Complex formation of cetirizine drug with bivalent transition metal(II) ions in the presence of alanine: synthesis, characterization, equilibrium studies, and biological activity studies

Abstract

Mononuclear cobalt(II), nickel(II), and copper(II) complexes of cetirizine·2HCl (CTZ = 2-[2-[4-[(4-chlorophenyl)phenyl methyl]piperazine-1-yl]-ethoxy]acetic acid) in the presence of alanine (Ala) as a representative example of amino acids were synthesized and elucidated by different physical techniques. All complexes have been characterized with the help of elemental analyses, molecular weights, molar conductance values, magnetic moments, and spectroscopic data. The measured molar conductance values in DMSO indicate that the complexes are nonelectrolytes. Quantum chemical calculations were performed with semi-empirical method to find the optimum geometry of complexes. The metal–oxygen bond length in the synthesized complexes obeys the order M–OH₂ > M–O_CTZ > M–O_Ala. Formation equilibria of the ternary complexes have been investigated. Ternary complexes are formed by a simultaneous mechanism. Stoichiometry and stability constants for the complexes formed are reported. The concentration distributions of various species formed in solution were also evaluated as a function of pH. CTZ and its metal chelates have been screened for their antimicrobial activities against some selected types of gram-positive (G⁺) and gram-negative (G⁻) bacteria. They were more active against (G⁺) than (G⁻) bacteria.

The present article reports on the synthesis, characterization, and their electronic absorption spectra of M(II)–ternary complexes involving CTZ as antihistamine drug and alanine as a representative example of amino acids. The geometry of the studied M(II) complexes has been fully optimized using parameterized PM3 semi-empirical method. Protonation and complex formation equilibria were investigated. The antimicrobial activities were investigated.

Keywords:

• Cetirizine
• Potentiometry
• Alanine
• Molecular modeling
• Spectra
• Biological activity

Acknowledgement

The authors express their sincere thanks to the Northern Border University for financial support of the project number (435-077-8).