Mononuclear π-complexes of Pd(II) and Pt(II) with 1-allyl-3-(2-hydroxyethyl)thiourea: Synthesis, structure, molecular docking, DNA binding ability and genotoxic activity

Five π-complexes [M(HL)X₂] (M = Pd²⁺, Pt²⁺; X = Cl⁻, Br⁻, I⁻) have been obtained by the reactions of [MCl₄]²⁻ with 1-allyl-3-(2-hydroxyethyl)thiourea (HL) in the presence of HCl and/or KBr/KI. (Br/I)-Containing chelated π-type complexes of this type are presented for the first time. A comprehensive structural and spectral characterization has revealed an identical atomic arrangement, with the Cl- and Br-bearing phases adopting the same triclinic structure (space group P), while [Pt(HL)I₂] crystallizes in the monoclinic P2₁/n space group. The molecules of HL are coordinated in a bidentate manner with the formation of six-membered chelate metallocycles. The diagonal arrangement of “soft-hard” donor atoms (S–X, C–X) in the coordination sphere leads to Pearson's effect of “molecular antisymbiosis in the trans effect” that causes the interaction of M:L in a ratio of 1:1. The similarity of the structures of the synthesized complexes with that of cisplatin implies the same mechanism for their antitumor action, whilst different halide anions in the coordination sphere of the metal affects the cytotoxic activity of the complexes. Among the new cisplatin analogues, two of the platinum π-complexes are promising compounds, the action of which slows or completely stops cell division, causes a decrease in nucleus size and increases the proportion of heterochromatin in the structure of interphase nuclei, thus reducing the activity of transcriptional processes. A molecular docking study showed that the general mechanism of action for the complexes can be characterized by the formation of single and double-stranded breaks of DNA plasmid. The presence of the OH-group has a positive impact on the “ligand – DNA binding”.