New copper(II) thiohydantoin complexes: Synthesis, characterization, and assessment of their interaction with bovine serum albumin and DNA

Abstract

New copper(II) complexes of 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones: (5Z)-2-(methylsulfanyl)-3-(prop-2-en-1-yl)-5-(pyridin-2-ylmethylidene)-3,5-dihydro-4H-imidazol-4-one) (1a), (5Z,5'Z)-2,2'-(ethan-1,2-diyldisulfanyldiyl)bis(5-(2-pyridilmethylen)-3-allyl-3,5-dihydo-4Н-imidazole-4-one) (2a) and (5Z,5'Z)-3,3'-hexan-1,6-diylbis[5-(2-pyridilmethylen)-2-methylthiotetrahydro-4Н-imidazole-4-one)] (3a) were synthesized as possible anticancer drugs. Their structures were characterized by ¹H NMR spectroscopy, elemental analysis, and X-ray crystallography. The composition of the complexes were found for 1a (Cu:L=1:1), 2a (Cu:L=2:1), and 3a (Cu:L=2:1). The chelation constants were found by competitive complexation with ethylenediamine tetraacetate: 1a (6.7±0.6)×10¹⁵M^-1, 2a=(4.9±0.4)×10¹⁹M^-2, and 3a (5.7±0.5)×10¹⁹M^-2. Supramolecular binding with calf thymus DNA by competitive ethidium bromide quenching was made for complex 2a as the most promising anticancer model, the Stern-Volmer constants were found to be K_SV=(8.0±0.4)×10⁶M^-1, K_q=(6.5±0.4)×10⁵M^-1. The binding of the complex 2a to BSA was made by the Scatchard method, the value of the constant is K_b=(1.9±0.2)×10⁶M^-1.

Keywords: 2-Alkylthio-5-arylmethylene-4H-imidazolin-4-one; BSA conjugation; Calf thymus DNA intercalation; Copper(II); Stability constant; Thiohydantoin.