Tazarotene copper complexes: Synthesis, crystal structure, DFT and biological activity evaluation

Abstract

New mononuclear copper(II) complexes of the first topical receptor-selective retinoid drug, Tazarotene (Tz), of the type [Cu(Tz)2X2] (X=Cl (1) and Br (2a)) were synthesized, characterized (elemental analysis, TG, FT IR, UV–Vis, EPR, magnetic susceptibility, molar conductance measurements and single crystal X-ray analysis) and tested for their antimicrobial activities against Staphylococcus aureus and Escherichia coli. Tazarotene behaves as a neutral monodentate ligand via the pyridine nitrogen atom. Complex 1 crystallizes in the monoclinic P21/c space group. The environment around the metal center in 1 could be described as an intermediate between tetrahedral and square–planar geometries. Crystals of the polymeric {[Cu(Tz)(μ-Br)]}n (2b) complex were obtained by the slow evaporation of the reaction filtrate of complex 2a. The distorted tetrahedral environment around Cu(I) is formed from the pyridine N atom of Tz, the S atom of another Tz molecule as well as two bridged bromine atoms, with a Cu…Cu′ distance of 3.327Å. Time-dependent density functional theory calculations were carried out to understand the electronic structure and to explain the related experimental findings. The electronic arrangement, type of hybridization and nature of bonding were obtained from natural bond orbital analysis.