PROTOLITICAL EQUILIBRIA 3-(TRIFLUOROACETHYL) IMIDAZO [1,2-a] PYRIMIDINE IN MICELLAR SOLUTIONS OF ANIONIC AND ZWITTERIONIC SURFACTANTS

Authors

DOI:

https://doi.org/10.11603/2312-0967.2019.2.10181

Keywords:

imidazole derivative, dissociation constant, micellar solutions of surfactants (surfactants), absorption spectra

Abstract

The aim of the work. To research of the protolytic properties and spectral characteristics of the first synthesized 3-(trifluoroacetyl)imidazo[1,2-a] pyrimidine, promising as antifungal agent, in micellar solutions of anionic and zwitterionic surfactants.

Materials and methods of research. The standard spectrophotometric method with potentiometric control of the pH of the aqueous phase was used in the work.

Results and discussion. There are two protolytic equilibria in the aqueous solutions of 3-(trifluoroacetyl)imidazo[1,2-a] pyrimidine: in the alkaline solutions, a molecular deprotonated form R is observed; the HR+ form exists in the range of pH from 7 to 4, dikation H2R2+ appears in a strongly acidic medium (pH <1).

The acid-base properties and spectral characteristics of the new derivative imidazole in micellar solutions of surfactants have been investigated in this work: anionic surfactant - sodium n-dodecyl sulfate (н-C12H25OSO3Na, CMC ~ 8´*10–3 М) and a zwitterionic surfactant - cetyldimethylammoniumpropanesulfonate (C16H33N(CH3)2(CH2)3SO3-, CMC ~ 5´*10–5 М).

The constants of the stepwise dissociation of substance in water and the "apparent" constants of dissociation in the micellar systems are calculated.

The results showed that in the micellar solutions of anionic surfactants the constants of dissociation are increased in comparison with aqueous solutions due to the additional contribution of the electrostatic component of the micellar surface which binds by the substrate. In the micellar solutions of the zwitterionic surfactant, the values of the dissociation constants of the test substance slightly change in comparison with the aqueous solutions, indicating a low distribution of the imidazole derivative between the aqueous phase and the micellar pseudo-phase, because of the neutral surface of the micelle of the zirconium surfactant.

Conclusions. The acid-base and spectral characteristics of the first synthesized 3- (trifluoroacetyl)imidazo[1,2-a]pyrimidine, promising as an antifungal agent, in water and in micellar solutions of anionic and zwitterionic surfactants were investigated. The constants of the stepwise dissociation of substance in all investigated systems were calculated.

Author Biographies

O. O. Zavada, Kharkiv National Medical University

PhD (Pharmacy), Senior teacher of Medical and Bioorganic Chemistry Department

N. О. Vodolazka, V. Karazin Kharkiv National University

DS (Chemistry), Professor, Professor of the Physical Chemistry Department

I. O. Zhuravel, Kharkiv Medical Academy of Postgraduate Education

DS (Chemistry), Professor, Chief of Clinical biochemistry, forensic medical toxicology and pharmacy Department

References

Grujić M., Popović M., Popović G. Nikolic, Agbaba D. Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants. Journal of Pharmaceutical Sciences. 2016;105(8):2444-52. DOI:10.1016/j.xphs.2016.06.007. DOI: https://doi.org/10.1016/j.xphs.2016.06.007

Popović-Nikolic M.R., Popovic G. V., Agbaba D. D. The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid-Base Equilibria of Verapamil. J. Chem. Eng. Data. 2017; 62 (6):1776–81. DOI: 10.1021/acs.jced.6b00864. DOI: https://doi.org/10.1021/acs.jced.6b00864

Vodolazkaya N.A., Mchedlov-Petrossyan N.O. [Acid-base equilibrium indicator dyes in organized solutions]. Kh. : KhNU im. V. N. Karazyna. 2014; 460 p. Ukrainian.

Popovic M. R, Popovic G.V., Agbaba D. D. The Effects of Anionic, Cationic, and Nonionic Surfactants on Acid–Base Equilibria of ACE Inhibitors . J. Chem. Eng. Data. 2013;58(9):2567-73. DOI: 10.1021/je400397p. DOI: https://doi.org/10.1021/je400397p

Abdel-Fattah L., Abdel-Aziz L., Gaied M. Enhanced spectrophotometric determination of Losartan potassium based on its physicochemical interaction with cationic surfactant. Spectrochimica Acta Part: Molecular and Biomolecular Spectroscopy. 2015;136:178-84. DOI:10.1016/j.saa.2014.09.007 DOI: https://doi.org/10.1016/j.saa.2014.09.007

Zavada O.O., Borysov O. V., Shherbak O. M., Zhuravel I. O., Kovalenko S. M. [Synthesis and study of derivatives of imidazo [1,2-a] pyrimidine as potential antifungal agents] Ukr biopharmac journ. 2013;5(28):50-4. Ukrainian.

Mchedlov-Petrossyan N.O. [Differentiation of the strength of organic acids in true and organized solutions] Kh. : KhNU im. V. N. Karazyna. 2004; 322 p. Ukrainian.

N. A. Vodolazkaya, Yu. V. Ysaenko, S. T. Goga. [Ultramicroheterogeneous systems, their effect on acid-base equilibria and solvatochromic properties of indicators: proc. Allowance] Kh. : KhNU im. V. N. Karazyna. 2006; 64 p. Ukrainian.

Zavada O.O., Gusarov V. I., Gubar S. M., Zhuravel I. O., Kovalenko S. M.

[Development and validation of the method of determination of the accompanying impurities in the substance 3- (trifluoroacetyl) imidazo [1,2-a] pyrimidine at the stage of pharmaceutical preparation of the drug] Upr., ekonomika ta zabezp. yakosti v farmaciyi. 2013;5(31):4-8.

Mchedlov-Petrossyan N.O., Vodolazkaya N.A., Gurina Yu.A., Sun W.-C., Gee K.R. Medium effects on the prototropic equilibria of fluorescein fluoro derivatives in true and organized solution. J. Phys. Chem. 2010;114(13):4551-64. DOI: 10.1021/jp909854s. Ukrainian. DOI: https://doi.org/10.1021/jp909854s

Mchedlov-Petrossyan N.O., Vodolazkaya N.A., Kamneva N.N. Acid-base equilibrium in aqueous micellar solutions of surfactants. In: Micelles: Structural Biochemistry, Formation and Functions and Usage.2013.N. Y.: Nova Publishers, 2013; 321 p. Ukrainian.

Vodolazkaya N.A. [Acid-base and tautomeric equilibria of fluorescein in mixed micelles of zwitterionic sulfobetaine surfactant with cationic, anionic and non-ionic surfactant] Xymyya, fyzyka y texnologyya poverxnosty. 2014;5(1):64-73. Ukrainian.

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Published

2019-06-12

How to Cite

Zavada, O. O., Vodolazka N. О., & Zhuravel, I. O. (2019). PROTOLITICAL EQUILIBRIA 3-(TRIFLUOROACETHYL) IMIDAZO [1,2-a] PYRIMIDINE IN MICELLAR SOLUTIONS OF ANIONIC AND ZWITTERIONIC SURFACTANTS. Pharmaceutical Review Farmacevtičnij časopis, (2), 43–51. https://doi.org/10.11603/2312-0967.2019.2.10181

Issue

No. 2 (2019)

Section

Analysis of drugs

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