Spectral and theoretical studies on the molecular complexes of azacyclonol with new π-acceptors, alkoxysubstituted 1,4-benzoquinones

Article abstract of DOI:10.1016/j.molstruc.2012.09.033

The molecular complexes of a series of new electron acceptors, 1,4-benzoquinones possessing variety of alkoxy substituents, with azacyclonol have been investigated using various spectral techniques such as UV-Vis, ¹H NMR, FT-IR, fluorescence and LC-MS. The stoichiometry of the complexes was determined by Job's continuous variation method and was found to be 1:1, in all the cases. The results of equilibrium, and kinetic studies were well supported by ab initio DFT calculations. Correlation of formation constants of the complexes with Taft's polar and steric constants indicated that both these factors play significant role in governing the reactivity. Also, the results indicated that an increase in electron releasing property of the alkoxy group makes these acceptors increasingly weaker while an increase in steric property of the substituent decreased the formation constant.

Full text of DOI:10.1016/j.molstruc.2012.09.033

Journal of Molecular Structure 1035 (2013) 157–164
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Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Spectral and theoretical studies on the molecular complexes of azacyclonol
with new
p-acceptors, alkoxysubstituted 1,4-benzoquinones
⇑
C. Balraj, A. Satheshkumar, K. Ganesh, Kuppanagounder P. Elango
Department of Chemistry, Gandhigram Rural Institute (Deemed University), Gandhigram 624 302, India
h i g h l i g h t s
"
"
"
Different new alkoxy substituted 1,4-benoquinones were employed as electron acceptors.
The molecular complexes were characterized using various spectral techniques.
Taft correlation indicated that both polar and steric effects of substituents govern reactivity.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 July 2012
Received in revised form 12 September
2012
Accepted 12 September 2012
Available online 21 September 2012
The molecular complexes of a series of new electron acceptors, 1,4-benzoquinones possessing variety of
alkoxy substituents, with azacyclonol have been investigated using various spectral techniques such as
UV–Vis, 1H NMR, FT-IR, fluorescence and LC–MS. The stoichiometry of the complexes was determined
by Job’s continuous variation method and was found to be 1:1, in all the cases. The results of equilibrium,
and kinetic studies were well supported by ab initio DFT calculations. Correlation of formation constants
of the complexes with Taft’s polar and steric constants indicated that both these factors play significant
role in governing the reactivity. Also, the results indicated that an increase in electron releasing property
of the alkoxy group makes these acceptors increasingly weaker while an increase in steric property of the
substituent decreased the formation constant.
Keywords:
Charge transfer
Benzoquinones
Azacyclonol
Ó 2012 Elsevier B.V. All rights reserved.
Taft correlation
Fluorescence
1. Introduction
are required. To achieve this, many attempts have been made to
synthesize quinone systems with substituted phenyl rings directly
Quinones are one of the most significant classes of organic com-
pounds, as their applications ranges into various fields like biology
[1,2], pharmaceutical [3], water management [4] and agriculture
[5], etc. In many biological electron transfer processes quinones
play an integral role [6,7]. It is established that the biological activ-
ity of these compounds is due to the redox chemistry of the
quinone system [1,8]. The quinone ring accepts one or two elec-
trons to form corresponding radical-anion (QÅꢀ) and hydroquinone
dianion (Q2ꢀ). These species interact with crucial cellular mole-
cules such as DNA, proteins and oxygen tuning their biological
activity by accepting the electrons in the correct site [1,8,9].
The ability of the quinones to accept one or two electrons de-
pends directly on their chemical structures [10]. It is known that
the redox chemistry of these substances can be modified either
by directly adding a substituent to the quinone ring or by attaching
a substituted phenyl ring to the quinone system [11]. However, for
some applications, fine tuning of the electron accepting properties
attached to it and to study their redox chemistry. The biological
activities of such systems have also been documented [12].
Over the years, a great deal of research has been carried out on
the charge transfer complexes of quinones because of their wide
applications ranging from chemistry, material science, medicine
to biology [13–15]. In biological systems quinones exit in the form
of substituted p-benzoquinones such as plastoquinones [16],
Vitamin K [17], ubiquinones [2,18]. Also, these naturally occurring
quinones possess variable number of methoxy groups. Though
good amount of work, on the study of charge transfer (CT)
complexes of number of quinones with variety of donors, has been
carried out [19–22], reports related to quinones with systematic
variation of substituents is rare in literature. Azacyclonol (chemi-
cally known as diphenyl(piperidin-4-yl)methanol) is an anti
histamine drug that inhibits the action of histamine blocking it
from attaching to the histamine receptors, or it may inhibit the
enzymatic activity of histidine decarboxylase, catalyzing the trans-
formation of histidine into histamine and are commonly used for
the relief of allergies caused by intolerance of proteins [23,24].
⇑
Corresponding author. Tel.: +91 451 2452371; fax: +91 451 2454466.
E-mail address: drkpelango@rediffmail.com (K.P. Elango).
0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2012.09.033

158
C. Balraj et al. / Journal of Molecular Structure 1035 (2013) 157–164
The main objective, therefore, of the present endeavor is to study
the charge transfer complexes of azacyclonol drug with different
1,4-benzoquinones possessing variety of alkoxy groups. Though
these chosen quinones are known to synthetic organic chemists
as intermediates, to the best of our knowledge this is the first sys-
tematic investigation on the charge transfer complexes of these
quinones as electron acceptors. In the frame of Density Functional
Theory (DFT) we have also performed the complete optimization of
the geometry for these quinones. An attempt has also been made to
correlate Taft’s polar (rꢁ) and steric (Es) substituent constants [25]
with the formation constants of the CT complex formed between
the quinones and the donor.
temperature. Then the reaction mixture was added to 200 ml of
water and stirred for 1 h at RT. The crude material formed was fil-
tered through a filter paper, the residue was purified using column
chromatography (Silica gel 60–120 by using 5–10% ethyl acetate
petether mixture) and MQ was obtained as the major product.
EQ was prepared using sodium ethoxide under identical conditions
adopted for the preparation of MQ. For the preparation of IPQ and
BQ, the corresponding alcohols along with 1 eqv. of Na2CO3 were
used as the starting materials. The reaction mixture was stirred
for 12 h at 90 °C, cooled to room temperature and 200 ml of water
was added and stirred for 1 h at RT. The crude material was filtered
through the filter paper, the solid residue was purified using col-
umn chromatography (see Scheme 1).
2. Experimental
2.2.1. 3,5,6-Trichloro-2-methoxycyclohexa-2,5-diene-1,4-dione (MQ)
1H NMR (DMSO-D6, 300 MHz), d(ppm) 4.19 (s, 3H); FT-IR (KBr,
cmꢀ1): 1680 (C@O), 1668 (C@O), 1567 (C@C); UV–Vis in 1,2-
2.1. Materials and measurements
dichloroethane (kmax): 295 nm (p– e 4.24; Anal. Calcd. for
pꢁ), log
The electron acceptors of alkoxy substituted 1,4-benzoquinones
derivatives (MQ, EQ, IPQ, BQ) were prepared by reported method
[26]. Spectroscopy grade solvents (Merck, India) were used as re-
ceived. The electron donor drug azacyclonol was obtained as gift
sample from a locally available pharmaceutical company and was
used as received. The purity of the donor was ascertained using
its m.p. (found 161 °C; Lit.160–163 °C). The structures of donor
and the acceptors are shown below.
C7H3Cl3O3: C, 34.82; H, 1.25; N, 0.0; found: C, 36.17; H, 1.74; N,
0.0; m.p. 172 °C.
2.2.2. 3,5,6-Trichloro-2-ethoxycyclohexa-2,5-diene-1,4-dione (EQ)
1H NMR (DMSO-D6, 300 MHz), d(ppm) 1.39 (t, J = 6 Hz, 3H),
4.45–4.53 (m, 2H); FT-IR (KBr, cmꢀ1): 1676, 1608 (C@O); UV–Vis
in 1,2-dichloroethane (kmax): 293 nm (p– e 4.12; Anal.
pꢁ), log
Calcd. for C8H5Cl3O3: C, 37.61; H, 1.97; N, 0.0; found: C, 36.87; H,
1.84; N, 0.0; m.p. 112 °C.
HN
2.2.3. 3,5,6-Trichloro-2-isopropoxycyclohexa-2,5-diene-1,4-dione
(IPQ)
OH
1H NMR (DMSO-D6, 300 MHz), d(ppm) 1.34 (d, J = 6 Hz, 6H),
4.98–5.10 (m, 1H); FT-IR (cmꢀ1): 1670, 1648 (C@O), UV–Vis in
1,2-Dichloroethane (kmax): 293 nm (p– e 4.33; Anal. Calcd.
pꢁ), log
for C9H7Cl3O3: C, 40.11; H, 2.62; N, 0.0; found: C, 40.81; H, 2.56;
N, 0.0; m.p. 74 °C.
Azacyclonol
2.2.4. 2-Butoxy-3,5,6-trichlorocyclohexa-2,5-diene-1,4-dione (BQ)
1H NMR (DMSO-D6, 300 MHz), d(ppm) 0.9 (t, J = 6 Hz, 3H), 1.35–
1.48 (m, 2H), 1.63–1.74 (m, 2H), 4.45 (t, J = 6 Hz, 2H); FT-IR (cmꢀ1):
1672, 1649 (C@O), UV–Vis in 1,2-dichloroethane (kmax): 293 nm
1O
O
Cl
Cl
6
(p– e 4.16; Anal. Calcd. for C10H9Cl3O3: C, 42.36; H, 3.20;
pꢁ), log
R
N, 0.0; found: C, 42.14; H, 3.18; N, 0.0; m.p. 88 °C.
5
3
4
Cl
120
2
O
Acceptors
AZA-MQ
AZA-EQ
MQ (R= methyl); EQ (R= ethyl); IPQ (R= iso propyl); BQ (R= n-butyl)
AZA-IPQ
100
AZA-BQ
Solutions for the spectroscopic measurements were prepared
by dissolving accurately weighed amounts of donor (D) and accep-
tor (A) in appropriate volume of solvent immediately before run-
ning the spectra. The electronic absorption spectra were recorded
on a JASCO (V630, Japan) double beam spectrophotometer using
1 cm matched quartz cells. The temperature of the cell holder
was controlled with a water flow ( 0.1 °C). FT-IR spectra were re-
corded in a JASCO (FT-IR 460 Plus, Japan) spectrometer. 1H NMR
spectra were recorded at Madurai Kamaraj University, Madurai
in a Brucker NMR spectrometer (300 MHz, Switzerland).
80
60
40
20
2.2. Preparation and characterization of substituted quinones
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Molefraction of Donor
An excess amount of sodium methoxide was added into a stir-
red solution of chlroanil in methanol at RT under N2 atm. The reac-
tion mixture was stirred for 12 h at 70 °C and was cooled to room
Fig. 1. Job’s continuous variation plots for AZA–MQ, AZA–EQ, AZA–IPQ, and AZA–
BQ in 1,2-dichloroethane at 298 K.

C. Balraj et al. / Journal of Molecular Structure 1035 (2013) 157–164
159
2.3. Kinetic procedure
0.9
The kinetics of the interaction of azacyclonol with the acceptors
(MQ, EQ, IPQ and BQ) was followed at three different temperatures
in 1,2-dichloroethane under pseudo-first-order conditions, keeping
[D] ꢂ [A]. The increase in absorbance of the corresponding new
peaks around at 564 nm for the all the systems with elapse of time
was recorded. The pseudo-first-order rate constants (k1) were cal-
0.6
0.3
0.0
culated from the gradients of log (A –At) against time plots, where
1
A
1
and At represent the absorbance at infinity and time t, respec-
D
tively. The second order rate constants were calculated by dividing
k1 by [D] [27,28].
Product
every 3 min
C
A
3. Results and discussion
3.1. Stoichiometry of the interaction
300
400
500
600
700
800
The stochiometry of the CT complexes formed between AZA and
the acceptors was determined by Job’s continuous variation meth-
od using emission data [29]. In all the cases, symmetrical curves
with maximum at 0.5 mol fraction indicated the formation of a
1:1 (D:A) CT complex (Fig. 1). The photometric titration measure-
ments were also performed for the determination of the stoichiom-
etry in these interactions. For that, the concentration of the donor
in the reaction mixtures was kept constant while the concentra-
tions of the acceptors were varied over a wide range. The results
of the photometric curves (Fig. 2) also indicated that the stoichi-
ometry of the interaction, in all the cases, was 1:1 (D:A) [30,31].
Wavelength (nm)
Fig. 3. Electronic spectra of AZA with EQ in 1,2-dichloroethane at 298 K.
1.2
1.5
1.0
product
0.5
0.8
3.2. Electronic spectra and kinetics of the interaction
0.0
The electronic spectra of the acceptors (MQ, EQ, IPQ and BQ)
exhibited a peak around 295 nm which is characteristic peak of
800
400
600
D
A
0.4
0.0
p–
pꢁ transition in quinone systems. The kinetics of the interaction
C
every 3 min
of the donor (AZA) and the acceptors, under pseudo-first-order
condition, i.e. [D]/[A] > 100 as a function of time were recorded.
On mixing 1,2-dichloroethane solutions of AZA and EQ, there was
an instantaneous formation of deep blue color with a low energy
absorption maximum at 564 nm and also other absorption maxi-
mum appeared at 345 nm (Fig. 3). The intensity of these bands in-
creased with elapse of time while that of the band at 295 nm
decreased. Two clear isosbestic points were appeared at 308 and
276 nm. The interaction of MQ, IPQ and BQ (Figs. 4–6) exhibited
400
600
800
Wavelength (nm)
Fig. 4. Electronic spectra of AZA with MQ in 1,2-dichloroethane at 298 K.
1.6
AZA-MQ
AZA-EQ
AZA-IPQ
AZA-BQ
1.2
0.9
1.2
0.8
0.4
0.6
Product
D
A
0.3
every 3 min
C
0.0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
300
400
500
600
700
800
Ratio [D]/[A]
Wavelength (nm)
Fig. 2. Photometric titration plot for AZA–MQ, AZA–EQ, AZA–IPQ, AZA–BQ in 1,2-
dichloroethane at 298 K.
Fig. 5. Electronic spectra of AZA with IPQ in 1,2-dichloroethane at 298 K.

160
C. Balraj et al. / Journal of Molecular Structure 1035 (2013) 157–164
0.9
0.6
0.3
0.0
The pseudo-first-order rate constants (k1), for the formation of
the products, as a function of [D] and [A] are collected in Table 1.
It is evident from the results that the rate of the interaction is inde-
pendent of initial concentration of A indicating first order depen-
dence on [A]. The rate constant values increased with an increase
in [D] and in all the cases, a plot of log k1 versus log [D] is linear
(r > 0.95) with a slope close to one, indicating first order depen-
dence of rate on [D]. This was further supported by the constancy
in k2 values [27,28]. These observations indicated that the interac-
tion of AZA with these acceptors proceed via the following plausi-
ble mechanism (Scheme 2).
Product
D
C
every 3 min
The above mechanism leads to the following rate law
A
Rate ¼ k½CT complexꢃ
or
Rate ¼ k1½Dꢃ½Aꢃ
300
400
500
600
700
800
where k1 = Kk.
Wavelength (nm)
The rate constants as a function of temperature along with ther-
modynamic parameters are collected in Table 2. It is evident from
the results that the enthalpy of activation, which is a measure of
strength of the interaction between the donor and the acceptor
in a molecular complex [32], follows the order AZA–MQ > AZA–
EQ > AZA–BQ > AZA–IPQ.
Fig. 6. Electronic spectra of AZA with BQ in 1,2-dichloroethane at 298 K.
similar electronic spectral behavior. These observed new low en-
ergy bands cannot be considered as the characteristic absorption
bands of an outer complex because: the formation of outer com-
plex may be an instantaneous process and the concentration of
which may be very low to detect and also this may immediately
be converted to the final product. This is well supported by the fact
that the final product extracted, in all these cases, exhibited super
imposable electronic spectrum.
An attempt was also made to characterize the charge transfer
complexes formed in these reactions. For that the absorbance of
the new low energy bands were measured using constant acceptor
concentration and varying concentrations of the donor, but always
[D] ꢂ [A] [29,33]. The formation constants (K) and molar extinc-
tion coefficients (e) of the CT complexes were determined spectro-
photometrically using the Scott equation [34]. The values of K and
e
determined are given in Table 3. The observed high values of K
O
Cl
Cl
O
O
Cl
Cl
Cl
Cl
3
2
O
3
2
O
O
O
3
O
1
Cl
Cl
Cl
Cl
5,
2
O
O
Cl
Cl
O
Cl
Cl
O
Cl
Cl
O
O
2
4
Scheme 1. Preparation method for MQ, EQ, IPQ, BQ.
Table 1
Effect of concentration of the donor and the acceptors on the rate of the interaction at 298 K.
[D] (10ꢀ4 M)
[A] (10ꢀ5 M)
k1 (10ꢀ4 sꢀ1
)
k2 (s1 molꢀ1 dm3)
AZA–MQ
AZA–EQ
AZA–BQ
AZA–IPQ
AZA–MQ
AZA–EQ
AZA–BQ
AZA–IPQ
4
6
8
10
10
10
10
10
5
5
5
5
5
4
3
2
14.6
21.2
28.7
35.8
35.9
34.8
35.2
35.7
13.3
18.9
25.7
31.9
31.1
31.4
31.8
32.2
11.8
16.8
22.4
28.1
28.2
28.4
28.7
28.2
9.6
3.6
3.5
3.6
3.6
3.3
3.2
3.2
3.2
2.9
2.8
2.8
2.8
2.4
2.4
2.5
2.5
14.6
19.7
24.7
24.2
24.9
24.1
24.6

C. Balraj et al. / Journal of Molecular Structure 1035 (2013) 157–164
161
O
O
HN
O
N
Cl
O
O
Cl
Cl
K, Fast
OH
OH
Cl
Cl
O
k, slow
-HCl
+
;
Cl
NH
Cl
Cl
O
OH
O
O
Product
Donor
CT complex
Acceptor
Scheme 2. Interaction of AZA with EQ.
Table 2
Kinetic and thermodynamic parameters for the interaction of the donor with the
acceptors in 1,2-dichloroethane.
System
k (nm)
k1 (10ꢀ4 sꢀ1
)
D
H#
ꢀ
D
S#
D
G#
D
a
298
305
313 K
AZA–MQ
AZA–EQ
AZA–BQ
AZA–IPQ
564
564
570
570
35.8
31.9
28.1
24.7
39.6
37.2
33.2
30.2
42.5
39.7
37.2
34.6
6
289
282
272
264
92
93
93
94
b
9
12
14
c
d
D
H# kJ molꢀ1
;
D
S# J Kꢀ1 molꢀ1
;
D
G# kJ molꢀ1
.
e
f
suggested that the formed complexes are of a strong type [35] and
the linearity of the Scott plots (r > 0.97) further supports this result.
3.3. Characterization of the interaction product
In all the cases, the final product was obtained by stirring equi-
molar 1,2-dichloroethane solutions of the donor and the acceptor
at room temperature for 24 h. The solid obtained, after evaporation
of the solvent, was purified using column chromatography (Silica
gel 60–120 by using 5–10% ethyl acetate/petether mixture). The
products were characterized using analytical (CHN) and spectral
(1H NMR, FT-IR, LC–MS) techniques. The results obtained are:
280
320
360
400
Wavelength (nm)
Fig. 7. Fluorescence spectra for AZA–EQ system in 1,2-dichloroethane at fixed
concentrations of [D] = {8 ꢄ 10ꢀ4
M (curve d)} and variable concentration of
[A](ꢄ10ꢀ5) = {1 (curve a), 2 (curve b), 3 (curve c), 4 (curve d), 5 (curve e), 6 (curve
f)}M at 298 K.
3.3.1. AZA–MQ product: [2,5-dichloro-3-(4-(hydroxydiphenylmethyl)
piperidin-1-yl)-6-methoxycyclohexa-2,5-diene-1,4-dione]
3.3.3. AZA–IPQ product [2,5-dichloro-3-(4-(hydroxydiphenylmethyl)
piperidin-1-yl)-6-isopropoxycyclohexa-2,5-diene-1,4-dione]
1H NMR (DMSO-D6, 300 MHz), d(ppm) 1.28 (s, 6H), 1.37 (s,
2H),1.57–1.68 (m, 2H), 2.90 (t, J = 12 Hz, 1H), 3.20–3.29 (m, 2H),
3.77 (d, J = 12 Hz, 2H), 4.89–4.99 (m,1H), 5.41 (s, 1H), 7.16 (t,
J = 9 Hz, 2H), 7.30 (t, J = 6 Hz, 4H), 7.56 (d, J = 9 Hz, 4H); FT-IR
(KBr, cmꢀ1): 3380 (OAH), 1678, 1642 (C@O); LCMS: Calcd. for C27-
H27Cl2NO4: 500.4; found: 499.6.
1H NMR (DMSO-D6, 300 MHz), d(ppm) 1.24 (d, J = 3 Hz, 2H),
1.39 (d, J = 6 Hz, 2H), 2.90 (t, J = 9 Hz, 1H), 3.28 (t, J = 12 Hz, 2H),
3.76 (d, J = 12 Hz, 2H), 4.08 (s, 3H), 5.41 (s, 1H), 7.15 (t, J = 6 Hz,
2H), 7.30 (t, J = 9 Hz, 4H), 7.56 (d, J = 9 Hz, 4H); FT-IR (KBr, cmꢀ1):
3377 (OAH), 1677 (C@O), 1644 (C@O); LCMS: Calcd. for C25H23Cl2-
NO4: 472.36; found: 474.1. Anal. Calcd. for C25H23Cl2NO4: C, 63.57;
H, 4.91; N, 2.97: found: C, 63.38; H, 4.87; N, 2.89.
3.3.2. AZA–EQ product [2,5-dichloro-3-ethoxy-6-(4-(hydroxydi-
phenylmethyl)piperidin-1-yl)cyclohexa-2,5-diene-1,4-dione]
1H NMR (DMSO-D6, 300 MHZ), d(ppm) 1.30 (d, J = 9 Hz, 2H),
1.36 (d, J = 12 Hz, 3H), 1.64 (t, J = 9 Hz, 2H), 2.90 (t, J = 12 Hz, 1H),
3.19–3.28 (m, 2H), 3.76 (d, J = 12 Hz, 2H), 4.37–4.44 (m, 2H), 5.41
(s, 1H), 7.15 (t, J = 6 Hz, 2H), 7.30 (t, J = 9 Hz, 4H), 7.55 (d,
J = 6 Hz, 4H); FT-IR (KBr, cmꢀ1): 3425 (OAH), 1670, 1644 (C@O);
LCMS: Calcd. for C26H25Cl2NO4: 485.12; found: 486.2.
3.3.4. AZA–BQ product [2-butoxy-3,6-dichloro-5-(4-
(hydroxydiphenylmethyl)piperidin-1-yl)cyclohexa-2,5-diene-1,4-
dione]
1H NMR (DMSO-D6, 300 MHz), d(ppm) 1.33–1.39 (m, 4H), 1.43
(t, J = 6 Hz, 3H), 1.65 (t, J = 9 Hz, 4H), 2.80–2.90 (m,1H), 3.28 (t,
J = 12 Hz, 2H), 3.76 (d, J = 12 Hz, 2H), 4.39 (t, J = 6 Hz, 2H), 5.41 (s,
1H), 7.15 (t, J = 6 Hz, 2H), 7.30 (t, J = 9 Hz, 4H), 7.56 (d, J = 9 Hz,
Table 3
Formation constant and extinction coefficient of all the systems carried out in 1,2-dichloroethane at 298 K.
Systems
Formation constant K
Extinction coefficient log e
Association constant Kf
(dm3 molꢀ1) (absorption method)
(dm3 molꢀ1 cmꢀ1) (absorption method)
(mol lꢀ1) (emission method)
AZA–MQ
AZA–EQ
AZA–BQ
AZA–IPQ
1602
1362
1023
684
4.64
4.59
4.56
4.57
9.17 ꢄ 104
8.94 ꢄ 104
8.43 ꢄ 104
8.06 ꢄ 104

162
C. Balraj et al. / Journal of Molecular Structure 1035 (2013) 157–164
fluorescence of AZA through CT complexation. The experimental
AZA-MQ
AZA-EQ
AZA-IPQ
AZA-BQ
results indicated that the quenching efficiency increased with an
increase in the concentration of the acceptors at a fixed concentra-
tion of the drug (Fig. 7 and Fig. 9S-11S). For all the systems, the CT
interaction between the quencher and the fluorophore has been
observed at 292 nm. The fraction of the acceptor bound to the drug
(h) was determined using the following equation [36].
3.0
2.5
2.0
1.5
1.0
0.5
h ¼ ðF0 ꢀ FÞ=F0
ð1Þ
where F and F0 denote the fluorescence intensities of the drug in a
solution with a given concentration of the acceptor and without the
acceptor, respectively. From the values of h the association constant,
Kf, for the drug interaction with the acceptors was computed using
the method described in the literature [37]. It has been shown that
for equivalent and independent binding sites:
1=ð1 ꢀ hÞKf ¼ ½AT ꢃ=h ꢀ n½DT ꢃ
ð2Þ
1
2
3
4
5
6
7
where n is the number of binding sites, [AT] is the total acceptor
concentration and [DT] is the total drug concentration. The plot of
1/(1 ꢀ h) versus [AT]/h was found to be linear (r > 0.97), for all the
systems, indicating that under the experimental conditions all the
binding sites are equivalent and independent. The values of Kf ob-
tained from the plots for AZA–MQ, AZA–EQ, AZA–BQ and AZA–IPQ
systems were found to be 9.17 ꢄ 104, 8.94 ꢄ 104, 8.43 ꢄ 104 and
8.06 ꢄ 104 mol lꢀ1, respectively. Parallel to the observation made
under the electronic spectral studies, as enumerated earlier, the
strength of the complex formation between the partners is in the
order AZA–MQ > AZA–EQ > AZA–BQ > AZA–IPQ. The standard Gibbs
-5
[A] x 10
Fig. 8. Stern–Volmer plots for the fluorescence quenching of AZA with the
acceptors in 1,2-dichloroethane at 298 K.
4H); FT-IR (KBr, cmꢀ1): 3425 (OAH), 1670, 1644 (C@O); LCMS:
Calcd. for C28H29Cl2NO4: 514.44; found: 515.3.
3.4. Fluorescence study
energy change
DG° was calculated from the Kf using the relation
One of the most important binding forces that produce favor-
able binding of a drug to its target is the CT interaction. The nature
and magnitude of drug interaction significantly influences the bio-
logical activity of the drug. In the present study an attempt was
made to investigate the mode of CT interaction between AZA with
these acceptors using fluorescence spectroscopy. The fluorescence
spectra were recorded in 1,2-dichloroethane at room temperature
in the range of 230–730 nm upon excitation at 254 nm for all the
systems. It is observed that these acceptors quenched the
D
G° = ꢀ2.303 RT log10 Kf. The
D
G° values for AZA–MQ, AZA–EQ,
AZA–IPQ and AZA–BQ systems were found to be ꢀ28.31, ꢀ28.25,
ꢀ28.10 and ꢀ27.99 kJ, respectively, which indicated that the inter-
actions between the drug and the acceptors are spontaneous [38].
Fluorescence quenching can occur by different mechanisms viz.
static or dynamic or both. Stern–Volmer equation (Eq. (3)) is useful
in understanding the mechanism of fluorescence quenching.
F0=F ¼ 1 þ KSV½Qꢃ
ð3Þ
MQ
LUMO (-4.4017 eV)
AZA
HOMO (-5.1871 eV)
BQ
LUMO (-4.3326 eV)
EQ
IPQ
LUMO (-4.3370 eV)
LUMO (-4.3522 eV)
Fig. 9. The optimized structure for AZA with HOMO and acceptors with LUMO.

C. Balraj et al. / Journal of Molecular Structure 1035 (2013) 157–164
163
where F0 is emission intensity in the absence of quencher (Q), F is
3.6. Correlation analysis
emission intensity at quencher concentration [Q] and KSV is the
Stern–Volmer constant. In the present study, the linear Stern–
Volmer relationship observed suggested that either static or
dynamic quenching is dominant in all the systems (Fig. 8) [39,40].
The fluorimetric results indicated that the CT interaction between
AZA and these acceptors is spontaneous and an increase in the
strength of such interaction decreases the fluorescence intensity
of AZA.
A preliminary attempt has been made to correlate the results
(i.e. formation constants) with Taft’s polar and steric constants
[25]. The results of the correlation analysis are shown below:
K ¼ 4830rꢁ þ 1675
(r = 0.96; n = 4)
ð4Þ
3.5. Theoretical calculations
K ¼ ꢀ1671Es þ 1556
(r = 0.97; n = 4).
ð5Þ
To understand the foregoing experimental observations on the
CT complex formed between AZA and the acceptors, we have per-
formed the optimization of AZA, MQ, EQ, IPQ and BQ using Density
Functional Theory with the Backle3LYP hybrid functional, by using
a basis set of 6-31G. Computations have been performed using the
Gaussian 03 Revision D.01 program package [41]. The optimized
geometry of the donor along with HOMO and the acceptors along
with LUMO are depicted in Fig. 9.
As spelt in the introduction section, quinone moiety accepts one
electron or two electrons to form the corresponding radical-anion
(BQÅꢀ) and hydroquinone radical dianion (BQ2ꢀ). The electron
accepting capacity and several physicochemical/biological proper-
ties of a given quinone depends largely on the substituent present
in it.
The good correlations obtained, between the formation con-
stants of the CT complexes and Taft’s constants, indicated that both
polar and steric effects of the substituents play significant role in
governing the reactivity of the quinones. The positive correlation
observed between K and rꢁ (Eq. (4)) indicated that with an increase
in electron releasing power of the alkoxy substituent, makes the
quinone increasingly a weaker acceptor. While the negative corre-
lation found between K and Es (Eq. (5)) suggested that an increase
in steric nature of the substituent would makes the approach of the
quinone towards the donor (to form the CT complex) relatively
more difficult and consequently decreased the formation constant
of the CT complex. Hence, isopropoxy substituted quinone is the
weakest among the chosen acceptors as i-Pr group is the strongest
electron releasing and also possesses the highest steric effect
among these substituents.
O-
O-
O
The above observations indicated that the strength of the accep-
tor decrease in the order of the structures of the quinones:
.
+e-
+e-
O
O
O
O
O
BQ
O-
O
O
Cl
Cl
O
Cl
Cl
BQ.-
BQ2-
O
Cl
Cl
O
Cl
Cl
>
>
>
Cl
Cl
Cl
Cl
O
O
The optimized geometry of the acceptors indicated that the
LUMO resides on the carbonyl group of the quinones and in the do-
nor the HOMO resides on the NH moiety of the molecule (Fig. 9).
The energies of the frontier orbitals of the donor and the acceptors
along with the energy corresponds to the CT transition,
O
O
BQ
IPQ
EQ
MQ
D
E(=LUMOacceptor ꢀ HOMOAZA) [42–44], for all the systems are
shown in Fig. 10. It is evident from the figure that the
D
E depends
4. Conclusions
on the nature of the substituent present in the quinone.
The charge transfer interaction of 1,4-benzoquinones possess-
ing variety of alkoxy substituents with azacyclonol, for the first
time, has been investigated. Various spectral techniques have been
employed to characterize the final product of these interactions. In
all the cases, the stoichiometry of the CT interaction was found to
be 1:1. The trends in the rate constants and formation constants
showed that the strength of the complex formation is in the order
of AZA–MQ > AZA–EQ > AZA–BQ > AZA–IPQ. The observed equilib-
rium, kinetic and fluorescence study of these acceptors were found
to be well supported by theoretical calculations. Correlation of
formation constants of the CT complexes with Taft’s substitution
constant indicated that both polar and steric effects of the substit-
utents play significant role in governing the reactivity.
-0.155
BQ
IPQ
EQ
-0.160
MQ
LUMO
-0.165
-0.170
-0.175
-0.180
-0.185
Acknowledgements
The authors thank the University Grants Commission, New
Delhi for its financial assistance to carry out this research work.
One of the authors (C.B.) is thankful to the UGC, New Delhi for
the award of UGC-BSR Fellowship in Sciences for Meritorious
Students.
AZA
-0.190
HOMO
-0.195
Fig. 10. Relationship between energies of HOMOAZA and LUMOAcceptor
.

164
C. Balraj et al. / Journal of Molecular Structure 1035 (2013) 157–164
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