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

Spectrochim Acta A Mol Biomol Spectrosc. 2012 Aug:94:243-55. doi: 10.1016/j.saa.2012.03.055. Epub 2012 Mar 29.

Abstract

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 (1)H 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / drug effects
  • Cattle
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism*
  • Coordination Complexes / pharmacology
  • DNA / metabolism*
  • DNA / ultrastructure
  • Electricity
  • Electrochemical Techniques / methods*
  • Electrodes
  • Fungi / drug effects
  • Graphite / chemistry
  • Hydrogen-Ion Concentration / drug effects
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Oxidation-Reduction / drug effects
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Surface Properties / drug effects
  • Temperature*
  • Trimethoprim / chemical synthesis*
  • Trimethoprim / chemistry
  • Trimethoprim / metabolism*
  • Trimethoprim / pharmacology

Substances

  • Coordination Complexes
  • Graphite
  • DNA
  • calf thymus DNA
  • Trimethoprim