Synthesis, characterization, and binding properties towards CT-DNA and lipoxygenase of mixed-ligand silver(I) complexes with 2-mercaptothiazole and its derivatives and triphenylphosphine

Abstract

Mixed-ligand silver(I) complexes of formulae [AgCl(TPP)2(MTZD)] (1), {[AgCl(TPP)2(MBZT)]·(MBZT)·2(toluene)} (2), and [AgCl(TPP)2(CMBZT)] (3) were obtained by refluxing toluene solutions of silver(I) chloride with triphenylphosphine (TPP) and the appropriate heterocyclic thioamides 2-mercaptothiazolidine (MTZD), 2-mercaptobenzothiazole (MBZT), and 5-chloro-2-mercaptobenzothiazole (CMBZT). The complexes were characterized by the melting point, vibrational spectroscopy (Fourier transform mid-IR), 1H-NMR spectroscopy, UV–vis spectroscopy, and X-ray crystallography. DNA binding tests indicate the ability of complexes 1–3 to modify the activity of cells. The binding constants of 1–3 towards calf-thymus DNA (CT-DNA) [(3.5 ± 8.5) × 104 M−1 for 1, (10.0 ± 0.0) × 104 M−1 for 2, and (46.4 ± 7.0) × 104 M−1 for 3] indicate strong interaction of 3. Changes in the fluorescence of ethidium bromide in the presence of DNA suggest intercalation into or electrostatic interactions with DNA. The corresponding apparent binding constants (K app) towards CT-DNA calculated through fluorescence spectra are (3.5 ± 0.7) × 104 M−1 for 1, (10.0 ± 0.0) × 104 M−1 for 2, and (46.4 ± 7.0) × 104 M−1 for 3. Docking studies on DNA complexes confirm the binding of 1 and 2 in the major groove of CT-DNA and of 3 in the minor groove. Moreover, the influence of 1–3 on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase was studied kinetically and theoretically. The antibacterial effect of 1–3 against the bacterial species Pseudomonas aeruginosa and Escherichia coli was evaluated. Complex 1 exhibits the strongest activity. The silver(I) chloride complexes [AgCl(TPP)2(MTZD)] (1), {[AgCl(TPP)2(MBZT)]·(MBZT)·2(toluene)} (2), and [AgCl(TPP)2(CMBZT)] (3), where TPP is triphenylphosphine, MTZD is 2-mercaptothiazolidine, MBZT is 2-mercaptobenzothiazole, and CMBZT is 5-chloro-2-mercaptobenzothiazole, were structurally characterized. The binding affinity of 1–3 towards the intracellular molecules calf-thymus DNA and lipoxygenase were studied to determine the ability of complexes 1–3 to modify the activity of cells.

DOI: 10.1007/s00775-014-1089-6

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@article{Kyros2014SynthesisCA, title={Synthesis, characterization, and binding properties towards CT-DNA and lipoxygenase of mixed-ligand silver(I) complexes with 2-mercaptothiazole and its derivatives and triphenylphosphine}, author={Loukas Kyros and Christina N Banti and Nikolaos Kourkoumelis and Maciej Kubicki and Ioannis Sainis and S. K. Hadjikakou}, journal={JBIC Journal of Biological Inorganic Chemistry}, year={2014}, volume={19}, pages={449-464} }