Rational design of [Co(acacen)L2]+ inhibitors of protein function

摘要: Cobalt(III) Schiff base complexes, such as [Co(acacen)L2]+, inhibit the function of Zn(II)-dependent proteins through dissociative exchange axial ligands with key histidine residues target protein. Consequently efficacy these compounds depends strongly on lability ligands. A series [Co(acacen)L2]+ complexes various was investigated using DFT to determine kinetics and thermodynamics ligand hydrolysis. Results showed excellent agreement experimental data, indicating that is determined by several factors: pKa ligand, kinetic barrier dissociation, relative thermodynamic stability before after exchange. Hammett plots were constructed if can be modulated addition an electron-withdrawing group (EWG) either itself or equatorial acacen ligand. predict EWG will shift so promote exchange, while decrease lability. These investigations aid in design next generation [Co(acacen)L2]2+, allowing researchers develop new, more effective inhibitors.