Synthesis of new Cr(III) complexes derived from antipyrine-based ligands: Elucidation, conformation, cytotoxicity and genotoxicity via in-vitro and in-silico approaches

Abstract

• Novel antipyrine-based ligands were used to synthesize their Cr(III) complexes. • The new complexes were structurally elucidated by analytical, spectral and modeling tools. • The cytotoxicity and genotoxicity were tested for the new compounds. • In silico ways were used to confirm the practical results. Two antipyrine-based ligands were prepared and characterized to synthesize such new Cr(III) complexes; [Cr(OAc)(CA)].(OAc).2H 2 O and [Cr(OAc)(AOB)].(OAc).H 2 O. The formulae of such complexes were elucidated from elemental, IR, UV–Vis, Mass, thermogravimetric (TGA), XRD, SEM, and EDX analysis. Both of the ligands coordinated as a neutral bidentate towards the Cr(III) ion through (C = O) 1 and (C = O) amide groups. The ligand field transitions within the two complexes were assigned to 4 A 2 g(F)→ 4 T 1 g (F)(υ 3 ) and 4 A 2 g(F)→ 4 T 2 g(F)(υ 2 ) types. The octahedral geometry was suggested for the two complexes and further optimized by an advanced quantum-based program (Gaussian 09) under 6-31G* basis set. The high nucleophilic feature recorded for O(6) and O(8) donors supports their priority in coordination with chromium ion. The calculated reactivity indexes assert on the favorable bioactivity of [Cr(OAc)(CA)].(OAc).2H 2 O complex. Regarding liver (HepG-2) and prostate (PC3) cancer cells, interestingly this complex showed so high cytotoxicity which exceeds the standard drug (5-FU). In addition, the genomic action recorded for such complex by agarose-gel electrophoresis, indicating its effective impact on pathogen growth. For verification, we examined the studied compounds in- silico towards 1jnx and 7jx9 proteins of DNA-polymerase enzyme and liver cancer cell, respectively. According to docking criteria, we expect an excellent inhibiting role of [Cr(OAc)(CA)].(OAc).2H 2 O complex against DNA-polymerase enzyme. While, the excellent inhibiting role of [Cr(OAc)(AOB)]. (OAc).H 2 O complex was expected versus liver cancer cells. This outcomes coincide with the practical results obtained, indicating the high credibility of silico tools used in this investigation.