Tuning of the properties of rhodopsin-based molecular switches

Article abstract of DOI:10.1016/j.tetlet.2014.04.054

The modification of relevant chemical properties of rhodopsin-based molecular photoswitches is presented. We show how both the substituents present and the nitrogen atom quaternization are capable to change the wavelength of absorption and the thermal sta

Full text of DOI:10.1016/j.tetlet.2014.04.054

Tetrahedron Letters 55 (2014) 3361–3364
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Tetrahedron Letters
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Tuning of the properties of rhodopsin-based molecular switches
⇑
Marina Blanco-Lomas, David Martínez-López, Pedro J. Campos, Diego Sampedro
Departamento de Química, Centro de Investigación en Síntesis Química (CISQ), Universidad de La Rioja, Madre de Dios 51, 26006 Logroño, La Rioja, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The modification of relevant chemical properties of rhodopsin-based molecular photoswitches is pre-
sented. We show how both the substituents present and the nitrogen atom quaternization are capable
to change the wavelength of absorption and the thermal stability of the photoisomer. Adjusting these
properties, the molecular switches could be turned into useful compounds for solar energy storage
devices.
Received 27 March 2014
Revised 10 April 2014
Accepted 15 April 2014
Available online 24 April 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Photoswitches
Molecular devices
Solar energy storage
Photochemistry
Photophysics
Introduction
molecular photoswitch and the difference in energy between the
two states could be released once an energy barrier for the back-
In recent years, the use of molecular switches to control diverse
properties has become increasingly popular.1,2 Among the different
types of reported switches, photoswitches have received consider-
able attention due to practical advantages such as high temporal
and spatial resolution and lack of wastage products.3 Also, molec-
ular photoswitches can be subsequently divided into two main
classes: switches based on cyclization and E/Z isomerization.
Fulgides,4 diarylethenes,5 spiropyran compounds6 and dihydroazu-
lenes2 are molecular switches based on photocyclization processes,
while azobenzenes, overcrowded alkenes and retinal-based
switches are based on photoisomerizations.7 The use of these and
other molecular photoswitches has led to a number of amazing
applications of the photocontrol of different properties from poly-
mers8,9 to liquid crystals10 or peptide conformations.11 Most of
these applications rely on the use of light to interconvert the sys-
tem between two different states, although usually some thermal
reversion can also take place at different temperatures. Thus, the
uses of switches in applications that need the photoisomer to be
stable require higher temperatures to revert the isomerization.
Additionally, the two isomers may not be isoenergetic and the
temperature for interconversion may prevent or, at least, hamper
the back-reaction under certain conditions. If this can be achieved,
the switch could be used not only to affect a complex system, but
also to provide a potential use in its own as energy storage. Specif-
ically, the energy of a photon could be absorbed and stored in a
reaction is surmounted. If the absorbed light is solar energy, the
switch turns into a solar energy storage device. This concept is
called Molecular Solar Thermal system (MOST) and it has gained
some attention in the last years as an alternative to other energy
conversion systems due to its functioning as a closed cycle and lack
of emissions.12 Stilbene-like molecules,13 fulvalene ruthenium
complexes,14 and norbornadienes15 have already been explored
as MOST energy storages.
We have been involved in a long term effort to design,16,17 syn-
thesize18–21 and characterize22 diverse molecular photoswitches.
Herein we report how a well-known type of molecular switch
could be tuned to act as a part of a MOST system. Specifically, we
prepared diverse derivatives of
a rhodopsin-based molecular
photoswitch in order to adjust their properties.
We based our study on the methylated and protonated versions
of the previously reported rhodopsin-based molecular switches 1–
4 (Scheme 1).19 These compounds were prepared through an expe-
dient and versatile synthetic route. In all cases, the E isomer was
found to be the more stable isomer. Irradiation of the switches
between 1 and 3 h at 270–300 nm produced the photoisomeriza-
tion under the reaction conditions (immersion well, medium-
pressure Hg lamp, Pyrex filter). Also, the photoswitches could be
reset after heating. These features turned the rhodopsin-based
compounds into promising candidates for their use as photos-
witches in diverse applications. Taking these compounds as
starting points, we tried to modify the properties of these
molecules to explore the possibility to turn them into potential
candidates for MOST systems. To do this, the features required to
⇑
Corresponding author. Tel.: +34 941299647.
E-mail address: diego.sampedro@unirioja.es (D. Sampedro).
http://dx.doi.org/10.1016/j.tetlet.2014.04.054
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

3362
M. Blanco-Lomas et al. / Tetrahedron Letters 55 (2014) 3361–3364
O
O
Ph
PO(OEt)2
Ph
R1
Ph
PPh3
R1CHO
N
R1
N3
N3
1-4
Scheme 1. Retrosynthesis of rhodopsin-based photoswitches.
Table 1
be changed are the wavelength of absorption and the thermal sta-
bility. First, in order to act as a MOST system, the chromophore
should absorb substantially in the visible region of the spectrum.
Second, the back-reaction should take place only when needed
and thus, thermal relaxation should be minimized at low temper-
atures. These two modifications were addressed separately. Also,
the kinetics of photoisomerization for the derivatives were
assessed. Additionally, theoretical calculations were performed in
order to provide the required background for further development.
Synthesized methylated derivatives*
Neutral compound
R1
Derivative
Yield (%)
1
2
3
4
Ph
p-MeOPh
p-NO2Ph
5
6
7
8
95
90
97
85
2-Naphthyl
*
Protonated derivatives 9–11 were formed quantitatively.
acetonitrile. The obtained spectra for each compound were plotted
in the same graph as the spectrum of their corresponding neutral
compound. In Figure 1, the UV–vis spectra of compounds 1 and 5
are represented. As can be seen, a bathochromic shift of the maxi-
Results and discussion
Two main modifications were considered in order to prepare
derivatives suitable for acting as MOST systems, R1 substitution
and nitrogen atom quaternization. Modification of the substituent
present in R1 has been shown to have an effect on different prop-
erties of these molecules acting as molecular switches, as the
Photostationary State (PSS) and the thermal stability. However,
the influence of R1 on the wavelength of absorption is small.19
On the other hand, it is well-known the influence of the quatern-
ization on the photophysics of the rhodopsin and rhodopsin-based
molecules.23 A red-shift of the absorption band is usually found
when comparing the quaternized salts with the neutral analogues.
Thus, we explored these two types of modifications in order to
tune the properties of these molecules to match the MOST system
requirements.
Starting from the neutral molecular switches previously synthe-
sized,19 we prepared new compounds by quaternization of the
nitrogen atom of the imine bond. To this purpose, protonation or
methylation of diverse compounds with substituents of the aro-
matic ring with different electronic properties was carried out by
adding one equivalent of tetrafluoroboric acid (HBF4) or methyl tri-
flate (CF3SO3CH3). For the methylated analogues 5–8, after the
addition of the triflate in dry toluene, the iminium salt precipitates
and can be easily isolated from the filtrate. For the protonated
derivatives 9–11, the addition of one equivalent of acid led to the
quantitative formation of the salt as determined by 1H NMR. In this
case, the use of different acids such as triflic acid (CF3SO3H) or HCL
causes an analogous effect as previously shown in similar com-
pounds.21 Results are shown in Chart 1 and Table 1.
mum of the absorption band (Dkmax = 45 nm) when methylating 1
is observed. Similar results were obtained for 2–4 and their meth-
ylated analogues 6–8 (see Supplementary material). Interestingly,
the protonated derivatives 9–11 share all the features with the
methylated compounds. This implies that the quaternization of
the switches yields different compounds, under different reaction
conditions but with the same properties. In turn, this would
be of practical importance for the implementation of these
compounds as applied systems.
After analysing the UV–vis spectra of the quaternized ana-
logues, we proceeded to irradiate them. To compare the isomeriza-
tion process of the neutral and methylated compounds, similar
graphs were obtained for the isomerization of the neutral and
methylated compounds. The results obtained are summarized in
the following Table 2 (see Supplementary material). Again, the pro-
tonated compounds 9–11 yielded a PSS with the same composition
than the methylated analogues.
From these results, we can deduce that in all cases the percent-
age of the Z isomer (photochemically obtained isomer) at the PSS is
higher when the compounds are in their neutral form than when
0,8
1
5
334
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0,0
289
Prior to the irradiation of these methylated and protonated
compounds, their UV–vis spectra were recorded to compare the
results obtained to the UV–vis spectra of the neutral compounds.
Therefore, we prepared 10À5 M solutions of compounds 5–8 in
Ph
Ph
Ph
H
N
N
N
R1
R1
R1
R1 = Ph 5
= p-MeOPh 6
= p-NO2Ph 7
= 2-Naphthyl 8
R1 = Ph 1
= p-MeOPh 2
= p-NO2Ph 3
= 2-Naphthyl 4
R1 = Ph 9
= p-NO2Ph 10
225
250
275
300
325
350
375
= 2-Naphthyl 11
Wavelenght (nm)
Figure 1. UV–vis spectra of 1 and 5 in acetonitrile.
Chart 1. Studied compounds.

M. Blanco-Lomas et al. / Tetrahedron Letters 55 (2014) 3361–3364
3363
Table 2
stabilization for the cationic species. Table 3 shows some of the
data obtained (see Supplementary material).
PSS and relative ratios for neutral and quaternized switches
**
Compound
E isomer* (%)
Z isomer* (%)
kmet/neutral
A qualitative agreement between the experimental and the
computed bands was found. In all cases, the computed bands are
red-shifted by 20–30 nm with respect to the experimental bands.
Again, the protonated and methylated derivatives show the same
behaviour, with the low-energy absorption band caused by the
HOMO–LUMO transition (see Supplementary material). In all
cases, this transition implies the displacement of electron density
from the HOMO (mainly located at the R1 substituent) to the LUMO
(located at the pyrroline moiety). In addition, in order to under-
stand the different thermal behaviour of 1 and 4, we also computed
the transition structures (TS’s) for the thermal conversion (Fig. 2,
see Supplementary material).
1
5
2
6
3
7
4
8
70
90
56
68
34
40
48
75
30
10
44
32
66
60
52
25
1.5
1.4
1.1
1.2
*
Isomers ratio at the photostationary state. For the protonated compounds 9–11
the same results were obtained.
**
Relative kinetic constants (kmet/neutral).
Interestingly, both TS’s share similar geometrical features
although small differences can account for the diverse experimen-
tal outcome. In both cases, the TS features a twisting along the cen-
tral C@C bond (74° vs 57°) that causes the molecule to divide into
two halves. The second aromatic ring in 4 causes an extended con-
jugation in the naphthyl moiety that leads to an increased C–C dis-
tance. This fact, in turn, causes a bigger destabilization in the
structure as the initial C@C bond is more distorted. Thus, a TS
higher in energy was found (57.6 kcal/mol for 1, 71.8 kcal/mol for
4) causing that the thermal back-reaction is hampered when R1
is naphthyl. It should be noted that the computed energy barriers
are too high. This may be due to the performance of the theoretical
level. The energy barriers for the methylated derivatives 5 and 8
follow the same trend with barriers of 53.4 kcal/mol and
69.6 kcal/mol, respectively.
they are quaternized. From the linear relationship between the
first points of each graph for each pair of compounds (representing
ln[A0]/[A] vs irradiation time and doing a linear fit), we can calcu-
late the values for the kinetic constants of each process, and there-
fore, the value of the relative kinetic constant that relates the rate
of both processes (see Table 2). In all cases, being the kinetic con-
stant for the neutral compounds kneutral = 1, we noticed that the
E?Z isomerization process for the quaternized compounds is
approx. 1.5 times faster than the E?Z reaction for the neutral
compounds. Therefore, methylation of the photoswitches caused
only a mild acceleration of the isomerization reaction rate.
We then checked the thermal stability of the quaternized com-
pounds. We measured the back-reaction of the irradiated samples
for both the methylated and protonated derivatives. For the deriv-
atives of 5–7, the reversion to the thermodynamically stable E iso-
mer takes place within hours. Clearly, these results would imply a
serious drawback in practical applications that require a delayed
energy liberation at rt. Interestingly, for 8 and 11 no back reaction
was detected by 1H NMR in 6 days. However, the E isomer recovery
could be easily performed by heating the sample at 60 °C. In this
case, the energy barrier prevents relaxation from the higher to
the lower energy isomer, exactly as the functioning of the MOST
systems require.
Conclusions
We have shown that small modifications in the general struc-
ture of a series of rhodopsin-based molecular photoswitches can
alter their properties to match the requirements of MOST systems.
Interestingly, the nitrogen atom quaternization and the substitu-
tion can be used to independently modify both the regions on
the spectrum in which these molecules absorb and the barrier
for reversion. This approach has proven useful in the preparation
of compounds subject to taking part in technological devices. Fur-
ther studies to design, synthesize and characterize new candidates
for MOST systems are currently underway.
In order to understand the changes made in the chromophore
upon quaternization we performed some density functional theory
calculations on the tested compounds. This will be helpful also in
the rational design of new compounds with specific properties.
We started by computing 1 using B3LYP with the standard basis
set 6-31G* and acetonitrile as the solvent through the Polarizable
Continuum Model (PCM) method (see Supplementary material).
The inclusion of solvent is not critical for the neutral compounds,
but it is required to take into account the effect of charge
Experimental section
The methylated photoswitches were synthesized as follows: To
a solution of the neutral photoswitch (1 equiv) in dry toluene
(2 ml), under nitrogen atmosphere, was added methyl triflate CF3-
SO3CH3 (1 equiv). The resulting mixture was stirred vigorously for
Table 3
Experimental and computed absorption bands (nm)
Compound
Experimental
Computed
1
5
9
2
6
3
7
10
4
289
334
334
304
371
335
337
337
311
324
350
415
350
415
305
360
359
326
393
388
370
366
318
340
370
438
370
439
8
11
Figure 2. Computed transition structures and displacement vectors for the thermal
conversion for 1 (left) and 4.

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This research was supported by the Spanish Ministerio de
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Supplementary data
Supplementary data (experimental procedures, characteriza-
tion data and Cartesian coordinates for the computed geometries)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2014.04.054.
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