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

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.