Effects of Substituents on Metastable-State Photoacids: Design, Synthesis, and Evaluation of their Photochemical Properties

Article abstract of DOI:10.1002/asia.201801687

Recently, metastable-state photoacids have been widely used to control proton transfer in numerous chemical and biological processes as well as applications with visible light. Generally, substituents have a great influence on the photochemical properties of molecules, which will further affect their applications. Yet, the effects of substituents on metastable-state photoacids have not been studied systematically. In this work, 16 metastable-state photoacid derivatives were designed and synthesized on the basis of substituents having a large range of σ–π electron–donor–acceptor capabilities. The effects of substituents on the color display [or maximum absorption band(s)], solubility, pK_a values, dark/photoacidity, photosensitivity, and relaxation kinetic(s) were investigated in detail. This study will be helpful for the targeted design and synthesis of promising photoacids and the application of their photocontrolled proton-release processes in functional materials/devices.

Full text of DOI:10.1002/asia.201801687

CHEMISTRY
AN ASIAN JOURNAL
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Accepted Article
Title: Substituent Effect on Metastable-State Photoacids: Design,
Synthesis and Evaluation of their Photochemical Properties
Authors: Junning Liu, Wenqi Tang, Lan Sheng, Zhen Du, Ting Zhang,
Xing Su, and Sean Xiao-An Zhang
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Substituent Effect on Metastable-State Photoacids: Design,
Synthesis and Evaluation of their Photochemical Properties
Junning Liu,[a] Wenqi Tang,[b] Lan Sheng,*[b] Zhen Du,[a] Ting Zhang,[a] Xing Su,[b] and Sean Xiao-An
Zhang[ab]
Abstract: Recently, metastable-state photoacids have been widely
used to control proton transfer in numerous chemical and biological
processes as well as applications with visible light. Generally,
substituent groups have great influence on photochemical properties
of molecules, which will further affect their applications. Yet,
substituent effect on the metastable-state photoacid has not been
studied systematically. In this work, sixteen metastable-state
photoacid derivatives were designed and synthesized based on their
substituents involving a large range of σ-π electron-donor-acceptor
capability. Substituent effects main on their color display (or
maximum absorption peak(s)), solubility, pKa(s), dark-/photo-acidity,
photosensitivity and relaxation kinetic(s) were investigated in detail.
This study will be conducive to targetedly design and synthesize
promising photoacids as well as to apply their photo-controlled
proton-release processes in functional materials/devices.
(2.2 units of pH change), long lifetime (t1/2 = 76 s) and good
reversibility,[16] this metastable-state photoacid has attracted
considerable attentions and been utilized in various fields, such
as control of acid-catalyzed reactions,[22] supramolecular
assemblies,[23,24] microbial fuel cells,[25] bacteria killing,[26] waste
management of reactions,[27] cationic sensors,[28] odorant release
[29]
and biological function.[30] In recent, our group had
successfully extended the application of this photoacid to visible-
light-responsive rewritable paper.[31] However, these glamorous
applications are mostly based on the initial photoacid molecule
reported by Liao’s group[16], and there are few works on the
properties or applications of its derivatives.
As we all know, substituents have great influence on
photochemical properties of molecules, which will further affect
their applications. Therefore, it's necessary to study effect of
substituents on the properties of this kind of central concerned
metastable-state photoacid both from the perspectives of
fundamental research and practical application.
In this context, we designed and synthesized sixteen
metastable-state photoacid derivatives containing various
substituents at different position of the molecular skeleton, and
systematically investigated effect of the introduced substituents
on their photochemical properties. Several important nature of
the photoacids, such as displaying colors, solubility, molar
absorption coefficient, pKa, dark-/photo-acidity, photosensitivity,
relaxation kinetic, were demonstrated closely related to their
connected functional groups. Understanding how photochemical
behaviors of photoacids affected by the substituent groups in
this work is essential not only for targeted designing and
synthesizing promising photoacids but also for further exploiting
their potential applications.
Introduction
Photoacids, as a class of molecules whose acidity could be
controlled by light, have been intensively studied.[1–7] The
development of photoacids,[8,9] including irreversible and
reversible photoacids, has passed through three stages. At the
first stage, they were also called as photoacid generators, which
can irreversibly release strong acidic fragments upon photolysis
and be applied as photoinitiators for cationic polymerization or
photolithography.[10–12] Later, excited-state photoacids have
been systematically studied since the 1970s and been applied in
the studies of fast proton-transfer processes owning to short
lifetime of their proton-dissociation states.[13,14] Last but not least,
Liao and co-workers reported a metastable-state photoacid[15–21]
which could reversibly undergo a proton photodissociation
accompanied with a nucleophilic reaction to form a cyclic
spiropyran upon irradiation with a moderate intensity of visible
light and a thermal recovery in dark. Given its high efficiency
Experimental
General information
All synthetic raw materials were purchased from Energy
Chemical (Shanghai, China) and used without further purification.
Methanol (MeOH, HPLC) was purchased from Yuwang Group
(Shandong, China). Dimethyl sulfoxide (DMSO) was purchased
from Aladdin (Shanghai, China). Water (H2O) here used was
Wahaha purified water (Hangzhou, China). Acetonitrile (CH3CN)
was purchased from Fisher Chemical. If not otherwise stated, all
solvents and inorganic salts used were purchased from Beijing
Chemical Works (Beijing, China).
[a]
[b]
J. Liu, Z. Du, T. Zhang and Prof. Dr. Sean Xiao-An Zhang
State Key Laboratory of Supramolecular Structure and Materials,
College of Chemistry
Jilin University
Changchun, 130012, P. R. China
W. Tang, Dr. L. Sheng, X. Su and Prof. Dr. Sean Xiao-An Zhang
College of Chemistry
Jilin University
2699 Qianjin street, Changchun, 130012 (P. R. China.)
E-mail: shenglan17@jlu.edu.cn
1H NMR (500 MHz) and 13C NMR (126 MHz) spectra were
recorded on
a Bruker AVANCE500 at room temperature.
Chemical shifts were reported in delta (δ) units, parts per million
(ppm) downfield from TMS. LC-HRMS analysis was performed
on an Agilent 1290-micro TOF-Q II mass spectrometer
(electrospray ionization (ESI) source). Melting point was
Supporting information for this article can be found via a link at the
end of the document. It contain detailed experimental procedures of
synthesis, solubility and pKa test. Additional details on experimental
data including 1H NMR, 13C NMR, UV-vis, fluorescent spectra,
kinetics, etc.
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10.1002/asia.201801687
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determined using
apparatus (Shanghai, China). UV-vis absorption spectra were
measured using Shimadzu UV-2550 PC double-beam
spectrophotometer coupled with a Huber temperature-controlled
sample compartment, and the path length was 1 cm. The
fluorescence spectra were measured with a Shimadzu RF-5301
a
SGW X-4B microscopy melting point
As shown in Scheme 1, these photoacid derivatives (P-Xs)
were synthesized according to a three-step procedure[16] using
various phenylhydrazines (S1−16) with different substitutes as
starting materials. Firstly, 2,3,3-trimethylindolenine intermediates
(A1−16) were prepared by the classical method of Fischer indole
synthesis.[32] Then these 2,3,3-trimethylindolenines were
a
PC spectrofluorometer. Light power meter and sensor (ThorLabs, quaternized with 1,3-propanesultone to afford 2,3,3-trimethyl-1-
PM100A, SV120VC) used for measuring the light intensity (light
power density) were purchased from Thorlabs (Shanghai,
China). The light source used for irradiation experiments is a
Wota F25 fishing lamp with two switches (Ningbo, China)
providing 20 mW blue light (λmax = 447 nm，Fig. S1). The pH*(s)
of solutions were measured by a Sartorius basic pH meter PB-
10.
(3-sulfonatepropyl)-3H-indoliums (B1−16).[33] At last, P-Xs were
obtained by a Knoevenagel reaction between salicylaldehydes
and B1−16. The crude products were recrystallized from MeOH
to afford P-Xs as yellow or orange or orange-red solids.
General procedure Ⅰ for A1−16: The phenylhydrazine or
phenylhydrazine derivatives (1 eq.), 3-methyl-2-butanones (1.5
eq.), and H2SO4 were dissolved in glacial acetic acid and then
heated under reflux for 8 h under nitrogen. After the reaction, the
mixtures were cooled down to room temperature. Then the most
solvent was evaporated in vacuo. The remaining solutions were
added appropriate amount of deionized water, and then
neutralized with 10% NaOH, 10% Na2CO3 aqueous, respectively.
The mixture solutions were extracted with ether (Et2O) (3 × 50
ml), washed with saturated brines (4 × 50 ml), and organic layer
was combined and dried over anhydrous Na2SO4. The solutions
were evaporated in vacuo to remove solvent, and the 2,3,3-
trimethylindolenine was obtained by vacuum distillation (A1, A2,
A4−6, A8−12, A14, A16) whereas the 2,3,3-trimethylindolenine
derivatives (A3, A7, A13, A15) were purified by column
chromatography.
General procedure Ⅱ for B1−16: 2,3,3-trimethylindolenines
or its derivatives (A1−16) (1 eq.) and 1,3-propanesultone (1.2
eq.) were dissolved in MeCN and refluxed for 10 h under
nitrogen, and then the reaction was allowed to cool to room
temperature. The precipitate washed with ethyl acetate (EtOAc)
(3 × 20 ml). The resulting solids were recrystallized from MeCN
to afford 2,3,3-trimethyl-1-(3-sulfonatepropyl)-3H-indolium and
its derivatives (B1−16).
Design
Merocyanine-type photoacid typically contain
a
strong
electron-accepting moiety (e.g., indolinium derivatives) and a
weakly acidic nucleophilic moiety (e.g., phenol derivatives)
linked with a double bond.[9,16] The corresponding photoreaction
is actually a nucleophilic cyclization reaction to occur between
the two moieties. Thus, photochemical properties of the
photoacids could be adjusted by introducing different
substituents on the two moieties. Herein, we mainly studied
photoacid derivatives with substituents at para (R1), meta (R2)
and ortho (R3) positions of phenolic hydroxyl as well as at the
para (R) position of nitrogen within the indolinium moiety. To
systematically investigate how these substituents affect on
photochemical properties of photoacids, sixteen photoacids with
various groups, such as methoxy (−OMe), halogens (i.e., −F,
−Cl, −Br), cyano (−CN), trifluoromethyl (−CF3) and nitro (−NO2),
at above mentioned positions were designed.
Synthesis of photoacid derivatives (P-Xs)
General procedure
Ⅲ
for P-Xs: 2,3,3-trimethyl-1-(3-
sulfonatepropyl)-3H-indolium and its derivatives (B1−16) (1 eq.)
and corresponding substituted salicylaldehyde (C1−16) (1.3 eq.)
were dissolved in ethanol (EtOH) and refluxed for 12 h under
nitrogen. When the mixture was cooled down to room
temperature, the precipitation was collected by vacuum filtration.
The crude products were washed with EtOAc (3 × 30 ml), and
the pure products were recrystallized from MeOH. Detailed
synthesis and characterization information were supplied in
supplementary information.
Results and Discussion
Displaying color and absorption peaks of P-Xs
In general, the as-mentioned metastable-state photoacids in
forms
of
protonated
merocyanines
(MEHs)
were
Scheme 1. General route for synthesis of photoacid derivatives (P-Xs) with
various substituent groups.
thermodynamically stable. Upon irradiation with a blue light, they
would transform to cyclic spiropyrans (SPs) accompanying with
releasing a proton (Fig. 1a). Meanwhile, the formed SPs could
reversibly return to the MEHs in dark. During these processes,
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reversible color changes could be observed generally.
Substituents conjugated to molecular skeletal structures usually
influence colors of molecules. For better evaluating the
relationship between substituents and the colors, maximum
absorption peaks (λmax) of the synthesized sixteen photoacids in
MeOH before and after irradiation were measured and
summarized (Fig. 1b, c and Fig. S2). P-1, as a most widely
studied photoacid, was taken as a reference herein, which was
marked with blue color.
because of stronger resonance effect and weaker inductive
effect of bromine. EWGs (e.g., −NO2, −CF3 and −CN) on R1
could produce large blue-shifts of λmax (>20 nm). In addition, the
stronger the electron affinity, the greater the blue shift (i.e., λmax
(P-NO2) < λmax (P-CF3) < λmax (P-CN)). On the contrary,
introduction of EDGs (e.g., −OMe) onto R1, a large red-shift was
observed (i.e., P-OMe versus P-1). Using these rules, electronic
effects of other substituents on R1 could be evaluated. As
mentioned above, halogen both have inductive effect and p-π
conjugation effect (resonance effect) for aryl halide. Photoacids
(i.e., P-F, P-Cl and P-Br) with halogen on R1 had slight red-shifts
of λmax compared with λmax of P-1. The result indicated that p-π
conjugation effect of the halogen plays a major role herein.
Furthermore, in order to investigate effect of the same
substituents on molecular color at different positions of phenol
moiety, photoacids with fluorine on R2 (i.e., P-m-F) and R3 (i.e.,
P-o-F) were compared with fluorine on R1 (i.e., P-F). Result
showed that λmax of photoacid with substituent on R3 was the
smallest, on R2 was second, and on R1 was largest (i.e., λmax (P-
o-F) < λmax (P-m-F) < λmax (P-F), which indicated that inductive
effect of the halogen was dominant when it on R2 or R3. This rule
also applies to photoacids with other substituents (i.e., P-o-Cl
versus P-Cl and P-m-OMe versus P-OMe).
After irradiation with blue light, apart from the solution of P-
OMe without significant change, the other solutions of
photoacids faded to colorless or near colorless with λmax mainly
centered at 297 nm (Fig. 1c). It suggests that the photoreactions
for forming SPs from MEHs of these photoacids occurred. The
slight change of P-OMe is due to that only a small part (i.e., less
than 50%) of it underwent photoreaction even irradiation with a
high power (10 mW cm–2) blue light with a long time (Fig. S4). It
indicates that introduction of EDG to R1 restricted photoreaction
of the corresponding photoacid from its MEH form to its SP form.
Besides, compared to P-1, photoacids with nitro-group on R or
R1 (i.e., NO2-P, P-NO2) had large red-shifted SPs. It was
because the conjugation of molecules was effectively prolonged
by delocalized π electrons of nitro group.
Figure 1. (a) Reversible photoreaction of metastable-state photoacids
between their merocyanine states (MEHs) and spiropyrans state (SPs)
accompanying with releasing a proton. Photographs and λmax(s) for solutions
of P-Xs in MeOH (C = 1×10–3 M) (b) before and (c) after irradiation with blue
light.
In a short, the colors (or λmax(s)) of photoacids before
irradiation depended greatly on the nature and position of the
substituents. The study is benefit for adjusting appropriate
substituent groups on the photoacid to match its initial color and
absorption wavelength up with emission wavelength of
commercial laser light source. This is not only important to
achieve precise photo-stimulation but also meaningful for its
practical application.
As shown in Fig. 1b (above), before irradiation, methanol
(MeOH) solutions of these photoacids with various substituents
all displayed yellow or orange colors, except for P-OMe, which
showed a red color. Almost all of their λmax were distributed in
the blue light region (i.e., 400−450 nm), which were affected by
electronic effects of the conjugated substituent groups at
different positions (i.e., R, R1, R2, R3) (Fig. 1b, below).
Introduction of electron withdrawing groups (EWGs) onto R of
the photoacid (i.e., NO2-P) might result in a transformation from
its MEH to SP thermodynamically even without blue light
irradiation. It’s most likely due to that −NO2 increased the
positive charge of indolinium moiety and enhanced its
electrophilicity for ring-closing, the conjecture which was proven
by the NMR spectroscopy (Fig. S3). Electron-donating groups
(EDGs) on R of the photoacid (i.e., MeO-P) would lead to a red-
shift of λmax. For halogen on R (i.e., F-P, Br-P), it produced
different effect on λmax. Fluorine is always inductively electron
Physicochemical property
Considering practical applications of photoacids, their
properties of solubility, molar absorption coefficient (ɛ) and pKa
are very important influence factors. Therefore, substituent effect
on these physical and chemical parameters of the photoacids
were measured and summarized in Table 1. Firstly, in view of
amphoteric structures of the photoacids, their solubilities were
tested mainly in three polar solvents, that is, H2O, MeOH and
DMSO. Detailed solubility test procedure of P-Xs information
was supplied in supplementary information (Fig. S5-7). Results
withdrawing,[34,35] but electron donating by resonance[36]
.
Therefore, absorption peaks nearly had no difference between
P-1 and F-P. As for Br-P, we observed a little red-shift (18 nm)
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show that the solvents order for solubilities of the photoacids in
general is DMSO > MeOH > H2O. Besides, their solubilities in
these solvents were also influenced by their substituents.
Introduction of either EWGs or halogen groups on R or R1
decreased generally solubilities of photoacids in H2O; yet, EDGs
on phenolic moiety or halogen on R3 could improve solubility of
photoacids. In their MeOH solutions: introduction of different
substituent groups on indolinium moiety (R) could reduce
solubility of photoacids; while methoxy group on phenolic moiety
could increase solubility of photoacids no matter its position at
(i.e., P-OMe, P-m-OMe versus P-1) which might be due to
similar compatibility principle; For the photoacids substituted
with EWGs on R1: −NO2 or −CN could decrease their solubilities,
while −CF3 increased its solubility due to that trifluoromethyl
group is a lipophilic group. Solubilities of halogen attached
photoacids in MeOH were depended on position of the halogen.
That is, the solubility of P-F, P-Cl and P-Br increased
successively which may be related to their polarization ability; P-
o-F and P-o-Cl also had an increase in solubility compared with
P-1, but the solubility of P-m-F was slightly reduced.
Interestingly, any substituents introduced to photoacids would
increase their solubilities in DMSO. Conversely, it demonstrates
that DMSO is a very good solvent medium for photoacids.
the basis of effectively photoinduced acidity for photoacids.
Given that, ɛ(s) of the photoaicds were measured (Fig. S8-23).
As shown in Table 1, taking P-1 as a reference, introduction of
substituents on indolinium moiety had minor effect on ɛ of
photoacids. In contrast, almost all of substituents placed at
phenolic moiety could reduce ɛ of photoacids. Noticeably, P-m-
OMe is an exception. Its ɛ is as high as 47600 M–1cm–1, which is
almost 1.5 times higher than that of other photoacids. These
results indicate that modifying EDGs on R2 or substituents (apart
from EWGs) on R was contributed to improve ɛ and thereby
increased the photoreation efficiency for photoacids.
pKa(s) of the photoaicds would affect their application as well,
thus pKa(s) of the photoaicds were measured using the method
of S curve[19,37], which was tested via UV-vis spectroscopy (Fig.
S24-39). Introduction of EWGs (i.e., −NO2, −CF3 and −CN) as
well as halogen (i.e., −F, −Cl, −Br) could reduce their pKa values,
yet introduction of EDGs (i.e., −OMe) would increase their pKa
values, which is mainly caused by their electronic effects.
Among them, pKa values of NO2-P (2.3) and Br-P (5.39) were
lower than those of P-NO2 (4.72) and P-Br (5.71), respectively;
pKa value of MeO-P (7.05) was higher than that of P-OMe (6.20).
These results suggest that substituents linked to the indolinium
ring had a greater influence than to the phenol ring on the pKa
values of photoacids. Furthermore, pKa values of P-o-F (5.72)
and P-o-Cl (5.20) were lower than those of P-F (5.90) and P-Cl
(5.83), respectively; while pKa values of P-m-F (6.12) and P-m-
OMe (6.51) were higher than those of P-F (5.90) and P-OMe
(6.20). These facts show that halogen on R3 or electron-donating
groups on R2 would reduce or increase pKa values of
corresponding photoacids, compared with those with the same
substituent on R1.
Table 1. Physical and chemical properties of photoacids.
Solubility / mM (20°C )
ɛ / (λ / nm)[a]
104 M-1cm-1
[b]
Photoacid
pKa
H2O
MeOH
DMSO
MeO-P
F-P
0.34
0.28
0.28
0.35
0.28
5.31
6.46
5.47
12.40
5.36
36.57
55.28
95.15
18.70
51.25
3.26 (450)
3.06 (441)
3.30 (448)
3.27 (440)
2.95 (414)
7.05
6.20
5.39
6.23
4.72
Dark- and Photo-acidity
Br-P
Acidities before (called as dark-acidity) and after irradiation
(called as photo-acidity) are the most important property for
photoacids in various applications. In order to evaluate effect of
substituents on dark- and photo-acidity of photoacids, their
apparent pH (pH*) values in 70% aqueous MeOH solutions
before and after irradiation by a blue light were measured. The
light intensity on surface of the solutions was set to be 10 mW
cm–2 and irradiation time was 3 min. A series of concentrations
P-1
P-NO2
P-CF3
P-CN
P-F
0.17
0.19
0.23
0.56
0.37
0.25
0.25
1.03
0.56
0.43
54.00
5.84
79.51
37.99
36.30
44.71
75.91
240.87
72.92
86.53
136.29
68.24
3.04 (418)
2.80 (419)
2.72 (443)
2.68 (422)
3.03 (432)
2.67 (443)
2.75 (443)
2.74 (421)
1.68[c],2.09[d]
4.76 (468)
5.66
5.46
5.90
5.72
6.12
5.71
5.83
5.20
6.20
6.51
8.49
P-o-F
P-m-F
P-Br
22.20
10.84
56.75
11.74
100.71
35.67
33.21
ranging from 0.05 mM to
2 mM were tested, and the
corresponding pH*s were measured using a pH meter. Overall,
the concentration would influence pH* values of the photoacids
solutions both before and after irradiation, and the effect on the
latter was greater than the former except for P-OMe (Fig. 2a).
Photo-acidity experiments showed that the pH* of MeOH
solution of P-OMe slightly dropped upon irradiation in different
concentrations, which indicated P-OMe had very weak
photoactivity and the result was consistent with the UV-vis
absorption data discussed previously. Furthermore, the effect of
concentration on the photo-acidity (pH*') of remaining
photoacids was shown in a more direct way (Fig. 2b). It was
clearly observed that pH*'(s) decreased sharply with the
increase of concentration from 0.05 mM to 1 mM except for P-
m-OMe. Unlike other photoacids, P-m-OMe can only completely
P-Cl
P-o-Cl
P-OMe
P-m-OMe
[a] Experiments measured in MeOH. [b] Experiments measured in PBS.
[c] λ1 (381 nm). [d] λ2 (486 nm)
The photoinduced cyclization as well as proton-dissociation of
photoacids is actually a process of converting light energy into
chemical energy. Thus, the absorption efficiency (ɛ) for light is
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release protons upon irradiation at concentrations below 0.1 mM. introduction of EDGs (i.e., −OMe) would increase their pKa
When the concentration beyond 0.1 mM, photoirradiation does
not effectively induce MEH-to-SP transformation, and thus pH*'
would not change obviously. In addition, the pH*' for each other
photoacids nearly reached the theoretical value for a complete
proton dissociation under the concentration of 1 mM. Increasing
their concentration further (i.e., 2 mM), the pH*'s decreased less.
It reveals that the optimum concentration of photoacids for
photoinduced proton-dissociation was about 1 mM. In fact, the
solutions of photoacids with concentrations beyond 1 mM hardly
faded to colorless even irradiated by a stronger blue light with a
long time. It was due to that the isomerization equilibriums of
photoacids from MEHs to SPs were restrained by the
acidochromism of the SPs induced by the released proton at a
high concentration.
values, MeO-P, P-OMe and P-m-OMe have higher pH*s in
solutions than that of P-1, especially MeO-P. The ground state
pKa of MeO-P is 7.05, which is the largest one of all photoacids,
corresponding to the highest pH* (6.10). The electron-
withdrawing groups on R1 could increase dark-acidity (or
decrease pH*) for photoacids. And the stronger electron-
withdrawing capability of groups, the higher dark-acidity (or
lower pH*) of the photoacids (e.g., P-NO2 versus P-CF3 versus
P-CN), which is due to that EWGs could promote the MEH-to-
SP and MEH-to-ME transformations (ME refers to deprotonated
merocyanine), which was proven by the UV-vis spectroscopy
(Fig. S40). During these transformations, photoacids can release
protons and reduce the pH* of their solutions, which is also why
they have lower pKa(s). For photoacids substituted with halogen:
fluorine-substituted one (i.e., F-P, P-m-F) have similar pH* to P-1,
while pH*s for bromine- or chlorine- substituted photoacids had
a different degree of reduction, which indicates the fluorine atom
here does not exhibit an inductive effect for photoacids, probably
due to the same significant of resonance effect.
After irradiation, almost all of the pH*' of the photoacids
solutions dropped to 3.25 except for P-OMe and P-m-OMe. Both
P-OMe and P-m-OMe are less effective than P-1 in lowering the
pH*' on photolysis due to their weak photoactivity, especially P-
OMe. In sharp contrast to that, MeO-P performed excellent
photo-acidity property. The pH* of MeO-P changed from 6.10 to
3.31 upon irradiation, exhibiting a largest acidity gap (∆ pH* =
2.8), which is due to its low dark-acidity. These results indicate
that EDGs on indolinium ring was contributed to improvement of
photo-acidity gap for photoacids, while EDGs on phenol ring
could weaken the photo-acidity. This may be because the MEH
of corresponding photoacids cannot undergo proton dissociation
efficiently to generate ME when EDGs on phenol ring. Modifying
EWGs on R1, these photoacids showed small acidity gaps due
to their high dark-acidity (i.e., P-NO2, P-CN, P-CF3). Noticeable,
with halogen on R, F-P had a little larger acidity gap than that of
P-1, while Br-P showed a smaller one than that of P-1. For
photoacids with halogen on R1, their acidity gaps decreased in
the order of P-F < P-Cl < P-Br, which mainly depends on the
order of their dark-acidity. Besides, it needs to be mentioned that
halogen at the meta of hydroxyl group would increase the acidity
gap while at the ortho of hydroxyl group would decrease the
acidity gap compared with the para position substituted
photoacids, and this rule also applies to EDGs (i.e., P-m-F
versus P-F, P-m-OMe versus P-OMe, or P-o-F versus P-F, P-o-
Cl versus P-Cl). This seems to indicate that the electronic effect
of substituents is weakened at R2 and strengthened at R3.
In short, photoacids with halogen (especially fluorine group) or
EDGs attached at the indolinium moiety or halogen on para
position of the phenolic hydroxyl (R1) possessed excellent photo-
acidity and acidity gap, which would endow these photoacids
with tremendous potential applications. Besides, introduction of
EDGs onto the indolinium moiety of photoacids could passivate
effectively their dark-acidity for special needs (high pH system)
of applications.
Figure 2. (a) pH*s of photoacids in 70% MeOH aqueous solutions with
different concentrations before and after light irradiation. (b) Acidity of the
photoacids solutions after irradiation (pH*') with concentration from 0.05 mM to
2 mM. (c) The pH* changes of the photoacids solutions (1 mM) before and
after irradiation.
For the sake of inquiry the relationship between substituents
and photoacidity, pH* values of these photoacids in MeOH
aqueous solutions with concentration of 1 mM before and after
irradiation were investigated (Fig. 2c). As a reference, the pH* of
P-1 in solution changed from 5.40 to 3.23 upon irradiation,
exhibiting an obvious “acidity gap” (i.e., pH* difference for
photoacid before and after irradiation). Introduction of
substituents onto the photoacids influenced their pH*s both
before and after irradiation.
Before irradiation, these solutions of photoacids showed dark-
acidity with varying strengths, mainly due to the different
degrees of proton dissociation of these photoacids in the dark,
which is determined by their pKa(s) of the ground state. Since
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Photosensitivity
(Fig. 3b). As mentioned before, introduction of EDGs to R1 (i.e.,
P-OMe) led to its weak photosensitivity; introduction of EWGs
(i.e., P-CF3, P-NO2, P-CN) or halogen (i.e., P-F, P-Cl, P-Br) to
R1 produced light-sensitivity of the photoacids slowing down,
especially for P-NO2 (Fig. 3c). That is, roughly 21% of P-NO2 still
kept in its MEH form after 27 s irradiation, while approximately
98.1% of P-1 transformed to its SP form upon the same time of
irradiation. In a further study, we found P-NO2 had a strong red
fluorescence-emission under the excitation of the blue light
which reduced the efficiency of cyclization reaction (Fig. S42).
Effect of substituents on the phenolic hydroxyl at different
positions (i.e., R1/R2/R3) on photosensitivity of photoacids was
considered as well (Fig. 3d). It is worth noting that P-m-OMe has
the largest ɛ value, but it does not perform a high sensitivity to
light. The main reason may be that its methoxy at the phenol
moiety hinders the dissociation of the phenolic hydroxyl group,
partly due to its fast reverse reaction (Fig. S43). In contrast to P-
F and P-Cl, respectively, P-o-F and P-o-Cl became hard to
undergo cyclization reaction upon irradiation. This might be
owing to P-o-F and P-o-Cl easy to form intramolecular hydrogen
bonds between −F or −Cl and the phenyl hydroxyl group which
inhibits the release of protons from the photoacids. While P-m-F
performed too photosensitive compared with P-F. That is,
approximately 80% of P-m-F transformed to its SP form within
the first 9 s irradiation. Similarly, the photosensitivity of P-m-
OMe was also faster than P-OMe. These results indicate that
introduction of substituents attached at meta position of the
phenol ring could improve photosensitivity of the photoacids
compared with at the para position.
Photosensitivity refers to the speed of photocyclization as well
as releasing acid of photoacid, which is an important factor for
their applications. In order to reduce the effects of the reverse
reaction during the test, a suitable solvent should be chosen first.
Thus we measured the recovery process (SP-to-MEH process)
of P-1 in different solvents, such as H2O, MeOH and DMSO (Fig.
S41). The results show that P-1 has a much slower reverse
reaction rate in DMSO than in other solvents, so DMSO is an
ideal solvent for testing photosensitivity of photoacids. To
assess the effect of substituents on photosensitivity of the
photoacids, their photoreactions in DMSO were monitored by
UV-Vis spectroscopy with every irradiation time of 3 s. A LED
light with emission wavelength mainly centered at 447 nm was
used and its intensity was controlled to be 1.26 mW cm–2 by
adjusting the distance between the LED light and the measured
samples. We took P-1 as an example as well as a reference to
show the experiment in detail, and the data acquisition was
completed as the solution was changed to nearly colorless or its
absorption in visible light range ( > 400 nm) disappeared (Fig.
3a). Then a curve of the ratio of its absorption intensity after
irradiation (AMEH') to its initial intensity (AMEH) at the maximum
absorption peak (λmax) (i.e., 438 nm) of P-1 against irradiation
time was obtained. In the same way, similar curves for other
photoacids were acquired.
Relaxation kinetics
At last, substituent effect on the life of the proton-dissociation
state, referring to the time of SPs-to-MEHs transformation for
photoacids, was investigated. Which is closely related to the
recovery processes of photoacids after irradiation. Relaxation
kinetics of the photoacids after irradiation were monitored by
UV-vis spectroscopy. P-1 was taken as an example and
reference again. As shown in Fig. 4a, a curve of absorption
intensity at λmax of P-1 (i.e., 440 nm) against time was recorded.
It revealed that it took about 6000 s for SP form of P-1 reverting
back to its original level. The kinetic data in the first 3600 s
(approximately first 60% of relaxation process) of this relaxation
process fitted into a pseudo first-order reaction in methanol (Fig.
4b), which may be related to the acidity of the solvent.
Interestingly, we found that the data collected at early stage of
the reverse reaction (approximately first 10% of relaxation
process) can fit well into both a first-order rate equation (Fig. 4c)
and a second-order rate equation (Fig. 4d). The latter is
consistent with Liao’s report in different solvents,[17] including
water, ethanol, and DMSO. This result is caused by solvent
effect, high concentration of various species in the initial stage of
the reaction and so on. Accordingly, the rate constants k’1 of the
pseudo first-order reaction could be evaluated as 2.77×10–4 s–1
from the slope of the fitted straight line with a coefficient of
determination R2 of 0.9997. And its life of the proton-dissociation
state for P-1 were obtained to be 1.67 h from relaxation curve
Figure 3. (a) UV/vis absorption spectra of P-1 in DMSO (5×10–5 M) with
irradiation time (scans were taken by every 3 s of irradiation); (b)−(d) Curves
of the ratios of absorption intensity after irradiation (AMEH') to its initial intensity
(AMEH) at their maximum absorption peak (λmax) for P-Xs, which were divided
according to the position of their containing substituents.
For the sake of investigation of substituent effect, the obtained
curves were divided into three groups according to the position
of the substituents (i.e. R, R1 and R1/R2/R3) (Fig. 3b−d).
Photoacids with substituents on R behaved similarly with P-1 to
light, which seemed to indicate substituents at this position had
minor effect on photosensitivities of corresponding photoacids
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(Fig. 4a). Relaxation kinetics for other photoacids were also
investigated, and the results showed their reverse reactions also
fitted into pseudo first-order reactions in approximately first 60-
80% of relaxation processes. (Fig. S44-56). Thus, the rate
constants (k’1) and their coefficient of determination (R2) for
other photoacids were also summarized in Table 2.
photoacids; EWGs on R1 (i.e., P-NO2, P-CF3, P-CN), especially
for −NO2 and −CN, would extremely slow down reverse
reactions for these photoacids, which needed about 1 day for
completely returning to their MEH forms in the dark. This may be
because EDGs can increase the reaction activation energy for
corresponding photoacids from SPs and MEHs, while EWGs
could reduce the activation energy. Detailed mechanistic study
is required to quantitatively define the suitable energy levels of
MEH and SP, which is beyond the scope of this article.
Introduction of halogen, no matter on R1 (i.e., F-P, Br-P) or R
position (i.e., P-F, P-Br, P-Cl), would slow down relaxation
processes of these photoacids. However, when the halogens on
R2 or R3 position (i.e., P-o-F, P-m-F, P-o-Cl), they would greatly
accelerate the recovery processes of the corresponding
photoacids.
Above all, it is obvious that the substituents bring an
enormous impact on the relaxation processes of the photoacids.
Thus, a large range of lifetimes, from minutes to days, for the
photoacids keeping proton-dissociation have been achieved.
This is easy to meet different application needs for photoacids.
Conclusions
A series of metastable-state photoacids containing EDGs (i.e.,
−OMe), EWGs (i.e., −CN, −CF3, −NO2) or halogen (i.e., −F, −Cl,
−Br) were designed and synthesized to elucidate systematically
substituent effects on their photochemical properties. Taking the
commonly used non-substituted photoacid (P-1) as a reference,
color display (or maximum absorption peak(s)), solubility, pKa(s),
dark-/photo-acidity, photosensitivity and relaxation kinetic of the
photoacids had been evaluated. It was found that 1) EWGs (e.g.
−NO2, −CF3 and −CN) on para positions of phenolic hydroxyl
(R1) could produce large blue-shifts of λmax, and the stronger the
electron withdrawing, the greater the blue shift (i.e., λmax (P-NO2)
< λmax (P-CF3) < λmax (P-CN)); on the contrary, EDGs onto R1
generated a large red-shift (i.e. P-OMe). Using these rules,
electronic effects of other substituents on para positions of
phenolic hydroxyl for photoacids could be estimated.; 2) the
solvents order for solubilities of the photoacids in general is
DMSO > MeOH > H2O; 3) substituents on the indolinium moiety
(R) have larger influence on the pKa of photoacids compared to
them on the phenol moiety (i.e., MeO-P versus P-OMe, Br-P
versus P-Br and NO2-P versus P-NO2); 4) both EDGs and
EWGs on the phenol moiety would weaken photo-induced
acidity capability of photoacids, whereas photoacids with
halogen at R or R1 performed excellent photo-acidity; 5) EWGs
(i.e., −NO2) on R1 or halogen on R3 at the phenol moiety would
slow down the MEHs-to-SPs process of the photoacids due to
existence of strong fluorescence emission (the former) or
intramolecular hydrogen bonding (the latter); 6) the primeval
relaxation kinetics (SPs-to-MEHs) of these photoacids mainly
fitted into pseudo first-order reactions in approximately first 60-
80% of relaxation processes; 7) EWGs on R1 would extremely
slow down recovery processes for these photoacids, while the
influence of halogens on the recovery processes of these
photoacids depends on their position. These results confirmed
Figure 4. (a) A plot of absorbance at λmax (440 nm) of P-1 in MeOH (5 ×10-5
M) against time after irradiation in the dark; (b) A plot of the kinetic data in the
first 3600 s of this relaxation process fitted into a pseudo first-order rate
equation; a plot of the kinetic data in the first 600 s of this relaxation process
fitted into both a first-order rate equation (c) and a second-order rate equation
(d).
Table 2. The relaxation kinetics parameters of photoacids
Photoacid
P-1
k’1 / (×10-4) s-1
2.77
R2
Photoacid
Br-P
k’1 / (×10-4) s-1
0.58
R2
0.999
0.999
0.991
0.999
0.999
0.999
0.999
0.997
0.998
0.999
0.999
0.998
0.999
0.999
MeO-P
P-m-OMe
P-NO2
P-CF3
P-CN
4.72
P-F
1.68
143.9
0.15
P-Cl
2.96
P-Br
1.40
0.54
P-o-F
P-m-F
P-o-Cl
15.60
21.60
15.30
0.25
F-P
2.67
The relaxation processes of photoacids were tested at 22 °C.
According to the results of the obtained values of k’1, the
following results could be summed up: EDGs (i.e. −OMe) (i.e.
MeO-P, P-m-OMe), especially on R2 (i.e. P-m-OMe), would lead
to accelerations for the recovery processes of corresponding
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Junning Liu, Wenqi Tang, Lan Sheng,*
Zhen Du, Ting Zhang, Xing Su, and
Sean Xiao-An Zhang
Sixteen metastable-state photoacid
derivatives containing various
substituents were designed and
synthesized. Substituent effects on
their color display (or maximum
absorption peak(s)), solubility, pKa(s),
dark-/photo-acidity, photosensitivity
and relaxation kinetic(s) were
Page No. – Page No.
Substituent Effect on Metastable-
State Photoacids: Design, Synthesis
and Evaluation of their
Photochemical Properties
investigated systematically. This study
will be conducive to targetedly design
and synthesize promising photoacids
as well as apply their photo-controlled
proton-release processes in functional
materials/devices
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