Spectroscopic studies on the interaction of cimetidine drug with biologically significant σ- and π-acceptors

Article abstract of DOI:10.1016/j.saa.2010.01.017

Spectroscopic studies revealed that the interaction of cimetidine drug with electron acceptors iodine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted through the initial formation of ionic intermediate to charge transfer (CT) complex. The CT-complexes of the interactions have been characterized using UV-vis, ¹H NMR, FT-IR and GC-MS techniques. The formation of triiodide ion, I₃^-, is further confirmed by the observation of the characteristic bands in the far IR spectrum for non-linear I₃^- ion with C_s symmetry at 156 and 131 cm^-1 assigned to ν_as(I-I) and ν_s(I-I) of the I-I bond and at 73 cm^-1 due to bending δ(I₃^-). The rate of formation of the CT-complexes has been measured and discussed as a function of relative permittivity of solvent and temperature. The influence of relative permittivity of the medium on the rate indicated that the intermediate is more polar than the reactants and this observation was further supported by spectral studies. Based on the spectroscopic results plausible mechanisms for the interaction of the drug with the chosen acceptors were proposed and discussed and the point of attachment of the multifunctional cimetidine drug with these acceptors during the formation of CT-complex has been established.

Full text of DOI:10.1016/j.saa.2010.01.017

Spectrochimica Acta Part A 75 (2010) 1462–1469
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 cimetidine drug with biologically
significant ␴- and ␲-acceptors
M. Pandeeswaran, K.P. Elango∗
Department of Chemistry, Gandhigram Rural Institute-Deemed University, Gandhigram 624302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Spectroscopic studies revealed that the interaction of cimetidine drug with electron acceptors iodine and
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted through the initial formation of ionic inter-
mediate to charge transfer (CT) complex. The CT-complexes of the interactions have been characterized
using UV–vis, 1H NMR, FT-IR and GC–MS techniques. The formation of triiodide ion, I3−, is further con-
Received 13 October 2009
Received in revised form
31 December 2009
Accepted 29 January 2010
−
firmed by the observation of the characteristic bands in the far IR spectrum for non-linear I3 ion with
Cs symmetry at 156 and 131 cm−1 assigned to ꢀas(I–I) and ꢀs(I–I) of the I–I bond and at 73 cm−1 due to
bending ı(I3−). The rate of formation of the CT-complexes has been measured and discussed as a function
of relative permittivity of solvent and temperature. The influence of relative permittivity of the medium
on the rate indicated that the intermediate is more polar than the reactants and this observation was
further supported by spectral studies. Based on the spectroscopic results plausible mechanisms for the
interaction of the drug with the chosen acceptors were proposed and discussed and the point of attach-
ment of the multifunctional cimetidine drug with these acceptors during the formation of CT-complex
has been established.
Keywords:
Spectrokinetics
Charge transfer complex
Cimetidine
DDQ
Iodine
Solvent effects
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
cimetidine (CTD) drug with a ␲-acceptor, DDQ, and a ␴-acceptor,
iodine.
The survey of the literature revealed that an enormous amount
of work has been reported on the CT-complexes of organic com-
pounds with variety of acceptors [1–10]; as they are significant in
many fields. Some of such reports include the interactions involv-
ing 2-aminopyrimidines and ␴- and ␲-acceptors [11], thiourea
and benzoquinones [12], azacrowns and antipyrine and 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and iodine [13,14],
N,Nꢀ-diphenylthiourea and chloranil [15], imidazole and DDQ
[16], n-butylamines and 2,3-dichloro-1,4-naphthoquinone [17],
N,Nꢀ-dibenzyl-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane and
iodine [18], 3,6,9,14-tetrathiabicyclo[9.2.1]tetradeca-11,13-diene
and iodine [19] and styrene and DDQ [20]. However, studies on
the spectral and kinetic aspects of such reactions, involving drug
molecules are relatively fewer in number. We are interested in
the spectrokinetic studies on the CT interactions of drugs with
biologically significant electron acceptors [21–24]. In continua-
tion of our earlier works on the spectrokinetic studies on the
interaction of drug molecules with DDQ and iodine, here in this
article we report the spectral characterization of the interaction of
Cimetidine, which is the most celebrated drug of its class, is
used to treat ulcers; gastroesophageal reflux disease, a condi-
tion in which backward flow of acid from the stomach causes
heartburn and injury of the food pipe; and conditions where the
stomach produces too much acid, such as Zollinger–Ellison syn-
drome. Over-the-counter cimetidine is used to prevent and treat
symptoms of heartburn associated with acid indigestion and sour
stomach.
Iodine is well known for its electron accepting properties and is
being used as a model acceptor to investigate the electron donat-
ing properties of organic molecules [25]. In human biology, iodine is
required for the biosynthesis of the thyroid hormones, triiodothyo-
nine and thyroin, which regulate metabolic rate [26–29]. Quinones
are one of the well-known biologically important electron accep-
tors [30–33]. The studies of quinones for their CT interaction
stem from their possible role in biological reactions. Quinones are
known to be important in many biological fields [3]. Thus, the
mechanism of interaction of iodine and quinones with drugs, in
general, is a research topic of significant interest and hence the
present study. The primary objective, therefore, of the present arti-
cle is to study the spectral and kinetics aspects of the interaction
between the electron acceptors DDQ and iodine with cimetidine
drug with an aim to investigate the functional group (in a mul-
∗
Corresponding author. Tel.: +91 451 2452371.
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.2010.01.017

M. Pandeeswaran, K.P. Elango / Spectrochimica Acta Part A 75 (2010) 1462–1469
1463
tifunctional molecule) which involve in CT interaction with these
acceptors.
2. Experimental
2.1. Material and methodology
The electron acceptors DDQ (minimum assay 98%) and iodine
(minimum assay 99.9%) was obtained from Aldrich, India. Commer-
cially available spectroscopy grade solvents (Merck, India) 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 permittivity of the medium. The electron donor
drug cimetidine was obtained as gift sample from locally available
pharmaceutical company and was used as received. The purity of
the drug was checked by its m.p. 139 ◦C and its FT-IR spectrum. The
structure of the donor drug is shown below.
Fig. 1. Photometric titration plots for CTD with DDQ and Iodine. CTD–DDQ system
in iso-butanol, CTD-iodine system in ethyl acetate at 298 K.
Solutions for the spectroscopic measurements were prepared by
dissolving accurately weighed amounts of donor (D) and acceptor
(A) in the appropriate volume of solvent immediately before run-
ning the spectra. The electronic absorption spectra were recorded
on a JASCO (V 630, Japan) double beam spectrophotometer using
1 cm matched quartz cells. The temperature of the cell holder was
controlled with a water flow ( 0.2 ◦C). FT-IR spectra were recorded
in a JASCO (FT-IR 460 Plus, Japan) spectrometer. The far FT-IR data
were collected at Indian Institute Technology, Madras utilizing a
Thermo Scientific Nicolet 6700 (USA) FT-IR spectrometer using the
solid-substrate beamsplitter, Ever-Glo IR source and polyethylene-
windowed. Samples were positioned in the sample compartment
and nitrogen purge was used to eliminate interference from atmo-
spheric water. 1H NMR spectra were recorded at Madurai Kamaraj
University, Madurai. The GC–MS spectra were obtained from Cen-
tral Salt and Marine Research Institute, Bhavanagar, India. The
conductance of the solutions was measured on an Elico, India Con-
ductivity Bridge. For conductance measurements equimolar stock
solutions of D and A were thermostated to a constant tempera-
ture 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.
The symmetrical curves with maximum at 0.5 mole fraction indi-
cated the formation of a 1:1 (D:A) CT-complex (figure not shown).
The photometric titration measurements were also performed for
the determination of the stoichiometry in these interactions. The
concentration of the donor in the reaction mixtures was kept fixed
while the concentrations of iodine and DDQ were varied over a wide
range. The results of the photometric curves (Fig. 1) also indicated
that the stoichiometry of the interaction, in both the cases, is 1:1
(D:A) [35].
3.2. Characterization of the complex
In both CTD-I2 and CTD–DDQ cases, the CT-complex was
obtained by allowing the reactants to react for 24 h under equal
molar conditions in a given solvent as reported [39] and sub-
jected to MPLC separation. The FT-IR spectra of the products were
recorded and the peak 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 CT-complex relative to the free molecules. Some
of the significant shifts are: the peak due to ꢀ(N–H) vibrations of
the free cimetidine occurs at 3225 cm−1 and in DDQ and iodine
complexes they are appear at 3158 and 3152 cm−1, respectively
indicating the involvement of one of the N–H groups in the CT inter-
action with the acceptor. The ꢀ(C–CH3) and ı(C–CH3) vibrations of
the free cimetidine occur at 2943 and 2933 cm−1 and for the DDQ
and iodine complexes they are appear at 2925 and 2925 cm−1 and
2857 and 2862 cm−1 respectively. The ꢀ(C O), ꢀ(C N) and ꢀ(C–Cl)
stretching vibrations in the DDQ species appeared at 1679, 2226
and 799 cm−1 respectively. In the CT-complexes these stretching
vibrations occurred at 1598, 2169 and 764 cm−1, respectively. Such
a bathochromic shift could be indicative of a higher charge density
on the carbonyl and cyano groups of the DDQ molecule [21].
The 1H NMR spectra of the donor and CTD–DDQ complex were
recorded in DMSO-d6 and are shown in Fig. 2. Using the proton
NMR technique, we can identify the nature of interaction between
the donor and acceptor in the resulted complex. The characteristic
pyrazole N–H peak lies at 11.78 ppm in the free donor. In the com-
plex, it appeared at 14.17 ppm. In the donor the pyrazole C–H lies at
2.2. Kinetic procedure
In both CTD-I2 and CTD–DDQ cases, the kinetics of the inter-
action was followed at three different temperatures in various
solvents under pseudo-first-order conditions, keeping [D] ꢁ [A].
The increase in absorbance of the new peaks around 400 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) 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 [34].

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M. Pandeeswaran, K.P. Elango / Spectrochimica Acta Part A 75 (2010) 1462–1469
Table 1
Infrared wavenumbers (cm−1
) and tentative band assignments for the CTD,
CTD–DDQ and CTD-I2 complexes.
CTD
CTD–DDQ
CTD-I2
Assignments
3225m
2943m
2922w
3158w
2925m
2857w
2777w
2226s
2169s
1679s
1598s
1556s
1452w
1409m
3152w
2925m
2862w
2765w
ꢀ(N–H)
ꢀ(C–H); aliphatic,
ı(C–CH3); bend overtone and 2◦
amine –CH3 aliphatic
ꢀ(C N); DDQ
ꢀ(C N); aliphatic
ꢀ(C O); DDQ
2177s
1622s
2169s
1600s
ꢀ(C C);
ꢀ(C C); DDQ
1587s
1454m
1525w
1503m
1423w
1369m
1238w
1185m
ꢀ(C C); aromatic
ı(CH2); aliphatic methylene
bend
ı(C–H); aliphatic methyl bend
ꢀ(C-N); aliphatic
ꢀ(C–C); aliphatic
ꢀ(C–Cl); DDQ
1389s
1283w
1202m
1242w
1213w
799m
Fig. 3. Electronic spectra for the cimetidine-iodine system in tert-butyl alcohol at
298 K.
730w
746w, 713w
ꢀ(C–S); aliphatic
ꢀ(N–H); wagging and aliphatic
methylene rock
measurably. The absorption located at about 250 nm corresponds
to intermediate iodide ion and the one about 360 nm is the blue-
shifted iodine band. The absorption band around 460 nm, which
is attributed to the ␲–␴* electronic transition in free iodine,
is hypsochromically shifted due to its complexation with the
donor. The observed hypsochromic shift in the free iodine band
could be attributed to the perturbation of the iodine molecular
orbital ␴* by a repulsive complex. Accordingly, a more repul-
sive 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 lim-
iting value of this shift is at about 2−90 and 360 nm, which is
the characteristic absorption of the I3 ion in solution. Parallel
observations were made by several investigators in the study of
molecular complexes of iodine with 4-(dimethylamino) pyridine
[38], dibenzo-18-crown-6 [39], ferrocenes [40], 2-aminomethyl-
15-crown-5 [41], 2-3-diaminodyridine [42], 4-aminobyridine [43]
etc. Such an observed variation in the electronic spectrum of the
mixture indicated the interaction between the donor and the accep-
tor.
s, strong; m, medium; w, weak; br, broad; ꢀ, stretching; ı, bending.
7.44 ppm and in the complex at 8.89 ppm. This down field shift indi-
cated the participation of the pyrazole nitrogen atom of the donor
in the CT interaction with the acceptor. There is no appreciable
shift in the other N–H groups of the donor in the complex [36,37].
The mass spectrum of the CTD–DDQ complex gave only the corre-
sponding donor and acceptor ionization peaks rather than a peak
for a new species. This indicated that the D and A participate in CT
interaction only and there is no chemical reaction followed by the
CT interaction leading to a new species.
3.3. Interaction of cimetidine with iodine
On mixing tert-butyl alcohol solutions of CTD and iodine, there
was an instantaneous formation of lemon yellow color with new
absorption maxima centered about 290 and 360 nm in the UV–vis
spectrum (Fig. 3), where neither the donor nor the acceptor absorb
The observed time dependence of the electronic spectra of the
system under investigation is due to a transformation of the initially
formed outer complex into an inner complex followed by a fast
reaction of the resulting inner complex with free iodine molecule
to form a triiodide ion, as depicted below [11,14,44]. The intensity
of the bands at about 250 and 500 nm decreased while the intensity
of the characteristic I3− ion bands (290 and 360 nm) increased with
elapse of time. Consequently, the change in absorbance of the solu-
tion, at 360 nm, was measured as a function of time. No attempt
was made to measure the decrease in intensity of the peak at about
250 and 500 nm, as they reach a constant value quickly in majority
of the solvents. Two clear isosbestic points were observed (Fig. 3) at
265 and 460 nm. Such an observed variation in the electronic spec-
trum of the mixture indicated the interaction between the donor
and acceptor.
Drug + I2 ꢀ Drug − I2(outercomplex) Fast
Drug − I2 ꢀ [Drug − I]+ I−(innercomplex) Slow
(1)
(2)
(3)
−
[Drug − I2] + I− + I2 ꢀ [Drug − I]+ I3
Fast
The far-infrared spectrum of the solid CTD-I2 complex is shown
in Fig. 4 and the assignments are given in Table 2. The results
strongly confirmed the formation of the proposed triiodide com-
plex,−[(CTD)I]+ I3−. The spectrum showed the characteristic band
of I3 ion at 156, 131 and 106, and 73 cm−1. It is well known
Fig. 2. (a) 1H NMR spectrum of cimetidine. (b) 1H NMR spectrum of CTD–DDQ
complex.
−
that I3 ion exists as one unit with either linear or bent structures

M. Pandeeswaran, K.P. Elango / Spectrochimica Acta Part A 75 (2010) 1462–1469
1465
Table 3
Effect of concentration of donor and acceptor on the rate of the reaction at 298 K.
103 [D] (M)
105 [A] (M)
104 k1 (s−1
)
k2
CTD-I2 (in iso-butyl alcohol at 357 nm)
1.54
2.30
3.07
3.84
5.91
5.91
5.91
5.91
6
9
12
16
0.39
0.39
0.39
0.41
3.84
3.84
3.84
3.84
5.91
4.73
3.55
2.36
16.0
15.8
16.1
15.9
CTD–DDQ (in tert-butyl alcohol at 383 nm)
2.43
3.64
4.86
6.07
6.17
6.17
6.17
6.17
2.3
4.3
6.1
7.5
0.10
0.11
0.12
0.12
2.43
2.43
2.43
2.43
6.17
5.29
4.23
3.17
2.3
2.5
2.3
2.4
−
Fig. 4. Far-infrared spectrum of [(CTD)I]+ I3
.
Thus, the observed dependence of rate with relative permittivity of
the medium in all likelihood may be as a result of specific solute-
solvent-solvent interactions. This solvent dependence of k1 values
suggested that there may be some charge separation in the trans-
formation of CT-complex. Formation of such a more polar transition
state is well supported by the large negative entropies of activation.
Further, negative 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 correlation (Fig. 6, r = 0.997) between ꢁH# and ꢁS# values
indicating the operation of a common mechanism in all the solvents
studied. A perusal of data in Table 4 indicated that a solvent change
from ethyl acetate to iso-propyl alcohol caused ∼18 fold rate accel-
eration for the interaction which corresponds to a decrease in ꢁG#
[42]. The obtained far-infrared spectrum of [(CTD)I]+ I3 complex
−
−
agrees quite well with the triiodide, I3 being non-linear with Cs
symmetry where group theoretical analysis show that the three
vibrations should be infrared active. The 156 cm−1 is assigned to
the antisymmetric stretch of the I–I bond, ꢀas(I–I). The correspond-
ing symmetric stretch, ꢀs(I–I); is observed at 131 and 106 cm−1
[45,46]. The band at 61 cm−1 is assigned to the bending vibration,
ı(I3−). These ass−ignments are exactly similar to those known for
the non-linear I3 ion.
The pseudo-first-order rate constants, k1, for the interaction
of iodine with CTD were evaluated by employing the increase in
absorbance of 360 nm band at different temperatures and solvents.
The pseudo-first-order rate constants as a function of [D] and [A]
are given in Table 3. The pseudo-first order rate constants were
independent of initial concentrations of iodine indicating first order
dependence in [I2]. The k1 increased with an increase in [D] and
the slope of the plot of log k1 versus log [D] was found to be 1.05
(r = 0.998) suggesting the order with respect to [D] is also unity.
This was further supported by the constancy of second order rate
constants, k2.
of 7 kJ mol−1
.
The rate constants as a function of temperature and solvent
along with thermodynamic parameters for the CTD-I2 reaction are
collected in Table 4. The k1 values increased with an increase in
the relative permittivity of the medium. A plot of log k1 versus εr is
fairly linear with positive slope (Fig. 5). It is evident from the figure
that, there is deviation from linearity especially at higher relative
permittivity values. This may be due to the fact that with an increase
in polarity of the medium solvent-solvent interaction becomes
increasingly significant in addition to solute-solvent interactions.
Table 2
−
Fundamental vibrations for I3 ion.
Compound
Assignments
Reference
−
ı(I3 )
ꢀas(I–I)
ꢀs(I–I)
−
[(DAPY)I]I3
151
144
132
150
156
156
132
110
109
102
112
131, 106
61
60
60
76
69
73
[42]
[45]
[45]
[46]
[60]
Present work
−
[(HMTACTD)I]I3
−
(TACPD)I+I3
−
[Fe(acac)3]2I+I3
−
−
[(PTZ)I]I3
[(CTD)I]I3
Fig. 5. Plot of log k1 versus relative permittivity of the medium.

1466
M. Pandeeswaran, K.P. Elango / Spectrochimica Acta Part A 75 (2010) 1462–1469
Table 4
Kinetic and thermodynamic parameters for the interaction of iodine with cimetidine.
Solvent
εr
ꢂ (nm)
104 k1 (s−1
)
ꢁH#
−ꢁS#
ꢁG#
298 K
305 K
313 K
Ethyl acetate
6.02
8.93
10.36
12.47
16.56
17.93
364
364
362
357
357
359
1.3
1.8
2.1
2.4
16
2.2
3.2
3.3
3.6
18
5.9
3.9
4.6
13
29
33
79
35
37
85
27
14
56
197
192
31
207
248
95
94
94
94
89
88
Dichloromethane
1,2-Dichloroethane
tert-Butyl alcohol
iso-Butyl alcohol
iso-Propyl alcohol
24
28
εr, relative permittivity of the medium; ꢁH#, kJ mol−1; ꢁS#, J K−1 mol−1; ꢁG#, kJ mol−1
.
3.4. Interaction of cimetidine with DDQ
Conductimetry has been often employed to study the CT inter-
actions [47–49]. In the present study, a mixture of tert-butyl alcohol
solutions of CTD and DDQ exhibits appreciable conductivities than
that of the constituents, which may be due to the formation of a CT-
complex. The conductivity-mole fraction plot yielded maximum at
a D:A molar ratio of 1:1 as evidenced from Fig. 7. The increase in con-
ductivity observed upon the CT-complex formation may be due to
the fact that the CT-complex formed between D and A may undergo
dissociation into ionic intermediate in solvents of sufficient high
relative permittivity give rise to appreciable conductivity [21,50].
D + A ꢁ DA
DA ꢁ [D+A−]
(4)
(5)
The electronic absorption spectra of DDQ in the presence of a
large excess of the donor, was obtained as a function of time in dif-
ferent solvents and a representative spectrum is shown in Fig. 8.
The electronic absorption spectra of the mixture of methanol solu-
tions of CTD and DDQ show a group of absorption bands at 434,
462, 510 and 565 nm. These absorption bands are characteristic
for the absorption of the radical anion DDQ− [13,16,39,41]. The
observed enhanced absorption band intensities, immediately after
mixing D and A, supports the fact that the CT-complex formed is
of the dative-type structure which consequently converts to an
ionic intermediate possessing the spectral characteristics of radi-
cal ion [21]. Further, the observed gradual decrease in the intensity
of the CT bands in the 400–600 nm spectral regions could be due
Fig. 7. Conductivity versus mole fraction of DDQ plot for the CTD–DDQ system in
tert-butyl alcohol.
to the consumption of the ionic intermediate, while the continu-
ous increase of the 402 nm band with elapse of time is indicative
of the formation of the CT-complex [51]. A clear isosbestic point at
425 nm was observed.
The nature of the intermediate formed in the interaction
between CTD and DDQ was identified using the following exper-
iment. Chloroform solutions of the acceptor and donor were
Fig. 6. Relation between enthalpy and entropy of activations for the interaction of
CTD with DDQ and Iodine.
Fig. 8. UV–vis spectra of CTD–DDQ system in methanol at 298 K.

M. Pandeeswaran, K.P. Elango / Spectrochimica Acta Part A 75 (2010) 1462–1469
1467
states of the system, due to ion-solvent interaction. It is possible
that the solvent interaction could also influence the first step (Eq.
(4)), perhaps accompanied by an alteration of charge in the com-
plex. Hereto, increase in polarity of the solvent could enhance the
contribution of dative state and hence lead to a stronger charge
transfer [53]. The results in Table 5 indicated that the k1 val-
ues increased with an increase in the relative permittivity of the
medium. This may be due to the fact that there is some charge sepa-
ration during the interaction. Involvement of such a polar transition
state is well supported by the large negative entropies of activation
and also the negative values of 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 pro-
cess. The correlation between ꢁH# and ꢁS# values was found to
be linear (Fig. 6, r = 0.993) indicating the operation of a common
mechanism in the solvents investigated. In CTD–DDQ case also the
plot of log k1 versus εr is linear initially with positive slope (Fig. 5)
and there is deviation from linearity especially at higher relative
permittivity values which indicated that the solvent-solvent inter-
action becomes increasingly significant, with an increase in polarity
of the medium, in addition to solute-solvent interactions. The sol-
vent change from tert-butyl alcohol to DMSO caused 34 fold rate
acceleration at 298 K for the interaction which corresponds to a
Fig. 9. Absorption spectra of CTD–DDQ systems. D – donor and A – acceptor.
extracted separately with water and the water extracts were mixed
together. Theelectronicspectrumofthemixture, recordedimmedi-
ately after mixing the water extracts, is shown in curve C1 of Fig. 9. It
is observed that there was no appreciable change in the absorption
spectrum of the mixture even after 24 h (curve C2), which indi-
cated that there is no reaction between the acceptor and donor in
aqueous medium. Whereas the chloroform solutions of the accep-
tor and donor were mixed together and the brown colored solution
thus obtained was extracted with water. The absorption spectrum
of the extract, recorded immediately, is shown in curve C3 and that
recorded after 24 h is shown in curve C4. The curve C3 is charac-
teristic of DDQ− radical ion and curve C4 is characteristic of the
CT-complex as shown in Fig. 8. This observation suggests the for-
mation of a polar intermediate in the interaction between CTD and
DDQ [52].
In order to obtain further information about the kinetics and
mechanism of the interaction of DDQ with CTD, the increase in
absorbance at about 400 nm was monitored as a function of time
in different solvents under pseudo-first-order conditions keeping
large excess of [CTD] over [DDQ]. The pseudo-first-order rate con-
stant (k1) values for the formation of the CT-complex as a function
of [CTD] and [DDQ] are also collected in Table 3. It is evident from
the results that the rate is independent of initial concentration of
DDQ indicating first order dependence on [DDQ]. The rate constant
values increased with an increase in [CTD] indicating first order
dependence of rate on [CTD] was found to be linear (r = 0.995) and
which was further supported by the constancy in k2 values [21,22].
The effect of solvent on the interaction between CTD and DDQ
was also investigated. It seems reasonable to assume that anion
radicals are formed from electron donor-acceptor interaction, as
depicted in equations 4 and 5. Increase in polarity of the solvent
would tend to stabilize the radical ion state, with respect to other
decrease in ꢁG# of 5 kJ mol−1
.
Based on the foregoing results and discussions the following
plausible mechanism for the interaction DDQ with CTD has been
proposed.
K
1
DDQ + DrugꢁDDQ : Drug (Fast)
K
2
DDQ : DrugꢁInner complex (Fast)
ꢀ
k
Inner complex−→ CT complex (Slow)
The above mechanism leads to the following rate law.
d[CT-complex]/dt = kꢀ[Innercomplex]
or
d[CT-complex]/dt = k[DDQ][CTD]
where k = kꢀ K1 K2.
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 [CTD].
3.5. Characteristics of the CT-complexes
In both CTD-I2 and CTD–DDQ systems, as enumerated earlier,
initial reactants were converted in to CT-complexes. Hence, an
attempt was made to characterize the CT-complexes formed in
these reactions. For that the absorbance of the new bands were
measured using constant acceptor concentrations (in a given sol-
vent) and varying concentrations of the donor depending on the
Table 5
Kinetic and thermodynamic parameters for the interaction of DDQ with cimetidine.
Solvent
εr
ꢂ (nm)
104 k1 (s−1
)
ꢁH#
−ꢁS#
ꢁG#
ꢂ (nm)
298 K
305 K
313 K
tert-Butyl alcohol
iso-Propyl alcohol
Methanol
DMF
DMSO
12.47
17.93
32.70
36.50
46.68
383
400
402
493
438
2.3
3.0
7.5
19
3.7
3.3
11
34
118
7.0
5.6
14
81
153
54
28
29
60
74
132
217
206
117
50
94
93
91
95
89
575
574
567
347
362
76
εr, relative permittivity of the medium; ꢁH#, kJ mol−1; ꢁS#, J K−1 mol−1; ꢁG#, kJ mol−1
.

1468
M. Pandeeswaran, K.P. Elango / Spectrochimica Acta Part A 75 (2010) 1462–1469
Fig. 10. Concentration variation spectra for cimitidine/iodine system in tert-
butyl alcohol at 298 K, [A] = 5.5158 × 10−5
M
and [D]: (1) 7.9384 × 10−4 M; (2)
1.5877 × 10−3 M; (3) 2.3815 × 10−3 M; (4) 3.1754 × 10−3 M; (5) 3.9692 × 10−3 M.
Fig. 12. Scott linear plots for CTD–DDQ and CTD-I2 systems in tert-butyl alcohol at
298 K.
solvent, but always [D] ꢁ [A] (Figs. 10 and 11). The formation con-
stants (K) and molar extinction coefficients (␧) of the CT-complexes
were determined spectrophotometrically in the temperature range
298–313 K using the Scott equation [54]. A representative Scott plot
is shown in Fig. 12 and the values of K and ␧ determined are given
in Table 6. The observed high values of K suggested that the formed
CT-complexes are of a strong type [55] and the linearity of the Scott
plots further supports this result.
The values of oscillator strength (f) which is a measure of inte-
grated intensity of the CT band and transition dipole moment
(ꢃ), were calculated as described elsewhere [56] and the values
thus obtained are also given in Table 6. The values of f are rather
relatively large indicating a strong interaction between the donor-
acceptor pairs with relative high probabilities of CT-transitions
[57,58]. Out of the many applications of the CT-complexes, one
important application is to calculate the ionization potential of the
donor. The ionization potential (Ip) of the highest filled molecu-
lar orbital of the donor was estimated from the CT energies of its
complexes with the acceptor making use of the following empirical
Table 6
Spectral properties of the CTD–DDQ and CTD-I2 complexes in tert-butyl alcohol
solvent at 298 K.
Property
CTD–DDQ complex
CTD-I2 complex
−
ꢂmax (nm)
hꢀCT (eV)
575
2.16
5.22
724
357
290 (I3
4.28
)
3.47
8.40
6603
1014 ꢀmax (s−1
)
10.34
702
Formation constant,
K (dm3 mol−1
Extinction
)
2747
1297
21,831
coefficient, ε
(dm3 mol−1 cm−1
)
Oscillator strength, f
Dipole moment, ꢃ
Ionization potential
(eV)
Dissociation energy
(eV)
0.0158
1.39
0.0231
1.32
0.4348
5.18
9.42
8.40
8.19
4.34
1.64
2.06
equations reported by Aloisi and Pignataro [59,60].
Ip (eV) = 5.76 + 1.52 × 10−4ꢀ¯DDQ (cm−1
Ip (eV) = 2.90 + 1.89 × 10−4ꢀ¯iodine (cm−1
)
)
(9)
(10)
The calculated Ip value for molecular orbital participating in CT
interaction of the drug is listed in Table 6. In the present study,
ionization potential values computed from the CT energies of the
two acceptors are in fairly good agreement with each other. Further
evidence for the nature of CT-interaction in the present systems is
the calculation of the dissociation energy (W) of the charge trans-
fer excited state of the complexes. The dissociation energies of
the complexes were calculated as described earlier [61] and the
calculated values of W (Table 6) suggested that the investigated
complexes are reasonably strong and stable under the studied con-
ditions with higher resonance stabilization energy [55].
4. Conclusions
Spectroscopic studies revealed that the interaction of iodine and
2,3-dichloro-5,6-dicyano-1,4-benzoquinone with cimetidine drug
was found to be proceed through the formation ionic intermedi-
ates to the formation of CT-complexes. The cimetidine-I2 system
was characterized by the formation of triiodide ion while the
Fig. 11. Concentration variation spectra for CTD–DDQ system in tert-butyl alcohol
at 298 K, [A] = 6.1671 × 10−5 M and [D]: (1) 7.9384 × 10−4 M; (2) 1.5877 × 10−3 M;
(3) 2.3815 × 10−3 M; (4) 3.1754 × 10−3 M; (5) 3.9692 × 10−3 M.

M. Pandeeswaran, K.P. Elango / Spectrochimica Acta Part A 75 (2010) 1462–1469
1469
cimetidine-DDQ system was characterized by the formation of the
DDQ− radical ion. The rate of the reaction was observed to increase
with an increase in the relative permittivity of the medium. Fur-
ther, the results revealed that at higher relative permittivity regions
solvent-solvent interaction is also significant in addition to solute-
solvent interactions. Both the acceptors form a 1:1 CT-complex
with the donor and these complexes were found to be strong as
evidenced from its equilibrium and spectral parameters. The spec-
tral studies on the interaction of CTD drug with this acceptor clearly
revealed the point of attachment of the multifunctional drug cime-
tidine with the acceptors as shown below.
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Acknowledgement
The authors thank the Council for Scientific and Industrial
Research (CSIR) for its financial assistance to carry out this research
work.
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