Platinum(II) dithiocarbamate complexes [Pt(S₂CNR₂)Cl(PAr₃)] as anticancer and DNA-damaging agents

Following the fortunate discovery of cisplatin as an anti-cancer drug the search for new effective Pt-containing analogues with high potency but reduced side effects and resistance is of great importance. Herein, we report four new monofunctional platinum(II) dithiocarbamate complexes, [Pt(S₂CNR₂)Cl(PAr₃)], and their activity against selected cancer cell lines. DFT-optimized structures reveal steric hindrance, similar to phenanthriplatin, from an axial C[sbnd]H site of the triarylphosphine. High activity against selected cancer cell lines, MCF-7 > LU > Hepa-IcIc7, can be attributed to the axial protection offered by the aromatic C[sbnd]H moiety, together with the lipophilicity and formation of bulkier and more hydrophobic DNA adducts. DNA binding, denaturing and plasmid cleavage studies demonstrate their potential to cleave DNA via electrostatic or covalent interactions. DFT and experimental studies show the ability to replace chloride with different nucleophiles; substitution with smaller nucleophiles being fast while with larger nucleophiles is slow.