Novel isatin-based complexes of Mn(II) and Cu(II) ions: Characterization, homogeneous catalysts for sulfides oxidation, bioactivity screening and theoretical implementations via DFT and pharmacokinetic studies

Two mononuclear manganese(II) and copper(II) complexes were prepared from the coordination of 3,5-di-tert-butyl isatin hydrazone derivative (HLOEt) with either 2 : 1 or 1 : 1 M ratio for Mn(II) or Cu(II) ion, within octahedral and square planar geometries (Mn(LOEt)(2) and CuLOEt), respectively. The catalytic potential of both M(II)-complexes was evaluated in the oxidation of sulfides, i.e. diphenyl sulfide (DPS) and methylphenyl sulfide (MPS), by tert-butyl hydroperoxide ((BuOOH)-Bu-t) in acetonitrile. The chemo- and regio-selectivity of the redox system was determined by formation of mono-oxoproducts, diphenyl sufoxide (DPO) and methylphenyl sulfoxide (MPO), with detection of further products of mainly dioxide-product of diphenyl sufone (DPN) and methylphenyl sulfone (MPN). With Mn(LOEt)(2), the reaction gave 55 and 54% (ee, 79% of S and 21% of R) yields of DPO and MPO, respectively. The catalytic activity of CuLOEt was slightly more progressed than that of Mn(LOEt)(2), which awarded 52 and 56% (ee, 83% of S and 17% of R) percentages of DPO and MPO, respectively. The higher catalytic reactivity of CuLOEt catalyst was based on their geometrical structures to facilitate the approach of the oxidant and substrate in the redox systems. Their reactivity was studied against some common strains of bacteria and fungi. Moreover, their bio-potential was explored as anticancer reagents versus some human cancer cell lines. Both M(II)-complexes exhibited high biological action against the microorganism and cancer growth. The effect of M(II) ion in thier complexes was examined through the interaction of with ctDNA (calf thymus DNA). Such interaction was tested spectroscopically and via changes in ctDNA viscosity. The reactivity was measured by the binding constant values (K-b = 3.19, 13.85 and 15.39 x 10(8) mol(-1) dm(3) for HLOEt, Mn(LOEt)(2) and CuLOEt, respectively), which reflects high interaction with ctDNA. Furthermore, the Gibbs' free energy values supported their high potential against ctNDA, with -1.24, -1.36 and -1.37 kJ mol(-1), respectively. Furthermore, HLOEt, CuLOEt and Mn(LOEt)(2) were optimized by DFT/B3LYP method under either of 6-31G* of SDD basis set to estimate the essential physical characteristics. On the other hand, in silico approaches were utilized through online software as Swiss-ADME and Pharmacophore beside the molecular docking program. Pharmacokinetic, drug-likeness and the interaction with iso-enzymes were investigated for CuLOEt complex versus receptor tyrosine kinase (2a91, 2src) and human oestrogen receptor (2iok, 4rj3), as well as, liver cancer cells via 6jxt and (PCSK9) Proprotein Convertase Subtilisin/Kexin type 9 (4nmx, 4ne9). Only the proteins 4nmx and 4ne9 from liver cancer cells were found to be effectively inhibited by CuLOEt complex. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, two mononuclear manganese and copper complexes were synthesized and evaluated for their catalytic activity in the oxidation of sulfides. The copper complex showed higher catalytic activity and exhibited good interactions with DNA and liver cancer cells. These findings are important for the further development of anticancer and antimicrobial drugs.