Designing of Eight-Coordinate Manganese(II) Complexes as Bio-Active Materials: Synthesis, X-Ray Crystal Structures, Spectroscopic, DFT, and Molecular Docking Studies

Abstract

Two new manganese(II) complexes based on bisaroylhydrazone derivatives: [MnII(L1)2(NO3)2] (1) and [MnII(L2)2(NO3)2] (2) were synthesized via the reaction of manganese (II) nitrate tetrahydrate with bisaroylhydrazone derivative in acetonitrile at room temperature. The synthesized organic ligands and manganese (II) complexes underwent thorough characterization, and their structures were elucidated using various techniques. The X-ray crystallography results confirmed that compounds 1 and 2 are mononuclear manganese (II) complexes, where the Mn(II) ion is eight-fold coordinated within a distorted pseudo-dodecahedral coordination environment. The coordination is achieved through the binding of the metal ion to N and O atoms of two bisaroylhydrazone molecules (bi-dentate ligands) and two nitrate ions. Furthermore, density functional theory (DFT) calculations were conducted to optimize the geometry of the complexes, generate molecular electrostatic potential (MEP) maps, and analyze vibrational spectra. Additionally, time-dependent DFT (TD-DFT) calculations were carried out to investigate their electronic transitions. In order to calculate the structure-activity relationship and binding energies for the most suitable conformation, bond between Mn(II) complexes and enzymes has been examined using molecular modeling software. In addition, in vitro enzyme inhibition and antimicrobial activity have been investigated. Moreover, pharmacokinetics and enzyme kinetic mechanism studies were performed. Molecular docking results suggested that our complexes have a high affinity for binding to the two selected enzymes. Enzymatic kinetics research findings strongly suggested that our molecules are noncompetitive urease inhibitors, suggesting that those substances may be able to withstand significant structural modification regardless of the design of the active site cavity and could be used as a lead candidate for the creation of novel urease inhibitors. Compound 1 showed a competitive inhibition for & alpha;-glucosidase enzyme, while compound 2 exhibited a noncompetitive inhibition. Antimicrobial activity study of L1, L2, 1, and 2 against some selected pathogenic bacteria showed good activity with respect to their MIC values. The ADME profile also demonstrated information on the compounds general properties, with some of the examined metrics showing a parameter from the expected range.