Synthesis and photochemical properties of unsymmetrical phthalocyanine bearing two 1-adamantylsulfanyl groups at adjacent peripheral positions

Article abstract of DOI:10.1016/j.inoche.2012.10.002

A novel unsymmetrical magnesium(II) 2,3-bis(1-adamantylsulfanyl) phthalocyanine was prepared by mixed macrocyclization reaction of two phthalonitriles (phthalonitrile and 4,5-bis(1-adamantylsulfanyl)phthalonitrile) and characterized using UV-vis, MALDI MS and NMR methods. Precursor adamantyl disubstituted phthalonitrile was synthesized from 4,5-dichlorophthalonitrile. Absorption and emission properties of this novel phthalocyanine were investigated, including determination of fluorescence quantum yields, fluorescence lifetimes and solvatochromic effects. This newly synthesized phthalocyanine can be considered as a potential photosensitizer, as its singlet oxygen quantum yield (Φ_Δ) of 0.49 was found in DMF and DMSO.

Full text of DOI:10.1016/j.inoche.2012.10.002

Inorganic Chemistry Communications 27 (2013) 56–59
Contents lists available at SciVerse ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Feature article
Synthesis and photochemical properties of unsymmetrical phthalocyanine bearing
two 1-adamantylsulfanyl groups at adjacent peripheral positions
Michal Kryjewski a, Michal Nowak b, Piotr Kasprzycki c, Piotr Fita c, Czeslaw Radzewicz c,
a,
Tomasz Goslinski b, , Jadwiga Mielcarek
⁎
⁎
a
Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60–780 Poznan, Poland
Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6, 60–780 Poznan, Poland
Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Hoza 69, 00–681 Warsaw, Poland
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel unsymmetrical magnesium(II) 2,3-bis(1-adamantylsulfanyl)phthalocyanine was prepared by mixed
macrocyclization reaction of two phthalonitriles (phthalonitrile and 4,5-bis(1-adamantylsulfanyl)phthalonitrile)
and characterized using UV–vis, MALDI MS and NMR methods. Precursor adamantyl disubstituted phthalonitrile
was synthesized from 4,5-dichlorophthalonitrile. Absorption and emission properties of this novel phthalocya-
nine were investigated, including determination of fluorescence quantum yields, fluorescence lifetimes and
solvatochromic effects. This newly synthesized phthalocyanine can be considered as a potential photosensitizer,
as its singlet oxygen quantum yield (ΦΔ) of 0.49 was found in DMF and DMSO.
Received 24 April 2012
Accepted 1 October 2012
Available online 8 October 2012
Keywords:
Phthalocyanine
Adamantane
Singlet oxygen
Photosensitizer
Solvatochromic effects
© 2012 Elsevier B.V. All rights reserved.
Contents
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Appendix A.
References .
Supplementary material .
. . . . . . . . . . . . .
.
Phthalocyanines are synthetic macrocyclic compounds with unique
optical and electrochemical properties. Apart from their traditional use
in the pigment industry, they have been examined as materials for opto-
electronic devices, non-linear optical materials [1], optical filters [2] and
solar cell materials [3,4]. Moreover, phthalocyanines have been exten-
sively investigated as photosensitizers for photodynamic therapy [5,6].
Phthalocyanines possess many desirable features of ideal photosensitiz-
er, of which the most important are efficient singlet oxygen generation,
high light absorption in the red part of the spectrum, and high thermal
and light stability [7]. Moreover, phthalocyanines and their aza-
analogues have been examined as fluorescence probes [8] for photody-
namic diagnosis. Phthalocyanines possess in the UV–vis spectrum two in-
tense absorption bands – Soret or B-band at 300–400 nm and a Q-band
at 600–800 nm. As the strong light absorption at longer wavelength
above 700 nm is advantageous for photodynamic therapy, there is a con-
stant interest in synthesis of novel substituted phthalocyanines [5,9].
Many adamantane-substituted compounds have potential uses in
medicinal chemistry, as has been recently reviewed by Liu at al. [10].
Tetraazaadamantane-substituted phthalocyanine has been tested
against the human immunodeficiency virus [11] and revealed cytotoxic-
ity. In addition, zinc pthalocyanines bearing one or four adamantylethoxy
groups have been tested as photosensitizers towards human red blood
cells [12]. For this reason adamantyl substituents have been frequently
introduced into phthalocyanine macrocycles in various manners.
One of the options for phthalocyanine functionalization with
adamantane is the axial substitution of central silicon ion with
adamantane-containing alcohols. Remarkably, phthalocyanines
enriched with bulky adamantane groups possess many desirable fea-
tures for photodynamic therapy, including high photostability, efficient
singlet oxygen production and no tendency to form aggregates [13].
⁎
Corresponding author. Tel.: +48 61 854 6604; fax: +48 61 854 6609.
E-mail addresses: tomasz.goslinski@ump.edu.pl (T. Goslinski),
jmielcar@ump.edu.pl (J. Mielcarek).
1387-7003/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.inoche.2012.10.002

M. Kryjewski et al. / Inorganic Chemistry Communications 27 (2013) 56–59
57
Some phthalocyanines have been peripherally functionalized with
annulated adamantaneimide [14] and –ketal [15] skeleton. Although
the peripheral and nonperipheral substitution of phthalocyanines with
4, 8 or 16 adamantane moieties by nitrogen or oxygen linking bridges
has been often applied [11,12,16], there are much fewer examples of
using sulfur for this purpose. Later Vior et al. reported the synthesis of
series of tetrasubstituted phthalocyanines with 2-adamantyloxy and
1-adamantylsulfanyl groups. Macrocycles have been isolated and
characterized as mixtures of isomers. Interestingly, an adamantanyl-
heteroatom substitution of phthalocyanine ring resulted in bathochromic
shift of a Q-band in comparison to unsubstituted ones [17]. Moreover,
1-adamantylsulfanyl substituted phthalocyanine has been formulated
into nanoemulsions [18] and liposomes [19]. By choosing applied sym-
metrical phthalonitrile, in our fast two-step synthetic approach towards
phthalocyanine macrocycle functionalized with adamantane sulfur
moieties, we aimed to obtain and characterize well defined phthalocy-
anine derivative different from the complex inseparable macrocyclic
mixtures analyzed in previous studies.
The subject of our study was to obtain a new phthalocyanine,
bearing 1-adamantylsulfanyl moieties. Scheme 1 presents the synthe-
sis of novel 4,5-bis(1-adamantylsulfanyl)phthalonitrile (3) and
magnesium(II) 2,3-bis(1-adamantylsulfanyl)phthalocyanine (5). Fol-
lowing Wöhrle's et al. procedure [20] 4,5-dichlorophthalonitrile (1)
was substituted with 1-adamantanethiol (2) in DMF, in the presence
of potassium carbonate as a base at room temperature [21] to give 3
in quantitative 99% yield. Mass spectrum, elemental analysis and
NMR experiments confirmed formation of the desired product. In
1H NMR spectrum of 3 three broad singlet signals at 2.02, 1.89 and
1.63 ppm were observed and ascribed to 1-adamantane moieties.
Moreover, a sharp singlet at 8.15 ppm derived of aromatic protons
was observed. 13C NMR revealed eight separate signals, correspond-
ing well with phthalonitrile 3 structure.
1.92 ppm; and a pseudoquartet at 1.54 ppm. Hydrogen atoms present
at non-peripheral positions adjacent to 1-adamantylsulfanyl groups
resonated as a singlet at 10.32 ppm. Resonances from non-peripheral
hydrogen atoms present in phthalocyanine ring were found as three
multiplets at 9.79–9.80, 9.70–9.73, and 9.67–9.73 ppm, while those of
the peripheral atoms were found as a multiplet at 8.17–8.24 ppm.
Photosensitizing properties of 5 were referred to those previously
established for the standard zinc(II) phthalocyanine (ZnPc) [24–27].
1,3-Diphenylisobenzofuran (DPBF) was used as a chemical quencher
of singlet oxygen. Solution of 5 and DPBF was irradiated with mono-
chromatic light at the wavelengths of 685 nm in DMF and 688 in
DMSO, corresponding to the maximum of the Q-band. DPBF oxidation
was UV–vis monitored with its absorbance decrease at 417 nm
(Fig. 1). Comparison of DPBF oxidation kinetic parameters of 5 and
ZnPc allowed determination of the singlet oxygen generation yield
values to be ΦΔ=0.49 in both DMF and DMSO.
Fluorescence spectra of 5 were recorded in DMF, DMSO and THF. The
fluorescence quantum yields were calculated according to the method
given by Ogunsipe et al. [28], using ZnPc as a reference. The quantum
yields were found to be as follows: 0.28 in DMF, 0.31 in DMSO and
0.33 in THF. Interestingly, they were higher than that of ZnPc (Φf=
0.17 in DMF, 0.20 in DMSO, 0.23 in THF [28]). The Stokes shifts are
minor, which confirms a small difference between geometry of the mol-
ecule in its ground and singlet S1 state.
Mixed macrocyclization reaction [22] of 3 with some excess of
phthalonitrile 4, and magnesium butoxide as a base in n-butanol
resulted in unsymmetrical phthalocyanine 5 [23]. MALDI MS confirmed
formation of a novel disubstituted phthalocyanine. 1H and 13C NMR
were applied to confirm its structure. 1H-1H COSY, 1H-13C HSQC and
1H-13C HMBC experiments were helpful to assist allocation (see Supple-
mentary). The 1H NMR spectra revealed three signals assigned to two
equivalent adamantane moieties; two broad singlets at 2.35 and
Scheme 1. Reagents and conditions: (i) K2CO3, DMF, r.t., 20 h; (ii) Mg(n-OBu)2, n-BuOH,
reflux, 19 h.
Fig. 1. Changes in the UV–vis spectra of DPBF and 5 in (a) DMF and (b) DMSO during
irradiation at Q-band. Insets present first-order plots for oxidation of DPBF.

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M. Kryjewski et al. / Inorganic Chemistry Communications 27 (2013) 56–59
The fluorescence decays of 5 recorded in THF, DMF and DMSO were
Q-bands with the maximum absorbance wavelengths (λmax) in the
range of 680–692 nm and Soret bands with λmax in the range of
346–353 nm. Positions and intensities of the bands were affected by
the type of the solvent applied with the most significant changes in
the Q-band region. The largest red shift of the Q-band was observed
in 1-chloronaphtalene, while the greatest blue shift in acetonitrile.
The 1/F value is a rational function of the solvent's refractive index
(n), calculated from the equation F=(n2−1)/(2n2+1) [28–30].
The wavelength corresponding to the maximum of the Q-band,
monoexponential (Fig. 2), DMSO curve was not shown due to overlap
with DMF curve. Decay times τFl slightly decrease when changing sol-
vent from THF (τFl=5.2 0.1 ns), through DMF (τFl=4.8 0.1 ns) to
DMSO (τFl=4.7 0.1 ns). The similarity of the fluorescence lifetimes
indicates that the molecule weakly interacts with the solvent. The fluo-
rescence lifetimes are relatively long for the tested phthalocyanine and
significantly longer than that of ZnPc in DMSO (3.3 ns), which corre-
sponds to the higher fluorescence quantum yield.
Solvent effects on electronic absorption spectra of 5 were studied
in protic and aprotic solvents. The UV–vis spectra revealed broad
λmax, was plotted against 1/F. Linear correlation characterized by
r2 =0.925 was found for 12 solvents (Fig. 3). However, there was
no correlation between the dipole moment of the solvent and λmax
of the Q-band. Good linear correlation between the Q-band λmax
and 1/F values may indicate that the changes observed in the elec-
tronic absorption spectra are mainly a result of solvation, and that
the coordinating strength of the solvent has little influence on the
red shift [28].
In summary, phthalonitrile and its adamantyl 4,5-disubstituted
analogue were used in a mixed macrocyclization reaction to
produce unsymmetrical magnesium(II) phthalocyanine bearing two
1-adamantylsulfanyl moieties at adjacent peripheral positions. This
novel macrocyclic compound was characterized using UV–vis, MALDI
MS and NMR methods and subjected to absorption and emission prop-
erties measurements, including determination of its fluorescence life-
times, solvatochromic effects and fluorescence quantum yields (ΦΔ=
0.49 in both DMF and DMSO). The unsymmetrical phthalocyanine de-
scribed in this report is expected to find diverse applications as a poten-
tial photosensitizer. The direction of this research will be continued and
reported in due course.
Acknowledgements
The authors acknowledge financial support for the project from the
Polish Ministry of Science and Higher Education (NN404 069440) and
by the National Science Centre (2011/01/B/ST2/02053).
Appendix A. Supplementary material
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.inoche.2012.10.002.
Fig. 3. Correlation between the λmax of the Q-band for 5 and (2n2 +1)/(n2 −1)
value. Solvents: (1) 1-chloronaphthalene, (2) chlorobenzene, (3) toluene, (4) DMSO,
(5) dichloromethane, (6) DMF, (7) 1,4-dioxane, (8) THF, (9) triethylamine, (10) ethyl ac-
etate, (11) acetone, (12) acetonitrile.
Fig. 2. Absorption, excitation and steady state fluorescence spectra of 5 in (a) DMF
and (b) THF. Fluorescence decays of 5 in DMF and THF (c). IRF, instrument response
function.

M. Kryjewski et al. / Inorganic Chemistry Communications 27 (2013) 56–59
59
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