Synthesis, spectroscopic, thermal, structural investigations and biological activity studies of charge-transfer complexes of atorvastatin calcium with dihydroxy-p-benzoquinone, quinalizarin and picric acid

Article abstract of DOI:10.1016/j.molstruc.2020.128564

The charge-transfer interactions between n-electron donor, atorvastatin calcium (ATC) and the electron acceptors, 2,5-dihydroxy-1,4-benzoquinone (DHBQ), 1,2,5,8-tetrahydroxy-9,10-anthraquinone (quinalizarin, Quiz), and 2,4,6-trinitrophenol (picric acid, P

Full text of DOI:10.1016/j.molstruc.2020.128564

Journal of Molecular Structure 1219 (2020) 128564
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis, spectroscopic, thermal, structural investigations and
biological activity studies of charge-transfer complexes of atorvastatin
calcium with dihydroxy-p-benzoquinone, quinalizarin and picric acid
a
b, *
S. Niranjani , K. Venkatachalam
a
Department of Chemistry, SDNB Vaishnav College for Women, Chrompet, Chennai, 600044, Tamilnadu, India
Department of Analytical Chemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamilnadu, India
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 April 2020
Received in revised form
The charge-transfer interactions between n-electron donor, atorvastatin calcium (ATC) and the electron
acceptors, 2,5-dihydroxy-1,4-benzoquinone (DHBQ), 1,2,5,8-tetrahydroxy-9,10-anthraquinone (quinali-
zarin, Quiz), and 2,4,6-trinitrophenol (picric acid, PA) as
p-acceptors have been studied spectrophoto-
27 May 2020
metrically in methanol by giving highly colored charge transfer complexes. The isolated solid charge-
transfer complexes were characterized by elemental, IR, NMR, mass and thermal analysis to elucidate
the chemical structure of the obtained solid CT complexes. The stoichiometry of the complexes was
found to be 1:2 in [ATC]:[reagent] at DHBQ, quinalizarin, picric acid. This ratio gave the formed charge-
Accepted 28 May 2020
Available online 5 June 2020
Keywords:
Atorvastatin calcium
DHBQ
Quinalizarin
Picric acid
2 2 2
transfer complexes in the formulas [(ATC)(DHBQ) ], [(ATC)(Quiz) ], and [(ATC)(PA) ] which was also
confirmed by elemental and mass analysis. Their biological activities were also screened against various
bacterial organisms. The obtained results are suitable for the estimation of antihyperlipidemic drug, ATC
in pharmaceutical dosage forms.
Charge transfer complexes
Antibacterial activity
© 2020 Elsevier B.V. All rights reserved.
1. Introduction
limiting step in the cholesterol synthesis mevalonate pathway
[15]. The inhibition of HMG-CoA uses to reduce cholesterol in the
The interaction between a donor and an acceptor involves a
formation of weak bonds called charge-transfer complex (CTC)
which was first introduced by Mulliken and coworkers [1,2]. These
molecular interactions produce colored CTC, which usually absorbs
in the visible region [3]. The charge-transfer complexation is the
principal director of specificity, rate control and reversibility of
many biochemical reactions [4]. It plays an important role in bio-
molecules [5]. The CT complexes show potent antimicrobial prop-
erties against Gram-positive and Gram-negative bacteria [6e12].
Atorvastatin calcium (ATC), chemically [R-(R*,R*)]-2(4-
blood and to increase the synthesis of low-density lipoprotein re-
ceptors. As a result, it increases LDL cholesterol from the blood-
stream [16]. Statins have been investigated for their antibacterial
action [17]. It is official in United States Pharmacopoeia 34, Indian
Pharmacopoeia [18,19]. ATC shows some anti-bacterial activities
[17,20].
The literature survey revealed several analytical methods were
available for the determination of ATC. Wani et al. [21] used
microwell-plate absorbance reader and prepared charge-transfer
complex with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
fluorophenyl)-
b,
d-dihydroxy-5(1-methlyethyl)-3-phenyl-4 (phe-
in the linear range of ATC in 10e150 mg/mL. Ergin et al. [22] pre-
nylamino)]-1H-pyrrole-1-heptonoic acid, calcium salt (2:1) is a
second generation synthetic 3-hydroxy-3-methylglutaryl-coen-
zyme A (HMG-CoA) reductase inhibitor [13]. ATC, which is shown
in Fig. 1 is the most efficient and potent antihyperlipidemic drug
that is widely used for the treatment of hypercholesterolaemia [14].
The enzyme, HMG-CoA reductase is accountable for the rate-
pared CTC of statins with 7,7,8,8-tetracyanoquinodimethane
(TCNQ) in acetonitrile. A UVevisible spectrophotometric method
was developed and validated for ATC with iodine in acetonitrile by
Ramadan et al. [23]. Several works have been done for CTC with
different acceptors such as iodine, chloranil, chloranilic acid, DDQ,
TCNQ, 2,5-dihydroxy-1,4-benzoquinone, quinalizarin and picric
acid [24e37].
To give the fundamental data that can be used to realize
drugereceptor mechanism, the CT complexes of ATC as donor with
*
Corresponding author.
E-mail address: venkatachalam@unom.ac.in (K. Venkatachalam).
https://doi.org/10.1016/j.molstruc.2020.128564
022-2860/© 2020 Elsevier B.V. All rights reserved.
0

2
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
single quadrupole mass spectrometer with electrospray ionization
ESI) in the positive ionization mode was used for all samples.
(
Thermogravimetric (TG) and differential thermogravimetric (DTG)
analysis were carried out for ATC and also all CT-complexes using
Shimadzu TGA-50H thermal analyzer. The rate of heating of the
ꢁ
ꢀ1
sample was kept at 10 C min under nitrogen flow. Copper sulfate
pentahydrate was used as a calibration standard. High Resolution
scanning electron microscope (FESEM) was taken using the model
FEI, Quanta FEG 200. Elemental analysis was carried out using the
model PerkinElmer CHN 2400, USA elemental analyzer.
2
2
.3. Procedures
Fig. 1. Chemical structure of atorvastatin calcium (ATC).
.3.1. Synthesis of ATC-acceptors CT-complexes
1
mmol of ATC (0.1155 g) which was dissolved in 10 mL of
2
,5-dihydroxy-1,4-benzoquinone (DHBQ), quinalizarin (Quiz) and
methanol was mixed with 1 mmol of the acceptors, DHBQ, Quiz and
PA dissolved in the same solvent. They were stirred at room tem-
perature for 20 min. The obtained solid was filtered off, washed
several times with the same solvent and allowed to evaporate
slowly at room temperature. The solids were dried in vacuum un-
der anhydrous calcium chloride for 24 h. The obtained solids were
characterized spectrophotometrically and also by elemental
analysis.
picric acid (PA) as p-acceptors were synthesized and spectroscop-
ically investigated. The newly synthesized CT complexes have been
1
structurally characterized via elemental analysis; infrared (IR), H
NMR, mass and electronic absorption spectroscopy; thermal anal-
ysis; scanning electron microscopy (SEM) to interpret the behav-
iour of the interactions. Their bonding nature was determined by
the physical parameters using thermodynamic equations. Finally,
the biological activity of ATC-CT complexes were tested for their
antibacterial activities.
2
.3.2. Preparation of standard stock solutions of ATC and the
acceptors
Stock solutions of pure ATC and the acceptors namely, DHBQ,
2
. Experimental
ꢀ
3
Quiz and PA at a concentration of 5.0 ꢂ 10 M were freshly pre-
pared before the experiments by dissolving accurately weighed
amounts in the appropriate volume of methanol. All experiments
were done in dry conditions. They were sheltered from light. The
concerned standard solutions were prepared from the corre-
sponding stock solutions.
2.1. Chemicals
API atorvastatin calcium ([R-(R*,R*)]-2-(4-fluorophenyl)-b,d-
dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)
carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1),
68CaF 10; 1155.34) was gifted from Orchid Pharmaceutics,
India. Analytical grade reagents namely, DHBQ (2,5-dihydroxy-1,4-
benzoquinone, 140.09), quinalizarin (Quiz, 1,2,5,8-
tetrahydroxy-9,10-anthraquinone, C14 ; 272.21), and picric
acid (PA, 2,4,6-trinitrophenol; C ; 229.10) were purchased
C
66
H
2 4
N O
C
6
H
4
O
4
;
2.3.3. Spectrophotometric titration procedure
H
8
O
6
Photometric titration measurements were performed for the
reactions between the donor, ATC and each of the acceptors, DHBQ,
Quiz, PA at wavelengths of 355 nm, (588 and 638 nm) and 382 nm,
respectively, in methanol solutions at room temperature in order to
determine the reaction stoichiometries according to the literature
method [6e11]. The experiments were carried out with the fixed
6 3 3 7
H N O
from SigmaeAldrich, USA, and used as received. Commercially
available HPLC grade methanol was used as solvent from Fisher
Scientific Company.
ꢀ
4
concentration (1.00 mL of 5.0 ꢂ 10 M) of ATC in the varying
2.2. Instrumentation
concentration (0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50 or
ꢀ
4
4
.00 mL of 5.0 ꢂ 10 M) of the acceptors, namely, DHBQ, Quiz, PA
All electronic absorption spectra were recorded using Aglient
453 model with a diode array detector (DAD) in the range
in the same methanol solutions. 5.0 mL was fixed as the total vol-
ume of the mixture. As a result, donor:acceptor molar ratio was
maintained from 1:0.25 to 1:4. The peak absorbancies of the
formed CT-complexes were measured for all solutions in each case
and plotted as a function of the acceptor to donor molar ratio.
8
190e1100 nm with a quartz cell of 1.0 cm path length. The mid-
infrared spectra of ATC and the obtained CT-complexes were
recorded on Shimadzu, IRTracer 100 FTIR spectrophotometer with
ꢀ1
ATR mode with 45 number of scans at 2 cm resolution in the
ꢀ11
range 4000e400 cm . H NMR spectra were obtained on a Bruker
BioSpin GmbH-500 spectrometer operating at 500 MHz in 293.8 K
with a dual 5 mm probe head. H NMR data were expressed in parts
per million (ppm) using DMSO (dimethylsulfoxide, d ) as a solvent
6
and tetramethylsilane (TMS) as an internal reference. The signals
were referenced internally to the residual proton impurity in DMSO
and reported in chemical shift. LC-MS 2020 system equipped with
2.3.4. Biological assay
1
The antibacterial activities of the newly synthesized ATC-CT
complexes and the pure solvent, DMSO were tested in vitro
against Gram-positive bacteria, Eggerthella lenta (ATCC 43055) and
four Gram-negative bacteria, Enterobacter aerogenes (MTCC 111),
Alcaligenes faecalis (MTCC 3104), Klebsiella pneumoniae (MTCC 109)
Table 1
Spectroscopic data for the obtained ATC-acceptor complexes.
Complexes
Color
Absorbed wavelength (nm)
Stoichiometry (Donor:Acceptor)
[
[
[
(ATC)(DHBQ)
(ATC)(Quiz)
(ATC)(PA)
2
]
Pink
Dark Purple
Yellow
355
588, 638
382
1:2
1:2
1:2
2
]
2
]

S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
3
Fig. 2. Naked-eye visible strong color changes of (A) [(ATC)(DHBQ)
2
], (B) [(ATC)(Quiz)
2 2
] and (C) [(ATC)(PA) ] charge-transfer complexes.
ꢀ
4
ꢀ4
Fig. 3. Electronic absorption spectra of ATC-DHBQ in MeOH. (A) [ATC]
[
¼
2
ꢂ
10
M; (B) [DHBQ]
¼
2
ꢂ
10
M; (C) 1:2 ATC-DHB CTC at 355 nm where
ATC] ¼ [DHBQ] ¼ 2 ꢂ 10ꢀ M. Fig. 3A Photometric titration curve for ATCeDHBQ in MeOH at 355 nm.
4
Fig. 4. Electronic absorption spectra of ATC-Quiz in MeOH. (A) [Quiz] ¼ 1 ꢂ 10ꢀ M; (B)1:2 ATC-Quiz CTC at 588 nm and 638 nm where [ATC] ¼ [Quiz] ¼ 1 ꢂ 10ꢀ4 M. Fig. 4A
4
Photometric titration curve for ATCeQuiz in MeOH at 588 and 638 nm.
and Acinetobacter baumannii (MTCC 1425) using a modified
BauereKirby disc diffusion method. Test pathogens (100 L) which
autoclaving. The dry, sterilized discs of diameter 6 mm were kept
using a sterile forceps and loaded with the test compounds of
m
were grown in 10 mL fresh medium were spread on Mueller-Hinton
agar (MHA) plates. Bacteria were cultivated overnight, and the
broth was diluted to 10 colony forming units (CFU)/mL with sterile
distilled water and was introduced onto the surface of sterile MHA
plates using a sterile glass spreader for even distribution of the
pathogenic culture. Discs measuring 6 mm in diameter were pre-
pared from Whatman No. 1 filter paper and sterilized by
known concentrations. The screening was performed using 10 mg/
mL ATC-CT complexes. Blank test showed that DMSO used in the
preparation of the test solutions did not affect the bacteria. The
plates after inoculation were inverted and incubated for 24 h at
6
ꢁ
37 C. The zone of inhibition around the disc, which was calculated
edge to edge zone of the confluent growth usually corresponds to
the sharp edge of the zone and was measured using slipping

4
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
Fig. 5. Electronic absorption spectra of ATCePA in MeOH. (A) [PA] ¼ 4 ꢂ 10 M; (B)1:2 ATC-PA CTC at 382 nm where [ATC] ¼ [PA] ¼ 4 ꢂ 10ꢀ4 M. Fig. 5 A Photometric titration curve
ꢀ4
for ATCePA in MeOH at 382 nm.
calipers from the National Committee for Clinical Laboratory
Standards (NCCLS, 1993) [38] and was expressed in millimeters
3.2. Electronic absorption spectra
(
mm). All tests were repeated three times and average data was
The electronic absorbance maximum bands of the obtained
taken as a final result. An antibiotic disc of Ciprofloxacin (10
mg/disc,
2 2 2
solid complexes [(ATC)(DHBQ) ], [(ATC)(Quiz) ] and [(ATC)(PA) ]
Hi-Media) was used as a positive control.
were shown in Table 1. Photometric titration curves which were
based on electronic absorption spectra of these solid charge-
transfer complexes were examined and the results obtained were
in good agreement with the elemental analysis.
3
. Results and discussion
The electronic spectra were recorded in the region
200e1100 nm for the reaction of DHBQ, Quiz and PA with ATC
3
.1. Elemental analysis
which were shown in Figs. 3e5. ATC showed maximum absorption
at 248 nm. The new characteristic absorption bands for ATC-CT
complexes were found which was absent in the free acceptors. A
strong change in color was observed on complexation with the
acceptors shown in Fig. 2. The bands corresponded to the charge
transfer complex of ATC with DHBQ, Quiz and PA were 355 nm, (588
and 638 nm) and 382 nm. Photometric titration curves were given
for all these complexes in these characteristic absorption bands. All
these complexes showed the reaction molar ratio as 1:2. The for-
mation of 1:2 CT-complex in all cases was very good agreement
with elemental analysis, mass spectra as well as thermal analysis
TGeDTG. The obtained CT-complex were formulated as
Elemental analysis of the obtained CT complexes of ATC was
given as follows: (theoretical values were shown in brackets).
(ATC)(DHBQ)
] pink complex (M.wt. ¼1435 g): C, 65.29% (65.20%);
H, 5.37% (5.29%); N, 3.95% (3.89%); m. pt 120e125 C; [(ATC)(Quiz)
Dark purple complex (M.wt. ¼1700 g): C, 66.45% (66.39%); H, 5.00%
[
2
ꢁ
2
]
ꢁ
(
4.95%); N, 3.39% (3.35%); m. pt 186e192 C and [(ATC)(PA)
2
] Yellow
complex (M.wt. ¼ 1613 g): C, 58.01% (58.10%); H, 4.60% (4.63%); N,
ꢁ
.66% (8.69%); m. pt 132e137 C. The obtained values were in good
8
agreement with the theoretical values, and also with the deter-
mined molar ratios from the spectrophotometric titration curves.
The stoichiometry of CT complexes of ATC was found to be 1:2 ratio
in ATC-DHBQ, ATC-Quiz and ATC-PA. Based on the obtained data,
2 2 2
[(ATC)(DHBQ) ], [(ATC)(Quiz) ] and [(ATC)(PA) ].
the formed CT complexes were formulated as [(ATC)(DHBQ)
2
],
3.3. Calculation of the spectroscopic and physical data
[
(ATC)(Quiz) ] and [(ATC)(PA) ]. The formation of these complexes
2
2
1
was powerfully supported by IR, H NMR as well as mass analysis.
All absorbance values which were obtained from the spectra of
Table 2
The values for Benesi-Hildebrand plots for ATC-CT complexes.
( ꢂ 10ꢀ4M)
C
( ꢂ 10ꢀ4M)
C
(
(4C
þ C
)
(C
) C
2
[(ATC)(DHBQ)
]
[(ATC)(Quiz)
]
[(ATC)(PA)
C
d
a
a
d
a
a
d
2
2
2
]
ꢀ
8
ꢀ12
ꢂ 10 M) ( ꢂ 10 M)
2
2
2
2
A at 355 nm (C
a
) C
d
/A
A at 588 nm (C
a
) C
d
/A
A at 638 nm (C
a
) C
d
/A
A at 382 nm (C ) C /A
a d
ꢂ 10 12M)
ꢀ
( ꢂ 10 M)
ꢀ12
( ꢂ 10 M)
ꢀ12
( ꢂ 10 M)
ꢀ12
(
0
0
0
1
1
2
2
3
3
4
.25
.50
.75
.00
.50
.00
.50
.00
.50
.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
2.00
3.00
4.00
5.00
7.00
9.00
11.00
13.00
15.00
17.00
0.25
0.50
0.75
1.00
1.50
2.00
2.50
3.00
3.50
4.00
0.0585
0.1089
0.1566
0.1996
0.2757
0.3413
0.3975
0.4464
0.4905
0.5284
4.2735
4.5914
4.7893
5.0100
5.4407
5.8599
6.2893
6.7204
7.1356
7.5700
0.1991
0.3669
0.4259
0.5634
0.6798
0.8141
0.9164
1.1466
1.2275
1.3135
1.2557
1.3628
1.4922
1.6225
1.8594
2.1111
2.3596
2.6164
2.8513
3.0453
0.1167
0.2228
0.3101
0.3979
0.5435
0.6636
0.759
0.8522
0.928
0.995
2.1423
2.2442
2.4186
2.5132
2.7599
3.0139
3.2938
3.5203
3.7716
4.0201
0.05999
0.1177
0.1728
0.2239
0.3238
0.4149
0.4997
0.5761
0.6516
0.7191
4.1674
4.2481
4.3403
4.4663
4.6325
4.8204
5.003
5.2074
5.3714
5.5625

S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
5
2 2 2
Fig. 6. Benesi-Hildebrand plots of (A) [(ATC)(DHBQ) ], (B) [(ATC)(Quiz) ] and (C) [(ATC)(PA) ] charge-transfer complexes.
Table 3
Spectroscopic and physical data of ATC-CT complexes.
ꢁ
eDG (kJ/mol)
Complex CT (eV)
l
max (nm)
E
KCT (L/mol)
εmax (L/mol/cm)
f
m
(Debye)
I
p
(eV)
R
N
(eV)
6
4
[
[
(ATC) (DHBQ)
(ATC)(Quiz)
2
]
355
588
3.50
2.12
1.95
3.26
5.51 ꢂ 10
1.21 ꢂ 10
6.65 ꢂ 10
2.35 ꢂ 10
4.64 ꢂ 10
8.21 ꢂ 10
7.96 ꢂ 10
1.07 ꢂ 10
48.28
42.55
50.88
61.41
60.35
72.93
83.25
70.60
10.07
8.36
8.16
9.77
1.90
0.48
0.44
0.77
38.47 ± 0.003
40.42 ± 0.002
38.93 ± 0.004
36.35 ± 0.005
7
6
6
4
4
5
2
]
638
[
2
(ATC)(PA) ]
382
ATC-CT complexes were taken and plotted as a function of the C
ratio according to modified Benesi-Hildebrand equation [39].
The donor, ATC formed 1:2 CT complexes with DHBQ, Quiz and
PA. The BH equation (1) used for 1:2 CTcomplexes [40] was given as
follows:
d
:C
a
The formation constant (KCT) and molar absorptivity (εCT) values
for the obtained ATC-CT complexes were shown in Table 3. The
higher value of KCT associates with the high stability of ATC-CT
complexes with higher values of εCT. As a result, strong donation
from ATC was occurring with the three acceptors, DHBQ, Quiz and
PA which have high electron affinity in the high dielectric permit-
tivity of methanol. The nature of the acceptor strongly depends on
electron withdrawing substituents present in it. The formation
constant (KCT) values of ATC-CTcomplexes in decreasing order were
ꢀ
ꢁ.
.ꢀ
ꢁ
ꢀ .
ꢁ
ꢀ
ꢁ
2
ðC
a
Þ C
A ¼ 1
KCT
ε
CT
þ 1 ε
C
a
4C þ C
a
(1)
d
CT
d
where C
a
and C
d
were the initial concentration of the acceptors
[(ATC)(Quiz)
decreasing order of molar absorptivity (εCT
[(ATC)(PA) ] > [(ATC)(Quiz) ] > [(ATC)(DHBQ) ].
The oscillator strength (f), the transition dipole moment (
2
]
>
[(ATC)(DHBQ)
2
]
>
[(ATC)(PA)
2
]
while the
(
DHBQ, Quiz and PA) and the donor, ATC, respectively, and A is the
) values were
2
absorbance of the identified CT-band. The values for C
, C
a d
, (C
a
) C
d
,
2
2
2
2
C
a
(4C
d
þ C
a
) and (C
a
) C
d
/A were calculated and tabulated as shown
m), the
2
in Table 2. A plot of (C
a
) C
d
/A values against C
a
(4C
d
þ C
a
) gave a
CT. Fig. 6
ionization potential (I
P
), the resonance energy (R
N
), energy (ECT) and
ꢁ
straight line with a slope of 1/εCT and an intercept of 1/KCT
showed BenesieHildebrand plots for ATC-CT complexes.
ε
the standard free energy (
D
G ) were calculated for ATC-CT

6
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
complexes at room temperature. The transition probability of ATC-
CT band is given by the oscillator strength (f) which is a dimen-
sionless quantity [41]. The following formula can be used to find out
the value of oscillator strength (f) from ATC-CT absorption spectra.
ð
f ¼ 4:319 ꢂ 10ꢀ
9
ε
CT
dv
(2)
where !εCTdv is the area under the curve of the molar extinction
coefficient of the absorption band plotted as a function of fre-
quency. For a first calculation, the following equation (3) is used.
f ¼ 4:319 ꢂ 10ꢀ
9
ε
CT
v
½
(3)
where εCT is the molar extinction coefficient of ATC-CT band, and n
½
ꢀ1
is the half-bandwidth in cm (i.e., the bandwidth at half of the
maximum extinction coefficient). The transition dipole moments
(m) of ATC-CT complexes were calculated from eqn. (4) [42,43]:
½
m
¼ 0:0958½ðεCT
v
½
Þ=vmax
ꢃ
(4)
If a particular transition is allowed, the transition dipole
moment ( ) can be determined, i.e., the transition from a bonding
-orbital to an antibonding *-orbital is allowed because the in-
tegral that defines the transition dipole moment is non zero. The
ionization potentials (I ) of ATC-CT complexes were calculated us-
m
p
p
P
ing the empirical equation derived by Aloisi and Pignataro [44]
represented in eqn (5):
ꢀ
ꢁ
ꢀ4
I ðeVÞ ¼ 5:76 þ 1:53 ꢂ 10
v
CT
(5)
P
ꢀ1
where
n
CT is the wavenumber in cm which is inversely propor-
Fig. 7. Infrared spectra of ATC and its charge-transfer complexes.
tional to the maximum wavelength of the CT band formed from the
interaction between ATC and the acceptors. The electron-donating
power of ATC was measured by its ionization potential, which is the
Table 4
Infrared wavenumbersa (cm ) and tentative band assignments for ATC, and their CT-complexes, [(ATC)(DHBQ)
ꢀ1
2 2 2
], [(ATC)(Quiz) ] and [(ATC)(PA) ].
ATC
[(ATC)(DHBQ)
3247 s, br
3066 vw, 2873 vw
3034 vw
2969 w
2930 w
1729 w
1711 s
1649 s
2
]
[(ATC)(Quiz)
3376 s, br
3055 w, 2908 w
3027 w
2961 s
2908 w
1731 w
1725 w
1603 s
2
]
[(ATC)(PA)
3398 s, br
3067 vw, 871 vw
3035 vw
2970 vw
2925 vw
1735 vw
1710 vw
1634 ms
2
]
Assignments
3
3
3
2
2
1
1
1
396 br
061 w, 2875 w
031 w
965 m
933 m
738 m
720 w
655 s
n
n
n
n
n
(NeH);
(CeOH)
(CeH) in pyrrole ring
(CeH) in methyl group
(CeH) in methylene group
n(OeH) in DHBQ, Quiz and PA
n
n
s
(C]O) in COOH
as(C]O) in COOH
n
n
n
(C]O) in asymmetric amide; DHBQ; Quiz
(N]O); PA
(C]C) in aromatic ring
1612 w
1595 s, 1435 s
1558 ms, 1527 m
1506 s
1591 s, 1438 s
1521 w
1510 s
1447 s
1513 vw
1492 w
1599 s, 1440 s
1550 s, 1530 s
1509 s
coupling of
d
(NeH) and
n(CeH) in amide; DHBQ
n(CeC) in ring
1401 s
coupling of
n(C]O) with
n(C]C) in DHBQ
1
365 m
n
(NeO); PA
(CeN) in aromatic
1313 s
1319 s
1259 s
1317 s
n
1
1
1
297 vw,
174 vw, 1074 s
276 s
in-plane bending vibrations of DHBQ
n
(CeO) in DHBQ
(CeF)
1
8
7
6
6
222 s, 1155 s
44 s, 814 m
52 s, 694 s
67 w
1227 s, 1152 s
842 m, 810 m
757 s, 691 s
671 vw
1219 w, 1070 w
865 w, 794 s
697 s
661 w
633 vw
1229 m, 1156 s
840 s, 808 w
748 s, 691 s
673 vw
n
d
d
(CeH) para-substituted out-of-plane in aromatics
(CeH) mono-substituted out-of-plane in aromatics
NeH wagging band in secondary amide
(CeH) out-of-plane in pyrrole ring
Out-of-plane deformation vibration of n(C]O)
20 w
615 vw
612 vw
d
604 s
a
s, strong; m, medium; w, weak; br, broad; v, very;
n, stretching;
n
s
, symmetrical stretching;
n
as, asymmetrical stretching; , bending vibrations
d

S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
7
Fig. 8. 1H NMR spectrum of [(ATC)(DHBQ)
] (500 MHz, DMSO‑d ).
2 6
Fig. 9. 1H NMR spectrum of [(ATC)(Quiz)
] (500 MHz, DMSO‑d ).
2 6

8
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
Fig. 10. 1H NMR spectrum of [(ATC)(PA)
] (500 MHz, DMSO‑d ).
2 6
ꢁ
The standard free energy of complexation (DG ) for each com-
plex was calculated from the formation constants (KCT) using
equation (8):
energy required to remove an electron from the highest occupied
molecular orbital. The resonance energy (R ) was derived by using
equation (6) developed by Briegleb and Czekalla theoretically [45]:
N
ꢀ
ꢁ.
Gꢁ ¼ ꢀ 2:303RT log K
D
(8)
4
CT
ε
¼
7:7 ꢂ 10
½ðhvCT =R Þ ꢀ 3:5ꢃ
(6)
CT
N
ꢁ
DG is the standard free energy change of ATC-CT complexes
where
kJ/mol), R is the gas constant (8.314 J/molK), T is the absolute
where εCT is the molar extinction coefficient of ATC-CT complex at
the maximum wavelength of ATC-CT absorption, CT is the fre-
is the resonance energy of
(
n
temperature in K (298 K) and KCT is the formation constant of ATC-
CT complex (L/mol) at room temperature.
ꢀ1
quency of ATC-CT peak in cm , and R
N
the complex in the ground state, which gives the information about
the stability constant of the CT complex (a ground-state property).
All calculated spectroscopic and physical values for ATC-CT
complexes using these equations (1)e(8) were given in Table 3.
The higher value of oscillator strength (f) for [(ATC)(PA) ] complex
2
indicated the strong interaction between the drug, ATC and the
acceptor, PA which is a strong electron acceptor having three nitro
The energy values (ECT) of the n-
ATC donor and the three acceptors were calculated using equation
7) derived by Briegleb [46]:
p* and pep* interactions between
(
2
groups. [(ATC)(DHBQ) ] complex showed the highest values of
ECT ¼ hvCT ¼ 1243:667=
l
(7)
ionization potential (I
P
), resonance energy (R
N
) and energy of that
CT
ꢁ
CT complex. The standard free energy change
[(ATC)(DHBQ) ], [(ATC)(Quiz) and [(ATC)(PA)
(
DG ) for
where
lCT is the maximum wavelength of ATC-CT absorption band.
2
2
]
2
]
complexes
Table 5
1
H NMR data of ATC and their charge-transfer complexes.
Complexes
ATC
1H at C(1)
2H, eCH
2
at C(2)
1H, eCH at C(3)
2H, eCH
2
at C(4)
1H, eCH at C(5)
2
2H, eCH at C(6)
e
3.40; 3.41
3.15e3.21
3.37e3.41
3.24e3.31
3.82
3.15
3.41
3.79
1.71; 1.73
1.35e1.43
1.60e1.66
1.59e1.68
3.63
3.15
3.41
3.79
2.27; 2.30
2.10e2.23
2.18e2.25
2.09e2.18
[
[
[
(ATC)(DHBQ)
(ATC)(Quiz)
(ATC)(PA)
2
]
]
9.60
9.84
9.83
2
]
2
]
Complexes
2H, eCH
2
at C(7)
4H in 4-FPh
5H in Ph (2:2:1)
5H in amidePh (2:2:1)
1H, eCH(CH
3
)
2
3 2
6H, eCH(CH )
ATC
4.42; 4.44
3.82e4.19
3.85e4.26
3.99e4.39
7.25; 7.43
7.51; 7.47; 7.42
7.53; 7.42; 7.09
7.49; 7.38; 7.24
7.56; 7.35; 7.23
7.51; 7.29; 7.09
7.28; 6.84; 6.76
7.52; 7.08; 7.00
7.53; 7.08; 7.00
3.49
3.15
3.41
3.55
1.43; 1.45
1.14e1.42
1.38e1.44
1.38e1.46
[
[
[
(ATC)(DHBQ)
(ATC)(Quiz)
(ATC)(PA)
2
6.84e7.29; 7.00e7.51
7.08e7.23; 7.20e7.39
7.08e7.31; 7.19e7.38
2
]
2
]

S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
9
2 2 2
Fig. 11. Mass spectra of (A) [(ATC)(DHBQ) ], (B) [(ATC)(Quiz) ] and (C) [(ATC)(PA) ] charge-transfer complexes.
ꢀ
1
were ꢀ38.47; (ꢀ40.42, ꢀ38.93); ꢀ36.35 kJ/mol, respectively which
showed that the interaction between ATC and the three acceptors
was spontaneous.
considered for hydroxyl group in free DHBQ at 3300-3200 cm .
ꢀ
1
The free DHBQ band for
n(C]O) at 1625 cm were shifted slightly
ꢀ1
to higher wave number, 1649 cm while the combined
n
(C]O)
suggested the
presence of DHBQ in anionic form which was observed in the
ꢀ
n(C]C) stretching vibration at 1380 cm
1
and
ꢀ
1
3.4. Interpretation of IR spectra
complex at 1401 cmꢀ1
free ligand was shifted to 1276 cm
bending vibration of DHBQ at 1310, 1200 and 1110 cm and out-
n(CeO) stretching vibration at 1270 cm in
ꢀ1
in the complex. In-plane
ꢀ
1
The FTIR spectra for donor, ATC and CT complexes
ꢀ1
[
2 2 2
(ATC)(DHBQ) ], [(ATC)(Quiz) ] and [(ATC)(PA) ] were recorded in
of-plane deformation vibration of n(C]O) at 691 cm were shif-
ꢀ
1
ꢀ
1
the frequency range 4000e400 cm (Fig. 7) and the corresponding
band assignments were given in Table 4. These most important
bands were assigned to the products, CT complexes which con-
tained the bands of both donor, ATC and the corresponding ac-
ceptors, DHBQ, Quiz and PA. The obtained FTIR spectra of all CT
complexes were compared with the two reactants, donor and ac-
ceptors. It strongly confirmed the formation of the CT-complexes.
However, the percentage transmittance values of ATC and the
various acceptors used in the obtained CT complexes showed some
appreciable changes in band intensities. There were also some
small shifts in IR frequency wavenumber values. This shift proved
that there should be a change in electronic structures of both ATC
and the acceptors in their CT complexes with respect to the free
reagents.
ted in the complex at 1297, 1174, 1074 and 604 cm . All these shifts
corresponded to the mechanism that outer-sphere ATC and DHBQ
CT-complex was initially formed which was rearranged as
hydrogen-bonded charge transfer complex.
The
lower wavenumber as 1259 cm which showed CT interaction in
methanol as polar solvent. For [(ATC)(PA) ] complex, (NO ) vi-
bration was occurring at 1612 cm which was appeared in free PA
2
n(CeN) vibration for the complex [(ATC)(Quiz) ] appeared at
ꢀ1
2
n
2
ꢀ
1
ꢀ1
as 1860 cm and proved the interaction between ATC and PA. A
proton was accepted from Quiz or PA to ATC, so that there was a
deformation in the electronic structure of ATC. As a result, there
was the appearance of new bands on complex formation. A new
ꢀ
1
broad band in [(ATC)(Quiz) ] or [(ATC)(PA) ] complex at 3376 cm
2 2
ꢀ
1
or 3398 cm confirmed the hydrogen bonding in these complexes
which was absent in Quiz or PA. It corresponded to the stretching
ꢀ
1
In [(ATC)(DHBQ)
showed the presence of
2
] complex, the broad peak at 3247 cm
(OeH) stretching vibrations which was
n

10
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
Fig. 12. TG and DTG curves of (A) [(ATC)(DHBQ)
2
], (B) [(ATC)(Quiz)
2
] and (C) [(ATC)(PA)
2
] charge-transfer complexes.
1
vibration of a proton which was connected to the donation site of
oxygen ion in the carboxylate anion of ATC [47]. This was confirmed
by the decrease in the intensity or broadening in the stretching of
OeH group of Quiz or PA due to intermolecular hydrogen bond
formation inside that complex. There was a reflection in the shift of
3.5. Interpretation of H NMR spectra
The 500 MHz 1H NMR spectra of free donor, ATC and their
complexes of the investigated drug with DHBQ, Quiz and PA ac-
ceptors were taken in dmso-d as solvent at room temperature and
6
the IR bands, i.e., donor to acceptor charge transfer of
p
ep
inter-
shown in Figs. 8e10. Chemical shifts in ppm of proton NMR for all
action, HOMO to LUMO transition [48]. The presence of different
bands in ATC-CT complexes powerfully supported the charge-
transfer interaction process between the donor, ATC and three
acceptors.
complexes were given in Table 5. Carboxylate anion gets the label
C(1) and the carbon attached to pyrrole ring gets the label C(7). The
1
H
NMR spectra of ATC-CT complexes exposed several in-
terpretations. ATC-CT complexes showed the peaks which were
Table 6
Thermogravimetric data for the formed ATC-CT complexes.
Complexes
Stages
TG range (⁰C)
DTG max (⁰C)
TG % mass loss
Found
Lost species
Calculated
[
[
[
(ATC)(DHBQ)
2
]
I
II
20e300
300e550
295
403
18.64
27.18
54.18
30.35
08.50
61.15
01.62
06.16
14.42
22.20
18.90
27.06
54.04
30.23
09.07
60.70
01.53
05.98
14.81
22.32
4C
ATC
Residual carbon
8C
þ 8CO
ATC
Residual carbon
NO
C H OH(NO )
5 2 2 2
ATC
Residual carbon
2
H
2
þ 4CO
2
Residue
I
II
Residue
I
II
III
(ATC)(Quiz)
2
]
20e430
430e550
286, 426
451
2
H
2
2
(ATC)(PA)
2
]
20e150
150e300
300e550
125
256
360, 396
2
Residue

S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
11
2
Scheme 1. Scheme for the obtained [(ATC)(DHBQ) ] CT complex.
also present in ATC and three acceptors signifying the formation of
ATC-CT complexes. The proton signals of the donor, ATC were up-
field shifted to lower ppm values indicating a charge migration
from ATC towards the acceptors, DHBQ, Quiz and PA. The obtained
results from elemental analysis, infrared spectra and photometric
titrations clearly gave the same result with H NMR spectra of ATC-
CT complexes which interpreted the interaction between ATC and
all acceptors studied.
complexes, this shift appeared. This confirms that the formation
of charge transfer complexes between ATC and the acceptors,
DHBQ, Quiz and PA. The two hydroxyl groups present at C and C
3 5
carbons in ATC were also observed in their complexes within the
range of 1e3.0 ppm as a singlet.
1
In the case of [(ATC)(DHBQ)
signal of two symmetrical protons at C
2
] complex, the singlet resonance
and C carbons in DHBQ
3
6
(5.26 ppm) [49] was lower shifted to 4.93 ppm and 4.26 ppm as
singlet due to the CT interaction between ATC and DHBQ. The signal
due to hydroxyl proton (11.60 ppm) of DHBQ was disappeared in
ATC-DHBQ CT complex confirming the formation of hydrogen-
bonded ATC-DHBQ CT complex. A new signal at 9.60 ppm was
identified which was lower shifted from 10.00 ppm and assigned to
ATC formed hydrogen-bonded type charge transfer complexes
[
12] with three acceptors, DHBQ, Quiz and PA. A hydrogen atom was
transferred from the acceptors to the carboxylate anion of ATC. As a
result, a carboxylic acid group in ATC was formed which was
1
somewhat upfield shifted. In H NMR spectra of all ATC-CT
2
Scheme 2. Scheme for the obtained [(ATC)(Quiz) ] CT complex.

12
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
3.7. Thermal analysis measurements
Thermogravimetric (TG) and differential thermogravimetric
(
DTG) analysis were done in order to confirm the decompositions
and the structures of the obtained solid CT-complexes. In Fig. 12,
the thermograms of [(ATC)(DHBQ) ], [(ATC)(Quiz) and
(ATC)(PA) ] were shown. Table 6 gave the thermogravimetric data
2
2
]
[
2
of ATC-CT complexes which supported the calculated formulas and
structures of the obtained CT-complexes. The degradations steps
and their related temperatures differed from one complex to
another, depending on the type of components as well as on the
stoichiometries in each case. Evidently, these two factors have
definite effects on the type of bonding, relative complex stabilities
and geometries.
2
The thermal decomposition of [(ATC)(DHBQ) ] complex showed
two main degradation steps within the temperature range
ꢁ
ꢁ
2
2
0e550 C. The first decomposition within the temperature range
ꢁ
0e300 C at 295 C which was corresponded to the loss of 2C
molecules with an estimated mass loss of 18.64% in
agreement of with calculated value 18.90%. The second decompo-
2 2
H
and 2CO
2
ꢁ
ꢁ
sition step within the temperature range 300e550 C at 403
C
(
obs. ¼ 27.18%, calc. ¼ 27.06%) which are reasonably accounted by
the removal of ATC moiety with contentious decomposition of the
donor molecule ended with a final residual carbons. The overall loss
of mass from the TG curve was 45.82% of this complex.
There were two successive decomposition steps ((286, 426) and
ꢁ ꢁ
2
51 C) for [(ATC)(Quiz) ] in the temperature range 20e550 C. The
4
2
Scheme 3. Scheme for the obtained [(ATC)(PA) ] CT complex.
first decomposition step (obs. ¼ 30.35%, calc. ¼ 30.23%) within the
ꢁ
temperature range 20e430 C may be specified to the liberation of
Quiz moieties. The second decomposition step (obs. ¼ 8.50%,
carboxylic acid in [(ATC)(DHBQ)
were also found in all protons of ATC in this complex.
In [(ATC)(Quiz) ] complex, the shift in H from Quiz acceptor to
oxygen ion of the carboxylate group in ATC was found due to the
interaction of ATC with Quiz. As a result, a new characteristic hy-
2
] complex. The same lower shifts
ꢁ
calc. ¼ 9.07%) within the temperature range 430e550 C provided
for the removal of ATC moieties. The decomposition of ATC and
Quiz molecules ended with a final residue of carbon atoms. The
2
overall loss of mass from the TG curve was 38.85% of [(ATC)(Quiz)
complex.
2
]
droxyl group peak of carboxylic acid in [(ATC)(Quiz)
.84 ppm was observed. Thus, the formation of hydrogen-bonded
ATC-Quiz CT complex was confirmed. Four protons present at C
, C and C carbons in Quiz were obtained at 7.35 ppm as
2
] complex at
2
In [(ATC)(PA) ] CT-complex, the first step in the temperature
9
ꢁ
ꢁ
range 20e150 C was the mass loss at 125 C (obs. ¼ 1.62%,
calc. ¼ 1.53%) which corresponded to the loss of one NO group
from PA acceptor. The loss of C OH(NO
3
,
2
C
4
6
7
5
H
2
2
)
2
(obs. ¼ 06.16%,
multiplet. The broad singlet peak was observed at 4.71 ppm due to
the hydroxyl groups present in Quiz which weren’t involved in CT
interaction.
ꢁ
calc. ¼ 05.98%) was observed at 256 C in the temperature range of
ꢁ
continuous heating from 150 to 300 C. The donor, ATC was
ꢁ
ꢁ
decomposed on further steps at 360 C and 396 C within the
In [(ATC)(PA)
symmetrical protons at C
2
] CT-complex, the singlet resonance signal of two
and C carbons in PA (8.57 ppm) was
ꢁ
temperature range 300e550 C (obs. ¼ 14.42%, calc. ¼ 14.81%). The
3
5
final decomposition of this complex was the residual carbon atoms.
somewhat higher shifted to 8.61 ppm due to the CT interaction
between ATC and PA. The signal due to hydroxyl proton (11.96 ppm)
of PA was disappeared in ATC-PA CT complex confirming the for-
mation of hydrogen-bonded ATC-PA CT complex. Thus, deproto-
nation from PA to ATC was occurred. The shift in H of carboxylic
acid from 10.00 ppm in ATC to 9.83 ppm in this complex was
observed. Thus, high field shift was obtained. The OH proton in PA
was transferred to the O-ion of the carboxylate anion of the donor,
ATC. The upfield (lower shift) of most signals in this complex were
observed due to the interaction between ATC and PA.
The overall loss of mass from the TG curve was 22.20% of
[
(ATC)(PA)
.8. Structural interpretation
The structures of ATC-CT complexes with DHBQ, Quiz and PA
2
] complex.
3
acceptors were confirmed by the techniques such as elemental
1
analysis, spectrophotometric titration, IR, H and mass spectra and
thermal analysis data. The proposed structures of ATC-CT com-
plexes were shown in Schemes 1e3. In ATC, there is the possibility
of the presence of more than one electron-donating sites (carbox-
ylate anion, two OH groups of the side chain and the nitrogen atom
of pyrole ring). Among these reaction centres, carboxylate anion
was hydrogen bonded with the three acceptors due to the high
electron density of oxygen atom which were positioned on the two
oxygen atoms of the carboxylate anion [47,50].
3.6. Mass spectra of ATC-CT complexes
2 2
The mass spectrum of [(ATC)(DHBQ) ], [(ATC)(Quiz) ] and
2
[(ATC)(PA) ] complexes showed the ionization peaks which corre-
sponded to ATC and the acceptors, DHBQ, Quiz and PA (Fig. 11).
There was no formation of new chemical species, i.e., new peak for
the joint complex. This one confirmed that the interaction between
ATC and the three acceptors was due to charge transfer interaction
rather than a chemical reaction.
3.9. Morphology characterization
Scanning electron microscopy (SEM) which tells the micro-
structure, the particle size, the porous structures of the surfaces and

S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
13
2 2 2
Fig. 13. SEM images and EDX spectrum of (A) [(ATC)(DHBQ) ], (B) [(ATC)(Quiz) ] and (C) [(ATC)(PA) ] CT complexes.
the chemical composition was used to find out the morphology of
ATC-CT complexes. Similarly, energy-dispersive X-ray diffraction
distributed homogeneously in these complexes. The particles of
[(ATC)(DHBQ) ] complex appeared as agglomerates which were
displayed in a large surface area. [(ATC)(Quiz) ] and [(ATC)(PA)
complexes showed flake-shaped particles. The elemental compo-
sitions for ATC-CT complexes were clearly represented and the
obtained results agreed with the proposed structures.
2
(
EDX) was used to get the information about the chemical com-
positions of ATC-CT complexes. Both SEM and EDX data for
(ATC)(DHBQ) ], [(ATC)(Quiz) ] and [(ATC)(PA) ] CT complexes
2
2
]
[
2
2
2
were shown in Fig. 13. Depending on the acceptors, the particle
sizes were varied with respect to each other, where acceptors were
Table 7
The inhibition zone diameter values (mm) for ATC and its CT complexes.
Sample
inhibition zone diameter (mm/mg sample)
þ
a
Eggerthella lenta, (G )
Enterobacter
aerogenes, (G )
Alcaligenes
faecalis, (G )
Klebsiella
pneumoniae, (G )
Acinetobacter
e
e
e
e
baumannii, (G )
Control: DMSO
0
0
0
0
0
Ciprofloxacin (an antibacterial agent)
ATC
22
8
25
7
20
6
20
8
21
6
[
[
[
(ATC)(DHBQ)
(ATC)(Quiz)
(ATC)(PA)
2
]
11
12
10
10
13
11
10
9
12
11
10
11
12
10
13
2
]
2
]
a
G: Gram reaction.

14
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
2 2 2
Fig. 14. Plate diagrams for the antibacterial activity of ATC-CT complexes (c-ciprofloxacin; M-DMSO; 1-ATC; 2-[(ATC)(DHBQ) ]; 3-[(ATC)(Quiz) ]; 4-[(ATC)(PA) ]).
3
.10. Biological activity
was used as the positive control. The screening data were listed in
Table 7. Plate diagrams and statistical representations of ATC-CT
complexes were shown in Figs. 14 and 15. The results indicated
that ATC-CT complexes exhibited moderate inhibitory results
against all of the Gram-positive and Gram-negative bacterial spe-
cies. It was found that the biological activities of ATC-CT complexes
were more than that of free pure ATC drug. But, the biological ac-
tivity of ATC drug and its CT complexes are lower than ciprofloxacin
standard.
The antibacterial activity of ATC and its three CTcomplexes were
screened in vitro against Gram-positive bacteria, Eggerthella lenta
and four Gram-negative bacteria, Enterobacter aerogenes, Alcali-
genes faecalis, Klebsiella pneumoniae and Acinetobacter baumannii.
The ATC-CT complexes to be tested were dissolved in DMSO to
obtain 100
determined by measuring the inhibition zone diameter values
mm) of the complexes against the microorganisms. Ciprofloxacin
mg/mL stock solutions. The antibacterial activity was
(

S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
15
Fig. 15. Statistical representation for the antibacterial activity of ATC-CT complexes.
4
. Conclusion
New York, 1971.
[
6] H.H. Eldaroti, S.A. Gadir, M.S. Refat, A.M.A. Adam, Charge-transfer interaction
of drug quinidine with quinol, picric acid and DDQ: spectroscopic character-
ization and biological activity studies towards understanding the
drugereceptor mechanism, J. Pharm. Anal. 4 (2014) 81e95, https://doi.org/
ATC is used to reduce cholesterol in the blood. ATC formed CT
complexes with three acceptors, DHBQ, Quiz and PA which were
clearly explained in this paper. The obtained ATC-CT complexes
were characterized using various spectroscopic techniques
including electronic, IR, H NMR and mass spectroscopy and scan-
ning electron microscopy, EDX and thermogravimetric (TG) ana-
10.1016/j.jpha.2013.06.003.
[
7] H.H. Eldaroti, S.A. Gadir, M.S. Refat, A.M.A. Adam, Preparation, spectroscopic
and thermal characterization of new charge-transfer complexes of ethidium
bromide with p-acceptors. In vitro biological activity studies, Spectrochim.
Acta, Part A 109 (2013) 259e271, https://doi.org/10.1016/j.saa.2013.03.032.
8] I.M. Khan, A. Ahmad, S. Kumar, Synthesis, spectroscopic characterization and
1
[
lyses. It was found that the formula, [(ATC)(DHBQ)
2 2
], [(ATC)(Quiz) ]
structural investigations of
a new charge transfer complex of 2,6-
and [(ATC)(PA) ] were proved by the analysis where the reaction
2
diaminopyridine with 3,5-dinitrobenzoic acid: DNA binding and antimicro-
bial studies, J. Mol. Struct. 1035 (2013) 38e45, https://doi.org/10.1016/
j.molstruc.2012.09.016.
stoichiometry was 1:2 in all cases. Physical parameters, formation
constant (KCT), molar extinction coefficient (εCT) and other spec-
troscopic data have been studied. These complexes were stable and
screened for their antibacterial activities using the disc diffusion
method. ATC-CT complexes showed higher antibacterial activities
when compared with the free donor, ATC. Thus, the obtained
investigation might raise the possibility of a potentially important
antibacterial effect of complexes of ATC.
[
9] I.M. Khan, A. Ahmad, M.F. Ullah, Synthesis, spectroscopic investigations,
antimicrobial and DNA binding studies of a new charge transfer complex of o-
phenylenediamine with 3,5-dinitrosalicylic acid, Spectrochim. Acta, Part A
102 (2013) 82e87, https://doi.org/10.1016/j.saa.2012.10.027.
[
[
[
10] A.M.A. Adam, Synthesis, spectroscopic, thermal and antimicrobial in-
vestigations of charge-transfer complexes formed from the drug procaine
hydrochloride with quinol, picric acid and TCNQ, J. Mol. Struct. 1030 (2012)
26e39, https://doi.org/10.1016/j.molstruc.2012.07.017.
11] M.S. Refat, Spectroscopic and thermal investigations of charge-transfer com-
plexes formed between sulfadoxine drug and different types of acceptors,
J.
Mol.
Struct.
985
(2011)
380e390,
https://doi.org/10.1016/
CRediT authorship contribution statement
j.molstruc.2010.11.026.
12] A.S. Gaballa, A.S. Amin, Preparation, spectroscopic and antibacterial studies on
S. Niranjani: Conceptualization, Methodology, Formal analysis,
Investigation, Resources, Data curation, Writing - original draft,
Writing - review & editing. K. Venkatachalam: Visualization, Su-
pervision, Project administration.
charge transfer complexes of 2-hydroxypyridine with picric acid and 7,7’,8,8’-
tetracyano-p-quinodimethane, Spectrochim. Acta, Part
02e312, https://doi.org/10.1016/j.saa.2015.03.005.
A 145 (2015)
3
[
13] J.M. Malinowski, Atorvastatin: a hydroxymethylglutaryl-coenzyme A reduc-
tase inhibitor, Am. J. Health Syst. Pharm. 55 (1998) 2253e2303, https://
doi.org/10.1093/ajhp/55.21.2253.
[14] A.P. Lea, D. McTavish, Atorvastatin. A review of its pharmacology and thera-
peutic potential in the management of hyperlipidaemias, Drugs 53 (1997)
Acknowledgement
828e847, https://doi.org/10.2165/00003495-199753050-00011.
The author, Dr. K. Venkatachalam gratefully acknowledges the
financial assistance from Department of Science and Technology,
India for DST-SERB Project (Ref.no. EEQ/2016/000559, Dt.: February
[15] Y.S. Chatzizisis, K.C. Koskinas, G. Misirli, C. Vaklavas, A. Hatzitolios,
G.D. Giannoglou, Risk Factors and drug interactions predisposing to statin-
induced myopathy: implications for risk assessment, prevention and treat-
ment, Drug Saf. 33 (2010) 171e187, https://doi.org/10.2165/11319380-
000000000-00000.
0
6, 2017).
[
16] D.W. Schneck, R.H. Knopp, C.M. Ballantyne, R. McPherson, R.R. Chitra,
S.G. Simonson, Comparative effects of rosuvastatin and atorvastatin across
their dose ranges in patients with hypercholesterolemia and without active
arterial disease, Am. J. Cardiol. 91 (2003) 33e41, https://doi.org/10.1016/
s0002-9149(02)02994-6.
References
[
[
[
1] R.S. Mulliken, Structures of complexes formed by halogen molecules with
aromatic and with oxygenated solvents, J. Am. Chem. Soc. 72 (1950) 600e608,
https://doi.org/10.1021/ja01157a151.
2] R.S. Mulliken, Molecular compounds and their spectra. III. The interaction of
electron donors and acceptors, J. Phys. Chem. 56 (1952) 801e822, https://
doi.org/10.1021/j150499a001.
[17] M. Masadeh, N. Mhaidat, K. Alzoubi, S. Al-azzam, Z. Alnasser, Antibacterial
activity of statins: a comparative study of atorvastatin, simvastatin, and
rosuvastatin, Ann. Clin. Microbiol. Antimicrob. 11 (2012) 13, https://doi.org/
10.1186/1476-0711-11-13.
[18] The United States Pharmacopoeia 37, NF 32, United States Pharmacopoeia
Convention, Mack, Easton, PA, 2011, 1949.
[19] Indian Pharmacopoeia, government of India, Ministry of Health and Family
Welfare, the Indian Pharm. Comm. (2007) 749e1574. New Delhi 2 and 3.
[20] T.P. de Paula, P.C. Santos, R.D.D.N. Arifa, A.T. Vieira, L.D.M. Baltazar, T.V. Avila,
3] R.S. Mulliken, W.B. Pearson, Molecular Complexes, Wiley Publishers, New
York, 1969.
[
[
4] R. Foster, Charge-Transfer Complexes, Academic Press, London, 1969.
5] M.A. Slifkin, Charge-Transfer Interaction of Biomolecules, Academic Press,

16
S. Niranjani, K. Venkatachalam / Journal of Molecular Structure 1219 (2020) 128564
C.T. Fagundes, Z.M. Garcia, R.L. Lima, M.M. Teixeira, D.G. Souza, Treatment
Synthesis and electrochemical studies of charge-transfer complexes of thia-
zolidine-2,4-dione with and acceptors, Spectrochim. Acta, Part A 75
(2010) 983e991, https://doi.org/10.1016/j.saa.2009.12.019.
with atorvastatin provides additional benefits to imipenem in a model of
Gram-negative pneumonia induced by Klebsiella pneumoniae in mice, Anti-
microb. Agents Chemother. 62 (2018) 1e14, https://doi.org/10.1128/
AAC.00764-17.
s
p
[35] N. Singh, I.M. Khan, A. Ahmad, Spectrophotometric and spectroscopic studies
of charge transfer complexes of p-toluidine as an electron donor with picric
acid as an electron acceptor in different solvents, Spectrochim. Acta, Part A 75
(2010) 1347e1353, https://doi.org/10.1016/j.saa.2009.12.085.
[
[
[
[
21] T.A. Wani, N.Y. Khalil, H.M. Abdel Rahman, I.A. Darwish, Novel microwell-
based spectrophotometric assay for determination of atorvastatin calcium in
its pharmaceutical formulations, Chem. Cent. J. 5 (2011) 57, https://doi.org/
[36] A.A. El-Habeeb, F.A. Al-Saif, M.S. Refat, Charge-transfer interactions of meto-
1
0.1186/1752-153X-5-57.
clopramide nausea drug against six kind of p-acceptors: spectral and thermal
discussions, Spectrochim. Acta, Part A 123 (2014) 455e466, https://doi.org/
10.1016/j.saa.2013.12.093.
22] G. Ergin, S. Caglar, A. Onal, S. Erturk Toker, Spectrophotometric de-
terminations of 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors
in pharmaceutical preparations, Turk. J. Chem. 37 (2013) 171e181, https://
doi.org/10.3906/kim-1106-58.
23] A.A. Ramadan, H. Mandil, J. Sabouni, Determination of atorvastatin calcium in
pure and its pharmaceutical formulations using iodine in acetonitrile by uv-
visible spectrophotometric method, Int. J. Pharm. Pharmaceut. Sci. 7 (2015)
[37] N. Sultana, M. Saeed Arayne, S.N. Ali, Synthesis and spectrophotometric
determination ibuprofen charge transfer complexes with p-chloranil, 7,7,8,8-
tetracyanoquinodimethane, bromothymol blue, methyl orange and picric
acid, J. Bioanal. Biomed. 5 (2013) 122e129, https://doi.org/10.4172/1948-
593X.1000092.
[38] National Committee for Clinical Laboratory Standards, Methods for Antimi-
crobial Susceptibility Testing of Anaerobic Bacteria: Approved Standard M11-
A3, NCCLS, Wayne, PA, USA, 1993.
4
27e433.
24] K.M. Al-Ahmary, M.M. Habeeb, E.A. Al-Solmy, Spectrophotometric study on
the charge-transfer reaction between 4-aminopyridine with 2,5-dihydroxy-p-
benzoquinone in methanol and the binary mixture 50% acetonitrile þ 50% 1,4-
dioxane (v/v), Phys. Chem. Liq. 51 (2013) 621e634, https://doi.org/10.1080/
[39] H.A. Benesi, J.H. Hildebrand,
A spectrophotometric investigation of the
interaction of iodine with aromatic hydrocarbons, J. Am. Chem. Soc. 71 (1949)
2703e2707, https://doi.org/10.1021/ja01176a030.
0
0319104.2013.764500.
[
[
[
[
25] K.M. Al-Ahmary, Synthesis and spectroscopic studies of charge transfer
complex between dihydroxy-p-benzoquinone and 4-dimethylaminopyridine
in different solvents, Phys. Chem. Liq. 52 (2014) 234e250, https://doi.org/
[40] R. Abu-Eittah, F. Al-Sugeir, Charge-transfer interaction of bithienyls and some
thiophene derivatives with electron acceptors, Can. J. Chem. 54 (1976)
3705e3712, https://doi.org/10.1139/v76-532.
[41] A.B.P. Lever, Inorganic Electronic Spectroscopy, second ed., Elsevier, Amster-
dam, Netherlands, 1985.
[42] E.M. Voigt, C. Reid, Ionization potentials of substituted benzenes and their
charge-transfer spectra with tetracyanoethylene, J. Am. Chem. Soc. 86 (1964)
3930e3934, https://doi.org/10.1021/ja01073a005.
[43] R. Rathore, S.V. Lindeman, J.K. Kochi, Charge-transfer probes for molecular
recognition via steric hindrance in donor-acceptor pairs, J. Am. Chem. Soc. 119
(1997) 9393e9404, https://doi.org/10.1021/ja9720319.
10.1080/00319104.2013.832248.
26] R.M. Alghanmi, Solvation and temperature effect on the charge-transfer
complex between 2-amino-4-picoline with 2,5-dihydroxy-p-benzoquinone,
Phys.
Chem.
Liq.
51
(2013)
635e650,
https://doi.org/10.1080/
00319104.2013.764501.
27] A.A. Gouda, M. Kasssem, Novel spectrophotometric methods for determina-
tion of desloratidine in pharmaceutical formulations based on charge transfer
reaction, Arabian J. Chem. 9 (2012) S1712eS1720, https://doi.org/10.1016/
j.arabjc.2012.04.050.
28] M. Keskar, R. Jugade, Spectrophotometric determination of norfloxacin in
pharmaceutical formulations based on charge transfer reaction with quina-
[44] G.G. Aloisi, S. Pignataro, Molecular complexes of substituted thiophens with
s
and acceptors. Charge transfer spectra and ionization potentials of the do-
p
nors, J. Chem. Soc., Faraday Trans. 1 (69) (1973) 534e539, https://doi.org/
10.1039/F19736900534.
lizarin, Anal. Chem. Lett.
2297928.2015.1129287.
5 (2015) 319e328, https://doi.org/10.1080/
2
[45] G. Briegleb, J. Czekalla, Intensity of electron transition bands in electron
donator-acceptor complexes, Z. Phys. Chem. 24 (1960) 37e54, https://doi.org/
10.1524/zpch.1960.24.1_2.037.
[29] A.S. Amin, Spectrophotometric determination of piroxicam and tenoxicam in
pharmaceutical formulations using alizarin, J. Pharmaceut. Biomed. Anal. 29
(
2002) 729e736, https://doi.org/10.1016/S0731-7085(02)00035-3.
[46] G. Briegleb, Electron affinities of organic molecules, Angew. Chem. 76 (1964)
326e341, https://doi.org/10.1002/anie.196406171.
[
30] M.S. Refat, S.A. El-Korashy, I.M. El-Deen, S.M. El-Sayed, Charge-transfer
complexes of sulfamethoxazole drug with different classes of acceptors,
[47] M.E. Mohamed, E.Y.Z. Frag, A.A. Hathoot, E.A. Shalaby, Spectrophotometric
determination of fenoprofen calcium drug in pure and pharmaceutical
preparations, spectroscopic characterization of the charge transfer solid
complexes, Spectrochim. Acta, Part A 189 (2018) 357e365, https://doi.org/
10.1016/j.saa.2017.08.027.
[48] R.D. Kross, V.A. Fassel, Regularities in the infrared spectra of picric acid mo-
lecular complexes1, J. Am. Chem. Soc. 79 (1957) 38e41, https://doi.org/
10.1021/ja01558a008.
[49] R.M. Alghanmi, Synthesis, characterization, and biological evaluation of a new
hydrogen-bonded charge-transfer complex of 2-amino-4-methoxy-6-
methylpyrimidine, Hindawi J. Chem. (2019) 1e14, https://doi.org/10.1155/
2019/1743147. Article ID 1743147.
J.
Mol.
Struct.
980
(2010)
124e136,
https://doi.org/10.1016/
j.molstruc.2010.07.004.
[
31] M.S. Refat, A. Elfalaky, E. Elesh, Spectroscopic and physical measurements on
charge-transfer complexes: interactions between norfloxacin and ciproflox-
acin drugs with picric acid and 3,5-dinitrobenzoic acid acceptors, J. Mol.
Struct. 990 (2011) 217e226, https://doi.org/10.1016/j.molstruc.2011.01.049.
32] A.A. El-Habeeb, F.A. Al-Saif, M.S. Refat, Charge transfer complex of some
nervous and brain drugs e Part 1: synthesis, spectroscopic, analytical and
biological studies on the reaction between haloperidol antipsychotic drugs
[
with
p-acceptors, J. Mol. Struct. 1034 (2013) 1e18, https://doi.org/10.1016/
j.molstruc.2012.08.045.
[
33] M.S. Refat, L.A. El-Zayata, O.Z. Yesilel, Spectroscopic characterization of
charge-transfer complexes of morpholine with chloranilic and picric acids in
[50] R.M. Alghanmi, S.M. Soliman, M.T. Basha, M.M. Habeeb, Electronic spectral
studies and DFT computational analysis of hydrogen bonded charge transfer
complexes between chloranilic acid and 2,5-dihydroxy-p-benzoquinone with
2-amino-4-methylbenzothiazole in methanol, J. Mol. Liq. 256 (2018)
433e444, https://doi.org/10.1016/j.molliq.2018.02.056.
organic
media:
crystal
structure
of
bis(morpholinium
2,4,6-
trinitrocyclohexanolate), Spectrochim. Acta, Part
https://doi.org/10.1016/j.saa.2009.11.049.
A
75 (2010) 745e752,
[34] P. Singh, P. Kumar, A. Katyal, R. Kalra, S.K. Dass, S. Prakash, R. Chandra,