Synthesis of trimethoprim metal complexes: Spectral, electrochemical, thermal, DNA-binding and surface morphology studies

Complexes of trimethoprim (TMP), with Cu(II), Zn(II), Pt(II), Ru(III) and Fe(III) have been synthesized. Then, these complexes have been characterized by spectroscopic techniques involving UV–vis, IR, mass and 1H NMR. CHN elemental analysis, electrochemical and thermal behavior of complexes have also been investigated. The electrochemical properties of all complexes have been investigated by cyclic voltammetry (CV) using glassy carbon electrode. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV spectroscopy and cyclic voltammetry. UV studies of the interaction of the complexes with DNA have shown that these compounds can bind to CT DNA. The binding constants of the complexes with CT DNA have also been calculated. The cyclic voltammograms of the complexes in the presence of CT DNA have shown that the complexes can bind to CT DNA by both the intercalative and the electrostatic binding mode. The antimicrobial activity of these complexes has been evaluated against three Gram-positive and four Gram-negative bacteria. Antifungal activity against two different fungi has been evaluated and compared with the reference drug TMP. Almost all types of complexes show excellent activity against all type of bacteria and fungi. The morphology of the CT DNA, TMP, metal ions and metal complexes has been investigated by scanning electron microscopy (SEM). To get the SEM images, the interaction of compounds with CT DNA has been studied by means of differential pulse voltammetry (DPV) at CT DNA modified pencil graphite electrode (PGE). The decrease in intensity of the guanine oxidation signals has been used as an indicator for the interaction mechanism.

Graphical abstractUV spectra of [Cu(Cl)2(TMP)] in buffer solution in the presence of CT DNA at increasing amounts. [Cu(Cl)2(TMP)] = 1 × 10−5 M. The arrow shows the intensity changes upon increasing concentration of CT DNA.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Mononuclear metal(II/III) complexes of trimethoprim were synthesized and characterized by elemental analyses, FT-IR, 1H NMR, electronic and atomic absorption spectra, molar conductance and mass spectral data. ► The resultant mononuclear complexes were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). ► The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV spectroscopy, cyclic and differential pulse voltammetry. ► Antibacterial and antifungal properties of TMP and complexes were studied against both Gram-positive and Gram-negative bacteria. ► The morphology of the CT DNA, TMP, metal ions and metal complexes were investigated by scanning electron microscopy (SEM).