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Spectrochimica Acta Part A 67 (2007) 573–577

Spectroscopic studies of charge transfer complexes betweencolchicine and some � acceptors

Mustafa Arslan ∗, Hulya DuymusSakarya University, Faculty of Arts and Sciences, Chemistry Department, Sakarya 54140, Turkey

Received 9 February 2006; accepted 23 June 2006

bstract

Charge transfer complexes between colchicine as donor and � acceptors such as tetracyanoethylene (TCNE), 2,3-dichloro-5,6-dicyano-p-enzoquinone (DDQ), p-chloranil (p-CHL) have been studied spectrophotometrically in dichloromethane at 21 ◦C. The stoichiometry of theomplexes was found to be 1:1 ratio by the Job method between donor and acceptors with the maximum absorption band at a wavelength of 535,

85 and 515 nm. The equilibrium constant and thermodynamic parameters of the complexes were determined by Benesi–Hildebrand and van’toff equations. Colchicine in pure form and in dosage form was applied in this study. The formation constants for the complexes were shown toe dependent on the structure of the electron acceptors used.

2006 Elsevier B.V. All rights reserved.

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eywords: Spectrophotometry; Charge transfer complexes; Colchicine; � acce

. Introduction

Colchicine is an anti gut drug chemically knowns N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]eptalen-7-yl) acetamide [1] and shown below.

Investigation of the physicochemical properties and mecha-ism of action of drug compounds in solution is important inharmacokinetics. Spectroscopic and thermodynamic investi-ations lead to a measure of the strength of binding of the drugompounds to other substances present in living systems [2].

Charge transfer complexation is important phenomenon in

iochemical and bioelectrochemical energy transfer process [3].harge transfer phenomena was introduced first by Mulliken.he term charge transfer gives a certain type of complex result-

∗ Corresponding author. Tel.: +90 264 346 0373; fax: +90 264 346 0371.E-mail addresses: marslan@sakarya.edu.tr, arslanmustafa66@yahoo.com

M. Arslan).

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386-1425/$ – see front matter © 2006 Elsevier B.V. All rights reserved.oi:10.1016/j.saa.2006.06.045

ng from interactions of donor and acceptor with the formation ofeak bonds [4,5] and discussed widely by Foster [6]. Molecular

nteractions between electron donors and acceptors are generallyssociated with the formation of intensely colored charge trans-er complexes (CTC) in which absorb radiation in the visibleegion [6].

Molecular complexation and structural recognition aremportant processes in biological systems. For example drugction, enzyme catalysis and ion transfer through lipophilicembranes all involve complexation [7]. The feature of non-

ovalent interaction are the primary directors of specificity, rateontrol and reversibility in many biochemical reactions [8].

Many drugs are easy to be determined by spectrophotome-ry based on color charge transfer complexes formed betweenlectron acceptors, either � or � and drugs as electron donorsither � or �. Reported methods for analysis of many drugsre mostly by direct UV-spectrophotometry [9–12], fluorome-ry [13], polarography [14], colourimetry [15] and HPLC [16].nd also our previous works showed that the charge transfer

omplexes have good non-linear optical properties and electri-al conductivities [17–20].

This paper reports simple, direct and sensitive spectropho-ometric method for the determination of colchicine with some

acceptors such as TCNE, DDQ and p-CHL. Colchicine wassed as drug both in dosage and pure form. Stoichiometry,

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74 M. Arslan, H. Duymus / Spectroch

quilibrium constant and thermodynamic parameters of theomplexes were determined.

. Experimental

Materials: The materials used in this study were obtainedrom local suppliers; colchicine, TCNE (Merck), p-CHLMerck), DDQ (Merck), colchicine tablets as Kolsin Draje (I.E.lagay Drug Company, Istanbul, Turkey). Dichloromethane

Merck) was redistilled before using. All laboratory reagentsere freshly prepared.

.1. Preparation of standard solutions

Acceptors: A stock solution of acceptors at a concentrationf 1 × 10−2 M was prepared in different volumetric flask by dis-olving 12.8, 22.7, 24.6 mg of TCNE, DDQ and p-CHL powderccurately weighed in dichloromethane and making up to 10 mlith the same solvent.Colchicine: A standard solution of colchicine was prepared

y dissolving 39.9 mg of pure colchicine in a 10 ml volumetricask using dichloromethane.

Absorption spectra: A 2 ml volume of colchicine and accep-ors were scanned separately through a UV–vis spectrophotome-er (Shimadzu 2401) to their wavelength of maximum absorp-ion. When 2 ml of acceptor solution and 2 ml of donor solutionere mixed, a color charge transfer complex was formed. Theavelength of maximum absorption of the resulting solutionas determined from spectrophotometer.

.2. Stoichiometries of the complexes

Job’s method of continuous variations was used to deter-ine the stoichiometries of the complexes [21,22]. Master solu-

ions of equimolar concentrations of the drug and acceptor inichloromethane were used in this experiment. Aliquots of solu-ions were varied alternately from 0.2 to 0.8 ml for donor andhloranil solutions to hold the total volume at 1 ml in the cuvettey using a 1 ml syringe. Average optical densities were calcu-ated from three runs on the same sample and average valuest 790–800 nm were subtracted from the average values at theaxima. The complex for the each reaction mixture stand for

0 min at room temperature to form stable complexes beforenalysis at the maximum absorbance.

.3. Determination of equilibrium constants

Benesi–Hildebrand equation [23] was used for the determi-ation of the equilibrium constants of the complexes. 2.56 mgf TCNE was weighed in the cuvette and added in 2 ml of× 10−4 M colchicine solution as a donor. Then, each time.2 ml of 3 × 10−4 M colchicine solution was added in cuvettend maximum absorptions were determined at indicated wave-

engths for 10 times. After adding each time, waited for 10 minor getting stable complex. The UV–vis spectrum was measuredfter each addition of 0.1 ml of solution. About 10 dilutions wereun with each sample. The reverse concentration method, which

fiew

Acta Part A 67 (2007) 573–577

nvolves keeping the drug concentration constant and adding aolution of acceptor to the sample cuvette is applied due to lessolubility of DDQ and p-CHL and followed as described above.

.4. Thermodynamic constants

The thermodynamic constants of the complexes betweenonor and acceptor was determined by van’t Hoff equation..5 ml of 10−2 M colchicine and 1.5 ml of 10−2 M of accep-or from stock solution were mixed and wavelength of maxi-

um absorption was determined at the five different temper-tures such as 7, 14, 21, 28 and 35 ◦C. Acceptor was useds a background. Samples were measured three times at theame temperature. From the averaged data was subtracted thebsorbance due to donor compounds in the solvent (CH2Cl2)easured separately. The concentrations were corrected for the

olume changes at the different temperature. The constants werealculated by plotting ln(Abs)/ε − ln(Do − Abs/ε)(Ao − Abs/ε)ersus 1/T (K). The temperatures were maintained by keepinghe reaction mixtures in a thermostated water bath.

.5. Colchicine tablets

Fourty Kolsin tablets were finely powdered and amountquivalent to 40 mg colchicine base was accurately weighed.ransferred to a beaker containing 10 ml of dichloromethanend shaken for a while to dissolve the drug. Then the solu-ion was filtered to the 10 ml of volumetric flask and filled byichloromethane to provide a theoretical 10−2 M solution ofolchicine. Two millilitres of acceptor solution was added toml of resulting solution. The absorbance was determined at35 nm with TCNE, 585 nm with DDQ and 515 nm with p-CHL,espectively. Percentage recoveries of donor from the Kolsinablet were calculated by reference to the Beer’s plot.

. Results and discussion

The absorption spectra of solutions containing donor andcceptors together exhibit new absorptions at longer wavelengthhan either the donors (λ < 400 nm) or the acceptor (λ < 450 nm)lone.

A solution of TCNE, DDQ and p-CHL in dichloromethanead cream, orange and yellow color with the maximum wave-ength at lower than 450 nm. Purple, green and pale yellowolors were obtained on interaction of the TCNE, DDQ and-CHL acceptor solutions and colorless solution of colchicinen dichloromethane mentioned a charge transfer complex for-

ation. Scanning of the complex in the visible range between00 and 800 nm showed maximum peaks at 535, 585, and 515,espectively, and shown in Fig. 1.

During the complex formation, charge transfer transitionsccur with the excitation of an electron from donor to an emptyrbital of acceptor. Charge transition involves an electron trans-

er from HOMO of the donor to LUMO of the acceptor. Thiss shown schematically in Scheme 1 in which hνCT depicts thenergy of the CT transitions. The lowest energy CT transitionill involve promotion of an electron residing in the highest

M. Arslan, H. Duymus / Spectrochimica Acta Part A 67 (2007) 573–577 575

Fig. 1. Charge transfer complexes of colchicine with TCNE (1), DDQ (2) andp-CHL (3) in dichloromethane at 21 ◦C.

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cheme 1. Charge transfer transitions for HOMOs of the donor compounds andUMOs of the acceptor compounds.

ccupied molecular orbital (HOMO) of the donor to the acceptors shown for hνCT. Charge transfer transitions involving elec-rons in lower energy orbitals also are possible and would result

n higher energy CT transitions as shown hν1

CT.The interaction between the donor and acceptors gave �–�*

ransitions by the formation of radical ion pairs as shown incheme 2.

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Scheme 2. The molecular structure of compound and cha

Fig. 2. The plot of Job’s method for colchicine with TCNE.

The stoichiometry of the complex formation was determinedy Job’s method of continuous variation [21]. A 1:1 ratio ofomplex was determined for the donor and acceptor interactionsFigs. 2–4) which may be represented as

+ A � [D,A]

here D is the donor (colchicine), A the acceptor (TCNE, DDQnd p-CHL) and [D, A] represents the complex form.

The 1:1 complexation ratio indicates that colchicine has onlyne strong basic and electron containing center.

The constants of the complexes were calculated by theenesi–Hildebrand equation [23] shown below:

D0

Abs= 1

Kε[A0]+ 1

εor

[A0]

Abs= 1

Kε[D0]+ 1

ε

here [A0] is the concentration of the acceptor; [D0] the con-entration of the donor; Abs, the absorbance of the complex;the molar absorptivity of the complex formed and K is the

ssociation constant of the complex. On plotting of the values

rge transfer transition between donor and acceptor.

576 M. Arslan, H. Duymus / Spectrochimica Acta Part A 67 (2007) 573–577

Fig. 3. The plot of Job’s method for colchicine with DDQ.

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Fig. 6. Benesi–Hildebrand plots for colchicine with DDQ.

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Fig. 4. The plot of Job’s method for colchicine with p-CHL.

D0]/Abs versus 1/[A0] or plotting of the values [A0]/Abs versus/[D0] straight lines were obtained in Figs. 5–7. The slope andntercept of the regression lines were used to get the values of

olar absorptivity, correlation coefficient and association con-

tant given in Table 1.

The results shown in Table 1 reveal that the K values of chargeransfer complexes with DDQ are higher than the correspond-ng values with p-CHL and TCNE. This is consistent with the

Fig. 5. Benesi–Hildebrand plots for colchicine with TCNE.

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Fig. 7. Benesi–Hildebrand plots for colchicine with p-CHL.

ecrease in electron affinity of TCNE relative to DDQ [24]. Onhe other hands, the results indicate the ability of DDQ to acceptlectrons is higher than that of p-chloranil and also electronccepting ability of p-chloranil is higher than that of TCNE.

The thermodynamic constants of the electron donor–acceptoromplexes of drug with acceptors were determined by van’t Hoffnd Beer–Lambert equations:

ln(Abs)

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The slope of the plot was used to calculate enthalpies (�H)nd relative entropies can be calculated from intercept of thelot and shown in Fig. 8.

�G◦ values of the complexes were calculated from Gibbsree energy of formation according to the equation:

G◦ = −RT ln KCT

able 1ormation constants of the complexes of colchicine with TCNE, DDQ, p-CHL

n dichloromethane at 21 ◦C

cceptors-drug KBH Stoichiometry r2 λmax (nm)

CNE 4.67 1:1 0.990 535-CHL 5.85 1:1 0.985 515DQ 10 1:1 0.998 585

M. Arslan, H. Duymus / Spectrochimica

Fig. 8. van’t Hoff plot for colchicine with TCNE (+), DDQ (�) and p-CHL (©)at 7, 14, 21, 28, and 35 ◦C.

Table 2Thermodynamic parameters of the complexes of colchicine with TCNE, DDQ,p-CHL in dichloromethane at 7, 14, 21, 28, 35 ◦C for �S, �H and 21 ◦C for�G◦

Acceptors-drug �H (cal mol−1) �S (Eu) �G◦ (cal mol−1) r2

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CNE −402 −6.57 −897 0.988-CHL −1021 −8.10 −1028 0.991DQ −1657 −7.9 −1340 0.995

here �G◦ is the free energy of the charge transfer complexes;the gas constant (1.987 cal mol−1 ◦C); T the temperature in

elvin degrees; KCT the association constant of donor–acceptoromplexes (l mol−1). The �S, �H and �G◦ values of the com-lexes are given in Table 2. The obtained results reveal that theT complex formation process is exothermic and spontaneous.here is a good agreement with the literature values of the con-tants. When increasing electron affinity of acceptors, the valuesf the constants increases [25].

. Conclusions

The spectroscopic methods have advantage of being simple,ensitive, accurate and suitable for routine analysis in labora-ories. The methods used here are a single step reactions andingle solvent. Dichloromethane used here as a solvent to avoid

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Acta Part A 67 (2007) 573–577 577

ny interactions of solvent with donor and acceptors. The meth-ds can be used as general methods for the spectrophotometricetermination of drugs in bulk powder and in commercial for-ulations.

cknowledgement

This work was supported by Sakarya University Scientificesearch foundation.

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21] R. Job, Advanced Physicochemical Exp., Pitman, London, 1964.22] M. Stalko, J.F. Yanus, J.M. Pearson, Macromolecules 9 (1976) 715.23] H.A. Benesi, J.H. Hildebrand, J. Am. Chem. Soc. 71 (1949) 2703.24] A.A.A. Borqei, Spectrochim. Acta A 58 (9) (2002) 1895.25] E.H. El-Mossalamy, J. Mol. Liquids 123 (2006) 118.