Efficient Light-Induced pKa Modulation Coupled to Base-Catalyzed Photochromism

Article abstract of DOI:10.1002/anie.201801270

Photoswitchable acid–base pairs, whose pK_a values can be reversibly altered, are attractive molecular tools to control chemical and biological processes with light. A significant, light-induced pK_a change of three units in aqueous medium has been realized for two thermally stable states, which can be interconverted using UV and green light. The light-induced pK_a modulation is based on incorporating a 3-H-thiazol-2-one moiety into the framework of a diarylethene photoswitch, which loses the heteroaromatic stabilization of the negatively charged conjugate base upon photochemical ring closure, and hence becomes significantly less acidic. In addition, the efficiency of the photoreactions is drastically increased in the deprotonated state, giving rise to catalytically enhanced photochromism. It appears that protonation has a significant influence on the shape of the ground- and excited-state potential energy surfaces, as indicated by quantum-chemical calculations.

Full text of DOI:10.1002/anie.201801270

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Accepted Article
Title: Efficient Light-Induced pKa-Modulation coupled to Base-
Catalyzed Photochromism
Authors: Johannes Gurke, Simon Budzak, Bernd Schmidt, Denis
Jacquemin, and Stefan Hecht
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201801270
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Efficient Light-Induced pKa-Modulation coupled to Base-Catalyzed
Photochromism
Johannes Gurke, Šimon Budzák, Bernd M. Schmidt, Denis Jacquemin, and Stefan Hecht*
Abstract: Photoswitchable acid-base pairs, allowing for a reversible
alteration of their pKa values, are attractive molecular tools to control
chemical and biological processes by light. A significant, light-induced
pKa change of three units in aqueous medium has been realized
involving two thermally stable states, which can be interconverted
using UV and green light. The light-induced pKa modulation is based
on incorporating a 3-H-thiazol-2-one moiety into the framework of a
diarylethene photoswitch, which upon photochemical ring-closure
loses the heteroaromatic stabilization of the corresponding, negatively
charged base and hence, becomes significantly less acidic. In
addition, the efficiency of the photoreactions in the deprotonated state
is drastically increased, thereby giving rise to catalytically enhanced
photochromism. It appears that protonation has a significant influence
on the shape of ground and excited state potential energy surface as
indicated by quantum chemical calculations. Using this concept of
interconnected photoisomerization and acid-base equilibria allows to
adjust the degree of photoconversion by the pH of the solution and
constitutes a powerful tool to precisely and remotely control the
charge state by light.
that can efficiently be interconverted between thermally stable
states associated with sufficiently large acidity modulation
(DpKa ³ 2.5) remains an important objective in the field.
Coupling orthogonal thermal and photochemical equilibria allows
for light-gated ground-state reactivity as well as chemically gated
photochromism, which can be combined in multistate reaction
cycles to construct functional molecular systems, controlled and
driven by light.[1] We have targeted the remote modulation of acid-
base equilibria as one of the most fundamental chemical reactions
highly relevant for material and life sciences. Beyond changing
chemical reactivity and related catalytic activity,[2] reversible
control over a compound’s pKa should have profound influence on
key properties such as solubility, intermolecular interactions[3] as
well as bioavailability[4] that are critical for drug design. In order to
affect a sufficient light-induced acidity change, defined here by
interconverting 95% of a protonated species (acid) to 95% of a
deprotonated species (corresponding base), would require a
(reversible) pKa modulation by at least 2.5 units.[5] A variety of
reversible[6] photoacids have been developed over the past 50
years, in particular by exploiting the acidity difference between
ground and excited states to realize large pKa shifts, which
however are associated with very short lifetimes only.[7] Much
longer lifetimes have been achieved using photoisomerization
between two metastable ground-state species.[8] For this purpose,
various spiropyran,[8a-d] azobenzene,[8e-i] and diarylethene
(DAE)[8j-m] derivatives have been investigated (Figure 1a) but
either exhibit thermal instability[8a-I,9] or insufficient pKa
modulation.[8j-m] Hence, the development of photoswitchable acids
Figure 1. Background information: (a) Selected pKa photoswitches in water or
[a] methanol/water 5/2, [b] acetonitrile/water 8/2 (b) pKa-structure relationship of
linear and cyclic carbamates.
We focus here on the use of DAE photoswitches in analogy to
the group of Lehn, who pioneered their use to modulate acid-base
properties.[8j] In comparison to other classes of photochromic
molecules, optimized DAE derivatives display efficient, (nearly)
quantitative,
and
robust
photoconversion
in
both
photoisomerization directions.[10] In view of these advantageous
photochemical behavior and the absence of thermal
interconversion (P-type photochromism),[11] DAEs enable precise
adjustment of the system between two distinct and temporally
independent forms. This property has successfully been used to
modulate chemical reactivity,[12] most frequently taking advantage
of relocating double bonds during the light-induced 6p
electrocyclic ring-opening/closure.[13] Inspired by the pKa
dependence observed for oxazolinones and oxazolones
(Figure 1b),[14] we herein explore this powerful concept to control
the acidity of an integrated 3H-thiazol-2-one moiety by
photochemically removing and re-installing an internal carbon-
carbon double bond and thus tuning the aromatic stabilization of
its corresponding base (Figure 2).
[*]
J. Gurke, Dr. B. M. Schmidt, Prof. S. Hecht
Department of Chemistry & IRIS Adlershof
Humboldt-Universität zu Berlin
Brook-Taylor-Str. 2, 12489 Berlin, Germany
E-mail: sh@chemie.hu-berlin.de
Dr. S. Budzak, Prof. D. Jacquemin
Laboratoire CEISAM, UMR CNRS 6230
Université de Nantes, 2 Rue de la Houssinière
BP 92208, 44322 Nantes Cedex 3, France
Supporting information for this article is given via a link at the end
of the document.
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furthermore reduces the acidity of the closed isomers 1cH.
Irradiation with visible light should induce ring-opening and
therefore reverse these effects.
Titration of 1o (Figure 3a) in an aqueous 0.15 M KCl solution
containing 30 vol% acetonitrile with 0.7 M HCl (in the same
solvent composition) gives a solvent-mixture specific[17] ꢃꢃꢀꢁꢂ of
4.0 ± 0.1 (DGa = 5.0 kcal×mol-1) whereas titration of the isomer 1c
Figure 2. Light-induced pKa-modulation: (a) Four-state reaction cycle involving
photoisomerization (1oH → 1cH, 1o → 1c) and thermal acid-base (1oH ⇌ 1o,
1cH ⇌ 1c) equilibria of a thiazolone-based diarylethene (EDG = 4-methoxy-
phenyl) at working pH = 5. Deprotonation of the open isomer 1oH leads to
aromatic and thus stable negatively charged 1o, which undergoes ring-closure
upon UV irradiation with high quantum yield. ⇌ The negative charge in the
closed form 1c is isolated, leading to protonation and thus formation of 1cH,
which undergoes cycloreversion to 1oH upon irradiation with visible light to
close the cycle. (b) Schematic potential energy diagram for an ideal pKa switch.
Target molecule 1oH (Figure 2a, for synthesis see the
Supporting Information (SI)) is composed of a 4-(4’-methoxy-
phenyl)-2-methylthien-3-yl residue connected to the commonly
used hexafluorocyclopentene bridge,[15] which also carries a
4-trifluoromethyl-3H-thiazol-2-on-5-yl substituent serving as the
acidic site. Deprotonation leads to the negatively charged 1o,
which is primarily stabilized due to its aromatic character. The
strong electron-accepting nature of the hexafluorocyclopentene
bridge[16] and the adjacent trifluoromethyl group provide additional
stabilization of the anion 1o. This is supported by the fact that the
HOMO of 1o is located on the thiazole moiety whereas it is
centered on the thiophene ring in 1oH (see Figure S16 in the SI).
Upon UV light-induced ring-closure and resulting double bond
migration, acidity and hence stability of 1c should significantly
decrease for several reasons: i) loss of aromatic stabilization, ii)
cross-conjugation with the electron-withdrawing bridge, and iii)
decoupling from the (-I) effect of the trifluoromethyl group. In
addition, the electron-donating methoxy group attached to the
opposite terminus of the DAE becomes p-conjugated and thus
Figure 3. UV/vis experiments of compound 1 in aqueous 0.15 M KCl solution
(30 vol% MeCN): (a) titration of open and closed isomers with aqueous 0.7 M
HCl solution (30 vol% MeCN); (b) UV/vis spectra of all four species; (c)
photokinetic data at different pH-values.
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gives a ꢃꢃꢀꢁꢂ of 6.8 ± 0.1(DGa = 8.5 kcal×mol-1). This corresponds
to a pKa shift of 2.8 units, consistent with DFT calculations that
predict a change of 2.6 units (see section 5 in the SI). Therefore,
complete protonation and deprotonation of both isomers can be
achieved by using 0.1 M HCl and KOH solutions, respectively.
Both open isomers (1oH and 1o) show a strong absorption in the
UV region until 330 nm (Figure 3b), which according to TD-DFT
results is attributed to a combination of high-lying states. In 1oH,
the lower energy S0 ® S1 transition is much less intense, which is
a consequence of the small overlap between the HOMO and the
LUMO, whereas it has a significant intensity in 1o (band at ca.
360 nm) as a result of the stronger overlap (see Figure S16 in the
SI). Irradiation with UV light (313 nm) leads to the rise of an
intense absorption band at 500 nm in both cases due to formation
of the protonated and deprotonated closed isomers (1cH and 1c),
which present similar orbital topologies. Irradiation with green light
(546 nm) induces quantitative ring-opening and thus leads to
complete reversion. Spectral analyses of both cyclization and
cycloreversion show clean photoreactions, in the protonated as
well as in the deprotonated cases (see Figure S7 in the SI).
Photokinetic analysis of the ring closure and ring opening show a
strong dependence of rate and conversion of the photoreaction
on the protonation state (Figure 3c).
of the photostationary states (PSSs) after UV-irradiation, which
show much higher conversion in the deprotonated state (amount
of closed isomer cc(PSS) = 85 ± 5%) as compared to the
protonated state (cc(PSS) = 35 ± 5%). It is important to point out
that no thermal ring opening was observed, neither in the
protonated nor in the deprotonated form. At this point, we
underline that according to DFT there should be a strong
preference of 1o for adopting the anti-parallel conformation (98%
estimated population), which is a very favorable case in DAEs
since the photochemical ring-closure originates solely from this
conformation. In addition to thermal stability, photochemical
fatigue was investigated as well showing photodegradation upon
313 nm irradiation under strongly basic conditions whereas only
marginal fatigue occurs in an acidic milieu (see Figures S10 in the
SI). Furthermore, a rather slow thermal side reaction of the closed,
deprotonated form 1c with water was noticed.[8j,m,19]
Our system describes a four-state reaction cycle, which due to
the wavelength selectivity of the photochemical ring-closure and
-opening steps and the thus altered acid-base equilibrium allows
for a unidirectional operation (counter-clockwise in Figure 2a). If
the pH is adjusted to a value in between the two different pKa
values of the open and closed isomers, a catalytic cooperative
interconnection can achieved in which the efficiency of the
photoisomerization is significantly enhanced by coupling it to the
thermal acid-base equilibrium. Indeed, irradiation of the solution
with UV light (313 nm) at pH = 5 leads to complete conversion
and a reaction rate comparable with the one for the ring closure
of the deprotonated form, i.e. 1o ® 1c (see Figure 3c as well as
PSS compositions and effective quantum yields at the bottom of
Table 1). At pH = 5, cycloreversion occurs with the rate of the
protonated species, 1cH ® 1oH, as confirmed by calculation of
the corresponding effective quantum yield (see Table 1). Thus our
four-state system can be described by a catalytic cycle, where the
photoisomerization of compound 1 (at 10-5 M concentration) is
catalyzed by the presence of base, i.e. small amounts of
hydroxide (ca. 10-9 M) in aqueous medium at pH = 5 in this case.
Table 1. Spectroscopy and photochemistry in dependence of the pH in aqueous
0.15 M KCl solution (30 vol% MeCN).
PSS [c]
e313nm
(e546nm
/
F 313nm
cc
l
max (emax)
ꢃꢃꢀꢁꢂ
/
F
)
(
)
(lirrad
/
)
546nm
nm
/
(M-1∙cm-1)
M-1∙cm-1
%
% (nm)
295
(22900 ± 460)
35 ± 5
1.3
1.3
9.0
9.0
16900 ± 340
2.1 ± 0.2
1oH
1cH
1o
(313 ± 6[a]
)
)
497
(15600 ± 780)
9000 ± 450
(8600 ± 430)
8.3 ± 1
(3.6 ± 0.4)
3 ± 5
(546 ± 6[a]
295
(19900 ± 400)
85 ± 5
(313 ± 6)
15600 ± 310
47 ± 5
500
(14000 ± 700)
15200 ± 760
(7500 ± 380)
5.2 ± 0.5
(9.6 ± 1)
0 ± 5
1c
(546 ± 6[a]
)
)
100 ± 5
5.0
5.0
34 ± 3[b]
(313 ± 6[a]
To obtain an in-depth understanding of the energetics (Figure 4),
calculations to map critical points on the ground- and excited-state
energy surface were carried out in acetonitrile solution (note that
the photochromism shows the same trends in pure acetonitrile as
in acetonitrile containing 30 vol% water, investigated above; see
Figure S6 in the SI). In agreement with a thermally forbidden
conrotatory ring-opening/-closure computational results indicate
that the transformation between closed and open isomers in the
ground state is prevented by large barriers for the neutral
molecules (ΔG‡ = 52.5 kcal×mol-1 was calculated for 1cH ® 1oH)
as well as the deprotonated switch (ΔG‡ = 51.1 kcal×mol-1 for
1c ® 1o). In both cases, the open isomer is thermodynamically
more stable, in the neutral form by ΔGr = - 7.6 kcal×mol-1 (1cH ⇌
1oH) and in the deprotonated form by ΔGr = - 4.0 kcal×mol-1
(1c ⇌ 1o). Both protonated forms (1oH and 1cH) as well as the
closed, deprotonated form (1c) exhibit an excited-state energy
diagram (see Sections 5 of the SI for details) similar to already
characterized DAEs.[20] The irradiation of 1oH results in excitation
to the S2 state. Direct excitation of S1 is less likely due to its very
low oscillator strength (TD-DFT f = 0.02) and thus it is mostly
(4.0 ± 0.4)[b]
0 ± 5
(546 ± 6[a]
)
[a] Monochromator bandwidth; [b] Effective quantum yields; [c] Mole fraction
of 1cH, 1c or their mixture.
While the protonated form 1oH shows a low conversion to the
closed isomer and a slower rate of conversion, the deprotonated
form 1o shows a much higher conversion and faster rate. In both
cases, cycloreversion is complete (due to selective excitation of
the closed isomers) yet again the rates of the photoinduced ring
opening are faster for the deprotonated 1c as compared to the
protonated 1cH. Evaluation of these photokinetic data (Table 1)
shows that the quantum yields for cyclization differ by more than
one order of magnitude between the deprotonated and
protonated forms (F1o 1c = 47 ± 5% vs. F1oH 1cH = 2.1 ± 0.2%,
®
®
see Table 1). Note that the quantum yields of the ring-opening
show not only a dependency on the protonation state but also on
the irradiation wavelength, as reported for DAEs in the
literature.[18] The interplay of the differences in quantum yields and
extinction coefficients is consequently reflected in the composition
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populated indirectly via internal conversion. The S1 relaxes in a
barrier-less fashion towards a conical intersection. In agreement
with previous reports on DAEs,[11a,18a,21] small barriers were found
along the cycloreversion path in the excited state for both acidic
as well as basic milieu. In contrast, the calculations suggest that
the excited-state energy surface for photocyclization of the
deprotonated form (1o ® 1c) differs from other DAEs since an
additional local minimum is found between the Franck-Condon
point and the conical intersection, separated by a small barrier.
This might seem counterintuitive in regard to the observed
quantum yield, yet the reaction dynamics of DAEs are known to
be complex and a local minimum might indeed be able to "focus"
the reaction as a smaller portion of the Potential Energy Surface
is explored. Excitation of 1o results in direct population of the S1
state, which exhibits a much higher oscillator strength as
compared to 1oH.
Acknowledgements
The authors are indebted to Yves Garmshausen, Sergey Kovalenko,
and Martin Quick for their help and fruitful discussions. Generous
support from the European Research Council (ERC via ERC-2012-
STG_308117 ‘‘Light4Function’) as well as the German Research
Foundation (DFG via Cluster of Excellence “Unifying Concepts in
Catalysis” EXC 314-2) is gratefully acknowledged.
Keywords: acidity • aromaticity • diarylethenes • photochromism
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Figure 4. Qualitative potential energy diagram of a model compound: (a)
deprotonated isomers 1o and 1c with ΔGǂ = 51.1 kcal×mol-1 and
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The herein presented four-state system (Figure 2a) enabled us
to realize two important and interwoven functions: On the one
hand, we were able to establish a light-induced pKa modulation of
Dꢃꢃꢀꢁꢂ = 2.8 ± 0.2 units between two thermally stable isomers. On
the other hand, we demonstrated base-catalyzed photochemical
ring-closure of DAE 1, thereby expanding the area of pH-gated
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to affect the excited-state energy surface and thus the dynamics
of the system. Currently, we are trying to decipher the underlying
reasons of the accelerated photocyclization in the deprotonated
species (1o). Future work will be devoted to further maximizing
the extent of light-induced pKa modulation and to shift the
operating pH to physiological conditions in order to harness the
systems to control biological processes. Furthermore, the use of
1o as a photoactive buffer to modulate the pH of an aqueous
solution will be investigated.
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10.1002/anie.201801270
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
J. Gurke, M. Quick, S. Kovalenko, S.
Budzak, B. M. Schmidt, D. Jacquemin,
S. Hecht*
Page No. – Page No.
Efficient Light-Induced pKa-
Modulation coupled to Base-
Catalyzed Photochromism
Text for Table of Contents
Switching a thermally stable acid on and off using visible and UV light, respectively, has been achieved offers many opportunities
to design photoresponsive supramolecular (bio)systems.
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