An efficient approach to diarylethene-amino acid photochromic fluorescent hybrids

Article abstract of DOI:10.1016/j.molstruc.2021.130758

An effective approach to the synthesis of diarylethene-amino acid hybrids DE-Gly, DE-AABA and DE-DAA (5a-d - 7-a-d) was developed via condensation of furan-2,5-dione-based diarylethenes (DE) and ethyl esters of glycine (Gly), α-aminobutyric acid (AABA) and D-aspartic acid (DAA) with moderate to good yields. According to X-ray diffraction data, DE-Gly hybrid 5a exists in an antiparallel conformation with a distance of 4.549 ? between the reactive carbon atoms C(1)-C(11), potentially capable of forming a single bond, which is suitable for the conrotatory photocyclization reaction allowed by the Woodward-Hoffman rules. The structures of the obtained compounds were proved by ¹H, COZY, HSQC, HMBC and ¹³C NMR spectroscopy. The hybrids DE-Gly, DE-AABA and DE-DAA absorb at 443–456 nm, which corresponds to their existence in a ring-open form O, and display fluorescence at 531–612 nm. Irradiation with light of 436 nm results in their rearrangement into ring-closed colored nonfluorescent isomers C. Backwards re-opening occurs under the action of visible light (λ > 500 nm). Spectral kinetic investigation of 5a,c revealed that the efficiency of photocyclization, as well as the emission quantum yield, decreases with the growth of solvent polarity. The ring-closed isomer C of sterically hindered 5a (R² = R³ = Me) is stable at room temperature, whereas for 5c (R³ = H), ring opening readily occurs with the speed increasing with the polarity of the solvent. The internal emission of sterically hindered hybrids 5a, 6a and 7a (R² = R³ = Me) is reversibly modulated in a binary response with good fatigue resistance under successive irradiation with light of 436 and 540 nm.

Full text of DOI:10.1016/j.molstruc.2021.130758

Journal of Molecular Structure 1243 (2021) 130758
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
An efficient approach to diarylethene-amino acid photochromic
fluorescent hybrids
Vitaly А. Podshibyakina, Еvgenii N. Shepelenkob, Olga Yu. Karlutovaa,
Lyudmila G. Kuzminac, Alexander D. Dubonosovb,∗, Vladimir A. Brena, Vladimir I. Minkina
a Institute of Physical and Organic Chemistry, Southern Federal University, Rostov on Don 344090, Russian Federation
b Federal Research Centre the Southern Scientific Centre of the Russian Academy of Sciences, Rostov on Don 344006, Russian Federation
c Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Moscow 117901, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
An effective approach to the synthesis of diarylethene-amino acid hybrids DE-Gly, DE-AABA and DE-DAA
(5a-d - 7-a-d) was developed via condensation of furan-2,5-dione-based diarylethenes (DE) and ethyl
esters of glycine (Gly), α-aminobutyric acid (AABA) and D-aspartic acid (DAA) with moderate to good
yields. According to X-ray diffraction data, DE-Gly hybrid 5a exists in an antiparallel conformation with a
Received 18 February 2021
Revised 20 May 2021
Accepted 21 May 2021
Available online 27 May 2021
˚
distance of 4.549 A between the reactive carbon atoms C(1)-C(11), potentially capable of forming a single
bond, which is suitable for the conrotatory photocyclization reaction allowed by the Woodward-Hoffman
rules. The structures of the obtained compounds were proved by 1H, COZY, HSQC, HMBC and 13 C NMR
spectroscopy. The hybrids DE-Gly, DE-AABA and DE-DAA absorb at 443–456 nm, which corresponds to
their existence in a ring-open form O, and display fluorescence at 531–612 nm. Irradiation with light
of 436 nm results in their rearrangement into ring-closed colored nonfluorescent isomers C. Backwards
re-opening occurs under the action of visible light (λ > 500 nm). Spectral kinetic investigation of 5a,c
revealed that the efficiency of photocyclization, as well as the emission quantum yield, decreases with
the growth of solvent polarity. The ring-closed isomer C of sterically hindered 5a (R2 = R3 = Me) is
stable at room temperature, whereas for 5c (R3 = H), ring opening readily occurs with the speed increas-
ing with the polarity of the solvent. The internal emission of sterically hindered hybrids 5a, 6a and 7a
(R2 = R3 = Me) is reversibly modulated in a binary response with good fatigue resistance under succes-
sive irradiation with light of 436 and 540 nm.
Keywords:
Diarylethene
Amino acids
Photochromism
Fluorescence
X-ray diffraction
© 2021 Elsevier B.V. All rights reserved.
1. Introduction
ological molecules or pharmacophore groups is the most obvious
chemical method for obtaining photocontrolled hybrid systems. In
The design and synthesis of multifunctional systems contain-
ing both bioactive and photochromic moieties constitute an ur-
gent task in the field of medicine as well as in the field of in-
dustrial technology [1-5]. The main goal of creating such hybrids
is to control the biological activity of molecules using light. It is
well known that light is normally non-invasive and does not cause
contamination of a biological sample. The wavelength and inten-
sity of the irradiation can be adjusted in a wide range with great
precision. However, light can affect the pharmacokinetic or phar-
macodynamic properties of certain molecules. The combination of
photochemistry and pharmacology within a single molecule pre-
determined a new branch of chemistry – photopharmacology [6-
9]. Functionalization of bistable photochromic compounds by bi-
this regard, azobenzene derivatives capable of reversible trans/cis
photoisomerization are the most studied photo switches. Their bio-
conjugates with peptides, proteins and nucleic acids were obtained
and investigated [10,11]. However, they have at least two signif-
icant drawbacks: the absorption spectra of trans and cis isomers
overlap substantially, and the emission properties are either absent
or poorly expressed.
From this point of view, diarylethenes (DE) capable of reversible
changing their configuration, absorption spectra, and fluorescent
properties under irradiation, as well as possessing effective fatigue
resistance and high thermal stability in both open and cyclic iso-
mers, are very attractive for biological applications [12-16]. The
mechanism of their light-induced transformation consists of the
hexatriene-cyclohexadiene rearrangement of the ring-open isomer
into the ring-closed form. The geometry of the DE molecule is cru-
cial for the efficiency of this process [12,14]. First, and most im-
∗
Corresponding author.
E-mail address: aled@ipoc.sfedu.ru (A.D. Dubonosov).
https://doi.org/10.1016/j.molstruc.2021.130758
0022-2860/© 2021 Elsevier B.V. All rights reserved.

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
portantly, X-ray diffraction analysis showed that heterocyclic sub-
stituents attached to the bridged fragment of DE must have an
antiparallel conformation, providing the conrotatory cyclization al-
lowed by the Woodward-Hoffman rules, while DE having a parallel
conformation are nonreactive [17-20]. Secondly, when the distance
was solved by direct methods and refined with anisotropic ther-
mal parameters for all non-hydrogen atoms. Position of hydrogen
atoms was calculated and refined using a riding model. All calcu-
lations were performed by Olex-2 software [33,34].
CCDC 2,009,312 contains the supplementary crystallographic
data for 5a. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cam-
bridge Crystallographic Data center, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: (+44) 1223–336–033; or by e-mail: de-
posit@ccdc.cam.ac.uk.
˚
between the reactive carbon atoms is about 4.20 A photocycliza-
tion can occur even in the crystal molecules [21]. However, the
upper limit of this distance is not too critical. In any case, even
˚
at 4.62 A, the photocyclization of DE in solutions is quite effective
[22].
In this study, we chose furan-2,5-dione-bridged DE capable of
transformation into 1-substituted pyrrole-2,5-diones, which them-
selves possess biological activity, and their derivatives are capable
of sensing some vital ions [23-27]. Amino acids seem most suit-
able for developing a new synthetic method for creating photo-
controlled bioactive hybrids. Glycine (Gly) is the simplest and at
the same time a major amino acid. It plays an important role in
protein synthesis and is a precursor for the synthesis of biologi-
cally important substances such as porphyrins, heme and purines
[28]. α-Aminobutyric acid (AABA) is a non-proteinogenic amino
acid formed in living organisms during protein metabolism. It was
recently discovered that AABA modulates glutathione homeostasis
in the myocardium [29]. D-Aspartic acid (DAA) plays an important
role in the metabolism of nitrogenous substances, participates in
the formation of pyrimidine bases and urea, and is an endogenous
neurotransmitter [30]. In addition, all three amino acids are used
to some extent in pharmaceutical substances.
2.3. General procedure for the synthesis of DE-Gly (5a-d), de-aaba
(6a-d) and de-daa (7a-d) hybrids
NaHCO3 (0.5 g, 6 mmol) was added with intensive stirring to
a solution of ethyl ester hydrochloride of glycine, α-aminobutyric
or d-aspartic acid (3 mmol) in CH2Cl2 (10 mL) and H2O (10 mL)
at 0–5 °C and pH = 7 and left for 30 min. The organic layer was
separated and dried with Na2SO4. A solution of the correspond-
ing furan-2,5-done-bridged DE [35,36] 4a-d (0.5 mmol) in EtOH
(30 mL) was added to the obtained reaction mixture. The solution
was evaporated to 20 mL and then heated at reflux for 6 h. The
solvent was removed with a rotary evaporator. The residue was pu-
rified by column chromatography (sorbent SiO2, eluent CHCl3) and
recrystallized from EtOH.
Thus, the purpose of this work was to incorporate ethyl esters
of glycine, α-aminobutyric acid and D-aspartic acid into the furan-
2,5-dione-bridged DE moiety and to investigate the structure, spec-
tral, luminescent and photochromic properties of the obtained DE-
Gly, DE-AABA and DE-DAA hybrid compounds.
2.4. Ethyl
2-(3-(2,5-dimethylthiophen-3-yl)−4-(5–methoxy-1,2-dimethyl-1H-
indol-3-yl)−2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetate
(5a)
2. Experimental
2.1. General
The 1H, COZY, HSQC, HMBC and 13C NMR spectra were
recorded on integrated analytical LC-SPE-NMR-MS system AVANCE-
600 (Bruker) (600 MHz, 1Н; 150.96 MHz for 13С) in CDCl3. The
signals were referred with respect to the signals of residual pro-
tons of deutero-solvent (7.24 ppm). The IR spectra were recorded
on a Varian Excalibur 3100 FT-IR instrument using the attenu-
ated total internal reflection technique (ZnSe crystal). The elec-
tronic absorption spectra were obtained on a Varian Cary 100
spectrophotometer. The electronic emission spectra were recorded
on a Varian Cary Eclipse spectrofluorimeter. The solutions were
irradiated in a quartz cell (l = 1 cm) with filtered light of a
high pressure Hg lamp on a Newport 66,941 equipment supplied
with a set of interferential light filters. The intensity of light was
3.1•1016 photons•s−1 for the spectral line 436 nm. The fluores-
cence quantum yields were determined by the Parker-Rees method
using 3-methoxybenzanthrone in toluene (ϕ = 0.1) as a standard
luminophore [31]. Hexane, toluene, acetonitrile and methanol of
spectroscopic grade (Aldrich) were used to prepare solutions. Ele-
mental analysis was carried out using a KOVO CHN analyzer. Melt-
ing points were determined on a PTP (M) instrument.
Yield 0.14 g (60%), orange powder, mp 135–137 °C. IR νmax
(cm−1): 1622 (C=С), 1703 (C = O), 1754 (C = O). 1H NMR (CDCl3)
ꢀ
ꢀ
δ (ppm): 1.28 (t, 3Н, J = 7.2 Hz, 10 ’-Me), 1.69 (s, 3Н, 7 -Me), 2.33
ꢀ
(s, 3Н, 10-Me), 2.37 (s, 3Н, 6 -Me), 3.55 (s, 3Н, 8-OMe), 3.66 (s, 3Н,
ꢀ
ꢀ
9-Me), 4.22 (q, 2Н, J = 7.2 Hz, 9 ’-CH2), 4.38 (s, 2Н, 6 ’-CH2), 6.35–
6.36 (m, 1H, 4-CH), 6.75 (dd, 1H, J = 8.4 Hz, H Ar, 6/7-CH), 6.83
ꢀ
2.2. X-ray diffraction study
(s, 1H, 4 -CH), 7.09 (d, 1H, J = 8.4 Hz, 6/7-CH). 13C NMR (CDCl3) δ
ꢀ
ꢀ
ꢀ
(ppm): 12.67 (10-C), 14.11 (10 ’-C), 14.89 (7 -C), 15.03 (6 -C), 29.66
ꢀ
ꢀ
A single crystal of DE 5a suitable for X-ray structure deter-
mination was mounted on a Bruker CCD area SMART APEX-II
diffractometer under a stream of cooled nitrogen, where crystallo-
graphic parameters and intensities of X-ray reflections were mea-
(3-C), 30.01 (9-C), 39.30 (6 ’-C), 55.29 (8-C), 61.66 (9 ’-C), 101.54
ꢀ
(4-C), 109.61 (6/7-C), 112.09 (6/7-C), 126.02 (4а-C), 126.46 (4 -C),
127.47 (5 -C), 130.15 (3 ’-C), 132.11 (7а-C), 133.70 (2 -C), 136.46 (4 ’-
C), 139.08 (3 -C), 139.47 (2-C), 154.54 (5-C), 167.66 (7 ’-C), 170.49
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
˚
sured [150 K, Mo-K radiation (λ = 0.71073 A), ω scan mode]. Data
(2 ’, 5 ’-C), 170.68 (2 ’, 5 ’-C). Anal. Calcd (%) for C25H26N2O5S: C,
α
reduction was performed using SAINT program [32]. The structure
64.36; H, 5.62; N, 6.00. Found: C, 64.31; H, 5.55; N, 6.09.
2

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
2.5. Ethyl 2-(3-(1-benzyl-5–methoxy-2-methyl-1H-indol-3-yl)−4-(2,5-
dimethylthiophen-3-yl)−2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetate
(5b)
2.7. Ethyl 2-(3-(1-benzyl-5–methoxy-2-methyl-1H-indol-3-yl)−2,5-
dioxo-4-(thiophen-3-yl)−2,5-dihydro-1H-pyrrol-1-yl)acetate
(5d)
Yield 0.20 g (79%), red powder, mp 120–122 °C. IR νmax (cm−1):
1618 (C=С), 1715 (C = O), 1744 (C = O). 1H NMR (CDCl3) δ (ppm):
ꢀ
Yield 0.13 g (46%), orange powder, mp 148–150 °C. IR νmax
(cm−1): 1619 (C=С), 1702 (C = O), 1754 (C = O). 1H NMR (CDCl3)
1.28 (t, 3Н, J = 7 Hz, 10 ’-Me), 2.27 (s, 3Н, 16-Me), 3.55 (s, 3Н,
ꢀ
ꢀ
8-Me), 4.22 (q, 2Н, J = 7 Hz, 9 ’-СН2), 4.40 (s, 2Н, 6 ’-СН2), 5.32
(s, 2Н, 9-СН2), 6.48–6.49 (m, 1H, 4-H Ar), 6.74–6.76 (m, 1H, 6/7-H
Ar), 7.01–7.02 (m, 2H, H Ar), 7.10–7.14 (m, 2H, H Ar), 7.19–7.20 (m,
1H, H Ar), 7.23–7.25 (m, 1H, H Ar), 7.28–7.30 (m, 2H, H Ar), 8.06–
8.07 (m, 1H, H Ar). 13C NMR (CDCl3) δ (ppm): 12.71 (16-C), 14.11
ꢀ
ꢀ
δ (ppm): 1.28 (t, 3Н, J = 7 Hz, 10 ’-Me), 1.73 (s, 3Н, 7 -Me), 2.24
ꢀ
(s, 3Н, 16-Me), 2.37 (s, 3Н, 6 -Me), 3.56 (s, 3Н, 8-Me), 4.21 (q, 2Н,
ꢀ
ꢀ
J = 7 Hz, 9 ’-СН2), 4.39 (s, 2Н, 6 ’-СН2), 5.28 (s, 2Н, 9-СН2), 6.42–
ꢀ
6.43 (m, 1H, 4-H Ar), 6.68–6.72 (m, 1H, 6/7-H Ar), 6.84 (s, 1H, 4 -
ꢀ
ꢀ
H Ar), 6.94–6.96 (m, 2H, 14/15-H Ar), 7.03–7.06 (m, 1H, 6/7-H Ar),
7.18–7.22 (m, 1H, 13-H Ar), 7.27–7.29 (m, 2H, 11/12-H Ar). 13C NMR
(10 ’-C), 29.66 (3-C), 39.24 (6 ’-C), 47.06 (9-C), 55.52 (8-C), 61.73
ꢀ
(9 ’-C), 102.44, 102.79, 110.37, 112.18, 124.97, 125.94, 125.94, 126.27,
ꢀ
ꢀ
ꢀ
(CDCl3) δ (ppm): 12.57 (16-C), 14.11 (10 ’-C), 14.89 (7 -C), 15.05 (6 -
127.57, 127.70, 128.91, 129.24, 129.59, 130.61, 130.71, 132.18, 136.84,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
C), 29.66 (3-C), 39.31 (6 ’-C), 47.00 (9-C), 55.31 (8-C), 61.68 (9 ’-C),
101.67 (4-C), 103.79, 110.18 (6/7-C), 112.42 (6/7-C), 125.87, 125.87,
126.24, 126.39, 127.40, 127.55, 128.86, 130.79, 131.81, 133.64,
139.01, 154.73, 167.60 (7 ’-C), 170.46 (2 ’/5 ’-C), 170.64 (2 ’/5 ’-C).
Anal. Calcd (%) for C29H26N2O5S%: C, 67.69; H, 5.09; N, 5.44. Found:
C, 67.62; H, 4.99; N, 5.49.
ꢀ
ꢀ
ꢀ
136.60, 136.75, 139.15, 139.24, 154.69, 167.64 (7 ’-C), 170.37 (2 ’/5 ’-
ꢀ
ꢀ
2.8. Ethyl
C), 170.62 (2 ’/5 ’-C). Anal. Calcd (%) for C31H30N2O5S: C, 68.61; H,
2-(3-(2,5-dimethylthiophen-3-yl)−4-(5–methoxy-1,2-dimethyl-1H-
indol-3-yl)−2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoate
(6a)
5.57; N, 5.16. Found: C, 68.65; H, 5.65; N, 5.09.
Yield 0.13 g (53%), orange powder, mp 112–113 °C. IR νmax
(cm−1): 1620 (C=С), 1698 (C = O), 1750 (C = O). 1H NMR (CDCl3)
δ (ppm): 0.99 (t, 3Н, J = 6.6 Hz, Me), 1.26 (t, 3Н, J = 6.6 Hz,
Me), 1.69 (s, 3Н, Me), 2.25 (q, 2Н, J = 6.6 Hz, CH2), 2.32 (s, 3Н,
Me), 2.36 (s, 3Н, Me), 3.55 (s, 3Н, Me), 3.65 (s, 3Н, Me), 4.19–
4.21 (m, 2H, CH2), 4.69 (t, 1H, J = 7.2 Hz, CH), 6.35 (s, 1H, H
Ar), 6.74 (d, 1H, J = 8.4 Hz. H Ar), 6.84 (s, 1H, H Ar), 7.09 (d,
1H, J = 8.4 Hz, H Ar). 13C NMR (CDCl3) δ (ppm): 11.10, 12.71,
14.13, 14.90, 15.01, 22.34, 29.65, 30.00, 54.18, 55.30, 61.51, 101.63,
109.59, 111.97, 126.04, 126.49, 127.52, 129.73, 132.11, 133.26, 136.42,
139.01, 139.44, 154.50, 169.66, 170.73, 171.01. Anal. Calcd (%) for
C27H30N2O5S: C, 65.57; H, 6.11; N, 5.66. Found: C, 65.51; H, 6.16;
N, 5.71.
2.6. Ethyl 2-(3-(5–methoxy-1,2-dimethyl-1H-indol-3-yl)−2,5-dioxo-4-
(thiophen-3-yl)−2,5-dihydro-1H-pyrrol-1-yl)acetate
(5c)
2.9. Ethyl 2-(3-(1-benzyl-5–methoxy-2-methyl-1H-indol-3-yl)−4-(2,5-
dimethylthiophen-3-yl)−2,5-dioxo-2,5-dihydro-1H-pyrrol-1-
yl)butanoate
Yield 0.19 g (87%), orange powder, mp 114–116 °C. IR νmax
(cm−1): 1615 (C=С), 1713 (C = O), 1758 (C = O). 1H NMR (CDCl3)
(6b)
ꢀ
δ (ppm): 1.28 (t, 3Н, J = 7 Hz, 10 ’-Me), 2.35 (s, 3Н, 10-Me),
Yield 0.13 g (45%), orange powder, mp 73–76 °C. IR νmax
3.50 (s, 3Н, 8-Me), 3.70 (s, 3Н, 9-Me), 4.23 (q, 2Н, J = 7 Hz,
(cm−1): 1622 (C=С), 1699 (C = O), 1748 (C = O). 1H NMR (CDCl3)
δ (ppm): 0.99 (t, 3Н, J = 6.6 Hz, Me), 1.25 (t, 3Н, J = 6.6 Hz, Me),
1.75 (s, 3Н, Me), 2.26–2.27 (m, 5Н, CH2, Me), 2.37 (s, 3Н, Me), 3.57
(s, 3Н, Me), 3.80–3.85 (m, 2Н, CH2), 4.19–4.22 (m, 1Н, СН), 4.19–
4.21 (m, 2H, CH2), 4.69 (t, 1H, J = 7.2 Hz, CH), 5.29 (m, 2Н, CH2),
6.44 (s, 1H, H Ar), 6.70 (d, 1H, J = 8.4 Hz, H Ar), 6.85 (s, 1H, H
Ar), 6.96–6.98 (m, 2H, H Ar), 7.04–7.06 (m, 1H, H Ar), 7.13 (d, 1H,
J = 8.4 Hz, H Ar), 7.22–7.24 (m, 2H, H Ar). 13C NMR (CDCl3) δ
(ppm): 11.12, 12.62, 14.14, 14.90, 15.03, 29.66, 40.94, 47.00, 54.21,
ꢀ
ꢀ
9 ’-СН2), 4.39 (s, 2Н, 6 ’-СН2), 6.35–6.36 (m, 1H, 4-H Ar), 6.76–
6.80 (m, 1H, 6/7-H Ar), 7.11–7.19 (m, 3H, H Ar), 8.02–8.03 (m,
ꢀ
1H, H Ar). 13C NMR (CDCl3) δ (ppm): 12.81 (10-C), 14.11 (10 ’-C),
ꢀ
ꢀ
29.67 (3-C), 30.05 (9-C), 39.24 (6 ’-C), 55.51 (8-C), 61.72 (9 ’-C),
102.09, 102.41(4-C), 109.83, 111.88, 124.82, 125.93, 127.88, 129.00,
ꢀ
ꢀ
ꢀ
130.70, 130.83, 132.47, 139.22, 154.57, 167.63 (7 ’-C), 170.60 (2 ’/5 ’-
ꢀ
ꢀ
C), 170.73 (2 ’/5 ’-C). Anal. Calcd (%) for C23H22N2O5S: C, 63.05; H,
5.05; N, 6.39. Found: C, 63.00; H, 4.99; N, 6.45.
3

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
55.32, 61.53, 101.75, 103.26, 110.18, 112.30, 125.89, 125.89, 126.26,
126.43, 127.47, 127.56, 128.87, 130.39, 131.83, 133.22, 136.58,
136.77, 139.11, 139.23, 154.67, 169.65, 170.65, 170.97. Anal. Calcd
(%) for C33H34N2O5S: C, 69.45; H, 6.00; N, 4.91. Found: C, 69.51;
H, 6.14; N, 4.88.
2.36 (s, 3Н, Me), 3.09–3.13 (m, 1Н, СН2), 3.31–3.35 (m, 1Н, СН2),
3.57 (s, 3Н, Me), 4.14–4.23 (m, 4H, 2CH2), 5.28 (s, 2H, CH2), 6.42
(br. s, 1H, H Ar), 6.70–6.71 (m, 1H, H Ar), 6.83 (s, 1H, H Ar),
6.95–6.99 (m, 2H, H Ar), 7.04–7.05 (m, 1H, H Ar), 7.13–7.14 (m,
1H, H Ar), 7.23–7.25 (m, 2H, H Ar). 13C NMR (CDCl3) δ (ppm):
12.61, 14.07, 14.14, 14.90, 15.03, 29.66, 34.43, 47.01, 48.87, 55.31,
60.90, 62.11, 101.68, 103.26, 110.21, 112.39, 125.89, 125.90, 126.23,
126.38, 127.36, 127.58, 128.88, 130.55, 131.82, 133.46, 136.63,
136.74, 139.23, 139.33, 154.70, 168.57, 170.13, 170.13, 170.39. Anal.
Calcd (%) for C35H36N2O7S: C, 66.86; H, 5.77; N, 4.46. Found: C,
66.80; H, 5.71; N, 4.53.
2.10. Ethyl 2-(3-(5–methoxy-1,2-dimethyl-1H-indol-3-yl)−2,5-dioxo-
4-(thiophen-3-yl)−2,5-dihydro-1H-pyrrol-1-yl)butanoate
(6c)
Yield 0.12 g (51%), red powder, mp 122–123 °C. IR νmax (cm−1):
1622 (C=С), 1710 (C = O), 1747 (C = O). 1H NMR (CDCl3) δ (ppm):
1.00 (t, 3Н, J = 7.2 Hz, Me), 1.25 (br. s, 3Н, Me), 2.25 (q, 2Н,
J = 6.6 Hz, CH2), 2.35 (s, 3Н, Me), 3.52 (s, 3Н, Me), 3.69 (s, 3Н,
Me), 4.20–4.21 (m, 2H, CH2), 4.69–4.72 (m, 1H, CH), 6.36–6.39 (m,
1H, H Ar), 6.78–6.80 (m, 1H, H Ar), 7.11–7.21 (m, 3H, H Ar) 8.04
(br. s, 1H, H Ar). 13C NMR (CDCl3) δ (ppm): 11.09, 12.84, 14.13,
22.24, 22.36, 29.66, 30.04, 54.11, 55.53, 61.57, 102.54, 109.82, 111.75,
124.79, 127.93, 128.54, 129.04, 130.47, 130.73, 132.49, 139.24,
154.55, 169.63, 170.84, 171.00. Anal. Calcd (%) for C25H26N2O5S: C,
64.36; H, 5.62; N, 6.00. Found: C, 64.31; H, 5.54; N, 6.09.
2.14. Diethyl 2-(3-(5–methoxy-1,2-dimethyl-1H-indol-3-yl)−2,5-
dioxo-4-(thiophen-3-yl)−2,5-dihydro-1H-pyrrol-1-yl)succinate
(7c)
Yield 0.16 g (59%), orange powder, mp 134–136 °C. IR νmax
(cm−1): 1618 (C=С), 1704 (C = O), 1736 (C = O). 1H NMR (CDCl3)
δ (ppm): 1.23–1.24 (m, 6Н, Me), 2.33–2.35 (m, 3Н, Me), 3.11 (br.
s, 1Н, СН2), 3.31–3.34 (m, 1Н, СН2), 3.51 (s, 3Н, Me), 3.68 (s, 3Н,
Me), 4.13–4.21 (m, 4H, 2CH2), 5.31–5.33 (m, 1H, CH), 6.33–6.39
(m, 1H, H Ar), 6.77–6.79 (m, 1H, H Ar), 7.12–7.19 (m, 3H, H Ar),
8.03 (br. s, 1H, H Ar). 13C NMR (CDCl3) δ (ppm): 12.28, 12.82,
14.10, 30.03, 34.37, 40.96, 48.75, 55.49, 60.91, 62.13, 102.45, 103.14,
109.83, 110.27, 111.80, 112.83, 124.80, 127.89, 129.15, 130.60, 132.45,
139.33, 154.54, 165.64, 168.52, 170.11, 170.38. Anal. Calcd (%) for
C27H28N2O7S: C, 61.82; H, 5.38; N, 5.34. Found: C, 61.88; H, 5.31;
N, 5.42.
2.11. Ethyl 2-(3-(1-benzyl-5–methoxy-2-methyl-1H-indol-3-yl)−2,5-
dioxo-4-(thiophen-3-yl)−2,5-dihydro-1H-pyrrol-1-yl)butanoate
(6d)
Yield 0.14 g (51%), red powder, mp 124–126 °C. IR νmax (cm−1):
1618 (C=С), 1715 (C = O), 1744 (C = O). 1H NMR (CDCl3) δ
(ppm): 1.00 (t, 3Н, J = 7.2 Hz, Me), 1.24–1.26 (m, 3Н, Me), 2.25–
2.29 (m, 5Н, CH2, Me), 3.55 (s, 3Н, Me), 4.20–4.21 (m, 2Н, СН2),
4.71–4.73 (m, 1Н, CH), 5.33 (s, 2Н, CH2), 6.45–6.50 (m, 1H, H
Ar), 6.75–6.76 (m, 1H, H Ar), 7.02–7.03 (m, 2H, H Ar), 7.11–7.13
(m, 2H, H Ar), 7.21–7.24 (m, 2H, H Ar), 7.28–7.31 (m, 2H, H
Ar), 8.08 (s, 1H, H Ar). 13C NMR (CDCl3) δ (ppm): 11.11, 12.76,
14.14, 22.24, 22.38, 29.67, 47.07, 54.14, 55.54, 61.59, 102.59, 102.78,
110.36, 112.06, 124.92, 125.97, 125.97, 127.59, 127.80, 128.93, 129.13,
129.22, 130.36, 130.66, 132.22, 136.86, 139.09, 154.72, 169.61,
170.73, 170.94. Anal. Calcd (%) for C31H30N2O5S: C, 68.61; H, 5.57;
N, 5.16. Found: C, 68.68; H, 5.51; N, 5.09.
2.15. Diethyl 2-(3-(1-benzyl-5–methoxy-2-methyl-1H-indol-3-yl)−2,5-
dioxo-4-(thiophen-3-yl)−2,5-dihydro-1H-pyrrol-1-yl)succinate
(7d)
Yield 0.17 g (55%), orange powder, mp 132–133 °C. IR νmax
(cm−1): 1620 (C=С), 1706 (C = O), 1738 (C = O). 1H NMR (CDCl3)
δ (ppm): 1.22–1.26 (m, 6Н, Me), 2.24–2.29 (s, 3Н, Me), 3.11–3.15
(m, 1Н, СН2), 3.32–3.35 (m, 1Н, СН2), 3.56 (s, 3Н, Me), 4.14–4.23
(m, 4H, 2CH2), 5.32–5.35 (m, 4H, CH2, 2СН), 6.43–6.50 (m, 1H,
H Ar), 6.74–6.76 (m, 1H, H Ar), 7.01–7.02 (m, 2H, H Ar), 7.11–
7.14 (m, 2H, H Ar), 7.19 (br. s, 1H, H Ar), 7.23–7.25 (m, 1H, H
Ar), 7.28–7.30 (m, 2H, H Ar), 8.06–8.07 (m, 1H, H Ar). 13C NMR
(CDCl3) δ (ppm): 12.75, 14.08, 14.13, 29.67, 34.38, 47.08, 48.78,
55.52, 60.95, 62.17, 102.53, 102.71, 110.39, 112.15, 124.96, 125.97,
125.97, 126.17, 127.61, 127.70, 127.80, 128.94, 129.36, 130.56, 132.22,
136.84, 139.01, 139.19, 154.74, 168.53, 170.14, 170.36, 170.36. Anal.
Calcd (%) for C33H32N2O7S: C, 65.98; H, 5.37; N, 4.66. Found: C,
65.91; H, 5.30; N, 4.61.
2.12. Diethyl
2-(3-(2,5-dimethylthiophen-3-yl)−4-(5–methoxy-1,2-dimethyl-1H-
indol-3-yl)−2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)succinate
(7a)
Yield 0.14 g (49%), red powder, mp 69–71 °C. IR νmax (cm−1):
1620 (C=С), 1705 (C = O), 1737 (C = O). 1H NMR (CDCl3) δ (ppm):
1.23–1.25 (m, 6Н, Me), 1.69 (s, 3Н, Me), 2.32 (s, 3Н, Me), 2.36
(s, 3Н, Me), 3.08–3.12 (m, 1Н, СН2), 3.30–3.34 (m, 1Н, СН2), 3.55
(s, 3Н, Me), 3.65 (s, 3Н, Me), 4.12–4.23 (m, 4H, CH2), 5.31–5.33
(m, 1H, CH), 6.34 (s, 1H, H Ar), 6.74–6.75 (m, 1H, H Ar), 6.84
(s, 1H, H Ar), 7.09 (d, 1H, J = 9 Hz, H Ar). 13C NMR (CDCl3) δ
(ppm): 12.71, 14.06, 14.14, 14.90, 15.02, 29.66, 30.03, 34.45, 48.86,
55.29, 60.89, 62.09, 101.57, 109.64, 112.07, 126.02, 126.45, 127.43,
129.90, 132.12, 133.53, 136.50, 139.15, 139.56, 154.55, 168.59,
170.15, 170.24, 170.46. Anal. Calcd (%) for C29H32N2O7S: C, 63.03;
H, 5.84; N, 5.07. Found: C, 63.10; H, 5.77; N, 5.02.
3. Results and discussion
3.1. Synthesis
Previously, we obtained furan-2,5–dione-bridged DE 4a-d from
1-substituted indoles and 3-thiophenacetic acids [35,36] using one
pot synthesis (Scheme 1). The acylation of indoles 1 with oxalyl
chloride afforded the corresponding acid chlorides 2. The reactions
of compounds 2 with 3-thiophenacetic acids 3 gave DE 4a-d.
Their interaction with ethyl esters of Gly, AABA and DAA leads
to novel 1-substituted hybrid pyrrole-2,5–dione-bridged DE 5a-d
(DE-Gly), 6a-d (DE-AABA) and 7a-d (DE-DAA) (Scheme 1). The cor-
responding components were heated at reflux in ethanol for 6 h
and the obtained compounds were thoroughly purified by column
chromatography (sorbent SiO2, eluent CHCl3). Ethyl esters were ob-
tained in situ from the corresponding hydrochlorides.
2.13. Diethyl 2-(3-(1-benzyl-5–methoxy-2-methyl-1H-indol-3-yl)−4-
(2,5-dimethylthiophen-3-yl)−2,5-dioxo-2,5-dihydro-1H-pyrrol-1-
yl)succinate
(7b)
Yield 0.14 g (45%), red powder, mp 75–77 °C. IR νmax (cm−1):
1619 (C=С), 1705 (C = O), 1738 (C = O). 1H NMR (CDCl3) δ
(ppm): 1.23–1.26 (m, 6Н, Me), 1.74 (s, 3Н, Me), 2.25 (s, 3Н, Me),
It should be noted that the condensation of furan-2,5–dione-
bridged DE with amino acid esters is
a more complex task
4

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
Scheme 1. Synthesis of diarylethenes 5a-d, 6a-d and 7a-d.
Table 1
compared to obtaining, for example, N-aryl derivatives due to
the known specificity of the amino acids. Apparently, the self-
polymerization reaction of the free amino acid esters significantly
affects the final product yields. This requires not only the protec-
tion of the carboxyl group and strict compliance with the reaction
conditions - temperature and pH, but also careful chromatographic
purification of the reaction products [37].
Crystal data and structure refinement for 5a.
CCDC no.
2,009,312
C25H26N2O5S
Empirical formula
Formula weight
Temperature
Crystal system
Space group
466.54
150 K
Monoclinic
P21/c
˚
a, A
10.7071(4)
25.4957(10)
8.9299(4)
90.00°
˚
b, A
3.2. Structural characterization
˚
c, A
α
A single crystal of compound 5a suitable for X-ray diffraction
was prepared. The crystallographic data are summarized in Table 1.
Full lists of bond lengths and bond angles, etc. are given in Ta-
bles S1-S6 (Supplementary data). The molecular structure of the
diarylethene-amino acid hybrid DE-Gly 5a is shown in Fig. 1. Fig. 2
shows a fragment of the crystal structure of 5a, which demon-
strates that neither intermolecular hydrogen bonds nor any other
secondary interactions are observed.
β
γ
111.235(2)°
90.00°
3
˚
Volume
2272.21(16) A
Z
4
ρcalc
μ
F(000)
1.364 g/cm3
0.183 mm-1
984.0
0.65 × 0.04 × 0.014 mm3
MoKα (λ = 0.71073)
3.2 to 52.94°
Crystal size
Radiation
2ꢀ range for data collection
Index ranges
The molecule 5a exists in the ring-open hexatriene isomeric
form. The bond lengths in the thiophene cycle S(1)-C(1) = 1.730(2),
S(1)-C(4) = 1.732(2), C(1)-C(2) = 1.361(3), C(3)-C(4) = 1.349(3),
−13 ≤ h ≤ 13, -31 ≤ k ≤ 31, -11 ≤ l ≤ 11
31,201
Reflections collected
Independent reflections
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I>2σ(I)]
Final R indices [all data]
Largest diff. peak/hole
4681 [Rint = 0.0750, Rsigma = 0.0519]
4681 / 0 / 304
˚
C(2)-C(3) = 1.433(3) A indicate a rather essential π-localization
1.027
of the double bonds C(1)=C(2) and C(3)=C(4). These bond lengths
and angles (Table S4, Supplementary data) in the thiophene ring
correlate well with similar data for molecules in which the thio-
phene cycle is bound to pyrazole in a twisted conformation (di-
hedral angle ~ 66–78°) [38,39]. The bond lengths in the pyrrole
bridge are as follows: O(1)-C(7) = 1.209(2), O(2)-C(10) = 1.211(2),
N(1)-C(7) = 1.388(3), N(1)-C(10) = 1.388(3), C(7)-C(8) = 1.486(3),
C(8)-C(9) = 1.350(3), C(9)-C(10) = 1.505(3). These values also ev-
idence the lacking of π-delocalization over the pyrrole fragment.
This is due to the fact that the thiophene substituent (as well as
the indole substituent) is strongly rotated relative to the plane of
the pyrrole bridge, which practically interrupts the conjugation of
these substituents. Indeed, the torsion angle of thiophene C(9)-
R1 = 0.0492, wR2 = 0.1046
R1 = 0.0849, wR2 = 0.1136
−3
˚
0.30/−0.29 e.A
C(8)-C(2)-C(1) is 51.8(3) degrees, and the torsion angle of indole
C(8)-C(9)-C(12)-C(13) - 34.9(4) degrees. At the same time, both
heterocyclic substituents, thiophene and indole, are in an antipar-
allel conformation, which, according to the crystallographic data
of the previously studied DE [17-20], creates the conditions for
the conrotatory photocyclization reaction into the ring-closed cy-
˚
clohexadiene isomer. The distance of 4.549 A in DE 5a between
5

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
Fig. 1. ORTEP diagram of the molecule 5a with thermal ellipsoids drawn at 50% probability.
Fig. 2. A fragment of the crystal packing of 5a.
the reactive C(1)-C(11) carbon atoms, potentially capable of form-
3.3. Spectroscopic characterization
ing a new single bond between the heterocyclic fragments dur-
ing the cyclization, is too long for photocyclization to occur in the
crystal [21], but shorter than that in the non-photochromic crys-
tal of 3-(1,2-dimethyl-1H-indol-3-yl)−4-[(E)–prop-1-enyl]furan-2,5–
dione [22]. This allows us to assume that in solutions of 5a, the
free rotation of thiophene and indole moieties around single bonds
should provide the necessary distance between the reaction cen-
ters [12-14].
IR spectra of DE 5a-d, 6a-d and 7a-d contain the characteristic
bands of stretching vibrations of C = C groups (1616–1622 cm−1
)
and pyrroledione and amino acid carbonyl groups (1695–1717 and
1704–1751 cm−1). Singlet signals of protons of the indole methyl
groups are found at 2.33–2.42 (CMe), 3.40–3.58 (OMe) and 3.65–
3.73 ppm (NMe). Signals of protons of the NBn methylene group
are also recorded as singlets at 4.85–5.35 ppm. Singlet signals of
protons of the thiophene methyl groups appear in the spectral re-
gion of 1.69–2.37 ppm. In the electronic absorption spectra of 5a-
6

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
Table 2
Absorption and fluorescence spectra of DE 5a-d, 6a-d and 7a-d in hexane (c 5.10−5 M).
Ring-open form O
Ring-closed form C
No
Absorption, λmax., nm (ε•10−3, L mol−1 cm−1
)
Fluorescence, λmax., nm (Ifl, a.u.)
Absorption, λmax., nm (A)a
5a
5b
5c
5d
6a
6b
6c
6d
7a
7b
7c
7d
446 (7.0)
445 (7.7)
456 (7.0)
452 (7.3)
447 (9.1)
446 (8.9)
455 (8.8)
452 (8.7)
446 (8.1)
443 (8.2)
455 (8.0)
450 (7.1)
531 (680)
534 (590)
531 (630)
535 (610)
532 (640)
533 (610)
535 (710)
528 (400)
532 (670)
535 (420)
530 (610)
546 (395)
574 (0.13)
565 (0.15)
553 (0.22)
555 (0.35)
572 (0.14)
562 (0.12)
560 (0.28)
555 (0.31)
571 (0.18)
564 (0.19)
552 (0.40)
557 (0.31)
a
A – optical density parameter at the absorption band maximum of the photoinduced form C in photostationary state
upon irradiation with light of 436 nm.
d, 6a-d and 7a-d in hexane, long-wavelength absorption bands are
observed at 443–456 nm (Table 2).
The structure and nature of the amino acid residue R1 do
not significantly affect the position and intensity of the absorp-
tion bands. The spectral absorption data indicate that the obtained
compounds exist as ring-open hexatriene isomers O, since the
ring-closed cyclohexadiene forms C must be deeply colored and
absorb in a much longer wavelength region of the spectrum [12-
16].
3.4. Fluorescence characteristics
Fig. 3. Electronic absorption spectra of diarylethene 6d in hexane before (1) and
after irradiation with light of 436 nm for 30 (2), 50 (3), 100 (4), 200 (5), 360 (6) and
720 s (7) (c 6.9.10−5 mol L–1). The photo shows the color 6d in a hexane solution
before (left cuvette) and after irradiation (λirr 436 nm) for 12 min (right cuvette).
The ring-open forms O possess fluorescence in the region of
552–574 nm (Table 2). Emission properties are not initially inher-
ent in all “small molecules” - photoswitches, so it is usually nec-
essary to add additional fluorogenic substituents to the molecule
[2,3,5,40]. Photoswitchable molecules that are capable of alternat-
ing fluorescence position or intensity in their two bistable iso-
meric forms consist the basis of the modern approach to the de-
sign of bioconjugates [41-43]. “On-off” or “off-on” emission modu-
lation increases the sensitivity of observation by an order of mag-
nitude compared to nonfluorescent molecules and is already suc-
cessfully used for monitoring the ionic composition of living cells
[44]. Previously investigated photoswitchable amino acids, nucle-
osides and DNA analogues containing a biocomponent mostly in
a side chain represent cyclopentene-bridged diarylethenes [45-48].
Their synthesis is much more complex than our method. Moreover,
the presence of two symmetrical thienyl [45,46] or even pyrim-
idine(pyrrolopyrimidine) and thienyl substituents [47,48] did not
provide fluorescent properties. Light-sensitive hydrogelator con-
taining amino acid fragments in a lengthy maleimide bridge also
showed no emission activity due to the presence of symmetrical
thienyl groups [49]. From this point of view, the choice of non-
symmetric fluorescent DE 5–7 looks more attractive.
Scheme 2. Photoisomerization of diarylethenes 5a-d, 6a-d and 7a-d.
the intensity of the initial absorption and the appearance of new
long-wavelength maxima, while four clear isosbestic points are ob-
served (Fig. 3).
As in most of the previously described cases, even long-term ir-
radiation does not lead to a complete transformation into a cyclic
form C, and results in the establishment of the photostationary
state (PSS) due to the substantial overlap of the absorption bands
(S1←S0 transition) of the initial form O and S2←S0 transition of
the photo induced isomer C [8,25]. The formation of PSS was also
detected for the previously mentioned diarylethene bioconjugates
[46-49]. While the amino acid residue R1 does not affect the ther-
mal stability of ring-closed С isomers, the structure of heterocy-
cles plays a crucial role in this process. It turned out that only the
forms C with the maximum number of methyl substituents R2 and
R3 in the indole and thiophene moieties, namely, 5a, 6a and 7a,
possess very high thermal stability in the absence of irradiation.
No noticeable spectral changes for their solutions were observed
for at least 48 h at 293 K. However, irradiation of all photoin-
duced isomers C of DE 5a-d, 6a-d and 7a-d with visible light λ >
500 nm results in the complete reopening reaction with the forma-
As in the case of absorption, the structure and nature of the
amino acid substituent R1 have little effect on the emission pat-
tern. Analysis of the fluorescence excitation spectra showed that
the emission shown in Table 2 belongs exclusively to the ring-open
form O, whereas the cyclic form C is nonfluorescent.
3.5. Photochromic properties
Irradiation of solutions of hybrid DE 5a-d, 6a-d and 7a-d in
hexane with light of 436 nm results in the rearrangement into
ring-closed cyclohexadiene colored isomers C that absorb in the
longer wavelength part of the spectrum at 552–574 nm (Table 2,
Scheme 2). Photoreaction O → C is characterized by a decrease in
7

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
Table 3
Spectral kinetic characteristics of DE 5a, c.
Opened form O
Cyclic form C
Absorption,
max., nm
Emission
max., nm
Absorption,
max., nm
Comp.
−
1
Solvent
λ
λ
kC→O.104, s
λ
ϕ
5a
Hexane
Toluene
MeOH/H2O
(4:1)
446
462
469
531
566
590
0.20
0.04
0.006
574
579
581
Stable
Stable
Stable
CH3CN
460
456
468
466
612
532
558
589
0.005
0.14
Not forming
553
–
5c
Hexane
Toluene
MeOH/H2O
(4:1)
2.9
20.0
–
0.02
574
0.006
Not forming
CH3CN
468
586
0.004
Not forming
–
Fig. 5. Normalized emission spectra of 5a in hexane (1), toluene (2), MeOH/H2O
(4:1) mixture (3) and acetonitrile (4).
Fig. 4. Normalized absorption spectra of 5a in hexane (1), toluene (2), MeOH/H2O
(4:1) mixture (3) and acetonitrile (4).
tion of the initial ring-opened forms O. For DE 2b-d, 3b-d and 4b-d
in hexane at room temperature, a gradual thermal rearrangement
into the starting isomer O is observed. To the best of our knowl-
edge, such structural effects have not been previously observed in
diarylethene-based bioconjugates [8,45,50].
Since the resulting photo form C, unlike the initial isomers O,
does not have emission properties, a gradual decrease in the flu-
orescence intensity is observed during the photo process. After
the completion of the reverse thermal or photochemical reaction
C → O, the intensity of the starting emission is fully restored.
Fig. 6. The kinetic curve of thermal reopening decoloration reaction C → O of 5c
at 555 nm in hexane, T = 293 K.
3.6. Spectral kinetic characteristics
The rearrangements shown in Scheme 2 depend significantly on
the nature of the solvent. This relationship has been studied in
more detail for DE 5a, c (Table 3). Thus, the formation of the C
isomer in acetonitrile is barely noticeable. In a water-alcohol mix-
ture, a ring-closed colored C isomer is formed only in the case of
the sterically hindered compound 5a (R2 = R3 = Me). The previ-
ously mentioned diarylethene-based bioconjugates in general pos-
sess slightly better solubility and have been studied in CH3CN [47],
MeOH [45] and H2O (pH 10) [49]. Therefore, increasing the solubil-
ity in water constitutes one of the most important problems in the
design of diarylethene bioconjugates.
As can be seen from Table 3, the thermal stability of the ring-
closed isomer C of sterically hindered 5a (R2 = R3 = Me) depends
slightly on the polarity of the solvent, whereas for 5c (R3 = H) its
formation occurs only in low-polar solvents. Reducing the number
of methyl substituents, increasing the polarity of the solvent, or
even replacing nonpolar hexane with low-polar toluene increases
the speed of ring opening (Figs. 6,7).
The data obtained are consistent with the empirical rule that
bulky substituents in heterocyclic fragments of DE can enhance the
efficiency of formation and stability of the ring-closed cyclic form C
[12-15]. An increase in the polarity of the solvent not only reduces
the possibility of a photocyclization reaction O → C, probably due
to the rise in the content of non-photoactive parallel conformation
of heterocyclic substituents [12], but also significantly decreases
the stability of the cyclic form C.
In the absorption spectra, a moderate red shift of long wave-
length maximum is observed with an increase in the polarity
of the solvent or its proton-donating ability. However, the cor-
responding red shift of the emission band is much larger and
the Stokes shift reaches ꢁν values of 5400 cm−1 in acetonitrile
(Figs. 4, 5). The quantum yield of fluorescence noticeably decreases
from hexane to polar acetonitrile.
8

V.А. Podshibyakin, Е.N. Shepelenko, O. Yu. Karlutova et al.
Journal of Molecular Structure 1243 (2021) 130758
Spectral luminescent and kinetic studies of 5a,c show that the
efficiency of photoinduced cyclization and fluorescence quantum
yields decrease with increasing solvent polarity. The sterically hin-
dered cyclic isomer of 5a (R2 = R3 = Me) is stable for at least
48 h at 293 K, while 5c (R3 = H) demonstrates re-opening into
the initial form at a rate increasing with the solvent polarity. Hy-
brids 5a, 6a and 7a (R2 = R3 = Me) are capable of emission mod-
ulation with good fatigue resistance under consecutive irradiation
with light of 436 and 540 nm.
The obtained data are of interest for creating photocontrolled
fluorescent bioactive systems conjugated with diarylethenes. First,
condensation of nonsymmetric fluorescent furan-2,5–dione deriva-
tives with amino-containing compounds, for example, oligopep-
tides, nitrogenous bases (adenine, cytosine, guanine), nucleosides
(adenosine, guanosine), vitamins (methylcobalamin, folic acid), etc.
may be a synthetically simpler method than embedding them
in side chains. Secondly, thiazole-based diarylethenes can also be
used for these purposes, since they allow modification of the NH-
bridge.
Fig. 7. The kinetic curve of thermal reopening decoloration reaction C → O of 5c at
565 nm in toluene, T = 293 K.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper.
Acknowledgements
The research was financially supported by the Ministry of Sci-
ence and Higher Education of the RF in the framework of the State
assignment in the field of scientific activity No. 0852–2020–0019.
E.N. Shepelenko and A.D. Dubonosov worked in the framework of
the State assignment of the Southern Scientific center of the RAS
No. 01201354239.
Fig. 8. Fatigue resistance of compound 7a irradiated with light of 436 nm and vis-
ible light (λ > 540 nm) alternately.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.molstruc.2021.130758.
3.7. Fatigue resistance
Resistance to photodegradation and emission modulating abil-
ity of all sterically hindered dihetarylethenes 5a, 6a and 7a were
studied.
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