Isothiocyanate l-argininato copper(II) complexes - Solution structure, DNA interaction, anticancer and antimicrobial activity

Chem Biol Interact. 2021 Oct 1:348:109636. doi: 10.1016/j.cbi.2021.109636. Epub 2021 Sep 8.

Abstract

l-argininato copper(II) complexes have been intensively investigated in a variety of diseases due to their therapeutic potential. Here we report the results of comprehensive structural studies (ESI-MS, NIR-VIS-UV, EPR) on the complexes arising in aqueous solutions of two ternary copper(II) complexes with molecular formulas from crystal structures, [Cu(l-Arg)2(NCS)](NCS)·H2O (1) and [Cu(l-Arg)(NCS)2] (2) (l-Arg = l-arginine). Reference systems, the ternary Cu(II)/l-Arg/NCS- as well as binary Cu(II)/NCS- and Cu(II)/l-Arg, were studied in parallel in aqueous solutions by pH-potentiometric titration, EPR and VIS spectroscopy to characterize stability, structures and speciation of the formed species over the broad pH range. Comparative analysis of the obtained results showed that at a pH close to 7.0 mononuclear [Cu(l-Arg)2(NCS)]+ is the only species in water solution of 1, while equilibrium between [Cu(l-Arg)(SCN)]+ and binary [Cu(l-Arg)2]2+ was detected in water solution of 2. According to DNA binding studies, the [Cu(l-Arg)2(NCS)]+, [Cu(l-Arg)(SCN)]+ and [Cu(l-Arg)2]2+ species could be considered as strong minor groove binding agents causing, in the presence of H2O2, the involvement of ROS in plasmid damage. The human carcinoma cells (A549 cell line) were generally significantly more sensitive to cytotoxic and antiproliferative effect of compounds 1 and 2 than human normal cells. The studied compounds shown antimicrobial activity against bacteria belonging to Enterobacteriaceae family.

Keywords: Antimicrobial properties; Cytotoxic and antiproliferative potential; Free radicals; Isothiocyanate ions; NIR−Vis−UV and EPR spectroscopies; Potentiometric; l−Arginine.

MeSH terms

  • A549 Cells
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Coordination Complexes / chemistry*
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • Copper / chemistry*
  • DNA / metabolism*
  • Humans
  • Isothiocyanates / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Solutions

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Coordination Complexes
  • Isothiocyanates
  • Solutions
  • isothiocyanic acid
  • Copper
  • DNA