Synthesis and study of new photochromic spiropyrans modified with carboxylic and aldehyde substituents

Article abstract of DOI:10.1016/j.molstruc.2019.06.094

Three new photochromic spiropyrans containing a carboxylic group in the indoline fragment and an aldehyde substituent in the [2H]-chromene moiety were synthesized. The structure of the compounds obtained was studied using ¹H and ¹³C NMR, IR and elemental analysis. Single crystal X-ray analysis was used to refine the molecular structure of 8′-formyl-1,3,3,6′-tetramethyl-spiro[indoline-2,2′-2H-chromene]-5-carboxylic acid. It was found out that in the solid state the molecules of that compound are arranged in dimeric associates due to the formation of intermolecular hydrogen bonds between carboxylic groups of two adjacent molecules. All the spiropyrans were shown to be photochromic with the lifetimes of the open forms in the range of 1.5–46.0 s.

Full text of DOI:10.1016/j.molstruc.2019.06.094

Journal of Molecular Structure 1196 (2019) 409e416
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis and study of new photochromic spiropyrans modified with
carboxylic and aldehyde substituents
,
,
Ilya V. Ozhogin a *, Valentina V. Chernyavina b, Boris S. Lukyanov a c, Vasily I. Malay a,
Irina A. Rostovtseva a, Nadezhda I. Makarova a, Valery V. Tkachev d
,
,
e
Maria B. Lukyanova a, Anatoly V. Metelitsa a, Sergey M. Aldoshin d
a Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka Ave., 344090, Rostov-on-Don, Russian Federation
b Department of Chemistry, Southern Federal University, Zorge St., 7, 344090, Rostov-on-Don, Russian Federation
c Don State Technical University, 1 Gagarin Sq., 344000, Rostov-on-Don, Russian Federation
d Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 Akad. Semenova Ave., 142432, Chernogolovka, Moscow Region, Russian
Federation
e Institute of Physiologically Active Substances, 1 Severny Proezd, 142432, Chernogolovka, Moscow Region, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Three new photochromic spiropyrans containing a carboxylic group in the indoline fragment and an
aldehyde substituent in the [2H]-chromene moiety were synthesized. The structure of the compounds
obtained was studied using 1H and 13C NMR, IR and elemental analysis. Single crystal X-ray analysis was
used to refine the molecular structure of 80-formyl-1,3,3,60-tetramethyl-spiro[indoline-2,20-2H-chro-
mene]-5-carboxylic acid. It was found out that in the solid state the molecules of that compound are
arranged in dimeric associates due to the formation of intermolecular hydrogen bonds between car-
boxylic groups of two adjacent molecules. All the spiropyrans were shown to be photochromic with the
lifetimes of the open forms in the range of 1.5e46.0 s.
Received 7 May 2019
Received in revised form
20 June 2019
Accepted 26 June 2019
Available online 27 June 2019
Keywords:
Spiropyran
Photochromism
Merocyanine
© 2019 Elsevier B.V. All rights reserved.
Molecular switch
Indoline
Single crystal X-ray analysis
1. Introduction
switches and actuators for using in different areas of material
chemistry and biomedicine [6e14].
Nowadays organic photochromic compounds are widely used
for development of different stimuli-responsive smart materials
[1e5]. Spiropyrans belong to one of the most interesting and
intensely studied classes of organic photochromic compounds.
Their photochromic properties are caused by the photolytic disso-
It is well known that the introduction of electron-withdrawing
substituents into 2H-chromene part of the molecule facilitates
the processes of thermo- and photoinitiated cleavage of the
CspiroeO bond [15,16]. This is why many studies of photochromic
and thermochromic behavior of spiropyrans were focused on spi-
ropyrans containing a nitro group in para-position to the oxygen
atom of the 2H-chromene cycle. At the same time, the presence of a
nitro group in the molecule leads to the involvement of low-lying
triplet excited states of the molecule into the photophysical
mechanism of the photoinduced transformations of spiropyrans
[17] and causes its tendency to photodegradation and probable
phototoxicity for living matter. That is why searching for new spi-
rocyclic structures modified with electron-acceptor substituents
differing from the nitro group is a quite prospective research di-
rection. Carbonyl-containing substituents seem to be very prom-
ising candidates to replace the nitro group due to their sufficient
ciation of the
CspiroeO bond with subsequent isomerization
through the double bond system, which leads to the formation of a
brightly colored merocyanine form (Scheme 1). In addition to the
spectral absorption changes, this transformation results in strong
changes of the dipole moment of the molecule, its acidity, affinity
for metal ions, fluorescence, etc. These features along with multi-
responsiveness to a number of external stimuli (light, pH, metal
ions, mechanical force, etc.) make spiropyrans promising molecular
* Corresponding author.
E-mail address: iozhogin@sfedu.ru (I.V. Ozhogin).
https://doi.org/10.1016/j.molstruc.2019.06.094
0022-2860/© 2019 Elsevier B.V. All rights reserved.

410
I.V. Ozhogin et al. / Journal of Molecular Structure 1196 (2019) 409e416
Scheme 1. Photoinduced isomerization of target spiropyrans (1a-c).
acceptor effect and increased functionality.
[30].
Spiropyrans containing formyl or carboxy groups can not only
be readily modified due to their high reactivity [18e21] but can also
provide compounds with different useful properties such as solid-
phase photochromism [22], the controlled morphology of spi-
ropyran nanostructures [23], pH-dependent fluorescence for im-
aging of bacterial cells in extreme pH-conditions [24], capability of
fluorescent sensing of hydrazine molecules and chromogenic
detection of metal ions [25]. Nowadays spiropyrans are with the
increasing frequency used in different biomedical applications such
as light-driven drug delivery, photopharmacology and bio-imaging.
To be effectively utilized in these areas photoactive molecules
should possess increased solubility and low toxicity. The use of
Melting points were determined on a Fisher-Jones apparatus
(Fisher Scientific).
2.2. Synthetic methods
5-carboxy-1,2,3,3-tetramethyl-3H-indolium iodide (2) was
synthesized by the known method [31]. Aldehydes (3a-c) were
obtained by the Duff formylation procedure described earlier
[32,33].
8′-formyl-1,3,3,6′-tetramethyl-spiro[indoline-2,2′-2H-chro-
mene]-5-carboxylic acid (1a). 690 mg (2 mmol) of 5-carboxy-
1,2,3,3-tetramethyl-3H-indolium iodide (2) was added to a hot
solution of 344 mg (2.1 mmol) of aldehyde (3a) in 10 ml of iso-
propanol. Then 0.4 ml of triethylamine was carefully added drop-
wise. The mixture was refluxed for 2 h. Then it was cooled to room
temperature and poured into 1 M HCl to form precipitate. The
precipitate was filtered off, washed with water and dried. The crude
product was purified by column chromatography on SiO2 with
chloroform as eluent. Yield 62%. mp 253ꢀС.
carboxy-substituted indoline spiropyrans allowed creating
a
reversible ‘turn-off’ fluorescent sensor for -Glutamyl-cysteinyl-
g
glycine (GSH) which is non-toxic, soluble in aqueous media and
displays an excellent selectivity for GSH over other biologically
related analytes [26]. Also, based on spiropyrans containing free
carboxylic groups an effective fluorescent sensor for lithium ions
[27] and new zinc(II)-responsive drug-delivery system with real-
time intracellular sensing capabilities [28] were invented.
Previously we demonstrated that introduction of a formyl sub-
stituent to the position 80 of the 2H-chromene moiety of the spi-
ropyran molecule activates photochromic properties of the
compounds even in the case of less active 1,3-benzoxazine de-
rivatives [18,22,29]. The aim of the current research was to syn-
thesize new indoline spiropyrans (1) containing an aldehyde group
at the same position 80, a free carboxylic group at the position 5 of
the indoline fragment and different substituents at the position 60
of the benzopyran moiety, and to investigate their molecular
structure and photochromic properties.
IR spectrum,
nС¼С); 1273, 1251 1233 (
NMR 1H (CDCl3)
n
, cmꢁ1: 1675e1685(nС¼О); 1588e1610, 1504
С-N); 981e976, 938 ( С-O).
, ppm (J, Hz): 1.20 (s, 3H, 3-СН3), 1.36 (s, 3H, 3-
(
n
n
d
СН3), 2.26 (s, 3H, 60-СН3), 2.81 (s, 3H, N-СН3), 5.75 (d, 1H, J ¼ 10.3,
30-H), 6.52 (d,1H, J ¼ 8.2, 7-H), 6.88 (d,1H, J ¼ 10.3, 40-H), 7.09 (s,1H,
70-H), 7.44 (s, 1H, 50-H), 7.78 (s, 1H, 4-H), 8.01 (d, 1H, J ¼ 8.2, 6-H),
10.11 (s, 1H, 80-CHO).
NMR 13C (CDCl3) , ppm: 188.56 (80-CHO), 171.70 (5-COOH),
d
154.89 (C-90), 152.32 (C-8), 136.41 (C-9), 133.52 (C-50), 132.18 (C-6),
129.80 (C-60), 129.19 (C-40), 127.80 (C-70), 123.77 (C-4), 122.41 (C-80),
120.20 (C-5), 119.62 (C-100), 119.48 (C-30), 106.01 (C-7), 105.14
(Cspiro), 51.64 (C-3), 28.76 (N-СН3), 25.74 (3-СН3), 20.44 (3-СН3),
20.26 (60-CH3).
2. Experimental
Anal. calc. for C22H21NO4, %: С 72.71; Н 5.82; N 3.85. Found, %: С
72.65; Н 5.87; N 3.88.
2.1. Materials and methods
8′-formyl-6′-methoxy-1,3,3-trimethyl-spiro[indoline-2,2′-
2H-chromene]-5-carboxylic acid (1b). Was synthesized according
to the previously described method for the compound (1a) using
aldehyde (3b). Yield 78%. mp 251ꢀС.
All reagents were purchased from “Alfa Aesar” and “Merck” and
were used as received. Organic solvents used were purified and
dried according to standard methods.
NMR spectra were recorded on
a
Bruker AVANCE-600
IR spectrum,
1284, 1244 ( С-N); 1027, 963, 935 (
NMR 1H (CDCl3)
, ppm (J, Hz): 1.20 (s, 3H, 3-СН3), 1.36 (s, 3H, 3-
n
, cmꢁ1: 1686, 1666 (nС¼О); 1607, 1588 (nС¼С);
(600 MHz) spectrometer. The signals were assigned according to
the signals of residual protons of the deuterated solvent (CDCl3,
n
nС-O).
d
d
¼ 7.26 ppm).
СН3), 2.82 (s, 3H, N-СН3), 3.76 (s, 3H, 60-OСН3), 5.81 (d, J ¼ 10.3, 1H,
30-H), 6.52 (d, J ¼ 8.3, 1H, 7-H), 6.87 (d, J ¼ 10.3, 1H, 40-H), 6.89 (d,
J ¼ 3.1, 1H, 70-H), 7.13 (d, J ¼ 3.1, 1H, 50-H), 7.78 (d, J ¼ 1.6, 1H, 4-H),
8.01 (dd, J ¼ 8.2, 1.7, 1H, 6-H), 10.11 (s, 1H, 80-CHO).
IR spectra of the compounds were recorded on a Varian Excal-
ibur 3100 FT-IR using a partial internal reflection method.
Electronic absorption spectra and kinetic curves of the investi-
gated compounds were recorded on an “Agilent 8453” spectro-
photometer equipped with the thermostatic cell. The irradiation of
solutions with filtered light of a high-pressure Hg lamp was per-
formed on a “Newport 66902” equipment. Acetonitrile of the
spectroscopic grade (“Aldrich”) was used to prepare solutions.
Elemental analysis was carried out by a conventional method
NMR 13C (CDCl3)
d, ppm: 188.13, 172.05, 153.25, 152.31, 151.54,
136.39, 132.18, 128.98, 123.73, 122.77, 120.95, 120.74, 120.69, 120.24,
109.36, 105.99, 104.89, 55.83, 51.66, 28.78, 25.75, 20.48.
Anal. calc. for C22H21NO5, %: С 69.64; Н 5.58; N 3.69. Found, %: С
69.59; Н 5.60; N 3.72.
8′-formyl-6′-methoxycarbonyl-1,3,3-trimethyl-spiro

I.V. Ozhogin et al. / Journal of Molecular Structure 1196 (2019) 409e416
411
[indoline-2,2′-2H-chromene]-5-carboxylic acid (1c). Was syn-
thesized according to the previously described method for the
compound (1a) using aldehyde (3c). After chromatography, the
product was recrystallized from acetone to form soft pink solid.
Yield 32%. mp 229ꢀС.
Collection of reflections, determination and refinement of the unit
cell parameters was carried out using the specialized software
package CrysAlis PRO [34]. Yellow crystals of (1a), C22H21NO4 are
triclinic, with the following parameters of the crystal unit cell:
a ¼ 6.6746(4), b ¼ 7.9483(4), с ¼18.5211(9) Å,
a
¼ 85.369(4),
IR spectrum,
1254, 1224 ( С-N); 1023, 937, 928 (
NMR 1H (CDCl3)
, ppm (J, Hz): 1.22 (s, 3H, 3-СН3), 1.36 (s, 3H, 3-
n
, cmꢁ1: 1716, 1693, 1672 (nС¼О); 1609, 1589 (nС¼С);
С-O).
b
¼ 81.388(5),
g
¼ 66.475(5)ꢀ. V ¼ 890.51(8) Å3, space group P-1.
n
n
The structure was decoded by the direct method and refined by the
full-matrix least squares method with respect to F2 in the aniso-
tropic approximation for non-hydrogen atoms. Hydrogen atoms are
localized in difference electron density syntheses and refined in an
isotropic approximation. The final refinement parameters:
R1 ¼0.048, GOF ¼ 0.942. All calculations were performed using
SHELXTL program set [35]. The full information about the structure
under the study was deposited with the Cambridge Crystallo-
graphic Data Centre (CCDC 1914337) and can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or
from the Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: þ44 1223 336033).
d
СН3), 2.84 (s, 3H, N-СН3), 3.88 (s, 3H, 60-COOCH3), 5.85 (d, J ¼ 10.4,
1H, 30-H), 6.56 (d, J ¼ 8.3, 1H, 7-H), 6.99 (d, J ¼ 10.4, 1H, 40-H), 7.80
(d, J ¼ 1.1,1H, 4-H), 7.97 (d, J ¼ 2.0,1H, 50-H), 8.03 (dd, J ¼ 8.2,1.3,1H,
6-H), 8.33 (d, J ¼ 2.0, 1H, 70-H), 10.10 (s, 1H, 80-CHO).
NMR 13C (CDCl3)
d, ppm: 187.49, 171.97, 165.81, 159.81, 152.03,
136.06, 133.43, 132.26, 130.13, 128.91, 123.78, 122.72, 122.45, 120.70,
120.15, 119.82, 106.60, 106.24, 52.19, 51.99, 28.76, 25.76, 20.25.
Anal. calc. for C23H21NO6, %: С 67.80; Н 5.20; N 3.44. Found, %: С
67.72; Н 5.25; N 3.47.
2.3. Single crystal X-Ray analysis methods
3. Results and discussion
Crystals suitable for single crystal X-ray analysis were grown by
slow evaporation of the solution of SP (1a) in CHCl3. Parameters of
the crystal unit cell and a three dimensional set of intensities were
obtained on an Agilent Xcalibur diffractometer equipped with CCD
detector EOS (Agilent Technologies UK Ltd, Yarnton, Oxfordshire,
3.1. Synthesis
The necessary for the synthesis of target spiropyrans 5-carboxy-
1,2,3,3-tetramethyl-3H-indolium iodide (2) was obtained starting
from 4-hydrazinobenzoic acid by the Fischer protocol for indole
synthesis followed by alkylation of the intermediate indolenine
England) at 150(1) K using MoK
a-irradiation (
l
¼ 0.71073 Å). The
occupancy of the experimental array (2
q
¼ 58.12ꢀ) was 99.8%.
Scheme 2. Synthesis of intermediate compounds and target spiropyrans (1a-c).

412
I.V. Ozhogin et al. / Journal of Molecular Structure 1196 (2019) 409e416
[31]. The aldehydes (3) were obtained from corresponding 4-
substituted phenols by the excessive Duff formylation reaction
with hexamethylenetetramine in TFA using known method [32,33].
New spiropyrans of indoline series were synthesized by the
cyclocondensation reaction of 5-carboxy-1,2,3,3-tetramethyl-3H-
indolium iodide (2) with corresponding diformyl-substituted
phenols (3) under the reflux in 2-propanol in presence of the
excess of triethylamine (Scheme 2). To remove residual organic
base after synthesis the reaction mixture was poured into diluted
HCl, after that the crude product was purified by column chroma-
tography and/or recrystallization.
protons 30 and 40 forming a cis-configured AB-system appeared as
doublet signals with characteristic J-constants of 10.3e10.4 Hz in
the ranges of 5.75e5.85 and 6.88e6.99 ppm accordingly. The
formyl group protons were found at about 10.10 ppm.
The 13C NMR spectra of spiropyrans showed the signals of all the
carbon atoms presented in the molecules of (1a-c) and also
confirmed the spirocyclic form predomination at room tempera-
ture. In the region of 104.9e106.2 the characteristic signals of spi-
rocyclic carbon atoms were observed. The peaks corresponding to
the formyl carbons were found at 187.5e188.6, while carboxylic
carbons e at 172.0 ppm. The combination of COSY 1He1H, 1He13C
HSQC and 1He13C HMBC 2D NMR (Figs. S3eS5) methods allowed us
to unambiguously align all the carbon signals for the compound
(1a). The presence of a single nitrogen atom in the molecule and its
correlation with the adjacent protons of N-CH3 group and 30-H was
revealed by 1He15N HMBC NMR (Fig. S6).
The structure of the obtained compounds was confirmed by
NMR and IR spectroscopy, elemental analysis and single crystal X-
ray analysis (for (1a)).
3.2. Spectral characterization
3.2.1. FT-IR spectra
3.3. Single crystal X-ray analysis
FT-IR spectra of all the studied spiro-compounds exhibited
intensive absorption bands corresponding to the stretching vibra-
tions of the carbonyl groups from carboxylic and formyl sub-
The molecular structure of spiropyran (1a) was studied by single
crystal X-ray analysis. Crystals suitable for analysis were grown by
slow evaporation of the chloroform from the solution of the com-
pound. The structure of the molecule (1a) according to the XRD
results is shown in Fig. 1 in the projection of least overlapping.
The most important bond lengths and angles are provided in
stituents in the range of 1666e1693 cmꢁ1
. The peak of
carbomethoxyl group of (1c) was found at 1716 cmꢁ1. The absorp-
tion frequencies of aromatic CeH occurred at 2854e2954 cmꢁ1. The
peaks appearing at 1588e1610 сmꢁ1 were related to C]C double
bonds’ stretch of the 2H-chromene cycle. The characteristic ab-
sorption frequencies of CspiroeO bond were observed in the region
of 928e938 сmꢁ1 and confirmed the spirocyclic structure of target
compounds. The stretching vibrations of the CeN bonds were
observed in the regions of 1304e1307 and 1251e1258 cmꢁ1. The
intensive bands corresponding to the stretching vibration of the
CeOMe bonds of the compounds (1b) and (1c) appeared at 1244
and 1224 cmꢁ1 accordingly.
Table 1
Selected bond lengths, l [Å], and angles,
u
[deg], for (1a).
Bond
l, Å
Bond
l, Å
O(1)eC(13)
O(2)eC(13)
N(1)eC(8)
N(1)eC(10)
N(1)eC(202)
C(3)eC(9)
C(3)eC(202)
1.245
1.30
C(202)eO(10)
1.464
1.494
1.326
1.366
1.443
1.406
1.474
1.211
C(202)eC(30)
1.385
1.452
1.460
1.516
1.580
1.468
C(30)eC(40)
O(10)eC(90)
C(40)eC(100)
C(90)eC(100)
3.2.2. NMR study results
C(80)eC(120)
The position of the signals in the 1H NMR spectra of compounds
(1a-c) in deuteriochloroform solutions, their integral intensities
and the spin-spin interaction constants fully corresponded to the
presented structures. In the aliphatic protons region, the non-
equivalent singlet signals of the protons of the gem-methyl
groups at the position 3 appeared at about 1.20 and 1.36 ppm, the
signals of N-CH3 were in the region of 2.81e2.84 ppm and the
three-proton singlet signals of the corresponding methyl, methoxy-
and carbomethoxy groups of the 2H-chromene fragment were
observed at 2.26, 3.76 and 3.88 ppm for spiropyrans (1a), (1b) and
(1c) as follows. In the aromatic protons region, the signals of
C(5)eC(13)
O(20)eC(120)
Angle
u
, deg.
Angle
u
, deg.
C(8)eN(1)eC(10)
C(8)eN(1) eC(202)
C(10)eN(1)eC(202)
C(9)eC(3)eC(202)
N(1)eC(8)eC(7)
N(1)eC(8)eC(9)
C(4)eC(9)eC(3)
O(1)eC(13)eO(2)
O(2)eC(13)eC(5)
N(1)eC(202)eC(3)
121.66
109.83
119.11
101.10
128.17
110.16
130.68
122.33
116.15
103.27
N(1)eC(202)eO(10)
N(1)eC(202)eC(30)
O(10)eC(202)eC(30)
C(90)eO(10)eC(202)
O(10)eC(202)eC(3)
C(30)eC(202)eC(3)
C(40)eC(30)eC(202)
C(30)eC(40)eC(100)
C(90)eC(100)eC(40)
O(20)eC(120)eC(80)
107.69
110.91
112.17
122.46
106.11
116.01
123.08
121.33
117.97
124.87
Fig. 1. ORTEP diagram of the molecule of 80-formyl-1,3,3,60-tetramethyl-spiro[indoline-2,20-2H-chromene]-5-carboxylic acid (1a).

I.V. Ozhogin et al. / Journal of Molecular Structure 1196 (2019) 409e416
413
Fig. 2. Representation of intermolecular hydrogen bonding in a single crystal of (1a) resulting in the formation of dimeric associates.
Table 1. In the indoline fragment of the molecule atoms С(3) e С(9)
and N(1) lie in one plane with an accuracy of 0.02 Å. Atoms of the
carboxylic group О(1), С(13) and О(2) deviate from this plane for
0.05, ꢁ0.10 and ꢁ0.30 Å correspondingly. The plane of atoms N(1),
С(3), С(8), С(9) and С(202) is bent along the line N(1) e С(3) with an
angle of 21.9ꢀ. The sum of the angles at the nitrogen atom
N(1) ¼ 350.6ꢀ, the atom N(1) deviates from the plane of the atoms
C(8), C(202) and C(10) by 0.26 Å. This indicates a pyramidal
configuration of the nitrogen atom and a noticeable sp3-character
of the lone pair of electrons on atom N(1). The orientation of the
valent bonds at atom N(1) corresponds to the trans-arrangement of
the lone pair on the nitrogen atom relative to the CspiroeO bond.
In the 2H-chromene part of the molecule, atoms C(30) e C(100)
and O(10) lie in the same plane with an accuracy of 0.02 Å. Atoms
C(110), C(120) and O(20) deviate from it for 0.05, 0.05 and 0.15 Å in
one direction, respectively, and the C(202) atom e for 0.15 Å in the
other direction, realizing a bend of 11.4ꢀ along the O(10) e C(30) line.
It should be noted that the molecules of studied spiropyran are
arranged in dimer associates in its single crystals due to the for-
mation of two intermolecular hydrogen bonds between hydrogen
and carbonyl oxygen atoms of the adjacent molecules (Fig. 2).
The molecules of carboxy-substituted spiropyran (1a) in its
single crystal are combined in pairs by the symmetry elements
[-x þ 1, -y þ 2, -z þ 1]* and intermolecular hydrogen bonds H(2)
….O(1)* with the following parameters: O(2)eH(2) ¼ 0.88, H(2)
….O(1)* ¼ 1.738, O(1)* ….O(2) ¼ 2.616 Å, the angle O(2)eH(2)e
O(1)* ¼ 174.6ꢀ. The dimeric associates are located in a crystal in
such a way that the closest intermolecular contact of 2.58 Å be-
tween the molecules belonging to different dimers is observed
between the O(20) atom of one molecule and the hydrogen atom at
the C(7) atom of the neighboring one.
It should be noted that the group of Prof. Yin previously
observed the formation of dimeric associates of carboxy-
spiropyrans in their self-assembled nanostructures on silica and
described the possibilities of tuning the morphology of spiropyran
assemblies with help of this phenomenon [23]. To the best of our
knowledge, now we have the first example of the spiropyran
strong-coupled dimers formation proven by single crystal X-ray.
3.4. Studies on photochromic properties
Photochemical studies of spiropyrans (1a-c) were carried out in
their acetonitrile solutions at room temperature. Under ambient
conditions compounds (1a-c) exist in a closed spirocyclic form SP
Table 2
Spectral properties of isomeric forms, the lifetimes of merocyanine forms and the rate constants of the thermal recyclization reaction in acetonitrile for the compounds (1a-c),
T ¼ 293 K.
No.
Structure
Form
lmax, nm (ε$10ꢁ4
,
Мꢁ1$cmꢁ1
)
tMC, s
kMC-SP, sꢁ1
1a
SP
MC
357 (0.6), 299 (2.43), 272 (2.08), 243sh (2.20), 228sh (2.59), 205 (3.83)
630
5.4
0.185
1b
SP
MC
379 (0.64), 299 (2.46), 281sh (2.23), 246sh (2.12), 230sh (2.69), 206 (4.08)
660
1.5
0.667
1c
SP
MC
343 (0.36), 300 (1.61), 235 (3.70), 200 (2.12)
579
46.0
0.022
she shoulder.

414
I.V. Ozhogin et al. / Journal of Molecular Structure 1196 (2019) 409e416
Fig. 5. Absorption spectra changes of compound (1c) under UV irradiation
(
lirr ¼ 365 nm, dt ¼ 1 s) in acetonitrile, C ¼ 2.9$10ꢁ5 M, T ¼ 293 K.
Fig. 3. Absorption spectra changes of compound (1a) under UV irradiation
(
lirr ¼ 365 nm, dt ¼ 1 s) in acetonitrile, C ¼ 4.2$10ꢁ5 M, T ¼ 293 K.
oxygen atom of merocyanine MC causes a hypsochromic shift and
electron donating methoxy-group leads to a bathochromic shift of
the absorption maximum for 51 and 30 nm respectively in com-
parison with methyl-substituted spiropyran (1a).
(Scheme 1) and their absorption spectra are characterized by ab-
sorption maxima in the region 200e379 nm
(ε ¼ 3600e40800 Mꢁ1 cmꢁ1) (Table 2). It should be noted that the
location of the long-wave absorption maximum of SP depends on
the nature of the substituents at the position 60 of the benzopyran
moiety. Thus, the introduction of the electron withdrawing
eCOOCH3 group (1c) leads to a hypsochromic shift (Dl ¼ 14 nm)
while the introduction of the electron donating eOCH3 group (1b)
leads to a bathochromic shift (Dl ¼ 22 nm) of the absorption
maximum in comparison with methyl-substituted spiropyran (1a).
Under exposure to UV-light (365 nm), an appearance of new
absorption bands with maxima at 579e660 nm was observed
(Figs. 3e5) due to the photoinduced isomerization of spiropyran
molecules and formation of their merocyanine forms (Scheme 1).
This process induces deep coloration of the compounds’ solutions.
The photographs of the cell with the MeCN solution of the com-
pound (1c) before and after irradiation are presented in Fig. 6. As in
the case with SP forms of the compounds, presence of electron
withdrawing substituent (1c) at the para-position to the phenolic
The reverse cyclization reaction leading to the formation of
spirocyclic forms of the compounds occurs spontaneously under
ambient conditions after UV irradiation ending. The kinetic curves
of the thermal relaxation processes are satisfactorily fitted by the
monoexponential function (Figs. 7, S10, S11). The lifetimes of MC
isomers (tMC) are varied in the range of 1.5e46.0 s (Table 2)
depending on the substituent at position 60 of the molecule. As it
was expected the presence of the electron withdrawing eCOOCH3
group causes enhancement of photocolorability of the spiropyran
solution and increases the lifetime of merocyanine up to 46 s which
is comparable with nitro-substituted spiropyrans [15,17]. This
positive influence of EWG located at para-position to the phenolic
oxygen atom of the MC isomer on photochromic properties can be
explained by delocalization of the excessive negative charge pro-
duced at corresponding oxygen atom during photoinduced trans-
formation due to eM-effect of the methoxycarbonyl substituent,
which stabilizes MC isomer and increases its lifetime. Irradiation of
pre-stained spiropyran solutions with visible light accelerates the
recyclization (Fig. 8), which indicates an occurrence of a reverse
Fig. 4. Absorption spectra changes of compound (1b) under UV irradiation
(
Fig. 6. The photographs of the cell with the MeCN solution of spiropyran (1c) before
and after irradiation.
lirr ¼ 365 nm, dt ¼ 1 s) in acetonitrile, C ¼ 3.5$10ꢁ5 M, T ¼ 293 K.

I.V. Ozhogin et al. / Journal of Molecular Structure 1196 (2019) 409e416
415
substituents can lead to a significant increase in their photo-
colorability and enhance the lifetime of the merocyanine form in
8e30 times.
We believe that in future our novel carboxy- and formyl-
substituted spiropyrans can be used for the creation of new reac-
tive chromogenic chemo- and biosensors, while the data obtained
will be useful for the development of new polyfunctional materials
with predetermined properties.
Acknowledgements
This work was carried out with the financial support of Southern
Federal University.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.molstruc.2019.06.094.
Fig. 7. The kinetic curve of thermal recyclization reaction at MC-maximum of the
compound (1c) in acetonitrile, T ¼ 293 K. Dots - experimental data, line e the result of
approximation by mono-exponential function.
References
[1] L. Wang, Q. Li, Photochromism into nanosystems: towards lighting up the
future nanoworld, Chem. Soc. Rev. 47 (2018) 1044e1097, https://doi.org/
10.1039/c7cs00630f.
[2] Z.L. Pianowski, Recent implementations of molecular photoswitches into
smart materials and biological systems, Chem. Eur J. 25 (2019) 5128e5144,
https://doi.org/10.1002/chem.201805814.
[3] S. Wang, L. Ma, G. Liu, S. Pu, Diarylethene-based fluorescent and colorimetric
chemosensor for the selective detection of Al3þ and CNꢁ, Dyes Pigments 164
(2019) 257e266, https://doi.org/10.1016/j.dyepig.2019.01.029.
[4] Y.S. Wang, F. Duan, G. Liu, P. Liu, C. Fan, S. Pu, Diarylethene-based multi-
controllable switch with pyridinepiperazine-linked, Tetrahedron 75 (2019)
2284e2290, https://doi.org/10.1016/j.tet.2019.02.056.
[5] Z. Chen, J. Zhang, M. Song, J. Yin, G.-A. Yu, S.H. Liu, A novel fluorene-based
aggregation-induced
emission
(AIE)-active
gold(I)
complex
with
crystallization-induced emission enhancement (CIEE) and reversible mecha-
nochromism characteristics, Chem. Commun. 51 (2015) 326e329, https://
doi.org/10.1039/C4CC08087D.
[6] G. Berkovic, V. Krongauz, V. Weiss, Spiropyrans and spirooxazines for mem-
ories and switches, Chem. Rev. 100 (2000) 1741e1754, https://doi.org/
10.1021/cr9800715.
[7] H. Bouas-Laurent, H. Dürr, Organic photochromism (IUPAC technical report),
Pure Appl. Chem. 73 (2001) 639e665, https://doi.org/10.1351/
pac200173040639.
[8] V.I. Minkin, Photo-, thermo-, solvato-, and electrochromic spiroheterocyclic
compounds, Chem. Rev. 104 (2004) 2751e2776, https://doi.org/10.1021/
cr020088u.
[9] B.S. Lukyanov, M.B. Lukyanova, Spiropyrans: synthesis, properties, and
application. (Review), Chem. Heterocycl. Comp. 41 (2005) 281e311, https://
doi.org/10.1007/s10593-005-0148-x.
Fig. 8. The kinetic curves of thermal recyclization (black squares) and photobleaching
(red circles) reaction at MC-maximum of the compound (1c) in acetonitrile, T ¼ 293 K.
[10] S.V. Paramonov, V. Lokshin, O.A. Fedorova, Spiropyran, chromene or spi-
rooxazine ligands: insights into mutual relations between complexing and
photochromic properties, J. Photochem. Photobiol. C Photochem. Rev. 12
(2011) 209e236, https://doi.org/10.1016/j.jphotochemrev.2011.09.001.
[11] M. Natali, S. Giordani, Molecular switches as photocontrollable “smart” re-
ceptors, Chem. Soc. Rev. 41 (2012) 4010, https://doi.org/10.1039/c2cs35015g.
[12] V.I. Minkin, Light-controlled molecular switches based on bistable spirocyclic
organic and coordination compounds, Russ. Chem. Rev. 82 (2013) 1e26,
https://doi.org/10.1070/RC2013v082n01ABEH004336.
photoreaction and confirms the fact that MC can be converted back
to SP form both thermally and photochemically.
4. Conclusions
[13] R. Klajn, Spiropyran-based dynamic materials, Chem. Soc. Rev. 43 (2014)
148e184, https://doi.org/10.1039/C3CS60181A.
[14] M.M. Lerch, M.J. Hansen, G.M. van Dam, W. Szymanski, B.L. Feringa, Emerging
targets in photopharmacology, Angew. Chem. Int. Ed. 55 (2016)
10978e10999, https://doi.org/10.1002/anie.201601931.
[15] R.C. Bertelson, Spiropyrans, in: J.C. Crano, R.J. Guglielmetti (Eds.), Organic
Photochromic and Thermochromic Compounds, Kluwer Academic Publishers,
2002, pp. 11e83, https://doi.org/10.1007/0-306-46911-1_2.
In summary, three new photochromic spiropyrans of indoline
series were synthesized and studied. All the compounds obtained
were modified with several carbonyl substituents, such as car-
boxylic, formyl and methoxycarbonyl groups. The structure of
target compounds was confirmed by NMR, IR spectroscopy and
elemental analysis. The molecular structure of spiropyran (1a) was
refined by single crystal X-ray analysis which revealed that the
molecules of studied spiropyran are arranged in dimer associates in
its single crystals due to the formation of two intermolecular
hydrogen bonds between hydrogen and carbonyl oxygen atoms of
the adjacent molecules.
[16] S. Aldoshin, Structural studies by X-ray diffraction, in: J.C. Crano,
R.J. Guglielmetti (Eds.), Organic Photochromic and Thermochromic Com-
pounds, Kluwer Academic Publishers, 2002, p. 297, https://doi.org/10.1007/
b115590.
€
[17] A.K. Chibisov, H. Gorner, Photoprocesses in spiropyran-derived merocyanines,
J. Phys. Chem. A 101 (1997) 4305e4312, https://doi.org/10.1021/jp962569l.
[18] A.D. Pugachev, M.B. Lukyanova, B.S. Lukyanov, I.V. Ozhogin, A.S. Kozlenko,
I.A. Rostovtseva, N.I. Makarova, V.V. Tkachev, N.A. Aksenov, New photo-
chromic indoline spiropyrans containing cationic substituent in the 2H-
chromene moiety, J. Mol. Struct. 1178 (2019) 590e598, https://doi.org/
10.1016/j.molstruc.2018.10.062.
Photochemical studies showed photochromic activity for each
of the compounds. It was shown that careful modification of
indoline spiropyrans with different electron withdrawing carbonyl

416
I.V. Ozhogin et al. / Journal of Molecular Structure 1196 (2019) 409e416
[19] M.B. Lukyanova, V.V. Tkachev, B.S. Lukyanov, S.M. Aldoshin, A.N. Utenyshev,
S.O. Bezuglyi, V.I. Minkin, V.A. Kogan, Photo-and thermochromic spiranes
31.*Structure and photochromic properties of functionalized benzoxazine
spiropyrans, Chem. Heterocycl. Comp. 44 (2008) 1384e1390, https://doi.org/
10.1007/s10593-009-0189-7.
[20] M. Tomasulo, S.L. Kaanumal, S. Sortino, F.M. Raymo, Synthesis and properties
of benzophenone-spiropyran and naphthalene-spiropyran conjugates, J. Org.
Chem. 72 (2007) 595e605, https://doi.org/10.1021/jo062004d.
(2017) 36, https://doi.org/10.3390/bios7030036.
[27] D.B. Stubing, S. Heng, A.D. Abell, Crowned spiropyran fluoroionophores with a
carboxyl moiety for the selective detection of lithium ions, Org. Biomol. Chem.
14 (2016) 3752e3757, https://doi.org/10.1039/C6OB00468G.
[28] S. Heng, X. Zhang, J. Pei, A. Adwal, P. Reineck, B.C. Gibson, M.R. Hutchinson,
A.D. Abell, Spiropyran-based nanocarrier: a new Zn2þ-responsive delivery
system with real-time intracellular sensing capabilities, Chem. Eur J. 25 (2019)
854e862, https://doi.org/10.1002/chem.201804816.
[21] A.V. Laptev, A.Y. Lukin, N.E. Belikov, K.V. Zvezdin, O.V. Demina,
V.A. Barachevsky, S.D. Varfolomeev, A.A. Khodonov, V.I. Shvets, Synthesis and
studies of photochromic properties of spirobenzopyran carboxy derivatives
and their model compounds as potential markers, Russ. Chem. Bull. 63 (2014)
2026e2035, https://doi.org/10.1007/s11172-014-0695-3.
[22] B.B. Safoklov, B.S. Luk’yanov, A.O. Bulanov, A.V. Metelitsa, V.I. Minkin,
V.V. Tkachev, S.M. Aldoshin, Photo- and thermochromic spiropyrans 21. 8ꢀ-
formyl-3,6ꢀ-dimethyl-4-oxospiro(3,4-dihydro-2H-1,3-benzoxazine-2,2ꢀ-[2H]
chromene) possessing photochromic properties in the solid phase, Russ.
Chem. Bull. 51 (2002) 462e466, https://doi.org/10.1023/A:1015556201886.
[23] Z. Wu, K. Pan, B. Lü, L. Ma, W. Yang, M. Yin, Tunable morphology of spiropyran
assemblies: from nanospheres to nanorods, Chem. Asian J. 11 (2016)
3102e3106, https://doi.org/10.1002/asia.201601114.
[29] I.V. Ozhogin, V.V. Tkachev, B.S. Lukyanov, E.L. Mukhanov, I.A. Rostovtseva,
M.B. Lukyanova, G.V. Shilov, N.D. Strekal, S.M. Aldoshin, V.I. Minkin, Synthesis,
structure and photochromic properties of novel highly functionalized spi-
ropyrans of 1,3-benzoxazin-4-one series, J. Mol. Struct. 1161 (2018) 18e25,
https://doi.org/10.1016/J.MOLSTRUC.2018.02.027.
ꢀ
[30] N.E. Gelman, E.A. Terentꢀeva, T.M. Shanina, L.M. Kiparenko, Metody Koli-
chestvennogo Organicheskogo Elementnogo Analiza [Methods of Quantitative
Organic Elemental Analysis], Khimiya, Moscow, 1987, p. 296 (in Russian).
[31] C.J. Roxburgh, P.G. Sammes, A. Abdullah, Steric and substituent effects on the
photoreversibility of novel indolospirobenzopyrans: acid deuterolysis, UV and
1H NMR spectroscopy, Dyes Pigments 82 (2009) 226e237, https://doi.org/
10.1016/j.dyepig.2009.01.006.
€
[32] B. Ingenfeld, S. Straub, C. Frombgen, A. Lützen, Synthesis of mono-
[24] S. Wan, Y. Zheng, J. Shen, W. Yang, M. Yin, “Oneoffeon” switchable sensor: a
fluorescent spiropyran responds to extreme pH conditions and its bioimaging
applications, ACS Appl. Mater. Interfaces 6 (2014) 19515e19519, https://
doi.org/10.1021/am506641t.
[25] G. Yu, Y. Cao, H. Liu, Q. Wu, Q. Hu, B. Jiang, Z. Yuan, A spirobenzopyran-based
multifunctional chemosensor for the chromogenic sensing of Cu2þand fluo-
rescent sensing of hydrazine with practical applications, Sensor. Actuator. B
245 (2017) 803e814, https://doi.org/10.1016/j.snb.2017.02.020.
functionalized calix[5]arenes, synthesis (stuttg), vol. 50, 2018, pp. 676e684,
https://doi.org/10.1055/s-0036-1589127.
[33] T. Routasalo, J. Helaja, J. Kavakka, A.M.P. Koskinen, Development of bis(2-
picolyl)amineezinc chelates for imidazole receptors, Eur. J. Org. Chem.
(2008) 3190e3199, https://doi.org/10.1002/ejoc.200700926, 2008.
[34] CrysAlis PRO Version 171.35.19, Agilent Technologies UK Ltd, Yarnton,
Oxfordshire, England, 2011.
[35] G.M. Sheldrick, SHELXTL V. 6.14, Structure Determination Software Suite,
Bruker AXS, Madison, Wisconsin, USA, 2000.
[26] S. Heng, X. Zhang, J. Pei, A. Abell, S. Heng, X. Zhang, J. Pei, A.D. Abell,
A rationally designed reversible ‘Turn-Off’ sensor for glutathione, Biosensors 7