Volume 47
Number 6
14 February 2023
Pages 2685–3186

NJC
New Journal of Chemistry

A journal for new directions in chemistryrsc.li/njc

ISSN 1144-0546

PAPER
Yousuke Ooyama et al.
Synthesis and optical properties of phenazinone-based
photosensitizers for singlet oxygen generation

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PAPER

Cite this: New J. Chem., 2023,
47, 2711

Synthesis and optical properties ofphenazinone-based photosensitizers
for singlet oxygen generation†
Kazuki Ohira,

Masahiro Yamamoto, Keiichi Imato

and Yousuke Ooyama*

Phenazinone derivatives PZ1–3 where a carbonyl group is incorporated into the chromophore aredesigned and developed as halogen-atom-free-heteroanthracene-based photosensitizers possessing
the ability to generate singlet oxygen (1O2). Compared to the phenazine-2,3-diol (PZ) without a carbonylgroup, the molar absorption coefficients of PZ1–3 at around 480 nm increased by a factor of five to six.
Furthermore, the values of fluorescence quantum yields (Ffl) of PZ1–3 were significantly low (0.03 for
PZ1, 0.04 for PZ2, and 0.05 for PZ3). To evaluate the 1O2 generation ability of PZ1–3, the 1O2 quantum
yields (FD) of PZ1–3 were estimated and it was demonstrated that PZ1 exhibited a higher FD value thanrose bengal (RB) known as a reference photosensitizer to generate 1O2 (0.86 for PZ1, 0.54 for PZ2,
0.069 for PZ3, and 0.68 for RB). Moreover, the rate constants (kr, knr, kISC, and kIC) of PZ1–3 indicatedthat the reason for the low FD of PZ2 and PZ3 comes from the vibrational relaxation caused by a flexible
methoxymethoxy and 4-chlorobenzoate group, respectively. Density functional theory (DFT), timeReceived 31st October 2022,
Accepted 17th December 2022

dependent DFT (TD-DFT), and natural transition orbital (NTO) calculations suggested that for PZ1–3, theintersystem crossing (ISC) processes from the lowest excited singlet state (S1) to the third triplet state

DOI: 10.1039/d2nj05322e(T3) are thermodynamically feasible and facilitated based on El-Sayed’s rule. Consequently, we proposethat the phenazinone skeleton is one of the promising halogen-atom-free-heteroanthracene-based

rsc.li/njc

chromophore photosensitizers.

Introduction
Photosensitizers (PSs) possessing the singlet oxygen (1O2) generation ability have attracted much attention because of theiruseful applications such as in water purification,1 antivirals,2and photodynamic therapy (PDT) for cancer treatment.3 These
PSs generally produce 1O2 through the following processes:
initially, the photosensitizer (S0) absorbs light (hn) to generate
the singlet excited state of the photosensitizer (Sn), and then thephotoexcited sensitizer (Sn) undergoes intersystem crossing(ISC) to generate the triplet excited state (Tn). After internalconversion (IC) to the lowest excited triplet state (T1), subsequent energy transfer from the photoexcited PS (T1) to triplet
oxygen (3O2) produces 1O2.4 Indeed, phthalocyanine dyes,5phenothiazine dyes,6 xanthene dyes,7 and boron-dipyrromethene (BODIPY) dyes8 are known to show high 1O2 quantum
yield (FD) values. For these PSs, halogen atoms such as iodide
Applied Chemistry Program, Graduate School of Advanced Science and Engineering,
Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima, 739-8527, Japan.
E-mail: yooyama@hiroshima-u.ac.jp† Electronic supplementary information (ESI) available. CCDC 2194829, 2194831
and 2194832. For ESI and crystallographic data in CIF or other electronic format
see DOI: https://doi.org/10.1039/d2nj05322e

and bromide atoms are often introduced into the chromophores to promote ISC based on spin–orbit coupling,9 but it
raises concerns about dark cytotoxicity.10 To overcome thedrawbacks, halogen-atom-free PSs11 such as a family of heteroanthracenes have been extensively studied. Among them,
methylene blue (MB) is used as a reference PS for the evaluationof FD.12 Therefore, in order to create a new type of halogenatom-free-heteroanthracene-based PS, we have focused on thephenazine skeleton, because to the best of our knowledge there
are few reports on the evaluation of 1O2 generation ability
for phenazine derivatives.13 In our previous study,14 we havedeveloped phenazine-2,3-diol-based PSs (KO-0–3) and demonstrated that the modification of the phenazine-2,3-diol chromophore with formyl groups promotes ISC, leading to efficient
1O2 generation (Fig. 1a). According to the El-Sayed rule,15
formyl and carbonyl substituents in a chromophore skeleton
allow ISC by a change in the molecular orbital type, such as1(np*) to 3(pp*) and 1(pp*) to 3(np*) transitions. Indeed, thesePSs exhibited moderate photosensitizing properties for 1O2
generation (FD = 0.41 for KO-3).
Recently, in our continuous work to develop halogen-atomfree PSs based on El-Sayed’s rule, it was found that 3-hydroxy10-methylphenazin-2(10H)-one (PZ1) incorporating a carbonyl

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Scheme 1

Fig. 1 (a) Chemical structures of phenazine-2,3-diol-based PSs KO-0–3
and their FD values employed in our previous study. (b) Chemical structures of phenazine-2,3-diol (PZ) and phenazinone-based PSs PZ1–3
designed and synthesized in this study.

group into the chromophore possesses highly eﬃcient photosensitizing capabilities compared to phenazine-2,3-diol-based
PSs (Fig. 1b). Indeed, PZ1 without halogen atoms possesses
the superior 1O2 generation ability to RB (FD = 0.68 in THF)
with many halogen atoms as well as MB (FD = 0.57 indichloromethane)21 without halogen atoms. Based on our previous study and El-Sayed’s rule, it was assumed that the
carbonyl moiety in PZ1 plays an essential role in the eﬃcient
ISC, that is, high FD value. In order to confirm the presence of acarbonyl group in PZ1, X-ray single crystal structure analyses
were required. Therefore, we have designed and synthesized
the phenazinone derivative PZ3 with a 4-chlorobenzoate group.
It is well known that the 4-chlorobenzoate group is able toimprove crystallizability.16 Fortunately, we succeeded in performing X-ray single crystal structure analyses for PZ1 as well as
PZ3. Furthermore, it was found that the FD values are significantly diﬀerent between PZ1 and PZ3. Therefore, in order toinvestigate the substituent eﬀects on the optical and 1O2
generation properties between the phenazinone-based PSs, weprepared PZ2 with a methoxymethoxy group as a substitute forthe hydroxy group. Moreover, the density functional theory(DFT), time-dependent DFT (TDDFT), and natural transition
orbital (NTO) calculations were performed to evaluate the
ISC eﬃciency of phenazinone-based PSs. Herein, we report
the phenazinone chromophore as a new family of heteroanthracene-based PSs without halogen atoms for eﬃcient 1O2
generation.

Synthetic routes of PZ1–3.

methyl ether or 4-chlorobenzoyl chloride gave PZ2 and PZ3,
respectively. These PSs were obtained in moderate yields(62–63%) and successfully characterized by 1H NMR, 13C
NMR, FTIR, and high-resolution mass spectrometric analysis.
Furthermore, X-ray single crystal analysis was performed on
the PSs.
X-Ray crystal structures
As shown in Fig. 2, for all the three PSs, the bond lengths ofC2–O1 and C3–O2 are ca. 1.25 Å and ca. 1.36 Å, respectively.
Therefore, C2–O1 and C3–O2 have typical CQO double bondand C–O single bond lengths, respectively, indicating undoubtedly that the three PSs have a phenazinone skeleton. Interestingly,
PZ1, PZ2, and PZ3 have high planarity with small root-meansquare deviations of 0.0487, 0.0717, and 0.1033 Å, respectively,
despite the presence of an sp3 nitrogen atom.
Optical properties
The photoabsorption and fluorescence spectra of PZ1–3 in THF
are shown in Fig. 3 with comparison to those of phenazine-2,3diol (PZ), and their optical data are summarized in Table 1. PZ
showed two photoabsorption maximums (labsmax): a narrow bandat around 390 nm is attributed to the p - p* transition of thephenazine skeleton which is supported by DFT calculations(Table S6 and Fig. S16, ESI†), and the other weak band ataround 480 nm (molar extinction coefficient (e) = 1700 M 1 cm 1)is ascribable to the formation of phenoxide ions by thepartial deprotonation of the hydroxyl groups.13 On the other
hand, PZ1 exhibited an intense photoabsorption band with a1labscm 1) at 478 nm17 compared to PZ. It was
max (e = 10 900 M
found that the introduction of the methoxymethoxy group or
4-chlorobenzoate group into the phenazinone chromophore

Results and discussion
Synthesis
PZ1 was prepared in one step by the cyclodehydration of
N-methyl-o-phenylenediamine and 2,5-dihydroxy-1,4-benzoquinone (Scheme 1). In order to perform X-ray single crystal
structure analyses, we designed phenazinone derivative PZ3
with a 4-chlorobenzoate group which is able to improve
crystallizability.16 In addition, in order to investigate the substituent eﬀects on the optical and 1O2 generation properties, we
devised PZ2 with a methoxymethoxy group as a substitute forthe hydroxy group. The reactions of PZ1 with chloromethyl

2712 | New J. Chem., 2023, 47, 2711–2718

Fig. 2 X-Ray crystal structures of (a) PZ1, (b) PZ2, and (c) PZ3. Selectedbond lengths (Å): C2–O1 1.2566(18), 1.2418(16), and 1.2422(15),
C3–O2 1.3436(18), 1.3582(15), and 1.3906(15) for PZ1, PZ2, and PZ3,
respectively.

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Fig. 3 (a) Photoabsorption and (b) fluorescence (lex = 361–390 nm)
spectra of PZ and PZ1–3 (1.0  10 4 M) in THF.

leads to a further bathochromic shift of the photoabsorption
band (labsmax = 487 nm for PZ2 and 510 nm for PZ3). TDDFT
calculations demonstrated that the values of excitation energy
from the S0 state to the S1 state are 2.86 eV for PZ1, 2.87 eV for
PZ2, and 2.73 eV for PZ3 (Fig. 5 and Table S6, ESI†). Moreover,the DFT calculations revealed that the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecularorbital (LUMO) energy levels of PZ3 are lower than those of PZ1,
but the lowering in the LUMO energy level is larger than that in
the HOMO energy level (Fig. S15, ESI,† HOMO = 5.78 eV,
LUMO = 2.64 eV for PZ1 and HOMO = 6.00 eV, LUMO =2.94 eV for PZ3). Thus, the bathochromic shift of the photoabsorption bands from PZ1 to PZ3 is mainly attributed to thestabilization of the LUMO energy level through the introduction of the electron-withdrawing 4-chlorobenzoyl group into thephenazinone skeleton, resulting in a decrease in the HOMO–
LUMO band gap (DEH–L = 3.14 eV and 3.06 eV for PZ1 and PZ3,
respectively). Consequently, the bathochromic shift of thecalculated photoabsorption bands from PZ1 to PZ3 was in good
agreement with the experimental results (Fig. 3a and Table 1).
In addition, PZ2 with a methoxymethoxy group also exhibited a
photoabsorption band in a longer wavelength region by 9 nm,
compared to PZ1. However, the DFT and TDDFT calculations
showed almost the same values of DEH–L (3.14 eV for PZ1 and3.16 eV for PZ2) and excitation energy (2.86 eV for PZ1 and2.87 eV for PZ2) between PZ1 and PZ2, in which the HOMO andthe LUMO energy levels of PZ2 (HOMO = 5.72 eV and LUMO =2.56 eV) are slightly higher than those of PZ1 (HOMO =5.78 eV and LUMO = 2.64 eV). Meanwhile, the bathochromic
shift of the photoabsorption bands from PZ1 to PZ2 would be
explained based on the extended Hammett equation.18 Thus, it

Table 1is suggested that the substitution of a methoxymethoxy groupfor a hydroxy group reduces the electron-donating effect on thephenazinone chromophore because the substituent constantsof hydroxy and methoxy groups are 0.37 and 0.268, respectively, leading to the bathochromic shift of the photoabsorption
bands from PZ1 to PZ2. In the corresponding fluorescence
spectra, PZ showed two fluorescence bands with a fluorescencemaximum wavelength (lflmax) at 440 nm and 555 nm, which
would originate from the phenazine skeleton and its phenoxideion, respectively. On the other hand, PZ1, PZ2, and PZ3 showeda fluorescence band with a lflmax of 554 nm, 579 nm, and597 nm, respectively, originating from phenazinone skeleton.
The fluorescence quantum yields (Ffl) of PZ1, PZ2, and PZ3
were significantly low (0.03 for PZ1, 0.04 for PZ2, and 0.05 for
PZ3), which is attributed to ISC and IC as discussed later.
1O2 generation

Thus, we evaluated the 1O2 generation ability of the phenazinone PSs PZ1–3. It is well-known that 1,3-diphenylisobenzofuran (DPBF) acts as an efficient 1O2 scavenger to produce
its oxidized product, o-dibenzoylbenzene.19 Thus, 1O2 generation by PZ1–3 in THF was investigated by monitoring thephotoabsorption spectral changes of DPBF accompanied by
the reaction of DPBF with the generated 1O2 (Fig. 4a–c). THF
was bubbled with air for 10 min prior to preparing solutions.
Air-saturated THF solutions containing DPBF and each PS were
irradiated with monochromatic light at 509 nm (300 mW cm 2)that was obtained by passage of a xenon light source through a
monochromator. In all the solutions, the photoabsorption of
DPBF at around 413 nm decreased with photoirradiation time,
which indicates that DPBF reacted with 1O2 generated by thephotoexcitation of the PSs. However, the decrements in absorbance at 413 nm were significantly different between the PSs.
Thus, the changes in optical density (DOD) of DPBF at 413 nm
were plotted against photoirradiation time to estimate FDvalues of these PSs (Fig. 4d): the FD values were estimated fromthe slopes (msam) of the plots using rose bengal (RB, FD = 0.68
in THF) as a standard sample (Table 1). The correlation
coefficient (R2) values for the calibration curves of PZ1–3 andRB were 0.992–0.999, which indicates good linearity, and themsam values increased in the order of PZ3 (0.0010) o PZ2(0.0070) o RB (0.0083) o PZ1 (0.010). As the result, the FD
values were estimated to be 0.54, and 0.069 for PZ2 and PZ3,
respectively. It is worth noting here that PZ1 exhibited the

Optical data and 1O2 quantum yields (FD) of PZ and PZ1–3 in THF

Dye

1
labs
cm 1))max (nm), (e (Mlflmax (nm), (Ffla)

tflb (ns)

FDc

PZ
PZ1
PZ2
PZ3

390 (17 500), 480 (1700)
378 (15 700), 478 (10 900)
361 (10 500), 487 (8300)
349 (7700), 510 (8100)

440, 555 (o0.02), 558 (0.09)554 (0.03)
579 (0.04)
597 (0.05)

2.13, 3.54,d 2.89e
3.40e
3.26e
1.14e

0.28
0.86
0.54
0.069

a

b
Fluorescence quantum yields (lex = labs
Fluorescence lifetimes. c 1O2max) were determined by using a calibrated integrating sphere system.
quantum yields (relative decomposition rate of DPBF (1,3-diphenylisobenzofuran)) using RB as a standard (FD = 0.68 in THF) and DPBF as a 1O2
scavenger. The FD values were estimated under assumption that the reactivity of 1O2 was independent of the kind of solvents. d Photoexcited at
366 nm. e Photoexcited at 451 nm.

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Table 2Rate constants in photophysical processes for PZ1–3

Dyekr (107 s 1)

knr (107 s 1)

kISC (107 s 1)

kIC (107 s 1)

PZ1
PZ2
PZ3

1.3
0.86
2.5

28.1
29.8
85.3

25.4
16.7
6.1

2.8
13.1
79.2

resulting in a high kIC/knr value (= 0.93). This high kIC/knr value
is ascribable to the vibrational relaxation to the lowest excitedstate caused by a flexible 4-chlorobenzoate group. On the other
hand, PZ1 without a flexible substituent showed a significantly
low kIC/knr value (= 0.10), and thus the kISC value accounts formuch of the knr value. PZ2 showed a relatively small kIC/knr
value (= 0.44) due to the methoxymethoxy group with moderate
flexibility, resulting in the moderate kISC.24 Consequently, theseevaluations suggested that FD values of PZ1–3 depend on kISC,
and thus PZ1 with high kISC shows a high FD value.
Theoretical calculations
Fig. 4 Photoabsorption spectra of DPBF (5  10 5 M) in the presence of(a) PZ1, (b) PZ2, and (c) PZ3 (abs.@509 nm = ca. 0.03) upon irradiation withmonochromatic light (509 nm, 300 mW cm 2) in THF. Insets are magnifications of peak tops in the spectra around 410 nm. (d) Plots of DOD ofDPBF at 413 nm against photoirradiation time (509 nm, 300 mW cm 2) inthe presence of PZ1, PZ2, PZ3, and RB.

highest 1O2 generation ability (FD = 0.86). Indeed, the FD values
of PZ1 and PZ2 are higher than those of KO-0–3 as well as PZ(FD = 0.036–0.41 for KO-0–3 and 0.33 for PZ). Thus, it was foundthat the phenazinone-based PS PZ1 without halogen atoms
possesses the superior 1O2 generation ability to RB (FD = 0.68
in THF) with many halogen atoms as well as MB (FD = 0.57 indichloromethane)21 without halogen atoms.
Photophysical processes
In order to clarify the optical factors aﬀecting the FD values, weinvestigated the photophysical processes of the phenazinonebased PSs PZ1–3 for 1O2 generation. In this context, theradiative (kr) and nonradiative (knr) decay rate constants were
evaluated from the Ffl and fluorescence lifetime (tfl) values(Table 1) according to eqn (1) and (2):22
kr = Ffl/tfl
knr = (1Ffl)/tfl(1)(2)

In addition, the ISC (kISC) and IC (kIC) rate constants were also
evaluated according to eqn (3) and (4):kISC = FT/tfl(3)

knr = kIC + kISC

(4)

where the triplet generation quantum yield (FT) was approximated by FD.23 Table 2 summarizes the values of kr, knr,
kISC, and kIC for PZ1–3. The kr values of all these PSs were low(0.86–2.5  107 s 1) due to the low Ffl values (r0.05). PZ3
showed a significantly low kISC value relative to the knr value,

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To further understand the photophysical processes, DFT and
TDDFT calculations were performed for PZ and PZ1–3 at theB3LYP/6-311G(d,p) level,26 in which the methoxymethyl groupof PZ2 was replaced with the methyl group for convenience of
calculation. The optimized structures of PZ1–3 showed
high planarity despite the presence of an sp3 nitrogen atom
(Tables S2–S5 and Fig. S11–S14, ESI†) and are in good agreement with those obtained from the X-ray single crystal analysis.
In the TDDFT calculations, the vertical excitation energies fromthe S0 state to the Sn and Tn states for PZ and PZ1–3 were
calculated using the S0 state geometry (Fig. 5, Tables S6, S7, andFig. S16, ESI†). The oscillator strengths (f) for the S0 to the S1state of PZ1–3 were higher than that of PZ (0.025 for PZ, 0.12 for
PZ1 and PZ2, and 0.19 for PZ3), indicating that the phenazinone PSs show stronger photoabsorption as observed in thephotoabsorption spectra (Fig. 3a). The TDDFT calculations also
showed that each singlet and triplet excited states consisted ofseveral types of transitions (Tables S6 and S7, ESI†). Therefore,
in order to simplify the process for characterizing transitions ineach excited state, the NTO calculations25 were performed
based on TDDFT results. As shown in Fig. 5, the unoccupied
and occupied NTOs are expressed as ‘‘particle’’ and ‘‘hole’’transition orbitals, respectively. It was found that for PZ1–3 theenergy gaps (DEST) between the S1 state and the T3 state weresimilar to each other (DEST = 0.34, 0.33, and 0.20 eV for PZ1,
PZ2, and PZ3, respectively, Fig. 5 and Table S9, ESI†), indicatingthat ISC transitions from the S1 state to the T3 state were
thermodynamically feasible. In addition, the hole of the T3
state for PZ1–3 is localized on the carbonyl oxygen with then-orbital character, and the others (i.e., the particle of the S1and the T3 state, and the hole of the S1) are delocalized over thephenazinone skeleton with the p-orbital character. These
results suggested that the S1 states of the PZ1–3 are 1(pp*),which would undergo the transition to the T3 state characterized by 3(np*) according to the El-Sayed rule.15 Thus, the NTO
calculations demonstrated that the n orbitals on the carbonyl
oxygen in the PZ1–3 play an essential role in facilitating ISC

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Experimental
GeneralAll solvents and reagents were used as received unless otherwise
noted. Rose bengal (RB) was purchased from Sigma Aldrich andrecrystallized from methanol twice. 1,3-Diphenylisobenzofuran(DPBF) was purchased from Tokyo Chemical Industry and recrystallized from a mixture of dichloromethane and methanol.
1
H NMR and 13C NMR spectra were recorded using Varian400 (400 MHz) and Varian-500 (500 MHz) FT NMR spectrometers. FT-IR spectra were recorded using a Shimadzu
IRTracer-100. High-resolution mass spectral data were acquired
using a Thermo Fisher Scientific LTQ Orbitrap XL. Photoabsorption spectra were recorded using Shimadzu UV-3600plus spectrophotometers. Fluorescence spectra were measured
using a Hitachi F-4500 and HORIBA FluoroMax-4 spectrophotometer. The fluorescence quantum yields (Ffl) were determinedusing a Hamamatsu C9920-01 instrument equipped with CCD
by using a calibrated integrating sphere system. Fluorescencedecay measurements were performed using a HORIBA DeltaFlex modular fluorescence lifetime system, using a Nano LED
pulsed diode excitation source (366 nm and 451 nm). The
irradiance of monochromatic light (509 nm) for photosensitizing reactions was adjusted using a Newport 1918-C
optical power meter.
Synthesis
Fig. 5 Schematic diagrams showing vertical excitation energies of (a) PZ1,(c) PZ2, and (e) PZ3 for three lowest singlet and five lowest triplet excitedstates, and natural transition orbital (NTO) images of S1 and T3 excitedstates of (b) PZ1, (d) PZ2, and (f) PZ3. The methoxymethyl group of PZ2
was replaced with the methyl group for convenience of calculation.

from the S1 to the T3 state. Consequently, this work revealed
that the phenazinone chromophores possess thermodynamically feasible ISC characteristics from the S1 to the T3 state(DEST = 0.20–0.36 eV) based on the El-Sayed rule, and thus
the FD values of PZ1–3 are dominated by the kISC, which isdecreased by the flexible substituent.

Conclusions
In conclusion, we have designed and developed the phenazinone derivatives PZ1, PZ2, and PZ3 with a hydroxy, a methoxymethoxy, and a 4-chlorobenzoate substituent, respectively, as
halogen-free-heteroanthracene-based PSs. It was found that thephenazinone incorporating a carbonyl group into the skeleton
allows an eﬃcient ISC based on the El-Sayed rule. Indeed, PZ1
exhibited a high 1O2 generation ability (FD = 0.86), which isa superior photosensitizing ability to PZ2 (FD = 0.54) and PZ3(FD = 0.069) with a flexible substituent. Consequently, we
propose that the phenazinone skeleton is one of the promising
halogen-atom-free-heteroanthracene-based chromophores as
photosensitizers.

3-Hydroxy-10-methylphenazin-2(10H)-one (PZ1). A solutionof 2,5-dihydroxy-1,4-benzoquinone (0.145 g, 1.04 mmol) andN-methyl-o-phenylenediamine (0.127 g, 1.04 mmol) in ethanol(40 mL) was stirred at 80 1C. After the disappearance of thereactants, the reaction mixture was cooled to room temperature, and the precipitate was filtered and washed with a small
amount of ethanol to give PZ1 as a black solid (0.146 g, 62%
yield); m.p. over 300 1C; IR (ATR): ṽ = 3179, 1587, 1572, 1545,
1501, 1468 cm 1; 1H NMR (400 MHz, DMSO-d6, ppm): d = 7.86–
8.07 (m, 2H, aromatic), 7.72 (dd, J = 6.7 Hz, 1.5 Hz, 1H,
aromatic), 7.51 (dd, J = 7.5 Hz, 0.5 Hz, 1H, aromatic), 6.86
(s, 1H, aromatic), 6.37 (s, 1H, aromatic), 3.94 (s, 3H, CH3);
13
C NMR (125 MHz, DMSO-d6, ppm): d = 176.28, 156.64, 147.93,
136.55, 135.53, 130.60, 130.13, 129.45, 124.25, 115.21, 105.89,
97.04, 34.40; HRMS (APCI): m/z found 227.08127 [M + H]+,calculated for C13H11N2O2 [M + H]+: 227.08150.
3-Methoxymethoxy-10-methylphenazin-2(10H)-one(PZ2).
A solution of sodium hydride abt. 60% oil suspension(80.6 mg) and PZ1 (45.9 mg, 0.203 mmol) in DMF (30 mL)
was stirred at 0 1C for 30 min. Then, chloromethyl methyl ether(150 mL, 1.98 mmol) was added to the solution, and the mixture
was stirred at 0 1C overnight. The reaction was quenched withwater, and then the solution was extracted with CH2Cl2. The
organic layer was dried over anhydrous MgSO4, filtered, andconcentrated. The resulting residue was dissolved in CH2Cl2
and subjected to reprecipitation by hexane to aﬀord PZ2 as a
reddish brown solid (35.5 mg, 63.4% yield); m.p. 195–198 1C; IR(ATR): ṽ = 2967, 2918, 2828, 1630, 1591, 1572, 1545, 1508 cm 1;
1
H NMR (500 MHz, acetone-d6, ppm): d = 7.92 (dd, J = 8.1 Hz,

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1.5 Hz, 1H, aromatic), 7.86 (d, J = 8.7 Hz, 1H, aromatic), 7.70
(dd, J = 7.0 Hz, 1.5 Hz, 1H, aromatic), 7.46 (dd, J = 7.0 Hz, 1.2
Hz, 1H, aromatic), 7.03 (s, 1H, aromatic), 6.17 (s, 1H, aromatic),
5.39 (s, 2H, CH2), 3.91 (s, 3H, CH3), 3.50 (s, 3H, CH3); 13C NMR(125 MHz, acetone-d6, ppm): d = 177.56, 156.98, 149.54, 136.77,
131.91, 131.14, 124.61, 115.36, 110.68, 99.93, 95.55, 56.90,
34.35; HRMS (APCI): m/z found 271.10785 [M + H]+, calculated
for C15H15N2O3 [M + H]+: 271.10772.
3-(p-Chlorobenzoyl)-10-methylphenazin-2(10H)-one (PZ3). A
solution of sodium hydride abt. 60% oil suspension (39.5 mg)
and PZ1 (46.0 mg, 0.203 mmol) in DMF (30 mL) was stirred at
0 1C for 20 min. Then, 4-chlorobenzoyl chloride (128 mL,
1.00 mmol) was added to the solution, and the mixture wasstirred at 0 1C overnight. The reaction was quenched withwater, and then the solution was extracted with CH2Cl2. The
organic layer was dried over anhydrous MgSO4, filtered, andconcentrated. The crude was dissolved in toluene, and GPC was
performed to give PZ3 as a red solid (47 mg, 63% yield); m.p.
233–236 1C; IR (ATR): ṽ = 3067, 3044, 2924, 2853, 1923 cm 1;
1
H NMR (400 MHz, DMSO-d6, ppm): d = 8.08–8.17 (m, 2H,
aromatic), 7.99–8.08 (m, 2H, aromatic), 7.84 (t, J = 7.8 Hz, 8.0
Hz, 1H, aromatic), 7.67–7.77 (m, 3H, aromatic), 7.56 (t, J = 7.8
Hz, 7.6 Hz, 1H, aromatic), 6.40 (s, 1H, aromatic), 3.93 (s, 3H,CH3); 13C NMR (100 MHz, acetone-d6, ppm): d = 174.04, 162.62,
151.75, 146.16, 139.08, 137.52, 135.29, 132.85, 131.70, 131.43,
130.39, 129.13, 127.28, 124.38, 121.82, 115.27, 98.81, 34.43;
HRMS (ESI): m/z found 365.06900 [M + H]+, calculated for
C20H14N2O3Cl [M + H]+: 365.06875.
X-Ray crystallographic analysis
The reflection data were collected at 100 K on a Bruker AXS
SMART APEX II ULTRA diﬀractometer using monochromated
Mo-Ka (l = 0.71073 Å). The structure was solved by the SHELXT
2014/5 method and refined based on full-matrix least squares
on F2 using SHELXL-2017/1. The non-hydrogen atoms wererefined anisotropically. Hydrogen atoms were fixed geometrically and not refined. Crystallographic data have been deposited in the S3 Cambridge Crystallographic Data Centre (CCDC
2194829 for PZ1, CCDC 2194831 for PZ2, and CCDC 2194832
for PZ3).†
Crystal of PZ1. A suitable crystal of PZ1 was recrystallized
from a mixed solvent of CH2Cl2/hexane as an air-stable, dark
red block crystal. Crystallographic data: C13H10N2O2, M = 226.23,
monoclinic, a = 6.7461(17), b = 6.8315(18), c = 21.892(6) Å, b =93.503(3)1, V = 1007.0(4) Å3, Dcalcd = 1.492 g cm 3, space groupP2(1)/n (no. 15), Z = 4, 4448 reflections measured, 2397 unique(Rint = 0.0477), which were used in all calculations. The final
R1(reflections) = 0.0434 (1714) [I 4 2s(I)], wR2(reflections) = 0.1197(2397). GOF = 1.055 (Table S1, ESI†).
Crystal of PZ2. A suitable crystal of PZ2 was recrystallized
from a mixed solvent of CH2Cl2/hexane as an air-stable, dark
red block crystal. Crystallographic data: C15H14N2O3, M =270.28, monoclinic, a = 10.8605(18), b = 11.1311(18), c =10.3566(17) Å, b = 96.649(2)1, V = 1243.6(4) Å3, Dcalcd =1.444 g cm 3, space group P2(1)/c (no. 14), Z = 4, 6956 reflections measured, 2984 unique (Rint = 0.0335), which were used in

2716 | New J. Chem., 2023, 47, 2711–2718

all calculations. The final R1(reflections) = 0.0389 (2449) [I 42s(I)], wR2(reflections) = 0.1037 (2984). GOF = 0.998 (Table S1,
ESI†).
Crystal of PZ3. A suitable crystal of PZ3 was recrystallized
from a mixed solvent of CH2Cl2/hexane as an air-stable, red
block crystal. Crystallographic data: C20H13ClN2O3, M = 364.77,
monoclinic, a = 12.9125(8), b = 17.0395(10), c = 7.2712(4) Å,
b = 93.9830(10)1, V = 1595.96(16) Å3, Dcalcd = 1.518 g cm 3, spacegroup P2(1)/c (no. 14), Z = 4, 12 633 reflections measured, 3827
unique (Rint = 0.0202), which were used in all calculations. The
final R1(reflections) = 0.0340 (3316) [I 4 2s(I)], wR2(reflections) =0.0818 (3827). GOF = 0.921 (Table S1, ESI†).
Evaluation of 1O2 quantum yield
Quantum yields (FD) for singlet oxygen (1O2) generation by PZ1,
PZ2, and PZ3 were evaluated by monitoring the changes in thephotoabsorption spectra of 1,3-diphenylisobenzofuran (DPBF),
a 1O2 scavenger, in tetrahydrofuran (THF) upon photoirradiation. DPBF traps the generated 1O2 to be oxidized. THF wasbubbled with air for 10 min, prior to the preparation of thesolutions. The concentration of DPBF was 5  10 5 M in the
air-saturated THF solutions. The concentration of the photosensitizers (PSs) and rose bengal (RB) was adjusted so that theabsorbance was ca. 0.03 at the irradiation wavelength (509 nm).
The THF solutions containing DPBF and PZ1, PZ2, or PZ3 were
irradiated with monochromatic light (509 nm, 300 mW cm 2)that was obtained by passage of a xenon light source (HAL-320,
Asahi Spectra) through a monochromator (CMS-100, Asahi
Spectra). Except for the nonirradiated solutions, each spectrum
was measured immediately after photoirradiation for 1 min.
The procedure was promptly repeated until the total photoirradiation time reached 10 min. The changes in optical density(DOD) of DPBF were plotted against photoirradiation time toobtain the slopes (m) and estimate FD values. W. Wu et al.
reported that RB shows a high 1O2 generation with the FD =0.80 in MeOH.20 To correct the diﬀerence of FD values between
MeOH and THF, the FD values in THF were estimated from thefollowing equation.
FDRB,THF = FDRB,MeOH  [(mRB,THF/mRB,MeOH)
 (LRB,MeOH/LRB,THF)]
where mRB,MeOH and mRB,THF are slopes in the plots of DOD at
the photoabsorption maximum wavelength of DPBF (413 nm)
against photoirradiation time, and LRB,THF and LRB,MeOH arelight harvesting eﬃciencies, which are given by L = 1–10 A(‘‘A’’ is the absorbance at the photoirradiation wavelength). The
FDRB,THF value was estimated to be 0.68 (Fig. S10, ESI†). The FD
values of PZ1, PZ2, and PZ3 were determined by the relative
method using RB (FD = 0.68 in THF) as a standard according to
the following equation:
FDsam = FDref  [(msam/mref)  (Lref/Lsam)]where FDsam and FDref are 1O2 quantum yields of phenazinonebased PSs and RB, respectively, msam and mref are slopes in theplots of DOD at the photoabsorption maximum wavelength ofThis journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2023

NJC
DPBF (413 nm) against photoirradiation time, and Lsam and Lref
are light harvesting eﬃciencies, which are given by L = 1–10 A(‘‘A’’ is the absorbance at the photoirradiation wavelength).
Theoretical calculations
The Gaussian 16 program26 was used for density functional
theory (DFT) calculations, time-dependent DFT (TD-DFT) calculations, and natural transitional orbital (NTO) analysis. The
S0 geometries of PZ and PZ1–3 were optimized via frequency
calculations at the B3LYP/6-311G(d,p) level. There are no imaginary frequencies for all optimized structures. The TD-DFT
calculations of both excited singlet and triplet states were
performed using the optimized S0 geometry at the B3LYP/
6-311G(d,p) level. The methoxymethyl group of PZ2 was
replaced with the methyl group for convenience of calculations.

Conflicts of interest
There are no conflicts to declare.

Acknowledgements
This work was supported by a Grants-in-Aid for Scientific
Research (B) from the Japan Society for the Promotion of
Science (JSPS) KAKENHI Grant Number 22H02123 and by the
Futaba Foundation.

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