce, Chem.
Rev., 94, p243, 1994. The materials of the present invention may
show such effects and be used in such devices. In particular the
distortion of the delocalised B system of the AzaPc which may be
induced by the pyridine ring may be expected to produce novel
properties as compared with prior art PCs used for this
purpose.
[0104] Redox Applications
[0105] The compounds of the present invention allow for electronic
interaction of substituents with the Azaphthalocyanine ring. The
redox properties of the Azaphthalocyanines described by the current
invention may be easily modified by the altering the identity of
the various substituents. The compounds described by the current
invention are therefore useful in any one or more of the following:
electrocatalysis, photocatalysis, photovoltaics (e.g. solar cells),
electric conduction, photoconductivity and electrochromism and
other applications which exploit redox properties.
[0106] Polyelectrolytes
[0107] Polyethylene oxides can complex alkali metal ions, for
example Li+ and have been used as polyelectrolytes in solid state
battery applications, see Charadame in `Macromolecules`, ed. Benoit
and Rempp, Pergamon press, New York, 1982, p226. The compounds of
the invention may also be useful as polyelectrolytes, they are able
to stabilise charge, therefore there exist a number of applications
within battery technology.
[0108] Further aspects of the invention:
[0109] As well as use in the methods described above, in a further
aspect of the invention there is a disclosed a method of preparing
the compounds of the present invention, substantially as described
hereinafter.
[0110] Dimers or higher oligomers comprising or consisting of the
compounds of the present invention are also embraced within its
scope. Particularly embraced are "edge-to-face" dimers, including
mixed dimers formed between one compound of the present invention
and another Pc or AzaPc.
[0111] It may be advantageous to polymerise certain of the
compounds described by the current invention. Polymerised
phthalocyanines may be used in, for example, LB films. There are
numerous ways by which the phthalocyanine compound may be
polymerised. Polymerisation may be effected via one or more of the
positions R.sub.n or R.sub.p as described in formula I of the
current invention or via the central metal atom or metal compound,
or polymerisation may be realised by a combination of the above
methods. An example of a suitable phthalocyanine substituent which
may be used to effect polymerisation is an unsaturated substituent
such as an alkene group.
[0112] Main chain or side chain liquid crystal polymers may also be
made using the compounds of the present invention, or metal-linked
liquid crystal polymers.
FIGURES
[0113] FIG. 1(a) shows Pc
[0114] FIG. 1(b) shows Formula I
[0115] FIG. 1(c) shows Formula II
[0116] FIG. 1(d) shows Formula III
[0117] FIG. 1(e) shows Formula IV
[0118] FIG. 1(f) shows Formula V
[0119] FIG. 1(g) shows Formula VI
[0120] FIG. 1(h) shows:
[0121] Top. 250-800 nm spectrum of 1a as a solution in cyclohexane
at 1.46.times.10.sup.-6M; .lambda..sub.max 710 nm (.epsilon.
1.36.times.10.sup.5). 687 nm (.epsilon. 0.95.times.10.sup.5). Inset
spectrum (scale not shown) shows the Q-band absorption at
1.46.times.10.sup.-4M; .lambda..sub.max 709 nm (.epsilon.
6.23.times.10.sup.4), 687 nm (.epsilon. 5.85.times.10.sup.4), 652
nm (.epsilon. 4.33.times.10.sup.4).
[0122] Middle, as above but for 1b at 1.04.times.10.sup.-6M;
.lambda..sub.max 694 nm (.epsilon. 1.16.times.10.sup.5), 679 nm
(.epsilon. 1.17.times.10.sup.5). Inset spectrum, Q-band absorption
at 1.04.times.10.sup.-4M: .lambda..sub.max 690 nm (.epsilon.
5.61.times.10.sup.4), 679 nm (.epsilon. 6.15.times.10.sup.4), 643
nm (.epsilon. 4.27.times.10.sup.4).
[0123] Bottom, as above but for 1c at 1.24.times.10.sup.-6M;
.lambda..sub.max 716 nm (.epsilon. 0.86.times.10.sup.5). Inset
spectrum, Q-band absorption at 1.24.times.10.sup.-4M;
.lambda..sub.max 715 nm (.epsilon. 1.25.times.10.sup.5), 679 nm
(.epsilon. 0.75.times.10.sup.5).
[0124] FIG. 2
[0125] Transmission electron micrograph of 1b as a THF gel on a
carbon coated copper grid. The field of view is 453.times.294
nm.
[0126] FIG. 3
[0127] The visible region spectra of spin coated films of 1a (FIG.
3a), 1b (FIG. 3b) and 1c (FIG. 3c). FIG. 3d shows the film of 1c
after exposure of HCl vapour. Within 30 days after exposure to HCl,
the film gives a spectrum the same as that in FIG. 3c.
[0128] FIG. 4
[0129] A liquid crystal device as described in Example 4.
[0130] FIG. 5
[0131] Some of the compounds of the present invention which were
produced as described in Example 1.
[0132] FIG. 6
[0133] A putative mixed ("edge to face") dimer complex of the
present invention.
[0134] FIG. 7
[0135] Scheme 1, showing phase transitions determined by DSC and
optical microscopy. Enthalpy data were determined by DSC at a
heating/cooling rate of 10.degree. C. min.sup.-1. K and K.sub.1
refer to crystal phases. The higher temperature mesophase for 1a
and 1b appears as a fan texture when viewed through a polarised
light microscope, characteristic of a columnar mesophase with
hexagonal cross sectional symmetry in which the columns are
disordered; ie D.sub.2. The lower temperature mesophase shows a
needle type texture comparable with that assigned elsewhere to a
second D.sub.1 mesophase within the octaalkylphthalocyanine
series.
EXAMPLES
Example 1
Preparation of Compounds of the Present Invention
[0136] Briefly, the novel macrocyclic derivative Formula VI,
wherein M was 2H (designated 1a) was obtained by reaction of
3,4-dicyanopyridine with excess 3,6-dioctylphthalonitrile.sup.9
under basic (lithium pentyloxide) conditions. Following
conventional workup, 1a (10%) was separated chromatographically
from the principal by-product,
1,4,8,11,15,18,22,25-octaocrylphthalocyanine..sup.9
[0137] The compounds 81 to 88 shown in FIG. 5 were generated from
the metal-free compound 80 (=1a) as exemplified by the Cu, Zn and
Ni derivatives described below.
[0138] Preparation of
1,4,8,11,15,18-(hexaoctyl)tribenzo-3,4-pyrdinoporphy- razine
[0139] In a typical procedure, 3,6-dioctylphthalonitrile (3.17 g, 9
mmol) and 3,4-dicyanopyridine (0.13 g, 1 mmol) in dry pentan-1-ol
(30 ml) were heated under reflux with stirring and lithium metal
(0.2 g) was added slowly in small portions. The solution turned an
intense green colour immediately and reflux was continued for 6
hours, then the mixture was allowed to cool to room temperature and
glacial acetic acid (50 ml) was added and stirring continued for 30
minutes. The solvents were removed under reduced pressure and the
mixture washed onto a filter with methanol (500 ml) to remove
non-phthalocyanine impurities, the rest of which were left on the
filter when the Pcs were taken up in THF. The solvent was removed
under reduced pressure and the mixture was separated using column
chromatography over silica gel. The first green fraction contained
only metal-free 1,4,8,11,15,18,22,25-octaoctylphthalocyanine using
as eluent light petroleum. The next green fraction was collected,
eluent THF, and further purified by column chromatography over
silica gel, eluent cyclohexane-THF (9:1) and recrystallised from
THF-methanol to afford
1,4,8,11,15,18-(hexaoctyl)tribenzo-3,4-pyridinoporphyrazine as a
blue solid (125 mg, 10% based on 3,4-dicyanopyridine). Mp
142.degree. C. (K-D), 242EC (D-I); FAB-MS (LSIMS) m/z 1188. (Found:
C, 79.54; H, 9.55; n, 10.65. C.sub.79H.sub.113N.sub.9 requires: C,
79.82; H, 9.58; n, 10.60). .nu..sub.max (DCM)/cm.sup.-1: 3285 (NH)
and 1600 (aromatic); .delta..sub.H (270 MHZ: C.sub.6D.sub.6): -2.17
(br s, 2H), 0.85-0.96 (m, 18H), 1.20-1.95 (m, 60H), 2.2-2.5 (m,
12H), 4.10 (br s, 4H), 4.43 (M, 4H), 4.54 (m, 4H), 7.65-7.8 (m,
4H), 7.86 (s, 2H), 8.53 (d, 1H), 9.14 (d, 1H), 10.35 (s, 1H);
.lambda..sub.max (cyclohexane)/nm: 328, 687 and 710. The third
fraction to be collected was obtained using cyclohexane-THF (2:1)
as eluent and recrystallised from THF-methanol to afford
di-3,4-pyridino-1,4,8,11-(tetraoctyl)dibenzo-porphyrazine as a dark
blue solid (5 mg, 1% based on 3,4-dicyanopyradine). Mp 250EC (K-D),
326 (D-I); FAB (LSIMS) m/z 966; (Found: C, 77.25; H, 8.53; N, 14.24
C.sub.62H.sub.80N.sub.10 requires: C, 77.14; H, 8.35; N, 14.51).
.delta..sub.H (270 MHz; C.sub.6D.sub.6; 50EC): -4.35--3.83 (t,
211), 0.95 (t, 12H), 2.15-2.41 (m, 8H), 3.94 (m, 4H), 4.20 (m, 4H),
7.59-7.74 (m, 4H), 8.19-8.30 (m, 2H), 8.96-9.03 (m, 2H),
10.04-10.15 (t, 2H), .lambda..sub.max (cyclohexane)/nm: 324, 669,
705.
[0140] Preparation of Copper
1,4,8,11,15,18-(hexaoctyl)tribenzo-3,4-pyridi- noporphyrazine
[0141] In a typical procedure, copper(II) acetate (0.2 g) was added
to a stirred solution of
1,4,8,11,15,18-(hexahexyl)tribenzo-3,4-pyridinoporphy- razine (70
mg) in pentan-1-ol (20 ml) and heated under reflux for 90 minutes.
The solvent was removed under reduced pressure and the residue
purified using column chromatography over silica gel using as
eluent cyclohexane-THF (5:1) and recrystallised from THF-methanol
to afford copper
1,4,8,11,15,18-(hexaoctyl)tribenzo-3,4-pyridinoporphyrazine as a
blue solid (48 mg, 65%). Mp 134.degree. C. (K-D), 319.degree. C.
(D-I); FAB (LSIMS) m/z 1249; (Found: C, 75.84: H, 9.00; N, 9.90.
C.sub.79H.sub.111N.sub.9Cu requires: C, 75.89; H, 8.95; N, 10.08).
.lambda..sub.max (cyclohexane)/nm: 325, 343 629, 649, 686, 701.
[0142] Preparation of Nickel and Zinc Derivatives
[0143] The Ni derivative (designated 1b) or Zn derivative
(designated 1c) were produced by reactions of 1a with nickel
acetate and zinc acetate in refluxing pentanol generated 1b (53%)
and 1c (78%). Each gave a satisfactory elemental analysis and low
resolution FAB-ms as follows: Found: C, 79.54; H, 9.55; N, 10.65;
C.sub.79H.sub.113N.sub.9 requires: C, 79.82: H, 9.58; N, 10.60. 1b,
Found: C, 76.10; H, 9.00; N, 9.95; C.sub.79H.sub.111N.sub.9Ni
requires: C, 76.18; H, 8.98; N, 10.12. 1c, Found: C, 75.68; H,
8.78; N, 9.95; C.sub.79H.sub.111N.sub.9Zn requires: C, 75.78; H,
8.94; N, 10.07.
[0144] All three compounds (1a, 1b, 1c) showed good solubility in
solvents such as THF, toluene, cyclohexane and dichloromethane.
[0145] Compounds of the present invention based on a
napthalocyanine structure (i.e. azanapthalocyanines) can be
prepared by methods analogous to those described above, in
conjunction with the disclosure of Cammidge et al (1997) J
Porphyrins Pthalocyanines 1:77-86.
Example 2
Spectra of the Compounds
[0146] The properties of the substituted
pyridino[3,4]-tribenzoporphyrazin- es, 1, prove to be highly
dependent upon the atom(s) at the centre of the macrocycle and
reflect the individual compound's propensity for forming either
Face-to-Face assemblies or Edge-to-Edge complexes. The Q-band
absorptions in the visible region spectra of solutions of 1a (2H)
and 1b (Ni) in cyclohexane at ca. 1.times.10.sup.-6M are shown in
FIG. 1. The two component Q-band of 1a, top spectrum in FIG. 1, is
similar to that of a metal-free Pc. The Q-band of 1b, the middle
spectrum, is also split .lambda..sub.max 694 and 679 nm, differing
from that of simple metallated Pcs but consistent with the lower
symmetry of the system..sup.10 Otherwise, the high extinction
coefficients of the Q-bands, see legend to FIG. 1, and the very low
intensity absorptions to the blue are characteristic of Pc
compounds which are essentially non aggregated. At high
concentrations, however, Face-to-Face type aggregation becomes
apparent, manifested by the characteristic enhanced absorption in
the region 600 to 690 nm (see the inset spectra in FIG. 1) and the
lower extinction coefficients of the lowest energy bands.
[0147] The zinc derivative, 1c, shows different behaviour. The
spectrum of 1c in cyclohexane, the bottom spectrum in FIG. 1, and
in dichloromethane shows enhanced separation of the main Q-band
components .lambda..sub.max 716 and 675 nm, within a band envelope
which is essentially invariant over the concentration range ca.
1.times.10.sup.-7M. In particular, extinction coefficients remain
high at the higher concentrations. Absence of Face-to-Face
aggregation is signified by the lack of significant absorption in
the visible region to the blue of these main bands. The gel
permeation chromatogram obtained for elution of 1c as a solution in
dichloromethane through PLgel 100A and 500A, 30 cm, 5 micron
columns and calibrated against polystyrene gives a peak molecular
mass, Mp, of 2050 (M.sub.w 1630 and M.sub.n 1390). Elution of three
model phthalocyanine derivatives under the same conditions showed
that the "polystyrene equivalent" molecular masses for these
macrocycles are consistently 20-25% lower than the actual molecular
mass. Thus the Mp obtained for 1c suggests that under the
conditions of the GPC experiment, the material has formed a dimeric
complex.
[0148] Thus we assign the visible region spectrum of 1c, above, to
a dimeric species (or lower oligomeric species) arising from
intermolecular axial ligation of a pyridyl nitrogen of one
macrocycle with the zinc atom of a second, to form an Edge-to-Face
complex. In support of this, we note that addition of pyridine or
THF changes the band shape to one closely resembling that of
non-aggregated 1b; this we attribute to disruption of the
homoligated complex of 1c. Similarly, excitation of 1c
(.lambda..sub.ex 650 nm) as a solution in toluene at
1.2.times.10.sup.-5M shows fluorescence emission at
.lambda..sub.max 731 nm. Addition of 100 Fl pyridine raises the
emission intensity by a factor of two and shifts the emission band
to 720 nm. In contrast 1a under the same conditions shows
.lambda..sub.em 721 nm, essentially unchanged when pyridine is
added.
[0149] Further confirmation of the formation of Edge-to-Face
complexes by 1c was obtained by .sup.1H-NMR spectroscopy. The
spectrum of 1c in benzene-d.sub.6 shows no signals downfield of
.delta. 8.32. Upon addition of pyridine-d.sub.5, the spectrum
simplifies and is very similar to that of 1a. In particular, the
pyridyl protons of 1c now appear at 9.25, 9.43 and 11.12 ppm. We
believe it likely that higher oligomers may be present at the
higher solution concentrations used in the NMR experiment.
[0150] NMR spectroscopy of 1a (Ni derivative) at 1 mM suggests some
degree of edge-to-face structure, in addition to UV-VIS evidence
suggesting face-to-face structures which is discussed above.
Example 3
TEM
[0151] Transmission electron microscopy highlighted differences in
packing in the condensed states of 1a, 1b and 1c. A drop of a
solution of each compound in THF (2 mg per ml) was administered
onto a copper grid, blotted dry, and viewed through a JEOL 100CX
Electron Microscope as the solvent evaporated. FIG. 2 shows the
micrograph obtained for 1b. It clearly shows the generation of a
columnar structure, formally analogous to the "molecular wires"
observed by Nolte et al..sup.11 for a more complex Pc derivative.
Compound 1a showed similar behaviour. The width of the assembly
depicted in FIG. 2 is ca. 15 times the approximate diameter of the
individual molecules of 1b. In contrast, 1c forms a distinctly
different structure, the micrograph showing an apparently
featureless film with no evidence of column formation.
Example 4
LC Properties
[0152] The differences in the molecular packings in the condensed
phase lead to different behaviour on heating and cooling. Thus,
compounds 1a and 1b exhibit thermotropic columnar mesophases;
polarised light microscope shows a fan type structure on cooling
from the isotropic liquid consistent with the hexagonal columnar
mesophase exhibited by other non-peripherally alkyl-substituted
Pcs..sup.12 Phase transition data are reported in Scheme 1 (FIG.
7). In contrast, 1c does not exhibit a mesophase during either
heating of the solid sample or upon cooling from the liquid phase;
this we attribute to the orthogonal packing of adjacent molecules
in the solid state and, presumably, in the liquid state just prior
to crystallisation.
Example 5
Spin Coated Films
[0153] Large area evaporated films were formulated by the spin
coating technique by administering a drop of solution of each
compound in THF (ca. 2 mg in 0.5 ml) onto a glass slide rotating a
2000 rpm. Films so formed were transparent and showed no
crystallites when viewed under an optical microscope. Their visible
region spectra are shown in FIGS. 3a-3c. Those for the films of 1a
and 1b are closely similar to the spectra of films of metal-free
and nickel 1,4,8,11,15,18,22,25-octa-octyl- phthalocyanines
respectively.sup.[12] whereas the film spectrum for 1c, FIG. 3c, is
similar to its solution phase spectrum, albeit blue-shifted by ca.
10 nm. Exposure of the latter film to pyridine vapour did not
change the spectrum. However, the assembly became disrupted upon
exposure to HCl vapour. The new spectrum is shown in FIG. 3d.
Within 30 days the original spectrum was recovered, implying that
the response to HCl is fully reversible and the molecules
reassemble to give the intermolecular complex.
[0154] In conclusion, we have identified a phthalocyanine type
macrocycle whose molecular packing is governed by the central metal
ion. Both Face-to-Face and Edge-to-Face packing has been
identified. The latter is promoted by the propensity for zinc to
undergo strong axial ligation and columnar liquid crystal
behaviour, otherwise inherent within the series, is inhibited.
Nickel complexes may also undergo weak axial ligation. However, 1b
at UV/vis concentrations and in the liquid crystal phases favours
Face-to-Face structures in which the Ni(II)d.sup.8 ion is
presumably in its favoured spin paired, square-planar four
coordinate state.
Example 6
An LCD Device
[0155] An example of the use of a compound of Formula I in a liquid
crystal material and device embodying the present invention will
now be described with reference to FIG. 4.
[0156] The liquid crystal device consists of two transparent
plates, 1 and 2, in this case made from glass. These plates are
coated on their internal face with transparent conducting
electrodes 3 and 4. An alignment layer 5, 6 is introduced onto the
internal faces of the cell so that a planar orientation of the
molecules making up the liquid crystalline material will be
approximately parallel or at a small angle to the glass plates 1
and 2. For some types of display the plane of the molecules is
approximately perpendicular to that of the glass plates, and at
each glass plate the alignment directions are orthogonal. The
electrodes 3, 4 may be formed into row and column electrodes so
that the intersections between each column and row form an x, y
matrix of addressable elements or pixels. A spacer 7 e.g. of
polymethyl methacrylate separates the glass plates 1 and 2 to a
suitable distance e.g. 2 microns. Liquid crystal material 8 is
introduced between glass plates 1, 2 by filling the space in
between them. The spacer 7 is sealed with an adhesive 9 in a vacuum
using an existing technique. Polarisers 10, 11 are arranged in
front of and behind the cell. For some devices, only one or even no
polarisers are required.
[0157] The device may operate in a transmissive or reflective mode.
In the former light passing through the device, e.g. from a
tungsten bulb, is selectively transmitted or blocked to form the
desired display. In the reflective mode a mirror (12) is placed
behind the second polariser 11 to reflect ambient light back
through the cell and two polarisers. By making the mirror partly
reflecting the device may be operated both in a transmissive and
reflective mode.
[0158] The alignment layers 5, 6 have two functions one to align
contacting liquid crystal molecules in a preferred direction and
the other to give a tilt to these molecules--a so called surface
tilt--of a few degrees typically around 4 or 5.degree.. The
alignment layers 5, 6 may be formed by placing a few drops of the
polyimide onto the cell wall and spinning the wall until a uniform
thickness is obtained. The polyimide is then cured by heating to a
predetermined temperature for a predetermined time followed by
unidirectional rubbing with a roller coated with a nylon cloth.
Example 7
Gas Sensor
[0159] In another example a layer of liquid crystal material is
exposed to a gas to provide a gas sensor.
Example 8
Mixed Dimers
[0160] Upon introduction of 1.0 eq of Zn
1,4,8,11,15,18,22,25-octahexylpht- halocyanine (designated 6Zn in
FIG. 6) into the .sup.1H NMR solution of compound 80 in
C.sub.6D.sub.6 there was no signal observed downfield of
.delta.8.05. Prior to this addition the signals for the pyridyl
protons appeared 8.53, 9.14, 10.35 ppm. Instead of three signals
representing the methylene protons next to the ring, four signals
appear. This seems to suggest that on formation of a dimeric
complex through the coordination of the pyridine unit of compound
80 to the zinc centre of the 67Zn; the ring current of the 6Zn
shields two methylene protons of 80 to a significant degree causing
an upfield shift of 0.43 ppm. The N--H proton of 80 is shifted
downfield by 0.55 ppm.
REFERENCES
[0161] 1. Phthalocyanines--Properties and Applications, eds.
Leznoff and Lever, VCH Publishers, New York, 1989.
[0162] 2. Cook, in Spectroscopy of New Materials, eds. Clark and
Hester, Wiley, Chichester, 1993,p.87.
[0163] 3. Simon and Bassoul, in Phthalocyanines--Properties and
Applications, eds. Leznoff and Lever, VCH Publishers, New York,
1993, vol.2,p.223.
[0164] 4. See, for example, Mason et al. J.Chem.Soc., Dalton Trans.
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[0165] 5. Pomogailo and Wohrle, in Macromolecule-Metal Complexes,
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[0167] 7. Linstead et al., J.Chem.Soc., 1937,911.
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[0169] 9. Chambrier et al., J.Mater.Chem., 1993,3,841.
[0170] 10. cf. Kobayashi et al., J.Am.Chem.Soc., 1996,118,1073;
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[0171] 11. van Nostrum et al., Angew.Chem., Int.Ed.Engl.,
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[0172] 12. Cherodian et al., Mol.Cryst.Liq.Cryst.,
1991,196,103.
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