Solvent, structural, quantum chemical study and antioxidative activity of symmetrical 1-methyl-2,6-bis[2-(substituted phenyl)ethenyl]pyridinium iodides

Article abstract of DOI:10.1007/s13738-018-1437-5

15 symmetric 1-methyl-2,6-bis[2-(substituted phenyl)ethenyl]pyridinium iodides were synthesized in this work. Their structures were characterized using IR, ¹H and ¹³C NMR, and UV–Vis spectroscopy. DFT calculations indicated that s-trans/s-trans conformation prevail in all compounds. The effects of specific and non-specific solvent–solute interactions on the UV–Vis absorption maxima shifts were evaluated using linear solvation-free energy relationships (LSER), i.e., Kamlet–Taft and Catalán models. A linear free energy relationship (LFER) in the form of single substituent parameter equations (SSP) was used to postulate quantitative structure–property relations of substituent effect on NMR data. TD-DFT results showed dependence of electronic transition on the substituent effects. The push–pull character of these compounds was analyzed by differences in ¹³C chemical shift of the ethylenic double bond in 2- and 6-positions of cross-conjugated with pyridinum central ring. Also, the quotient of the occupations for the bonding π and anti-bonding π* orbitals of this bond was considered. Good correlations of the selected parameter between double bond lengths with π*/π and ¹³C chemical shift differences of the bridging group proved them to be adequate descriptor of push–pull character. Synthesized compounds were screened for the antioxidant activity, using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical methods, and results demonstrated moderate antioxidant potential.

Full text of DOI:10.1007/s13738-018-1437-5

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1437-5
ORIGINAL PAPER
Solvent, structural, quantum chemical study and antioxidative activity
of symmetrical 1-methyl-2,6-bis[2-(substituted phenyl)ethenyl]
pyridinium iodides
Milena D. Milošević1 · Nevena Ž. Prlainović2 · Miloš Milčić3 · Vesna Nikolić3 · Aleksandra Božić4 · Miljan Bigović5 ·
Aleksandar D. Marinković1
Received: 20 December 2017 / Accepted: 22 June 2018
© Iranian Chemical Society 2018
Abstract
15 symmetric 1-methyl-2,6-bis[2-(substituted phenyl)ethenyl]pyridinium iodides were synthesized in this work. Their struc-
tures were characterized using IR, 1H and 13C NMR, and UV–Vis spectroscopy. DFT calculations indicated that s-trans/s-
trans conformation prevail in all compounds. The effects of specific and non-specific solvent–solute interactions on the
UV–Vis absorption maxima shifts were evaluated using linear solvation-free energy relationships (LSER), i.e., Kamlet–Taft
and Catalán models. A linear free energy relationship (LFER) in the form of single substituent parameter equations (SSP)
was used to postulate quantitative structure–property relations of substituent effect on NMR data. TD-DFT results showed
dependence of electronic transition on the substituent effects. The push–pull character of these compounds was analyzed
by differences in 13C chemical shift of the ethylenic double bond in 2- and 6-positions of cross-conjugated with pyridinum
central ring. Also, the quotient of the occupations for the bonding π and anti-bonding π* orbitals of this bond was considered.
Good correlations of the selected parameter between double bond lengths with π*/π and 13C chemical shift differences of
the bridging group proved them to be adequate descriptor of push–pull character. Synthesized compounds were screened for
the antioxidant activity, using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic
acid) (ABTS) radical methods, and results demonstrated moderate antioxidant potential.
Keywords Solvatochromism · Kamlet–Taft · Catalán · Antioxidant activity
Introduction
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-018-1437-5) contains
Development of new technologies over the past several
supplementary material, which is available to authorized users.
years resulted in craving for the synthesis of new com-
pounds and materials with promising application in biol-
ogy and medicine. Compounds able to interact directly
with nucleic acids are of great importance in cancer
chemotherapy. In particular, molecules able to exert their
biological effects by binding reversibly to the receptors
include aromatic or heteroaromatic moieties. In that con-
text, systems which belong to the class of the so called
push–pull (donor–acceptor system, D–A) molecules
have attracted a great attention. The study of this class
of compounds is growing tremendously with particular
focus on the pyridine and its derivatives. Due to their
aromatic structures, high dipolar interaction and strong
electronegativity arising from the presence of nitrogen
atom, derivatives of pyridine molecule show significant
biological activity. Fortunately, simple syntheses of the
* Milena D. Milošević
milenamilosevictmf@gmail.com
Aleksandra Božić
aleksandrabozictmf@gmail.com
1
Faculty of Technology and Metallurgy, University
of Belgrade, Karnegijeva 4, 11000 Belgrade, Serbia
2
Innovation Centre of Faculty of Technology and Metallurgy,
University of Belgrade, Karnegijeva 4, 11000 Belgrade,
Serbia
3
Faculty of Chemistry, University of Belgrade, Studentski trg
12-16, 11000 Belgrade, Serbia
4
5
Belgrade Polytechnic, Brankova 17, 11000 Belgrade, Serbia
Faculty of Science and Mathematics, University
of Montenegro, Bulevar Džordža Vašingtona bb,
81000 Podgorica, Montenegro
Vol.:(0123456789)
1 3

Journal of the Iranian Chemical Society
aromatic aldehydes with pyridines provide an opportu-
nity for easy preparation and modification of the desired
chemical structures [1]. Thus, chemical modification
by various heteroaromatic substituents provides deriva-
tives that possess the ability to contribute to lung A549
and breast X226 cancer therapy [2, 3]. Some derivatives
have attracted significant interest after numerous in vitro
and in vivo studies showed their antiproliferative [2, 4]
and antioxidant activity [5–7]. In addition, due to their
mentioned structure as push–pull molecules, researchers
expanded their application in other fields of science and
technology such as: nanotechnology, optics and optoe-
lectronics, analytical, and environmental sciences [8, 9].
They are, also, used as non-linear optical materials, as
fluorescent probes [1, 9–11].
Scheme 1 Reaction path of 1-methyl-2,6-bis[2-(substituted phenyl)
ethenyl]pyridinium iodides synthesis
investigated for their antioxidant potential using DPPH and
ABTS methods.
Compounds containing styrene unit connected to a
pyridine ring are an important class of organic molecules
endowed with a highly polarizable π-electron system. Due
to their interesting biological activity, spectroscopic, photo-
physical and photochemical properties thousands of differ-
ent styryl compounds have been investigated [1, 12–14]. To
study specific properties of styryl derivatives, it is essential
to fully characterize molecular structure and obtain valu-
able information from the spectroscopic results. Therefore,
several spectroscopic techniques have been developed and
applied to investigate structure peculiarity, i.e., the position
of pyridine nitrogen, conjugation throughout the molecule,
and rotational isomerism [15–17]. Spectral and photochemi-
cal studies in a variety of solvents confirmed dynamic equi-
librium of different conformational isomers, and therefore
they showed complex UV–Vis spectra. Even more complex
behavior, compared to the most commonly studied neutral
molecules, shows their pyridine salts. Methylation of the
pyridine nitrogen atom converts those molecule to a cross-
conjugated systems with better performances as non-linear
optic materials [18].
Experimental section
Materials and characterization methods
Details on materials and characterization methods are given
in Supplementary materials.
Synthesis of symmetrical
1‑methyl‑2,6‑bis[2‑(substituted phenyl)
ethenyl]‑pyridinium iodide (1–15)
The series of symmetrical compound 1–15 was synthesized
by the condensation reaction of N-methyl-2,6-lutidine iodide
and appropriate aromatic aldehyde (Scheme 1). The descrip-
tion of the syntheses of 1-methyl-2,6-dimethylpyridinium
iodide is given in the Supplementary Material (Scheme S1)
[13]. Compounds 1 [19], 5 [13], and 11 [20] have, already,
been known in the literature. All the compounds presented
in this work were synthesized according to the modified lit-
erature procedure [13], and their purity was verified through
a melting point determination and elemental analysis. We
found that the solubility of product was better in methanol/
piperidine mixture instead of ethanol/piperidine mixture, as
described previously [13]. Therefore, with better solubility
higher product yields (44–67%) were obtained in only 2 h
instead of 3 days. A detailed description of the experimental
procedures and the characterization of reported compounds
are given in the Supplementary Material.
In this study, the synthesis of the 15 symmetric
1-methyl-2,6-bis[2-(substituted phenyl)ethenyl]pyridinium
iodides, i.e., 1-methyl-2,6-bis(substituted styryl)pyridinium
iodides (Scheme 1), is presented. UV–Vis spectra, recorded
in 20 solvents of various polarity, were used for study-
ing solute/solvent interactions by the use of linear solva-
tion energy relationships (LSER) using both Kamlet–Taft
and Catalán models. The linear free energy relationship
(LFER) principles were applied to get an insight into fac-
tors influencing NMR chemical shifts and νmax value. DFT/
TD-DFT was used for geometry calculations and analysis
of the extent of ICT during excitation. Calculations of the
bond lengths and occupying coefficient were used for the
quantification of the push–pull effect. According to this
concept, appropriate conclusions of the substituent effects,
steric hindrance, and push–pull character of the compound
have been made. In addition, synthesized compounds were
Detail characterization of known compounds is given in
Supplementary Material, while data of newly synthesized
compounds are reported below. 1-D (1H and 13C, Figs.
S1–S4) spectra of the selected compounds are also given in
Supplementary Material. Atom numbering of synthesized
compounds is outlined in Scheme 1.
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Journal of the Iranian Chemical Society
1-Methyl-2,6-bis[2-(2-naphthyl)ethenyl]pyridinium iodide
(2)
=N+–CH3), 7.30 (2H, d, J=7.5 Hz, CH=CH), 7.40 (4H, m,
CH=CH and C6H4); 7.62–7.70 (6H, m, C6H4 and pyridine),
8.29 (2H, d, J=7.6 Hz, C6H4); 8.45 (1H, d, J=6.4 Hz, pyri-
dine); 13C-NMR (50 MHz, DMSO–d6, δ/ppm): 21.7 (–CH3),
40.2 (=N+–CH3), 124.25 (C7 and C7), 128.3 (C3 and C5),
128.9 (C10 and C10), 129.2 (C14 and C14), 130.4 (C12 and
C12), 131.5 (C11 and C11), 134.7 (C8 and C8), 137.3 (C13
and C13), 139.61 (C9 and C9), 153.1 (C4), 155.2 (C2 and C6).
Yellow powder; yield: 67%; m.p. 253 °C, Elem. Anal: Calcd.
for C30H24IN (Mw =525.42 g mol−1): C, 68.58; H, 4.60; N,
2.67%. Found: C, 69.08; H, 5.10; N, 3.17%; IR (KBr, cm−1):
3042 (C–H stretching of pyridine group), 2924 (=N+–CH3
stretching), 2853 (C–H stretching of –CH3 group attached
to nitrogen), 1610, 1568, (C=C stretching of aromatic
ring), 1488 (C=C asymmetric stretching of aromatic ring),
1248, 1173 (C–N stretching of pyridine ring), 966 (=CH
assigned to out-of-plane deformation of trans alkenes), 775
(–CH out-of-plane deformation of phenyl group); 1H-NMR
(200 MHz, DMSO-d6, δ/ppm): 4.31 (3H, s, =N+–CH3); 6.91
(2H, d, J=7.2 Hz, CH=CH), 7.38–7.45 (6H, m, CH=CH,
pyridine and C6H4), 7.63 (4H, dd, J = 7.9 Hz, J = 5.6 Hz,
C6H4), 7.80–7.85 (4H, m, C6H4), 8.00 (4H, dd, J=6.8 Hz,
J = 5.1 Hz, C6H4), 8.30–8.36 (4H, m, C6H4), 8.45 (1H,
br.m.ovl., pyridine); 13C-NMR (50 MHz, DMSO–d6, δ/
ppm): 41.5 (=N+–CH3), 124.5 (C7), 128.2 (C3), (C5) 128.6
(C14), 129.2 (C13), 130.0 (C17), 130.4 (C16), 133.2 (C18),
113.9 (C15), 134.2 (C12a), 134.6 (C8), 138.2 (C9), 138.6
(C11), 153.6 (C4), 155.8 (C2).
1-Methyl-2,6-bis[2-(3-hydroxyphenyl)ethenyl]pyridinium
iodide (6)
Dark yellow powder; yield: 54%, m.p. 197.1–187 °C, Elem.
Anal: Calcd. for C22H20INO2 (Mw = 457.30 g mol−1): C,
57.78; H, 4.41; N, 3.06%; Found: C, 57.33; H, 3.91; N,
3.54%; IR (KBr, cm−1): 3320 (O–H stretching), 3045 (C–H),
2926 (=N+–CH3), 2852 (C–H), 1608, 1570 (C=C), 1488
(C=C), 1265, 1235 (C–N), 1171 (C–O stretching), 965
(=CH), 790 (–CH); 1H-NMR (200 MHz, DMSO-d6, δ/ppm):
4.27 (3H, s, =N+–CH3), 6.74 (2H, d, –OH), 7.10–7.18 (6H,
m, C6H4 and CH2=CH), 7.44 (2H, d, J=7.4 Hz, CH=CH),
7.65 (4H, m, pyridine and C6H4), 7.88 (2H, td, J=4.9 Hz,
J=4.5 Hz, C6H4), 8.26 (1H, d, J=7.8 Hz, pyridine); 13C-
NMR (50 MHz, DMSO–d6, δ/ppm): 40.5 (=N+–CH3),
113.89 (C14 and C14), 114.27 (C12 and C12), 119.74 (C10 and
C10), 124.43 (C7 and C7), 128.24 (C3 and C5), 130.30 (C11
and C11), 139.12 (C8 and C8), 142.86 (C9 and C9), 153.52
(C4), 158.09 (C2 and C6).
1-Methyl-2,6-bis[2-(4-methylphenyl)ethenyl]pyridinium
iodide (3)
Yellow crystal; yield: 55%, m.p. 203.8–208.8 °C, Elem.
Anal: Calcd. for C24H24IN (Mw =453.36 g mol−1): C, 63.58;
H, 5.34; N, 3.09%. Found: C, 64.08; H, 5.69; N, 3.59%; IR
(KBr, cm−1): 3050 (C–H), 2917 (=N+–CH3), 2857 (C–H),
1615, 1560 (C=C), 1483 (C=C), 1449 (C–H), 1287, 1246
1-Methyl-2,6-bis[2-(4-fluorophenyl)ethenyl]pyridinium
iodide (7)
1
(C–N), 979 (=CH), 809 (C–H); H-NMR (200 MHz,
Dark red crystals; yield: 57%, m.p. 213.5 °C, Elem. Anal:
Calcd. for C22H18F2IN (Mw =461.29 g mol−1): C, 57.28; H,
3.93; N, 3.04%. Found: C, 57.68; H, 4.28; N, 3.24%; IR
(KBr, cm−1): 3077 (C–H), 2933 (=N+–CH3), 2853 (C–H);
1560, 1595 (C=C), 1484 (C=C), 1288 (C–N), 1233, 1189
(C–F stretching); 971 (=CH); 1H-NMR (200 MHz, DMSO-
d6, δ/ppm): 4.30 (3H, s, =N+–CH3), 7.00 (2H, d, J=8.8 Hz,
CH=CH), 7.36–7.71 (4H, m, CH=CH, and pyridine), 7.93
(4H, t, J = 7.0 Hz, C6H4), 8.09–8.28 (4H, m, C6H4), 8.44
(1H, dd, J=7.9, J=4.4 Hz, pyridine); 13C-NMR (50 MHz,
DMSO–d6, δ/ppm): 48.32 (= N+–CH3), 115.11 (C11, C13,
C10, and C13), 124.28 (C7 and C7), 130.86 (C3 and C5),
131.42 (C10, C14, C10, and C14), 133.73 (C9 and C9), 140.59
(C8 and C8), 143.56 (C4), 153.48 (C2 and C6), 155.57 (C12
and C12).
DMSO-d6, δ/ppm): 2.37 (6H, s, –CH3), 4.28 (3H, s,
=N+–CH3), 7.32 (2H, s, J=8.0 Hz, CH=CH), 7.65 (2H, d,
J=8.0 Hz, CH=CH), 7.68–7.74 (6H, m, pyridine and C6H4),
8.26 (4H, d, J=7.4 Hz, 2C6H4), 8.42 (1H, dd, J=8.0 Hz,
J = 5.6 Hz, pyridine); 13C-NMR (50 MHz, DMSO–d6, δ/
ppm): 22.4 (–CH3), 40.5(=N+–CH3), 124.3 (C7 and C7),
128.3 (C3 and C5), 128.9 (C10, C14, C10, and C14), 129.1
(C11, C13, C11, and C13), 134.5 (C8 and C8), 134.5 (C9 and
C9), 142.4 (C12 and C12), 153.2 (C4), 155.4 (C2 and C6).
1-Methyl-2,6-bis[2-(3-methylphenyl)ethenyl]pyridinium
iodide (4)
Yellow powder; yield: 56%, m.p. 204.2–203.2 °C, Elem.
Anal: Calcd. for C24H24IN (Mw =453.36 g mol−1): C, 63.58;
H, 5.34; N, 3.09%. Found: C, 64.10; H, 5.67; N, 3.60%; IR
(KBr, cm−1): 3041 (C–H), 2919 (=N+–CH3), 2853 (C–H),
1607, 1566 (C=C), 1488 (C=C), 1459, 1331 (C–H), 1283,
1234 (C–N), 975 (=CH), 687 (C–H); 1H-NMR (200 MHz,
DMSO-d6, δ/ppm): 2.37 (6H, s, –CH3), 4.31 (3H, s,
1-Methyl-2,6-bis[2-(4-chlorophenyl)ethenyl]pyridinium
iodide (8)
Yellow powder; yield: 61%, m.p. 208 °C, Elem. Anal:
Calcd. for C22H18Cl2IN (Mw = 494.20 g mol−1): C, 53.47;
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Journal of the Iranian Chemical Society
H, 3.67; N, 2.83%. Found: C, 53.70; H, 3.32; N, 2.59%; IR
(KBr, cm−1): 3026 (C–H), 2929 (=N+–CH3), 2858 (C–H);
1622, 1564 (C=C), 1487 (C=C), 1280, 1248 (C–N), 1081
1-Methyl-2,6-bis[2-(4-nitrophenyl)ethenyl]pyridinium
iodide (12)
1
(C–Cl stretching), 971 (=CH); H-NMR (200 MHz,
Black crystals; yield: 61%, m.p. 204.2–203.2 °C, Elem.
Anal: Calcd. for C22H18IN3O4 (Mw = 515.30 g mol−1): C,
51.28; H, 3.52; N, 8.15%, Found: C, 51.70; H, 3.84; N,
7.85%; IR (KBr, cm−1): 3002 (C–H), 2921 (=N+–CH3),
2853 (C–H); 1624, 1519 (C=C), 1490 (C=C), 1280 (C–N),
1345 (N–O stretching of –NO2 group); 971 (=CH); 1H-NMR
(200 MHz, DMSO-d6, δ/ppm): 4.30 (3H, s, =N+–CH3);
7.20–7.52 (4H, m, CH=CH and pyridine), 7.60 (2H, d,
J = 6.8 Hz, CH=CH), 8.20 (4H, d, J = 7.4 Hz, C6H4),
8.36 (4H, d, J= 7.4 Hz, C6H4), 8.57–8,62 (1H, br.m.ovlp,
pyrdine); 13C-NMR (50 MHz, DMSO–d6, δ/ppm): 42.3
(=N+–CH3), 124.2 (C11, C13, C110, and C13), 124.6 (C7 and
C7), 126.9 (C3 and C5), 125.6 (C10, C14, C10, and C14), 137.8
(C9 and C9), 139.5 (C8 and C8), 144.9 (C12 and C12), 155.2
(C4), 157.5 (C2 and C6).
DMSO-d6, δ/ppm): 40.30 (3H, s, =N+–CH3), 7.02 (2H, d,
J=7.7 Hz, CH=CH); 7.26–7.52 (4H, m, CH=CH and pyr-
idine), 7.73 (4H, d, J = 7.2 Hz, C6H4), 8.05–8.18 (4H, m,
C6H4), 8.45 (1H, dd, J=8.1 Hz, J=5.5 Hz, pyridine); 13C-
NMR (50 MHz, DMSO–d6, δ/ppm): 48.30 (=N+–CH3),
124.31 (C7 and C7), 128.80 (C11, C13, C11, and C13), 130.42
(C10, C14, C10, and C14), 131.01 (C3 and C5), 135.6 (C9 and
C9), 138.2 (C8 and C8), 144.58 (C4), 145.57 (C12 and C12),
154.50 (C2 and C6).
1-Methyl-2,6-bis[2-(2,6-dichlorophenyl)ethenyl]pyridinium
iodide (9)
Yellow powder; yield: 45%, m.p. 204.1–203.7 °C, Elem.
Anal. Calcd. for C22H16Cl4IN (Mw = 563.09 g mol−1): C,
46.93; H, 2.86; N, 2.49; %, Found: C, 46.43; H, 2.41; N,
2.29%; IR (KBr, cm−1): 3038 (C–H), 2929 (=N+–CH3),
2852 (C–H), 1615, 1575 (C=C), 1481 (C=C), 1268 (C–N),
1-Methyl-2,6-bis[2-(4-methoxyphenyl)ethenyl]pyridinium
iodide (13)
Yellow powder; yield: 59%, m.p. 207.8 °C, Elem. Anal.
Calcd. for C24H24INO2 (Mw = 485.36 g mol−1): C, 59.39;
H, 4.98; N, 2.89%, Found: C, 59.63; H, 5.21; N, 2.60%; IR
(KBr, cm−1): 3046 (C–H), 2936 (=N+–CH3), 2833 (C–H
stretching of –CH3 group attached to nitrogen and oxy-
gen), 1599, 1560 (C=C); 1484 (C=C), 1325, 1254 (C–N),
1175 (C–O asymmetric stretching of –OCH3 group), 1023
1
1075 (C–Cl), 964 (=CH); H-NMR (200 MHz, DMSO-
d6, δ/ppm): 4.24 (3H, s, =N+–CH3), 7.47–7.52 (4H, m,
CH=CH and pyridine), 7.61 (2H, d, J = 4.1 Hz, CH=CH),
7.62–7.69 (4H, m, –C6H3), 8.33–8.37 (2H, d, J = 8.1 Hz,
–C6H3), 8.60 (1H, m, pyridine); 13C-NMR(50 MHz,
DMSO–d6, δ/ppm): 42.82 (=N+–CH3), 126.16 (C7 and
C7), 128.61 (C3 and C5), 129.43 (C11, C13, C11, and C13),
131.56 (C12 and C12), 134.12 (C10, C14, C10, and C14),
136.48 (C8 and C8), 145.16 (C9 and C9), 152.87 (C4),
156.47 (C2 and C6).
1
(C–O stretching of –OCH3 group), 978 (=CH); H-NMR
(200 MHz, DMSO-d6, δ/ppm): 3.84 (6H, s, –OCH3), 4.26
(3H, s, =N+–CH3), 6.81 (4H, d, J=7.8 Hz, C6H4), 7.06 (2H,
d, J=8.4 Hz, CH=CH), 7.51 (2H, d, J=8.4 Hz, CH=CH),
7.79 (2H, dd, J = 7.5 Hz, J = 4.8 Hz, pyridine), 8.22 (4H,
d, J = 7.8 Hz, C6H4), 8.34–8,37 (1H, m, pyridine); 13C-
NMR (50 MHz, DMSO–d6, δ/ppm): 43.1 (=N+–CH3), 55.3
(–OCH3), 114.1 (C11, C13, C11, and C13), 126.3 (C7 and C7),
128.4 (C3 and C5), 139.2 (C10, C14, C10, and C14), 140.1 (C9
and C9), 141.93 (C8 and C8), 152.7 (C4), 153.84 (C2 and C6),
159.8 (C12 and C12).
1-Methyl-2,6-bis[2-(2-chloro-6-fluorophenyl)ethenyl]
pyridinium iodide (10)
Black crystals; yield: 44%, m.p. 170 °C, Elem. Anal:
Calcd. for C22H16Cl2F2IN (Mw = 530.18 g mol− 1): C,
49.84; H, 3.04; N, 2.64%, Found: C, 49.62; H, 3.34; N,
3.14%; IR (KBr, cm−1): 3072 (C–H), 2929 (=N+–CH3),
2853 (C–H), 1603, 1576 (C=C), 1486 (C=C), 1242
1-Methyl-2,6-bis[2-(3,4-dimethoxyphenyl)ethenyl]
pyridinium iodide (14)
1
(C–N), 1172 (C–F), 1062 (C–Cl), 977 (=CH); H-NMR
(200 MHz, DMSO-d6, δ/ppm): 4.26 (3H, s, =N+–CH3),
7.49–7.56 (4H, m, CH=CH and pyridine), 7.60 (2H, d,
J = 4.7 Hz, C6H3), 7.64–7.94 (6H, m, pyridine, C6H3 and
CH=CH), 7.99 (2H, d, J = 8.1 Hz, C6H3), 8.60 (1H, m,
pyridine); 13C-NMR (50 MHz, DMSO–d6, δ/ppm): 45.20
(=N+–CH3), 115.51 (C13 and C13), 128.12 (C7 and C7),
129.51 (C3 and C5), 130.5 (C11 and C11), 134.22 (C10 and
C10), 145.5 (C9 and C9), 137.9 (C8 and C8), 150.08 (C4),
153.62 (C2), 160.22 (C14 and C14).
Orange powder; yield: 58%, m.p. 235 °C, Elem. Anal. Calcd.
for C26H28INO4 (Mw =545.41 g mol−1): C, 57.26; H, 5.17; N,
2.57%, Found: C, 57.61; H, 4.89; N, 3.01%; IR (KBr, cm−1):
3045 (C–H), 2925 (=N+–CH3), 2852 (C–H), 1599, 1561
(C=C), 1484 (C=C), 1357, 1322 (C–N), 1273, 1249 (C–O),
1
1016 (C–O), 965 (= CH); H-NMR (200 MHz, DMSO-
d6, δ/ppm): 3.85 (12H, s, J = 7.4 Hz, –OCH3), 4.29 (3H,
s, =N+–CH3), 7.07 (2H, d, J=8.4 Hz, C6H4), 7.40 (2H, d,
CH=CH and pyridine), 7.49–7.68 (6H, m, J=8.4 Hz, C6H4,
1 3

Journal of the Iranian Chemical Society
pyridine and CH=CH), 8.21 (2H, d, J=7.9 Hz, C6H4); 8,38
(1H, t, J=7.1 Hz, pyridine); 13C-NMR (50 MHz, DMSO–d6,
δ/ppm): 43.2 (=N+–CH3), 56.40 (–OCH3), 60.71 (–OCH3),
110.71 (C14 and C14), 114.14 (C11 and C11), 119.74 (C3 and
C5), 122.79 (C10 and C10), 126.40 (C7 and C7), 136.79 (C4),
140.8 (C9 and C9), 141.40 (C8 and C8), 153.61 (C2 and C6),
155.68 (C12 and C12), 159.79 (C13 and C13).
orbitals of partial double bonds were theoretically calculated
with the B3LYP/Def2TZVP wave function, using natural
bond orbital (NBO) [24] population analysis for electron
localization procedure. All quantum chemical calculations
were done in Gaussian09 [25] program package.
LSER and LFER analysis
1-Methyl-2,6-bis[2-(3,4,5-trimethoxyphenyl)ethenyl]
pyridinium iodide (15)
The non-specific solvent effect, i.e., solvent dipolarity/
polarizability, and specific ones, i.e., solvent–solute hydro-
gen bonding interactions, were evaluated by means of the
LSER models in first instance applying the Kamlet–Taft
equation [26]:
Orange crystals; yield: 61%, m.p. 236 °C, Elem. Anal.
Calcd. for C26H28INO4 (Mw = 605.46 g mol−1): C, 55.54;
H, 5.33; N, 2.31; %, Found: C,55.21; H, 5.83; N, 2.73%; IR
(KBr, cm−1): 3045 (C–H), 2935 (=N+–CH3), 2833 (C–H),
1596, 1568 (C=C), 1484 (C=C), 1345, 1326 (C–N), 1247,
1122, (C–O), 1020 (C–O), 964 (=CH); 1H-NMR (200 MHz,
DMSO-d6, δ/ppm): 3.86 (18H, d, J=7.4 Hz, –OCH3), 4.30
(3H, s, =N+–CH3), 7.08 (2H, d, J=8.4 Hz, C6H4), 7.40–7.43
(4H, m, CH=CH and Py), 7.49–7.68 (6H, m, J = 8.4 Hz,
C6H4, pyridine and CH=CH), 8.21 (2H, d, J = 7.9 Hz,
C6H4), 8.38 (1H, br.m.ovlp, pyridine); 13C-NMR (50 MHz,
DMSO–d6, δ/ppm): 43.2 (=N+–CH3), 56.20 (–OCH3), 60.90
(–OCH3), 73.22 (–OCH3), 105.4 (C14 and C14), 106.80 (C10
and C10), 113.8 (C11 and C11), 119.85 (C3 and C5), 126.35
(C7 and C7), 140.65 (C8 and C8), 141.15 (C9 and C9),136.45
(C4), 153.8 (C2 and C6), 145.6 (C12 and C12), 156.1 (C13
and C13).
ꢀmax = ꢀo + sꢁ∗ + bꢂ + aꢃ
(1)
where νmax is the absorption frequency maxima; π* is an
index of the solvent dipolarity/polarizability; β is a measure
of the solvent hydrogen-bond acceptor (HBA) basicity; α
is a measure of the solvent hydrogen-bond donor (HBD)
acidity, and νo is the regression value in cyclohexane as a
reference solvent. The regression coefficients s, b, and a in
Eq. (1) represents measure of the relative susceptibilities of
the absorption frequencies to the solvent effect. The solvent
parameters used in Eq. (1) are given in Table S1.
To obtain more specific separation of solvent effects the
Catalán equation was used [27]:
ꢀmax = ꢀo + cSP + dSdP + bSB + aSA
(2)
where SP, SdP, SA, and SB characterize solvent polarizabil-
ity, dipolarity, basicity, and acidity, respectively; and a–d are
the regression coefficients describing the sensitivity of the
absorption maxima to the different types of the solvent–sol-
ute interactions. The solvent parameters used in Eq. (2) are
given in Table S2. Separation of non-specific solvent effects,
term π* in Eq. (1), into two terms: dipolarity and polarizabil-
ity, SP and SdP in Eq. (2), contributes to the advantageous
analysis of the solvatochromism of the studied compounds.
NMR chemical shifts were subjected to the linear free
energy relationship analysis (LFER). The transmission of
substituent effects was studied using single substituent
parameter equation (SSP) in the form:
Molecular geometry optimization and theoretical
absorption spectra calculation
The ground state geometries of isomers, i.e., s-trans/s-trans
and s-cis/s-cis, (explanation for conformers naming is given
in previous paper [13]) of compounds 1–15 (considered as
cations) were optimized in gas phase with the DFT method.
Halogen anions were not included in computational consid-
erations in this work. First, the conformational search for
every isomer was conducted by varying C7–C8–C9–C10
torsional angle from 0° to 180° by 20° increment and fully
optimizing the structure using B3LYP method with Def-
2SVP basis set. After that, conformer with the lowest energy
was re-optimized using the same functional but with larger
Def2TZVP basis set [21]. Global minima were found for
each optimized compound and confirmed by calculations of
harmonic vibrational frequencies (no imaginary frequency
were found). Theoretical absorption spectra were calcu-
lated in DMSO solution with the TD-DFT method, more
specifically with CAM-B3LYP long range corrected func-
tional,[22] and Def2TZVP basis set on gas phase optimized
geometries. Solvent in the TD-DFT calculations was simu-
lated with standard polarized continuum model (PCM) [23].
Occupations of valence anti-bonding (π*) and bonding (π)
S = ꢀꢁ + h
(3)
where S is a substituent–dependent value: absorption fre-
quencies (νmax) or NMR chemical shifts; ρ is the propor-
tionality constant reflecting the sensitivity of the chemical
shifts spectral data to the substituent effects, σ is the cor-
responding substituent constant, and h is the intercept (i.e.,
describes the unsubstituted member of the series) [28]. The
substituent parameters used in Eq. (3) are given in Table S3,
were σ values correspond to an additive blend of polar and
π-delocalization effects.
1 3

Journal of the Iranian Chemical Society
where Asample and Acontrol refer to the absorbances at 734 nm
Regression and correlation
of ABTS in the sample and control solutions, respectively.
The dependence of the parameter solvents and absorption
frequencies were interpreted using multiple linear regres-
sion analysis. All correlations were performed at the 95%
confidence level. The quality of the correlation model was
shown through the value of the correlation coefficient, stand-
ard error and the Fisher’s test (F).
Results and discusion
Chemistry
The investigated compounds were synthesized by con-
densation of 1-methyl-2,6-dimethylpyridinium iodide and
appropriate aldehyde (Scheme 1). Chemical structures of
the synthesized compounds 1–15 were confirmed using IR
and NMR spectroscopy, and the purity was verified by the
melting point determination and elemental analysis. Due to
a well-known fact about possibility of rotational isomerism
around ethylenic bond it was necessary to perform molecu-
lar geometry optimization taking into account all possible
rotational isomers and stepwise procedure to obtain structure
with the lowest energy.
Antioxidant activity
Antioxidant activity was determined using 1,1-diphenyl-
2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzo-
thiazoline-6-sulfonic acid) (ABTS) radical scavengers.
DPPH method
Test solutions were prepared by dissolving ten different
amounts of compound in methyl alcohol. Commercially
available DPPH radical was dissolved in methanol at con-
centration of 5.34 × 10−5 mol L−1. A 96-well microplate
was loaded with 140 µL of DPPH solution and 10 µL of
test solution or pure methanol as the control. The micro-
plate was incubated for 30 min at room temperature in
the dark. After incubation, absorbance of DPPH radi-
cal was measured at 517 nm using a Thermo Scientific
Appliskan. All the measurements were carried out in
triplicate. The scavenging activity was calculated using
equation Eq. (4):
Geometry optimization and TD‑DFT calculations
The investigated compounds contain two symmetric sub-
stituted aryl rings attached to the central pyridine ring by
ethylenic bridging group. The physico–chemical properties
of these compounds are determined by either existence of
dominant conformational species or the dynamic equilib-
rium between the isomers. The inter-conversion between
possible rotational isomers occurs by the rotation of the
arylvinyl moieties around the quasi-single bonds with the
central pyridine through the thermal or photochemical pro-
cesses [29]. The state of the s-cis/s-cis and s-trans/s-trans
forms equilibria in solvents of different polarity depends on
the energy of the appropriate form, activation energy neces-
sary for inter-conversion or type and strength of the solute/
solvent interactions. It has been previously published that, in
the solid state, preferred conformation of compound is deter-
mined by the magnitude of weak steric interactions between
two vinyl hydrogen atoms and one found at lower distance
on pyridyl ring. This can, also, be of appropriate significance
in the solution [30].
((
)
)
%DPPH radical scavenging activity = Acontrol − Asample ∕Acontrol × 100
(4)
where Asample and Acontrol refer to the absorbances at 517 nm
of DPPH in the sample and control solutions, respectively.
Ascorbic acid was used as the reference compound.
ABTS method
ABTS solution was prepared by dissolving 19.2 mg of
ABTS in 5 mL of K2S2O8 solution (33 mg K2S2O8 in 50 ml
H2O) and diluting with methanol to obtained absorbance
of 0.700 0.020 at 734 nm. Experiments were performed
on the UV/Vis spectrophotometer. The reaction mixture is
consisted of 2.8 mL of ABTS radical solution and 0.2 mL of
tested compound solution in methanol (total volume, 3 mL).
After incubation in the dark for 20 min, the absorbance
was recorded at 734 nm. As a control, solution of ABTS
in methanol (2.8 mL of ABTS and 0.2 mL methanol) was
used. Ascorbic acid was used as a reference. The scavenging
activity was calculated using equation Eq. (5):
Results of the electronic energy calculations on the most
stabile geometry of both isomers, performed at B3LYP/
Def2TZVP level, are given in Table 1. Structures and ele-
ments of the optimized geometries are shown in Fig. 1 and
Table S4, respectively.
Energies of the optimized structures in gas phase
(Table 1) indicate dominant presence of the s-trans/s-trans
form of all synthesized derivatives, which is in consistence
with the reported crystallographic data of the most stable
conformation of similar compounds [31]. According to the
geometry optimization results for 4-hydroxy substituted mol-
ecule (5), obtained using DGDZVP basis set, s-cis/s-trans
(
)
%ABTS radical scavenging activity = 1 − (Asample∕Acontrol) × 100
(5)
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Journal of the Iranian Chemical Society
Table 1 Energies of optimized structure of studied compounds 1–15
likely, due to competitive positive resonance and negative
inductive effect of halogen atoms bond lengths remain simi-
lar as one found in the unsubstituted molecule. Conversely,
length of C7=C8 (C7′=C8′) double bonds decreases with elec-
tron accepting, and increases with electron-donating groups.
In general, the largest decrease and increase of the bond
lengths is found in compounds with the strongest electron-
accepting group, i.e., NO2 group, and the strongest electron-
donating group, i.e., N(CH3)2 group, respectively.
Comp. Energy (hartrees) (B3LYP/Def2TZVP)
ΔE (kcal mol−1
)
s-trans/s-trans isomer s-cis/s-cis isomer
1
−905.23742
−1212.63497
−983.90554
−983.90280
−1055.75594
−1055.74958
−1103.79731
−1824.48456
−2743.71593
−2023.03443
−1173.29633
−1314.39540
−1134.38775
−1363.50965
−1592.63340
−905.22834
−1212.62578
−983.89653
−983.89390
−1055.74715
−1055.74088
−1103.78806
−1824.47538
−2743.70593
−2023.02504
−1173.28752
−1314.38607
−1134.37902
−1363.50185
−1592.62566
−5.70
−5.77
−5.65
−5.58
−5.51
−5.46
−5.80
−5.76
−6.28
−5.89
−5.53
−5.86
−5.48
−4.90
−4.86
2
3
4
5
In addition, compared to the unsubstituted compound (1),
bond angles vary in different derivatives. As can be seen
in Table S4, halogens in the ortho-position have the most
prominent influence on the angles. This can be related to
the specific 4nature (balanced contribution of both +R and
−I effects with additional ortho-effect) and the small volu-
minosity of the halogens, especially fluorine. These effects
cause appropriate geometry adjustment as a response to
the electronic demands of the environment. These effects
cause appropriate geometry adjustment as a response to the
electronic demands of the environment. From the values of
dihedral angles (Table S4) it can be seen that deviation of the
planarity increases with the increase of the electron-accept-
ing ability of the substituents, while the derivative with the
strongest electron-donating group shows higher planarity.
6
7
8
9
10
11
12
13
14
15
Only structure of cation was considered (counter ion was excluded
from calculation)
conformation has been found as the most stable [13]. How-
ever, the basis set used in the mentioned work differs from
the basis set used in the present work, and thus the results
are not comparable.
Solvatochromism of the studied compounds:
multi‑parameter correlations
Depending on the type and number of the groups attached
to the two symmetric benzene rings bonds length and the
geometrical arrangement vary among the synthesized deriv-
atives. Bond distances and angles, defined by the numbering
according to the Scheme 1 and S2, and the sizes of dihedral
angles of interest, presented in Fig. 2, are given in Table S4.
The influence of the substituents on the C1–N1 bond
length is negligible for the electron-accepting groups
while the electron-donating groups, especially the strong-
est N(CH3)2, cause decrease in this bond length. The
most prominent substituent effect can be observed on the
lengths of C2–C7–C8–C9 and C6–C7′–C8′–C9′ unsaturated
bonds (Schemes 1 and S2). Electron-donating groups cause
decrease in the C2–C7 (C6–C7′) and C8–C9 (C8′–C9′) bonds
length (except ones in m-position), while opposite is true for
the electron-acceptor substituted compounds. The influence
is slightly more noticeable on the C8–C9 (C8′–C9′) bonds due
to the proximity of the substituent. Electron donors in the
para-position have the strongest impact on the bond length
decrease due to high contribution of extended π-electron
delocalization. The smaller influence of the electron-donat-
ing group in the ortho-position is related to the steric hin-
drance, so called ortho-effect, which can cause modification
of the extent of π-electron delocalization. On the contrary,
electron-accepting groups increase the length of those four
bonds with the exception of halogens in the p-position. Most
LSER analysis is frequently used as core concept of predic-
tive analysis related to study of the relationship between the
structure and properties of the investigated molecules. With
the aid of theoretical absorption spectra, behavior of the
studied compounds can be described by electronic structure
in both, ground and excited states induced by the change of
the solvent properties. Results of DFT calculations on the
stability of theoretically possible isomers show that s-trans/
s-trans form dominates in both, gas phase and solution.
Because the energy necessary for the effective rotation is
much higher than the thermal energy of the isomeric forms,
s-trans/s-trans isomer is dominant in the solution. Similar
results related to the structure of absorption bands in systems
with the ethylenic bridge in the ortho-position with respect
to the nitrogen heteroatom of central pyridine ring have,
already, been obtained as a result of the influence of double
bond [16]. Their common characteristic is the presence of a
strong absorption band in the 350–450 nm range that origi-
nates from the s-trans isomer. Bands of medium intensity
are also present at a shorter wavelength (275–315 nm), and
are ascribed to the cis-rotamer [32].
The absorption spectra, recorded in 20 solvents, are com-
plex and show presence of 2 or 3, not well separated, elec-
tronic transitions. Examples of the spectra of all compounds
in four solvents are given in Fig. 3. Intensity and absorption
1 3

Journal of the Iranian Chemical Society
Fig. 1 Optimized geometries of the most stable s-trans/s-trans conformations of compounds 1–15 in DMSO
frequencies of the main absorption bands (Table S5) depend
on the electronic structure of the studied compounds and the
solvent properties. In general, compared to the compound 1,
in all used solvents, electron-donating groups cause increase
in π-conjugation and induce batochromic shift, due to more
effective π-electronic transfer through substituted styryl moi-
eties, while the opposite effect is noticed for the electron-
acceptors [33].
As described by Wang et al. [18], absorption and emis-
sion maxima of N-methyl-2,3-distyryl-pyridine are strik-
ingly red shifted upon methylation which creates cross-
conjugated system, very similar to cyanine array. Analysis
of the substituent effect on the disturbance/enhancement of
Fig. 2 Dihedral angles used in conformational analysis of investi-
gated compounds
1 3

Journal of the Iranian Chemical Society
Fig. 3 Absorption spectra of compounds 1–15 in a EtOH, b AcN, c DMSO, and d F
π-electron delocalization in studied compounds is in accord-
ance with the known fact that increased electron conjugation
produces larger batochromic shift. Derivatives with electron-
donating group in p-position support effective π-electron
conjugation and, thus they show larger batochromic shift.
Presence of methyl group in the m-position disturbs the
conjugation, and, compared to compound 1, compound 4
shows hypsochromic shift. Considering the magnitude of
the νmax shift of p-OH substituted derivatives it can be seen
that more polar solvents produce larger batochromic shift.
The effect of substituent position can be explained by com-
paring solvatochromic behavior of the compounds 13–15 on
one side, and 9 and 10 on the other. UV–Vis spectra of the
compounds 13–15 (mono, di, and three substituted deriva-
tives with electron-donating methoxy group) are red shifted
in comparison to the compound 1. It is expected that com-
pound 15, with three strong electron-donating groups, shows
the largest shift. However, cross-effect of two meta and one
para methoxy groups contributes to lower π-electron delo-
calization and thus lowers red shift compared to the com-
pound 14. On the other hand, compared to the derivative
12 (the strongest electron-accepting group), compounds 9
and 10 show larger hypsochromic effect. Halogen atoms
show complex influence due to position-dependent contri-
bution of positive resonance and negative inductive effect,
and also steric interference of atom in the ortho-position.
Moreover, as expected for compound 11 (the strongest elec-
tron-accepting substituent) additional red shift of peak at
νmax = 20.34 cm−1 compared to the other compounds sug-
gests more pronounced ICT interaction in the molecule.
LSER analysis: correlation with multi‑parameter
solvent polarity scales
The position, intensity, and shape of bands in the absorption
spectra depend on the solvent properties. Multi-parameter
approach is often used to describe/evaluate the influence
of solvent effects on the absorption maxima change. The
interactions between solute and solvent molecules have been
quantified using Kamlet–Taft and Catalán LSER models.
The correlation coefficient (R), the standard error of the esti-
mate (sd), Fisher’s significance test (F), regression values ν0,
1 3

Journal of the Iranian Chemical Society
Table 2 Results of the correlations for compounds 1–15 obtained according to Kamlet–Taft equation
Comp. ν0 ×10−3 (cm−1
)
s×10−3 (cm−1
)
b×10−3 (cm−1
)
a×10−3 (cm−1
)
Ra
Sdb Fc
Solvent excluded from the correlation
THF, acetone, TCM, AcN, anisole, NMF
1
2
25.19 0.19
26.45 0.20
0.90 0.1
0.18 0.21
0.95 0.20
0.72 0.18
0.34 0.09
0.55 0.12
0.93 0.11 20.94
0.93 0.14 21.08
Acetone, EtOAc, DMF, DMSO, EtOH,
dioxane
3
4
5
6
26.41 0.08
27.44 0.08
27.26 0.33
27.04 0.15
0.10 0.08
−0.11 0.07
−0.78 0.33
−0.31 0.16
0.17 0.09
−0.34 0.08
−2.21 0.27
−1.41 0.14
−0.40 0.04
−0.28 0.04
−0.72 0.18
0.27 0.09
0.96 0.05 42.89
0.94 0.06 31.41
0.95 0.22 34.68
0.95 0.11 32.81
Anisole, TCM, t-AmOH, THF
Anisole, TCM, THF, DMF
EtAc, THF, dioxane, 2-PrOH, AcN
EtAc, THF, DMSO, DMA, anisole,
1-PrOH
7
22.03 0.11
0.28 0.11
−0.90 0.14
−0.19 0.06
0.95 0.08 33.09
Anisole, acetone, TCM, t-Amylol,
2-PrOH
8
9
26.81 0.11
29.84 0.07
−0.17 0.13
−0.14 0.08
−0.22 0.11
−0.12 0.07
0.48 0.07
−0.29 0.05
0.93 0.08 24.90
0.93 0.05 20.21
DMF, DMSO, t-amylol, AcN, NMF
iPrOH, NMF, MeOH, t-AmOH anisole,
THF
10
11
12
28.26 0.31
20.15 0.20
28.93 0.28
−1.17 0.59
0.44 0.20
0.75 0.54
−0.69 0.23
−0.17 0.24
−0.69 0.22
−0.54 0.13
0.69 0.15
0.93 0.23 19.90
0.94 0.14 23.39
0.95 0.14 28.20
t-AmOH, NMF, acetone, MeOH, THF,
DMA
iBuOH, t-AmOH, anisole, DMSO, F,
DMA, NMF
−1.60 0.39
iBuOH, t-AmOH, anisole, DMSO, F,
DMA, NMF
13
14
25.38 0.12
22.14 0.20
−0.94 0.15
0.42 0.19
0.77 0.13
0.13 0.18
−0.36 0.08
0.10 0.11
0.94 0.09 20.92
0.93 0.13 14.16
F, iPrOH, AcN, dioxane, DMA, NMP
Dioxane, EtAc, acetone, AcN, anisole,
DMSO, iPrOH
15
23.90 0.08
0.48 0.09
0.40 0.08
0.21 0.05
0.93 0.06 25.28
Dioxane, EtAc, NMF, DMA
aCorrelation coefficient
bStandard deviation
cFisher’s test of significance
s, a, and b (Kamlet–Taft), and c, d, a, and b (Catalán) are
presented in Tables 2 and 3, respectively. Statistical analysis
from multi linear analysis shows that both equations, i.e.,
Kamlet–Taft and Catalán, could be used successfully in
LSER analysis of investigated symmetrical compound.
Large diversity of correlation results, related to the sign
and values of solvatochromic parameters given in Table 2,
indicate that both, solvent and substituent effects determine
the position of UV maxima shifts. Negative sign of coeffi-
cient s, observed for compounds 4–6, 8–10, and 13, indicates
batochromic (red) shift with increasing solvent dipolarity/
polarizability. A hypsochromic shift (positive s coefficient),
observed for others compounds, suggests better stabiliza-
tion of excited state relative to ground state. Strong electron-
accepting effect of nitro group contributes to larger stabili-
zation of dipolar structure in excited state. Similar results
found for compound 10 reflect synergetic influence of elec-
tron-accepting/resonance ability of F atom and steric effect
of both substituents to larger stabilization of excited state.
Otherwise, solvent effects on νmax change for compounds
with electron donor, i.e., hydroxy substituted compounds 5
and 6, contribute to larger stabilization of excited state. Such
behavior, also observed, earlier, for similar compounds [13],
has been assumed to originate from the high symmetry of
the investigated compounds. In addition, synthesized com-
pounds contain no lone electron pair at the pyridine nitrogen
capable for proton accepting interaction with solvent. How-
ever, HBD solvents can be achieved through interactions
with the oxygen or nitrogen from the substituent. According
to the similarity of the values of coefficient a diversity of the
stabilization of either ground state (compounds 1, 2, 6, 8, 12,
14, and 15) or excited state found for other ones is found.
Such specific solvent effect largely depends on hydrogen
bonding ability of appropriate sites of investigated com-
pounds and their conformational arrangement.
The highest values of coefficient b, found for com-
pounds 5 and 6, implies that HBA solvent effect exert
through interactions of the ‘lone’ pair in OH groups on
the outer phenyl with HBD probe in surrounding solvent
shell. The negative value of b means batochromic shift
and greater stabilization of excited state with increasing
HBA power of the solvent. Obtained results indicate that
proton-donating capabilities of OH in para-position is
significantly enhanced due to directional effect with pyri-
dinium cation which causes increased proton-donating
capability with respect to one in meta-position (− 2.21
versus − 1.41, respectively). It should be noted that HBD
probe exerts significantly weaker interactions with the nitro
1 3

Journal of the Iranian Chemical Society
Table 3 Results of the correlation analysis for compound 1–15 according to the Catalán equation
Comp. ν0 ×10−3 (cm−1) c×10−3 (cm−1) d×10−3 (cm−1) b×10−3 (cm−1) a×10−3 (cm−1) Ra
Sdb Fc
Solvent excluded from the
correlation
1
2
25.77 0.29
27.13 0.48
0.33 0.33
1.81 0.61
0.92 0.12
1.80 0.26
0.20 0.12
0.76 0.21
0.72 0.12
0.94 0.09 18.63 THF, EtAc, NMF, EtOH,
DMA
−0.72 0.19
0.96 0.13 22.98 DMA, AcN, dioxane, EtOH,
NMP, THF
3
4
25.29 0.23
27.27 0.27
0.04 0.26
−1.07 0.33
1.11 0.13
0.87 0.13
0.41 0.10
−0.22 0.11
−0.50 0.09
−0.48 0.09
0.95 0.08 29.88 Dioxane, THF, EtAc
0.95 0.28 25.36 Dioxane, EtAc, AcN THF,
EtOH
5
6
29.10 0.71
27.73 0.60
−3.69 0.87
−0.37 0.969 −0.81 0.24
0.67 0.31
−2.92 0.33
−1.50 0.24
−1.63 0.30
0.39 0.24
0.96 0.24 30.74 EtAc, iPrOH THF
0.93 0.17 14.93 NMF, DMA, DMSO, EtAc,
THF
7
8
9
20.76 0.29
28.32 0.24
30.44 0.25
−0.18 0.32
−2.10 0.28
−0.97 0.34
1.20 0.17
−0.10 0.10
−0.23 0.09
−0.29 0.14
−0.44 0.10
−0.41 0.11
−0.13 0.11
−0.85 0.10
−0.55 0.09
0.94 0.09 17.81 Dioxane, THF, EtAc, TCM
0.96 0.07 30.89 DMSO, DMF, MeOH
0.93 0.05 14.80 iPrOH, AcN, acetone, NMF,
MeOH
10
11
12
33.11 0.72
19.17 0.59
28.91 0.73
−2.31 0.92
−1.98 0.50
0.60 0.73
−0.57 0.30
1.75 0.43
−1.96 0.45
1.02 0.32
−0.14 0.20
−0.27 0.38
−2.51 0.36
−0.32 0.21
1.76 0.29
0.93 0.22 16.20 NMF, acetone, MeOH, THF
0.95 0.14 35.20 Dioxane, DMA, THF, EtOH
0.94 0.20 20.44 DMA, dioxane, iBuOH,
EtAc, AcN
13
27.24 0.29
−2.65 0.36
−0.38 0.10
0.27 0.11
−0.70 0.13
0.94 0.07 17.82 F, NMF, 1-BuOH, DMSO,
iPrOH
14
15
22.83 0.37
24.29 0.21
−1.26 0.44
0.42 0.26
1.53 0.20
0.53 0.10
0.25 0.16
0.21 0.09
0.15 0.15
0.43 0.09
0.95 0.12 26.90 Dioxane, EtAc, THF
0.94 0.06 19.78 Dioxane, DMSO, MeOH
aCorrelation coefficient
bStandard deviation
cFisher’s test of significance
group of compound 12 with highest contribution of solvent
dipolarity/polarizability.
the number of methoxy groups in the compounds 13–15.
The highest value of dipolar interaction for the compound
12 can be a consequence of superposition of two opposite
electron-accepting effects of nitro group and pyridinium
moiety. In general, dielectric properties of molecular frame-
work under solvent influences can modify the π-electron
density mobility which means that polarization effect is not
necessarily transmitted in the direct line from the substitu-
ent to the probe sites.
Results of the quantitative separation of the non-specific
solvent effect into polarizability and dipolarity term (coef-
ficients c and d) performed using Catalán equation, Eq. (2),
are given in Table 3. The results obtained by the use of
Catalán equation provide better understanding of attractive/
repulsive solvent/solute interactions and enable estimation
of their appropriate contribution to νmax shift in UV–Vis
spectra. Correlation results (Table 3) confirm that the sol-
vent polarizability and dipolarity are the principal factors
influencing the shift of νmax, whereas solvent acidity and
basicity have moderate-to-low contribution. Synthesized
compounds have permanent electric dipole moment due
to symmetrical structure [17, 32], and, as it is expected,
it is found that dipolar solvent–solute interactions have
proper significance, i.e., compounds 2 (1.80), 11 (1.75), 12
(−1.96), and 14 (1.53). It can be assumed that superposi-
tion of the local dipol, i.e., polarized pyridinium cationic
structure, and ones exerted by the substituent effect can con-
tribute to larger dipolar solvent/solute interactions. It means
that magnitude of dipolar interaction of the compounds
increases with increasing electron-accepting potential of
the substituent present in the outer rings, as well as with
The introduction of the substituents of different electronic
properties (from electron accepting to electron donating) and
the strength of their influence (strong, moderate, low.) causes
appropriate enhancement/attenuation of π-electron mobility,
and thus there is a wide range of the coefficient c values. The
highest contribution of solvent polarizability is exerted for
electron-rich substituents, which probably affect the mobil-
ity of π-electrons and more stabilize excited state relative to
ground state. Proportional trend in the change of coefficient
s and d is defined as follows: higher values of c correspond
to lower values of d. Exceptions are noticed for compounds
2, 4, 11, and 14.
Specific solvent–solute interactions realized through
hydrogen bonding are of less significance, except for the
compounds 5, 6, and 10, were high negative values of HBA
1 3

Journal of the Iranian Chemical Society
effect can be attributed to the OH groups. Both terms associ-
ated with the HBD and HBA influence of solvent (a and b)
have different sign, and relatively low values/variation, while
exceptions are found for compounds 5 and 10.
states of the investigated molecules have been stud-
ied by calculation of the energies of frontier orbital
(EHOMO/ELUMO) and energy gap (Egap) values in gas
phase, using B3LYP/Def2TZVP method. Obtained results
are presented in Fig. 4 and Table S6. Compared to the
unsubstituted molecule 1, Egap values generally decrease
for the molecules with electron-donating substituents and
increase for the compounds with electron-accepting sub-
stituents. Higher energy gap, observed for the strongest
Nature of molecular orbital: TD‑DFT study
Mechanism of electronic excitations and changes in the
overall charge distribution in both, ground and excited
Fig. 4 The HOMO/LUMO orbitals and Egap of compounds 1–15 in s-trans/s-trans form in DMSO
1 3

Journal of the Iranian Chemical Society
electron-acceptor substituted compound 12 and ortho-hal-
ogen disubstituted compounds 9 and 10, is a consequence
of higher HOMO orbitals stabilization, i.e., HOMO has
lower energy compared to unsubstituted compound.
Looking at the results of geometry optimization, given
in Table S6, it is clear that these are compounds with the
highest deviation from planarity.
orbitals (Fig. 4). Non-linear changes in the energy of HOMO
and appropriate decrease of LUMO energy orbitals were
observed. From the presented results it seems that complex
contribution of substituent effects, interplay between present
methoxy groups, position-dependent electronic effects and
their spatial arrangement influences in a different way of
HOMO/LUMO energies (Egap) and energies of optimized
structure (Table 1).
As a consequence of N-methylation of the central pyri-
dine ring, and the presence of the iodine counter ion, the
s-trans/s-trans is the most stable conformation for all com-
pounds. Qualitatively, HOMO of the parent compound and
naphthyl substituted one is delocalized over the entire mol-
ecule, while LUMO is shifted towards the central pyridin-
ium ring. The introduction of the weakly electron-donating
methoxy groups in compounds 3 and 4 does not produce
any appreciable change in the electron density of HOMO
and LUMO orbitals with respect to compound 1. The energy
gap of these compounds is similar to the energy gap of com-
pound 1, although the involvement of the naphthyl moiety
causes significant lowering of Egap. On the other hand, the
introduction of the strong electron-donating hydroxy group
in compounds 5 and 6 causes a shift of the electron density
of HOMO toward the outer phenyl rings. In addition, the
introduction of the fluoro and chloro substituents, i.e., com-
pounds 7–10, and dimethylamino and nitro groups, i.e., com-
pounds 11 and 12, respectively, leads to similar electronic
distribution in both HOMO and LUMO orbitals. Higher
stabilization of both HOMO and LUMO orbitals cause that
the energy gaps for the former compound are the highest,
while lowest are found for compound 11. In the compounds
13–15 both HOMO and LUMO orbitals are delocalized
over its bent core in symmetrical fashion over methoxy sub-
stituted phenyl ring in former an over central pyridinium
ring in later orbital. The results from theoretical calculation
showed appropriate differences in optimized geometries of
investigated compounds 13–15 regarding their conforma-
tional arrangement. The parallel orientation of para –OCH3
in compound 13 with the plane of phenyl ring (dihedral
angle 179.8°) provides condition for undisturbed interac-
tion (moderate electron-donating character) of p-OCH3 with
π-electron density at neighboring phenyl ring. Oppositely,
appropriate deviation (out-of-plane rotation) of this group
in compound 14 (130.0°) causes decreased effective trans-
mission of this interactions (attenuation effect) with undis-
turbed capability of methoxy group attached at C13 (179.9°)
Significant steric repulsion (crowdedness) in compound 15
causes deviation of two OCH3 groups attached at C11 and
C12 carbons for 141.5° and 135.1°, respectively. Such pre-
ferred orientation influences decrease of electron-donating
capability of para –OCH3 group, and electron-accepting
power of meta –OCH3 attached at C11 (Scheme 1). Moreo-
ver, electronic substituent effect on electronic density can
be seen in the overall charge distribution in HOMO/LUMO
The ICT process is more feasible in compounds with
increased π-electronic density, i.e., 2 and 13–15. This is a
consequence of higher polarizability, and thus the stabil-
ity of excited state with respect to the ground state, under
influences of surrounding solvent environment (Table 4).
Due to this, the excited and ground states are closer and
internal conversion takes place more effectively. Variation
of structural/substituent patterns clearly indicates that con-
tribution of both factors, structural and substituent/com-
pound donor–acceptor characters, are involved in the ICT
mechanism of the investigated molecules. Additional results
from TD-DFT calculations in DMSO solution, oscillator
strengths, vertical excitation energies and electronic transi-
tions are provided in Table 4. TD-DFT results indicate a
large contribution of single HOMO to LUMO excitations in
ground state to first excited state transition (greater than 80%
for all compounds; Table 4). It can, also, be noticed that,
for all compounds, there is an appropriate participation of
HOMO-1 to LUMO+1 excitation (in the range 4.8–10.3%)
and HOMO-2 → LUMO (5.4, 4.4 and 2.3% for compounds
2, 6, and 14, respectively) and HOMO-4 → LUMO (in the
range from 2.1 to 5.5% for compounds 3–9, 11, 13, and 15).
In conclusion, for all compounds, most of the calculated
Egap values and TD-DFT results are in consistent with the
experimental results from UV–Vis measurement.
Bond length and occupying coefficient
for quantifying the push–pull effect in the studied
compounds
The push–pull parameters, bond lengths d/Å and occupation
quotients π*/π, of the partial C7=C8 (C7′=C8′) double bond
in the donor–acceptor linking chain C2(6)–C7(7′)=C8(8′)–C9(9′)
are considered. Such analysis can envisage the geometrical
arrangement of the studied compound. Larger twisting of the
double bonds induces electron donation into the π* orbital,
which, on the other hand, means that lower values of occupa-
tion coefficients (π*C=C/πC=C) indicate lower degree of devi-
ation [34]. Calculated π*/π quotients for compounds 1–15
and the values of C7=C8 double bond lengths (Table 5) indi-
cate low twisting of symmetrical styryl moieties (Table S4).
Correlation results of d(C7=C8) versus π*/π, given in Fig. 5
and Table 6, indicate that increasing donor–acceptor char-
acter of the compounds 1–15 cause increase in length of
C7=C8 double bonds.
1 3

Journal of the Iranian Chemical Society
Table 4 Results of TD-DFT
calculations for transitions from
ground to first vertical excited
state for s-trans/s-trans isomers
in DMSO solution
Comp. no. Energy, (eV) Oscillator Excitation
strength
CI expansion % of single particle
coefficient
excitation contribution
1
2
3.3423
1.64
HOMO → LUMO
HOMO-1 → LUMO+1
HOMO → LUMO
0.669
0.180
0.633
89.5
6.5
80.1
6.9
3.1425
2.33
HOMO-1 → LUMO+1 −0.186
HOMO-2 → LUMO
HOMO-4 → LUMO
HOMO → LUMO
HOMO-1 → LUMO+1
HOMO-4 → LUMO
HOMO → LUMO
HOMO-1 → LUMO+1
HOMO → LUMO
HOMO-1 → LUMO+1 −0.196
0.164
0.108
0.665
0.189
−0.102
0.667
0.177
0.661
5.4
2.3
88.4
7.1
2.1
90.0
6.3
87.4
7.7
3
3.2372
1.81
4
5
3.3243
3.1170
1.68
1.80
HOMO-4 → LUMO
HOMO → LUMO
HOMO-2 → LUMO
HOMO-1 → LUMO+1 −0.155
HOMO-3 → LUMO+1 −0.105
0.114
0.648
0.148
2.6
84.0
4.4
4.8
2.2
6
3.3465
1.57
7
8
3.3134
3.2810
1.66
1.87
HOMO → LUMO
HOMO-1 → LUMO+1 −0.180
HOMO → LUMO 0.662
HOMO-1 → LUMO+1 −0.190
0.667
90.0
6.5
87.6
7.2
HOMO-4 → LUMO
HOMO → LUMO
HOMO-1 → LUMO+1
HOMO → LUMO
HOMO-1 → LUMO+1 −0.183
HOMO → LUMO
HOMO-1 → LUMO+1
HOMO-2 → LUMO
HOMO → LUMO
HOMO-1 → LUMO+1 −0.216
HOMO → LUMO+2
HOMO → LUMO
0.112
0.663
0.167
0.668
2.5
87.9
5.6
89.2
6.7
82.7
10.3
4.3
83.5
9.3
3.5
86.3
8.2
2.1
9
3.5346
3.4153
2.7069
1.46
1.62
2.24
10
11
0.643
0.227
0.147
0.646
12
13
14
3.3543
3.0670
2.9961
1.97
1.87
1.91
0.133
0.657
HOMO-1 → LUMO+1 −0.202
HOMO-4 → LUMO
HOMO → LUMO
0.102
0.646
83.5
8.7
HOMO-1 → LUMO+1 −0.209
HOMO-2 → LUMO
HOMO-4 → LUMO
HOMO → LUMO
HOMO-1 → LUMO+1 −0.204
HOMO-4 → LUMO 0.166
0.108
−0.110
0.645
2.3
2.4
83.2
8.3
5.5
15
3.0685
1.90
As can be seen in Fig. 5, compound 9 shows signifi-
cant deviation from the correlation. The highest values of
the dipole moment are obtained for the compounds with
the, electron-acceptor, nitro substituents (Table 5). It is
known that molecules of higher hyperpolarizability have
larger dipole moments, but the hyperpolarizability proves
to be much higher for application as NLO molecules [35].
A possible approach to increase push–pull character is
1 3

Journal of the Iranian Chemical Society
Table 5 Occupation numbers of anti-bonding π* and bonding π orbit-
als, bond lengths of the corresponding partial C7=C8 double bond,
and dipole moments µ of compound 1–15
enhancement of the electron-accepting pyridinium group
using strongly electron-donating substituents. A weaker
double bond is assumed to be reflected by a longer distance
between the donor and the acceptor groups. In that sense
summary vector of the molecule arise, as a result of super-
position of local vector (Fig. S5 represents overall contribu-
tion of local dipole moments assumed according electron-
donating or accepting properties of substituents while Fig.
S6 represents theoretically calculated summary vectors for
molecules with the strongest donating and accepting sub-
stituents), while in case of compound 12 the same direction
of all local vectors gave a summary vector with high value
of dipole moments (Table 5).
Comp.
π
π*
π*/π
d(Å) (C7=C8) µ (Debye)
1
1.82526 0.15876 0.0870 1.350
1.81746 0.17875 0.0984 1.353
1.82137 0.17052 0.0936 1.352
1.82415 0.16036 0.0879 1.351
1.81816 0.18795 0.1034 1.354
1.82614 0.15344 0.0840 1.350
1.82530 0.16726 0.0916 1.351
1.82407 0.16605 0.0910 1.351
1.84253 0.12374 0.0672 1.345
1.82999 0.15070 0.0824 1.350
1.80429 0.22558 0.1250 1.360
1.83057 0.14132 0.0772 1.348
1.81621 0.19164 0.1055 1.355
1.81328 0.20205 0.1114 1.356
1.81553 0.19041 0.1049 1.355
0.8966
1.5543
0.8267
1.1363
1.8774
1.4956
2.7830
3.4324
0.9777
1.1652
1.2702
7.3266
1.5326
2.2403
4.4609
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Chemical shift differences, Δδ, as a measure
of the push–pull effect
The strong polarization of the double bond is also read-
ily discernible by 13C NMR due to extremely deshielded
position of the alkenyl carbon on the donor side and the
contrastingly shielded position of the carbon atom on the
acceptor side of the push–pull alkene [34]. Chemical shift
differences of the two sp2-hybridized carbons constituting
the double bond (Δδ) is an important property of push–pull
molecules and it can be useful sensor of the corresponding
push–pull effect. Higher values of ΔδC7=C8, as a measure of
the push–pull effect, imply higher degree of resonance and
the presence of electron donor substituents in the phenyl
moiety.
Strongly activating electron donating groups (EDG) in
the p-position of the phenyl substituted compounds 5 and 11
cause an increase in ΔδC7=C8. On the contrary, EDGs in the
m-position of the phenyl ring (compound 6) or presence of
more than one EDG substituents, cause significantly lower
increase relative to the unsubstituted compound 1. Weakly
activating EDGs as CH3 in compounds 3 and 4 equaly
Fig. 5 Correlation of bond lengths d(C7=C8) in Å and occupation
coefficients π*/π of the partial C7=C8 double bond in 1–15
Table 6 Results of correlations of selected bond distances versus π*/π, ΔδC7=C8 and σ
Correlation
ρ
h
R
Sd
F
Comp. included in correlation
d(C2–C7) versus π*/π
d(C7=C8) versus π*/π
−0.274 0.013
0.31 0.03
0.24 0.005
−0.41 0.045
1.478 0.001
1.33 0.002
1.33 0.0005 0.997 0.0002 2137
1.49 0.004
0.0008 0.0001 0.953 0.001
0.0005 0.0007 0.973 0.0006 72.30
2.80 0.12
1.28 0.007
0.986 0.0007 428.84
0.952 0.0015 127.31
All
All
–
a
d(C8–C9) versus π*/π
d(C7=C8) versus ΔδC7=C8 1.34 0.002
0.934 0.002
81.79
49.50
All
5, 6, 7, 8, 10, and 12
1.35 0.0008
1, 3, 4, 11, 13, 14, and 15
b
µ versus σ
(2.42 0.32)σ2
(3.76 0.18)σ
(−2.97 0.07)σ2 (2.26 0.05)σ
0.997 0.22
0.999 0.011
258.65
1241.68
–
c
–
aCompound 9 excluded
bCompound 15 excluded
cCompound 1 excluded
1 3

Journal of the Iranian Chemical Society
reduce ΔδC7=C8 value. In the case of halogen substituted
compounds 7–10, small influence of the electron donating
group in the o-position, (compounds 9 and 10) decrease
π-electron delocalization and thus the ΔδC7=C8 value, rela-
tive to the p-substituted compounds 7 and 8. Strong electron-
accepting groups in compound 12 contribute to the lowest
ΔδC7=C8 value.
increases with increase of electron-withdrawing strength of
substituents.
This chemical shift alteration, i.e., alternation of ρ values
(Table 7), is the consequence of the establishment of a strong
interaction of donor–acceptor and acceptor–acceptor sys-
tems in which the pyridinium ring nitrogen acts as acceptor,
and the introduction of a substituent of different properties
cause an alternation of electron density at bridging structure
(Figs. S5 and S6).
Chemical shifts, given in Table S7, are correlated with
the corresponding bond lengths, the third reliable push–pull
effect indicator. Results are shown in the Supplementary
Material (Fig. S7). With increasing push–pull character
of the partial C7=C8 double bond, bond elongation, and
increase in chemical shift differences ΔδC7=C8 are expected,
and correlation still points into the right direction. The
obtained correlation results are given in Table 6.
According to the NMR data ortho-substituted compounds
9 and 10, shows the highest chemical shifts, in line with
nitro-substituted compounds 12. Steric effect includes all
those phenomena which result in structural changes at meas-
ured sites, such as bond lengths and angles, effects due to
size of the ortho-substituents. Due to that ortho-substitu-
ents exert larger influences on chemical shift, i.e., higher
deshielding at all carbons considered, than electron donor
and electron acceptor in 3- and 4-position. Spatial arrange-
ment/deviation from planarity due to the presence of two
halogen atoms in compounds 9 and 10 are in good accord-
ance with the inter-atomic distances of those atoms taken
from their optimized geometries. It is generally assumed
that substituent effect at the ortho-position can be broadly
classified as electronic, steric and anisotropic [36, 37] two
former being the most significant.
Linear free energy relationships (LFER) analysis
of NMR data
The influence of the substituent effects on the electron den-
sity alteration over π-conjugative paths of ethylenic bonds
is interested to study in line with push–pull character of
investigated compounds. The liner free energy relationships
(LFER) of NMR data provide better insight into the elec-
tronic effects on the electronic density shifts over studied
molecule. LFER analysis has been used to postulate quanti-
tative structure-properties relations of substituent effect on
NMR data, and the best correlation results, obtained for C2,
C7, C8, and C9 carbons, are presented in Table 7 and Figs.
S8–S11.
High negative value of proportionality constants for C2
(electron donor) and C8 carbons indicates accumulation of
positive charge on this atom with increasing electron donat-
ing capability of substituents. Explanation for the opposite
effect of the substituents on C2 and C8 carbons (for elec-
tron donor) lies in the π-polarization concept introduced by
Reynolds [38] and cross-polarization of methylated deriva-
tives,[18] explained by appropriate resonance structures with
contribution of π-polarization. The field effect, induced by
substituent dipole, causes secondary π-electrons polarization
in the subsequent independent π-electronic system without
net π-electron transfer (Fig. 6). This concept of localized π
-polarization and extended polarization is used for explana-
tion of polar substituent effects within aromatic side-chain
derivatives.
General conclusion derived from the results presented in
Table 7 is that substituents on the benzene rings of inves-
tigated compounds influence chemical shifts of the carbon
atoms of interest. The observed high values of proportional-
ity constants, ρ, for these carbons indicate significant suscep-
tibilities of the NMR chemical shifts to substituent electronic
effects. Chemical shifts of C7 and C9 carbon atoms show
normal effect with two separate correlations (Figs. S9 and
S11), which means that deshielding of the observed carbon
Table 7 Correlation results
Atom
ρ
h
R
F
Sd
Comp. excluded
from correlation
of the NMR data of studied
compounds with σ constants
obtained using Hammett Eq. (3)
C2
C7
−3.15 0.41
4.79 0.61
3.01 0.38
2.63 0.45
−5.38 0.41
4.36 0.50
3.07 0.72
153.22 0.21
0.975
0.976
0.970
0.932
0.978
0.962
0.925
58.05
0.29
0.48
0.45
0.41
0.59
0.65
0.85
5, 6
3, 10
–
12
1, 3, 4, 12
5
–
153.22 0.31
126.50 0.20
124.05 2.63
140.50 0.18
141.93 0.23
134.82 3.07
61.20
63.86
33.25
172.90
73.88
17.85
C8
C9
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Journal of the Iranian Chemical Society
Fig. 6 Resonance structures of
electron-acceptor substituted
compounds with contribution of
π-polarization
In structure (1) (Fig. 6), presence of an electron-acceptor
substituent induce a dipole on C–X. Electron-accepting
effect of induced dipole transmitted through the molecular
structure causes polarization of individual π units (localized
polarization) [Fig. 6; structure (2)]. The experimental results
can also be rationalized with the aid of the resonance polari-
zation concept of the entire conjugated system (extended
polarization). Resonance interaction in extended conjugated
system of studied compounds has an opposite effect to the
polarization caused by electron-acceptor substituent. The net
result is that the electron-acceptor substituents increase the
electron density on C2 (C2′) and C8 (C8′) carbons, hence,
an increase in the shielding. Reverse substituent effect is
operative at C2 for electron donor and C8 for all substituents.
ortho-Substituents of high electron-accepting power cause
a higher deshielding due to both, electron-withdrawing and
ortho-effect.
(structure e), at which reverse substituent effect is obtained
(Table 4).
From the values of dihedral angles in Table S4, appro-
priate deviation from the planarity indicates that transmis-
sion of the resonance effect from substituted phenyl ring
can be suppressed to some extent. Resonance interaction
in extended resonance system can, thus, be achieved by π,
π-conjugation, depending on the present substituent. In gen-
eral, electron-acceptor attracts electron density from pyri-
dinium ring causing an electron density shift over ethylenic
bond. Opposite is true for the electron-donor-substituted
compounds. Electron-donor substituents support electron-
accepting resonance interaction in the pyridinium unit thus
deshielding effect at C2 is a result of a type of a “push-effect”
of electron-rich phenyl ring, reflected through increased
electron density at C7 and C9 carbons.
The presentation of π-electronic conjugation throughout
such molecules, as help in understanding specifics behav-
ior of the change of chemical shifts of observed carbons, is
given by resonance structures in Fig. S12 (Supplementary
Material). Due to their particular position in the molecule,
on the C2 carbon atom reverse effects have influence. First,
pyridine nitrogen, due to vicinity, tends to decrease electron
density with its accepting properties (structure d) while, on
the other hand, π-resonance effect of the styrene part of the
molecule tends to increase electron density (structures e–h).
In addition, positive charge also occurs on the C8 carbon
Fig. 7 Scavenging activity of investigated compounds 1–15 obtained
DPPH (filled blue square) and ABTS (filled red square)
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Journal of the Iranian Chemical Society
density and may lead to decrease in the antioxidant potential.
This phenomenon is observed for compounds 7, 8, and 12,
were F, Cl and NO2 electron-withdrawing groups, respectively,
lower the antioxidant potential. In contrast to para halogen
monosubstituted phenyl rings in styryl derivatives, the pres-
ence of two halogen element in the ortho-position of the phe-
nyl ring strongly increases antioxidant activity (9 and 10). In
addition, antioxidant activity of all compounds is measured
using ABTS assay, and the results are presented in Fig. 7 The
tested compounds shows similar trend in antioxidant activity
as with DPPH method.
Antioxidant activity
The studied compounds shows wide variation of antiradi-
cal activity by inhibiting DPPH radical. The interaction of
synthesized compounds with the stable DPPH free radical
indicates their free radical scavenging ability, i.e., antiradical
activity of compounds (Fig. 7). The majority of compounds
show good antioxidant properties, and the maximum anti-
oxidant activity is observed for compounds in the following
order 5>9>10>6>15>14>13>11. These compounds
display more than 50% inhibition, which is comparable to
that of the standard (vitamin C) at a similar concentration.
It is assumed that higher capacity/ability of compounds to
lose hydrogen, i.e., creation of structurally stable radical is
correlated with higher scavenging activity of the studied
molecule. In addition, it is expected that structure of the
compounds and electronic properties of substituents have
a crucial role to the stabilization of generated radical [39,
40]. The presence of either electron-withdrawing or elec-
tron-donating groups in the aromatic rings and the presence
of a pyridine ring may play a functional role in the activity
[41, 42]. It is also demonstrated that antioxidant activity
is related to the number of induced substituent groups [5].
Therefore, the difference in the activity of the synthesized
compounds is not unexpected.
Conclusions
This work reports synthesis, spectral, and antioxidant proper-
ties of 15 symmetrical heterocyclic derivatives of 1-methyl-
2,6-bis[2-(substituted phenyl)ethenyl]pyridinium iodides. The
presence of double bond between two aromatic moieties con-
nected to central pyridinium ring provides means for rotation
and existence of synthesized compounds in different conform-
ers. Theoretical calculations show that s-trans/s-trans form is
dominant isomer for all synthesized derivatives.
Understanding the transmission of substituent electronic
effect by π-polarization mechanism is one of the goals of the
present investigation. Solvatochromic properties are analyzed
from the UV–Vis absorption spectra recorded in the solvents
of different polarity. LSER correlation results indicate that
increasing solvent polarity induce red shift of the absorption
spectra. Solvatochromic behavior of compounds 1–15 can be,
in a considerable extent, ascribed to the non-specific electro-
static interactions with the solvent, rather than to the specific
hydrogen bonding. Such behavior most probably stems from
the high symmetry of the investigated compounds. The influ-
ence of substitution, hydrogen bonding, and protonation states
on spectral and photophysical properties are described, along
with the analysis of the frontier orbitals of studied molecules,
obtained from calculations performed on TD-DFT level of
theory. Bond length of C7=C8 (C7′=C8′), occupation quotients
π*/π of that bond and ΔδC7=C8 are found to be applicable sen-
sors of the donor–acceptor character of the studied molecules.
As for the antioxidant properties all compound possess
moderate scavenging effect. The results of the antioxidant
screening by ABTS radical scavenging assay have revealed
better antioxidant activity compared to DPPH activity assay.
The eight moderate active compounds possess some spe-
cial structural features that can be depicted in the following,
explaining the relationship between structure and activity.
Both distyril derivatives with hydroxyl group in the meta- or
para-positions on the phenyl ring, i.e., compounds 5 and 6,
respectively, show good activity (60.03 and 67.77%, respec-
tively). However, meta hydroxy substituted compound (6)
shows lower activity. Addition of methoxy group at para
position (13) significantly improves antioxidant activity. This
result can be explained by the strong electron donation ability
of the hydroxyl group in para positions while this group in
meta-position shows negligible electron-accepting character
[43]. The results are confirmed by the successive addition
of another methoxy group in meta-position (compounds 14
and 15). Hypothetically, the electron donating group should
increase the electronic density in the stiryl part of the mol-
ecules. It is well established that this type of groups stabilize
the resulted styril radicals through the resonance effect (as in
methoxy substituted derivatives 13–15), thus lower the C-H
bond energy in styril part of the molecules and enhance the
radical scavenging activity [43]. On the basis of the results it
can be concluded that apart from the position of the electron
donating group in the phenyl ring, the activity of the com-
pound is influenced by the number of groups, i.e., increased
number of methoxy groups in phenyl rings contributes to
increase in antioxidant activity.
Acknowledgements The authors acknowledge financial support from
the Ministry of Education, Science and Technological development of
Serbia, Project no. ОI 172013.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Contrarily, the presence of an electron-withdrawing group
might destabilize the styril moiety by withdrawing electronic
1 3

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