Glycosylated zinc(II) phthalocyanines as efficient photosensitisers for photodynamic therapy. Synthesis, photophysical properties and in vitro photodynamic activity

Article abstract of DOI:10.1039/b802212g

Treatment of 3- or 4-nitrophthalonitrile with 1,2:5,6-di-O-isopropylidene- α-d-glucofuranose or 1,2:3,4-di-O-isopropylidene-α-d-galactopyranose in the presence of K₂CO₃ gave the corresponding glycosubstituted phthalonitriles. These precursors underwent self-cyclisation, or mixed-cyclisation with the unsubstituted phthalonitrile, to afford the tetra- or mono-glycosylated zinc(ii) phthalocyanines, respectively. As shown by absorption spectroscopy, these compounds were not significantly aggregated in organic solvents, giving a weak to moderate fluorescence emission. Upon irradiation these compounds could sensitise the formation of singlet oxygen in DMF, with quantum yields in the range of 0.40-0.66. The in vitro photodynamic activities of these compounds against HepG2 human hepatocarcinoma and HT29 human colon adenocarcinoma cells were also studied. The mono-glycosylated phthalocyanines exhibited significantly higher photocytotoxicity compared with the tetra-α-glycosylated analogues, having IC₅₀ values down to 0.9 μM. The tetra-β-glycosylated counterparts were essentially inactive. The lower photocytotoxicities of the tetra-glycosylated phthalocyanines are in line with their lower cellular uptake and/or higher aggregation tendency as reflected by weaker intracellular fluorescence, and lower efficiency at generating intracellular reactive oxygen species. For the mono-glycosylated phthalocyanines, the higher uptake can be attributed to their hydrophilic saccharide units, which increase the amphiphilicity of the macrocycles. The Royal Society of Chemistry 2008.

Full text of DOI:10.1039/b802212g

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Glycosylated zinc(II) phthalocyanines as efficient photosensitisers for
photodynamic therapy. Synthesis, photophysical properties and in vitro
photodynamic activity†
Chi-Fung Choi,a Jian-Dong Huang,a,b Pui-Chi Lo,a Wing-Ping Fongc and Dennis K. P. Ng*a
Received 8th February 2008, Accepted 17th March 2008
First published as an Advance Article on the web 18th April 2008
DOI: 10.1039/b802212g
Treatment of 3- or 4-nitrophthalonitrile with 1,2:5,6-di-O-isopropylidene-a-D-glucofuranose or
1,2:3,4-di-O-isopropylidene-a-D-galactopyranose in the presence of K2CO3 gave the corresponding
glycosubstituted phthalonitriles. These precursors underwent self-cyclisation, or mixed-cyclisation with
the unsubstituted phthalonitrile, to afford the tetra- or mono-glycosylated zinc(II) phthalocyanines,
respectively. As shown by absorption spectroscopy, these compounds were not significantly aggregated
in organic solvents, giving a weak to moderate fluorescence emission. Upon irradiation these
compounds could sensitise the formation of singlet oxygen in DMF, with quantum yields in the range
of 0.40–0.66. The in vitro photodynamic activities of these compounds against HepG2 human
hepatocarcinoma and HT29 human colon adenocarcinoma cells were also studied. The
mono-glycosylated phthalocyanines exhibited significantly higher photocytotoxicity compared with the
tetra-a-glycosylated analogues, having IC50 values down to 0.9 lM. The tetra-b-glycosylated
counterparts were essentially inactive. The lower photocytotoxicities of the tetra-glycosylated
phthalocyanines are in line with their lower cellular uptake and/or higher aggregation tendency as
reflected by weaker intracellular fluorescence, and lower efficiency at generating intracellular reactive
oxygen species. For the mono-glycosylated phthalocyanines, the higher uptake can be attributed to their
hydrophilic saccharide units, which increase the amphiphilicity of the macrocycles.
One of the major challenges in PDT is to develop selective
photosensitisers which can preferentially accumulate in malignant
Introduction
Phthalocyanines represent an important class of functional dyes.1
tissues relative to normal tissues. Although a level of selectivity
In addition to their use as advanced materials in various fields,
can be achieved by the confined illumination of the target
these macrocyclic compounds have also found application in
area, the use of selective photosensitisers, which can greatly
medicine. Owing to their strong and long-wavelength absorptions,
reduce the side effects and enhance the therapeutic outcomes,
high efficiency at generating reactive oxygen species (ROS), and
is still important. Various approaches have been explored to
ease of chemical modification, phthalocyanines have emerged
enhance the photosensitiser concentrations in target tissues, and
as a promising class of second-generation photosensitisers for
include encapsulation in colloidal carriers such as liposomes and
photodynamic therapy (PDT).2 Over the last decade, a sub-
stantial number of phthalocyanine-based photosensitisers have
been prepared and evaluated for their photodynamic activity,
with the focus on silicon, zinc and aluminium analogues as a
result of their desirable photophysical properties. To date, several
phthalocyanine systems such as the silicon(IV) phthalocyanine Pc4
and a liposomal preparation of zinc(II) phthalocyanine have been
in clinical trials. Photosenseꢀ, which is a mixture of sulfonated
aluminium(III) phthalocyanines, is clinically used in Russia for the
treatment of a range of cancers.2c
polymeric micelles,3 and conjugation to tumour-specific carrier
molecules such as antibodies, synthetic peptides, epidermal growth
factor and adenoviruses, etc.4 For the latter approach, only a
limited target specificity has been achieved so far.
In addition to these biomolecules, carbohydrates are also
promising candidates for bioconjugation to photosensitisers to
achieve targeted PDT. It has long been known that cancer cells
have increased levels of glucose uptake and glycolysis in order to
provide sufficient metabolic energy to sustain their proliferation.5
The transport of glucose across the cell membrane is mediated
by glucose transporter proteins, which are over-expressed in a
variety of human carcinomas.6 By taking advantage of this,
glycoconjugation of various photosensitisers such as porphyrins,7
chlorins,8 pyropheophorbides9 and hypocrellins10 has been carried
out with a view to enhancing their cellular uptake and eventually
the PDT efficacy. In a number of cases, particularly for the
unsymmetrically conjugated analogues, promising results have
been observed.7d,8a,c,9
R
aDepartment of Chemistry and Centre of Novel Functional Molecules,
The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
E-mail: dkpn@cuhk.edu.hk; Fax: +852 2603 5057; Tel: +852 2609 6375
bCollege of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou
350002, China
cDepartment of Biochemistry and Centre of Novel Functional Molecules,
The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
† Electronic supplementary information (ESI) available: 1H–1H COSY and
HMQC with BIRD spectra of 18 and UV–vis spectra of 6, 8 and 13. See
DOI: 10.1039/b802212g
In contrast to carbohydrate–porphyrin conjugates, glycocon-
jugated phthalocyanines are extremely rare despite their great
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potential in PDT.11 We have recently prepared a novel series of
silicon(IV) phthalocyanines with isopropylidene-protected glucose
and galactose moieties as the axial substituents.12 These com-
pounds exhibit a high cellular uptake and are highly potent
toward several cancer cell lines. The IC50 values, defined as
the dye concentration required to kill 50% of the cells, are as
low as 6 nM. Herein we describe an extension of this work,
focusing on zinc(II) analogues, which are generally more stable
than their silicon(IV) counterparts. Although the synthesis and
characterisation of several glycosylated zinc(II) phthalocyanines
have been reported,11 their photobiological properties remain
unexplored. In this paper, we report the synthesis, spectroscopic
characterisation and photophysical properties of a new series
of mono- and tetra-glycosylated phthalocyanines. The in vitro
photodynamic activities of this class of photosensitisers are also
reported for the first time.
solvents. It was difficult to find an appropriate solvent system to
isolate the C4 isomers by recrystallisation. Hence, compounds 6
and 7 were prepared as mixtures of structural isomers.
Subsequent metallation of these compounds with Zn(OAc)2·
2H2O in DMF gave the corresponding zinc(II) complexes 8 and
9 in good yields (75% and 79%, respectively). It was found that,
upon treatment with Zn(OAc)2·2H2O and DBU, phthalonitriles 4
and 5 could be directly converted to zinc phthalocyanines 8 and 9
respectively, but this one-step procedure seemed to produce more
side products, which slightly hindered the purification process.
By contrast, this one-step cyclisation method could be readily
employed to prepare the tetra-b-substituted analogues ZnPc(b-
PGlu)4 (13) and ZnPc(b-PGal)4 (14). As shown in Scheme 2, treat-
ment of 4-nitrophthalonitrile (10) with protected monosaccharide
2 or 3 gives the substituted product 11 or 12, which undergoes a
DBU-promoted self-cyclisation reaction using Zn(OAc)2·2H2O as
the template to give phthalocyanine 13 or 14. These compounds,
again as mixtures of structural isomers, could be readily purified by
Results and discussion
Synthesis and characterisation
Scheme 1 shows the synthetic route to tetra-a-glycosylated ph-
thalocyanines 6–9. Treatment of 3-nitrophthalonitrile (1) with the
isopropylidene-protected glucofuranose 2 or galactopyranose 3
in the presence of K2CO3 in DMF led to nucleophilic aromatic
substitution, giving the corresponding glycosylated phthalonitrile
4 or 5. These compounds then underwent a cerium-promoted
cyclisation reaction13 to afford the metal-free phthalocyanines
H2Pc(a-PGlu)4 (6) and H2Pc(a-PGal)4 (7) in moderate yields
(47% and 58%, respectively). By using the phthalonitrile with a
bulky 2,4-dimethyl-3-pentoxy group at the a-position, we have
found that the 1,8,15,22- (or C4) isomer is predominantly formed,
which can be isolated by column chromatography followed by
recrystallisation.13,14 However, the tetra-a-glycosylated phthalo-
cyanines 6 and 7 exhibited excellent solubility in most organic
Scheme 2
Scheme 1
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silica-gel column chromatography. The glycosylated phthalonitrile
11 and phthalocyanine 13 have been described previously, but only
the UV–vis data have been given.11a
To enhance the amphiphilicity of the molecules, which is
generally believed to be an advantageous characteristic in
photosensitisers,15 we also prepared the mono-glycosylated ana-
logues 16–19. These compounds were prepared (in 25–43% yields)
by mixed cyclisation of the glycosylated phthalonitrile 4, 5, 11
or 12 with an excess of the unsubstituted phthalonitrile 15 (9
equiv.) using lithium as the template, followed by metallation with
Zn(OAc)2·2H2O (Scheme 3). These A3B-type cyclised products
could be separated from the other side products by silica-gel col-
umn chromatography followed by size exclusion chromatography.
Fig. 1 1H–1H COSY spectrum of ZnPc(b-PGlu)4 (13) in CDCl3 with a
trace amount of pyridine-d5 (ca. 1% v/v); * indicates signals for residual
solvents.
four methyl groups). The assignment was supported by its 1H–1H
COSY spectrum (Fig. S1†). Due to the low symmetry of these
compounds, the 13C{ H} NMR signals for the phthalocyanine
1
Scheme 3
ring were split, but extensively overlapped. Nevertheless, some of
the phthalocyanine a- and b-ring carbon signals, as well as those
for the sugar ring could be identified using HMQC with BIRD
spectra [see the spectrum for 18 (Fig. S2†) given as an example].
The ESI mass spectra of all the phthalocyanines showed the
protonated molecular ion [(M + H)+] signal as the base peak,
of which the isotopic distribution was in good agreement with the
simulated pattern. The identity of these species was also confirmed
by accurate mass measurements.
Attempts were made to remove the isopropylidene protecting
groups of the zinc(II) phthalocyanines ZnPc(a-PGlu)4 (8) and
ZnPc(a-PGlu) (16) by treatment with trifluoroacetic acid and
water (v/v 9 : 1). Difficulties were encountered in the purification
of the products either by chromatography or recrystallisation.
1
The H NMR signals of the crude products in DMSO-d6 were
significantly broadened and were difficult to assign. It is likely that
the deprotected sugar moieties promote the aggregation of the
macrocycles through hydrogen bonding formation. This possible
phenomenon, together with the anomerisation of the sugar
moieties, complicates the spectra, hindering the characterisation
of these compounds. Due to these difficulties, deprotection of these
glycosylated phthalocyanines was not pursued further.
All the new compounds were unambiguously characterised
by various spectroscopic methods. For the tetra-b-glycosylated
phthalocyanines 13 and 14, although they exist as a mixture of
Electronic absorption and photophysical properties
The electronic absorption and basic photophysical data of these
glycosylated phthalocyanines are summarised in Table 1. The
absorption and fluorescence spectra of the tetra-substituted ph-
thalocyanines were recorded in chloroform, but for the mono-
substituted analogues, due to their limited solubility in neat
chloroform, the spectra were taken in THF. The UV–vis spectra
of these compounds were typical for phthalocyanines with a low
aggregation tendency, showing one (for zinc(II) analogues) or two
(for metal-free analogues) intense Q band(s) at the red visible
region. The Q bands for the a-substituted zinc(II) phthalocyanines
were significantly red-shifted by 18–20 nm (for tetra-substituted
analogues) or 5–6 nm (for mono-substituted analogues) compared
with those for the b-substituted counterparts [see the spectra of 6,
8 and 13 (Fig. S3†)]. a-Glycosylation also led to a weakening of the
fluorescence emission. For the tetra-substituted series (8, 9, 13 and
14), the change from b to asubstitution decreased the fluorescence
quantum yield by about four-fold (Table 1). These results are in
accord with the observations and theoretical calculations reported
previously for a series of metal-free and zinc(II) phthalocyanines.16
The effects of the sugar moieties are insignificant both on the
absorption and fluorescence emission properties.
1
structural isomers, the H NMR spectra recorded in CDCl3 in
the presence of a trace amount of pyridine-d5 are simpler than
expected. Three well-separated multiplets in the region d 7.7–9.5
were observed for the three sets of phthalocyanine ring protons.
The sugar protons resonated as six (for 13 at d 4.2–6.2) or three
(for 14 at d 4.4–5.8) multiplets, while the isopropylidene methyl
groups resonated as several singlets at d 1.3–1.9. The assignment
could be readily made with the aid of 1H–1H COSY spectra. Fig. 1
shows the spectrum of 13 for illustration.
The NMR spectra for the mono-glycosylated phthalocyanines
16–19 were also informative. Taking the H NMR spectrum of
1
18 as an example, it showed a multiplet at d 9.06–9.30 (7 H) and
a broad signal at d 8.85 (1 H) for the eight phthalocyanine a
ring protons. The seven b ring protons resonated as a multiplet
at d 7.93–8.11 (6 H) and a doublet at d 7.67 (1 H). The signals
for the protected glucose appeared as three doublets (for H1, H2
and H3 of the glucofuranose ring), one doublet of doublets (for
H4), two multiplets (for H5 and H6) and four singlets (for the
The singlet oxygen quantum yields (UD) of these glyco-
sylated phthalocyanines were also determined in DMF us-
ing 1,3-diphenylisobenzofuran (DPBF) as the scavenger. The
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Table 1 Electronic absorption and photophysical data for the glycosylated phthalocyaninesa
c
d
Compound
kmax/nm (log e)
kem/nmb
Uf
UD
H2Pc(a-PGlu)4 (6)
H2Pc(a-PGal)4 (7)
ZnPc(a-PGlu)4 (8)
ZnPc(a-PGal)4 (9)
ZnPc(b-PGlu)4 (13)
ZnPc(b-PGal)4 (14)
ZnPc(a-PGlu) (16)
ZnPc(a-PGal) (17)
ZnPc(b-PGlu) (18)
ZnPc(b-PGal) (19)
315 (4.68), 353 (4.65), 626 (4.43), 660 (4.59), 690 (5.06), 724 (5.11)
315 (4.68), 352 (4.59), 626 (4.42), 659 (4.56), 691 (5.05), 724 (5.10)
319 (4.57), 350 (4.56), 629 (4.49), 669 (4.41), 698 (5.20)
319 (4.56), 350 (4.58), 629 (4.54), 667 (4.44), 699 (5.31)
350 (4.82), 612 (4.38), 648 (4.31), 680 (5.09)
351 (4.89), 613 (4.48), 647 (4.43), 679 (5.15)
343 (4.88), 607 (4.65), 645 (4.62), 673 (5.40)
341 (4.76), 608 (4.53), 645 (4.49), 672 (5.28)
344 (4.85), 603 (4.59), 640 (4.53), 667 (5.38)
344 (4.92), 603 (4.65), 639 (4.59), 667 (5.42)
724
726
705
706
687
689
679
678
673
673
0.03
0.05
0.07
0.06
0.23
0.24
0.20
0.21
0.26
0.26
0.12
0.14
0.66
0.52
0.41
0.40
0.47
0.44
0.47
0.45
a Recorded in chloroform (for 6–9 and 13–14) or THF (for 16–19) unless otherwise stated. b Excited at 610 nm (for 13–14 and 16–19) or 625 nm (for
6–9). c Uf: fluorescence quantum yield relative to unsubstituted zinc(II) phthalocyanine (ZnPc) (Uf = 0.30 in 1-chloronaphthlene). d UD: singlet oxygen
quantum yield measured in DMF relative to ZnPc (UD = 0.56).
Table 2 IC50 values of the glycosylated zinc(II) phthalocyanines 8, 9 and
16–19 against HepG2 and HT29 cellsa
concentration of the quencher was monitored spectroscopically
at 411 nm along with time, from which the values of UD could be
determined by the method described previously.17 These data are
also compiled in Table 1. It can be seen that the tetra-a-substituted
zinc(II) phthalocyanines 8 and 9 give the highest UD values (0.66
and 0.52, respectively), while the metal-free phthalocyanines 6 and
Compound
For HepG2/lM
For HT29/lM
ZnPc(a-PGlu)4 (8)
ZnPc(a-PGal)4 (9)
ZnPc(a-PGlu) (16)
ZnPc(a-PGal) (17)
ZnPc(b-PGlu) (18)
ZnPc(b-PGal) (19)
4.7
5.1
1.1
1.7
1.8
1.5
4.0
3.5
1.0
1.7
2.0
0.9
7 are the least efficient at the generation of singlet oxygen (UD
=
0.12 and 0.14, respectively). This is in line with the higher triplet
quantum yields generally observed for zinc(II) phthalocyanines
compared with the metal-free analogues.18
a Defined as the dye concentration required to kill 50% of the cells.
In vitro photodynamic activities
The photodynamic activities of all the glycoconjugated zinc(II)
phthalocyanines in Cremophor EL emulsions were investigated
using two different cell lines, namely HT29 human colon ade-
nocarcinoma and HepG2 human hepatocarcinoma cells. In the
absence of light, all these compounds were essentially non-toxic to
the cells. Upon illumination, these compounds exhibited different
degrees of photocytotoxicity. While the tetra-b-glycosylated ph-
thalocyanines 13 and 14 remained non-cytotoxic up to 8 lM,
the other phthalocyanines, particularly the mono-substituted
analogues 16–19, were photodynamically active. Fig. 2 shows
the dose response curves for the galactosylated phthalocyanines
ZnPc(a-PGal)4 (9), ZnPc(b-PGal)4 (14), ZnPc(a-PGal) (17) and
ZnPc(b-PGal) (19) against HT29. A similar trend was observed
for the glucosylated series and for the HepG2 cells. The IC50
values of the tetra-a- (8 and 9) and mono-substituted (16–
19) photosensitisers against the two cell lines are compiled in
Table 2. It can be seen that the mono-glycosylated analogues
generally exhibit higher photocytotoxicity, with IC50 values down
to 0.9 lM. Apparently, the photocytotoxicity of these compounds
is higher than that of the tetrasulfonated zinc(II) phthalocyanine
and comparable if not better than that of the tetrasulfonated
Fig. 2 Effects of ZnPc(a-PGal)4 (9) (ꢀ), ZnPc(b-PGal)4 (14) (●),
ZnPc(a-PGal) (17) (ꢁ) and ZnPc(b-PGal) (19) (★) on HT29 cells in
the presence of light (k >610 nm, 40 mW cm−2, 48 J cm−2). Data are
expressed as mean values S. E. M. of three independent experiments,
each performed in quadruplicate.
R
aluminium(III) phthalocyanine and Photosenseꢀ, which are all
To account for the different photodynamic activities of these
compounds, their aggregation behaviour in the culture media
was examined by absorption and fluorescence spectroscopic
methods. Fig. 3a shows the UV–vis spectra of the galactosylated
phthalocyanines 9, 14, 17 and 19 in the DMEM medium (for
HT29 cells). It can be seen that the Q bands of 9, 17 and 19
remain sharp and intense, indicating that these compounds are
not significantly aggregated in the medium. By contrast, for the
tetra-b-substituted analogue ZnPc(b-PGal)4 (14), the Q band is
common phthalocyanine-based photosensitisers.19 Nevertheless,
compared with the silicon(IV) analogues prepared by us previously,
whose IC50 values could be as low as 6 nM,12 these zinc(II) gly-
cosylated phthalocyanines are substantially less photocytotoxic,
probably due to the higher intrinsic stacking tendency of these
non-axially substituted macrocycles. As shown in Table 2, the
sugar moieties do not have a significant effect on the photodynamic
activities of this series of compounds.
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Fig. 4 Fluorescence microscopic images of HT29 cells after being
incubated with (a) ZnPc(a-PGal)4 (9), (b) ZnPc(a-PGal) (17) and (c)
ZnPc(b-PGal) (19) (all at 8 lM) for 2 h.
the cells. The results can account for the trend in photocyto-
toxicity: 17 ≈ 19 > 9 > 14. A higher potency has also been
observed for unsymmetrical tetrapyrrolic photosensitisers having
three saccharide units compared with the symmetrical analogues
with four saccharide substituents.7d,8a
The intracellular production of ROS by these compounds in
HT29 cells was also studied using 2ꢀ,7ꢀ-dichlorodihydrofluorescein
diacetate (DCFDA) as the quencher. As shown in Fig. 5, all
the compounds cannot generate ROS in the absence of light.
Upon illumination, the efficiency at generating ROS follows the
order: 19 > 17 > 9 > 14, which is in accord with the trend in
photocytotoxicity.
Fig. 3 (a) UV–vis and (b) fluorescence spectra of ZnPc(a-PGal)4 (9),
ZnPc(b-PGal)4 (14), ZnPc(a-PGal) (17) and ZnPc(b-PGal) (19), formu-
lated with Cremophor EL, in the DMEM medium. The concentrations of
the phthalocyanines were fixed at 4 lM.
much weaker and significantly broadened. This indicates that
this compound is highly aggregated in the medium, which can
explain that even though it has a reasonably high singlet oxygen
quantum yield in DMF (Table 1), it shows no photocytotoxicity.
The higher aggregation tendency of 14 compared with the other
three compounds was in accord with its much weaker fluorescence
in the culture medium (Fig. 3b). Similar results were obtained
for the glucosylated counterparts and in the RPMI medium (for
HepG2 cells).
Fig. 5 ROS production induced by ZnPc(a-PGal)4 (9), ZnPc(b-PGal)4
(14), ZnPc(a-PGal) (17) and ZnPc(b-PGal) (19) in HT29 cells (all at 8
In addition to the cell viability studies, we also employed
fluorescence microscopy to investigate the uptake of the galac-
tosylated phthalocyanines 9, 14, 17 and 19 by HT29 cells. After
incubation with these compounds (formulated with Cremophor
EL) for 2 h, and upon excitation at 630 nm, fluorescence images
of the HT29 cells were captured. It was found that for the tetra-
b-substituted analogue ZnPc(b-PGal)4 (14), no fluorescence was
observed. This indicated that the cellular uptake is negligible
and/or the compound is highly aggregated within the cells, both
of which disfavour photodynamic action. Hence, this compound is
not photocytotoxic. By contrast, the mono-substituted analogues
17 and 19 gave strong intracellular fluorescence throughout the
cytoplasm. The intensity was stronger than that caused by the
tetra-a-substituted analogue ZnPc(a-PGal)4 (9) as shown in Fig. 4.
These results suggested that the mono-substituted analogues 17
and 19 have a better cellular uptake, probably due to their
amphiphilic character,15 and lower aggregation tendency within
lM). Each data point represents the mean value
independent experiments, each performed in quadruplicate.
S. E. M. of three
Conclusions
In summary, we have prepared and characterised a new series of
glycosylated zinc(II) phthalocyanines. Compared with the tetra-
substituted analogues, the mono-glycosylated phthalocyanines
16–19 exhibit a higher cellular uptake, lower aggregation tendency
and higher efficiency at generating intracellular ROS, leading to
higher in vitro photocytotoxicity. Their IC50 values against HepG2
and HT29 cells are as low as 0.9 lM. For the tetra-substituted
series, the position of the substituents (a or b) also exerts a
great effect on their photodynamic activity. Although the tetra-b-
glycosylated phthalocyanines 13 and 14 are efficient singlet oxygen
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1
generators in DMF, their high aggregation tendency in the culture
media means they have no photodynamic activity.
(3.39 g, 66%). H NMR: d 7.61–7.66 (m, 1 H, ArH), 7.30–7.37
(m, 2 H, ArH), 5.53 (d, J = 4.8 Hz, 1 H, H1), 4.68 (dd, J = 2.4,
7.8 Hz, 1 H, H3), 4.43 (dd, J = 1.2, 7.8 Hz, 1 H, H4), 4.35 (dd,
J = 2.4, 4.8 Hz, 1 H, H2), 4.23–4.32 (m, 3 H, H5 and H6), 1.55
(s, 3 H, Me), 1.44 (s, 3 H, Me), 1.35 (s, 3 H, Me), 1.34 (s, 3 H,
Experimental
Me). 13C{ H} NMR: d 161.1, 134.5, 125.4, 117.3, 116.9, 115.3,
1
Experimental details regarding the purification of solvents, instru-
mentation and in vitro studies are described elsewhere.12b Singlet
oxygen quantum yields (UD) were measured in DMF by the
method of chemical quenching of DPBF using ZnPc as a reference
(UD(ref) = 0.56).20 A mixture of DPBF (0.24 mM, 1 mL) and the
photosensitiser (the absorbance at the excitation position was
adjusted to ca. 0.1, 1 mL) in DMF was illuminated with red
light coming from a 200 W halogen lamp after passing through a
water tank for cooling and a colour glass filter (Newport, cut-on
at 610 nm). The decay of the DPBF, as shown by the decrease
in absorbance at 411 nm, was monitored along with time. The
singlet oxygen quantum yield of the photosensitiser was estimated
using the relationship: UD(sample) ≈ UD(ref)(Wsample/Wref), where W
represents the photobleaching rate of DPBF, taken as the slope of
the central linear region of the decay curve.17
112.8, 109.5, 109.1, 105.3, 96.2, 70.6 (3 overlapping signals), 68.3,
66.1, 26.1, 25.9, 24.9, 24.3. MS (ESI): m/z 409 [100%, (M + Na)+].
HRMS (ESI): m/z calc. for C20H22N2NaO6 (M + Na)+, 409.1370;
found, 409.1374. Anal. calcd for C20H22N2O6: C 62.17, H 5.74, N
7.25; found: C 62.10, H 5.73, N 6.93.
4-(1,2:5,6-Di-O-isopropylidene-a-D-glucofuranosyl)phthalonitrile
(11)
According to the general procedure, 4-nitrophthalonitrile (10)
(3.14 g, 18.1 mmol) was treated with protected glucose 2 (6.39 g,
24.5 mmol) in DMF (20 mL) to give 11 as a white crystalline solid
1
(5.14 g, 73%). H NMR: d 7.75 (d, J = 8.7 Hz, 1 H, ArH), 7.41
(d, J = 2.7 Hz, 1 H, ArH), 7.31 (dd, J = 2.7, 8.7 Hz, ArH), 5.95
(d, J = 3.9 Hz, 1 H, H1), 4.79 (d, J = 3.0 Hz, 1 H, H3), 4.54 (d,
J = 3.9 Hz, 1 H, H2), 4.28–4.31 (m, 1 H, H5), 4.24 (dd, J = 3.0,
8.7 Hz, H4), 4.15 (dd, J = 5.7, 8.7 Hz, 1 H, H6), 4.06 (dd, J =
4.5, 8.7 Hz, 1 H, H6), 1.56 (s, 3 H, Me), 1.42 (s, 3 H, Me), 1.33 (s,
General procedure for the preparation of glycosylated
phthalonitriles 4, 5, 11 and 12
3 H, Me), 1.28 (s, 3 H, Me). 13C{ H} NMR: d 159.8, 134.8, 126.2,
1
A mixture of 3- or 4-nitrophthalonitrile (1 equiv.), protected
monosaccharide 2 or 3 (1.5 equiv.) and K2CO3 (3 equiv.) in DMF
was stirred at 60 ◦C for 2 days (for 2) or room temperature for
4 days (for 3). The volatiles were evaporated in vacuo, then the
residue was dissolved in chloroform (250 mL). The solution was
washed with water (125 mL × 2), then dried over anhydrous
MgSO4. After evaporation under reduced pressure, the residue was
purified by silica-gel chromatography using ethyl acetate–n-hexane
(v/v 1 : 2) as the eluent. The crude product was further purified
by recrystallisation from chloroform layered with n-hexane.
118.1, 117.2, 115.0, 112.6, 105.9, 105.2, 82.7, 82.1, 79.0, 68.2, 64.0,
26.6, 26.2 (some of the signals are overlapped). MS (FAB): m/z
387 [15%, (M + H)+]. HRMS (FAB): m/z calc. for C20H23N2O6 (M
+ H)+, 387.1551; found, 387.1562.
4-(1,2:3,4-Di-O-isopropylidene-a-D-
galactopyranosyl)phthalonitrile (12)
According to the general procedure, 4-nitrophthalonitrile (10)
(2.56 g, 14.8 mmol) was treated with protected galactose 3 (5.39 g,
20.7 mmol) in DMF (20 mL) to give 12 as a white crystalline solid
(3.32 g, 58%). 1H NMR: d 7.70 (d, J = 8.7 Hz, 1 H, ArH), 7.33 (d,
J = 2.4 Hz, 1 H, ArH), 7.25 (dd, J = 2.4, 8.7 Hz, 1 H, ArH), 5.56
(d, J = 5.1 Hz, 1 H, H1), 4.67 (dd, J = 2.4, 7.8 Hz, 1 H, H3), 4.37
(dd, J = 2.4, 5.1 Hz, 1 H, H2), 4.32 (dd, J = 1.2, 7.8 Hz, 1 H, H4),
4.18–4.25 (m, 3 H, H5 and H6), 1.54 (s, 3 H, Me), 1.47 (s, 3 H,
3-(1,2:5,6-Di-O-isopropylidene-a-D-glucofuranosyl)phthalonitrile
(4)
According to the general procedure, 3-nitrophthalonitrile (1)
(1.08 g, 6.2 mmol) was treated with protected glucose 2 (2.42 g,
9.3 mmol) in DMF (10 mL) to give 4 as a white crystalline solid
(1.57 g, 65%). 1H NMR: d 7.67–7.72 (m, 1 H, ArH), 7.42–7.46 (m,
2 H, ArH), 6.01 (d, J = 3.9 Hz, 1 H, H1), 4.82 (d, J = 3.0 Hz,
1 H, H3), 4.59 (d, J = 3.9 Hz, 1 H, H2), 4.49 (ddd, J = 4.8, 6.0,
8.7 Hz, 1 H, H5), 4.26 (dd, J = 3.0, 8.7 Hz, 1 H, H4), 4.19 (dd,
J = 6.0, 8.7 Hz, 1 H, H6), 4.07 (dd, J = 4.8, 8.7 Hz, 1 H, H6),
1.55 (s, 3 H, Me), 1.41 (s, 3 H, Me), 1.32 (s, 3 H, Me), 1.30 (s, 3 H,
Me), 1.35 (s, 6 H, Me). 13C{ H} NMR: d 161.8, 135.1, 119.9, 119.5,
1
117.4, 115.6, 115.2, 109.8, 108.9, 107.5, 96.3, 70.8, 70.6, 70.3, 68.1,
66.2, 26.0, 25.9, 24.8, 24.4. MS (ESI): m/z 409 [100%, (M + Na)+].
HRMS (ESI): m/z calc. for C20H22N2NaO6 (M + Na)+, 409.1370;
found, 409.1374. Anal. calcd for C20H22N2O6: C 62.17, H 5.74, N
7.25; found: C 62.13, H 5.68, N 7.42.
1
Me). 13C{ H} NMR: d 159.7, 134.6, 126.2, 118.1, 117.2, 115.0,
112.6 (two overlapping signals), 109.5, 106.1, 105.3, 82.4, 82.2,
80.4, 71.7, 67.5, 26.9, 26.6, 26.2, 25.0. MS (FAB): m/z 387 [20%,
(M + H)+]. HRMS (FAB): m/z calc. for C20H23N2O6 (M + H)+,
387.1551; found, 387.1551. Anal. calcd for C20H22N2O6: C 62.17,
H 5.74, N 7.25; found: C 62.13, H 5.63, N 7.09.
1(4),8(11),15(18),22(25)-Tetrakis(1,2:5,6-di-O-isopropylidene-a-
D-glucofuranosyl)phthalocyanine (6)
A mixture of phthalonitrile 4 (1.33 g, 3.4 mmol) and CeCl3 (0.2
equiv.) in n-pentanol (6 mL) was heated to 100 ◦C, then 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) (0.8 mL) was added. The
mixture was heated further, to 150 ◦C, and kept at this temperature
overnight with stirring. The volatiles were evaporated in vacuo,
then the residue was purified by silica-gel chromatography using
ethyl acetate–n-hexane (changing gradually from v/v 1 : 2 to 1 : 1)
as the eluent to give 6 as a green solid (0.62 g, 47%). 1H NMR: d
9.09–9.27 (m, 4 H, Pc-Ha), 8.14–8.22 (m, 4 H, Pc-Hb), 7.81–7.94
3-(1,2:3,4-Di-O-isopropylidene-a-D-
galactopyranosyl)phthalonitrile (5)
According to the general procedure, 3-nitrophthalonitrile (1)
(2.30 g, 13.3 mmol) was treated with protected galactose 3 (5.10 g,
19.6 mmol) in DMF (20 mL) to give 5 as a white crystalline solid
2178 | Org. Biomol. Chem., 2008, 6, 2173–2181
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(m, 4 H, Pc-Hb), 6.50–6.64 (m, 4 H, H1), 4.22–5.88 (m, 24 H,
CH), 1.39–1.72 (m, 48 H, Me). MS (ESI): an isotopic cluster
peaking at m/z 1547 [100%, (M + H)+]. HRMS (ESI): m/z calc.
for C80H91N8O24 (M + H)+, 1547.6141; found, 1547.6151. Anal.
calcd for C80H90N8O24: C 62.09, H 5.86, N 7.24; found: C 62.36, H
6.00, N 6.84.
4.97–5.03 (m, 4 H, H2), 4.72–4.78 (m, 4 H, H5), 4.56–4.60 (m,
4 H, H4), 4.27–4.35 (m, 8 H, H6), 1.35–1.70 (m, 48 H, Me). MS
(ESI): an isotopic cluster peaking at m/z 1609 [100%, (M + H)+].
HRMS (ESI): m/z calc. for C80H89N8O24Zn (M + H)+, 1609.5276;
found, 1609.5273.
[2(3),9(10),16(17),23(24)-Tetrakis(1,2:3,4-di-O-isopropylidene-a-
D-galactopyranosyl)phthalocyaninato]zinc(II) (14)
1(4),8(11),15(18),22(25)-Tetrakis(1,2:3,4-di-O-isopropylidene-a-
D-galactopyranosyl)phthalocyanine (7)
According to the above procedure, cyclisation of phthalonitrile 12
(1.34 g, 3.5 mmol) gave 14 as a blue solid (1.08 g, 77%). 1H NMR:
d 9.30–9.39 (m, 4 H, Pc-Ha), 8.98–9.02 (m, 4 H, Pc-Ha), 7.77–7.80
(m, 4 H, Pc-Hb), 5.72–5.74 (m, 4 H, H1), 4.62–4.81 (m, 16 H, CH),
4.43–4.54 (m, 8 H, CH), 1.41–1.83 (m, 48 H, Me). MS (ESI): an
isotopic cluster peaking at m/z 1609 [100%, (M + H)+]. HRMS
(ESI): m/z calc. for C80H89N8O24Zn (M + H)+, 1609.5276; found,
1609.5272. Anal. calcd for C80H88N8O24Zn: C 59.65, H 5.51, N
6.96; found: C 59.62, H 5.48, N 7.05.
According to the above procedure, cyclisation of phthalonitrile
5 (1.28 g, 3.3 mmol) gave 7 as a green solid (0.74 g, 58%). H
1
NMR: d 8.95–9.18 (m, 4 H, Pc-Ha), 8.06–8.16 (m, 4 H, Pc-Hb),
7.62–7.94 (m, 4 H, Pc-Hb), 4.30–5.85 (m, 28 H, CH), 1.21–1.59
(m, 48 H, Me). MS (ESI): an isotopic cluster peaking at m/z 1547
[100%, (M + H)+]. HRMS (ESI): m/z calc. for C80H91N8O24 (M +
H)+, 1547.6141; found, 1547.6132. Anal. calcd for C80H90N8O24: C
62.09, H 5.86, N 7.24; found: C 62.46, H 5.98, N 6.93.
[1(4),8(11),15(18),22(25)-Tetrakis(1,2:5,6-di-O-isopropylidene-a-
D-glucofuranosyl)phthalocyaninato]zinc(II) (8)
General procedure for the preparation of mono-glycosylated
zinc(II) phthalocyanines 16–19
A solution of the metal-free phthalocyanine 6 (50 mg, 32 lmol) and
Zn(OAc)2·2H2O (2 equiv.) in DMF (5 mL) was stirred at 150 ◦C
overnight. The solvent was evaporated in vacuo, then the residue
was purified by silica-gel chromatography using ethyl acetate–n-
hexane (changing gradually from v/v 1 : 2 to 2 : 1) as the eluent to
give 8 as a green solid (39 mg, 75%). 1H NMR: d 9.16–9.25 (m, 4 H,
Pc-Ha), 8.06–8.14 (m, 4 H, Pc-Hb), 7.76–7.87 (m, 4 H, Pc-Hb), 6.48–
6.62 (m, 4 H, H1), 4.09–6.01 (m, 24 H, CH), 1.24–1.68 (m, 48 H,
Me). MS (ESI): an isotopic cluster peaking at m/z 1609 [100%,
(M + H)+]. HRMS (ESI): m/z calc. for C80H89N8O24Zn (M +
H)+, 1609.5276; found, 1609.5271.
Lithium (0.2 g, 29 mmol) was first dissolved in n-pentanol (20 mL)
at 100 ◦C, then a solution of glycosylated phthalonitrile 4, 5, 11,
or 12 (1 equiv.) and unsubstituted phthalonitrile (15) (9 equiv.)
in a minimum amount of tetrahydrofuran (THF) (ca. 10 mL)
◦
was added. The resulting mixture was stirred at 120 C for 5 h,
then Zn(OAc)2·2H2O (3 equiv.) was added. The resulting mixture
was stirred at this temperature overnight, then the volatiles were
removed under reduced pressure. The residue was redissolved
in THF and the suspension was filtered to remove some of the
unsubstituted ZnPc formed. The filtrate was adsorbed onto silica
gel which was then loaded onto a silica-gel column and eluted
with THF–n-hexane (changing gradually from v/v 1 : 2 to 1 : 1).
The crude product obtained was further purified by size exclusion
chromatography using THF as the eluent. A green band was first
developed, which was followed by a blue band containing the
desired A3B-type product. The product was further purified by
recrystallisation from THF layered with n-hexane.
[1(4),8(11),15(18),22(25)-Tetrakis(1,2:3,4-di-O-isopropylidene-a-
D-galactopyranosyl)phthalocyaninato]zinc(II) (9)
According to the above procedure, metallation of the metal-free
phthalocyanine 7 (50 mg, 32 lmol) with Zn(OAc)2·2H2O (2 equiv.)
1
gave 9 as a green solid (41 mg, 79%). H NMR: d 9.13–9.21 (m,
4 H, Pc-Ha), 8.05–8.12 (m, 4 H, Pc-Hb), 7.65–7.88 (m, 4 H, Pc-Hb),
4.24–5.83 (m, 28 H, CH), 1.21–1.53 (m, 48 H, Me). MS (ESI): an
isotopic cluster peaking at m/z 1609 [100%, (M + H)+]. HRMS
(ESI): m/z calc. for C80H89N8O24Zn (M + H)+, 1609.5276; found,
1609.5264. Anal. calcd for C80H88N8O24Zn: C 59.65, H 5.51, N
6.96; found: C 59.87, H 5.73, N 6.52.
[1-(1,2:5,6-Di-O-isopropylidene-a-D-
glucofuranosyl)phthalocyaninato]zinc(II) (16)
According to the general procedure, phthalonitrile 4 (0.16 g,
0.4 mmol) reacted with 15 to give 16 as a blue solid (0.09 g,
26%). 1H NMR: d 9.39–9.49 (m, 6 H, Pc-Ha), 9.20 (d, J = 7.5 Hz,
1 H, Pc-Ha), 8.11–8.20 (m, 7 H, Pc-Hb), 7.79 (d, J = 8.1 Hz, 1 H,
Pc-Hb), 6.52 (d, J = 3.6 Hz, 1 H, H1), 5.91–5.99 (m, 1 H, H5), 5.57
(d, J = 2.4 Hz, 1 H, H3), 5.19 (d, J = 3.6 Hz, 1 H, H2), 4.69–4.73
(m, 1 H, H4), 4.46–4.58 (m, 2 H, H6), 1.69 (s, 3 H, Me), 1.41 (s,
[2(3),9(10),16(17),23(24)-Tetrakis(1,2:5,6-di-O-isopropylidene-a-
D-glucofuranosyl)phthalocyaninato]zinc(II) (13)11a
A
mixture of phthalonitrile 11 (0.61 g, 1.6 mmol) and
1
Zn(OAc)2·2H2O (2 equiv.) in n-pentanol (5 mL) was heated to
100 ◦C, then DBU (0.8 mL) was added. The mixture was heated
further, to 150 ◦C, and kept stirring at this temperature overnight.
The volatiles were then evaporated in vacuo and the residue was
purified by silica-gel chromatography using ethyl acetate–n-hexane
(changing gradually from v/v 1 : 3 to 1 : 1) as the eluent. The
product 13 was isolated as a blue solid (0.37 g, 58%). 1H NMR: d
9.35–9.45 (m, 4 H, Pc-Ha), 9.06–9.10 (m, 4 H, Pc-Ha), 7.76–7.83
(m, 4 H, Pc-Hb), 6.13–6.16 (m, 4 H, H1), 5.39–5.42 (m, 4 H, H3),
3 H, Me), 1.35 (s, 3 H, Me), 0.90 (s, 3 H, Me). 13C{ H} NMR: d
154.2, 153.5, 153.4, 153.2, 152.8, 141.1, 139.0, 138.4, 138.1, 130.2
(Pc-Cb), 129.2 (Pc-Cb), 128.8 (Pc-Cb), 122.4 (Pc-Ca), 122.3 (Pc-
Ca), 116.5 (Pc-Ca), 113.7 (Pc-Cb), 112.3, 109.2, 106.0 (C1), 82.9
(C2), 81.6 (C3 or C4), 81.4 (C3 or C4), 72.5 (C5), 67.7 (C6), 26.9
(two overlapping signals, Me), 26.3 (Me), 25.0 (Me) (some of the
aromatic signals are overlapped). MS (ESI): an isotopic cluster
peaking at m/z 835 [100%, (M +H)+]. HRMS (ESI): m/z calc. for
C44H35N8O6Zn (M + H)+, 835.1966; found, 835.1960. Anal. calcd
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for C44H34N8O6Zn: C 63.20, H 4.10, N 13.40; found: C 62.69, H
4.72, N 13.48.
(Pc-Cb), 109.6, 108.9, 105.6 (Pc-Ca), 96.6 (C1), 71.2 (C4 or C6),
70.8 (two overlapping signals, C2 and C3), 67.2 (C4 or C6), 66.6
(C5), 26.3 (Me), 26.2 (Me), 25.0 (Me), 24.6 (Me) (some of the
aromatic signals are overlapped). MS (ESI): an isotopic cluster
peaking at m/z 835 [100%, (M + H)+]. HRMS (ESI): m/z calc. for
C44H35N8O6Zn (M + H)+, 835.1966; found, 835.1959. Anal. calcd
for C44H34N8O6Zn: C 63.20, H 4.10, N 13.40; found: C 63.45, H
4.85, N 12.66.
[1-(1,2:3,4-Di-O-isopropylidene-a-D-
galactopyranosyl)phthalocyaninato]zinc(II) (17)
According to the general procedure, phthalonitrile 5 (0.35 g,
0.9 mmol) was treated with 15 to give 17 as a blue solid (0.19 g,
25%). 1H NMR: d 9.42–9.50 (m, 1 H, Pc-Ha), 9.25–9.34 (m, 5 H,
Pc-Ha), 9.09 (d, J = 7.5 Hz, 1 H, Pc-Ha), 8.02–8.18 (m, 7 H, Pc-
Hb), 7.66 (d, J = 7.8 Hz, 1 H, Pc-Hb), 5.86 (d, J = 4.8 Hz, 1 H, H1),
5.40 (dd, J = 1.2, 7.8 Hz, 1 H, H4), 4.90–5.11 (m, 4 H, H3, H5 and
H6), 4.61 (dd, J = 2.4, 4.8 Hz, 1 H, H2), 1.57 (s, 3 H, Me), 1.55 (s,
Acknowledgements
We thank Prof. Wing-Hung Ko for technical support in the
fluorescence imaging study. This work was supported by a grant
from the Research Grants Council of the Hong Kong Special
Administrative Region, China (Project No. 402505) and a strategic
investments scheme administered by The Chinese University of
Hong Kong.
1
3 H, Me), 1.41 (s, 3 H, Me), 1.28 (s, 3 H, Me). 13C{ H} NMR: d
155.5, 152.9, 152.8, 140.7, 138.9, 138.3, 138.0, 137.8, 130.2 (Pc-Cb),
128.9 (Pc-Cb), 128.7 (Pc-Cb), 128.6 (Pc-Cb), 122.7 (Pc-Ca), 122.5
(Pc-Ca), 122.1 (Pc-Ca), 122.0 (Pc-Ca), 121.9 (Pc-Ca), 115.8 (Pc-Ca),
112.9 (Pc-Cb), 109.4, 109.0, 96.8 (C1), 71.4 (C2, C3 or C4), 71.0
(C2, C3 or C4), 70.9 (C2, C3 or C4), 67.3 (C5 or C6), 66.8 (C5
or C6), 26.4 (Me), 26.1 (Me), 25.1 (Me), 24.6 (Me) (some of the
aromatic signals are overlapped). MS (ESI): an isotopic cluster
peaking at m/z 835 [100%, (M + H)+]. HRMS (ESI): m/z calc. for
C44H35N8O6Zn (M + H)+, 835.1966; found, 835.1968. Anal. calcd
for C44H34N8O6Zn: C 63.20, H 4.10, N 13.40; found: C 63.23, H
4.92, N 13.93.
References
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[2-(1,2:5,6-Di-O-isopropylidene-a-D-
glucofuranosyl)phthalocyaninato]zinc(II) (18)
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According to the general procedure, phthalonitrile 11 (0.15 g,
0.4 mmol) was treated with 15 to give 18 as a blue solid (0.14 g,
43%). 1H NMR: d 9.06–9.30 (m, 7 H, Pc-Ha), 8.85 (br s, 1 H, Pc-
Ha), 7.93–8.11 (m, 6 H, Pc-Hb), 7.67 (d, J = 7.5 Hz, 1 H, Pc-Hb),
6.17 (d, J = 3.6 Hz, 1 H, H1), 5.42 (d, J = 2.4 Hz, 1 H, H3), 5.04
(d, J = 3.6 Hz, 1 H, H2), 4.80–4.86 (m, 1 H, H5), 4.63 (dd, J = 2.4,
7.5 Hz, 1 H, H4), 4.29–4.39 (m, 2 H, H6), 1.72 (s, 3 H, Me), 1.58
3 N. Nishiyama, W.-D. Jang and K. Kataoka, New J. Chem., 2007, 31,
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5 O. Warburg, Science, 1956, 123, 309.
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2006, 49, 2558; (e) M. Obata, S. Hirohara, K. Sharyo, H. Alitomo, K.
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1
(s, 3 H, Me), 1.42 (s, 3 H, Me), 1.41 (s, 3 H, Me). 13C{ H} NMR:
d 158.3, 152.8 (br s), 140.0, 137.9, 132.3, 128.6 (Pc-Cb), 123.6
(Pc-Ca), 122.2 (Pc-Ca), 118.1 (Pc-Cb), 112.4, 109.3, 107.3 (Pc-Ca),
105.5 (C1), 82.6 (C2), 80.9 (C4), 80.5 (C3), 72.5 (C5), 67.3 (C6),
27.0 (two overlapping signals, Me), 26.4 (Me), 25.4 (Me) (some of
the aromatic signals are overlapped). MS (ESI): an isotopic cluster
peaking at m/z 835 [100%, (M + H)+]. HRMS (ESI): m/z calc. for
C44H35N8O6Zn (M + H)+, 835.1966; found, 835.1973. Anal. calcd
for C44H34N8O6Zn: C 63.20, H 4.10, N 13.40; found: C 63.05, H
4.45, N 14.26.
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11, 1643; (b) S. Hirohara, M. Obata, S.-i. Ogata, K. Kajiwara, C.
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galactopyranosyl)phthalocyaninato]zinc(II) (19)
According to the general procedure, phthalonitrile 12 (1.06 g,
2.7 mmol) was treated with 15 to give 19 as a blue solid (0.91 g,
40%). 1H NMR: d 8.95–9.10 (m, 6 H, Pc-Ha), 8.79 (d, J = 8.1 Hz,
1 H, Pc-Ha), 8.43 (d, J = 2.1 Hz, 1 H, Pc-Ha), 7.93–8.00 (m, 6 H,
Pc-Hb), 7.49 (dd, J = 2.1, 8.1 Hz, 1 H, Pc-Hb), 5.80 (d, J = 5.1 Hz,
H1), 4.86 (dd, J = 2.1, 7.8 Hz, 1 H, H3), 4.66–4.73 (m, 3 H, H4
and H6), 4.57–4.63 (m, 1 H, H5), 4.51 (dd, J = 2.1, 5.1 Hz, 1 H,
H2), 1.76 (s, 3 H, Me), 1.67 (s, 3 H, Me), 1.53 (s, 3 H, Me), 1.46
1
(s, 3 H, Me). 13C{ H} NMR: d 160.1, 153.1, 152.9, 152.4, 140.1,
138.1, 131.5, 128.6 (Pc-Cb), 123.2 (Pc-Ca), 122.2 (Pc-Ca), 118.1
2180 | Org. Biomol. Chem., 2008, 6, 2173–2181
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