Additive-free photo-mediated oxidative cyclization of pyridinium acylhydrazones to 1,3,4-oxadiazoles: solid-state conversion in a microporous organic polymer and supramolecular energy-level engineering

Article abstract of DOI:10.1039/d0ra09581h

We discovered the efficient catalyst-free, photo-mediated oxidative cyclization reaction of bis-p-pyridinium benzoyl hydrazone (BH1) to 2-pyridinium-5-phenyl-1,3,4-oxadiazoles. This photoreaction is remarkable because it does not require additives (e.g., bases, strong oxidants, or photocatalysts), which are essential in previous reports, and proceeds very effectively even with solid-state microporous organic polymers. Interestingly, we found that the inclusion complexation of BH1 with cucurbit[7]uril (CB7) interferes with the photo-induced electron transfer from BH1 to molecular oxygen through modification of the LUMO energy level, thus inhibiting the photo-medicated oxidative cyclization. This journal is

Full text of DOI:10.1039/d0ra09581h

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Additive-free photo-mediated oxidative cyclization
of pyridinium acylhydrazones to 1,3,4-oxadiazoles:
solid-state conversion in a microporous organic
polymer and supramolecular energy-level
engineering†
Cite this: RSC Adv., 2021, 11, 1969
Kyung-su Kim,a You Kyoung Chung,a Hyunwoo Kim,a Chae Yeon Ha,a
abc
a
*
Joonsuk Huh
and Changsik Song
We discovered the efficient catalyst-free, photo-mediated oxidative cyclization reaction of bis-p-
pyridinium benzoyl hydrazone (BH1) to 2-pyridinium-5-phenyl-1,3,4-oxadiazoles. This photoreaction is
remarkable because it does not require additives (e.g., bases, strong oxidants, or photocatalysts), which
are essential in previous reports, and proceeds very effectively even with solid-state microporous
organic polymers. Interestingly, we found that the inclusion complexation of BH1 with cucurbit[7]uril
(CB7) interferes with the photo-induced electron transfer from BH1 to molecular oxygen through
modification of the LUMO energy level, thus inhibiting the photo-medicated oxidative cyclization.
Received 11th November 2020
Accepted 22nd December 2020
DOI: 10.1039/d0ra09581h
rsc.li/rsc-advances
conditions or the necessity for separation and purication
steps. Thus, the development of facile, mild, and additive-free
Introduction
photo-mediated protocols for 1,3,4-oxadiazole seems highly
demanding.
Herein, we discovered the photo-mediated oxidative cycli-
zation of pyridinium acylhydrazone conjugates, which forms
Acylhydrazones are well known to be converted from the E-
isomer to Z-isomer under visible or UV light irradiation, and
reversibly return to the E-isomer by thermal treatment1,2
(Fig. 1a). Moreover, acylhydrazones can be transformed to
oxadiazole derivatives by the oxidative cyclization reaction
under UV-irradiation including a photocatalyst or under the
condition of using a strong oxidizing agent. 1,3,4-Oxadiazoles
are an essential class of ve-membered heterocyclic compounds
that have been intensively studied for biological and medicinal
applications.3,4 There are two general methods for the
construction of 1,3,4-oxadiazoles from acylhydrazones via
oxidative cyclization. The rst method for oxidative cyclization
of acylhydrazones to 1,3,4-oxadiazole is to use strong oxidants
such as Dess–Martin reagent, ceric ammonium nitrate, bis(tri-
uoroacetoxy)iodobenzene, (diacetoxyiodo)benzene, or (2,2,6,6-
tetramethylpiperidin-1-yl)oxyl (TEMPO).5–11 The second method
is photo-driven oxidative cyclization using a photocatalyst.12,13
However, these synthetic methods for 1,3,4-oxadiazoles suffer
from by-product generation caused by harsh reaction
aDepartment of Chemistry, Sungkyunkwan University, 2066 Seobu-ro, Janan-gu,
Suwon-si, Gyeonggi-do 16419, Republic of Korea. E-mail: songcs@skku.edu
bSchool of Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon
16419, Republic of Korea
Fig. 1 (a) E–Z isomerization and oxidative cyclization of acylhy-
drazone. (b) Catalyst-free photo-mediated oxidative cyclization
reaction of pyridinium acylhydrazone, and the effect of inclusion
complexation on photoreaction.
cInstitute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Republic
of Korea
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra09581h
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1,3,4-oxadiazole without additional additives (base, strong acylhydrazones were UV-irradiated with 342 nm using the
oxidant, or photocatalyst) (Fig. 1b). In our previous report,14 bis- Lumatec Superlite 410. Scanning electron microscopy (SEM)
p-pyridinium benzoyl hydrazone (BH1, a cationic guest mole- images were captured on a JEOL 7800 eld emission SEM (FE-
cule) showed pH-dependent supramolecular assembly and SEM) operated at an accelerating voltage of 15 kV. FT-IR
dynamic covalent exchange reactions (transamination). spectra were recorded using a spectrometer Vertex 70 (Bruker
Initially, we tested the effect of inclusion complexation of BH1 Optic, Billerica, MA, USA), equipped with a diamond ATR unit.
with cucurbit[7]uril (CB7) to stimuli-responsiveness and self-
assembly. Cucurbit[n]urils (CBn), which consists of glycoluril Synthesis of microporous organic polymer (MOP)
units linked by methylene bridges, are considered to be suitable
candidates for the complexation with cationic molecules
because of their electronegative carbonyl functional groups and
Pyridinium acylhydrazone based MOP was synthesized by ball
milling method. Bis-(pyridinium aldehyde) 1 (1.0 g, 2.1 mmol)
and benzene-1,3,5-tricarbohydrazide 2 (0.35 g, 1.4 mmol) were
hydrophobic cavity with portals. Interestingly, the pyridinium
added to a 25 mL stainless steel vessel with two stainless steel
acylhydrazone conjugate appeared to form well the inclusion
balls (diameter 15 mm). The vessel containing the substrates
complex with CB7, which affected its supramolecular polymer-
was vibrated at 20 Hz for 60 min at room temperature. The
ization. What is more interesting, however, is that the photo-
reacted powder was collected and washed by DMSO, DMF,
mediated oxidative cyclization seems to be affected by the
acetone and MeOH. Yield: 1.2 g (88%).
inclusion complexation, presumably via energy level modica-
tion. The CBn-catalyzed or -templated photochemical reactions
General procedure for the photosynthesis of 1,3,4-oxadiazole
derivatives from H1, BH1, and PH-MOP
such as photohydrolysis15 and photodimerizations16–19 have
been intensively investigated, but in most cases CBn promotes
photoreaction by providing a cavity as a molecular container for
effective spatial arrangement of reactants. On the other hand,
the control of photoreaction through energy level tuning by
encapsulation of reactants with CB7, not by spatial arrange-
ment, is relatively rare and our work seems to provide with
a noteworthy strategy to control photo-mediated chemical
transformations.
1,3,4-Oxadiazole derivatives were synthesized by photo-
mediated oxidative cyclization reaction of pyridinium acylhy-
drazones (H1, BH1 and PH-MOP). A pyridinium acylhydrazone
was dissolved in DMSO (0.1 M) and then UV-irradiated with
342 nm for 4 h using the Lumatec Superlite 410. Aer
completion of the reaction monitored by 1H NMR analysis
except PH-MOP, the solvent was reduced, and then the residue
was recrystallized from DMSO. Yield: 18–33 mg (83–92%).
Synthesis of Oxa-H1. Oxa-H1 was obtained as a yellowish
Experimental
Materials
white powder by a general method of photosynthesis of 1,3,4-
oxadiazole using H1 (27 mg). Yield: 25 mg (92%). 1H NMR
(DMSO-d6, 700 MHz): d 9.24 (d, J ¼ 6.6 Hz, 2H), 8.81 (d, J ¼
Pyridinium hydrazone conjugates, H1 and BH1 were prepared
6.6 Hz, 2H), 8.27 (d, J ¼ 7.2 Hz, 2H), 7.77–7.70 (m, 3H), 4.45 (s,
following the published procedures.14 Cucurbit[7]uril (CB7) was
3H). 13C NMR (DMSO-d6, 175 MHz): d 166.48, 161.37, 147.48,
purchased from CBTECH (Pohang, Korea). 1-Adamantanamine,
137.60, 133.51, 130.10, 127.78, 124.57, 123.09, 48.71. HRMS
benzohydrazide, 4-pyridinecarboxaldehyde, p-xylene dibro-
(ESI+) [C14H12N3O1]: calcd [M]+ 238.0975, found: 238.0975.
mide, and iodomethane were commercially available and used
as received.
Synthesis of Oxa-BH1. Oxa-BH1 was obtained as a yellow
powder by a general method of photosynthesis of 1,3,4-oxadia-
zole using BH1 (38 mg). Yield: 33 mg (87%). 1H NMR (DMSO-d6,
Instruments
500 MHz): d 9.44 (d, J ¼ 6.9 Hz, 4H), 8.85 (d, J ¼ 6.9 Hz, 4H), 8.24
(d, 6.9 Hz, 4H), 7.78–7.61 (m, 6H), 7.69 (s, 4H), 5.98 (s, 4H).
HRMS (ESI+) [C34H26N6O2]: calcd [M + H]+ 551.2114, found:
551.2185.
Synthesis of Oxa-MOP. Oxa-MOP was obtained as a yellowish
white powder by a general method of photosynthesis of 1,3,4-
oxadiazole using PH-MOP (22 mg). Yield: 18 mg (83%). Solid
state 13C CP-MAS NMR (400 MHz, spinning speed of 14 kHz):
d 172.35, 164.13, 160.65, 150.06, 142.19, 134.69, 130.13, 62.17.
Ultraviolet-visible (UV-Vis) absorption data were acquired on
a UV-1800 (Shimadzu) spectrophotometer in spectroscopic
grade solvents without further purication. NMR measure-
ments were performed in standard 5 mm NMR tubes at 300 K.
All the data were acquired on a Bruker AVANCE III HD 500 and
700 MHz NMR spectrometer. Solid-state 13C CP/MAS NMR
spectra of PH-MOP and Oxz-MOP were recorded on a 400 MHz
solid state NMR spectrometer (AVANCE III HD, Bruker, Ger-
many) at KBSI Western Seoul center. Two-dimensional ROE
spectra were measured with a spectral width of 8 kHz in 2 K data
Computational calculations
points using 16 scans for each of the 512 t1 increments with 300 To obtain the local geometries and UV-Vis spectra of the inter-
ms as a mixing time. Cyclic voltammetry (CV) was performed ested molecules, we performed density functional theory (DFT)
using an Epsilon electrochemical analyzer (EC Epsilon, BASi), calculations by using a hybrid functional B3LYP and 6-311+g*
and carried out in a three electrodes system, with Ag/Ag+ as the basis set implemented in Gaussian 16 program. We also used
reference electrode, Pt foil as the counter electrode, and the the escf module integrated into Turbomole 7.3 program
platinum working electrode, with a scan rate of 100 mV sꢀ1. For utilizing the resolution of identity (RI) method under the
the photo-mediated oxidative cyclization reaction, pyridinium Conductor-like Screening Model (COSMO) condition in order to
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consider a DMSO-solvent-mediated effect for the excited state and 13C NMR (Fig. S3†), and high-resolution mass spectrometry
calculations.
(Fig. S4†) analyses. Similar with the case of H1, time-dependent
UV-Vis absorption measurements and NMR experiments of BH1
were also performed aer UV-irradiation (342 nm). The UV-Vis
absorption spectra of BH1 (0.33 mM in DMSO) under UV-
irradiation (Fig. S5†) showed blue-shied absorption (ꢁ65
nm), which was similar to the patterns of H1, and they showed
a more apparent isosbestic point at 295 nm. Aer the UV-
irradiation of BH1 for 2 h, the 1H NMR spectra of BH1
showed that the initial proton peaks of BH1 disappeared and
those of newly generated bis-p-(pyridinium 1,3,4-oxadiazole)
(Oxa-BH1) remained (Fig. S6†).
Results and discussion
Catalyst-free photo-mediated oxidative cyclization of
pyridinium acylhydrazones to 1,3,4-oxadiazoles
In order to investigate the photo-reactivity of pyridinium acyl-
hydrazones such as E–Z isomerization, we performed the time-
dependent UV-irradiation (342 nm) experiment for methylpyr-
idinium benzoyl hydrazone H1 (0.66 mM in DMSO) (Fig. 2a). H1
can be considered as a model for BH1 since it is a dimer of H1
with a 1,4-phenylene linker. Upon the UV-irradiation of H1
solution, we observed that the UV-Vis absorption band of H1
became blue-shied (ꢁ19 nm), and the intensity of the
absorption band at 348 nm considerably decreased (Fig. S1†).
Of note, similar changes of optical properties can be observed
during the E–Z isomerization process of acylhydrazones.1,2
However, aer performing thermal treatment and visible light
irradiation experiments, we can conrm that a certain irre-
versible photoreaction occurred that was not E–Z isomerization.
Of note, this reaction is important because it has simple,
economic, and environmental advantages compared to the
previously reported methods for obtaining 1,3,4-oxadiazole
from hydrazone. There is no need to worry about side reactions
because the proposed approach does not use strong oxidizing
agent; in addition, because no additional additives are used,
less effort is required for purication. We expected that elec-
tronic modulation by the introduction of pyridinium into acyl-
hydrazone would enable this additive-free photoreaction.
To support our experimental results observed by UV-Vis
spectra and photoreaction, the DFT calculations of electronic
states of H1 and 1,3,4-oxadiazole in a DMSO solution were
performed using B3LYP and 6-311+G* basis set (Fig. S7†). When
H1 was converted to 1,3,4-oxadiazole, a blue-shi of the
absorption band (from 348 nm to 324 nm) similar to the
experimental result was conrmed in simulated UV-Vis spectra
(from 335 nm to 316 nm) (Fig. 2c). A possible mechanism of
photo-mediated 1,3,4-oxadiazole synthesis from pyridinium
acylhydrazone is represented in Fig. 2d. Upon the absorption of
UV light, pyridinium acylhydrazone, H1, is excited to H1*,
which can be easily deprotonated owing to the electron-
accepting ability of conjugated pyridinium to form a zwit-
terion. A single electron transfer (SET) from H1* to oxygen
generates acyl radical A, which forms B by intramolecular
cyclization. The generated superoxide radical anion (O2ꢀ) by
SET from H1* attacks the proton of tertiary carbon of B to
produce 1,3,4-oxadiazole, C. In fact, we conrmed the existence
of superoxide radical anion (O2ꢀ) during the photo-mediated
oxidative cyclization reaction by the observation of hydrogen
peroxide in NMR spectra (10.2 ppm). It was observed that
hydrogen peroxide was initially formed at the same level as the
product 1,3,4-oxadiazole derivative in the photo-induced
oxidative cyclization of H1 (Fig. S2†). However, as shown in
Fig. 2b, it appears that hydrogen peroxide decomposed over
time under UV irradiation conditions, presumably due to
photolysis of hydrogen peroxide. Of note, this oxidative cycli-
zation reaction is carried out without additional strong oxidants
or photocatalysts, which were necessary in previous studies.5–13
We attempted to apply the additive-free, photo-mediated
1
Fig. 2b shows the H NMR spectra of H1 (0.66 mM in DMSO)
under UV-irradiation. Aer UV-irradiation for 1 h, the initial
proton signals for H1 decreased, and at the same time several
new proton peaks were observed in the spectra. Aer UV-
irradiation for 2 h, the proton peaks of H1 completely dis-
appeared, and only the newly observed peaks remained. We
conrmed that H1 changed to 2-methylpyridinium-5-phenyl-
1
1,3,4-oxadiazole (Oxa-H1) by UV-irradiation using H (Fig. S2†)
Fig. 2 (a) Catalyst-free photo-mediated oxidative cyclization from oxidative cyclization method to the synthesis of oxadiazole-
pyridinium acylhydrazones to 1,3,4-oxadiazoles. (b) Irradiation time-
based microporous organic polymer (Oxz-MOP) under air. Our
dependent 1H NMR spectra of H1 (500 MHz, 0.66 mM in DMSO-d6). (c)
strategy is to obtain Oxz-MOP through a solid-state conversion
Simulated and experimental UV-Vis absorption spectra of H1 and 2-
methylpyridinium-5-phenyl-1,3,4-oxadiazole. (d) Proposed mecha-
of a pyridinium-acylhydrazone-based microporous organic
polymer (PH-MOP), which can be prepared by facile conden-
sation reaction between bis-(pyridinium aldehyde) 1 and
nism of photo-mediated oxidative cyclization of pyridinium acylhy-
drazone, H1, to 1,3,4-oxadiazole.
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1
Fig. 4 (a) H NMR spectra of BH1 (500 MHz, 1.0 mM in DMSO-d6) in
the absence and presence of 1.0 equiv. of CB7. (b) UV-Vis absorption
spectra of BH1 in DMSO (0.33 mM) upon the addition of CB7. (c)
Energy-minimized structure for BH13CB7 obtained by DFT
calculation.
Fig. 3 (a) Synthesis of pyridinium acylhydrazone based microporous
organic polymer (PH-MOP) by ball milling method, and 1,3,4-oxadia-
zole based MOP (Oxz-MOP) by photo-mediated oxidative cyclization
of PH-MOP in the solid-state. (b) FT-IR spectra of PH-MOP (blue-line)
and Oxz-MOP (pink-line). Solid-state 13C CP/MAS NMR of (c) PH-MOP
and (d) Oxz-MOP.
helical wire-type self-assembly by direct intermolecular inter-
actions such as dipole–dipole, p–p, CH–p, and van der Waals
interactions.14 We tested whether BH1 made an inclusion
complex with CB7 (Fig. 4a) and its effect on the photo-mediated
oxidative cyclization. In the UV-Vis absorption spectra of BH1 in
DMSO (0.33 mM), the maximum absorption band initially at
benzene-1,3,5-tricarbohydrazide 2. Furthermore, we were able 340 nm showed a hypsochromic shi (ꢁ10 nm) and slightly
to synthesize PH-MOP successfully under ball milling condition increased absorptivity upon the addition of an increasing
at room temperature with a reactor frequency of 20 Hz for 1 h amount of CB7 (Fig. 4b). This blue-shi in UV-Vis absorption
(Fig. 3a). Ball milling is a mechano-chemical method that has spectra possibly originated from the changed microenviron-
been considered an attractive tool for synthesizing various ment of BH1 from bulk to macrocyclic upon encapsulation with
organic materials,20,21 due to advantages such as environment- CB7.27,28
friendliness, fast speed and simplicity. The 13C solid-state CP/
1H NMR titration experiments clearly showed the complex-
MAS NMR spectra of PH-MOP revealed the similar patterns ation event between BH1 and CB7. BH1 (1.0 mM in DMSO-d6)
with that of BH1 (Fig. S8†), which means that PH-MOP were well was titrated against CB7, and 1H NMR measurements were
synthesized resulting from hydrazone formation reactions performed, which allowed to determine the equilibrium and
between 1 and 2. Furthermore, to investigate the solid-state binding constant (K) (Fig. 4a and S10†). Upon the addition of
conversion of PH-MOP to oxadiazole-based microporous CB7, BH1 formed only a 1 : 1 complex (Fig. S11†) with
organic polymer (Oxz-MOP) by additive-free photo-mediated a considerable upeld shi in the protons of 1,4-xylylene and
oxidative cyclization under air, we performed Fourier trans- pyridinium, which indicated that CB7 with shielding cavity
form infrared (FT-IR) analysis of PH-MOP before and aer UV- make an internal complex with BH1.29,30 Owing to the slow
irradiation (Fig. 3b). In the FT-IR spectra of PH-MOP aer UV- exchange in complexation between CB7 and BH1 on the NMR
irradiation for 4 h, we could conrm that the disappearance time scale, we monitored the amount of formed inclusion
of the N–H stretching peak at 3445 cmꢀ1, and decrease of the complexes, BH13CB7, by integrating each NMR signal of a free
C]O stretching at 1681 cmꢀ1, which is consistent with the and bound state of BH1. The binding constant (K) of BH1 for
results with BH1 (Fig. S9†). The 13C solid-state CP/MAS NMR CB7 was calculated by tting using eqn (1),31 which allowed to
spectra of PH-MOP aer UV-irradiation for 4 h supported also determine the concentration of BH13CB7, which was obtained
that photo-mediated conversion from PH-MOP to Oxz-MOP was by the multiplication of BH13CB7 fraction and total concen-
occurred even in the solid state (Fig. 3c and d). Carbon signal of tration of BH1 ([BH1]0).
ꢀ
ꢁ
amide carbonyl carbon from PH-MOP at 167.7 ppm was
changed to two broad peaks, which were speculated to originate
from two carbons of 1,3,4-oxadiazole ring in Oxz-MOP. This
photoreaction is noteworthy in that it provides a new bypass
pathway to solve the difficulties in the synthesis and processing
of aromatic poly(oxadiazole) due to the problem of poor solu-
bility and high glass transition temperature (Tg).22–26
1
2
1
½BH13CB7ꢂ ¼
½CB7ꢂ þ ½BH1ꢂ þ
0
0
Ka
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ꢀ
ꢁ
ꢀ
½CB7ꢂ þ ½BH1ꢂ þ
2 þ 4½CB7ꢂ ½BH1ꢂ
1
0
0
0
0
Ka
(1)
Compared to a previously study on the binding constant of
the bis(pyridinium)-xylylene moiety with CB7,32 we obtained
a relatively lower K value (1.53 ꢃ 0.82 ꢄ 104 Mꢀ1), which was
presumably due to solvent DMSO; this solvent ts better into
Inclusion complexation of BH1 with CB7 and inhibited photo-
mediated oxidative cyclization reaction: mechanistic insight
Previously, our group reported bis-p-pyridinium benzoyl
hydrazone BH1 (Fig. 4), which exhibited a stimuli-responsive
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the cavity of a hydrophobic binding site than water.33 To re- Unlike the behavior in UV-Vis absorption spectra of BH1
evaluate the binding affinity of CB7 to BH1, the data obtained under UV light irradiation, the UV-Vis spectra of BH13CB7 did
from UV-Vis titration experiments of BH1 versus CB7, moni- not show any shi in absorption band, isosbestic point, or
tored at 330, 340, 360, 366, and 378 nm, were tted according to increase in absorption at 275 nm (Fig. 5a). The 1H NMR spectra
the 1 : 1 binding isotherm on the website http:// of BH13CB7 (0.66 mM in DMSO-d6), which were irradiated by
supramolecular.org (Fig. S12†),34 which showed a similar UV light for 4 h, did not show a signicant difference compared
binding constant (4.05 ꢄ 104 Mꢀ1). The 2-D rotating-frame to the initial NMR spectra of BH13CB7 (Fig. S14†). Additional
Overhauser effect spectroscopy (ROESY) NMR experiment was experiments on the photo-mediated oxidative cyclization reac-
performed for the detailed structural characterization of inclu- tion by varying the content of BH13CB7 in the solution of BH1
sion complexes (BH13CB7). As shown in Fig. S13,† ROE cross were carried out (Fig. 5b and S15†). The UV-irradiation time-
peaks between the proton of CB7 (H1) and protons of dependent 1H NMR spectra of 20% content of BH13CB7 in
bis(pyridinium)-1,4-xylylene on BH1 (Hb and Hg) were clearly the solution of BH1 showed that only unbound BH1 was
observed, which supported the formation of the 1 : 1 complex changed to photo-reacted oxadiazole, while the total amount of
between BH1 and CB7, in which CB7 was symmetrically cen- bounded BH1 (BH13CB7) remained. However, for 40% content
trally positioned on BH1. Assuming 1 : 1 complexation, we were of BH13CB7 and above, we could not observe photo-reacted
able to calculate the energy-minimized structure of the inclu- oxadiazole from BH1 in 1H NMR spectra, while the ratio of
sion complex (BH13CB7) in the ground state using the density the amount of BH1 and BH13CB7 was maintained. The iso-
functional theory (DFT) calculation at B3LYP/6-311+G*. As sbestic point, i.e., the existence of an equilibrium between BH1
shown in Fig. 4c, centrally positioned CB7 in the xylylene unit and photo-reacted oxadiazole, was also not observed in UV-Vis
and Z-like structures with two anti-parallel planes of pyridium- spectra. Therefore, we concluded that BH1 encapsulated into
acylhydrazone conjugates were observed. These structural CB7 was inhibited by the photo-mediated oxidative cyclization
characteristics have features that are similar to those in reaction, which also reduced the photo-reactivity of unbounded
previous studies on inclusion complexation between the BH1 (Fig. 5b).
bis(pyridinium)-1,4-xylylene unit and CB7.35,36
We have not yet understood this phenomenon, but one thing
UV-irradiation (342 nm) time-dependent UV-Vis absorption to note is that in the presence of BH13CB7 there seems to be an
measurements and NMR experiments of BH13CB7 were per- induction period or retardation effect, which intensies with
formed. Inclusion complexes, BH13CB7 (0.33 mM in DMSO- increasing CB7 content. Recently, Kaifer and coworkers re-
d6), which were prepared by the simple mixing of BH1 (0.66 mM ported the strong effect of the terminal carboxylate groups on
in DMSO-d6) and CB7 (0.66 mM in DMSO-d6) solutions with the dissociation kinetics of bis(pyridinium)-xylylene32 Through
1 : 1 stoichiometry, were excited at 342 nm by UV-irradiation. competitive binding analysis, the kinetic constants for dissoci-
ation were assessed; anionic carboxylates appear to act as
a kinetic barrier to exchange reactions, but dissociation was
much faster in the acid form of carboxyl groups. Similarly, an
exchange experiment of BH13CB7 was performed with
a
competing guest molecule, adamantanamine (binding
constant for CB7, 4.23 ꢃ 1.00 ꢄ 1012 Mꢀ1), using NMR titration
(Fig. S16†). The NMR spectrum of BH13CB7 changed to that of
BH1 within 30 minutes aer the addition of adamantanamine,
indicating that BH1 was completely exchanged to adamantan-
amine in the cavity of CB7 and the exchange kinetics appeared
very quickly. Thus, although the complex BH13CB7 is ther-
modynamically stable, it is kinetically labile so that the guest
exchange can be relatively fast. These hypotheses require
further investigation, but their relatively fast kinetics may
inuence the photo-mediated oxidative cyclization reaction of
BH1 in the presence of less than stoichiometric CB7. In other
words, guest exchanges in the cavity of CB7 between adjacent
BH1 molecules can occur at a relatively faster rate than oxidative
cyclization reactions, thereby suppressing photo-mediated
reactions below a stoichiometric amount.
To investigate the reason why photoreaction only occurred in
pyridinium acylhydrazone conjugates (H1 and BH1) and not in
pyridine acylhydrazone conjugate (PH) (Fig. S17†) and inclusion
complexes (BH13CB7), and whether photoreaction was
affected by their HOMO and LUMO energy levels, we measured
the redox potentials of H1, BH1, PH, and BH13CB7 by cyclic
voltammetry (Fig. S18†). The LUMO energy levels of H1, BH1,
Fig. 5 (a) UV-Vis spectra of BH13CB7 upon the 342 nm UV light
irradiation (black arrows indicate the direction of absorptivity with an
increase in irradiation time). (b) Amount of formed oxadiazole after the
photo-mediated oxidative cyclization reaction. (c) The LUMO and
HOMO energy diagram of PH, H1, BH1, and BH13CB7, and the
reduction potential of triplet oxygen.
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PH, and BH13CB7 were obtained from reduction potentials at
Acknowledgements
1.19, 1.19, 1.96, and 1.43 V vs. Fc/Fc+, respectively [ELUMO
¼
ꢀ(Ered + 4.8 V)]. To calculate the HOMO energy level, their UV-
Vis absorption spectra were used to estimate the HOMO–
LUMO energy gap (DE). The calculated HOMO and LUMO
energies of H1, BH1, PH, and BH13CB7 are shown in Fig. 5c.
The LUMO energies of pyridinium acylhydrazones H1 and BH1
were ꢀ3.61 eV and ꢀ4.00 eV, respectively, which were signi-
cantly lower than those of pyridine acylhydrazone PH (ꢀ2.84 eV)
and the inclusion complex BH13CB7 (ꢀ3.37 eV). All LUMO
energies are slightly above the reduction potential for triplet
oxygen (O2) (ꢀ4.32 eV).
This work was supported by the Nano Material Development
Program (2012M3A7B4049677) and Basic Science Research
Programs (2019R1A2C1004256 and 2020R1A6A3A01100092)
through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science, and Technology,
Republic of Korea. We also thank Prof. Ki Hyun Kim (School of
Pharmacy,
Sungkyunkwan
University)
for
HRMS
measurements.
Notes and references
Based on the obtained redox potentials and the proposed
mechanism for photo-induced electron transfer from acylhy-
drazone to O2 (Fig. 2d), we could conclude that the electron
transfer from photo-excited state to O2 occurs much favourably
in H1 and BH1 due to the small energy difference between their
LUMO and the reduction potential of O2, compared to the case
of PH and BH13CB7. According to Marcus theory, which
explains the rate of electron transfer reactions between donor
and acceptor, the electron transfer processes can be classied
into three types of regions according to the rate constant versus
reaction free energy: normal, activation-less, and inverted
regions.37–40 Among them, the ‘inverted region’ is where the
electron transfer becomes slower down as the reaction becomes
more exothermic. Apparently, it is consistent with the results of
our system since the rate of photo-induced electron transfer
seems slower as the energy gap becomes larger. It is likely that
the photo-induced electron transfer occurs via ‘inner sphere’
mechanism or bonded electron transfer41–44 through pre-
organization of oxygen molecules and the excited H1* or
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We described the photo-mediated oxidative cyclization reaction
of pyridinium acylhydrazones to 1,3,4-oxadiazole without
a photocatalyst or strong oxidant. This photoreaction proceeded
by single electron transfer from excited pyridinium acylhy-
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Conflicts of interest
There are no conicts to declare.
1974 | RSC Adv., 2021, 11, 1969–1975
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RSC Adv., 2021, 11, 1969–1975 | 1975