Pyrazinamide-based Co(II), Ni(II) and Cu(II) complexes: DFT exploration of structure, reactivity properties and in silico ADMET profiles

Context

In this paper, we present a theoretical study on the complexation of Co(II), Ni(II), and Cu(II) with a pyrazinamide ligand (PZA), which plays an important role in the treatment of tuberculosis and has biological and pharmacological benefits. It is a hybrid organic/inorganic material involving coordination between a metal ion and PZA ligand containing different coordination sites. This allows it to have different binding modes with metal ions and, therefore, provides a versatile ability to coordinate with metals. This study aimed to optimize the structures of the [M(PZA)₂Cl₂] complexes using density functional theory (DFT) at the B3LYP/6-311G + (d,p) level and the M06-2X functional is a high-nonlocality functional of double the amount of nonlocal exchange 2X. Various properties, including geometrical parameters, natural bonding orbital (NBO) to determine atomic charges, HOMO–LUMO energies, electronic properties, reactivity (ELF, LOL), NCI-RDG, and molecular electrostatic potential (MEP) on the surfaces of key metal-PZA complexes were determined and described. The AIM method has also been used to examine the chemical bonds. Furthermore, an in silico analysis aiming to explore the ADMET profiles of the compounds under investigation revealed promising aqueous solubility, oral bioavailability and gastrointestinal absorption, in addition to favorable druglikeness non-toxic and non-carcinogenic characteristics.

Methods

The DFT method was carried out using Gaussian 09 software and GaussView 5.0. Avogadro software was used to define the geometry of the complexes. The Multiwfn program was used to produce scatter plots of the reduced density gradient (RDG), non-covalent interactions (NCI), ELF, LOL, and to define the parameters selected for the topological analysis of the BCPs using Bader's AIM.