Synthesis of the Three Mixed-Ligand Metal Complexes and One Organic Salt of 3,5-Dinitrobenzoic Acid for Biopharmaceutical Optimization Through Monoethanol-Amine. Structures and Dft Studies of Complexes

Abstract

The simplest derivatives of benzoic acid show a wide spectrum of the biological action mostly being poor water soluble. In order to demonstrate on example of 3,5-dinitrobenzoic acid (DNBA) a possibility of the simultaneous enhancement of water solubility and antimicrobial activity the complexation (salt formation and metal coordination) approach has been examined. Monoethanolamine (MEA) is selected as the complexing agent. Three isomorphic mixed-ligand complexes of Cu, Ni, Co with DNBA and MEA as well one organic salt in the polymorphic form have been synthesized and their structures are characterized by the element analysis, FTIR and X-ray crystallography. Measurements of water solubility and determination of the antimicrobial activity attest that a solubility of the copper mixed-ligand complex and organic salt is increased about 4 and 8 times with simultaneous enhancement of the bioactivity. The DFT studies by B3LYP/def2-TZVP and B3LYP/6-311G(d,p) showed that Cu, Ni, and Co complexes with DNBA and MEA have high-spin ground electronic states as a doublet, triplet and quartet, respectively. Calculated bond lengths and bond angles of all metal complexes in higher-spin ground electronic states are in good agreement (about R 2 =0.97) with X-ray data. Additionally, the energies of the frontier MOs and frontier electron densities and also electrostatic potential of isostructural complexes have been analyzed by the DFT/6-311G(d,p) method.

Keywords: 1. Metal complex2. Organic salt 3. X-ray structure4. Bioactivity5. DFT study