INTRODUCTION:

2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ) was first synthesized almost a century ago by Thiele and Gunthe¹. It has been used as dehydrogenating agent^2,3 as well as electron acceptor in the formation of charge transfer complexes. DDQ strongly absorbs at 350 nm. One of the first characteristics of DDQ noted after its initial synthesis was the ready formation of intensely coloured solutions when it is dissolved in aromatic organic solvents. The colours of these solutions are attributed to the formation of Charge Transfer (CT) complexes between DDQ and aromatics⁴and the solutions exhibited CT bands with almost all aromatic hydrocarbons. The DDQ has been shown to form molecular complexes either in solution or in solid state with a variety of organic donors viz., benzene and substituted benzenes^5-7, methoxy benzenes⁸, polycyclic hydrocarbons^9,10, aromatic^11,12, carbonyl compounds^13,14, hetercyclic compounds^15,16, metal complexes¹⁷, polymers^18,19, nitrones²⁰, N-oxides²¹, imidazoles²², drugs^23,24, sulphur containing drugs²⁵ and paracyclophanes²⁶.

The charge-transfer interactions between the electron donor, Trimethylenedipiperidine (TMDP) and DDQ were studied spectrophotometrically in CHCI₃ solutions^27,28.

The literature revealed that CT complexes of the acceptors with the variety of donors having π-electron donor sites have been widely studied. As many of the drugs possess aromatic moieties in their structures, there is a scope to study CT complexes using drugs as donors. The study of CT complexes gives information about ionization potentials and spectral characteristics together with relative donor abilities of donor. It is therefore thought worthwhile to carry out a systematic study of CT complexes of drugs with acceptor, DDQ with a view to get insight into ionization potentials, spectral characteristics and relative donor abilities of a few drugs available in the market. The drugs used as donors for the study are carefully chosen so that they contain aromatic donor sites and are hopefully expected to form CT complexes with DDQ.

EXPERIMENTAL:

Materials:

The commercial sample of 2,3-dichloro-5,6- dicyano-p-benzoquinone (DDQ) obtained from Aldrich was recrystallized from benzene-chloroform (2:3) mixture (mp 213-314 ⁰C). The drugs used in study are procured from various bulk drug and pharmaceutical industries like Hetero drugs, Symed Pharma, Neo Spark, Syn-finechem and Sreenivas Pharma in and around Hyderabad. Most of the drugs procured are in the form of their acid salts. They have been neutralized by adding calculated amount of NaOH/NH₄OH as required followed by extraction with ether or CHCl₃. They were recrystallized from suitable solvent till TLC pure. A few drugs were salts of Na⁺ and are recrystallized before use. The solvents used in the study are Chloroform, Acetonitrile and 1,2-Dichloroethane. All the solvents were of spectrograde and are used without further purification. Other solvents like methanol and acetone used for other purposes than analysis are of LR grade.

Methods:

Preparation of Stock solutions:

60mg/100 ml(w/v) (2.6X10^-3M) solution of DDQ was freshly prepared in chloroform.1mg/ml Stock solutions of drugs are prepared in chloroform and are further diluted according to the requirement.

Procedure:

Different aliquots of solution of drugs were transferred into 10 ml calibrated standard flask containing a constant volume of reagent solution and volume was made to 10 ml by the solvent. The concentration of drug was varied so as to produce charge transfer complexes between 0.06 to 1.15 absorbance units.

The stoichiometry of each of the complex was determined from Job’s continuous variation method by using equimolar solutions of drug and acceptor.

Instrumentation:

The UV-Vis spectra of the individual components and the charge transfer complexes were recorded on Shimadzu 140 or Shimadzu-240 and Elico SL 210 UV- Visible double beam spectrophotometers using a matched pair of quartz cells of 10mm path length. The Shimadzu-240 instrument is fitted with thermostated sample compartment with digital temperature display. The temperatures above 25⁰C were attained by electrical heating of the sample compartment, while the lower temperatures by circulating cold water around the cuvettes. The spectra of molecular complexes of DDQ in chloroform and absorption data is collected at λ_max of CT band for the evaluation of stability constants and thermodynamic parameters of the complexes.

The absorption bands due to acceptor or donor individually have fallen to the base line much before the wavelength of CT absorption. However, the lower wavelength side of the CT bands is complicated by other absorption, probably due to complexed donor²⁹.The complicated CT bands were analysed by using the relation put forward by Briegleb and Czekella³⁰.

(n_h- n_l) / 2(n_m -n_l) @ 1.2

Where n_h and n_lrefer to the frequency at half the maximum intensity on the high and low frequency side of the peak located at n_m.

Evaluation of stability constants:

The formation constants of the complexes were evaluated by using Rose-Drago method. Consider the equilibrium

(1)

The equilibrium constant

K = [C] / ( [A_O] – [C] ) ( [Do] – [C] ) (2)

on rearrangement of this equation and by applying Beer’s law

K^-1 = d / ε – ( [D_O] + [A_O] ) + [D_O] [A_O] ε / d (3)

The Rose-Drago method involves a random selection of ε (molar extinction coefficient) values of the complex and calculating K^-1from a set of experimental data, namely absorbance d, [D_O], [A_O] and then K^-1 is plotted against the selected ε values. The procedure is repeated with different sets of donor and acceptor concentrations. All the plots intersect at a common point from which the experimental value of K and ε are determined. The plots normally intersect in small triangular area near common point. The area speaks of the error limits in the determination of K and ε.The effect of temperature on K yielded the thermodynamic parameters by using vant Hoff’s method. The proof from Job’s plot for the formation of 1:1 complex and the constancy of ε over the temperature range studied rule out the possibility of existence of complexes of other species than 1:1.

RESULTS AND DISCUSSION:

3.1 Molecular complexes of drugs with DDQ:

When pale yellow coloured solution of DDQ is mixed with drugs (Chart I) characteristic colors were observed. Each of the solution exhibited Charge Transfer (CT) band (s) in their electronic spectra. Irbesartan exhibited two charge transfer bands while Ofloxacin, Trazadone, Losartan K, Cisapride and Ramipril exhibited only one CT band. The appearance of color and exhibition of CT bands (Fig. 1) are attributed to the formation of charge transfer complexes between the drugs and DDQ since these absorption bands are uncharacteristic of the individual components. The wavelengths (l_max) of CT band of all the complexes together with other spectral characteristics are presented in Table 1.

Table 1: Spectral characteristics of charge transfer complexes of DDQ with drugs

S. No.	Name of the drug	λ_max(nm)	E_CT(eV)	υ_CT x 10^-3 (cm^-1)	IP(eV)	Dυ½(cm^-1)	ε_max	D	f
1	Ofloxacin	755	1.643	13.25	7.86	5472	6000	4.770	0.142
2	Trazadone	720	1.723	13.89	7.98	3885	5800	3.860	0.097
3	Losartan K	715	1.735	13.99	7.99	6232	5700	4.829	0.153
4	Irbesartan	710	1.747	14.09	8.01	4606	5600	4.100	0.111
5	Cisapride	590	2.531	20.41	9.13	6502	2700	2.810	0.076
6	Ramipril	475	2.611	21.05	9.25	5667	2525	2.497	0.062

Chart I : Structures of Drugs studied

Fig.1: Absorption spectra of a) Losartan K b) its molecular complex with DDQ

The appearance of CT band is attributed to the excitation of an electron from the highest occupied molecular orbital (HOMO) of the donor to the lowest unoccupied molecular orbital (LUMO) of the acceptor. The appearance of double CT band is attributed to the excitation of electron from ultimate and penultimate molecular orbitals of donor to the LUMO of the acceptors. The appearance of double CT bands may occur due to (a) excitation of electrons from two different levels of donor to the same vacant level of acceptor or (b) excitation of electron from HOMO of donor to two different vacant levels of acceptor. In the former type of CT complexes the energy difference between two CT bands DE = (E_CT1– E_CT2) depends upon the donor whereas in the later type of complexes it is independent of nature of donor i,e. ∆E is constant. In our study it is observed that ∆E differs from donor to donor hence the complexes are inferred to be of former type. The position of CT band (l_max) of the drugs with DDQ is in the order: Ofloxacin > Trazadone > Losartan K > Irbesartan > Cisapride > Ramipril. When two CT bands occurred the higher wavelength band is considered in the priority order. From the structures of the drugs it is clear that ofloxacin and trazadone containing N,N^’-dimethyl amino aniline groups in their structure should have the highest donor abilities of the drugs studied. Losartan and Irbesartan have biphenyl rings in their structures are expected to follow above donors in the basicity. Cisapride, a p-amino amide showed less basicity while Ramipril showed CT band at 475nm which is close to the CT band observed for toluene.

Energies of charge – transfer bands:

The energies of the inter molecular charge transfer bands are calculated from the frequencies of absorption, using the equation

E_CT= hn_CT

and the values are reported in Table 1.

Ionization potentials of the donors:

The energies of CT bands of DDQ are linearly related to the ionization potentials of the donors in CHCl₃ by the equation.

hn_{CT =}0.70I_d– 3.86

where n_CTis the frequency of the CT band, I_d is ionization potential of donor and h Planck’s constant. The ionization potentials of the donors are calculated using this equation and are reported in Table 1. The ionization potentials of donors in the present study are in the order: Ofloxacin < Trazadone < Losartan K < Irbesartan < Cisapride < Ramipril.

Stoichiometry of the complexes:

The stoichiometry of the complexes were determined by the Job’s continuous variation method using equimolar solutions (2.0 x 10^-3 M) of DDQ and drugs and stoichiometry is found to be 1:1 in each case. The Job’s plot of DDQ with ofloxacin is shown in Fig. 2.

ig. 2 Job’s continuous variation plot of DDQ – Ofloxacin [A₀] = [D₀] = 2x10^-3M

Extinction co-efficient (e), Oscillatory Strength (f) and Transition Dipole moments (D) of complexes:

The extinction coefficients of the complexes are determined at different temperatures from the intersection points of Rose- Drago plots and are reported in Table 1. The extinction coefficients of a CT complex is found to be almost constant over the temperature range studied. The oscillatory strengths defined by Mullikan³¹

f = 4.319 x 10^-9.e_max.Dn_1/2

have also been calculated. Transition Dipole moment of the complexes as defined by Tsubomura et al³²

D = 0.09582 (e_max.Dn_1/2/n_max)^1/2

have also been computed from the extinction coefficients and half–band widths and are reported in Table 1 together with the oscillatory strengths. The randomness of ε , f and D may be due to variation of _.Dn_1/2from drug to drug and also due to Contact Charge Transfer (CCT) which alters the ε to a greater extent³³.

For a given complex the extinction coefficients, the oscillatory strengths and the dipole moments are also found to be almost independent of temperature. The randomness in the values of ε, f and D may be due to CCT. The observed e value is related to e_maxof CT and e’_maxof CCT by

e_obs= e_CT+ (αe’/ K) (4)

where α is number of possible contact sites for the species in excess, around and molecule of the second species, e’ is the extinction coefficients for the CCT process based on the potential contact concentration and K is stability constant. Thus the e_obsobserved depends on the α, e’ and K which cannot be evaluated a priory. The values of e’are found to be order 10⁶, thus the second term of the equation determines the observed e.

Stability constants and Thermodynamic parameters:

The optical density (d) at λ_max CT is monitored by varying the concentration of donor while concentration of acceptor is held constant. The ‘d’ increased with increasing concentration of donor at a given temperature. The ‘d’ also is found to decrease with increasing temperature for a set of constant donor and acceptor concentration. The stability constants have been evaluated from the intersection point of Rose-Drago plots (Fig. 3). The stability constants of the complexes increased with electron releasing ability of the drug and are in the order: Ofloxacin > Trazadone > Losartan K > Irbesartan > Cisapride > Ramipril.

Fig. 3: Rose-Drago plot of DDQ-Ofloxacin Complex

The K values are also found to decrease with the increasing ionization potentials and a straight line was obtained when logarithmic functions of K are plotted against ionization potentials of donors with some exceptions because all the donors are not structurally related (there are mononuclear, binuclear aromatics and heterocyclics) (Fig. 4).

Fig. 4: A Plot of log K vs IP of donors

The thermodynamic parameters viz., ΔH and ΔS were evaluated from variation of stability constants with temperature using vant Hoff’s method. A plot of log K Vs 1/T gave straight line, (Fig. 5) from the slope and intercept of which the ΔH and ΔS have been evaluated. The ΔG values at 25⁰C were calculated using the equation

∆G = ΔH – TΔS

and are presented in Table 2.

Fig.5: Plot of logK Vs 1/T for DDQ complexes with drugs

Table 2: Stability constants and thermodynamic parameters of CT complexes of DDQ with drugs

S. No.	Name of the drug	Stability constants (K) at various temperatures					-ΔH K Cal mol^-1	-ΔS Cal deg^-1 mol^-1	-ΔG K Cal mol^-1
S. No.	Name of the drug	K₁₀^oC	K₂₀^oC	K₃₀^oC	K₄₀^oC	K₅₀^oC
1	Ofloxacin	254.5	145.64	86.46	53.06	33.57	9.2	21.50	3.11
2	Trazadone	211.85	123.37	74.45	46.40	29.78	8.9	20.84	3.01
3	Losartan K	194.61	114.09	69.28	43.43	28.03	8.8	20.62	2.96
4	Irbesartan	162.9	69.28	60.78	38.62	25.62	8.4	19.56	2.86
5	Cisapride	34.45	60.78	17.14	12.50	9.29	5.95	13.99	1.99
6	Ramipril	32.54	22.82	16.38	12.01	8.97	5.85	13.75	1.95

ACKNOWLEDGEMENTS:

Authors thank Prof. G Venkateshwarlu, Head, Department of Chemistry, Nizam College for his suggestions. TV is thankful to M Ravindra Reddy, Chairman, Managing Committee, SAP College, Vikarabad for providing facilities and to the UGC for financial assistance under Major Research Project. PKR is thankful to the Management of Siddhartha Junior College, Vikarabad for their help.

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Received on 23.08.2014 Modified on 09.09.2014

Asian J. Research Chem. 7(10): October- 2014; Page 863-869

*Corresponding Author E-mail: tadooru_veeraiah@rediffmail.com

INTRODUCTION:

on rearrangement of this equation and by applying Beer’s law