Design and synthesis of disubstituted and trisubstituted thiazoles as multifunctional fluorophores with large Stokes shifts

Article abstract of DOI:10.1016/j.dyepig.2019.02.051

A series of fluorophores based on a thiazole core have been synthesized and shown to be very sensitive to both structural changes and the microenvironment. Simple modifications of the substituents’ electronic nature, spatial effects and location in the mo

Full text of DOI:10.1016/j.dyepig.2019.02.051

Accepted Manuscript
Design and synthesis of disubstituted and trisubstituted thiazoles as multifunctional
fluorophores with large Stokes shifts
Polina O. Suntsova, Alexander K. Eltyshev, Tatiana A. Pospelova, Pavel A.
Slepukhin, Enrico Benassi, Nataliya P. Belskaya
PII:
S0143-7208(18)32673-1
https://doi.org/10.1016/j.dyepig.2019.02.051
DYPI 7385
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 5 December 2018
Revised Date: 12 February 2019
Accepted Date: 28 February 2019
Please cite this article as: Suntsova PO, Eltyshev AK, Pospelova TA, Slepukhin PA, Benassi E,
Belskaya NP, Design and synthesis of disubstituted and trisubstituted thiazoles as multifunctional
fluorophores with large Stokes shifts, Dyes and Pigments (2019), doi: https://doi.org/10.1016/
j.dyepig.2019.02.051.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Design and Synthesis of Disubstituted and Trisubstituted Thiazoles as
Multifunctional Fluorophores with Large Stokes Shifts
Polina O. Suntsova,a Alexander K. Eltyshev,a Tatiana A. Pospelova,a Pavel A. Slepukhin,a,b Enrico
Benassi,*c Nataliya P. Belskaya*a,b
aUral Federal University, 19 Mira Str., Yekaterinburg 620002, Russian Federation
bPostovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Science, 22 S.
Kovalevskaya Str., Yekaterinburg, 620219, Russian Federation
cDepartment of Chemistry, Hexi University, Zhangye, 734000, PR of China
*Corresponding authors: e-mail: n.p.belskaya@mail.ru, ebenassi3@gmail.com
Abstract
A series of fluorophores based on a thiazole core have been synthesized and shown to be very sensitive
to both structural changes and the microenvironment. Simple modifications of the substituents’
electronic nature, spatial effects and location in the molecule allow the tuning of the photophysical
properties of the investigated compounds and their susceptibility to the environment via the exhibition
of long-wavelength emission, large Stokes shifts and good quantum yields. Additionally, the thiazole-
2-acrylonitrile fluorophores demonstrate a multifunctional character with significant fluorescence
properties (i.e., quantum yields and a large Stokes shift in both the liquid and solid states). The
influences of different factors, including the solvent polarity, on the fluorescence properties of the
synthesized compounds are discussed in detail. Quantum mechanical methods are employed to
understand the underlying transitions and explain the experimental results. This work provides further
information for the design of new sensors that have large Stokes shifts.
Keywords: Thiazole, Arylidene, Fluorescence, Solvatochromism, Stokes Shift, Biosensor
1. Introduction
Substituted 1,3-thiazoles, as heterocyclic cores, are commonly found in nature and are a preferable
structural fragments in various drugs [1]. Monocyclic thiazole is an essential motif of fluorescent
molecules and can be used to construct multifunctional materials [2] and chemosensors [3]. Among the
fluorescent thiazoles, 4-hydroxy- and 4-alkoxy derivatives are considered to be outstanding
compounds. The structures of 4-hydroxy- and 4-alkoxy derivatives are very similar to that of luciferin
of fireflies, and they have been shown to exhibit remarkable emission properties [4]. 2- or 5-
aminoderivatives are another large group of thiazoles that have a large Stokes shift and long-
wavelength emission independent of their molecular structure [5]. Numerous investigations have been
devoted to the synthesis of fluorescent thiazoles, which have been demonstrated to have photophysical
properties that are strongly dependent on the electronic nature of the substituents at the 2-, 4- and 5-

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positions of the thiazole core and their combinations [4,5]. Some relationships between the structure
and fluorescence were found for thiazoles containing additional aryl- or heteroaryl rings with various
types of substituents. For example, Görls and co-workers [4c,d] showed that the combination of an
electron-donor moiety (OH or OAlk) at the 5-position and an electron-acceptor moiety at the 2-
position of the thiazole improved the charge-transfer character, which, therefore, increased the Stokes
shift and led to a redshift in the fluorescence emission. Yashita and co-workers [5b] supported the
conclusion that strong electron-accepting groups (4-NO2C6H4, 4-CF3C6H4) at the C2 thiazole atom can
cause large bathochromic shifts in the emission wavelength. Takitoh and co-workers [5d] synthesised a
series of 5-N-arylaminothiazoles, investigated their fluorescence and solvatochromic behaviour, and
confirmed that the combination of electron-donating groups at the C5 thiazole ring (N-
arylaminogroups) and an electron-accepting aromatic ring at the С2-atom of the heterocycle core was
optimal for shifting of the absorption and emission bands to longer wavelengths and that the 4-position
had no essential influence on the photophysical characteristics. You X.-Z. and co-workers [5c]
generated a family of linear symmetric and asymmetric D-π-A and D-π-D thiazoles and drew the same
conclusions as mentioned above regarding the relationship of the structure-fluorescence
characteristics. However, Hanusek J. and co-authors [4a] observed that changing the substituents in the
aromatic ring in 5-arylthiazoles from an electron-donor to an electron-acceptor group did not
substantially influence the fluorescence. In addition, it was shown that the 2-position of the thiazole
ring was very sensitive to the microenvironment [5c]. All the presented results led to similar
conclusions, and this knowledge about the optical properties of thiazoles can be considered to provide
us with a good platform for the synthesis of fluorophores with tunable emission. However,
Radhakrishman and Sreejalekshmi [5a] carried out an extensive investigation on the photophysical
properties of a 30-member library of thiazole-thiophene cores with an aromatic ring at the C4 position
and a strong electron-accepting 5-nitrothiophene moiety at the C5 thiazole. The fluorescence
characteristics of these library members were shown to have a strong dependence on the electronic
nature of the C4 aromatic ring. They found that this type of electronic structure relied on a new
additional channel (C4→C5) compared with the traditional channel (C5→C2). The results obtained in
some cases were the opposite of the aforementioned conclusions: electron-accepting substituents at the
C5-thiazole position were more important for colour tunability; the presence of electron-donating
groups at C4 of thiazole induced a redshift, and the electron-donating groups of diphenylamine and
dimethylaniline placed at C2 and C4 exhibited synergistic effects on the absorption and emission
wavelengths, respectively [5a]. All these findings indicate the need to perform further investigations to
examine the structure-photophysical properties of thiazoles for the future design of new fluorophores
based on the thiazole core. In addition, the main published results concerning thiazoles have included
high polar hydroxyl- or amino-groups or their derivatives with an extremely strong electron-donor

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effect of the substituents and atoms, which can take part in strong intermolecular interactions as donors
or acceptors of hydrogen bonds.
Another significant detail for the design of new fluorophores with long-wavelength emission is the
molecular configuration, which may include various types of spacers (bonds, cyclic structures, and
atoms) that bind the separate fragments/substituents/rings [6]. Various π-π linkers have been used to
increase the conjugative system (double and triple bond, heterocycles, azo- or azine group) at the
thiazole C5 atom [4c, 5g,i,k, 7]. Much less is known about the effect of linear or cyclic systems on
extending the conjugation chain attached at the 2-position of thiazole [8].
Recently, we generated new thiazole derivatives, 2 and 3 (Scheme 1), with flexible conjugated
linear systems involving enamine (ETZs 2) or aza-enamine (ATZs 3) side chains at the C2 ring atom
and determined that the type of spacer group that links the thiazole to the peripheral aromatic ring is
very important. For example, the Stokes shift of thiazoles 2 and 3 varies depending on the combination
of the electronic and spatial effects of the substituents on the aromatic cycles (A and B) over a large
range (31–112 nm / 1900–5500 cm−1) [9].
The aim of this study was to investigate the fluorescence of fluorophores based on thiazole
surrounded by two or three aromatic/heteroaromatic rings, with one of them (at the C2 atom) separated
from the key heterocycle by an acrylonitrile fragment. The electronic structures of these compounds
are tuned by the classical approach of coupling various combinations of the substituents (D(C4)-π-
A(C2), A(C4)-π-D(C2), A(C4)-π-A(C2), D(C5)-D(C4)-π-A(C2) and D(C5)-A(C4)-π-A(C2)) as well
their spatial parameters and locations within the aromatic rings A, B (at C4 thiazole ring) and C (at C5
atom thiazole). Several of the designed thiazoles did not include the C5 aromatic ring in their structure
to define its significance on the photochemical behaviour of the investigated compounds.
Scheme 1. Design of new fluorophores based on thiazoles.
2. Experimental
2.1. Instruments and Materials
13
1Н NMR and C NMR, spectra were recorded with a Bruker Avance II (Karlsruhe, Germany)
1
13
(400 MHz for H, 100 MHz for C) spectrometer. Chemical shifts are reported in parts per million

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1
(ppm) relative to TMS in H NMR, to the residual solvent signals in 13C as external reference.
Coupling constants (J) values are given in Hertz (Hz). Signal splitting patterns are described as a
singlet (s), doublet (d), triplet (t), quartet (q), sextet (sext), quintet (quin), multiplet (m), broad (br),
doublet of doublets (dd), doublet of triplets (dt) or AA′XX′ - spin system of para-substituted benzene
with two different substituents. The 13C NMR signal patterns for several compounds were analysed by
APT (attached proton test). The major isomer signal is highlighted with an asterisk (*). Mass spectra
were recorded with a Shimadzu GCMS-QP 2010 “Ultra” (Kyoto, Japan) mass spectrometer using the
electron impact (EI) ionization technique (40-200 °C, 70 eV). The abbreviation [M]+ refers to the
molecular ion. Spectra of exact mass were acquire on a quadrupole orthogonal acceleration time-of-
flight mass spectrometer (Synapt G2 HDMS, Waters, Milford, MA). Samples were infused at 3uL/min
and spectra were obtained in positive (or: negative) ionization mode with a resolution of 15000
(FWHM) using leucine enkephalin as lock mass. The Fourier-transform infrared (FT-IR) spectra were
obtained using a Bruker Alpha (NPVO, ZnSe) spectrometer (Ettlingen, Germany). Elemental analyses
were carried out using a CHNS/O analyzer Perkin-Elmer 2400 Series II instrument (Shelton, CT
USA). Melting points for compounds 1a-q,u, 2a,b, 3a,b, 4d, 7a,b, 8a, 9a were determined on a Stuart
SMP3 apparatus (Staffordshire, ST15 OSA, UK) for compounds 1r,t,v,w were determined using
method of Differential scanning calorimetry (Mettler-Toledo DSC822e module).
X-ray crystallographic analysis was performed with a Xcalibur diffractometer with CCD using a
standard procedure (MoK-irradiation, graphite, ω-scanning with step 1°). CCDC-1872988 (for 1c) is
given in the ESI and supplementary crystallographic data for this paper. These data can be obtained
free
of
charge
from
the
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
UV-Vis absorption spectra were recorded on a Perkin-Elmer Lambda 35 UV-Vis
spectrophotometer (Shelton, CT USA). Fluorescence of the sample solutions was measured using a
Hitachi F-7000 spectrophotometer (Tokyo, Japan). The absorption and emission spectra were recorded
in toluene, dioxane, CH2Cl2, CHCl3, THF, EtOH, EtOAc, acetone, MeCN, DMF, DMSO using 10.00
mm quartz cells. The excitation wavelength was at the absorption maxima. Atmospheric oxygen
contained in solutions was not removed. Concentration of the compounds in the solution was 5.0 × 10-5
M and 5.0 × 10-6 M for absorption and fluorescence measurements, respectively. The relative
fluorescence quantum yields (ΦF) were determined using quinine sulfate in 0.1 M H2SO4 as a standard
(ΦF = 0.546). Absolute quantum yield for solid state and time-resolution study were recorded on
Horiba FlouroMax 4 Spectrofluorometer (Kyoto, Japan) with Quanta-φ integrating sphere using
FluorEssence 3.5 Software.
The reactions were monitored by analytical thin-layer chromatography (TLC) on aluminium-
backed silica-gel plates (Sorbfil UV–254). Visualization of components was accomplished by short
wavelength UVlight (254 nm). Solvents were dried and distilled according to the common procedures.

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All solvents were of spectroscopic grade. Full experimental details for the synthesis of compounds 1a-
w, 2a,b, 3a,b, 4d, 7a,b, 8a and 9a as well as their NMR spectra, photophysical characterization, and
quantum mechanical calculation data are reported in the electronic Supplementary information (ESI).
2-Cyanoethanethioamide, halocarbonyl compounds 5a-g and arylaldehydes 6a,b were obtained
from Acros Organics and used without further purification.
Arylidenethioamides 4a-i, arylhydrazonothioacetamide 8a and arylaminothioacrylamide 9a were
prepared according to procedures reported in the literature and their spectral characteristics were
identical to the published data [9,10]. Thiazoles 11 were prepared according to procedures reported in
the literature and their NMR, IR, and mass-spectrometry data were identical to the published data [11,
12].
2.2. General synthetic procedures for thiazoles 1a-w (Scheme 2).
Scheme 2. Synthesis of ATAs 1a-w.
Method A Halocarbonyl compound 5 (1.0 mmol) was added to a solution of thioamide 4 (0.9 mmol)
in dimethylformamide (DMF; 1.0 mL) or ethanol (EtOH; 1.0 mL) for compounds 1r,t,m. The mixture
was stirred at 60 °C for 0.5–24.0 h until the thin layer chromatography (TLC) analysis indicated total
consumption of the starting thioamide. The resulting mixture was diluted with EtOH (1.0 mL) and
cooled in an ice-salt bath for 1 h. The precipitate was collected by filtration, washed with water-
ethanol solution (20 mL, 1 : 1), and dried.

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Method B. Aldehyde 6 (2.4 mmol) and N-methylmorpholine (0.01 mL, 0.1 mmol) were added to a
solution of thiazole 7 (2.0 mmol) in DMF (2.0 mL). The mixture was stirred at 60 °C for 1.5–2.5 h
until the TLC analysis indicated total consumption of the starting thiazole. The resulting mixture was
diluted with ethanol (2.0 mL) and cooled in an ice-salt bath for 1 h. The precipitate was collected by
filtration, washed with water-ethanol solution (20 mL, 1 : 1), and dried.
Table 1. Time for the conversion of compounds 4a–i in reaction with halocarbonyl compounds 5a–g
and aldehydes 6a–b condensation with thiazoles 7a–b and yields of ATAs 1a–w
Structure
R2
4-MeO
4-Cl
4-MeO
H
4-MeO
4-Cl
4-MeO
H
4-Cl
4-MeO
H
4-MeO
H
Time,
(h)
Yield,a
(%)
86
88
80
91
62
78
80
92
97
82
85
Entry Compd
Route
A
R3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1
2
3
4
5
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
5.0
3.0
3.0
1.0
6.0
3.5
3.5
1.5
1.0
3.0
2.0
1.5
2.0
2.5
24.0
2.0
4.0
8.0
5.0
1.0
7.0
20.0
23.0
I
I
I
1a
1b
1c
1d
1e
1f
4-ClC6H4
I
4-CF3C6H4
4-CF3C6H4
4-CNC6H4
4-CNC6H4
4-CNC6H4
4-NO2C6H4
4-NO2C6H4
Pyridin-4-yl
Pyridin-4-yl
Pyridin-4-yl
2-ClC6H4
II
II
I
I
I
I
I
II
I
II
I
I
I
I
I
I
I
I
I
6
7
8
9
1g
1h
1i
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1j
1k
1l
1m
1n
1o
1p
1q
1r
1s
56
63b
80
4-Cl
4-MeO
4-MeO
4-MeO
4-MeO
H
4-MeO
H
4-Cl
70
65
2,4-Cl2C6H3
2,6-Cl2C6H3
4-ClC6H4
H
H
4-MeOC6H4
Ph
4-MeOC6H4
Ph
80
63c
79
4-ClC6H4
4-CNC6H4
4-CNC6H4
4-CNC6H4
4-CNC6H4
88c
52
1t
1u
1v
1w
4-MeC6H4
Ph
62
93
4-Cl
a
b
Isolated yields after separation and purification. Condensation thioamide 4f with 2-bromo-1-phenylethan-1-
one 5c under reflux in EtOH. c Reaction conditions: reflux thioamides 4b,d with 2-chloro-1,2-diphenylethan-1-
one 5g in EtOH.
2.3. General synthetic procedure for ETZs 2 and ATZs 3 (Scheme 3).
Enaminethiazoles 2 and azaenaminethiazoles 3 were prepared according to procedures reported in
the literature [9]. Halocarbonyl compound 5 (1.0 mmol) was added to a solution of thioamide 8a or 9a
(0.9 mmol) in DMF (1.0 mL). The mixture was stirred at 80 °C for 4 h until the TLC analysis indicated
total consumption of the starting compound. The resulting mixture was diluted with ethanol (1.0 mL)
and cooled in an ice-salt bath for 1 h. The precipitate was collected by filtration, washed with water-
ethanol solution (20 mL, 1 : 1), and dried.

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Scheme 3. Synthesis of ETZs 2a,b and ATZs 3a,b.
2.4. General procedure for the synthesis of thiazoles 11 (Scheme 4).
Thiazoles 11a,b were prepared according to procedures reported in the literature [11, 12].
Halocarbonyl compound 5 (1.0 mmol) was added to a solution of a pyridine-4-thioamide 10a (0.9
mmol) in EtOH (1.0 mL) for compounds 1r,t,m. The resulting mixture was cooled in an ice-salt bath for 1
h. The precipitate was collected by filtration and dried.
Scheme 4. Synthesis of thiazoles 11a,b.
3. Result and discussion
2.1. Synthesis and characterization
To realize our desired goals, we attempted to employ a simple synthetic method to introduce
various combinations of substituents into the thiazole core. Syntheses of 3-aryl-2-(thiazol-2-
yl)acrylonitriles (ATAs) 1a–w were carried out according to the Hantzsch thiazole synthesis, in which
thioacetamides 4a,b,d
,
e
,
g,h,i were condensed with the opportune α-halocarbonilic compounds 5a–g in
f with 2-bromo-1-phenylethan-one 5c or 2-chloro-1,2-
DMF, while the reactions of thioamides 4b,d
,
diphenylethan-1-one 5g used ethanol (Table 1, entries 13, 18, 20) [9, 10]. The choice of solvent was
determined based on the solubility of substrates 4 and 5. The desired products 1a–d,g–k,m,o–w were
obtained after a single purification step with good overall yields (63–97%). The results are
summarized in Table 1. However, in the reaction of thioamides 4c,f with bromoacetophenones 5a,b,
the products 1e,f,l and n were scarcely obtained; instead of route I, they were synthesized at good
yields by another route (II) based on the reaction of the aldehydes 6a,b with the thiazoles 7a,b [11].
The synthetic procedures used for the preparation of the designed molecules are simple, efficient,
and sustainable. The important advantage of the classical Hantzsch synthesis is the probability of

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obtaining a large and diverse library of desirable compounds from inexpensive and available starting
materials. Furthermore, two rings can be simultaneously attached onto C4 and C5 atoms of thiazole by
using suitable 2-bromo(chloro)-1,2-diarylethan-1-ones. An alternative method, the palladium-catalysed
cross-coupling reaction, requires the additional steps of constructing the starting thiazole ring,
followed by this parent core being pre-functionalized with a halogen or metal at the position where the
aryl groups should be attached [4d, 13]. Sometimes, pre-functionalization by bromination or
chlorination leads to the formation of by-products that bear an additional halogen atom owing to the
presence of electron-donating substituents at the aryl group favouring their formation. Thus, the
thiazoles 1r and 1t could not be obtained by this cross-coupling procedure.
The structures for ATAs 1a–w were confirmed by Fourier-transform infrared spectroscopy
1
(FTIR), H nuclear magnetic resonance (NMR) spectroscopy, 13C NMR spectroscopy, mass
spectrometry and elemental analysis data. The details of the experimental procedures and data for
structural characterization are provided in the electronic supplementary information (ESI). Notably,
the NMR spectra show that compounds 1a–w each exist as one steric isomer (Figs. S1–23, ESI).
Additionally, the crystal structure of 1c was determined by single-crystal X-ray diffraction (XRD)
analysis. XRD quality crystals were grown from ethanol with slow evaporation at room temperature.
The representative bond lengths and torsion angles are presented in Fig. S33 (ESI), and the crystal
structure is shown in Fig. 1.
a
b
c
d
Fig. 1. (a, b) Crystal structure of the compound 1c and (c, d) the crystal packing diagram.
The results indicate that the compound crystalized in the monoclinic system with the P2/1c space
group. The molecule is essentially planar and exists as an E geometric isomer with respect to the C1-
C2 double bond.

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It is known that molecular packing plays a significant role in the photoluminescence efficiency [6,
14]. J- and X-stacking are preferable for increasing the emission intensity [15]. As shown in Fig. 1, the
molecules of ATA 1c were packed into parallel two-dimensional sheets (Fig. 1b), in which all of the
neighbour molecules were located in a head-to-tail arrangement. Adjacent sheets in the single-crystal
adopted a rotational angle of approximately 58º (Fig. 1с). In the crystal, packing molecules were partly
linked through intermolecular π-π interactions, which resulted in parallel stacking, and all of the
molecules were shifted with respect to each other. The perpendicular distance between the closest
sheets was 3.380 Å (Fig. 1b), and only weak interactions between the dye layers were expected [16].
The dipoles of the two molecules of compound 1c facing each other head-on in the same sheet (Fig.
1c) opposed each other. Consequently, the presence of excited state deactivation channels by internal
conversion and a subsequent radiation less decay to the electronic ground state (GS) is unlikely. Thus,
the crystal packing may be classified as being close to J-type, which explains the emission in the solid
state (vide infra).
2.2. Photophysical properties of ATAs
With the 23-member library of the synthesized ATAs 1a–w in hand, we estimated their
photophysical properties to validate their potential for use as fluorophores. Fig. 2 shows photographs
of solutions of 1a–w in acetonitrile (MeCN) under irradiation with UV light; the corresponding data
are listed in Table 2. Compounds 1a, 1b and 1d were non-fluorescent.
Fig. 2. Photographs of solutions of 1a–w in acetonitrile under irradiation with a hand-held UV lamp at
an emission wavelength of 365 nm.
Synthesized thiazoles exhibited substantial shifts in their absorption wavelength in the range of
357–407 nm, with a large range of values for the extinction molar coefficients (εmax = 7300–29200 M−1
cm−1). The displacement of the electron-accepting NO2- or CN-group at ring A instead of the electron-
donating MeO-group in combination with the 4-MeO-substituent ring B or rings B and C
simultaneously led to bathochromic shifts in the long wavelength absorption bands (Table 2, Entries 1,
10 and 20). Despite consideration of the whole set of absorption bands for the obtained compounds,
the influence of the electronic effects of the substituents is not obvious.

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Table 2. Photophysical data of ATAs 1a–w in solution (MeCN)
UV-Visa
Fluorescenceb
λem, (nm)
ФF,d (%)
Stokes shift
(nm/cm-1)
⟨τ⟩fe
(ns)
Entry Compd
εmax,
λabs,c (nm)
(M-1 cm-1)
17800
1
2
3
4
5
380
373
376
364
380
-
-
-
-
-
1a
1b
1c
1d
1e
23300
11900
29200
10200
472
543
480
555
0.2
4.8
0.3
1.5
99/5620
167/8180
116/6640
175/8300
3.61
-
-
359
12000
490
5.7
131/7450
1.20
1.43
3.40
2.85
-
2.85
1.92
4.85
4.24
3.93
3.05
4.07
3.63
-
6
7
8
9
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
1s
389
370
367
399
382
382
361
357
372
377
360
394
365
407
379
383
377
7300
16200
11200
11700
19100
9000
7600
8900
9000
9600
561
501
501
-
0.8
18.0
18.0
-
5.1
4.0
26.3
16.8
6.2
3.1
3.8
6.2
0.4
7.8
10.1
11.0
11.4
172/7880
131/7070
134/7290
-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
552
561
495
495
555
557
550
553
501
572
527
535
522
170/8060
179/8350
134/7300
138/7810
183/8860
180/8570
190/9600
159/7300
136/7440
165/7090
148/7410
152/7420
145/7370
8600
16200
13600
14500
16800
12200
13100
2.9
1t
3.20
3.02
2.48
1u
1v
1w
a Absorption measured in solution with a sample concentration of 5×10−5 M. b Emission measured at a
c
d
sample concentration of 5×10−6 M. Longest absorption maxima are only reported. Fluorescence
e
quantum yields (QYs) are measured relative to quinine sulfate (λexc = 366 nm; Ф = 0.53).
Fluorescence lifetime.
Dilute solutions of compounds 1a–w showed emission bands centred with maxima over a large
wavelength range from 472 to 572 nm; the data also demonstrated a strong dependence on the
substituent combination at rings A, B, and C and their locations. The increase in the electron-accepting
properties of the ring A substituents and decrease in the electron-accepting properties of the ring B
substituents caused a bathochromic shift in the fluorescence maxima of up to 561 nm (89 nm) for
diaryl-substituted ATA 1g. Introduction of the additional aromatic ring C to the C5 atoms of thiazoles
1r–w afforded an additional shift in the emission maxima to the red region (10–26 nm), especially for
ATAs 1r and 1t, which had electron-donating substituents on rings B and C; at the same time, this
increased their quantum yields (Table 2, entries 3, 7, 18, and 20). It should be mentioned that the
introduction of a second 4-methoxyphenyl moiety at the C5 position of the thiazole ring resulted in a
redshift of 18 nm and 11 nm in the absorption and emission bands, respectively (Table 2, entries 7 and
20). This behaviour may originate from the strengthening of the electronic coupling between the donor
and acceptor terminals of the molecule through the thiazole moiety and the acrylonitrile π-spacer.
Appearance of a second shorter conjugation system, in accordance with that established by

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Radhakrishman and Sreejalekshmi [5a], but with the opposite direction (C5→C4), may be the reason
for the larger long-wavelength shifts of 24 and 21 nm observed for compounds 1w and 1v, respectively
(Table entries 9, 22 and 23). Thus, a combination of substituents D(C5)-A(C4)-A(C2) supported the
possibility of a new intramolecular charge transfer (ICT) strengthening (C5→C4) as well as (C4→C5)
[5a], which can be used for the design of new effective fluorophores with a long-wavelength emission.
It should be noted that the emission characteristics depend on the location of the substituent on the
aromatic ring A. For example, displacement of the Cl atom from the 4- to the 2-position on ring A led
to a small redshift of the long-wavelength maxima (12 nm). This change was opposite to the blue shift
of the absorption maxima (4 nm) (Table 2, entry 3 and 15). However, the efficiency of fluorescence of
the 2-substituted compounds 1o-q increased because of the reduction in the non-radiative emission
owing to the spatial hindrances caused by rotating ring A.
The steric bulkiness (ring A) and increasing conjugation along C4 also had noticeable effects on
the emission, as evident from a comparison of the spectra of the 4-aryl-substituted thiazoles 1c,d,g,h,i
and 4,5-diaryl-substituted thiazoles 1r,w. Compounds 1a–w had fluorescence quantum yields (QYs)
that increased from 0.2 to 26.3% in acetonitrile (relative to quinine sulphate).
Thus, modification of every thiazole substituent (C2, C4 and C5 atoms) was identified to be
crucial for the π-conjugation network and, consequently, for manipulating the ATAs by a push-pull
effect.
We should emphasize that the main feature of the photophysical properties of the thiazoles
obtained was their remarkable Stokes shifts, which reached up to 9600 cm−1 (190 nm) in acetonitrile
(Table 2, entry 17). In addition, this is one of the largest values reported for Stokes shifts for both
thiazoles [4,5] and organic fluorophores in principle [17]. Furthermore, despite the considerable Stokes
shift, the ATAs retained quite significant values for the QY compared with examples in the literature,
as an increase in the Stokes shift usually results in a sharp drop in the quantum yield [4,5]. For
example, ATAs 1a–w in acetonitrile had an increased Stokes shift from 131 to 190 nm, which was
accompanied by a 7-fold decrease in the QY (from 27.2 to 3.8%), while 5(5-nitrothiophene-2-
yl)thiazoles [5a] showed an 84-fold drop in the QY (8.4 to 0.1%) with a similar change in the Stokes
shift (129–195 nm).
Fluorescence lifetime decay measurements of the thiazole solutions in acetonitrile were performed
(Table 2, Table S1, ESI). Fig. S35 (ESI) illustrates the excited-state decay curves for the dyes recorded
in acetonitrile. The detailed data for the corresponding decay parameters are included in Table S1
(ESI). In acetonitrile, thiazole had fluorescence lifetimes in the range of 1.20–5.30 ns. Importantly, the
pyridyl-derivatives of 1m and 1n possessed the longest average fluorescence lifetimes, which
indicated that they exhibited some of the best fluorescence properties, consistent with the absorption
and emission spectra. The values of the radiative (kr) and non-radiative decay constant (knr) of the
thiazoles in acetonitrile were calculated [6]. The larger non-radiative decay constant values of ATAs

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1g and 1f demonstrated the dominant dissipation of excitation energy through non-radiative channels
(Table S1, ESI).
2.3. Solvato (fluoro) chromism
Compounds 1c,g,h,k–n,u were studied in different solvents (hexane, toluene, CH2Cl2, EtOH, i-
PrOH, acetone, DMF, acetonitrile, DMSO, 1,4-dioxane, CHCl3, n-BuOAc, EtOAc) in aerated solutions
at room temperature. The strong influences of the electronic effect of the substituents in the molecules
and the polarity of the solvents on the photophysical properties were demonstrated. The
solvatochromic and solvatofluoric properties of the ATAs 1c,g,h,k–n and u are summarized in Fig. 3,
Fig. S37 and Table S2 (ESI).
The absorption spectra of the thiazoles 1c,h,k–n,u showed little dependence on the solvent
polarity. By contrast, solvent-dependent bathochromic shifts of more than 60 nm (60–97 nm) were
observed in the fluorescence spectra. Normalized emission spectra are shown in Fig. 3 and in Figs. S37
and S38 (ESI). As the solvent became polar, the emission exhibited increasing redshifts, indicating an
ICT behaviour, which is better stabilized in polar solvents. The observations outlined above suggest
emission from ICT, which seemed to have a greater dipole moment in the excited state than in the GS.
ATA 1k was more sensitive to the solvent polarity and demonstrated the largest shift to longer
wavelengths (97 nm).
The QY of 1c,g,h,k–n,u in various solvents revealed that the fluorescence intensity was very
strongly dependent on the structure and solvent used. The studied thiazole derivatives can be divided
into three groups. The first group includes ATAs 1k and 1l, which showed a more intense emission in
non-polar CH2Cl2 or toluene. Their structures included strong electron-accepting substituents at the
arylacrylonitrile fragment at the C2 atom and electron-donor groups at the aryl cycle at the C4 atom of
the thiazole ring. The second group involves compounds 1c and 1h, which have better fluorescence
intensity in more polar solvents, such as acetone or DMF. Finally, the third group includes ATAs 1m,
1n, and 1u, for which the largest QY values were observed in alcohols (EtOH, i-PrOH). The most
intense emissions were obtained for thiazole 1m in EtOH (60%). The large values of the QY in
alcohols for thiazoles 1m, 1n, and 1u suggested their strong potential to form intermolecular hydrogen
bonds, which decreased the molecular rotations during geometric relaxation and decreased the non-
radiative processes for energy loss. These findings [18] regarding the formation of intramolecular non-
covalent bonding, owing to dipole-dipole interactions or hydrogen bond formation, promote the use of
such compounds as chemo-sensors and bio-sensors.
Analysis of the Stokes shift values in different solvents for the investigated molecules (Fig. 3 and
additional spectra in Fig. S37, ESI) showed large Stokes shift values for most of the compounds. The
large increase in the values of the Stokes shift followed the increase in the solvent polarity, as
demonstrated for the compounds 1c,h,k–n,u in acetone, MeCN, DMF and DMSO, with values in the

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range of 127–179 nm. The high Stokes shift is very useful for small organic fluorophores [6, 17],
especially for their imaging applications [19].
More evidence that the strong ICT behaviour was correlated with the large difference in dipole
moments between the ground and excited states was the pronounced positive solvatochromism
exhibited by all of the molecules studied (Table S2). For example, in the case of 1c, upon increasing
the solvent polarity from n-hexane to DMSO, the emission band was redshifted by 83 nm (468 nm in
n-hexane and 551 nm in DMSO, Table S2). Such a high sensitivity to the microenvironment is
comparable to the sensitivity of oxythiazoles and aminothiazoles, which have heteroatoms that are
capable of forming intramolecular interactions [4a,e,g,j, 5a].
c
a
b
d
Fig. 3. (a) Absorption and (b) fluorescence spectra of ATA 1h in different organic solvents. For
absorption measurements, 1h concentration: 5×10−5 M, for fluorescence spectra, concentration: 5×10−6
M, excitation wavelength: 377 nm. Photographs of solutions of ATA 1h in acetonitrile under daylight
(с) and under irradiation (d) with a hand-held UV lamp at an emission wavelength of 380 nm.
Solvents: 1 − Hexane, 2 − Toluene, 3 − 1,4-Dioxane, 4 − CHCl3, 5 − CH2Cl2, 6 − THF, 7 − i-PrOH, 8
− EtOH, 9 − n-BuOAc, 10 − EtOAc, 11 − Acetone, 12 − DMF, 13 − MeCN, 14 – DMSO.
2.4. Fluorescence of ATAs in the solid state
The crystal compounds of the thiazoles 1a–w were yellow and bright-orange coloured. In addition
to the photophysical properties shown in Table 4, we found that ATAs 1a–w exhibited solid-state
fluorescence (Table 3, Fig. S40, ESI). All the dyes emitted at 477–584 nm with quantum yields in the
range of 0.1–19.2%. The emission maxima of the solid samples of all of the studied ATAs were
redshifted with respect to those of the corresponding solutions from 6 to 89 nm (Tables S3 and 4). The
value of the QY in the solid state largely depended on the interactions between the molecules in the
crystal packing, which was predicted and discussed above. It should be noted that the efficiency of the
emission in the solid is very close to that of hydroxy- and aminothiazoles [4a, 5b].

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Table 3. Photophysical data of thiazoles 1a–w in the solid state
Photograph of powders
a
λex,
(nm)
λem.solid
(nm)
,
Stokes shift
(nm /cm-1)
Entry
Compd
Фs,b (%)
day
UV-irradiationc
light
1
2
380
373
376
364
380
359
389
370
367
399
382
382
361
357
372
377
360
394
362
407
379
383
377
526
501
522
505
537
477
528
503
521
572
545
530
584
516
519
526
509
523
495
583
506
549
523
146/7300
128/6850
146/7440
141/7670
157/7690
118/6890
139/6770
133/71506
154/8050
173/7580
163/7830
148/7310
223/10580
159/8630
147/7610
149/7510
149/8130
129/6260
133/7420
176/7420
127/6620
166/7890
146/7400
7.2
19.2
9.8
11.3
3.5
5.2
12.8
2.8
15.2
0.1
0.6
0.8
-
1a
1b
1c
1d
1e
1f
3
4
5
6
7
1g
1h
1i
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1j
1k
1l
1m
1n
1o
1p
1q
1r
1s
3.2
9.3
13.6
1.3
7.7
3.0
2.6
1.6
6.1
8.7
1t
1u
1v
1w
a Excited at λex.solid. b Absolute fluorescence quantum yield. c Photographs showing the emission colours
of ATAs solids when excited with a UV lamp (λex = 365 nm).
2.5. Quantum mechanical calculations
To gain a better understanding of the nature of the electronic transitions underlying the absorption
and fluorescence spectra, quantum mechanical methods were used. The ATAs 1a–d,g–p,s,u were first
optimized in their ground electronic state (S0) and lowest lying excited singlet electronic state (S1) at
the (TD-)DFT level (the details of the quantum mechanical calculation are presented in the ESI).
The structures of the ATAs 1a–d,g–p,s,u had several isomers/rotamers, which were at
equilibrium. To determine the lowest energy structures for the investigated compounds, a
conformational study was performed, which accounted for solvent (acetonitrile) effects.
However, the differences in energies for the ATAs 1a–d,g–p,s,u between the different

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conformers were small at room temperature, which meant that the observed properties and
characteristics were average (Table S3, ESI). Therefore, in further computational
investigations, we had to account for several more stable isomers/rotamers. The bond lengths,
bond angles, and dihedral angles responsible for the photophysical parameters are listed in Tables S4–
S11 (ESI). The structure of the ATAs in both the ground and excited states was found to be distorted
from planarity (in acetonitrile). The dihedral angle θ1 formed by ring A and the linear spacer of the
dyes 1a–d,g–p,s,u was a twisted angle, which showed values of up to 33.7° for the 4-substituted
derivatives 1a–d,g–p,s,u and 57.5° for the 2-substituted ATA 1p in the GS, which remarkably dropped
(1.3–9.7°), even for the 2-substituted 1p, in their excited state (Tables S5, S6, ESI). The alignment of
ring B deviated from planarity with the thiazole plane by up to 17.9º for the 4-arylthiazoles 1a–d,g–p
and 40.8º for the diarylthiazoles 1s and 1u in the GS. In the excited states, the torsion angle θ2
decreased to 2.7–15.8º for the 4-arylthiazoles and only changed to 3.9–7.3º for the 4,5-disubstituted
derivative 1p. Thus, the excited state geometries for the ATAs 1a–d,g–p became more planar
compared with their geometries in the GS, apart from compound 1a, for which the structure was
twisted in the excited state owing to the increased torsion angle C1C2C3C5. The rotation of the
aromatic ring A can cause a significant energy loss and lack of fluorescence. The conjugated system
for most ATAs became stronger during excitation due to the shortening of the single bond lengths in
S1 (Tables S4 and S6, (ESI)). These data explain the insignificant influence of solvents on the ATAs
absorption and the strong increasing of the polar solvent effect on their emission. However, the results
of the geometry optimization showed some differences with the planarity observed in the single-crystal
structure, which may be explained by the strengthening of the intermolecular interaction in the solid
state.
The vertical excitations, major transitions of the absorption maxima, orbital contributing to the
major transition for absorption, emission wavelength maxima, and their respective Stokes shifts were
calculated using TD-DFT with the Polarizable Continuum Model (PCM in various solvents for the
stable isomers). There was a good correlation between the experimental and calculated absorption and
emission data (Tables S12, S13, ESI).
For compounds 1a–d,f, excitation to the first singlet excited state (S0 → S1) was preferable (f01 =
0.3901 – 1.0853, λmax = 361−392 nm). Then, the ATAs underwent the reverse transition, S1 → S0,
which was accompanied by emission (f10 = 0.5113–1.2076, λmax = 470−561 nm) (Table S12, ESI).
The dipole moment of the dyes 1a–b,g–p,s,u showed that the push-pull dye 1j had the largest dipole
moment in the GS, which increased during the excitation (Tables S12, S13, ESI). The dipole moments
of most of the investigated compounds remarkably increased in the vertical excited state, particularly
for the ATAs 1b,c,l,o,p,u. Moreover, for the 1u A and B rotamers, the dipole moment increased from
the GS (10.7 D) to the Frank-Condon state by up to 16.7 D and after geometric relaxation became 17.8

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D. Moreover, for ATA 1u, the increase of the dipole moment was accompanied by a substantial
change in the angle of the dipole moment vector (up to 164.8–165.1º in S1r (Table S12, ESI)).
The contour plots for the HOMO and LUMO levels of the dyes are presented in Fig. S44 (ESI).
The electron densities in the HUMO and LUMO were dependent on the substitution pattern and its
localization in the molecule. We classifies these behaviour into two types: in the first type, the electron
density was distributed almost evenly throughout the whole molecule for the ATAs 1a–c,s,u in the GS
and for 1i–k,m–p,s,u in the excited state. For the second type, the main part of the electronic density
was localized on the ethylene link, thiazole ring and cycle B or the two cycles together (B and C). This
pattern was observed for the compounds 1g,h–p. In the LUMO, the electron density of all of the
molecules was completely localized on the aromatic cycle A, thiazole ring, and linear double bond,
while aromatic ring B at the 4- or cycles B and C at the 4- and 5-carbon atoms of thiazole were
excluded from the common molecule conjugated system. This result indicated that the electron cloud
was mainly concentrated on thiazole and cycle A and almost absent on the aromatic cycle B or B and
C simultaneously. Thus, we concluded that rearrangement of the charge within the molecule takes
place when the molecule absorbs a quantum of light.
The molecular electrostatic potential (MEP) provides important information about the molecular
polarity in GS and ES and the probability of the intermolecular interactions, particularly dipole-dipole
and hydrogen bonding interactions and changes of the molecular polarity during the excitation. It is
understood from the MEP map that remarkable changes were accomplished by the transitions of the
molecules of the ATAs 1a,b,j–p to the excited state. These changes are an additional explanation of
their high sensitivity to the microenvironment in the excited state discussed above.
2.6. Influence of the acrylonitrile spacer on the photophysical properties of ATAs
To identify the role of the C2 acrylonitrile unit on the optical characteristics of the ATAs, we
replaced this link with another: for example, a hydrazone or enamine unit (Scheme 3). Thus, the new
compounds 2a,b and 3a,b were synthesized using a previously published procedure [9], and their
photophysical properties were measured and compared with those of the ATAs 1g and 1h (Table 4).
It was obvious that changing the hydrazono- and enamino-linkers in EATs 2 and AATs 3 to an
acrylonitrile fragment led to a sharp enhancement of the photophysical properties of ATAs. We
observed substantial increases in QY, as well as bathochromic shifts of the absorption and emission
maxima and increased Stokes shifts.

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Table 4. Absorption and emission properties of thiazoles 2a,b and 3a,b in different solvents
UV-Vis
Fluorescence
Stokes
shift,
Entry
Compd
Solvent
λabs,
(nm)
400
396
395
395
389
380
375
375
376
370
381
379
378
380
376
377
375
373
376
372
405
404
403
481
401
401
399
398
477
396
εmax,
λem,
ФF, (%)
(nm/cm-1)
119/5730
158/7200
160/7300
175/7770
172/7880
92/5130
115/6260
125/6670
131/6870
131/7070
60/3570
68/4010
66/3930
73/4240
75/4420
61/3690
62/3780
61/3770
60/3660
-
(M-1 cm-1)
11000
8600
(nm)
519
554
555
570
561
472
490
500
507
501
441
447
444
453
451
438
437
434
436
-
Toluene
DCM
EtOH
24.8
6.5
0.8
0.2
0.8
1
2
3
4
5
6
7
8
5100
11000
7300
1g
DMF
MeCN
Toluene
CH2Cl2
EtOH
17300
15700
12900
17600
16200
20500
17300
9000
31300
32300
29800
30200
20700
29900
34700
24100
18400
9400
9.8
13.1
18.0
27.2
18.0
0.3
0.1
0.1
0.3
0.1
<0.1
<0.1
<0.1
<0.1
-
1h
2a
2b
3a
3b
DMF
9
MeCN
Toluene
DCM
EtOH
DMF
MeCN
Toluene
DCM
EtOH
DMF
MeCN
Toluene
DCM
EtOH
DMF
MeCN
Toluene
DCM
EtOH
DMF
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
494
527
508
-
0.2
0.2
0.2
-
89/4450
123/5780
120/5700
-
104/5100
104/5100
93/4700
88/4500
-
27900
30500
24700
21000
23700
27400
26900
505
490
492
486
-
0.1
<0.1
<0.1
<0.1
-
MeCN
-
-
-
a
b
Absorption measured in solution of concentration 5×10−5 M. Emission measured at a sample
c
d
concentration of 5×10−6 M. Longest absorption maxima are only reported. Quantum yields (QYs)
are measured relative to quinine sulfate (λexc = 366 nm; Ф = 0.53).
To determine the importance of the acrylonitrile linker on the photoactive ability, additional
reference compounds were used, the thiazoles 11a,b, which did not include this fragment but
contained pyridine rings connected with the C2 atom thiazole ring by a σ-bond. The data for the
absorption and emission characteristics of these compounds are absent in the literature; therefore, we
synthesized these compounds and measured their absorption and emission spectra (Table 5).

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Table 5. Absorption and emission properties of ATAs 1l,m and thiazoles 11a,b in different solvents
UV-Vis
Fluorescence
Stokes
shift,
Entry
Compd
Solvent
λabs,
(nm)
392
389
392
388
382
390
372
418
370
368
361
371
340
401
340
340
394
341
376
325
323
370
325
εmax,
λem,
ФF, (%)
(nm/cm-1)
109/5550
153/7260
167/7620
171/7880
179/8350
171/7820
91/5280
(M-1 cm-1)
9700
(nm)
501
542
559
559
561
561
463
554
501
499
495
510
415
548
457
451
560
455
472
407
402
498
-
Toluene
CH2Cl2
EtOH
28.5
12.9
0.2
1.6
4.0
3.8
34.6
8.6
60.0
40.6
26.3
12.4
3.7
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
7900
8900
10200
9000
8500
10200
10300
9200
8700
7600
1l
DMF
MeCN
DMSO
Toluene
CH2Cl2
EtOH
136/5870
131/7070
131/7130
134/7500
139/7350
75/5300
147/6700
117/7500
111/7200
166/7500
114/7300
96/5400
82/6200
79/6100
128/6900
1m
DMF
MeCN
DMSO
Toluene
CH2Cl2
EtOH
7100
3900
3100
5000
4400
6300
5400
5100
5900
5200
9000
4500
8.9
22.0
15.8
0.2
16.3
28.0
4.8
4.1
55.8
-
11a
11b
DMF
MeCN
DMSO
CH2Cl2
EtOH
DMF
MeCN
DMSO
a
b
Absorption measured in solution of concentration 5×10−5 M. Emission measured at a sample
concentration of 5×10−6 M. Longest absorption maxima are only reported. Quantum yields
c
d
(QYs) are measured relative to quinine sulfate (λexc = 366 nm; Ф = 0.53).
a
b
c
d
e
f
g
h
Fig. 4. (a, e, i, m, q, u) Absorption and (b, f, j, n, r, v) fluorescence spectra of ATAs 11a,b in different
organic solvents. For the absorption measurement, the sample concentration was 5×10−5 M. For the

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fluorescence spectra, the sample concentration was 5×10−6 M with an excitation wavelength of 377
nm. Photographs of solutions of ATAs 11a,b under daylight (с, j, k, o, s, x) and under irradiation (d, h,
l, p, t, y) with a hand-held UV lamp at 365 nm. 1 − Hexane, 2 − Toluene, 3 − 1,4-Dioxane, 4 − CHCl3,
5 − CH2Cl2, 6 − THF, 7 − i-PrOH, 8 − EtOH, 9 − n-BuOAc, 10 − EtOAc, 11 − Acetone, 12 − DMF,
13 − MeCN, 14 – DMSO.
First, we should mention that compounds 11a,b had lower solubility in organic solvents, as we used
a smaller set of solvents for the investigation. The spectral data from a dilute sample in different
solvents demonstrated large differences to the absorption and emission maxima of the thiazoles 1l,m
and 11a,b: (1) the ATAs 1l and 1m exhibited a more obvious bathochromic shift in absorption (48–52
nm for 11a and 9–46 nm for 11b); (2) compounds 1l and 1m had larger Stokes shifts (91–829 and
1050–1848 cm−1 for 11a and 11b, respectively). Thus, the ATAs 1 possesses the advantage of a
relatively wide and adjustable range of fluorescence colours; (3) The ATAs maintained a remarkable
emission intensity despite exhibiting large Stokes shifts. (4) The diversity in the structures of these two
thiazole types resulted in the rather different behaviours observed in solvents. For example, the largest
value of the QY for the ATAs 11m was obtained in ethanol (60%), while thiazole 11b had the highest
QY (55.8%) in acetonitrile. Thus, we can conclude that the most important factor for high-intensity
and long-wavelength emission is the combination of an electron withdrawing substituent at the
periphery of the C2 structural fragment with the electron donating substituent on the C4 aromatic
cycle. In contrast to the results reported by Radhakrishman and Sreejalekshmi [5a], the key influence
of the C5 electron-accepting group was demonstrated for the case of the ATAs 1, for which good and
rich photophysical characteristics were found for compounds where the C5 substituent was absent or
had an electron-donating nature. It is obvious that the acrylonitrile spacer in the AТA structures plays
an important role in their solvato (fluoro) chromic behaviour.
3. Conclusions
We described the synthesis, structures, and photophysical properties of a series of arylidenethiazoles
ATAs 1a–w containing different types of substituents (electron-withdrawing and electron-donating
groups) on each benzene ring for which the fluorescence properties were previously unknown in the
literature. Despite the absence in their structures, polar substituents such as OH- or amino groups
demonstrated high photophysical properties. Furthermore, ATAs showed multifunctional properties
and exhibited fluorescence both in dilute solutions of different organic solvents and in the solid state
with good or high quantum yields, large Stokes shifts, and relatively long lifetimes, which supports
their potential for use as good fluorophores.
The obtained compounds demonstrated a strong effect of the electronic nature of the substituents
on their fluorescence properties, in accordance with the previous literature data for the structure-

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fluorescence relationship. In addition to these data, we showed the possibility of involving two ICT
channels in a molecule and the ability to handle their strength and direction.
One of the main conclusions that can be drawn is that including an acrylonitrile spacer at the С2
thiazole position has a significant effect that governs the optical properties; in particular, this fragment
changed the solvato (fluoro) chromic behaviour of thiazoles. In addition, our studies showed that this
group enhances the sensitivity of the thiazole molecule to the microenvironment at a large scale; thus,
they can be proposed for use as chemo- and biosensors. Studies on the further enhancement of the
optical properties of these thiazoles are currently in progress.
Conflicts of interest
The authors declare no competing financial interest.
Acknowledgements
The reported study was funded by RFBR according to the research project No. 18-33-00859 mol_a.
The Siberian Branch of the Russian Academy of Sciences (SB RAS) Siberian Supercomputer Center is
gratefully acknowledged for providing supercomputer facilities. E.B. acknowledges the participation
of undergraduate students Mr A. Karymsakov, Ms Zh. Mukanova, Ms G. Nurdildayeva, Mr M.
Segizbayev, and Mr A. Shakenov (Dept of Chemistry, School of Science and Technology, Nazarbayev
University, Astana, Rep. of Kazakhstan) for the preliminary quantum mechanical calculations.
Appendix A. The electronic supplementary material is available free of charge:
1H and 13C NMR spectra of all new compounds; X-ray crystallographic data for compound 1c (CCDC
1872988); Computational results and Cartesian coordinates (PDF).
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•
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•
•
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Fluorescent thiazoles sensitive to microenvironment were designed and synthesized.
The compounds demonstrated the large Stokes shift and significant quantum yield.
Relationship between structure and fluorescent characteristics was established.
Insertion of acrylonitrile group enhances the fluorescence of the thiazoles.
The basis for the synthesis of new extra sensitive thiazoles was created.