Doubly N-Confused Calix[6]phyrin Bis-Organopalladium Complexes: Photostable Triplet Sensitizers for Singlet Oxygen Generation

Article abstract of DOI:10.1002/asia.201801671

Triplet photosensitizers that generate singlet oxygen efficiently are attractive for applications such as photodynamic therapy (PDT). Extending the absorption band to a near-infrared (NIR) region (700 nm≈) with reasonable photostability is one of the major demands in the rational design of such sensitizers. We herein prepared a series of mono- and bis-palladium complexes (1-Pd-H₂, 2-Pd-H₂, 1-Pd-Pd, and 2-Pd-Pd) based on modified calix[6]phyrins as photosensitizers for singlet oxygen generation. These palladium complexes showed intense absorption profiles in the visible-to-NIR region (500–750 nm) depending on the number of central metals. Upon photoirradiation in the presence of 1,5-dihydroxynaphthalene (DHN) as a substrate for reactive oxygen species, the bis-palladium complexes generated singlet oxygen with high efficiency and excellent photostability. Singlet oxygen generation was confirmed from the characteristic spectral feature of the spin trapped complex in the EPR spectrum and the intact ¹O₂ emission at 1270 nm.

Full text of DOI:10.1002/asia.201801671

CHEMISTRY
AN ASIAN JOURNAL
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Accepted Article
Title: Doubly N-Confused Calix[6]phyrin Bis-Organopalladium
Complexes: Photostable Triplet Sensitizers for Singlet Oxygen
Generation
Authors: Poornenth Pushpanandan, Dong-Hoon Won, Shigeki Mori,
Yuhsuke Yasutake, Susumu Fukatsu, Masatoshi Ishida, and
Hiroyuki Furuta
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10.1002/asia.201801671
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Doubly N-Confused Calix[6]phyrin Bis-Organopalladium
Complexes: Photostable Triplet Sensitizers for Singlet Oxygen
Generation
Poornenth Pushpanandan,[a] Dong-Hoon Won,[a] Shigeki Mori,[b] Yuhsuke Yasutake,[c] Susumu
Fukatsu,[c] Masatoshi Ishida,*[a] and Hiroyuki Furuta*[a]
Abstract: Triplet photosensitizers that generate singlet oxygen
efficiently are attractive for applications such as photodynamic
therapy (PDT). Extending the absorption band to a near-infrared (NIR)
region (700 nm~) with reasonable photostability is one of the major
demands in the rational design of such sensitizers. We herein
prepared a series of mono- and bis-palladium complexes (1-Pd-H2, 2-
Pd-H2, 1-Pd-Pd, and 2-Pd-Pd) based on modified calix[6]phyrins as
photosensitizers for singlet oxygen generation. These palladium
complexes showed intense absorption profiles in the visible-to-NIR
region (500–750 nm) depending on the number of central metals.
Upon photoirradiation in the presence of 1,5-dihydroxynaphthalene
(DHN) as a substrate for reactive oxygen species, the bis-palladium
complexes generated singlet oxygen with high efficiency and
excellent photostability. Singlet oxygen generation was confirmed
from the characteristic spectral feature of the spin trapped complex in
the EPR spectrum and the intact 1O2 emission at 1270 nm.
organic chromophores (e.g., BODIPYs)[7], poly-pyridyl transition
metal complexes (PtII, RuII, IrII)[8] and metallo-macrocyclic
complexes with porphyrin/phthalocyanine scaffolds[9] have gained
much attention as they showed sufficient singlet oxygen
generation capabilities. In order to attain the higher efficiency for
singlet oxygen generation, 1) strong absorption (in the near-
infrared (NIR) biological window for PDT), 2) photostability, 3)
high triplet state quantum yields (effective intersystem crossing
(ISC)), 4) reasonably long-lived triplet state lifetime, and 5)
solubility in appropriate media, are essentially required for the
photosensitizers. For this purpose, the porphyrin-based
chromophores have some benefits; tunable photophysical
properties (i.e., molecular orbital symmetries and energies) by
facile modification of the parent frameworks and by changing the
central metal cations in the macrocyclic ligand.[10] Largely, the
metal complexes show reasonable durability even under the
strong photo-irradiation.
Introduction
Singlet oxygen (1Δg) is the lowest excited electronic state of
oxygen and is one of the most important reactive oxygen species
(ROS) playing a key role in many photoinduced oxidative
processes in biological/chemical systems.[1] Generally, singlet
oxygen can be generated by using molecular oxygen (3O2) under
UV illumination with triplet photosensitizers. The well accepted
microscopic mechanism is such that, the characteristic species in
the triplet state formed via intersystem crossing (ISC) from the
photo-excited singlet state transfers the energy to 3O2.[2] Such
photosensitizers are thus useful in many applications such as
photodynamic
therapy
(PDT),[3]
oxygen
sensing,[4]
photocatalysis,[5] and triplet-triplet annihilation upconversion.[6] To
date, many triplet sensitizers, such as heavy-atom-substituted
[a]
P. Pushpanandan, Dr. D.-H. Won, Dr. M. Ishida, Prof. Dr. H. Furuta
Department of Chemistry and Biochemistry
Graduate School of Engineering and Center for Molecular Systems
Kyushu University
Fukuoka 819-0395 (Japan)
Dr. S. Mori
Advanced Research Support Center
Ehime University
Matsuyama 790-8577 (Japan)
Figure 1. Strategic design of bis-Pd calix[6]phyrin complexes. Chemical
structures of previously reported complexes, Pt-calix[4]phyrin, Pt-doubly N-
confused calix[4]phyrin, bis-Pt calix[6]phyrin, and mono- and bis-Pd
calix[6]phyrin complexes used in this work.
[b]
[c]
Dr. Y. Yasutake, Prof. Dr. S. Fukatsu
Graduate School of Arts and Sciences
The University of Tokyo
Calixphyrin is a unique class of the porphyrin analogues
containing one or multiple sp3-hybridized meso-carbon bridges
providing intrinsic molecular flexibility to endure facile cation
bindings.[11] From the interest of the effect of the carbon-metal
Tokyo 153-8902 (Japan)
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bond in the macrocyclic core for photosensitizers, we have been
working on the modified (confused) porphyrin and
calix[4]phyrin(1.1.1.1) metal complexes.[12,13] Despite the
disrupted π-conjugation in the parent tetrapyrrolic scaffold, the
NIR light absorption was achieved by electronic perturbation
through an N-confusion modification of the platinum calix[4]phyrin
complexes (Figure 1).[13c] The doubly N-confused derivative
demonstrated the lowest energy absorption and subsequently
good singlet oxygen generation. Using this modification strategy,
we have also reported novel NIR luminescent dyes based on
doubly N-confused calix[6]phyrin(1.1.1.1.1.1) bis-platinum
complexes.[14] The core-expansion of the parent calix[4]phyrins
induces the lower energy optical properties as there are more π-
electrons in the scaffold. However due to the fact that the
complexes possess relatively short triplet lifetimes (~15 ns) and
insufficient triplet energy that could otherwise allow the energy
transfer to dioxygen, the photosensitization for singlet oxygen
generation remains yet to be achieved. Increasing the spin-orbit
coupling decreases the triplet state life time and spin orbital
coupling will increase with atomic number.[15] Thus, we envisioned
that replacing the platinum metal with palladium, in the row right
above in the group 10 element column, should allow one to fine-
tune the triplet state dynamics of the complexes. Moreover, the
bis-palladium complex of doubly N-confused hexaphyrin exhibited
a much lower energy absorption (~1470 nm) which should
discourage energy transfer to singlet oxygen even though it has
advantage in the absorption profile in the NIR region.[16]
crystallographic analysis, NMR, absorption, emission, and EPR
spectroscopies.
Results and Discussion
The synthetic route of the mono- and bis-palladium complexes, 1-
Pd-H2, 2-Pd-H2, 1-Pd-Pd, and 2-Pd-Pd, is shown in the Scheme
1. The freebase calix[6]phyrin ligands (transoid, 1 and cisoid, 2)
were previously reported by our group, which serve as the
rectangular-shaped macrocyclic ligands.[14] The two isomeric
macrocycles, 1 and 2, in which the arrangement of the nitrogen
atoms of the N-confused pyrrole rings (highlighted in green) is
different, provide two organopalladium cation pockets surrounded
by symmetrical and unsymmetrical coordination donor sites,
“NNNC-NNNC” and
“NNNN-NNCC”, respectively. The
corresponding bis-organopalladium metal complexes, 1-Pd-Pd
and 2-Pd-Pd, were formed smoothly using 3 equivalents of
Pd(OAc)2 under reflux condition in a CH2Cl2/MeOH mixture, in 60
and 72% yields, respectively. Along with the formation of bis-
palladium complexes, the mono-palladium complexes, 1-Pd-H2
and 2-Pd-H2, were also formed in 30% and 22% yields,
respectively. When one equivalent of Pd(OAc)2 was added into
the solution containing a ligand 1 or 2, mono-palladium complex,
1- Pd-H2 or 2-Pd-H2 was predominantly obtained in 80 and 75%
yields, respectively. The 1H and 19F NMR spectroscopy and high-
resolution mass spectrometry support the expected structures (cf.
supporting information). Specifically, the complex 1-Pd-H2 shows
two characteristic signals at d = 12.90 (inner NH) and 10.59 ppm
(inner CH) (Figure S1). However, the complex 2-Pd-H2 shows one
sharp inner CH signal at 10.26 ppm reflecting the molecular
symmetry in the 1H NMR spectrum (Figure S2). The symmetry of
1-Pd-H2 is also reflected in the 19F NMR spectra; the splitting
pattern of the para-substituted 19F signals of the peripheral aryl
groups in a 1:2:1 ratio for 1-Pd-H2 and a 2:1:1 ratio for 2-Pd-H2
We herein report the facile synthesis of novel mono- and bis-
palladium calix[6]phyrin complexes (1-Pd-H2, 1-Pd-H2, 1-Pd-Pd,
and 2-Pd-Pd) (Figure 1). The large π-conjugated scaffold based
on the expanded calixphyrins attained prominent photophysical
properties toward the NIR light region. The influence of the
structural factors (e.g., coordination environment and the number
of metal cations) on the photosensitized singlet oxygen
generation were systematically investigated by X-ray
Figure 2. Top and side views of the X-ray crystal structures of (a) 1-Pd-H2, (b) 2-Pd-H2, (c) 3-Pd-Pd, and (d) 4-Pd-Pd. The confused rings are highlighted in
green.
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depending on the molecular symmetry, the trans-configured
complexes show relatively intense shoulder bands in the lower
energy region.
Scheme 1. Synthesis of the palladium complexes, 1-Pd-H2, 1-Pd-H2, 1-Pd-Pd,
and 2-Pd-Pd. Conditions: a) Pd(OAc)2 (3 equiv) in CH2Cl2/MeOH 12 h reflux; b)
Pd(OAc)2 (1 equiv) in CH2Cl2/MeOH, 2 h reflux.
verifies their trans/cis configurations (Figures S1 and S2). These
results suggested the porphyrin-like N4 donor site in cis-
configured 2 can preferentially accommodate a palladium cation
before subsequent second palladium metalation occurs, to give
2-Pd-Pd. The absence of the inner protons in the low field region
(beyond 8 ppm) in the 1H NMR spectra implies the successful bis-
metalation in the core. The peripheral β-protons appear in the
typical sp2-CH region due to the non-global π-conjugation as seen
in the bis-platinum calixphyrin complexes.[14]
Figure 3. UV−vis-NIR absorption spectra of Pd complexes; 1-Pd-H2 (blue
line), 2-Pd-H2 (red), 1-Pd-Pd (black) and 2-Pd-Pd (green) in toluene.
The molecular structures of the complexes, 1-Pd-H2, 2-Pd-
H2, 3-Pd-Pd, and 4-Pd-Pd, were characterized by X-ray
crystallographic analysis (Figures 2 and S7, Table S1). The
palladium cations reside in a square planar geometry in the inner
coordination environments for all the complexes. The coplanar
tripyrrin planes are faced with tethering sp3-hybridized meso-
carbon centers located in the short axis side in the rectangular
geometry. The overall core structures of the complexes exhibit
bent-distortions along the longer molecular axis with the angles of
83–86°. The values for mean plane deviations (used with 36 core
atoms) were estimated to be 0.717, 0.671, 0.743, and 0.770 Å for
1-Pd-H2, 2-Pd-H2, 3-Pd-Pd, and 4-Pd-Pd, respectively (Table S2).
The formation of the organopalladium bonds may play an
important role in the stabilization of the complexes as well as in
the tuning of their electronic structures. Unfortunately, the
disorder of the inner nitrogen versus adjacent carbon atoms of the
confused pyrrole rings in the complexes hampered us to gain the
discrete bonding information of the organopalladium complexes.
The stronger bonding character of the Pd–C linkages than that of
the Pd–N was speculated due to the intrinsic donor character of
the anionic carbon sites.[17] The theoretical structures of the
complexes obtained from the density functional calculations
reproduced the experimental structures (vide infra, Figure S8).
In order to study the optical properties of the complexes, UV-
Vis-NIR spectra were recorded in toluene (Figure 3). All the
complexes exhibit the intense absorption bands in the visible
region (λabs = 500–700 nm) and tailing bands in the NIR region.
The peak maxima of the mono-Pd complexes, 1-Pd-H2 and 2-Pd-
H2, appear around 560 nm (ε ~ 80000 M–1 cm–1), whereas the
peaks for the bis-Pd complexes, 1-Pd-Pd and 2-Pd-Pd, are seen
in the lower energy region beyond 600 nm with relatively high
absorption coefficient (ε ~ 90000 M–1 cm–1) (Table 1). Interestingly,
Figure 4. Cyclic voltammograms of 1-Pd-H2, 2-Pd-H2, 1-Pd-Pd, and 2-Pd-Pd
in CH2Cl2 containing 0.1 M TBAPF6. The scan rate is 100 mV s–1, and the
concentration was set to 1 mM.
Owing to the severely broadened absorption features in the
NIR region, the HOMO-LUMO energy gap of the complexes was
analyzed using cyclic voltammetry (CV) and differential pulse
voltammetry (DPV) in dichloromethane containing 0.1
M
tetrabutylammonium hexafluorophosphate (TBAPF6) as the
supporting electrolyte (Figures 4, S13, and S14). In fact, the bis-
palladium complexes represent the similar redox profile: the
quasi-reversible oxidation waves and irreversible reduction waves
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were observed at Eox = 0.57 and 0.54 V (vs ferrocene/ferrocenium
couple) and Ered = -1.07 and -1.09 V, respectively. The
corresponding energy gaps are thus calculated to be 1.64 and
1.63 V for 1-Pd-Pd and 2-Pd-Pd, respectively. In contrast, the
irreversible oxidations at Eox = 0.65 and 0.69 V, and the reduction
at Ered = -0.95 and -1.24 V were observed for the mono-palladium
complexes, 1-Pd-H2 and 2-Pd-H2, respectively. The remarkably
narrow HOMO-LUMO gap of 1-Pd-H2 is originated from the
anodic shift of the reduction wave than that of 2-Pd-H2, which
implies the alteration of the electronic structures of the
macrocycles.
In an effort to further elucidate the electronic structures of the
complexes, density functional theory (DFT) calculations were
carried out using B3LYP/6-31G**+SDD method. The π-electron
present in the frontier molecular orbital diagrams was found to be
delocalized over the π-ligands for all the complexes except for 1-
Pd-H2 (Figure S8). The LUMO pair of 1-Pd-H2 indicated the partial
localization on the tripyrrin moieties, which induces the broken-
degeneracy of the LUMO/LUMO+1 pair. The feature in the
remarkably stabilized LUMO causes the intrinsically narrower
HOMO-LUMO gap of 2.07 V than that of the corresponding
isomer 2-Pd-H2 with the gap of 2.63 V. The surrounding metal-
coordination environment can also contribute to the HOMO
energy profiles; the palladium-carbon bonding nature within the
NNNC sphere in 1-Pd-H2 destabilizes the energy as reported for
other porphyrinoids.[18] The partial contribution from the d-orbital
(dyz) of organopalladium center in HOMO for 1-Pd-H2 may
influence the electronic alteration (but not for 2-Pd-H2). Similarly,
the influence of metal d-electron in the ground state molecular
orbitals for the organopalladium complexes was speculated
through the Pd–C bond linkage. There is partial contribution from
d-orbital in HOMO and HOMO-1, which should reflect to the
optical properties.
The spectral features were analyzed using time-dependent
(TD)-DFT calculations with B3LYP method (Figures S9–S12,
Tables S3–S5). As discussed above, the trans-configured
complexes, 1-Pd-H2 and 1-Pd-Pd, show intensified shoulder
peaks compared to their cis-form counterparts, 2-Pd-H2 and 2-Pd-
Pd, respectively. The TD-DFT calculations suggest that the
transition from HOMO–1 to LUMO orbital contributes mostly and
the oscillator strength of this transition is larger for the trans-form.
Interestingly, partial MLCT contribution exists in the trans-forms
Figure 5. Phosphorescence spectra of 1-Pd-H2, 2-Pd-H2, 1-Pd-Pd, and 2-Pd-
Pd in deaerated toluene at r.t. (λex = 532 nm).
more than in the cis-form. Moreover, calculations also suggest the
bathochromic shifts for bis-palladium complexes. As is the case
with bis-platinum calix[6]phyrin complexes (lem ~ 1020 nm), a
series of the palladium complexes indeed showed
phosphorescence in the NIR region at room temperature in
deaerated toluene (Figure 5 and Table 1). In terms of the energies,
the bis-Pd complexes showed similar spectral feature (E ~1.27
eV). In contrast, the mono-Pd complexes indicated the varied
emission energies in the order, 2-Pd-H2 (1.56 eV) > 1-Pd-H2 (1.40
eV) depending on the molecular symmetry.
The phosphorescence quantum yields and lifetimes of the
series of complexes were determined to analyze the triplet state
behaviors (Figures S15–S18). The phosphorescence lifetimes of
bis-palladium complexes, 1-Pd-Pd and 2-Pd-Pd, are determined
to be 183 and 174 ns, respectively, which are significantly larger
than the photoluminescent lifetimes of Pt-calix[6]phyrin
complexes (20–30 ns).[14] In the case of the mono-palladium
complexes, there is an apparent difference between the isomers;
2-Pd-H2 possesses a significantly longer triplet state lifetime of
536 ns, whereas 1-Pd-H2 has a short lifetime in the sub-
microsecond time scale. In this regard, the phosphorescence
quantum yields of 2-Pd-H2 (ΦPL= 3.9 × 10–3) is significantly larger
Table 1. Summary of the photophysical parameters for the palladium complexes.
λabs (nm)
kr
knr
[c]
Complex
λem (nm)
ΦPL[a] (1×10–3
)
τPL(ns)[b]
ΦΔ
(ε/ 104 M–1 cm–1
)
(103 s–1
)
(106 s–1
)
1-Pd-H2
2-Pd-H2
1-Pd-Pd
2-Pd-Pd
566 (7.11)
568 (6.29)
619 (7.67)
622 (9.07)
886
795
977
973
0.56
3.9
1.2
2.1
127
536
183
174
4.4
7.3
7.8
1.8
5.4
5.7
0.05
0.83
0.30
0.27
6.5
11.9
[a] Quantum yield was calculated using 4-Pt-Pt (ΦPL = 0.0027 in toluene, λex = 532 nm) as reference [14]. [b] Determined by TCSPC method with excitation at 532
nm. [c] Singlet oxygen quantum yield measured in CH2Cl2/MeOH with methylene blue as standard.[19]
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than that of 1-Pd-H2. In the decay process, excited-state
intramolecular proton transfer (ESIPT) of the pyrrolic NH moiety
with adjacent pyrrole imine could be attributed for 1-Pd-H2. In
contrast, the intrinsic strong C–H bonding nature of the N-
confused pyrrole ring in 2-Pd-H2 could have hindered this
process.[20] In the case of 1-Pd-Pd and 2-Pd-Pd, slightly smaller
values of ΦPL than that of 2-Pd-H2 were obtained for both the bis-
palladium complexes, probably due to the smaller energy gap.[21]
It is noteworthy that the cis-isomer was more luminescent than
the trans-isomer as observed for bis-platinum complexes,[14]
although a further study is necessary to clarify the effect of the
symmetrical/unsymmetrical coordination environments on the
excited states dynamics.
oxygen species (e.g., peroxide, superoxide) are generated under
this condition.[25]
Table 2. Chemical yield of conversion of DHN to juglone in the presence of
sensitizer after 60 minutes.
The emission due to the singlet oxygen (1Δg) was observed at
1270 nm from the solution of the palladium complexes during the
phosphorescence measurements under the aerobic conditions
(Figure S25). The palladium complexes in the triplet state could
sensitize the generation of singlet oxygen upon photoirradiation.
The efficiency of sensitization was systematically studied by
monitoring the UV-vis spectral changes of a well-known singlet
oxygen scavenger, 1,5-dihydroxynaphthalene (DHN: l ~ 340 nm)
in the presence of the photosensitizers (1-Pd-H2, 2-Pd-H2, 1-Pd-
Pd, 2-Pd-Pd, and methylene blue (MB) as a reference) in
CH2Cl2/MeOH (Figures S19–S24). Singlet oxygen generated in-
situ can oxidize DHN to juglone upon Xe lamp irradiation (λex;
450–800 nm) (Table 2).[22] The singlet oxygen quantum yields
were calculated using the following equation 1.[23]
% degradation
Complex
Chemical yield (%)
(60 min)
1-Pd-H2
2-Pd-H2
1-Pd-Pd
2-Pd-Pd
MB
73
83
97
92
98
3.1
48.7
2.6
2.7
30.1
ΦΔ = ΦΔstd × (νiIstd/νistdI),
(1)
where ΦΔ is the singlet oxygen quantum yield (ΦΔstd = 0.74, for MB)
in CH2Cl2/MeOH, νi is the initial rate of DHN consumption, and I
is the relative number of photons absorbed.[19] νi is determined
from the slope of the graph ln(Ct/C0) in the initial 3 minutes (Figure
6a). As the result, the quantum yields for singlet oxygen
generation using the palladium complexes were estimated to be
0.83 (2-Pd-H2) > 0.30 (1-Pd-Pd) > 0.27 (2-Pd-Pd) > 0.05 (1-Pd-
H2) based on the reference value 0.74 (MB) (Table 1). The long-
lived triplet excited state of photosensitizer has
a higher
probability to undergo bimolecular collision with ground state
oxygen to generate singlet oxygen.[2] The huge acceleration in the
conversion could be thus related to the triplet-state lifetime of the
photosensitizer.
To confirm the singlet oxygen generation in the
photosensitization, we conducted the EPR measurements using
spin labelling agents, 2,2,6,6-tetramethylpiperidine (TEMP) and
5,5-dimethyl-1-pyrroline-N-oxide (DMPO), respectively (Figure
6d). Photoirradiation of an air-saturated toluene solution
containing photosensitizer and TEMP resulted in the
characteristic three-line EPR spectrum after 3 min. The hyperfine
coupling constants, aN is 16.0 G which can be assigned to TEMPO
(TEMP and 1Δg react to form TEMPO).[24] The TEMPO signal
intensity is in the order 2- Pd-H2 > 1-Pd-Pd > 2-Pd-Pd > 1-Pd-H2,
which is well correlated to the quantum yields of singlet oxygen
generation. In contrast, no reaction occurred in the presence of
another spin labelling reagent, DMPO, indicating no other reactive
Figure 6. (a) Plot of ln(Ct/C0) versus irradiation time for palladium complexes
(1-Pd-H2, 2-Pd-H2, 1-Pd-Pd, and 2-Pd-Pd) and methylene blue (MB). (b)
Change in concentrations of the photosensitizers under the irradiation condition.
(c) Kinetics of chemical yields of juglone with respect to irradiation time in
CH2Cl2/MeOH. (d) EPR spectra of the spin trapped species using TEMP in the
presence of the palladium complexes in oxygen-saturated toluene solution
recorded after 3 minutes of light irradiation (450–800 nm).
Importantly, we tested the durability of the sensitizers under
the identical conditions and bis-palladium complexes, 1-Pd-Pd
and 2-Pd-Pd, were found to be remarkably stable under
photoirradiation (Figure 6b, Table 2).[19] As a result, the actual
chemical yields of juglone using the bis-palladium complexes, 1-
Pd-Pd (97%) and 2-Pd-Pd (92%), were found to be larger than
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that of 2-Pd-H2 (83%) in spite of its higher singlet oxygen quantum
yield (Figure 6c). Interestingly, the relatively less effective 1-Pd-
H2 generated juglone gradually but in high yield after 60 min
irradiation. In the case of most reactive 2-Pd-H2, juglone was
rapidly formed but the yield was saturated after 20 min,
presumably due to the instability of the complex under the
condition used. Based on the above analysis, the photostability of
the sensitizers is seen to be one of the most important factors for
practical use in applications such as PDT. Without sensitizers the
product was obtained only in 2% yield after 60 minutes, indicating
the critical role of photosensitizer in this reaction.
by the palladium complexes in O2 saturated toluene were recorded on an
SPEX Fluorolog-3-NIR spectrometer (HORIBA). The solution of
a
sensitizer with DHN was bubbled with oxygen for 15 minutes to get oxygen
saturated solution. Then the solution was irradiated with 450–800 nm light
using a bandpass filter and photoirradiation was carried out using a Xe
lamp of 300 W.
Time-Resolved
phosphorescence measurements were performed in the time-correlated
single photon counting mode using NIR-sensitive photomultiplier
(Hamamatsu H10330-75). The excitation source was a 532 nm frequency-
doubled passive-Q-switched Nd:YAG laser delivering μJ sub-
Emission
Spectroscopy.
Time-resolved
a
a
1
nanosecond (<0.7 ns) pulse train at a repetition rate of 8 kHz. The sample
solutions (toluene solvent) in the cell cuvette were carefully degassed by
argon (gas) bubbling with septum.
Conclusions
Theoretical Calculations. DFT calculations were performed with the
Gaussian16 program package without symmetry treatment.[26] Initial
structures were based on the X-ray crystal structure of the related
compounds. The geometries were fully optimized using Becke’s three-
parameter hybrid functional combined with the Lee–Yang–Parr correlation
functional, denoted as the B3LYP level of DFT, with the 6-31G(d,p), and
SDD (for Pd) basis set for all calculations.[27] Experimental absorption
spectra were analyzed by time-dependent DFT (TD-DFT) calculations with
the same level. Ground-state geometries were verified by the frequency
calculations, where no imaginary frequency was found. For visualization
of the optimized geometries and the molecular orbitals, GaussView
software was used.
In summary, we have synthesized a series of novel triplet
photosensitizers based on mono- and bis-palladium calix[6]phyrin
complexes, 1-Pd-H2, 2-Pd-H2, 1-Pd-Pd, and 2-Pd-Pd, for singlet
oxygen generation. These complexes have broad absorption
spectra from the visible to NIR region and appropriate triplet
energy (800–1000 nm) and reasonably longer lifetimes (~540 ns)
for the sensitization of singlet oxygen generation. The metal
number and coordination environment of the complexes play an
important role in modulation of the optical properties as well as
photostability. Because of the facile synthesis, good singlet
oxygen generation capability, and photostability, the current
calix[6]phyrin-based photosensitizers would hold promise for
applications such as PDT, photo-redox catalysts and so on.
X-ray Crystallography. Single-crystal X-ray structural analyses for 1-Pd-
H2, 2-Pd-H2, 3-Pd-Pd, and 4-Pd-Pd were performed on
a Saturn
diffractometer equipped with a CCD detector (Rigaku) using MoKα
(graphite, monochromatized, λ = 0.71069 Å) radiation. The data were
corrected for Lorentz, polarization, and absorption effects and refined
using the SHELXS-2014/7 program.[28] All of the positional parameters and
thermal parameters of non-hydrogen atoms were refined anisotropically
on F2 by the full-matrix least-squares method. Hydrogen atoms were
placed at calculated positions and refined using a riding model on their
corresponding carbon atoms. The crystal-to-detector distance was 45.00
mm.
Experimental Section
Materials and Instruments. All reactions were performed in dried vessels
under Ar or N2. Commercially available solvents and reagents were used
without further purification unless otherwise mentioned. CH2Cl2 was dried
by passing through a pad of alumina. Thin-layer chromatography (TLC)
was performed on an aluminum sheet coated with silica gel 60 F254 (Merck).
Preparative separation was performed by silica gel flash column
chromatography (KANTO silica gel 60N, spherical, neutral, 40−50 μm) or
silica gel gravity column chromatography (KANTO Silica Gel 60N,
spherical, neutral, 63-210 μm). 1H and 19F NMR spectra were recorded in
Synthesis of Precursors. The freebase doubly N-confused
calix[6]phyrins (1-4) were synthesized by following the procedure reported
previously.[14] Detailed characterization data for 1-Pd-H2, 2-Pd-H2, 1-Pd-
Pd, and 2-Pd-Pd is given in Supporting Information.
CDCl3 solutions on a JEOL ECX500 NMR spectrometer (500 MHz for 1
H
and 470 MHz for 19F). Chemical shifts were reported relative to CDCl3 (d =
7.26 ppm) for 1H in parts per million. Trifluoroacetic acid (0.02% in CDCl3)
was used as an external reference for 19F (d = –76.5 ppm). UV–vis–NIR
General method for synthesis of mono-palladium complexes (1-Pd-H2): A
mixture of free ligand, 1 (20 mg, 0.015 mmol) and Pd(OAc)2 salt (3.8 mg,
0.017 mmol) in CH2Cl2/MeOH (2:1) was stirred under argon for 2 h under
reflux conditions (40 °C). The solvents were removed in vacuo using high
vacuum pump. The crude product was purified using silica gel column
chromatography with CH2Cl2/hexane mixture.
absorption spectra were measured on
a Shimadzu UV-3150PC
spectrometer. Fluorescence spectra were recorded on an SPEX
Fluorolog-3-NIR spectrometer (HORIBA) with an NIR-PMT R5509
photomultiplier tube (Hamamatsu) in a 10 mm quartz fluorescence cuvette.
High-resolution mass spectra (HRMS) were obtained in fast atom
bombardment (FAB) mode with 3-nitrobenzyl alcohol (NBA) as a matrix on
a JEOL LMS-HX-110 spectrometer.
The complex, 2-Pd-H2 was also synthesized using 2 under the same
conditions.
Data for 1-Pd-H2: yield = 80% (17.2 mg); 1H NMR (CDCl3, ppm): d 12.90
(s, 1H), 10.59 (s, 1H), 6.65 (d, J = 4.8 Hz, 1H), 6.62 (d, J = 4.8 Hz, 1H),
6.59 (s, 1H), 6.54 (d, J = 4.5 Hz, 1H), 6.48 (d, J = 4.4 Hz, 1H), 6.36 (d, J =
4.3 Hz, 1H), 6.33 (d, J = 4.3 Hz, 1H), 6.19 (d, J = 4.2 Hz, 1H), 5.98 (s, 1H),
5.94 (s, 1H), 3.29 (s, 2H), 2.99 (s, 1H), 2.54 (s, 1H), 2.24 (s, 4H), 1.82 (m,
4H), 1.57 (m, 8H); 19F NMR (CDCl3, ppm): d –136.42 (s), –136.96 (s), –
137.24 (s), –137.62 (s), –138.21 (s), –138.69 (s), –138.94 ~ –139.15 (m),
–150.99 (d, J = 38.5 Hz), –151.82 (d, J = 34.0 Hz), –152.41 (d, J = 39.5
Singlet Oxygen Quantum Yields. Singlet oxygen quantum yields (ΦΔ)
were determined in CH2Cl2/MeOH by using 5 mol% of mono- and bis-
palladium complexes (1-Pd-H2, 2-Pd-H2, 1-Pd-Pd, and 2-Pd-Pd) (9 μM)
and methylene blue (MB) as the reference compound. The singlet oxygen
scavenger, dihydroxynaphthalene (DHN, 181 μM) was used as the singlet
oxygen scavenger. Alternately, emissions of the singlet oxygen sensitized
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Hz), –159.33 (s), –160.07 (s), –160.27 (d, J = 25.9 Hz), –160.70 (d, J =
64.1 Hz), –160.99 (s); HRMS (FAB+): m/z = 1371.1481 (found), 1371.1482
(Calcd for C64H33F20N6Pd), error –0.1 ppm.
Keywords: Triplet Photosensitizer
calix[6]phyrin • Singlet oxygen • Photostability
•
Palladium N-confused
Data for 2-Pd-H2: yield = 75 % (16.1 mg); 1H NMR (CDCl3, ppm): d 10.26
(s, 1H), 6.65 (d, J = 4.6 Hz, 1H), 6.50 (d, J = 4.6 Hz, 1H), 6.41 (d, J = 4.6
Hz, 1H), 6.36 (d, J = 4.5 Hz, 1H), 5.93 (s, 1H), 3.38 (s, 1H), 2.88 (s, 1H),
2.27 (s, 1H), 2.21 (s, 1H), 1.83 (s, 1H), 1.62 (m, 5H); 19F NMR (CDCl3,
ppm): d -136.69 (s), -137.28 (s), -138.57 (d, J = 23.9 Hz), -138.94 (s), -
151.13 (s), –152.32 (d, J = 38.7 Hz), –159.82 (s), –160.29 (s), –160.58 (s),
–160.90 (s); HRMS (FAB+): m/z = 1371.1484 (found), 1371.1482 (Calcd
for C64H33F20N6Pd), error + 0.1 ppm.
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General method for synthesis of bis-palladium complexes (1-Pd-Pd): A
mixture of free ligand 1 (20 mg, 0.015 mmol) and Pd(OAc)2 (11.4 mg, 0.052
mmol) in CH2Cl2/MeOH (2:1) was stirred under argon for 12 h under reflux
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Data for 1-Pd-Pd: yield = 60% (14 mg); 1H NMR (CDCl3, ppm): d 6.59 (d,
J = 4.5 Hz, 1H), 6.55 (d, J = 4.7 Hz, 1H), 6.48 (d, J = 4.6 Hz, 1H), 6.41 (d,
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J = 21.9 Hz), –139.13 (d, J = 24.7 Hz), –151.67 (d, J = 57.9 Hz), –159.73
(s), –160.08 (s), –160.61 (s), –160.93 (s); HRMS (FAB+): m/z = 1474.0290
(found), 1474.0282 (Calcd for C64H30F20N6Pd2), error + 0.5 ppm.
Data for 2-Pd-Pd: yield = 71% (16.5 mg); 1H NMR (CDCl3, ppm): d 6.64 (d,
J = 4.7 Hz, 1H), 6.48 (t, J = 5.2 Hz, 2H), 6.38 (d, J = 4.4 Hz, 1H), 5.93 (s,
1H), 3.21 (s, 1H), 3.09 (s, 1H), 2.25 (m, 2H), 1.80 (s, 2H), 1.55 (m, 4H);
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Data for 3-Pd-Pd: 1H NMR (CDCl3, ppm): d 6.52 (m, 4H), 6.48 (d, J = 4.7
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160.75 (s), –160.77 (d, J = 21.5 Hz), –160.72 ~ –161.52 (m); HRMS
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error + 2.0 ppm.
Data for 4-Pd-Pd: 1H NMR (CDCl3, ppm): d 6.60 (m, 2H), 6.47 (d, J = 4.6
Hz, 2H), 6.42 (m, 2H), 6.37 (d, J = 4.4 Hz, 2H), 5.97 (s, 2H), 2.27 (d, J =
10.1 Hz, 6H), 1.75 (d, J = 13.9 Hz, 6H); 19F NMR (CDCl3, ppm): d –137.53
(m, 26.8 Hz), –138.95 (d, J = 28.3 Hz), –139.35 (d, J = 28.8 Hz), –151.65
(t, J = 22.9 Hz), –159.79 (t, J = 21.7 Hz), –159.99 (t, J = 21.8 Hz), –160.83
(t, J = 21.5 Hz), –161.04 (t, J = 21.8 Hz); HRMS (FAB+): m/z = 1393.9658
(found), 1395.9656 (Calcd for C58H22F20N6Pd2), error + 0.1 ppm.
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Acknowledgements
The present work was supported by Grants-in-Aid (JP15K13646
to H.F.; JP16K05700 and JP17H05377 to M.I.; JP17H02773 and
JP18K19029 to S.F.) from the Japan Society for the Promotion of
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