OJPC  Vol.3 No.1 , February 2013
Influence of Solvent Polarity on the Physio-Chemical Properties and Quantitative Determinations of Tenofovir Disoproxil and Emtricitabine with Chloranilic Acid as Complexing Agent
Abstract: Purpose: Tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) are both second generation ant-retroviral drugs used in the “treatment” of HIV/AIDS. The aim of this study is to establish the physic-chemical properties of their reaction with chloranilic acid in different solvent systems and to justify the chemical basis for simultaneous quantitative determination of these drugs in their combined formulation. Method: TEN and EMT were individually isolated from their single formulations and purified by chromatography to obtain secondary standard. Purity of the isolates were tested for by comparison with literature values. Stock solution of chloranilic acid (CA) [3.0 × 10﹣3 M] was prepared in the following solvents of different polarities: ethanol, acetonitrile, ethylacetate, chloroform and hexane. Equal volumes of CA and TEN [3.0 × 10﹣2 M] and EMT [3.0 × 10﹣2 M] dissolved in different solvents were mixed whereby colored products were observed. Absorption maxima were determined. Calibration curves were generated and validated. Quantitative simultaneous determination of TEN and EMT was determined by standard protocol. Stoichiometric relationships between the drugs and CA were established. Equilibrium constants were determined at different temperatures from which the Gibb’s free energies were calculated. Arrhenius equation was used to calculate the enthalpy, entropy was similarly calculated. Results: Absorption maxima of CA in different solvents are as follows: Ethanol 310 nm; Acetonitrile 330 nm; Ethyl acetate 340 nm; Chloroform 350 nm and hexane 310 nm. The complex of CA and TEN in the different solvents are: Alcohol 525 nm, Acetonitrile 500 nm; Ethyl acetate 505 nm; Chloroform 510 nm and hexane 515 nm. For EMT complex absorption maxima are: Alcohol 510 nm; Acetonitrile 515 nm’ Ethyl acetate 520 nm’ Chloroform 505 nm and hexane 530 nm. Simultaneous quantitative recovery values for TEN are: Ethanol; 97.89% ± 1.21; Acetonitrile 101.17 V 1.51%; Ethyl acetate 96.55% ± 0.71%; Chloroform 99.11% ± 0.34% and hexane 98.03% ± 0.15%. For EMT the values are also: Ethanol: 98.92% ± 1.45%; Acetonitrile 100.471 ± 13; Ethyl acetate 97.06% ± 0.87%; Chloroform 99.31% ± 0.94% and Hexane 99.97% ± 1.63%. Stoichiometry of complexation showed a 1:1 ratio for both drugs. Equilibrium constants for TEN were highest in acetonitrile and least for Ethanol while for EMT, equilibrium constant was least for acetonitrile and highest in chloroform. Gibb’s free energy for TEN was least in ethanol and highest in acetonitrile. Gibb’s free energy for EMT was least in acetonitrile and highest in chloroform. Enthalpy for TEN was least in chloroform and highest in hexane. Similarly, the enthalpy for EMT was highest in chloroform and lowest in hexane. Conclusion: These results shows that solvent polarity influence charge transfer complexes in a non consistent fashion. The structure of the donor might have contributed to thermodynamics of complexation since orbital overlap may vary from solvent to solvent. For quantitative analysis hexane appears to be the most suitable solvent because it has the highest molar absorptivity and higher enthalpy of interactions. Molecules that can donate electrons and their stereochemistry could contribute to intensity of absorption maxima of the electronic transitions.
Cite this paper: J. Ogoda Onah, J. Eromi Odeiani and U. Ajima, "Influence of Solvent Polarity on the Physio-Chemical Properties and Quantitative Determinations of Tenofovir Disoproxil and Emtricitabine with Chloranilic Acid as Complexing Agent," Open Journal of Physical Chemistry, Vol. 3 No. 1, 2013, pp. 30-39. doi: 10.4236/ojpc.2013.31005.

[1]   R. S. Mulliken, “Molecular Complexes,” Journal of the American Chemical Society, Vol. 74, No. 3, 1952, pp. 811-813.doi:10.1021/ja01123a067

[2]   J. Weiss, “The Formation and Structure of Some Organic Compounds,” Journal of the Chemical Society, Vol. 65, 1942, pp. 245-247. doi:10.1039/jr9420000245

[3]   M. J. S. Dewar and C. C. Thompson, “Pi-Molecular Complexes III. A Critique of Charge-Transfer and Stability Constants for Some Tetracynoethylene-Hydrocarbon Complexes,” Tetrahedron, Vol. 22, Suppl. 7, 1966, pp 97-114. doi:10.1016/S0040-4020(01)99099-4

[4]   S. Moon and Park, “Charge-Transfer Complexes of Photochemically Interesting Organic Systems,” Texas Technical University, 1972, pp. 39-79.

[5]   R. Foster, “Organic Transfer Complexes,” Academic Press, London, 1969.

[6]   J. O. Onah and U. Ajima, “Quantitative Analysis of Tenofovir by Titrimetry, Extractive Ion-Pair Spectrophotometry and Charge-Transfer Complexation Methods,” Tropical Journal of Pharmaceutical Research, Vol. 10, No. 1, 2011, pp. 89-96.

[7]   M. U. Adikwu, K. C. Ofokansi and A. A. Attama, “Thermodynamic Studies of the Charge-Transfer Interaction of Chloranilic Acid with Moclobemide and Promethazine Hydrochloride,” Biological & Pharmaceutical Bulletin, Vol. 21, No. 12, 1998, pp. 1243-1246. doi:10.1248/bpb.21.1243

[8]   M. M. Ayad, S. F. Belal, M. S. El Adl and A. A. Al Kheir, “Spectrophotometric Determination of Some Corticosteroid Drugs through Charge-Transfer Complexation,” Analyst, Vol. 109, No. 11, 1984, pp. 1417-1422. doi:10.1039/an9840901417

[9]   F. A. Ibrahim, M. S. Rizk and F. Belal, “A Spectrophotometric Method for the Determination of Some Pharmaceutically Important Hydrazines and Pyrozoline Derivatives,” Analyst, Vol. 111, No. 11, 1986, pp. 1285-1288. doi:10.1039/an9861101285

[10]   M. U. Adikwu and K. C. Ofokansi, “Spectrophotometric Determination of Moclobemide by Charge-Transfer Complexation,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 16, No. 3, 1997, pp. 529-532. doi:10.1016/S0731-7085(97)00086-1

[11]   J. O. Onah and J. E. Odeiani, “Physico-Chemical Studies on the Charge-Transfer Complex Formed between Sulphadoxine and Pyrimethamine with Chloranilic Acid,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 29, No. 4, 2002, pp. 639-647. doi:10.1016/S0731-7085(02)00102-4

[12]   B. A. Benesi and J. Hildebrand, “Ultraviolet Absorption Bands of Iodine and Aromatic Hydrocarbons,” Journal of the American Chemical Society, Vol. 71, No. 8, 1949, pp. 1832-1833. doi:10.1021/ja01176a030

[13]   J. Grundnes, S. D. Christian, V. Cheam and S. B. Farnham, “Solvent Effects of Strong Charge-Transfer Complexes IV. Trimethylamine and Sulphur Dioxide in the Vapour Phase,” Journal of the American Chemical Society, Vol. 93, No. 1, 1971, pp 20-23. doi:10.1021/ja00730a003

[14]   M. S. Subhani, N. K. Bhatti, M. Mohammad and A. Y. Khan, “Spectrophotometric Studies of Charge-Transfer Complexes of 2,3-Dichloro-5.6-dcyano-pbenzoquinone,” Turkish Journal of Chemistry, Vol. 24, 2000, pp. 223-230.

[15]   J. O. Onah, “Thermodynamic and Analytical Studies on the Charge-Transfer Complex Formed between Chloranilic Acid and Derivative of Metronidazole,” Global Journal of Pure and Applied Sciences, Vol. 10, 2004, pp. 125-131.

[16]   L. A. Walker, S. Pullen, B. Donovan and J. Sension, “On the Structure of Iodine Charge-Transfer Complexes in Solution,” The Journal of Physical Chemistry Letters, Vol. 242, No. 1-2, 2000, pp. 177-183.