A chiral (1R,2R)-N,N′-bis-(salicylidene)-1,2-diphenyl-1,2-ethanediamine Schiff base dye: synthesis, crystal structure, Hirshfeld surface analysis, computational study, photophysical properties and in silico antifungal activity

Article abstract of DOI:10.1007/s13738-021-02237-5

We report synthesis, structural and computational studies, and photophysical properties of a chiral (1R,2R)-N,N′-bis-(salicylidene)-1,2-diphenyl-1,2-ethanediamine Schiff base dye (1). The structure of 1 was found to be in the enol-imine tautomer, stabiliz

Full text of DOI:10.1007/s13738-021-02237-5

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-021-02237-5
ORIGINAL PAPER
A chiral (1R,2R)‑N,N′‑bis‑(salicylidene)‑1,2‑diphenyl‑1,2‑
ethanediamine Schif base dye: synthesis, crystal structure, Hirshfeld
surface analysis, computational study, photophysical properties
and in silico antifungal activity
Alexey A. Shiryaev1,2 · Anastasiya N. Goncharenko1 · Tatyana M. Burkhanova1,3 · Larisa E. Alkhimova1 ·
Maria G. Babashkina4 · Ravikumar Chandrasekaran5 · Damir A. Safn1,2,3
Received: 16 December 2020 / Accepted: 5 March 2021
© Iranian Chemical Society 2021
Abstract
We report synthesis, structural and computational studies, and photophysical properties of a chiral (1R,2R)-N,N′-bis-
(salicylidene)-1,2-diphenyl-1,2-ethanediamine Schif base dye (1). The structure of 1 was found to be in the enol-imine
tautomer, stabilized by two intramolecular O–H···N hydrogen bonds. Molecules are packed into a 1D supramolecular chain
through intermolecular C–H···O interactions. 1D chains are interlinked through intermolecular C–H···π intercations. As a
result of intermolecular interactions, molecules of 1 are packed into a 3D supramolecular framework, yielding a pcu alpha-
Po primitive cubic; 6/4/c1; sqc1 topology defned by the point symbol of (412·63). Favoured intermolecular H···H, H···C
and H···O contacts are responsible for the overall crystal packing of the dye. Energy frameworks have been calculated to
additionally analyse the overall crystal packing of 1. The absorption spectra of 1 in THF, CH2Cl2 and CH3CN each exhibit
three intense bands in the UV region. The absorption spectra of 1 in EtOH, nPrOH, iPrOH and nBuOH, besides the same
three intense bands in the UV region, contain an additional band in the visible region centred at about 410 nm, corresponding
to the cis-keto-enamine tautomer. The absorption spectrum of 1 in MeOH contains an additional intense shoulder at about
350 nm. The emission spectrum of 1 in MeOH contains a broad band at 438 nm, arising from the emission of the enol-
imine* form. Theoretical calculations based on density functional theory (DFT) were performed to verify the structure of 1
as well as its electronic and optical properties. The global chemical reactivity descriptors were estimated from the energy of
the HOMO and LUMO orbitals. Molecular docking studies were performed to evaluate the antifungal activity of 1 against
cytochrome P450 14 alpha-sterol demethylase (CYP51).
Keywords N-salicylidene aniline dye · Crystal structure · Hirshfeld surface analysis · Optical properties · Molecular
docking · DFT
3
* Damir A. Safn
Kurgan State University, Sovetskaya Str. 63/4, Kurgan,
Russian Federation 640020
damir.a.safn@gmail.com
4
5
Institute of Condensed Matter and Nanosciences,
Université Catholique de Louvain, Place L. Pasteur 1,
1348 Louvain-la-Neuve, Belgium
1
University of Tyumen, Volodarskogo Str. 6, Tyumen,
Russian Federation 625003
2
Innovation Center for Chemical and Pharmaceutical
Thanthai Periyar EVR Government Polytechnic College,
Vellore, Tamilnadu 632002, India
Technologies, Ural Federal University named after the First
President of Russia B.N. Eltsin, Mira Str. 19, Ekaterinburg,
Russian Federation 620002
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
Introduction
Schif bases R1R2C = NR3 (R3 ≠ H), named after famous
chemist Hugo Schif, who discovered this type of com-
pounds [1] are a condensation product of primary amine
and ketone, yielding secondary ketimines R1R2C = NR3
(R3 ≠ H), or aldehyde, yielding secondary aldimines
R1R2C = NR3 (R1 or R2 = H, R3 ≠ H). The latter imines are
commonly referred to as azomethines. Of Schif bases,
diferent families can be highlighted. Particularly, Schif
bases R1R2C= NR3, where R3 = phenyl or substituted phe-
nyl (N-phenyl imines), are called anils [2, 3]. The other
famous family of Schif bases is bis-compounds referred
to as salen-type compounds. The term “salen” refers to a
tetradentate Schif base, derived from salicylaldehyde and
ethylenediamine, namely N,N′-ethylenebis(salicylimine).
In general, the salen-type Schif bases are the product
of condensation of a diamine with two equivalents of a
salicylaldehyde derivative. Metal complexes of the salen-
type ligands are of great importance in many felds of
practical application. For instance, a coordination com-
plex of CoII with salen, namely N,N′-bis-(salicylidene)
ethylenediaminocobalt(II) (salcomine), as well as its
derivatives are known as efcient carriers for O2, oxidation
catalysts and enzyme mimics [4–8]. Furthermore, a coor-
dination compound of MnIII with a chiral bulky salen-type
ligand, namely N,N′-bis-(3,5-di-tert-butylsalicylidene)-
1,2-cyclohexanediaminomanganese(III) chloride, is an
efcient asymmetric catalyst in the Jacobsen epoxidation
[9, 10]. A methyl-substituted salen derivative, namely
N,N′-1,2-propylenebis(salicylimine) (salpn), is known as
a metal deactivation additive in motor oils and motor fuels
[11].
Scheme 1. Isomeric forms of N-salicylidene aniline derivatives and
their colour panel
through yellow to red) as a result of diferent isomeric
forms (Scheme 1). Furthermore, colours can efciently be
induced by diferent stimuli, e.g. temperature, pH, solvent,
etc. The distinctive feature of the salicylaldehyde-derived
Schif bases is an intramolecular O–H···N hydrogen bond,
which is a characteristic for the enol-imine isomer, while
the cis-keto-enamine form is characterized by the intramo-
lecular N–H···O hydrogen bond (Scheme 1). The position
of this volatile proton is dictated not only by substituents
(R1 and R2, respectively; Scheme 1) but also, e.g., by the
solvent nature.
We also have extensively studied chromic properties of
the salicylaldehyde derived Schif bases [25–35]. In this
work, we have directed our attention to a chiral (1R,2R)-
N,N′-bis(salicylidene)-1,2-diphenyl-1,2-ethanediamine (1)
Schif base dye. We focused on optical properties of this
compound in diferent solvents as well as we studied its
crystal structure in details using Hirshfeld surface analy-
sis. Furthermore, energy frameworks have been calculated
to analyse the overall crystal packing of 1. Using in silico
molecular docking method, antifungal activity of 1 was also
investigated against Cytochrome P450 14 alpha-sterol dem-
ethylase (CYP51) (PDB ID: 1EA1) antifungal enzyme.
On the other hand, chirality is an important phenom-
enon in the nature [12–14]. Chiral Schif bases as well as
their metal complexes are of great importance for many
practical applications, e.g. catalysis [4–11]. Of chiral
Schif bases, chiral salen-type compounds play a piv-
otal role [4–11]. Obviously, in this type of compounds,
chirality can be generated either through the diamine or
the phenyl fragments, or both. For example, chiral (S,S)
and (R,R) 1,2-diaminocyclohexane or 1,2-diphenyl-
1,2-ethanediamine are facile and efcient transmitters of
chirality. Thus, being the most widely used chiral diamine
precursors.
Experimental
Schif bases obtained from salicylaldehyde derivatives
is an outstanding family due to the ortho-situated OH
group, which is responsible for the possible tautomeriza-
tion between the enol-imine and keto-enamine isomers,
of which the latter one can adopt either the cis- or trans-
isomers (Scheme 1) [15–24]. This type of Schif bases
are known for their rich colour pallete (from colourless
Physical measurements
The ATR-FTIR spectrum was recorded with a Nicolet iS20
FTIR spectrometer, while the FTIR spectrum in the KBr pel-
let was recorded with a JASCO-680 spectrometer. UV–vis
and fuorescent spectra from the freshly prepared solutions
in freshly distilled solvent were recorded on an Agilent 8453
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Journal of the Iranian Chemical Society
instrument and a RF-5301PC Shimadzu spectrofuorometer,
respectively. Elemental analysis was performed on a Thermo
Flash 2000 CHNS analyser.
Synthesis
A mixture of salicylaldehyde (10 mmol, 1.221 g) and
(1R,2R)-1,2-diphenyl-1,2-ethanediamine (5 mmol, 1.061 g)
in ethanol (20 mL) was stirred at refux for 1 h. The result-
ing hot solution allowed to cool to room temperature to give
yellow block-like crystals of 1. Yield: 1.640 g (78%). M. p.:
110–112 °C. Anal. Calc. for C28H24N2O2 (420.51): C 79.98,
H 5.75 and N 6.66; found: C 80.11, H 5.67 and N 6.74%.
8
12
16
20
24
28
32
36
40
44
48
2θ (°)
Fig. 1 Calculated (black) and experimental (red) X-ray powder dif-
fraction patterns of 1
Computational details
The ground state geometry of 1 was fully optimized without
symmetry restrictions. The calculations were performed by
means of the GaussView 6.0 molecular visualization pro-
gram [36] and Gaussian 09, Revision D.01 program pack-
age [37] using the density functional theory (DFT) with the
hybrid with Becke-3-Lee–Yang–Parr (B3LYP) functional
[38, 39] and 6–311++G(d,p) [38, 40] basis set. The crystal
structure geometry was used as a starting model for struc-
tural optimization. The vibration frequencies were calculated
for the optimized structure in gas phase and no imaginary
frequencies were obtained.
μ(Mo-Kα) = 0.076 mm−1, T = 296(2) K, refections: 6613
collected, 2068 unique, Rint = 0.122, R1(all) = 0.0399,
wR2(all)=0.0979, S=1.079.
CCDC 970499 contains the supplementary crystallo-
graphic data. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from
the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223–336-033;
or e-mail: deposit@ccdc.cam.ac.uk.
Results and discussion
X‑Ray powder difraction
The dye 1 was obtained by the condensation reaction of
(1R,2R)-1,2-diphenyl-1,2-ethanediamine with salicylalde-
hyde in ethanol (Scheme 2), yielding yellow X-ray suitable
block-like crystals, which are stable under ambient condi-
tions. A number of these crystals were tested by single-
crystal X-ray difraction, testifying to their identity and the
obtained crystallographic parameters are the same as for
the crystal structure of 1 found in the Cambridge Structural
Database (CCDC number 970499) [41, 42]. The correspond-
ing CIF fle was subtracted from the CSD for an in-depth
analysis (vide infra) of the crystal structure of 1. Further-
more, the bulk sample of 1 is free from phase impurities
as evidenced from comparison of the experimental X-ray
X-ray powder difraction for a bulk sample was carried
out using a Rigaku Ultima IV X-ray powder difractom-
eter. The Parallel Beam mode was used to collect the data
(λ=1.54184 Å).
Single crystal X‑ray difraction [41, 42]
Crystal data
C28H24N2O2, Mr = 420.49 g mol−1, orthorhombic, space
group P21212, a=10.2076(6), b=16.3507(10), c=6.9936(4)
Å, V = 1167.24(12) Å3, Z = 2, ρ = 1.196 g cm−3
,
Scheme 2. Synthesis of the
Schif base dye 1
O
EtOH
2
+
N
O
N
O
OH
H
H
H2N
NH2
1
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Journal of the Iranian Chemical Society
of 119.92(11) and 122.68(12)°, respectively, indicating the
sp2-hybridization of both the carbon and the nitrogen atoms
of the C7–N1 fragment in the structure of 1. The overall
X-shape of a molecule of 1 is dictated by the corresponding
dihedral angles between the least-square planes formed by
the phenylene and phenyl rings, which vary from 28.5° to
63.14(9)° (Table 1).
The crystal structure of 1 is stabilized by intramolecular
O–H···N hydrogen bonds (Fig. 3, Table 2), yielding two six-
membered hydrogen bonded heterocycles, which are almost
perfectly planar as evidenced from the corresponding dihe-
dral angles (Table 1).
3800
3400
3000
2600
2200
1800
1400
1000
600
Wavenumber (cm-1)
The structure of 1 is further stabilized by intermolecular
C–H···O interactions (Table 2), formed by one of the ortho-
hydrogen atoms of the phenyl fragments and the hydroxyl
oxygen atoms, yielding a 1D supramolecular chain, compris-
Fig. 2 ATR-FTIR spectrum (black) and FTIR spectrum, measured in
the KBr pellet (red), of 1
powder pattern with the calculated powder pattern generated
from the single-crystal X-ray data (Fig. 1).
ing R2 (20) H-bonded cycles (Fig. 4). These 1D chains are
2
further interlinked through intermolecular C–H···π interca-
tions (Table 2), formed by one of the hydrogen atoms of the
phenylene fragments and the π-system of the phenyl rings
(Fig. 4). As a result of intermolecular interactions, mole-
cules of 1 are packed into a 3D supramolecular framework
(Fig. 4). This 3D supramolecular framework was simplifed,
using the ToposPro software [47], resulting in a pcu alpha-
Po primitive cubic; 6/4/c1; sqc1 topology defned by the
point symbol of (412·63) (Fig. 4).
Compound 1 was characterized by the means of both
ATR-FTIR spectroscopy and FTIR spectroscopy in the KBr
pellet. Both spectra are the same in the fngerprint region
except that in the ATR-FTIR spectrum the most intense
bands were found at 701, 755 and 767 cm–1, while in the
FTIR spectrum recorded in the KBr pellet the most intense
band was observed at 1625 cm–1 (Fig. 2). The former three
bands were assigned as the C–H bending (our-of-plane) and
ring torsion vibrations of the aromatic fragments, while the
latter band was assigned as the ν(C=N) stretching, strongly
supporting the formation of the imine function upon con-
densation of the parent diamine with salicylaldehyde. Aro-
matic rings are further refected in the FTIR spectra of 1 as
a band at 1580 cm–1, corresponding to the C=C stretching
vibrations. Another intense band at 1278 cm–1 corresponds
to the C–O stretching. Notably, no bands characteristic for
the NH2 groups were observed in the FTIR spectra of 1
(Fig. 2), indicating the formation of the bifunctional Schif
base. The most crucial diference between two spectra is
the presence of broad low intense, although visible, band
centred at about 3440 cm–1 in the spectrum measured in the
KBr pellet, while the same band was not observed in the
ATR-FTIR spectrum (Fig. 2).
Crystal packing of 1 was further studied by a Hirshfeld
surface analysis [48], also refected in a set of correspond-
ing 2D fngerprint plots [49], which were generated using
CrystalExplorer 17 [50]. Additionally, the enrichment ratios
(E) [51] of the intermolecular contacts were also calculated
to estimate the propensity of two chemical species to be in
contact.
According to single-crystal X-ray difraction, 1 crystal-
lizes in the orthorhombic space group P21212. The mol-
ecule lies on a crystallographic twofold axis; thus, the
asymmetric unit comprises one half-molecule (Fig. 3). The
C7–N1 bond length in the structure of 1 is 1.2650(18) Å,
while the C8–N1 and C6–C7 bonds are similar and much
longer and of 1.4537(16) and 1.448(2) Å, respectively
(Table 1). The C1–O1 and C1–C6 bonds are 1.3474(19) and
1.4048(19) Å, respectively. Thus, all the discussed above
bond lengths strongly suggest the formation of an enol-
imine isomer of 1 in the solid state (Fig. 3) [43–46]. The
C7–N1–C8 and C6–C7–N1 bond angles are very similar and
Fig. 3 Crystal structure of 1. Colour code: H=black, C=gold,
N=blue, O=red; O–H···N hydrogen bond=dashed cyan line
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Journal of the Iranian Chemical Society
Table 1 Selected bond lengths (Å) and angles (°) in the structure of
1.a
the Hirshfeld surface of 1, mapped over curvedness, testify-
ing to the absence of reasonable π···π interactions (Fig. 5).
It was also found that intermolecular H···H, H···C and
H···O contacts, being about 55%, 35% and 9%, respectively,
occupy almost the whole Hirshfeld surface of 1 (Table 3).
The shortest H···H, H···C and H···O contacts are shown in
the corresponding fngerprint plots at de +di ≈ 2.4, 3.0 and
2.4 Å, respectively (Table 3). Notably, the H···C contacts are
shown in the form of “wings” (Table 3), and are recognised
as characteristic of C–H···π nature [49], while the H···O con-
tacts are shown as a pair of spikes due to the formation of
relatively strong C–H···O hydrogen bonds (Table 3). Fur-
thermore, according to the Hirshfeld surface analysis only a
very negligible proportion (1.0%) of the C···C contacts was
found, indicating the absence of π···π stacking interactions
(Table 3).
Experimental
DFT (B3LYP/6–
311++G(d,p))
Bond lengths
C7–N1
C8–N1
C1–O1
C1–C6
1.2650(18)
1.4537(16)
1.3474(19)
1.4048(19)
1.448(2)
1.2822
1.4526
1.3417
1.4183
1.4538
C6–C7
Bond angles
C7–N1–C8
C6–C7–N1
119.92(11)
122.68(12)
118.45
123.06
Dihedral angles
H1–O1–C1–C6
O1–C1–C6–C7
C1–C6–C7–N1
C6–C7–N1···H1
C7–N1···H1–O1
N1···H1–O1–C1
C6–C7–N1–C8
C7–N1–C8–C8_a
C7–N1–C8–C9
Cgphenylene···Cgphenylene_ab
Cgphenyl···Cgphenyl_ab
–5
–0.2
0.1
–0.5
0.6
–1.0
0.7
179.74
–116.68
118.36
4.0
5.2(2)
–3.1(2)
0.7
–0.7
3
173.78(12)
–124.69(13)
112.61(13)
34.7
28.5
63.14(9)
53.2
The H···C and H···O contacts in the structure of 1 are
highly favoured since the corresponding enrichment ratios
EHC and EHO are larger than unity and of 1.23 and 1.31,
respectively (Table 3). This is explained by a relatively
higher proportion of these contacts on the total Hirshfeld
surface area over a corresponding proportion of random con-
tacts RHC and RHO, respectively (Table 4). The H···H contacts
are less favoured since the EHH = 0.92 enrichment ratio is
less than unity, which is related to the high enrichment of
H···C and H···O contacts. The C···C contacts are signifcantly
impoverished as evidenced from the corresponding enrich-
ment ratio of 0.29.
0.4
53.6
53.5
b
Cgphenylene···Cgphenyl
Cgphenylene···Cgphenyl_ab
aSymmetry transformation used to generate equivalent atoms: _a
Voids in the crystal structure of 1 (Fig. 6) were calculated
using CrystalExplorer 17 [50]. It was found that the void
volume is 198.93 Å3 and the corresponding surface area is
537.83 Å2. With the porosity, the calculated void volume of
1 is about 17%.
b
1 – x, – y, z. Least-square planes, formed by the carbon atoms of
the phenylene and phenyl rings, respectively
It was found that a Hirshfeld surface of 1, calculated over
dnorm, contains two symmetrical pairs of bright red spots,
corresponding to donors and acceptors of the C–H···O inter-
molecular interactions (Fig. 5). The donors and the accep-
tors of these interactions can be evidenced as blue and red
regions around the participating atoms on the Hirshfeld
surface mapped over shape index corresponding to H···O
contacts (Fig. 5). Moreover, no fat regions were observed on
We have also calculated energy frameworks using Crys-
talExplorer 17 [50] to further analyse the crystal packing
of 1. A single-point molecular wavefunction at B3LYP/6-
31G(d,p) was applied for a cluster of radius 3.8 Å to perform
the energy calculation (Table 4, Fig. 7) [52]. The overall
topology of the energy distributions in the crystal struc-
ture of 1 was studied through the energy framework. It was
established that the structure is mainly characterized by the
Table 2 Hydrogen bond and
D–H···A
d(D–H)
d(H···A)
d(D···A)
∠(DHA)
C–H···π interaction lengths (Å)
and angles (°) in the structure
of 1.a
O1–H1···N1
0.82
0.93
d[H(I)···Cg(J)]
1.85
2.53
d[C···Cg(J)]
2.5813(14)
3.3516(19)
∠(CHCg)
148
148
γ
C10–H10···O1#1
C–H(I)···Cg(J)b
#2
C5–H5···C6H5
2.99
3.6511(19)
129
11.71
aSymmetry transformations used to generate equivalent atoms: #1 1 – x, –y, 1+z; #2 1/2+x; 1/2 – y,
b
1 – z. H(I)···Cg(J): distance of H to ring centroid; C···Cg(J): distance of C to ring centroid; ∠(CHCg):
C–H···Cg angle; γ: angle between Cg(J)···H(I) vector and ring J normal
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Journal of the Iranian Chemical Society
Fig. 4 (Top) Crystal packing of 1, constructed from intermolecu-
lar C–H···O and C–H···π interactions. Colour code: H=black,
C=gold, N=blue, O=red; N–H···O hydrogen bond=dashed cyan
line, C–H···O interaction=dashed yellow line, C–H···π interac-
tion=dashed magenta line. (bottom) A simplifed network of 1, con-
structed from intermolecular C–H···O and C–H···π interactions, with
the uninodal 6-connected pcu alpha-Po primitive cubic; 6/4/c1;
sqc1 topology defned by the point symbol of (412·63). Colour code:
1=grey
dispersion energy framework followed by the less signifcant
electrostatic energy framework contribution (Fig. 8).
We have further studied optical properties of 1 in diferent
solvents to examine the infuence of the solvent nature on the
enol-imine and keto-enamine tautomerization. Particularly,
we probed polar aprotic, namely THF, CH2Cl2 and CH3CN,
and a homologous series of polar protic solvents, namely
MeOH, EtOH, nPrOH, iPrOH and nBuOH. It was recently
established that the dipole moments for the keto-enamine
tautomers are larger than those for the enol-imine tautomers
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Journal of the Iranian Chemical Society
namely π*, α and β (Table 5). The parameter π* measures
the ability of the solvent to stabilize a charge or a dipole by
virtue of its dielectric efect. The parameter α describes the
ability of the solvent to donate a proton in a solvent-to-solute
hydrogen bond, while the parameter β provides a measure of
the solvent’s ability to accept a proton (donate an electron
pair) in a solute-to-solvent hydrogen bond.
The absorption spectra of 1 in THF, CH2Cl2 and CH3CN
are very similar and each exhibit three intense bands exclu-
sively in the UV region centred at about 220–230, 255–260
and 315–320 nm (Fig. 9). The two high-energy bands cor-
respond to the intramolecular π→π* transitions of the aro-
matic and imine moieties, while the low-energy band cor-
responds to the n → π* transition of the imine fragments.
The absorption spectra of 1 in EtOH, nPrOH, iPrOH and
nBuOH, besides the same three intense bands in the UV
region, contain an additional low intense band in the visible
region centred at about 410 nm (Fig. 9), corresponding to the
cis-keto-enamine tautomer. The most striking fnding is that
the absorption spectrum of 1 in MeOH, exhibiting the same
four bands as in the spectra of 1 in other alcohols, contains
an additional intense shoulder at about 350 nm (Fig. 9).
We have next studied emission properties of 1 in the
applied solvents. It was established that 1 is emissive in
MeOH at λexc = 350 nm (Fig. 10). The emission spectrum
exhibits one broad band centred at 438 nm. Comparison of
the excitation and UV–vis spectra of 1 in MeOH allowed
to conclude that the emission bands arise from the emis-
sion of the enol-imine* form. The resulting blue colour of
the emission of the solution of 1 in MeOH was quantifed
with the chromaticity coordinates (0.15, 0.06).
We have further applied the density functional theory
(DFT) calculations to examine fine features of 1. The
ground state geometry of 1 was frst fully optimized at the
B3LYP/6–311++G(d,p) [38–40] level. It was established
that the calculated values of bond lengths, bond angles
and dihedral angles are in good agreement with the values
obtained from single-crystal X-ray difraction (Table 1). The
observed diferences between the calculated and experimen-
tal geometrical parameters are obviously explained by the
fact that the DFT computations were performed in the gas
phase.
Fig. 5 Molecular Hirshfeld surfaces of 1 (top, middle, bottom denote
normalized distance dnorm, shape index and curvedness, respectively)
According to the DFT calculations, the dipole moment
of the fully optimized ground state geometry of 1 is
3.722719 Debye, while the energies of the frontier molecu-
lar orbitals are – 0.22825 and – 0.06403 eV for the high-
est occupied molecular orbital (HOMO) and lowest lying
unoccupied molecular orbital (LUMO), respectively
(Table 6). Both orbitals are delocalized over the (ortho-OH-
C6H4–CH=N–CH–)2 fragment except the imine CH group
for HOMO and the 5-CH group of the C6H4 fragment for
LUMO (Fig. 11). Delocalization of LUMO+1 is similar to
LUMO with some minor diferences, while the HOMO–1
[53, 54] that means that polar solvents shift the equilibrium
towards and stabilize the former tautomer. This, in turn, is
shown in the absorption spectrum by an additional band in
the visible region at λmax ≈ 400 nm. Furthermore, in order to
estimate the infuence of a solvent onto a solute, the so-called
solvatochromic comparison method is frequently applied
[55, 56]. This method constitutes three main parameters,
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Journal of the Iranian Chemical Society
Table 3 (Top) 2D and decomposed 2D fngerprint plots of observed contacts for 1. (bottom) Hirshfeld contact surfaces and derived “random
contacts” and “enrichment ratios” for 1
H
C
N
O
Contacts (C, %)a
H
C
N
54.5
35.1
0.0
–
–
–
0.0
0.0
–
–
–
1.0
0.0
0.0
O
9.4
0.0
Surface (S, %)
76.8
18.6
0.0
4.7
Random contacts (R, %)
H
C
N
59.0
28.6
0.0
–
–
–
0.0
0.0
–
–
–
3.5
0.0
1.7
O
7.2
0.2
Enrichment (E)b
H
C
N
O
0.92
1.23
–
–
0.29
–
0.0
–
–
–
–
–
–
–
–
1.31
b
aValues are obtained from CrystalExplorer 17 [50]. The “enrichment ratios” were not computed when the “random contacts” were lower than
0.9%, as they are not meaningful [51]
1 3

Journal of the Iranian Chemical Society
Table 4 Interaction energies
(kJ/mol) calculated for the
crystal structure of 1.a
b
b
b
b
b
N
symmetry operation
R
electron density
Eele
Epol
Edis
Erep
Etot
4
x+1/2, –y+1/2, –z 10.44 B3LYP/6-31G(d,p) –3.6
–0.8 –21.6
–0.2 –9.2
8.9 –17.7
3.8 –7.3
4
4
2
2
x, y, z
12.37 B3LYP/6-31G(d,p) –1.3
x+1/2, –y+1/2, –z 10.09 B3LYP/6-31G(d,p) –3.5
–1.0 –23.0 10.6 –17.8
–1.3 –34.6 17.7 –24.9
x, y, z
x, y, z
10.21 B3LYP/6-31G(d,p) –4.6
6.99 B3LYP/6-31G(d,p) –19.9 –6.8 –47.0 35.5 –45.2
aN is the number of molecules with an R molecular centroid-to-centroid distance (Å); colour codes in the
frst column are referenced to Fig. 7. bEele is the electrostatic energy, Epol is the polarization energy, Edis is
the dispersion energy, Erep is the exchange-repulsion energy, k values are scale factors; Etot =kele ×Eele +kpol
×Epol +kdis ×Edis +krep ×Erep =1.057×Eele +0.740×Epol +0.871×Edis +0.618×Erep [52]
Fig. 7 Colour-coded interaction mapping within 3.8 Å of the centring
molecule in the crystal structure of 1, calculated from a single-point
Fig. 6 Void plot for 1 (results under 0.002 a.u. isovalue)
molecular wavefunction at B3LYP/6-31G(d,p)
is delocalized over two ortho-OH-C6H4 fragments and
both imine nitrogen atoms (Fig. 11). HOMO–2, LUMO+2
and LUMO+3 are spread over the (CH=N–CH(C6H5)–)2,
(N–CH(C6H5)–)2 and (CH(C6H5)–)2 fragments, respectively,
while HOMO–3 is spread over the non-hydrogen atoms of
the whole molecule except the two (HO)C-carbon atoms
and two para-C-carbons of the phenyl fragments (Fig. 11).
The HOMO and LUMO values also establish the ioniza-
tion potential (I) and the electron afnity (A) value of the
molecule, respectively, according to the relation: I=–EHOMO
and A = –ELUMO (Table 6) [57]. These parameters are of
importance, and I and A determine the electron donating
ability and the ability to accept an electron, respectively.
Particularly, lower values of I are responsible for the better
donation of an electron, while higher values of A indicate
a better ability to accept electrons. Both the I and A values
for 1 are relatively low (Table 6), indicating that 1 is a good
electron donor.
We have also established values of the so-called global
chemical reactivity descriptors, which are derived from
the HOMO-LUMO energy gap, to estimate the relative
reactivity of a molecule of 1. The value of chemical poten-
tial (μ) for 1 is – 0.14614 eV, indicating the poor electron
accepting ability and the strong donating ability, which is
further supported with a low value of electronegativity, χ
(Table 6). The chemical hardness (η) describes the resist-
ance towards deformation/polarization of the electron cloud
of the molecule upon a chemical reaction, while softness
(S) is a reverse of chemical hardness [57]. Compound 1 is
1 3

Journal of the Iranian Chemical Society
Table 5 Solvatochromic
parameters of the applied
solvents [55, 56]
Solvent π*
α
β
THF 0.58 0.00 0.55
CH2Cl2 0.82 0.30 0.00
CH3CN 0.75 0.19 0.31
nBuOH 0.47 0.79 0.88
iPrOH
nPrOH
EtOH
0.48 0.76 0.95
0.52 0.78 0.90
0.54 0.83 0.77
0.60 0.93 0.62
MeOH
4.0
1.0
THF CH2Cl2 CH3CN MeOH
EtOH nPrOH iPrOH nBuOH
0.8
3.0
0.6
0.4
ε
2.0
0.2
0.0
350
375
400
425
450
475
ε
1.0
0.0
λ (nm)
200
250
300
350
400
450
500
λ (nm)
1.6
1.2
0.8
0.4
0.0
0.3
0.2
0.1
0.0
ε
200
250
300
350
400
450
500
λ (nm)
Fig. 9 (top) Experimental UV–vis spectra of 1 in diferent solvents
(concentration=10–4 M). (bottom) The calculated UV–vis spectrum
of the ground state of 1, obtained by using the TD-DFT/B3LYP/6–
311++G(d,p) method
characterized by a low value of η (0.08211 eV) and a high
value of S (6.08936 eV–1), respectively, indicating that 1
exhibits a remarkable tendency to exchange its electron
cloud with surrounding environment. The next descriptor,
namely electrophilicity index (ω), describes the energy of
stabilization to accept electrons [57]. The ω value for 1 was
found to be 0.13005 eV. This value is remarkably low, indi-
cating the strong nucleophilic nature of 1. Finally, compound
Fig. 8 Energy frameworks calculated for the crystal structure of 1, show-
ing the (top) electrostatic potential force, (moddle) dispersion force and
(bottom) total energy diagrams. The cylindrical radii are proportional to
the relative strength of the corresponding energies and they were adjusted
to the same scale factor of 250 within 5×3×2 unit cells
1 3

Journal of the Iranian Chemical Society
10.0
8.0
6.0
4.0
2.0
0.0
Table 6 Total energy, dipole moment, frontier molecular HOMO
and LUMO orbitals, gap value and descriptors for 1 in gas phase,
obtained by using the B3LYP/6–311++G(d,p) method
Dipole moment (Debye)
EHOMO (eV)
3.722719
–0.22825
–0.06403
0.16422
0.22825
0.06403
0.14614
–0.14614
0.08211
6.08936
0.13005
–0.01200
1.77981
ELUMO (eV)
ΔELUMO
– HOMO =ELUMO – EHOMO (eV)
Ionization energy, I=–EHOMO (eV)
Electron afnity, A=–ELUMO (eV)
Electronegativity, χ=(I+A)/2 (eV)
200
250
300
350
400
450
500
550
600
Chemical potential, μ=–χ (eV)
λ (nm)
Global chemical hardness, η=(I – A)/2 (eV)
Global chemical softness, S=1/(2η) (eV–1)
Global electrophilicity index, ω=μ2/(2η) (eV)
Global nucleophilicity index, E=μ×η (eV2)
Maximum additional electric charge, ΔNmax =–μ/ƞ
Fig. 10 Emission (red) and excitation (black) spectra of 1 in MeOH
(concentration=10–6 M; λexc =350 nm, λem =435 nm)
1 can accept about 1.78 electrons as evidenced from the
ΔNmax value (Table 6).
We have also applied the molecular electrostatic poten-
tial (MEP) analysis towards 1 to probe the electrophilic and
nucleophilic sites in a molecule. The MEP surface of 1,
generated from the fully optimized ground state geometry
obtained by using the B3LYP/6–311 ++ G(d,p) method,
exhibits the electrostatic potential regions denoted by dif-
ferent colour code, where the red and blue colours corre-
spond to electron rich (nucleophilic) and electron defcient
(electrophilic) regions, respectively (Fig. 12). In the MEP
surface of 1, the most negative potentials are located on both
hydroxyl oxygen atoms, indicating nucleophilic sites with
the strongest attraction for electrophilic attack. The most
positive potentials, coloured as blue regions, are located on
the hydrogen atoms of the imine groups, 6-H-atoms of the
phenylene rings, hydrogen atoms of the bridging CH–CH
fragment and one half of the hydrogen atoms of the phenyl
rings (Fig. 12), indicating electrophilic sites being the most
attractive for nucleophilic attacks.
To evaluate a potential antifungal activity of 1 we have
further applied in silico molecular docking studies against
cytochrome P450 14 alpha-sterol demethylase (CYP51).
The target enzyme was obtained from the Protein Data Bank
(PDB) [58]. Using the AutoDock MGL Tools package [59],
the heteroatoms and water molecules were removed from
the protein and polar hydrogens were added. Finally, the
prepared enzyme was converted into the pdbqt format for
docking process with AutoDock Vina [60]. The binding
free energy of resulting complex was calculated by docking
with active site residues with grid coordinates (x=–17.295,
y=–2.725, z=66.753). Interactions of the docked complex
were analysed using Discovery Studio visualizer [61].
To validate the docking procedure, the native ligand fu-
conazole was redocked with the enzyme. The docking results
revealed a higher docking energy for the complex with 1
(– 9.2 kcal/mol) than with fuconazole (– 8.6 kcal/mol).
The complex with 1 is stabilized by trifurcated conven-
tional hydrogen bonds (ARG96), one electrostatic π-cation
(ARG96), one hydrophobic π-sigma interaction (TYR76),
and two π-sulphur bonds (MET79) with the active residues
mentioned in parenthesis (Fig. 13). The presence of vari-
ous non-covalent interactions in the complex with 1 leads
to superior binding afnity and antifungal nature of 1 over
the native ligand fuconazole, which is a popular antifungal
drug. Hence, 1 may be considered as an efective inhibitor
of cytochrome P450 14 alpha-sterol demethylase (CYP51)
and an antifungal drug.
The absorption spectrum of the fully opti-
mized ground state geometry obtained by using the
B3LYP/6–311++G(d,p) method was simulated at the TD-
DFT/B3LYP/6–311++G(d,p) level. The calculated UV–vis
spectrum exhibits an intense absorption band centred at
about 263 nm accompanied with a shoulder at about 310 nm
(Fig. 9). Each absorption band comprises three transitions at
257–276 nm and 300–316 nm, respectively, with HOMO–3,
HOMO–2, HOMO–1, HOMO, LUMO and LUMO+1 being
the main contributors. (Fig. 9, Table 7). In general, the cal-
culated UV–vis spectrum is similar to the experimental ones
recorded in THF, CH2Cl2 and CH3CN (Fig. 9).
1 3

Journal of the Iranian Chemical Society
Fig. 11 Energy levels, and (left)
front and (right) side views on
the electronic isosurfaces of the
selected molecular orbitals of
the ground state of 1, obtained
by using the B3LYP/6–
311++G(d,p) method
1 3

Journal of the Iranian Chemical Society
Fig. 12 (left) Front and (right
(side) views of the molecular
electrostatic potential surface
of 1, obtained by using the
B3LYP/6–311++G(d,p)
method
Conclusions
Table 7 Values for the calculated UV–vis spectrum of the ground
state of 1 (Fig. 13), obtained by using the TD-DFT/B3LYP/6–
311++G(d,p) method
In summary, we report detailed structural studies as well
as photophysical properties of a chiral (1R,2R)-N,N′-bis-
(salicylidene)-1,2-diphenyl-1,2-ethanediamine Schif base
dye (1), obtained by the condensation reaction of (1R,2R)-
1,2-diphenyl-1,2-ethanediamine with two equivalents of
salicylaldehyde in ethanol.
λmax (nm)
Oscillator strength
0.0655
Transitions
257.6
HOMO–8→LUMO (20.5%)
HOMO–4→LUMO (61.4%)
HOMO–3→LUMO (82.4%)
HOMO–2→LUMO (97.7%)
HOMO–1→LUMO (21.2%)
HOMO→LUMO+1 (77.6%)
HOMO–1→LUMO (75.0%)
HOMO→LUMO+1 (18.4%)
HOMO–1→LUMO+1 (13.3%)
HOMO→LUMO (83.0%)
262.9
275.5
300.5
0.3002
0.0217
0.0178
Single crystal X-ray difraction revealed that the mol-
ecule of 1 lies on a crystallographic two-fold axis; thus, the
asymmetric unit comprises one half-molecule exhibiting
an enol-imine tautomer, stabilized by two intramolecular
O–H···N hydrogen bonds. The structure of 1 is further stabi-
lized by intermolecular C–H···O interactions, yielding a 1D
supramolecular chain, which, in turn, are further interlinked
through intermolecular C–H···π intercations. As a result of
intermolecular interactions, molecules of 1 are packed into
a 3D supramolecular framework, yielding a pcu alpha-Po
primitive cubic; 6/4/c1; sqc1 topology defned by the point
symbol of (412·63).
309.8
315.7
0.1358
0.0747
According to the Hirshfeld surface analysis data, favoured
intermolecular H···H, H···C and H···O contacts in the struc-
ture of 1 are responsible for the overall crystal packing.
Energy frameworks have been calculated to additionally
analyse the overall crystal packing of 1. It was established
that the structure is mainly characterized by the dispersion
energy framework followed by the less signifcant electro-
static energy framework contribution.
The absorption spectra of 1 in THF, CH2Cl2 and CH3CN
are very similar and each exhibit three intense bands exclu-
sively in the UV region centred at about 220–230, 255–260
and 315–320 nm. The absorption spectra of 1 in EtOH,
nPrOH, iPrOH and nBuOH, besides the same three intense
bands in the UV region, contain an additional low intense
band in the visible region centred at about 410 nm, cor-
responding to the cis-keto-enamine tautomer. Notably, the
absorption spectrum of 1 in MeOH, exhibiting the same four
bands as in the spectra of 1 in other alcohols, contains an
additional intense shoulder at about 350 nm. The emission
Fig. 13 Docking interactions of 1 and cytochrome P450 14 alpha-
sterol demethylase (CYP51) active site residues
1 3

Journal of the Iranian Chemical Society
11. W. Dabelstein, A. Reglitzky, A. Schütze, K. Reders, A. Brunner,
Ullmann’s Encyclopedia of Industrial Chemistry (Wiley, Wein-
heim, 2016).
spectrum of 1 in MeOH contains a broad band at 438 nm,
arising from the emission of the enol-imine* form. The
resulting blue colour of the emission of the solution of 1
in MeOH was quantifed with the chromaticity coordinates
(0.15, 0.06).
12. H.C. Aspinall, Chem. Rev. 102, 1807–1850 (2002)
13. J. Crassous, Chem. Soc. Rev. 38, 830–845 (2009)
14. M. Liu, L. Zhang, T. Wang, Chem. Rev. 115, 7304–7397 (2015)
15. E. Hadjoudis, M. Vitterakis, I. Moustakali, I. Mavridis, Tetrahe-
dron 43, 1345–1360 (1987)
According to the DFT calculation results it was estab-
lished that 1 is a good electron donor with a strong nucleo-
philic nature. The nucleophilic sites with the strongest attrac-
tion for electrophilic attack are located on both hydroxyl
oxygen atoms.
16. E. Hadjoudis, I.M. Mavridis, Chem. Soc. Rev. 33, 579–588 (2004)
17. K. Amimoto, T. Kawato, J. Photochem. Photobiol. C 6, 207–226
(2005)
18. T. Haneda, M. Kawano, T. Kojima, M. Fujita, Angew. Chem. Int.
Ed. 46, 6643–6645 (2007)
In silico molecular docking studies were carried out for 1
with cytochrome P450 14 alpha-sterol demethylase (CYP51)
and the results revealed that 1 has promising binding afnity
over fuconazole.
19. A. Filarowski, A. Koll, L. Sobczyk, Curr. Org. Chem. 13, 172–193
(2009)
20. V. Bertolasi, P. Gilli, G. Gilli, Curr. Org. Chem. 13, 250–268
(2009)
21. E. Hadjoudis, S.D. Chatziefthimiou, I.M. Mavridis, Curr. Org.
Chem. 13, 269–286 (2009)
Author contributions A. A. S. involved in conducting research and
partial analysis of results; A. N. G. involved in conducting research
and partial analysis of results; T. M. B. involved in planning research,
analysis results, and preparing a manuscript; L. E. A. involved in con-
ducting research and partial analysis of results; M. G. B. involved in
planning research, analysis results, and preparing a manuscript; R. C.
involved in conducting molecular docking and analysis of results; D.
A. S. involved in planning research, analysis results, and preparing a
manuscript.
22. V.I. Minkin, A.V. Tsukanov, A.D. Dubonosov, V.A. Bren, J. Mol.
Struct. 998, 179–191 (2011)
23. Y. Inokuma, M. Kawano, M. Fujita, Nat. Chem. 3, 349–358
(2011)
24. K.T. Mahmudov, A.J.L. Pombeiro, Chem. Eur. J. 22, 16356–
16398 (2016)
25. D.A. Safn, K. Robeyns, Y. Garcia, CrystEngComm 14, 5523–
5529 (2012)
26. D.A. Safn, K. Robeyns, Y. Garcia, RSC Adv. 2, 11379–11388
(2012)
Funding Not applicable.
27. D.A. Safn, Y. Garcia, RSC Adv. 14, 6466–6471 (2013)
28. D.A. Safn, M. Bolte, Y. Garcia, CrystEngComm 16, 5524–5526
(2014)
Availability of data and materials Not applicable.
29. D.A. Safn, M.G. Babashkina, K. Robeyns, M. Bolte, Y. Garcia,
CrystEngComm 16, 7053–7061 (2014)
Declarations
30. D.A. Safn, M. Bolte, Y. Garcia, CrystEngComm 16, 8786–8793
(2014)
Consent to participate Not applicable.
Consent to publish Not applicable.
31. D.A. Safn, M.G. Babashkina, K. Robeyns, Y. Garcia, RSC Adv.
16, 53669–53678 (2016)
32. D.A. Safin, K. Robeyns, M.G. Babashkina, Y. Filinchuk, A.
Rotaru, C. Jureschi, M.P. Mitoraj, J. Hooper, M. Brela, Y. Garcia,
CrystEngComm 16, 7249–7259 (2016)
Competing interests The authors declare that they have no conficts
of interest in this work.
33. D.A. Safn, K. Robeyns, Y. Garcia, CrystEngComm 18, 7284–
7296 (2016)
Ethical approval Not applicable.
34. A.A. Shiryaev, T.M. Burkhanova, G. Mahmoudi, M.G.
Babashkina, D.A. Safn, J. Lumin. 226, 117454 (2020)
35. D.S. Shapenova, A.A. Shiryaev, M. Bolte, M. Kukułka, D.W.
Szczepanik, J. Hooper, M.G. Babashkina, G. Mahmoudi, M.P.
Mitoraj, D.A. Safn, Chem. Eur. J. 26, 12987–12995 (2020)
36. R. Dennington, T.A. Keith, J.M. Millam, GaussView, Version 6.0,
Semichem Inc., Shawnee Mission, KS, 2016
References
1. H. Schif, Eur. J. Org. Chem. 131, 118–119 (1864)
2. IUPAC. Compendium of Chemical Terminology, 2nd ed. (the
"Gold Book"). Compiled by A.D. McNaught, A. Wilkinson.
Blackwell Scientifc Publications, Oxford (1997)
37. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A.
Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci,
G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian,
A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada,
M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Naka-
jima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery
Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers,
K.N. Kudin, V.N. Staroverov, T. Keith, R. Kobayashi, J. Normand,
K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi,
M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross,
V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann,
O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski,
R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Sal-
vador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas,
J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian 09,
Revision D.01 (2013)
3. https://goldbook.iupac.org/terms/view/A00357
4. S. Yamada, Coord. Chem. Rev. 190–192, 537–555 (1999)
5. P.G. Cozzi, Chem. Soc. Rev. 33, 410–421 (2004)
6. C. Baleizão, H. Garcia, Chem. Rev. 106, 3987–4043 (2006)
7. A. Decortes, A.M. Castilla, A.W. Kleij, Angew. Chem. Int. Ed.
49, 9822–9837 (2010)
8. S. Shaw, J.D. White, Chem. Rev. 119, 9381–9426 (2019)
9. W. Zhang, J.L. Loebach, S.R. Wilson, E.N. Jacobsen, J. Am.
Chem. Soc. 112, 2801–2803 (1990)
10. E.N. Jacobsen, W. Zhang, A.R. Muci, J.R. Ecker, L. Deng, J. Am.
Chem. Soc. 113, 7063–7064 (1991)
1 3

Journal of the Iranian Chemical Society
38. R. Krishnan, J.S. Binkley, R. Seeger, J.A. Pople, J. Chem. Phys.
72, 650–654 (1980)
50. M.J. Turner, J.J. McKinnon, S.K. Wolf, D.J. Grimwood, P.R.
Spackman, D. Jayatilaka, M.A. Spackman, CrystalExplorer17,
University of Western Australia, http://hirshfeldsurface.net (2017)
51. C. Jelsch, K. Ejsmont, L. Huder, IUCrJ 1, 119–128 (2014)
52. C.F. Mackenzie, P.R. Spackman, D. Jayatilaka, M.A. Spackman,
IUCrJ 4, 575–587 (2017)
39. A.D. Becke, J. Chem. Phys. 98, 5648–5652 (1993)
40. M.J. Frisch, J.A. Pople, J.S. Binkley, J. Chem. Phys. 80, 3265–
3269 (1984)
41. C.R. Groom, I.J. Bruno, M.P. Lightfoot, S.C. Ward, Acta Crystal-
logr. B 72, 171–179 (2016)
53. S.H. Alarcón, A.C. Olivieri, D. Sanz, R.M. Claramunt, J. Elguero,
J. Mol. Struct. 705, 1–9 (2004)
42. T. Wu, CSD Communication (2017)
43. T.M. Krygowski, K. Woźniak, R. Anulewicz, D. Pawlak, W.
Kolodziejski, E. Grech, A. Szady, J. Phys. Chem. A 101, 9399–
9404 (1997)
54. P.I. Nagy, W.M.F. Fabian, J. Phys. Chem. B 110, 25026–25032
(2006)
55. M.J. Kamlet, J.-L.M. Abboud, M.H. Abraham, R.W. Taft, J. Org.
Chem. 48, 2877–2887 (1983)
44. P.M. Dominiak, E. Grech, G. Barr, S. Teat, P. Mallinson, K.
Woźniak, Chem. Eur. J. 9, 963–970 (2003)
56. Y. Marcus, J. Solut. Chem. 20, 929–944 (1991)
57. P. Geerlings, F. De Proft, W. Langenaeker, Chem. Rev. 103, 1793–
1873 (2003)
45. G.M. Mercier, K. Robeyns, T. Leyssens, Cryst. Growth Des. 16,
3198–3205 (2016)
46. R.F. Martínez, E. Matamoros, P. Cintas, J.C. Palacios, J. Org.
Chem. 85, 5838–5862 (2020)
58. https://www.rcsb.org/structure/1EA1
59. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew,
D.S. Goodsell, A.J. Olson, J. Comp. Chem. 16, 2785–2791 (2009)
60. O. Trott, A.J. Olson, J. Comput. Chem. 31, 455–461 (2010)
61. Discovery Studio 2015: Dassault Systemes BIOVIA, Discovery
Studio Modelling Environment, Release 4.5, San Diego: Dassault
Systemes
47. V.A. Blatov, A.P. Shevchenko, D.M. Proserpio, Cryst. Growth
Des. 14, 3576–3586 (2014)
48. M.A. Spackman, D. Jayatilaka, CrystEngComm 11, 19–32 (2009)
49. M.A. Spackman, J.J. McKinnon, CrystEngComm 4, 378–392
(2002)
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