Synthesis and (fluoro)solvatochromism of two 3-styryl-2-pyrazoline derivatives bearing benzoic acid moiety: A spectral, crystallographic and computational study

Article abstract of DOI:10.1016/j.molliq.2021.115737

In this work we report the synthesis of two fluorescent 2-pyrazoline derivatives exhibiting remarkable (fluoro)solvatochromic behavior. The pyrazolines were synthesized in one step from the corresponding monocarbonyl curcuminoids and 4-hydrazinobenzoic acid in high yield and purity and were fully characterized by means of NMR and FT-IR spectroscopy and HRMS spectrometry. The structure of the novel derivative 2 was also characterized by means of X-ray crystallography. Both compounds were studied computationally in the gas phase. Additionally, the effects of solvent polarity on the absorption and fluorescence spectra of these derivatives were investigated in a solvent group consisting of various neat molecular solvents exhibiting hydrogen bond donating (HBD), hydrogen bond accepting (HBA), and/or dipolar behavior. The solvent effects observed were quantified and rationalized by employing suitable multiparametric Linear Solvation Energy Relationships (LSERs) involving dipolarity, HBD-acidity and HBA-basicity terms. The contribution of each of these parameters provided insights on the predominant solute-solvent interactions occurring in solution. Importantly, some differences in the (fluoro)solvatochromic aptitude/behavior were revealed among the derivatives and they were rationalized on the basis of their structural diversity.

Full text of DOI:10.1016/j.molliq.2021.115737

Journal of Molecular Liquids 331 (2021) 115737
Contents lists available at ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Synthesis and (fluoro)solvatochromism of two 3-styryl-2-pyrazoline
derivatives bearing benzoic acid moiety: A spectral, crystallographic
and computational study
c
d
e
Dimitris Matiadis a, , Katarzyna E. Nowak , Eleni Alexandratou , Antonios Hatzidimitriou ,
⁎
Marina Sagnou a, Raffaello Papadakis b,
⁎
a
National Center for Scientific Research “Demokritos”, Institute of Biosciences & Applications, 153 10 Athens, Greece
Department of Chemistry − Ångström, Uppsala University, 751 20 Uppsala, Sweden
Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland
Laboratory of Biomedical Optics and Applied Biophysics, School of Electrical and Computer Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece
Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
b
c
d
e
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work we report the synthesis of two fluorescent 2-pyrazoline derivatives exhibiting remarkable (fluoro)
solvatochromic behavior. The pyrazolines were synthesized in one step from the corresponding monocarbonyl
curcuminoids and 4-hydrazinobenzoic acid in high yield and purity and were fully characterized by means of
NMR and FT-IR spectroscopy and HRMS spectrometry. The structure of the novel derivative 2 was also character-
ized by means of X-ray crystallography. Both compounds were studied computationally in the gas phase. Addi-
tionally, the effects of solvent polarity on the absorption and fluorescence spectra of these derivatives were
investigated in a solvent group consisting of various neat molecular solvents exhibiting hydrogen bond donating
(HBD), hydrogen bond accepting (HBA), and/or dipolar behavior. The solvent effects observed were quantified
and rationalized by employing suitable multiparametric Linear Solvation Energy Relationships (LSERs) involving
dipolarity, HBD-acidity and HBA-basicity terms. The contribution of each of these parameters provided insights
on the predominant solute-solvent interactions occurring in solution. Importantly, some differences in the
(fluoro)solvatochromic aptitude/behavior were revealed among the derivatives and they were rationalized on
the basis of their structural diversity.
Received 5 November 2020
Received in revised form 16 February 2021
Accepted 19 February 2021
Available online 23 February 2021
© 2021 Elsevier B.V. All rights reserved.
1. Introduction
Abbreviations: Symbol/Abbreviation, Meaning/definition; A, Onsager's Cavity term; α,
HBD-acidity term in KAT equation; a, Coefficient of α term; β, HBA-basicity term in KAT
equation; b, Coefficient of β term; c0, Speed of light in vacuum; %C(i), Relaltive contribu-
Fluorescence is one of the most powerful tools for biosensing and im-
aging techniques allowing the scientists to investigate the biological sys-
tems in situ. The environment-sensitive probes are fluorophore dyes
having the ability to change their fluorescence intensity (fluorogenic
dyes) or color (solvatochromic dyes) [1]. The latter, are molecules that
change their color in response to polarity, usually via intramolecular
charge transfer. Therefore, these materials find applications in organic
light-emitting diodes [2,3], dye-sensitized solar cells [4,5], organic pho-
tovoltaics [6], as well as, detection and recognition probes for metal
ions [7] and hazardous [8] or biologically relevant molecules [9].
In particular, small molecule fluorescent compounds are considered
very important and valuable due to their advantages over other mate-
rials like fluorescent proteins [10]. They are applicable to almost any
sample, they are inexpensive and easy to handle and, generally, they
are easily tunable following proper modifications and chemical design.
Well-established examples of such molecules include fluorescein,
rhodamine and BODIPY. Fluorescein and rhodamine, xanthene-based
e e
e
tion of parameter i; δ, NMR Chemical shift; Δv, vabs−vem; ε, Relative permittivity; ε,
Molar extinction coefficient; ε0, Absolute permittivity of vacuum; EF, Maximum fluores-
cence energy; EHT , Maximum transition energy (high energy feature see Table 5); ELT,
Maximum transition energy (low energy feature see Table 5); ET(30), Reichardt's polarity
scale; f (ε, n), Solvent Polarity function involved in Lippert–Mataga model (Eq. 6); g (ε, n),
Solvent Polarity function involved in Bilot–Kawski model (Eq. 10); h, Planck's constant;
HBA, Hydrogen Bond Acceptor; HBD, Hydrogen Bond Donor; KAT, Kamlet Abboud Taft
(Equation); logε, Logarithm of Molar extinction coefficient; LSER, Linear Solvation
Energy Relation; μe, Dipole moment of the excited state; μg, Dipole moment of the ground
e
e
state; vf , Fluorescence maximum wavenumber; vabs, Absorption maximum wavenumber;
n, Refractive index; π*, Dipolarity/polarizability term in KAT equation; r, Square root of the
correlation coefficient; Rf, Retention factor (TLC); rSi, Relative contribution of parameter i;
rse, Residual Sum of Squeres; σ, Hammett's substituent parameter; s, Coefficient of π*
e e
e
term; Σv, vem þ vex; Sap, Aprotic solvent; Sp, Protic Solvent; φ (ε, n), Solvent Polarity func-
tion involved in Bilot–Kawski model (Eq. 9).
⁎
Corresponding authors.
E-mail addresses: dmatiadis@gmail.com, dmatiadis@gmail.com (D. Matiadis),
rafpapadakis@gmail.com (R. Papadakis).
https://doi.org/10.1016/j.molliq.2021.115737
0167-7322/© 2021 Elsevier B.V. All rights reserved.

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
fluorescent probes, typically absorb and emit light in the visible region.
As attractive target compounds, they have been in the focus of material
scientists, successively leading to the development of novel analogues
like the bora-fluoresceins (Fig. 1) [11], naphthofluoresceins [12] and
rhodamines NN (Fig. 1) [13]. On the other hand, BODIPY absorbs UV
strongly and emits sharp fluorescence peaks with high quantum yields.
It is sensitive to polarity and pH of their environment and widely used
for protein and DNA labelling. Over the years, this valuable scaffold
has been extensively modified (e.g. aza-BODIPY (Fig. 1), halogenated
and sulfo-analogues, aryl-substituted as well as compounds with substi-
tution of fluoride atoms in the BF2 group) [14,15]. (See Fig. 1)
Pyrazolines, or 4,5-dihydropyrazoles, constitute a versatile family of
five-membered heterocycles incorporating two adjacent nitrogen
(N\\N) atoms. They exhibit tunable properties due to the numerous
functionalization possibilities at four sites: the three carbon atoms and
the secondary nitrogen (N1). This motif, exists not only in biologically
active molecules exhibiting antidepressant [16], anticancer [17], anti-
inflammatory [18] and antiviral properties [19], but also in many mate-
rials in the field of optoelectronics [20], brightening agents [21] and
chemosensors (Fig. 1) [22,23]. Pyrazoline-based materials exhibit excel-
lent luminescent properties because they act as both the hole-transport
layer (HTL) and the fluorescence layer (EML) and provide optimum
highest occupied (HOMO) and lowest unoccupied (LUMO) molecular
orbital levels [24]. The pyrazoline nitrogen groups facilitate electron
transfer, and the extended conjugation results in bright luminescence
of the molecule [25]. More specifically, due to the nature of high quan-
tum yield and readily synthetic process, some pyrazoline derivatives
have been synthesized and used in fluorescence probes, for detecting
cation [26–28], hydrazine [29,30], thiols [31,32], and DNA [33].
An important feature of many fluorescent dyes is their solvatochromism
and fluorosolvatochromism [34]. The first term corresponds to the change
of color or shift in the absorption spectra whereas the second one to a
change of the emitted color or shift in fluorescence spectra of a compound
induced through solvent polarity changes [35]. The aforementioned phe-
nomena are of great importance as their study can lead to a better under-
standing of the main solute-solvent interactions occurring in solution as
well as to their application in new sensor technologies (e.g. sensors of sol-
vents or volatile organic compounds commonly known as VOCs). In all
cases a rationalization of the dominating interactions is vital for the devel-
opment of responsive and functional new compounds/materials with var-
ious sensing applications. Taken all above into account, in this work, a
thorough analysis of the solvatochromic and fluorosolvatochromic behav-
ior of two new pyrazoline dyes is reported. Linear Solvation Energy Rela-
tions (LSERs) [34] are employed in order to rationalize and quantify all
solute-solvent interactions affecting both the absorbance and fluores-
cence spectra of the two pyrazolines. (There are various solvation models
taking into account specific and non-specific solute-medium interactions
the most renown being the model by Kamlet, Abboud, and Taft (KAT)
[35] and Catalán's solvatochromic equation [36]. In this work, KAT equa-
tion is utilized for the rationalization and quantification of the (fluoro)
solvatochromism of the studied pyrazoline dyes). Computational analysis
and crystallographic measurements are also performed to complement
the understanding of the effects observed in solution. All the previously re-
ported pyrazoline-bearing fluorescent probes are derived from the
Fig. 1. Representative examples of modified fluorescein, rhodamine, aza-BODIPY compounds and benzenesulfonamide pyrazoline chemosensor for fluorometric appications.
2

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
Table 1
Crystal data and structure refinement for compound 2.
corresponding chalcone molecules. To the best of our knowledge there is
no study of the fluorescent properties or potential probe-like application
of any bis(arylidene) derived pyrazolines. Additionally, the two pyrazoline
compounds studied herein exhibit “dual” /inversed solvatochromic be-
havior (vide infra) which corresponds to a rare phenomenon. Even though
these compounds are not dramatically affected by solvent polarity (as
compared to established polarity indicators e.g. Reichardt's betaine or
Brooker's merocyanine) [35] they exhibit a different medium responsive
aptitude to HBD and HBA solvents and this feature could be beneficial
for the development of novel polarity indicators corresponding to various
categories of media e.g. water/organic solvent mixtures. Considering the
biocompatibility of these compounds along with their potential bioactivity
one could envision their use as sensors of biorelevant solute-centric mea-
surable effects. Moreover, the fact that both compounds exhibit solvent-
polarity responsive bahavior both in their ground and their excited states
(solvato- and fluorosolvato- chromism) renders these two dyes interest-
ing candidates for such applications.
Chemical formula
Mr
C28H28N2O6
488.54
Crystal system
Space group
Temperature (K)
a, b, c (Å)
Monoclinic
P21/c
295
10.7672 (10), 21.882 (2), 11.7930 (11)
β (°)
114.111 (3)
2536.1 (4)
4
V (Å3)
Z
Radiation type
μ (mm − 1)
Crystal size (mm)
Data collection
Diffractometer
Absorption correction
Tmin, Tmax
Mo Kα
0.09
0.18 × 0.17 × 0.14
Bruker Kappa Apex2
Numerical
0.98, 0.99
23,507
No. of reflections
Measured
4804
Independent observed
Rint
3331
0.029
0.611
2. Materials and methods
(sin θ/λ)max (Å−1
)
No. of parameters
Refinement
R [F2 > 2σ(F2)]
wR(F2)
325
All reagents were purchased from Sigma-Aldrich and TCI and used
without further purification. Melting points were determined with a
Gallenkamp MFB-595 melting point apparatus. NMR spectra were re-
corded with a Bruker Avance 500 MHz spectrometer operating at
500 MHz (1H) and 125 (13C) or with a Bruker Avance 250 MHz spec-
trometer operating at 250 MHz (1H) and 67.5 MHz (13C). Chemical
shifts are reported in ppm relative to DMSO‑d6 (1H: δ = 2.50 ppm,
0.042
0.052
1.00
0.13, −0.16
S
Δρmax, Δρmin (e Å−3
)
13C: δ = 39.52
0.06 ppm). IR spectra were recorded on a Perkin-
(6 ml) for 5 h. The solution was cooled to 50 °C and then poured into ice-
cold water (50 ml). The completion of the reaction was monitored by
TLC (n-hexane/AcOEt = 1:1 or 3:7) after mini work-up. The precipitate
was filtered and washed thoroughly with water (x3). The product was
dried in a desiccator over CaCl2 overnight and then precipitated from
hot ethanol.
Elmer 100 – IR spectrophotometer using KBr pellets. UV spectra were
recorded with a UV–Vis Hitachi 3010 spectrophotometer. Fluorescence
spectra were obtained using 4.5 ml volume cuvettes with a Perkin-
Elmer LS 45 Luminescence Spectrometer. Each sample was excited at
the wavelength that corresponds to its maximum absorption. The slit
width was set at 10 nm both for excitation and fluorescence. Scan
speed was adjusted to 480 nm min−1. All fluorescence measurements
were carried out at room temperature. The samples were freshly pre-
pared just before measurements. Compounds 3 and 4 were synthesized
as described previously [37].
X-ray quality crystals of 2 were grown from ethanol recrystalliza-
tion. Crystals of 2 suitable for X-ray diffraction, with dimensions
0.18 × 0.17 × 0.14 mm, respectively, were taken from the mother liquor
and mounted at room temperature on a Bruker Kappa APEX 2 diffrac-
tometer, equipped with a triumph monochromator, using Mo Kα radi-
ation. Cell dimensions and crystal system determination performed
using at least 173 high θ reflections with 10o < θ < 20o. Data collection
(φ- and ω- scans) and processing (cell refinement, data reduction and
numerical absorption correction based on dimensions) were performed
using the SAINT and SADABS programs [38,39]. The structures were
solved by SUPERFLIP package [40]. The CRYSTALS version 14.61 build
6236 program package was used for structure refinement (full-matrix
least-squares methods on F2) and all subsequently remaining calcula-
tions [41]. Molecular illustrations were drawn with use of the
CAMERON package [42]. All non‑hydrogen non disordered atoms were
anisotropically refined. All hydrogen atoms were found at their ex-
pected positions and were refined using proper riding constraints to
the pivot atoms. Crystallographic details for 2 are summarized in
Table 1. CCDC 2034933 contains the supplementary crystallographic
data for this paper. A crystal structure representation of compound 2
is depicted in Fig. 2). These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
2.1.1. (Ε)-1-(4-Carboxyphenyl)-5-phenyl-3-styryl-2-pyrazoline (1) [43]
Light yellow solid (162 mg, 88%); mp = 105–107 °C; Rf = 0.40 (n-
hexane/AcOEt = 1:1); FTIR (KBr, cm−1): 2989, 1670, 1596, 1518,
1409, 1327, 1278, 1172, 1130, 1094, 950, 840, 748, 690; 1H NMR
(DMSO‑d6) δ: 3.05 (1H, dd, JMX = 4.6 Hz, JAM = 17.2 Hz, CHAHM), 3.81
(1H, dd, JAX = 12.0 Hz, JAM = 17.2 Hz, CHAHM), 5.61 (1H, dd, JMX
=
4.6 Hz, JAX = 12.0 Hz, CHX), 6.87 (1H, d, J = 16.3 Hz, H16), 6.98 (2H, d,
J = 8.6 Hz, H7, H11), 7.22–7.39 (9H, m, H15, H19 to H21, H28 to H32),
7.59 (2H, d, J = 7.6 Hz, H18, H22), 7.72 (2H, d, J = 8.6 Hz, H8, H10),
2.1. Synthesis of 2-pyrazolines 1 and 2
A mixture of the appropriate curcuminoid 3 and 4 (0.50 mmol) and
4-hydrazinobenzoic acid (1.50 mmol) was refluxed in glacial acetic acid
Fig. 2. Cameron plot of compound 2 with 40% ellipsoids probability and selected labels.
3

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
ETðFÞ ¼ ETðFÞ,0 þ sπ⁎ þ aα þ bβ
ð2Þ
12.30 (1H, s, -COOH); 13C NMR (DMSO‑d6) δ: 41.9 (C4), 62.1 (C5), 112.0
(C7, C11), 120.1 (C9), 120.7 (C15), 125.6 (Ph), 126.9 (Ph), 127.6 (C18,
C22), 128.4 (Ph), 128.8 (Ph), 129.1 (Ph), 130.8 (C8, C10), 134.8 (C16),
136.2 (C17), 141.7 (C27), 146.4 (C6), 151.2 (C3), 167.2 (-COOH).
Through Eqs. 3–4 it is possible to determine the relative contribution
(rsi) of each of the involved parameters. The procedure has thoroughly
been described in previous works [54,55].
2.1.2.
(Ε)-1-(4-Carboxyphenyl)-5-(3,4-dimethoxyphenyl)-3-(3,4-
σi0
dimethoxystyryl)-2-pyrazoline (2)
rSi
¼
ð3Þ
ð4Þ
n
∑ σ0i
Yellow solid (199 mg, 82%); mp = 107–109 °C; Rf = 0.36 (n-hexane/
AcOEt = 3:7); FTIR (KBr, cm−1): 2972, 1673, 1596, 1512, 1417, 1331,
1259, 1169, 1136, 1090, 1023, 951, 841, 768; 1H NMR (DMSO‑d6) δ:
3.02 (1H, dd, JMX = 4.6 Hz, JAM = 17.1 Hz, CHAHM), 3.69 (3H, s, MeO),
3.71 (3H, s, MeO), 3.74 (1H, dd, JAX = 11.8 Hz, JAM = 17.1 Hz,
i¼1
and
vffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
u
u
u
u
u
u
t
ꢀ
À
ꢁ
m
2
CHAHM), 3.77 (3H, s, MeO), 3.81 (3H, s, MeO), 5.49 (1H, dd, JMX
=
∑
Sij−Si
j¼1
0
4.6 Hz, JAX = 11.8 Hz, CHX), 6.66 (1H, d, J = 7.8 Hz, H28), 6.79 (1H, d,
J = 16.2 Hz, H16), 6.88 (1H, s, H32), 6.88 (1H, d, J = 7.8, H29), 6.94
(1H, d, J = 8.4 Hz, H21), 6.96 (2H, d, J = 8.6 Hz, H7, H11), 7.07 (1H, d,
J = 8.4 Hz, H22), 7.19 (1H, d, J = 16.2 Hz, H15), 7.25 (1H, s, H18), 7.72
(2H, d, J = 8.6 Hz, H8, H10), 12.23 (1H, s, -COOH); 13C NMR
(DMSO‑d6) δ: 42.0 (C4), 55.5 (CH3O-), 61.8 (C5), 109.2 (C18), 109.5
(C32), 111.7 (C29), 111.9 (C7, C11), 112.2 (C21), 117.3 (C28), 118.8
(C15), 119.7 (C9), 120.8 (C22), 129.2 (C17), 130.8 (C8, C10), 134.1
(C27), 135.0 (C16), 146.7 (C6), 148.1 (C30), 149.0 (C31), 149.1 (C20),
149.4 (C19), 151.6 (C3), 167.2 (-COOH); HRMS: calcd for C28H29N2O6
489.2020; found 489.2015.
σ ¼ jσij
i
m
Á
2
∑ ETj−ET
j¼1
2.4. Dipole moment determinations
Two different approaches were employed in this work in order to
determine the dipole moments in the electronic ground and excited
states of dyes 1 and 2. The methods are analyzed below.
2.5. Lippert-Mataga method
2.2. Computations
Lippert-Mataga (LM) method [56,57] is a renown approach
employed when the determination of the dipole moment difference
between excited and electronic ground state of a dye is desired and
experimental data on the fluorescence and absorbance of the dye ob-
tained in solvents of known permittivity and refractive index are
available. For the determination of Δμ a simple correlation between
Calculations were performed using Gaussian 03 program [44] (and
GaussView 4.1 [45] program for visualization). First, structures were op-
timized using the Molecular Mechanics (MM) method. Then, in the DFT
calculations the Becke3-Lee-Yang-Parr (B3LYP) functional [46,47] and
6–311++G(d,p) basis set were used. This hybrid functional was used
by other authors to study 2-pyrazoline derivatives [48–53]. Time-
Dependent (TD)-DFT/B3LYP/6–311++G(d,p) calculations were also
performed.
f
e
e
Δν ¼ νabs−νf and the solvent polarity function Δf(ϵ,n) is required
(see Eqs.5–6). Determining the slope of the line obtained through lin-
ear regression analysis allows the determination of Δμ for a given
dye. Results of the LM method on dyes 1 and 2 are summarized in
Table 9.
2.3. LSERs and solvent polarity parameters contribution analysis
!
ꢂ
ꢃ
ꢀ
ꢁ
All correlations presented in this study were performed on R (ver-
sion 4.0.2). The multiparametric model by Kamlet Abboud and Taft
(KAT) was employed in order to assess the relative contribution of var-
ious solvatochromic parameters expressing solvent polarity.
KAT equation is one of the most widely used LSERs in physical chem-
istry [35]. In its most often used form it is a triparametric equation in-
volving solvent polarity scales describing specific and non-specific
solute-solvent effects on a physicochemical quantity (see XYZ in Eq. 1)
e.g. reaction rate constant, spectral shift etc.
μe−μg 2Δf þ const:
ð5Þ
ð6Þ
1
4πε0
2
f
e
e
Δν ¼ νabs−νf ¼
hc0A3
ꢂ
ε−1
ꢃ
n2−1
2ε þ 1 2n2 þ 1
Δfðε, nÞ ¼
−
2.6. Bilot-Kawski method
XYZ ¼ XYZ0 þ sπ⁎ þ aα þ bβ
ð1Þ
The method introduced by Bilot and Kawski [58,59] allows not only
for the determination of Δμ but also of μe and μg through the linear cor-
f
f
relations of Δν and Σν with solvent polarity functions φ(ϵ,n) and g
(ϵ,n) (Eq. 9 and 10 respectively). Determination of the slopes of the lin-
ear relations 7 and 8 finally results in solutions for μe and μg through
Eqs. 11 and 12.
In this work, XYZ will be the experimentally obtained energy of
maximum absorbance (ET) or energy of maximum fluorescence (Eem
)
of the dyes 1 and 2 and KAT equation is used in the form of Eq. 2. In
eq. 1 the empirical parameter π* expresses a mix of dipolarity and polar-
izability of the medium which is used to quantify the non-specific
solute-solvent effects. Parameters α and β are expressing the HBD-
acidity and HBA-basicity of a solvent respectively. They are used here
in order to quantity the specific solute-solvent effects which influence
the (fluoro)solvatochromism of the dyes 1 and 2. Finally, the intercept
of this triparametric linear equation corresponds to the absorbance or
fluorescence maximum energy in a solvent for which it is: π* = α =
β. The latter solvent is cyclohexane which corresponds to a solvent of
reference for KAT equation. Practically, the sensitivities s, a and b to pa-
rameters π*,α and β respectively and the intercept are determined
through multilinear regression using the statistical program R. Lists of
the results for all cases are presented in Table 6.
f
e
e
Δν ¼ νabs−νf ¼ m1φðε, nÞ þ const:0
ð7Þ
ð8Þ
00
f
e
e
Σν ¼ νabs þ νf ¼ −m2gðε, nÞ þ const:
ꢂ
ꢃꢂ
ꢃ
ε−1
ε þ 2 n2 þ 2
n2−1
2n2−1
n2 þ 2
φðε, nÞ ¼
−
ð9Þ
"
#
À
Á
ꢂ
ꢃꢂ
ꢃ
3 n4−1
ðn2 þ 2Þ2
ε−1
ε þ 2 n2 þ 2
n2−1
2n2 þ 1
n2 þ 2
gðε, nÞ ¼
−
þ
ð10Þ
4

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
ꢀ
ꢁ
2
Table 2
Selected bond lengths (Å) and bond angles (°) for 2.
2 μe−μg
m1
m2
¼
¼
ð11Þ
ð12Þ
hc0A3
N1—N2
N1—C5
N1—C6
N2—C3
C3—C4
C3—C15
C4—C5
C5—C27
C15—C16
1.3818 (15)
1.4796 (17)
1.3725 (17)
1.2818 (17)
1.495 (2)
1.443 (2)
1.5603 (19)
1.511 (2)
N2—N1—C5
N2—N1—C6
C5—N1—C6
N1—N2—C3
N2—C3—C4
N2—C3—C15
C4—C3—C15
112.61 (11)
119.76 (11)
127.00 (11)
109.79 (11)
113.38 (12)
118.99 (13)
127.63 (13)
ꢀ
ꢁ
2 μ2e −μ2g
hc0A3
The results of these correlations are presented in Table 9 (see also ESI
for more details).
3. Results and discussion
3.1. Chemistry
1.3173 (19)
Table 3
Hydrogen-bond geometry (Å, °) for 2.
The synthetic course towards the desired 2-pyrazolines, 1 and 2, is
outlined in Scheme 1. Symmetrical monocarbonyl curcuminoids 3 and
4 were synthesized via the base-catalyzed Claisen-Schmidt condensa-
tion reaction between acetone and the appropriate commercially avail-
able aromatic aldehydes, namely benzaldehyde and veratraldehyde,
respectively. Subsequently, the intermediate compounds 3 and 4 were
cyclized after treatment with excess of 4-hydrazinobenzoic acid in
refluxing glacial acetic acid to afford the target molecules in high yields
(up to 88%) and purities (>98% by NMR).
D—H···A
D—H
H···A
1.71
D···A
D—H···A
O14—H141···O13i
0.92
2.629 (2)
174
Symmetry codes: (i) − x + 2, −y + 1, −z + 3.
compound 1, as a model structure (Fig. 3), the characteristic signals
assigned to the C4 (HM, HA) and C5 of the pyrazolines ring can be de-
scribed as a typical AMX spin system [62]. Three doublets of doublets
appear at 3.04 (HA), 3.80 (HM) and 5.61 (HX) ppm. The coupling con-
stants conform to this abovementioned pattern having the following J
3.2. Single crystal X-ray diffraction studies
values: JAM = 17.2 Hz for both protons attached to the C4, JAX
=
4.6 Hz for cis-H C4 and C5 protons and JMX = 12.2 Hz for trans-H of C4
and C5. Moreover, the large J value (16.4 Hz) of the vinylic C15 and
C16 hydrogens, appearing at 6.79 and 7.20 ppm, respectively, confirmed
the E-configuration of the double bond in DMSO solution. The acidic hy-
drogen of the carboxylic group appeared at 12.30 ppm.
The IR absorption frequencies were recorded in the range
4000–400 cm−1. The 2-pyrazolines are characterized by the appearance
of the absorption bands at 1596–1594 cm−1 and 1280–1260 cm−1
assigned to the C_N and C\\N bonds, respectively. The presence of
the benzoic acid moiety is recognized by both a broad band from –OH
Compound 2 crystallizes in the monoclinic P21/c space group with
four neutral molecules in the unit cell (Table 1). Selected bond lengths
and angles of the compound are presented in Table 2. All interatomic
distances and bond angles are in the same range to similar compounds
found in the literature [60,61]. The structure observed contains a main
pyrazolinic ring with the five atoms members being nearly coplanar.
The maximum deviations are 0.034 Å for C4 placed lower and 0.033 Å
for C5 placed upper the mean plane formed. All peripheral phenyl
rings are nearly planar as expected with deviations for the atoms
forming them smaller than the error. If the pyrazolinic mean plane is
characterized as plane 1, the plane formed from C6 to C11 plane 2, the
plane formed from C17 to C22 plane 3 and finally the plane formed
from C27 to C32 plane 4, the formed angles between them can give a
clear description of the structure. Planes 1 and 2 are not far from copla-
narity with an angle of 11.18° between them. Nearly coplanar are planes
1 and 3 as the formed angle between them was found to be 4.05o while
the angle between 2 and 3 was found to be 14.08°. Plane 4 is nearly per-
pendicular to planes 1, 2 and 3 forming with them angles of 79.33°,
86.65° and 80.11° respectively.
One main intermolecular hydrogen bonding interaction is formed
(Table 3) between carboxylic groups from two neighboring molecules,
as expected for all protonated mono carboxylic acids, leading to the di-
merization of the molecular structure in the crystal lattice.
3.3. NMR and FT-IR spectroscopy
Fig. 3. Numbering of 1 according to the numbering of X-ray structure as a representative
compound to describe the AMX system and the assignments. The products are racemic
but single molecule is shown for clarity and simplicity purposes.
The purity of the pyrazolines derivatives were further determined by
NMR spectroscopy. In the 1H NMR spectrum (DMSO‑d6) of the
Scheme 1. Synthesis of pyrazolines 1 and 2 via the corresponding intermediate curcuminoids 3 and 4.
5

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
Table 4
electronic transitions related to the p-aminobenzoic moiety. As it is
shown in this work, the position (i.e. the energy of the transition) of
this band is mainly responsive to the basicity of the medium (vide
infra). Due to the non-canonical variation of the solvatochromic shifts
(especially UV-absorption shifts) among the solvent set studied in this
work, it is unsafe to conclude on the type of solvatochromism that the
dyes exhibit (positive or negative solvatochromism). For this reason de-
termination of the dipole moments of the dyes in their electronic
ground and excited states has been implemented (for dipole moments
determination see section: Determination of the type of (fluoro)
solvatochromism of 1 and 2). Our results indicate that for both dyes
the excited state is more polar than the ground state (μg < μe) which cor-
responds to positive solvatochromism [64]. This is in line with the reso-
nance structures depicted in Scheme 2. Structure II which is more
favored by the excited state of the dyes involves charge separation
whereas this is not the case for structure I which predominantly
adopted in the ground state.
The solute (compound 1 or 2) in ground and excited state can be
nicely displayed through the resonance structures, exemplified for 2 in
Scheme 2. Through intermolecular charge transfer occurring upon exci-
tation the molecules can attain fully conjugated structures (structure II,
Scheme 2) (pronounced mostly in the excited state) in which connec-
tion of the arylidene moiety to the pyrazoline core and the benzoate
N-terminal group is attained. Especially in case of compound 2, this
transition leads to “communication” of the electron donor p-OMe
group (with Hammett substituent constant σ = −0.268) [65] to the
strong electron accepting terminal -COOH moiety. This can partly ex-
plain the mild bathochromic shift of about 5 nm of the UV–Vis spectra
when comparing compound 2 to 1, as for example it is found in the
case of CHCl3 λ2(1) = 389 nm whereas λ 2(2) = 395 nm. In both
cases of dyes, due to the stabilization of the charge separated structure,
predominant in the excited state, through the more dipolar solvents, a
pronounced solvatochromic red-shift is observed when shifting from a
very dipolar solvent like water (dielectric constant = 80 at 20 °C [35])
to a very non-polar solvent e.g. n-hexane (dielectric constant =
1.89 at 20 °C [35]). An additional indication of the partly charged (i.e.
more dipolar) nature of each of the compounds can be derived from
1H NMR experiments focusing on the methine protons neighboring to
the benzoate vicinal N-atom. For compound 1, the chemical shift of Hx
(see Fig. 3) was recorded to be 5.49 ppm whereas for compound 2 it
was 5.61 ppm. It is worth mentioning that for alternative N1 substitu-
ents such as phenyl, 4-fluorophenyl and 2-pyridinyl the observed
chemical shifts of the Hx proton was 4.29, 4.53 and 4.90 ppm, respec-
tively. This is 0.7 to 1.3 ppm lower field than the corresponding protons
of compound 2 [66]. These results are in line with protons neighboring
to partly charged (quaternized) N-atoms and support experimentally
the proposed resonance structures of Scheme 2.
Calculated properties of 1 and 2 in the gas phase.
Compound
Dye 1
Dye 2
EHOMO [eV]
−5.448
−2.163
3.285
405.5 (1.202)
311.7 (0.1458)
−5.237
−1.962
3.275
407.6 (1.414)
321.5 (0.1702)
ELUMO [eV]
|Egap| [eV]
λ [nm] (f*)
*
f : Oscillator strength.
stretch around 3000 cm−1 and a medium intensity band from C_O
stretch near 1670 cm−1
.
3.4. Computational studies
Structures of pyrazolines 1 and 2 were optimized in the gas phase.
No significant differences in bond lengths and angles in the pyrazoline
core have been observed between the molecules studied. Calculated
properties of the pyrazolines are summarized in Table 4. The value of di-
pole moment obtained for pyrazoline 2 was significantly higher than
the value of 1. This may be related to the disubstitution pattern of the ar-
omatic ring with the presence of methoxy groups in compound 2 caus-
ing a significant increase in the value of dipole moment. Our pyrazolines
are more polar than similar 2-pyrazolines known from the literature
[63] which may be attributed to the presence of the carboxylic acid moi-
ety on the pyrazoline N-phenyl substitution. The Egap values for 1 and 2
are nearly the same. The HOMO and LUMO orbitals for molecules of
studied compounds are presented in Fig. 4. As can be seen, the HOMO
and LUMO density of electrons for 1 and 2 is distributed over pyrazoline
ring, benzoic acid and the styryl moieties.
There are two theoretical absorption peaks obtained by the TD-DFT/
B3LYP/6–311++G(d,p) for each compound molecule (Table 4). The
first one (lower) appears at 311 and 321 nm and the second (higher)
at 405 and 407 nm for 1 and 2, respectively. The presence of the two
methoxy substituents in the structure
2 is responsible for a
bathochromic shift of the theoretical absorption maximum compared
to those of compound 1. As can be seen, the HOMOs and LUMOs density
of electrons for 1 and 2 is distributed over pyrazoline ring, benzoic acid
and the styryl moieties.
3.5. Solvatochromism of compounds 1 and 2
3.5.1. General overview
Each of compounds 1 and 2 exhibits a main absorption band lying in
the near UV region (390–400 nm) which is attributed to the π-π* tran-
sitions of the molecules with logε varying within 4.18–4.60 for com-
pound 1 and logε varying between 4.48 and 4.78 for compound 2.
Additionally, each of compounds 1 and 2 exhibits a band of higher en-
ergy but of drastically lower logε lying in the region 285–300 nm (logε
between 3.60 and 4.00 for compound 1 and between 3.70 and 4.18 for
compound 2). The latter, is attributed to the π-π* as well as n-π*
The UV–Vis absorption spectra of 1 and 2 were recorded in 15 differ-
ent solvents including protic, aprotic and relatively non-polar solvents
as well as two cases of solvent mixtures which are collectively pre-
sented in Fig. 5–6 and Table 5. The results obtained clearly suggest
that both dyes exhibit solvatochromic properties (see Fig. 5–Fig. 6).
Fig. 4. LUMO (a) and HOMO (b) representations for 1 and 2 obtained on the B3LYP 6–311++G(d,p) level of theory.
6

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
Fig. 4 (continued).
ELT ¼ 74:50−1:728π⁎ þ 0:3170a þ 0:5251β
ð14Þ
These shifts are modest compared to strongly solvatochromic dyes
such as Reichardt's dye [34] or pentacyanoferrate(II) complexes
[64,67], yet, they clearly indicate the aptitude of the pyrazoline mole-
cules to respond to solvent polarity changes. The whole phenomenon
observed in case of the electronic spectra of 1 and 2 is in good agree-
ment with previously reported pyrazolines exhibiting solvatochromism
[68,69]. These two compounds though, differ to previous pyrazolines in
the nature of the terminal N1-substituent which is a carboxylic acid
group. It is apparent that the stabilization of each of the resonance struc-
tures of Scheme 2 is affected by the basicity of the medium in both
hydrogen-bond-acceptance and Lewis basicity terms due to the specific
interactions of the solvent molecules and the -COOH unit. In addition to
that, dipolarity and polarizability of the medium demonstrates an im-
portant role due to the evidently dipolar nature of each of the two com-
pounds, which is especially pronounced in their π-π* excited states.
In a similar fashion, eqs. 15–16 were obtained for compound 2.
EHT ¼ 90:28−5:639π⁎−0:1894a þ 15:46β
ð15Þ
ð16Þ
ELT ¼ 73:86−2:438π⁎ þ 0:3955a þ 1:3831β
In all cases the regression coefficient (r) is close to or higher than 0.8
indicating that KAT model provides a quite reliable description of the
solvatochromic effects (for both the low and the high energy solvent-
responsive transitions). The regression values (see Table 6) correspond
to the solvent exhibiting zero values of all KAT parameters π* = α =
β = 0 i.e. cyclohexane [35], which is a solvent with negligible dipolarity,
HBD-acidity and HBA-basicity. Unfortunately, both compounds 1 and 2
are insoluble in cyclohexane, however, the regression values obtained in
all cases are in good agreement with the recorded values pertaining to
the least polar solvent utilized in this study i.e. n-hexane (for compari-
sons the reader is appended to Table 6).
3.6. Rationalizing the solvatochromic shifts
To understand to which extent each of the aforementioned solvent
polarity characteristics/features contribute to the observed
solvatochromism, the Kamlet–Abboud–Taft (KAT) [70] equation was
employed. This linear solvation energy relationship (LSER) has been
employed in numerous studies pertaining to the rationalization and
quantification of solvent effects. Indeed, this equation has lately been
used in a vast range of solvatochromic dyes spanning from all-organic
betaines [71] to transition metal complexes [72] and even to supramo-
lecular solvatochromic systems [73]. (More details on this equation are
found in the Methods section). Through the triparametric linear regres-
sion analysis (see Methods section) the following equations (Eq.13 on
EHT and Eq.14 on ELT) for compound 1 were derived:
Moreover, through the statistical treatment, the contribution of each
of the parameters of KAT equation i.e. π*, α, and β was determined (see
Table 7).
Based on these results it becomes apparent that for the high energy
transitions mainly the specific solute-solvent interactions contribute to
the observed solvatochromism since the contribution of parameter π*
is negligible (%C(π*) = 3.3% for compound 1 and 8.2% for compound
2). This finding supports the assumption that this transition is attribut-
able to the transitions π-π* as well as n-π* in convolution ( n corre-
sponding to the lone pair of the N-atom vicinal to the p-benzoic
moiety). This comes as a result of the fact that the main interactions
of this part of the molecules are governed by H-bonding of the type
S:….HO2C-Pyr, where S is a solvent and Pyr corresponds to the rest of
the pyrazoline molecule excluding the -COOH moiety. The very good
EHT ¼ 87:05 þ 3:149π⁎−1:755a þ 16:58β
ð13Þ
Scheme 2. Two limiting resonance structures of compound 2. Left structure is dominant in the electronic ground state whereas right one (with charge separation) becomes more
important in the excited state. (These two resonance structures apply also to dye 1 where OMe groups are replaced by H-atoms)
7

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
Table 5
Measured maxima wavelengths and transition energies of compounds 1 and 2 in various solvents.a
Compound 1
Compound 2
Solvent
λ1(nm)
EHT (kcal/mol)
λ2(nm)
ELT (kcal/mol)
λ1(nm)
EHT (kcal/mol)
λ2(nm)
ELT (kcal/mol)
H2O
295.5
275.0
279.0
309.5
311.0
n.m.a
274.0
275.0
297.0
305.5
308.5
309.0
294.5(sh)
312.0
299.0(sh)
96.76
104.00
102.50
92.38
91.93
n.m.a
104.40
104.00
96.27
93.59
92.68
92.53
97.08
91.64
95.62
384.5
387.5
392.5
389.0
384.0
n.m.a
385.5
386.0
385.5
387.0
385.5
389.0
385.0
390.0
384.5
74.36
73.78
72.84
73.50
74.46
n.m.a
74.17
74.07
74.17
73.88
74.17
73.50
74.26
73.31
74.36
286.0
289.0
289.0
311.0
290.0
289.0
290.0
304.0
311.0
312.0
313.0(sh)
320.0
303.0
324.0
308.0
99.97
98.93
98.93
91.93
98.59
98.93
98.59
94.05
91.93
91.64
91.35
89.35
94.36
88.25
92.83
388.0
392.0
396.0
393.0
388.0
391.0
388.0
388.0
389.0
392.0
389.0
395.0
387.0
394.0
390.0
73.69
72.94
72.20
72.75
73.69
73.12
73.69
73.69
73.50
72.94
73.50
72.38
73.88
72.57
73.31
DMSO 1%
DMSO
DMF
MeOH
EtOH 50%
EtOH
iPrOH
AcMe
AcOH
AcOEt
CHCl3
Et2O
PhMe
n-C6H14
sh: shoulder. The measured λ values annotated with sh correspond to the determined maxima at a shoulder of a peak. These numbers are those utilized in all correlations presented in this
work.
a
n.m.: not measured.
correlation between EHT and parameter β or other family dependent
solvent basicity parameters (e.g. Basity, vide infra) and the very high
contribution of parameter β in Eqs. 13 and 15 (approx.. 90%) are in
line with this observation. Noteworthy, the correlation of EHT with the
solvent basicity parameter “Basity” introduced by Swain et al. [73] re-
vealed that aprotic solvents interact differently with molecule 2 when
compared to protic ones. Thereby, correlations involving Basity of
aprotic solvents, namely DMSO, DMF, AcMe, AcOEt, and Et2O), result
in a line with a negative slope (−3.752 kcal/mol) whereas correlations
involving protic solvents, such as H2O, MeOH, EtOH, iPrOH and AcOH,
produce a line with a large positive slop (10.89 kcal/mol). This is
clearly associated to the different mode solvent molecules can interact
with molecule 2.
On one hand protic solvents preferably take on H-bonding interac-
tions of the type Sp-H…O=C(R)-OH (Sp being a protic solvent) whereas
aprotic ones of the type: S…apHO-C(R) = O. In the first case the interac-
tions lead to an increase of the gap between ground and excited state
yet, in the second case they lead to a decrease of the gap between
ground and excited state hence the positive and negative slopes respec-
tively. Compound 1 exhibits a very similar behavior.
The low energy/high absorbance transition appearing at λmax
=
385–395 nm is less responsive to changes of each of the parameters
π*, α, or β of KAT equation compared to the high energy transition ana-
lyzed above. Yet, it exhibits a higher sensitivity to π* than each of param-
eters α and β (for instance in case of dye 2, s = −2.438 kcal/mol, a =
0.3955 kcal/mol and b = 1.383 kcal/mol). This band mainly responds
to solvent dipolarity changes and this explains the better correlations of
ELT with Reichardt's solvent polarity scale (ET(30)) as well as parameter
π* alone when compared to correlations with parameters expressing
specific effects. In a similar fashion to the correlations of the type: ET-
H ∝ Basity, correlations of ELT with Reichardt's polarity scale resulted in
two lines of opposite slope depending on the nature of solvent: protic
or aprotic (Fig. 8). A positive slope line was derived from the correlation
between ELT and ET(30) in case of protic solvents such as HOH, MeOH,
EtOH, iPrOH or AcOH whereas a line with negative slope was derived
for the group of aprotic solvents.
Interpretation of this effect can be provided in a similar way as in
case of the correlations with Basity (expressing solvent basicity). Even
though all dipolar solvents are anticipated to stabilize the (more
polar) excited state than the electronic ground state (see limiting reso-
nance structure of Scheme 2) and thus induce negative solvatochromic
shifts, the interactions of the aprotic solvents with molecules 1 or 2 are
mainly through the -COOH group. Yet, protic solvents can (also) interact
with nitrogen atoms of the pyrazoline as well as other side-substituents
such as -OMe groups (only present in case of 2).
Fig. 5. Full (top) and partial (bottom) absorption spectra of compound 1 measured in
various solvents.
8

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
Table 7
Contribution [%] of the three KAT equation parameters in the observed solvatochromism
for compounds 1 and 2.
Parameter
ETL
ETH
EF
%C(π*)
%C(α)
%C(β)
%C(π*)
%C(α)
%C(β)
70.6
21.5
7.9
67.7
7.3
3.3
3.4
93.3
8.2
3.8
53.2
3.1
43.7
62.4
11.1
26.5
Compound 1
Compound 2
25.0
88.0
Deviations from the regression plane become apparent in the high β/
low π* regions indicating that in this solvent polarity area the predic-
tions of the model for EHT become less accurate. This comes as a result
of the different way protic and aprotic solvents can interact with mole-
cules of 1 and 2 as already analyzed (see Fig. 7 and 8 and corresponding
discussion).
3.7. Fluorosolvatochromism of compounds 1 and 2
3.7.1. General overview
The fluorosolvatochromic shifts of compounds 1 and 2, are signifi-
cantly more intense than those pertaining to the UV–Vis solvatochromic
shifts. The dyes in their excited state attain more dipolar structures due
to charge separation which significantly alters the solute-solvent inter-
actions as compared to the ground state. As nicely illustrated through
the resonance structures depicted in Scheme 2 and further supported
by the DFT calculations, in either the crystalline compound 2 (See ESI,
Fig. S15) or in the gas phase for both compounds 1 and 2 (Fig. 4) the
more polar quinoidal resonance structure (pronounced in the excited
state) is fully in line with the more dipolar nature of the excited state
(see HOMO and LUMO representations of Fig. S15 (ESI) and Fig. 4).
Noteworthy, the fluorosolvatochromic shifts observed are more in-
tense when compared to the solvatochromic ones corresponding to ab-
sorption spectra (See Fig. 10). For instance, in the case of compound 2 a
Δλem = (486.5–424) nm = 62.5 nm (or 8.660 kcal/mol difference in
fluorescence energy) whereas Δλabs,1 = (286–308) nm = −22 nm
(or 7.140 kcal/mol difference) is observed when moving from the very
apolar solvent n-hexane to the most dipolar solvent used in this study
i.e. water (see Tables S1 (ESI) and Table 8). This indicates that
fluorosolvatochromism of dyes 1 and 2 is more responsive to medium
polarity changes and thus might be more suitable for the probing/eval-
uation of the polarity effects in their microenvironment.
Fig. 6. Full (top) and partial (bottom) absorption spectra of compound 2 measured in
various solvents.
The degree of success of the correlations EHT ∝(π*,α, β) and ETL∝(π*, α,
β) can be qualitatively assessed through the 3D plots of the experimen-
tally obtained values EHT or ETL and the two parameters of KAT equation
exhibiting the highest contribution on the solvatochromism. The plots
of Fig. 9 involve the regression planes for each correlation EHT ∝(π*,α, β).
Through this assessment it becomes apparent that the two main param-
eters influencing the solvatochromism of compounds 1 and 2 are π* and
β reflecting the dual dipolar and acidic character of both dyes 1 and 2.
Additionally, important fluorescence intensity differences were ob-
served among the solvents examined in this work. Interestingly, for
both cases of dyes, DMF was the solvent resulting in the highest fluores-
cence intensity for solutions of given dye concentration (2 × 10−5 M).
Nonetheless, the behavior in terms of hypo−/hyper- chromism depend-
ing on solvent polarity is different for each of the two dyes. The effects re-
lated to hypo−/hyper-chromism are not discussed in this work.
Table 6
Results of the correlations of transition and fluorescence energies with the KAT equation parameters for compounds 1 and 2.
a
Correlated parameter
ET,0 / EF,0
sa
aa
ba
rb
rsec
EHT (1)
ELT(1)
EHT (2)
ELT(2)
EF(1)
EF(2)
87.05 4.598
74.50 0.3612
90.28 1.854
73.86 0.5495
67.64 0.8037
68.11 0.9638
3.149 5.932
−1.755 2.749
0.3170 0.2484
−0.1894 1.692
0.3955 0.3779
0.04331 0.85837
−0.7025 0.9094
16.58 5.324
0.5251 04716
15.64 3.299
1.383 0.7174
−3.412 1.613
−2.549 1.770
0.7967
0.8267
0.8651
0.7353
0.8789
0.8693
3.806
0.3331
2.588
0.5068
1.161
1.422
−1.728 0.5329
−5.639 2.900
−2.438 0.8107
−3.965 1.458
−5.141 1.500
a
ET,0 / EF,0, s, a, b correspond to the regression values of coefficients involved in KAT equation. Note: s coefficient of parameter π*, a coefficient of parameter α, b coefficient of parameter β.
r corresponds to the square root of the correlation coefficient.
rse corresponds to the residual standard error of the regression.
b
c
9

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
3.8. KAT equation results on fluorosolvatochromism
The regression values for the coefficients of the KAT parameters (π*,
α, and β) listed in Table 8 indicate that both compounds are highly sen-
sitive to the dipolatrity/polarizability of the medium expressed through
parameter π* yet, less sensitive to the remaining two parameters ex-
pressing the aptitude of solvents to develop specific (H-bonding) inter-
actions with the solutes. This constitutes an important change from the
mainly H-bonding controlled solvatochromism of the absorption spec-
tra of the dyes 1 and 2 (for comparison see also Table 6 entries for ETH
and ELT). It, therefore, comes as no surprise that the contribution of the
three parameters for the fluorosolvatochromism follows the sequence:
Application of the KAT model on the fluorosolvatochromism of 1 and
2 resulted through multilinear regression analysis in a characteristic
equation for each of the dyes (Eq. 17 for compound 1 and Eq. 18 for
compound 2).
EF ¼ 67:64−3:965π⁎ þ 0:04331a−3:412β
EF ¼ 68:11−5:141π⁎−0:7025a−2:549β
ð17Þ
ð18Þ
Fig. 7. Correlation of EHT of compound 2 with the empirical solvent basicity parameter Basity. Solid line derives from correlations pertaining to protic solvents whereas dashed line from
correlations pertaining to aprotic solvents.
Fig. 8. Correlation of ELT of compound 2 with the Reichardt's solvent polarity scale. Solid line derives from correlations pertaining to protic solvents whereas dashed line from correlations
pertaining to aprotic solvents.
∗
Fig. 9. 3D Plots depicting the regression planes and experimental points EHT the correlations ETH ∝ (π ,β) pertaining to (A) compound 1 and (B) compound 2.
10

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
Fig. 10. Fluorescence spectra of compound 1 (top) and 2 (bottom) measured in various solvents. Arrows represent the hypsoochromism induced by decrease in solvent polarity.
%C(π*) > %C(β) > %C(α). Indeed, for both compounds it was: %C
(π*) > (%C(β) + %C(α)) underlining the dominating role of non-
specific solute-solvent interactions. A common characteristic of both
solvato- and fluorosolvato- chromism is that parameter β in all cases
contributes more than parameter α and this is unambiguously con-
nected to the acidic nature of the dyes derived by the presence of a
-COOH group. Noteworthy, when it comes to fluorescence, parameter
α exhibits an approx. four-fold higher contribution (%C(α)) in case of
compound 2 compared to compound 1. This is presumably associated
to the fact that compound 2 bears two methoxy groups which are
prone to develop hydrogen bonding interactions with HBD solvents
(mainly the protic ones) but as compound 1 has H-atoms in these aryl
positions it shows no such a propensity.
Table 8
Measured fluorescence maxima wavelengths of compounds 1 and 2 in various solvents.
Compound 1
em(nm)
Compound 2
em (nm)
Solvent
λ
Eem (kcal/mol)
λ
Eem (kcal/mol)
H2O
l.s.a
l.s.a
486.5
490.5
482.5
450.5
464.5
455.0
450.5
449.0
441.0
441.0
445.0
438.5
435.5
424.0
58.77
58.29
59.26
63.47
61.55
62.84
63.47
63.68
64.83
64.83
64.25
65.20
65.65
67.43
DMSO 1%
DMSO
DMF
MeOH
EtOH
iPrOH
AcMe
AcOH
AcOEt
CHCl3
Et2O
479.5
464.5
456.5
458.5
454.0
454.0
449.0
442.0
441.0
449.5
441.0
439.0
422.5
59.63
61.55
62.63
62.36
62.98
62.98
63.68
64.69
64.83
63.61
64.83
65.13
67.67
3.9. Determination of the type of (fluoro)solvatochromism of 1 and 2
Given the fact that the observed solvatochromic shifts of dyes 1 and
2 vary differently among the group of protic and the group of aprotic
solvents, determining the type of solvatochromism in these dyes is fea-
sible only through determination of the dipole moments of the dyes in
PhMe
n-C6H14
a
l.s.: no detection of signal due to low solubility.
11

D. Matiadis, K.E. Nowak, E. Alexandratou et al.
Journal of Molecular Liquids 331 (2021) 115737
Table 9
Dipole moments of the electronic ground and excited states of dyes 1 and 2 based on two determination methods.⁎, ⁎⁎, ⁎⁎⁎
Bilot-Kawski method
Lippert-Mataga Method
Dye
A (Å)
m1 (r)
m2 (r)
μg(D)
μe(D)
[Δμ(D)]ΒΚ
m (r)
[Δμ(D)]LM
1
2
4.73
5.17
2678.5 (0.933)
3406.5 (0.884)
−1908.3 (0.878)
−2134.8 (0.814)
0.143
0.240
−0.852
−1.05
0.709
0.806
4716.4 (0.933)
5764.5 (0.849)
0.706
1.23
⁎
⁎⁎
⁎⁎⁎
m1 and m2 slopes of lines 13 and 14 respectively (see Materials and Methods).
ꢀ
ꢁ
2
1
2
m ¼
∙
μe−μg
:
hc0 A3
4πε0
r square root of correlation coefficient.
the ground and excited state (μg and μe respectively). For this reason,
Lippert-Mataga (LM) method and the model by Bilot and Kawski (BK)
were employed (for details see the Materials and Methods section).
LM method provides the dipole moment difference between ground
an excited state ([Δμ(D)]LM see Table 9) however it does not provide in-
formation on the μg and μe separately. According to the results through
the LM method, dye 2 appears to have a more intense solvatochromic
behavior when compared to 1 since [Δμ(D)]LM(2) > [Δμ(D)]LM(1).
This is in line with the larger solvatochromic shifts observed between
two specific solvents for 2 compared to 1. On the other hand, through
BK model it was possible to determine the μg and μe for both dyes (see
Table 9). For both dyes it was found that |μg|<|μg| which corresponds
to positive solvatochromism [64]. As anticipated, dye 1 appears to be
less polar than dye 2 both in the ground and the excited state (since
[Δμ(D)]BK(2) > [Δμ(D)]BK(1)). The numerical results of Table 9 are
fully in line with the two resonance structures of Scheme 2. Structure
II of Scheme 2 which is pronounced in the excited state is zwitterionic
(exhibits charge separation) which justifies the result: |μg|< |μg| ob-
tained for both dyes 1 and 2.
Declaration of Competing Interest
The authors declare that there is no conflict of interest.
Acknowledgments
The authors acknowledge support of this work by the project “A
Greek Research Infrastructure for Visualizing and Monitoring Funda-
mental Biological Processes (BioImaging-GR)” (MIS 5002755) which is
implemented under the Action “Reinforcement of the Research and In-
novation Infrastructure”. The project is funded by the Operational Pro-
gramme “Competitiveness, Entrepreneurship and Innovation” (NSRF
2014–2020) and co-financed by Greece and the European Union
(European Regional Development Fund). The calculations were per-
formed in the Laboratory of Computer and Analytical Techniques, the
University of Lodz (Poland).
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