Spectroscopic studies on the interaction of cilostazole with iodine and 2,3-dichloro-5,6-dicyanobenzoquinone

Article abstract of DOI:10.1016/j.saa.2010.10.023

The electron accepting properties of the 2,3-dichloro-5,6- dicyanobenzoquinone and iodine and electron donating properties of the drug cilostazole have been studied using the UV-vis, FT-IR, GC-MS and Far-IR techniques. The interaction of cilostazole drug with iodine and 2,3-dichloro-5,6-dicyanobenzoquinone resulted via the initial formation of charge-transfer complex as an intermediate. The rate of formation of the product have been measured and discussed as a function of solvent and temperature. The complexes have been found by Job's method of continuous variation revealed that the stoichiometry of the complexes in both the cases was 1:1. The enthalpies and entropies of formation of the complexes have been obtained by determining their rate constant at three different temperature. The ionization potential of the donor was determined using the charge-transfer absorption bands of the complexes and the same was found comparable with that computed using MOPAC PM3 method.

Full text of DOI:10.1016/j.saa.2010.10.023

Spectrochimica Acta Part A 78 (2011) 375–382
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Spectroscopic studies on the interaction of cilostazole with iodine and
2,3-dichloro-5,6-dicyanobenzoquinone
M. Pandeeswarana, E.H. El-Mossalamyb, K.P. Elangoa,∗
a Department of Chemistry, Gandhigram Rural Institute-Deemed University, Gandhigram, Tamil nadu 624 302, India
b Chemistry Department, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 August 2010
Accepted 14 October 2010
The electron accepting properties of the 2,3-dichloro-5,6-dicyanobenzoquinone and iodine and electron
donating properties of the drug cilostazole have been studied using the UV–vis, FT-IR, GC–MS and Far-IR
techniques. The interaction of cilostazole drug with iodine and 2,3-dichloro-5,6-dicyanobenzoquinone
resulted via the initial formation of charge-transfer complex as an intermediate. The rate of formation of
the product have been measured and discussed as a function of solvent and temperature. The complexes
have been found by Job’s method of continuous variation revealed that the stoichiometry of the complexes
in both the cases was 1:1. The enthalpies and entropies of formation of the complexes have been obtained
by determining their rate constant at three different temperature. The ionization potential of the donor
was determined using the charge-transfer absorption bands of the complexes and the same was found
comparable with that computed using MOPAC PM3 method.
Keywords:
Spectrokinetics
Charge transfer complex
Cilostazole
DDQ
Iodine
Solvent effects
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
2. Experimental
Over the years scientists have paid much attention on the
spectral studies of charge-transfer (CT) complexes of 2,3-dichloro-
5,6-dicyanobenzoquinone (DDQ) and iodine with variety of donors
[1–12]. Quinones are biologically significant molecules and are
common constituent of many biologically relevant molecules. The
reversible oxidation–reduction reactions of quinones play a key
role in several biological processes [13,14]. Further, quinones are
one of the well-known electron acceptors and the studies of their
CT-interaction stem from their possible role in biological reactions
[15,16]. Likewise iodine is also a biologically significant molecule
[17–19]. Thus, the mechanism of interaction of these biologically
important acceptors with drugs, in general, is a research topic of
significant interest and hence the present study.
Chemically cilostazole is 6-(4-(1-cyclohexyl-1H-tetrazol-5-
yl)butoxy)-3,4-dihydroquinolin-2(1H)-one. It is used to reduce the
symptoms of intermittent claudication and helps people walk a
longer distance. Hence, in continuation of our earlier works on the
spectroscopic studies on the interaction of drug molecules with
these acceptors [20–23], the present work report the CT interac-
tion of cilostazole (CLZ) with DDQ and iodine. The spectral, kinetic
and thermodynamic characteristics of the interaction between the
donor drug and the acceptors were investigated and discussed.
2.1. Material and methodology
The electron acceptors DDQ (minimum assay 98%) and
iodine (minimum assay 99.9%) were obtained from Aldrich,
India. Commercially available spectroscopy grade chloroform,
dichloromethane, 1,2-dichloroethane, tert-butyl alcohol, iso-butyl
alcohol, iso-propyl alcohol, methanol, acetonitrile and DMSO (all
Merck, India, minimum assay > 99%) were used without further
purification. The selection of the solvents is based on the solubility
of the components and so as to have a wide range of relative per-
mittivity of the medium. The electron donor CLZ was obtained as
gift sample from a locally available pharmaceutical company and
was used after confirming the purity. The purity of CLZ was checked
by its m.p. (experimental 157–158 ◦C; theoretical 157–160 ◦C) and
also by comparing its FT-IR spectrum with that of the authentic
sample. The structure of the donor is shown below (Scheme 1).
Solutions for the spectroscopic measurements were prepared
by dissolving accurately weighed amounts of donor (D) and accep-
tor (A) in the appropriate volume of solvent just before running
the spectra. The electronic absorption spectra were recorded on a
Shimadzu (UV 240, Graphicord) double beam spectrophotometer
using 1 cm matched quartz cells. The temperature of the cell holder
was controlled with a water flow ( 0.2 ◦C). The FT-IR spectra were
recorded in a JASCO FT-IR 460 Plus spectrometer. The GC–MS spec-
tra of the reaction product were obtained from Central Salt and
Marine Research Institute, Bhavanagar, India. The molecular orbital
package, MOPAC 2000 version 1.11 (PM3 method) was used for the
∗
Corresponding author. Tel.: +91 451 245 2371; fax: +91 451 245 4466.
E-mail address: drkpelango@rediffmail.com (K.P. Elango).
1386-1425/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2010.10.023

376
M. Pandeeswaran et al. / Spectrochimica Acta Part A 78 (2011) 375–382
CLZ-I2
CLZ-DDQ
1.0
O
N
0.8
HN
O
N
N
N
Scheme 1. Chemical structure of cilostazole.
0.6
0.4
0.2
theoretical calculation of the ionization potential of the donor [24].
The conductance of the solutions was measured on an Elico, India
Conductivity Bridge. For conductance measurements, equimolar
stock solutions of D and A were thermostated to a constant temper-
ature and were mixed in the conductivity cell by varying the mole
fraction of A. The solutions were stirred after each addition and a
constant time interval was permitted to record the conductance.
2.2. Kinetic procedure
0.2
0.4
0.6
0.8
mole fraction of donor
In both CLZ–I2 and CLZ–DDQ cases, the kinetics of the interaction
was followed under pseudo-first-order conditions at three different
temperatures in various solvents, keeping [D] ꢀ [A]. The increase in
absorbance of the product around 350 nm in the case of DDQ and
around 360 nm in the case of iodine (depending on the solvent)
was followed as a function of time. The pseudo-first-order rate
constants (k1) were calculated from the gradients of log(A∞ − At)
Fig. 1. Job’s continuous variation method for CLZ–I2 in methanol and CLZ–DDQ in
acetonitrile at 298 K.
assignments for important peaks are given in Table 1. The results
indicated that the shifts in positions of some of the peaks could
be attributed to the expected symmetry and electronic structure
modification in both donor and acceptor units in the formed prod-
ucts relative to the free molecules. Some of the significant shifts
are: the peak due to ꢀ(N–H) vibrations of the free CLZ occurs
at 3322 cm−1 and in DDQ and iodine complexes they appear at
3316 and 3315 cm−1 respectively. The ꢀ(C O) and ꢀ(C–Cl) stretch-
ing vibrations in the DDQ species appeared at 1679 and 799 cm−1
respectively. In the product these stretching vibrations occurred at
1670 and 707 cm−1, respectively. Such a bathochromic shift could
be indicative of a higher charge density on the carbonyl and C–Cl
groups of the DDQ molecule [20,21]. As there are no significant
changes in the FT-IR spectrum of the CLZ–I2 complex when com-
pared to that of the constituents, we have recorded Far-IR spectrum
to explain the complex formation. The far infrared spectrum of the
against time plots, where A and At represent the absorbance at
∞
infinity and time t respectively. The second order rate constants
were calculated by dividing k1 by [D].
3. Results and discussion
3.1. Stoichiometry of the reaction
The stoichiometry of the CT-complex, in both the cases,
was determined by applying Job’s continuous variation method
[25]. The absorbances of several solutions, so as to have
[D] + [A] = constant, but with varying D:A ratio, are measured at
360 nm in methanol for the iodine complex and at 348 nm in ace-
tonitrile for the DDQ complex. The total concentrations of the donor
and acceptor are 9.02 × 10−4 M and 11.55 × 10−4 M in iodine and
DDQ systems, respectively. The symmetrical curves with maxi-
mum at 0.5 mole fraction indicated the formation of a 1:1 (D:A)
CT-complex (Fig. 1). The photometric titration measurements were
also performed for the determination of the stoichiometry in these
interactions. For that, the concentration of the donor in the reaction
mixtures was kept fixed while those of the acceptors were varied
over a wide range. In the case of iodine complex, the measurements
were carried out at 360 nm in methanol at a donor concentra-
tion of 2.15 × 10−4 M with acceptor concentration in the range of
5.42 × 10−5 to 2.17 × 10−4 M. In the case of DDQ complex, the mea-
surements were carried out at 334 nm in tert-butyl alcohol at a
donor concentration of 3.68 × 10−4 M with acceptor concentration
ranging from 9.25 × 10−5 to 3.70 × 10−4 M. The results of the pho-
tometric curves (Fig. 2) also indicated that the stoichiometry of the
interaction, in both the cases, is 1:1 (D:A) [26].
1.5
1.2
0.9
0.6
CLZ-I2
3.2. Characterization of the reaction products
CLZ-DDQ
0.3
In both CLZ–I2 and CLZ–DDQ cases, the reaction product was
obtained by allowing the reactants to react for 24 h under equal
molar conditions in a given solvent and subjected to MPLC (Medium
Pressure Liquid Chromatographic (Buchi, Switzerland)) separation.
The FT-IR spectra of the products were recorded and the peak
0
1
2
3
Volume of acceptor (ml)
Fig. 2. Photometric titration plots of CLZ with iodine in methanol and CLZ with DDQ
in tert-butyl alcohol at 298 K.

M. Pandeeswaran et al. / Spectrochimica Acta Part A 78 (2011) 375–382
377
Table 1
NC
Infrared wave number (cm−1) and tentative band assignments for the drug (CLZ),
and its complex with iodine and DDQ.
CN
O
O
CLZ
DDQ
CLZ–DDQ
CLZ–I2
Assignments
N
N
3430b
3322m
3183m
3112w
2934m
3433b
3316m
3182m
3105w
2934m
3432b
3315m
3187m
3111w
2928m
ꢀ(–OH) stretching
ꢀ(N–H); stretching
O
N
N
N
Cl
ꢀ(C–H); aliphatic
ꢀ(C≡N)
O
2226m
2203s
m/z = 165
m/z = 394
2228w
ꢀ(C≡N)
1679m
ꢀ(C O)
Scheme 2.
ꢀ(C C)
1669s
1595w
1505s
1478w
1455w
1399m
1269w
1243s
1670s
1591w
1505s
1474w
1455w
1399m
1274w
1243s
1660s
1592w
1505s
1471w
1453w
1396m
–
1243s
1195w
1038m
ꢀ(C O)
ꢀ(C C); aromatic
ı(N–H); bending
ı(CH2); bending
retical analysis showed that the three vibrations should be infrared
active. The 147 cm−1 is assigned to the antisymmetric stretch of the
I–I bond, ꢀas(I–I). The corresponding symmetric stretch, ꢀs(I–I); is
observed at 123 cm−1. The band at 54 cm−1 is assigned to the bend-
ing vibration, ı(I3−) [29,30]. These assignments are exactly similar
to those known for the non-linear I3− ion. The results in the present
study, therefore, indicated the presence of non-linear triiodide ion
in the CLZ–I2 complex. Based on the foregoing results the formula
ı(C–H); bending
ꢀ(C–N); aromatic
ꢀ(C–O); aromatic ether
ꢀ(C–C); aliphatic
ꢀ(C–O); aliphatic ether
ꢀ(C–Cl)
1197w
1038m
1196w
1038m
799s
771w
of the formed complex is [(CLZ) I]+ I3
.
−
707w
673m
–
–
ꢀ(C–Cl)
Product analysis, in the case of CLZ–DDQ system, was carried out
by employing GC–MS technique. The mass spectrum of the product
displayed the following major peaks at the given corresponding m/z
values confirms the structure of the reaction product (Scheme 2).
In the case of CLZ–I2 complex thermal analysis (TG) was also car-
ried out to a certain the proposed formula. The TGA curve (Fig. 4)
indicated that the complex undergoes decomposition in the tem-
perature range 296–694 ◦C with a weight loss of 97.1%. The DSC
curve with a maximum at 365 ◦C indicated that the compound
undergoes decomposition in a single step, exothermically. Parallel
observation was made by us in the study of charge transfer complex
of atenolol with iodine [31].
s, strong; m, medium; w, weak; br, broad; ꢀ, stretching; ı, bending.
ν
ν
3.3. Interaction of cilostazole with iodine
The solutions of cilostazole and iodine in iso-butyl alcohol are
mixed; there was an instantaneous formation of lemon yellow
color with new absorption maxima at 360 nm in the UV–vis spec-
trum (Fig. 5), which is the blue-shifted iodine band. The absorption
band around 460 nm, which is attributed to the ꢁ–ꢂ* electronic
transition in free iodine, is hypsochromically shifted due to its com-
plexation with the donor [32,33]. The observed hypsochromic shift
in the free iodine band could be attributed to the perturbation of
the iodine molecular orbital ꢂ* by a repulsive complex. Accord-
ingly, a more repulsive interaction would lead to a large blue shift
of the iodine band. Therefore, it is reasonable to consider the extent
of the blue shift in iodine band as a measure of the magnitude of
interaction between the donor and iodine molecules. The limiting
value of this shift is at 360 nm, which is the characteristic absorp-
tion of the I3− ion in solution. Parallel observations were made by us
[28,34] and also by several investigators in the study of molecular
complexes of iodine with variety of donor molecules [9,35].
δ
200
150
100
50
Wavenumber (cm-1)
−
Fig. 3. Far-IR spectra of [(CLZI)]+I3 complex.
CLZ–I2 complex is shown in Fig. 3 and the spectral data are collected
in Table 2. The spectrum showed the characteristic bands of I3− ion
at 147, 123 and 54 cm−1. It is well known that I3 ion exists as one
−
unit with either linear or bent structures [27,28]. The group theo-
It is observed that the intensity of the band at 460 nm decreased
−
while the intensity of the characteristic I3 ion band at 360 nm
Table 2
increased with elapse of time. A clear isosbestic point was observed
at 445 nm. Consequently, the change in absorbance of the solution,
at 360 nm, was measured as a function of time. No attempt was
made to measure the decrease in intensity of the peak at 460 nm, as
the peak reach a constant value quickly in majority of the solvents.
And also the increase in intensity of the peak at around 290 nm as
the intensity is very high.
−
Fundamental Far-IR vibrations for I3 ion.
Compound
Assignments
Reference
−
ı(I3 )
ꢀas(I–I)
ꢀs(I–I)
CsI3
149
151
150
144
147
103
132
102
110
123
69
61
76
60
54
[27]
[28]
[30]
[29]
−
[(DAPY)I] I3
−
[Fe(acac)3]2 I+ I3 −
[(HMTACTD)I] I3
The observed time dependent electronic spectrum of the sys-
tem under investigation is due to a transformation of the initially
−
[(CLZ)I]+ I3
Present work

378
M. Pandeeswaran et al. / Spectrochimica Acta Part A 78 (2011) 375–382
−
Fig. 4. TGA and DSC curves for [(CLZ) I]+ I3 complex.
-2.0
-2.5
-3.0
0.2
0.1
0.0
CLZ-I 2
CLZ-DDQ
7
every 5 mins
C
6
5
A
D
-3.5
4
3
5
4
3
2
300
400
500
600
2
1
-4.0
1
Wavelength (nm)
Fig. 5. Electronic absorbance spectrum of CLZ with iodine in iso-butyl alcohol at
0
5
10
15
20
25
30
35
40
45
50
298 K with elapse of time.
Relative permittivity
formedouter complex(CT complex)intoaninner complexfollowed
by a fast reaction of the resulting inner complex with iodine to form
a triiodide ion, as depicted below [9,22,35,36].
Fig. 6. Plot of log k1 vs. relative permittivity of the medium.
The rate constants as a function of temperature and solvent
along with thermodynamic parameters for the CLZ–I2 reaction are
collected in Table 3. The k1 values were found to increase with an
increase in the relative permittivity of the medium. There is a devi-
ation from linearity in the plot of log k1 versus relative permittivity
of the medium (εr) especially at higher εr values (Fig. 6). This may
be due to the fact that with increase in polarity of the medium
CLZ + I2
ꢀ
CLZ–I2
Fast
(1)
(2)
(3)
(outer complex)
CLZ–I2 ꢀ [CLZ–I]+I− Slow
(inner complex)
+
[CLZ–I] I− + I2 ꢀ [CLZI]+I3
Fast
−
Table 3
Kinetic and thermodynamic parameters for the reaction of iodine with cilostazole.
104k1 (s−1
)
ꢄH =/
−ꢄS =/
ꢄG =/
a
Solvent
εr
ꢃ (nm)
298 K
305 K
313 K
Dichloromethane
1,2-Dichloroethane
tert-Butyl alcohol
iso-Butyl alcohol
Methanol
8.93
364
363
361
360
360
1.0
1.2
1.9
2.0
2.2
1.4
1.8
2.4
2.7
2.8
1.5
7.2
7.1
4.1
4.4
21
93
65
35
34
252
8
99
200
201
95.8
95.9
94.5
94.1
94.0
10.36
12.47
16.56
32.70
a
Relative permittivity of the medium from Ref. [50]; ꢄH =/ , kJ mol−1; ꢄS =/ , J K−1 mol−1; ꢄG =/ , kJ mol−1
.

M. Pandeeswaran et al. / Spectrochimica Acta Part A 78 (2011) 375–382
379
100
75
8
7
6
5
50
Δ
CLZ-I2; r = 0.999
CLZ-DDQ; r = 0.984
25
0
100
200
300
-Δ
S# (JK-1 mol-1)
0.00
0.25
0.50
0.75
1.00
Mole fraction of DDQ
Fig. 7. Relation between enthalpy and entropy of activations for the interaction of
CLZ with DDQ and iodine in different solvents.
Fig. 8. Conductivity vs. volume of DDQ plot for CLZ–DDQ system in acetonitrile at
298 K.
solvent–solvent interaction becomes increasingly significant in
addition to solute–solvent interactions. This solvent dependence
of k1 values suggested that there may be some charge separation
in the transformation of CT complex to the final product. Forma-
tion of such a more polar transition state is well supported by the
large negative entropies of activation observed [20]. Further, neg-
ative entropy of activation indicated a greater degree of ordering
in the transition state than in the initial state, due to an increase in
solvation during the activation process. There exists linear corre-
lation between ꢄH =/ and ꢄS =/ values (Fig. 7, r = 0.999) indicating
the operation of a common mechanism in all the solvents studied.
A perusal of data in Table 3 indicated that a solvent change from
dichloromethane to methanol caused ∼2-fold rate acceleration for
the reaction which corresponds to a decrease in ꢄG =/ of 2 kJ mol−1
at 298 K.
[20,40].
D + A ꢁ DA
DA ꢁ [D+A−]
(4)
(5)
The electronic absorption spectra of DDQ in the presence of a
large excess of the donor, i.e. [D] ꢀ [A] was obtained as a function
of time in different solvents. The electronic absorption spectra of
the mixture of methanolic solutions of CLZ and DDQ show a group of
absorption bands at 430, 452, 548 and 590 nm (Fig. 9). These absorp-
tion bands are characteristic for the absorption of the radical anion
DDQ•− [4,17,22,41,42]. The observed enhanced absorption band
intensities, immediately after mixing D and A, supports the fact
that the CT complex formed is of dative-type structure which con-
sequently converts to an ionic intermediate possessing the spectral
characteristics of radical ion [20,21]. Further, the observed gradual
decrease in the intensity of the CT bands in the 400–600 nm spec-
tral regions with elapse of time could be due to the consumption of
the ionic intermediate through an irreversible chemical reaction,
while the continuous increase of the 350 nm band with elapse of
time is indicative of the formation of the final reaction product [39].
A clear isosbestic point at 360 nm was also observed.
3.4. Interaction of cilostazole with DDQ
Conductimetry has often been employed to study the interac-
tions of CT complexes [37–39]. In the present study, a mixture of
acetonitrile solutions of CLZ and DDQ exhibited appreciable con-
ductivities which may be due to the formation of a CT-complex.
The conductivity-mole fraction of DDQ plot, shown in Fig. 8, yielded
maximum at a D:A molar ratio of 1:1. The increase in conductivity
observed upon the CT-complex formation may be due to the fact
that the CT-complex formed between D and A may undergo disso-
ciation into ionic intermediate in solvents of sufficient high relative
permittivity give rise to appreciable conductivity as shown below
The effect of solvent on the reaction between the CLZ and DDQ
was also investigated. It seems reasonable to assume that anion
radicals are formed from electron donor–acceptor interaction via
a CT complex, as depicted in Eqs. (4) and (5). Increase in polarity
of the solvent would tend to stabilize the radical ion state, with
respect to other states of the system, due to ion–solvent interac-
Table 4
Kinetic and thermodynamic parameters for the reaction of DDQ with cilostazole.
104k1 (s−1
)
ꢄH =/
−ꢄS =/
ꢄG =/
a
Solvent
εr
ꢃ (nm)
298 K
305 K
313 K
Chloroform
4.90
351
350
354
334
352
348
354
1.0
1.4
2.5
2.7
3.9
4.2
63
1.9
1.5
2.6
3.2
6.4
6.1
76
4.0
2.0
3.5
5.6
7.7
72
17
15
36
33
52
29
82
263
263
195
202
136
189
95.9
95.9
93.7
93.5
92.3
92.4
86.0
Dichloromethane
1,2-Dichloroethane
tert-Butyl alcohol
iso-Propyl alcohol
Acetonitrile
8.93
10.36
12.47
17.93
37.50
46.68
12
116
DMSO
a
Relative permittivity of the medium from Ref. [50]; ꢄH =/ , kJ mol−1; ꢄS =/ , J K−1 mol−1; ꢄG =/ , kJ mol−1
.

380
M. Pandeeswaran et al. / Spectrochimica Acta Part A 78 (2011) 375–382
8
6
4
2
CLZ-I2; r = 0.999
CLZ-DDQ; r = 0.960
0
2
4
6
103 M [D]
Fig. 9. Electronic absorbance spectrum of CLZ with DDQ in acetonitrile at 298 K as
a function of time.
Fig. 10. Scott linear plots for CLZ–iodine in methanol and CLZ–DDQ in acetonitrile
at 298 K.
Table 5
Spectral properties of the CT complexes formed between the cilostazole with iodine
in methanol and DDQ in acetonitrile solvent at 298 K.
tion. It is possible that the solvent interaction could also influence
the first step (Eq. (4)), perhaps accompanied by an alteration of
charge in the complex. Hereto, increase in polarity of the solvent
could enhance the contribution of dative state and hence lead to a
stronger charge transfer [43]. The results in Table 4 indicated that
the k1 values increased with an increase in the relative permittivity
of the medium. This may be due to the fact that there is some charge
separation in the transformation of CT complex to the final product.
Involvement of such a polar transition state is well supported by the
large negative entropies of activation. The negative entropy of acti-
vation also indicated a greater degree of ordering in the transition
state than in the initial state, due to an increase in solvation during
the activation process [21]. A plot of log k1 versus relative permit-
tivity of the medium (Fig. 6) showed a deviation from linearity at
higher εr values indicating an enhanced solvent–solvent interac-
tion in these media. The correlation between ꢄH =/ and ꢄS =/ values
was found to be linear (Fig. 7, r = 0.984) indicating the operation
of a common mechanism in the solvents investigated. The solvent
change from chloroform to DMSO caused ∼63-fold rate accelera-
tion for the reaction which corresponds to a decrease in ꢄG =/ of
Property
DDQ
Iodine
ꢃmax (nm)
hꢀCT (eV)
589
2.11
5.09
261
360
3.46
8.36
13,092
7445
1014ꢀmax (s−1
)
Formation constant, K (dm3 mol−1
)
Extinction coefficient, ε (dm3 mol−1 cm−1
Oscillator strength, f
)
909
0.0005
0.8253
8.34 (8.55)a
4.32
0.1624
3.52
Dipole moment, ꢅ
Ionization potential (eV)
Dissociation energy (eV)
8.16 (8.55)a
2.01
a
Calculated by MOPAC (PM3) method.
3.5. Characteristics of the CT Complexes
In both CLZ–I2 and CLZ–DDQ systems, as enumerated earlier, ini-
tial reactants were converted in to final products via the formation
of CT complexes. Hence, an attempt was made to characterize the
CT complexes formed in these reactions. For that the absorbance
of the new bands at 589 nm and 360 nm for CLZ–DDQ and CLZ–I2
complexes, respectively, were measured using constant acceptor
concentration (in a given solvent) and varying concentrations of
the donor depending on the solvent, but always [D] ꢀ [A]. The
formation constants (K) and molar extinction coefficients (ε) of
the CT-complexes were determined spectrophotometrically in the
temperature range 298–313 K using the Scott equation [44]. For a
1:1 complex, this equation can be written as:
10 kJ mol−1
.
Based on the foregoing results and discussions the following
plausible mechanism for the interaction DDQ with cilostazole has
been proposed. The final product formed in the interaction has been
confirmed using GC–MS technique. The mass spectrum of the prod-
uct yielded a peak at m/z vales 560 indicated the formation of the
suggested product (Scheme 3).
The above mechanism leads to the following rate law.
[D]
ε
1
Kε
[A][D]
=
+
(6)
d
d[Product]
= k[Complex]
dt
where [A] and [D] are the initial molar concentrations of the elec-
tron acceptor and the electron donor, respectively. is the optical
path length of the cell and d is the absorbance of the complex. Eq. (6)
is applicable when [D] ꢀ [A] and the complex absorbs at a wave-
length where both electron acceptors and donors are completely
transparent. K and ε were calculated from the slope and the inter-
cept of the curve obtained from the linear plots of [A][D] /d against
[D]. A representative Scott plot is shown in Fig. 10 and the values
of K and ε determined are given in Table 5. The observed high val-
d[Product]
or
= kꢁ[DDQ][CLZ]
dt
where kꢁ = kK
The above rate law is in agreement with the observed kinetic
results, i.e. the rate of formation of the product is first each with
respect to [DDQ] and [CLZ].

M. Pandeeswaran et al. / Spectrochimica Acta Part A 78 (2011) 375–382
381
O
Cl
Cl
CN
CN
O
N
HN
O
N
N
N
O
Cilostazole
DDQ
Fast
K
N
N
N
N
O
O
O
Cl
Cl
CN
CN
NH
O
Complex
Slow
- HCl
k
N
N
N
NC
N
CN
O
O
O
N
Cl
O
Scheme 3.
ues of K suggested that the CT-complexes formed are of a strong
type [45] and the linearity of the Scott plots further supported this
result.
the theoretical (MOPAC PM3 method) and experimental ioniza-
tion potential values are in fairly good agreement with each other.
This fact supports the interpretation that the low energy band
can be regarded as the CT band. Further evidence for the nature
of CT-interaction in the present systems is the calculation of the
dissociation energy (W) of the charge-transfer excited state of the
complex. Hence the dissociation energies of the complex were cal-
culated from their CT-energy, hꢀCT, the ionization potential of the
donor, Ip and electron affinity, EA, of the acceptor using the empir-
ical relation [20,49] given in Eq. (9):
The values of oscillator strength (f) which is a measure of inte-
grated intensity of the CT-band and transition dipole moment
(ꢅ), were calculated as described elsewhere [22] and the val-
ues thus obtained are also given in Table 5. The values of f are
rather relatively large indicating a strong interaction between
the donor–acceptor pairs with relative high probabilities of CT-
transitions [46,47]. Out of the many applications of CT-complexes,
one important application is to calculate the ionization potential of
the donor. The ionization potential (Ip) of the highest filled molec-
ular orbital of the donor was estimated from CT energies of its
complexes with the acceptor making use of the empirical equations
reported in literature [48].
hꢀCT = Ip − EA − W
(9)
The calculated values of W (Table 5) suggested that the inves-
tigated complex is reasonably strong and stable under the studied
conditions with higher resonance stabilization energy [45].
Ip (eV) = 5.76 + 1.52 × 10−4ꢀ¯DDQ (cm−1
Ip (eV) = 2.90 + 1.89 × 10−4ꢀ¯Iodine (cm−1
)
(7)
(8)
4. Conclusions
)
The calculated Ip value for molecular orbital participating in CT-
interaction of the donor is listed in Table 5. In the present study,
Spectro-kinetic studies revealed that the interaction of iodine
and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone with CLZ was

382
M. Pandeeswaran et al. / Spectrochimica Acta Part A 78 (2011) 375–382
found to be proceed through three steps, out of these, the formation
of outer complex and its conversion to inner complex are extremely
fast, whereas the formation of the final product is the rate deter-
mining slow step. The spectral, kinetic and thermodynamic results
support the proposed mechanism. The rate of the reaction was
observed to increase with an increase in the relative permittivity of
the medium. The results revealed that at higher relative permittiv-
ity regions solvent–solvent interaction is also significant in addition
to solute–solvent interactions. The CLZ–I2 system was character-
ized by the formation of triiodide ion while the CLZ–DDQ system
was characterized by the formation of the DDQ•− radical ion. Both
the acceptors form a 1:1 CT complex with the donor and these com-
plexes were found to be strong as evidenced from its equilibrium
and spectral parameters. The mechanisms of the interaction of the
drug studied may be useful in understanding the binding of the
drug molecule in real pharmacokinetic study.
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Acknowledgement
The authors thank the Council of Scientific and Industrial
Research (CSIR) for its financial assistance to carry out this research
work.
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