Extremely Photostable Electron-Deficient Phthalocyanines that Generate High Levels of Singlet Oxygen

Article abstract of DOI:10.1002/chem.201805082

A robust lead-mediated synthetic procedure for the generation of phthalocyanines substituted with electron-withdrawing groups has been developed. The free-base phthalocyanine and various metal complexes were prepared without discernible degradation of the

Full text of DOI:10.1002/chem.201805082

A Journal of
Accepted Article
Title: Extremely Photostable Electron-Deficient Phthalocyanines That
Generate High Levels of Singlet Oxygen
Authors: Taniyuki Furuyama, Yusuke Miyaji, Kazuya Maeda, Hajime
Maeda, and Masahito Segi
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Extremely Photostable Electron-Deficient Phthalocyanines That
Generate High Levels of Singlet Oxygen
Taniyuki Furuyama,* Yusuke Miyaji, Kazuya Maeda, Hajime Maeda, and Masahito Segi
Abstract: A robust lead-mediated synthetic procedure for the
generation of phthalocyanines substituted with electron-withdrawing
groups has been developed. The free-base phthalocyanine and
various metal complexes were prepared without discernible
degradation of the peripheral electron-withdrawing substituents.
Upon irradiation with red light, some of the thus obtained metal
complexes generated high levels of singlet oxygen. Especially a
palladium complex exhibited attractive photostability upon exposure
to singlet oxygen as a bleaching agent. The photostability of such
complexes that may manifest concomitantly to the generation of high
levels of singlet oxygen was attributed to the presence of the
electron-withdrawing groups, which results in energetically low-lying
highest occupied molecular orbitals.
the Pc can lead to a broad variety of functions. Recently, we
have described main-group-element-substituted/mediated
phthalocyanines, which show unique
optical/electrochemical/aromatic properties.[6] Moreover, EWG-
substituted Pcs are expected to exhibit stabilized HOMOs, which
could decrease the orbital interaction with singlet oxygen
(Scheme 1a). Heavy metals can enhance the efficiency of the
generation of singlet oxygen via
a
spin-orbit coupling
mechanism, and various metals can be introduced into the
central core of free-base (metal-free) Pcs.[2a] Therefore, EWG-
substituted free-base Pcs and their metal complexes may
potentially represent a new type of photostable singlet oxygen
sensitizers upon exposure to red to near-IR light. The so-called
lithium method, which uses nucleophilic lithium alkoxides, is a
representative procedure to synthesize free-base Pcs.[2]
However, in EWG-substituted phthalonitriles, EWGs at the ipso-
position react with the nucleophiles (SNAr reaction),[7] which
results in the formation of a mixture of free-base Pcs with
various peripheral substituents (Scheme 1b).
Since the first accidental synthesis of phthalocyanines (Pcs) by
Braun and Tcherniac,[1] Pcs have been used as powerful
artificial dyes and pigments. Conventional Pcs exhibit an intense
absorption band in the red to near-IR (650–700 nm) region, the
so-called Q band. On account of their unique optical properties,
Pcs have found various applications in the field of biological
chemistry and materials science, such as organic photovoltaics
(OPV), photosynthesis, optical imaging, and photodynamic
therapy (PDT).[2] PDT, for example, involves the administration
of
a tumor-localizing photosensitizing agent, followed by
activation using light of a specific wavelength.[3] Photosensitizing
agents can generate singlet oxygen (O2(1Δg)), which leads to cell
death upon excitation, and the wavelength of irradiation is
crucial for any application. For instance, conventional
photosensitizers generally absorb light in the visible region,
which limits tissue penetration. On the other hand, specific red to
near-IR light (650-900 nm; the so-called near-IR window)
exhibits relatively low toxicity toward human tissue and offers
high levels of penetration, i.e., Pcs absorbing red to near-IR light
are promising prospectives for PDT photosensitizers.[4] However,
Pcs can also react with singlet oxygen. For example, the [4+2]-
cycloaddition between the pyrrole moiety in the Pc macrocycle
and singlet oxygen upon exposure to irradiation has been
reported.[5] Hence, Pcs with the ability to generate high levels of
singlet oxygen usually exhibit a concomitantly low photostability.
This behavior should most likely be rationalized in terms of an
interaction between the HOMO of the Pc and the LUMO of
singlet oxygen, which means that Pc derivatives with low-lying
HOMOs may exhibit increased photostability.
In the present study, we designed Pcs substituted with
electron-withdrawing groups (EWGs), which generate high
levels of singlet oxygen and exhibit high photostability. The
combination of peripheral substituents and central element of
[*]
Prof. Dr. T. Furuyama, Y. Miyaji, K. Maeda, Prof. Dr. H. Maeda,
Prof. Dr. M. Segi
Graduate School of Natural Science and Technology
Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan)
E-mail: tfuruyama@se.kanazawa-u.ac.jp
Scheme 1. (a) The effects of the introduction of peripheral electron-
withdrawing groups into phthalocyanines (Pcs) on the energy level of their
MOs. (b) Reaction mechanism for the lithium method.
Supporting information for this article is given via a link at the end of
the document.
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Scheme 2. Synthesis of EWG-substituted phthalocyanines. Reaction
conditions: (i) mCPBA (10 eq), CH2Cl2, rt, 2 days, 92%; (ii) nBuOLi, nBuOH,
reflux, 2 h, 26%; (iii) Zn(OAc)2⋅2 H2O (0.45 eq), DBU, pentanol, reflux, 6 h,
27%; (iv) PbO (0.9 eq), 270 °C, 2 h, 46%; (v) CF3COOH, CH2Cl2, rt, 15 min,
80%; (vi) metal salt (5 eq), DMSO, rt to 160 °C, 3–6.5 h, up to 68%; (vii)
mCPBA (35 eq), CH2Cl2, rt, 5 min, complex mixture was obtained (cf.
Supporting Information).
To overcome this problem, we have used lead ions as a
template for the Pc synthesis. The template synthesis of Pc lead
complexes proceeds in the absence of any nucleophiles.[8] As
the lead ions are relatively large their position deviates from the
Pc plane in the crystal.[9] The deviation indicates that the lead
ion could potentially be removed to deliver the corresponding
free-base Pcs.[8,10] We also motivated that some kinds of EWG-
substituted Pc metal complexes have been synthesized by
template method.[11] Based on this concept, the aryl sulfone
(ArSO2) group was chosen as a model EWG (Scheme 1a and
Scheme 2). The thioaryl (ArS) group is, in contrast,
a
representative electron-donating group (EDG). As described
above (Scheme 1b), the conventional lithium method is not able
to generate EWG-substituted Pcs, and merely complex mixtures
containing various alkoxy-substituted Pcs were obtained after
the phthalonitrile was treated with lithium alkoxide. Although the
Q band appeared clearly in the absorption spectrum of the thus
obtained Pc (1 (Li)) (Figure S2), the mass spectrum indicates
that 1 (Li) contains a mixture of randomly substituted butoxy-
substituted Pcs (Figure S3). Previously, ArSO2-substituted Pcs
have been generated by oxidation of ArS-substituted Pcs.[12]
However, this synthetic route suffers from low reproducibility,
given that the Pc macrocycle usually decomposes under typical
oxidation conditions. This is also reflected in the position of the
Q band, which shifts after a short (5 min) treatment of 7 with
mCPBA (Figure S4). However, the ESI-MS spectrum of the
reaction mixture indicated that the reaction was not completed
(Figure S5). When the reaction was continued, the Pc
macrocycle decomposed, and the targeted 1 was not obtained.
SAr
SAr
ArS
ArS
N
M
N
ArS
ArS
CN
CN
(ii)
N
N
N
N
N
N
SAr
SAr
ArS
ArS
Figure 1. (a) UV-vis-NIR absorption (1–8) and (b) emission spectra (1–6, λex
620 nm) of in CH2Cl2. Under these conditions, emission peaks for 3 and 4
were not observed.
=
7 (M = H2)
8 (M = Zn)
(iii)
(i)
SO2Ar
ArO2S
ArO2S
SO2Ar
N
M
N
Heating sulfone-substituted phthalonitrile and lead(II) oxide in
the solid state afforded the Pb complex PbPc, which
decomposed gradually into free-base complex 1 upon treatment
with trifluoroacetic acid, whereby a purification of PbPc was not
required. 1H NMR and HR-MALDI-FT-ICR-MS spectra confirmed
that all peripheral substituents of 1 remained intact under these
conditions (Figure S6). The solid-state condition is required to
obtain PbPc, and the conditions in high-boiling solvents, such as
quinoline and 1-chloronaphthalene were failed. The sharp peaks
in the 1H NMR spectra indicated that the Pcs in this study did not
aggregated even in the NMR concentration (~1 mM in CDCl3).
With this EWG-substituted free-base Pc in hand, we examined
metalation reactions. The synthesis of Pc magnesium
complexes typically requires either free-base Pc[13] or
ArO2S
CN
CN
N
N
N
N
(iv)
N
N
ArO2S
Ar =
SO2Ar
SO2Ar
ArO2S
ArO2S
(v)
PbPc (M = Pb)
1 (M = H2)
2 (M = Mg), 3 (M = Ni)
4 (M = Cu), 5 (M = Zn)
6 (M = Pd)
(vi)
(vii)
7 (ArSPc)
1 (ArSO2Pc)
nucleophilic magnesium alkoxides as
magnesium complex 2 was obtained from the metalation of 1
a
template,[14] while
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without any nucleophiles. Nickel, copper, zinc, and palladium
complexes (3-6) were also obtained from free-base 1 with high
chemoselectivity for the metallation. 1–6 showed good solubility
in common organic solvents. The solid-state structure of an
eightfold EWG-substituted Pc macrocycle was unambiguously
determined by X-ray diffraction analysis of single crystals
obtained from the diffusion of cyclohexane into a pyridine
solution of 5 (Figure S7). The structure of the core macrocycle of
5 exhibits typical Pc features.[15]
are comparable with those of fullerene derivatives such as
PCBM (Ered1 = ca. –1.0 V vs Fc+/Fc),[18] indicating that EWG-
substituted Pcs may potentially be applicable to soluble Pc-
based non-fullerene n-type semiconductors. In order to better
understand the electronic structures, MO calculations of models
Pcs 1’ (ArSO2) and 7’ (ArS) were carried out, where the
substituents at the sulfur atoms were replaced with methyl
groups for simplicity. Partial MO diagrams, theoretical
calculation spectra, and components of the transition energies
are summarized in Figure S10 and Table S3. The HOMO,
LUMO, and LUMO+1 are derived from the typical MOs of Pcs
with 18π-electron aromaticity. The low-lying MOs of 1’ are
consistent with the anodic shift of the redox potentials of 1, and
the stabilized HOMO should endow such EWG-substituted Pcs
with increased stability toward oxidative reactions.
Figure 2. Cyclic voltammograms for 1–7; [analyte] = 0.5 mM; solvent: o-DCB;
supporting electrolyte: 0.1 M [nBu4N][ClO4]. All potentials referenced to the
ferrocene/ferrocenium couple.
The absorption and fluorescence spectra of 1–8 are shown
in Figure 1. The absorption spectra in dichloromethane are
typical of nonaggregated Pcs, which strictly follow the Beer-
Lambert law (Figure S8). All EWG-substituted Pcs show intense
absorption bands (Q bands) in the far-red to near-IR region, and
the results of magnetic circular dichroism (MCD) spectra support
the presence of symmetrical chromophores (Figure S9). As the
substituent effect at the β position is lower than that at the α
position, similar Q band positions were obtained for 1 (ArSO2;
EWG) and 7 (ArS; EDG). Remarkably, free-base 1 as well as
the metal complexes 2 and 5 show intense emission in the near-
IR region with high fluorescence quantum yields (ΦF). Typical Pc
zinc complexes have low ΦFs values.[16] On the other hand,
Electron-deficient pyrazinoporphyrazines also show high ΦFs
values,[17] which could mean that EWGs may potentially
enhance the fluorescence process and thus render these dyes
potential near-IR fluorescence probes.
Figure 2 displays the cyclic voltammograms of 1–7 in o-
dichlorobenzene (DCB) and contains a summary of the first
redox potentials (Eox1 and Ered1). It is well established that the
position of the Q band correlates well with the gap between the
first redox potentials (Eox1 – Ered1). The similar gaps (1.54~1.68
V) of 1–7 support similar positions of their Q bands. The
observed values were also comparable to previously reported
voltammograms of other Pcs.[15] On the other hand, the redox
potentials of EWG-substituted 1–6 shifted anodically, and
multiple reduction waves were observed. The high Ered1 values
Figure 3. Time-dependent optical density of 1, 2, and 5, 7, and 8 at the
absorption maximum wavelength upon irradiation. The original optical density
before irradiation was normalized at the absorption maximum. Solutions of
compounds in air-saturated CH2Cl2 (ca. 5.0 x 10–6 M) were irradiated using a
halogen lamp (3,000 lx). The absorption intensities of 3, 4, and 6 remained
unchanged after irradiation for 1,200 min.
To gauge the photostability of the Pcs, changes in the
optical density at the Q band peak were measured under
irradiation with light (Figure 3 and Figure S11). Upon the
introduction of EWG groups, increased photostability was
observed. Pc zinc complexes exhibit low photostability due to
the generation of singlet oxygen. The decrease in intensity of 5
was less than that for the thioaryl-substituted free-base Pc 7.
The nickel, copper, and palladium complexes showed no
photobleaching after irradiation for 20 hours. The copper
complex is a robust organic dye, even though it could not
generate singlet oxygen upon irradiation with light. The
efficiency to generate singlet oxygen (ΦΔ) of the EWG-
substituted Pcs was quantified by a steady-state method using
1,3-diphenylisobenzofuran (DPBF) as the chemical quencher
(Figure 4). Unfortunately, this was not possible for thioaryl-
substituted 7 and 8, as their optical density decreased during the
irradiation due to their low photostability (Figure S12). The ability
to generate singlet oxygen depends on the central element of
the Pc complex. Nickel and copper complexes showed low
photosensitization, while the zinc and palladium complexes
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showed the generation of high levels of singlet oxygen (ΦΔ ≈
100%), comparing the reported zinc complex.[4d] The high singlet
oxygen generation abilities also supported that such Pcs did not
aggregate, since the aggregation reduced the singlet oxygen
quantum yield due to enhanced radiationless excited-state
dissipation.[19] Especially, palladium complex 6 is extremely
photostable, supporting the hypothesis that low-lying HOMOs
prevent the reaction with singlet oxygen, which is generated by 6
itself. The high production of singlet oxygen of 6 by irradiation
with red light was also demonstrated in a photooxygenation
reaction. For that purpose, a mixture of 9,10-diphenylanthracene
and 6 was exposed to red light under an atmosphere of O2,
which afforded the corresponding endoperoxide in high yield (cf.
Supporting Information), indicating that 6 can serve as a red-
light-responsive photooxidizing sensitizer.
This work was partly supported by JSPS KAKENHI grant
(15K05409 and 18K19071), the Sumitomo Foundation, the
TOBE MAKI Scholarship Foundation, the Japan Prize
Foundation, and Kanazawa University SAKIGAKE Project 2018.
The authors thank Prof. Soji Shimizu (Kyushu Univ.) for carrying
out fluorescence quantum yield measurements, Prof. Shigehisa
Akine and Dr. Yoko Sakata (Kanazawa Univ.) for single-crystal
X-ray diffraction measurements, and the Nanotechnology
Platform Program (Molecule and Material Synthesis) of the
MEXT for conducting mass spectrometry measurements (Dr.
Akio Miyazato at JAIST).
Keywords: phthalocyanine • electron-withdrawing group • lead •
singlet oxygen • photostability
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Supporting Information).
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In summary, we have developed a reliable and robust
synthesis of EWG-substituted Pcs using lead ions. Free-base
Pcs were obtained with high chemoselectivity, and various metal
complexes were prepared subsequently. All Pcs absorb red to
near-IR light, i.e., these EWG-substituted Pc macrocycles may
serve as a platform for red-to-near-IR materials. These Pcs
show various unique physical properties such as intense near-IR
fluorescence, high reduction potentials, and the generation of
high levels of singlet oxygen upon irradiation with red light. The
low-lying MOs prevent the decomposition of these Pcs upon
exposure to the singlet oxygen that they generate. Especially
palladium complex 6 combines an attractive ability to generate
high levels of singlet oxygen with high photostability. The Pcs
obtained in this work demonstrate that the designed synthetic
method and structure overcome the critical limitation of
applications to red-to-near-IR materials.
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Acknowledgements
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Extremely Photostable Electron-
Deficient Phthalocyanines That
Generate High Levels of Singlet
Oxygen
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