Ru(II)‐Nitrophenylhydrazine/Chlorophenylhydrazine Complexes: Nanoarchitectonics, Biological Evaluation and In silico Study

Abstract Ru(II)‐arene compounds are being investigated as anticancer agents due to the biocompatibility of ruthenium and their structural diversity. Two newly synthesized Ru(II) complexes, RuCl(η 6 ‐ p ‐cymene)(3‐DNPH) (chlorido(η 6 ‐ p ‐cymene)(3‐nitrophenylhydrazine‐k 2 N , N ′)ruthenium(II)) ( 1 ) and RuCl(η 6 ‐ p ‐cymene)(3‐CNPH) (chlorido(3‐chlorophenylhydrazine‐k 2 N , N ′)(η 6 ‐ p ‐cymene)ruthenium(II)) ( 2 ), are experimentally (IR, NMR) and theoretically (B3LYP/6‐31+G(d,p)(H,C,N,Cl)/LanL2DZ(Ru)) characterized. Experimental and theoretical values of 1 H and 13 C chemical shifts and position of the most intense vibrational bands showed high correlation coefficients and low mean absolute errors, proving the predicted structure and applicability of the selected level of theory. Cell viability studies performed on MDA‐MB‐468, BT‐474, and PC3 cells using MTT and CV assay indicated the activity of the second complex similar to the activity of cisplatin towards BT‐474 breast cancer cells. The spectrofluorimetric measurements of Bovine Serum Albumin showed the binding process‘s spontaneity of complexes and protein, with a binding energy of around −30 kJ mol −1 . Detailed molecular docking analysis allowed the elucidation of the binding mechanism through specific intermolecular interactions. Both compounds showed a higher affinity towards BSA than naproxen and cisplatin. Molecular docking simulations proved the spontaneity of the complexes binding to DNA. Based on these promising results, further biological examinations of these compounds are advised.