Novel ruthenium(iii) complexes with hydroxybenzophenones: experimental and theoretical characterization and in vitro leishmanicidal activity comparing complexes and ligands

Abstract

In this study, novel ruthenium(III) complexes with hydroxybenzophenones with the general formula cis-[RuCl2(HB)(dppb)] were obtained, where HB = 2-hydroxy-4-(octyloxy)benzophenone (C1), 2-hydroxy-4-methoxybenzophenone (C2), 2,2′-dihydroxy-4,4′-dimethoxybenzophenone (C3), 2,2′-dihydroxy-4-methoxybenzophenone (C4), 2,4-dihydroxybenzophenone (C5), and 2,4,4′-trihydroxybenzophenone (C6), and dppb = 1,4-bis(diphenylphosphine)butane. These compounds were characterized by elemental analysis, molar conductivity, cyclic voltammetry, infrared and UV-vis spectroscopy, and powder X-ray diffraction. The crystal structures of C2, C3, C4, and C5 were determined by single-crystal X-ray diffraction analysis which confirmed the bidentate coordination of the carbonyl and phenolate oxygens of HB with ruthenium(III). Additionally, the cis geometry and electronic transitions of C1–C6 were investigated using DFT calculations. Finally, the comparative activity against promastigote forms of L. amazonensis was made available for the ligands HB1–HB6 and C1–C6. The ligands significantly inhibited the proliferation of promastigote forms, confirming the results previously published by some of us. Unfortunately, their respective complexes showed no activity. It is important to emphasize that the leishmanicidal activity of 2,2′-dihydroxy-4,4′-dimethoxybenzophenone (HB3), 2,2′-dihydroxy-4-methoxybenzophenone (HB4), and 2,4,4′-trihydroxybenzophenone (HB6) ligands is reported here for the first time. Despite the fact that they were less active against promastigote forms when compared to amphotericin B, two of them (HB4 and HB6) were less cytotoxic to J774 macrophages.