Synthesis, X-ray structure, in silico calculation, and carbonic anhydrase inhibitory properties of benzylimidazole metal complexes

Abstract

Three coordination compounds of formula {M(bmim)2Cl2} were synthetised (M = Co, Zn, and Hg) and fully characterised. Each complex incorporates 1-benzyl-2-methylimidazole (bmim) as ligand. The coordination polyhedron around the metal center for all complexes has a quasi-regular tetragonal geometry. Density functional theory calculations were carried out on the title compounds and as well on hypothetical complexes (Cu, Ni), in order to elucidate their electronic and molecular structure. The calculations reproduced the Co, Zn, and Hg experimental structures and could predict stable complexes in the case of Ni(II) and Cu(II) ions. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the three complexes were investigated. Only compound {Hg(bmim)2Cl2} (3) exhibited a modest inhibitory effect against hCA I, probably due to the affinity of Hg(II) for His residues at the entrance of the active site cavity.

Synthesis, Crystal Structure, Inhibitory Activity and Molecular Docking of Coumarins/Sulfonamides Containing Triazolyl Pyridine Moiety as Potent Selective Carbonic Anhydrase IX and XII Inhibitors

“…The initial geometries of the synthesized compounds were taken from the Xray structures and were optimized by the DFT method to minimize energy using the GAUSSIAN-09 program [49]. In the case of the two rhenium compounds, DFT methods were used to give correct results for transition metal-containing systems [50]. Among the different density function methods, the hybrid B3LYP [51,52] proves to be a suitable choice for fac-Re(CO) 3 complexes specifically.…”

New triorganotin(iv) compounds with aromatic carboxylate ligands: synthesis and evaluation of the pro-apoptotic mechanism

“…23 Tin metal complexes have been shown to induce caspase dependent apoptosis in cancer cells. 24 Metal complexes have largely been employed in medicinal chemistry as bioactive molecules which are effective carbonic anhydrase inhibitors, 25 antimicrobial, 26 and anticancer 27 agents. Various metals can be used to achieve libraries of these metallodrugs with structural diversities.…”

A novel class for carbonic anhydrases inhibitors and evaluation of their non‐zinc binding

“…[ 37 ] D'Ambrosio et al [ 38 ] reported the first structural information on the CA inhibition mechanism of catechol, showing that they adopt a peculiar binding mode to the enzyme active site, involving the zinc‐bound water molecule and the “deep water.” Besides organic compounds, some of the organometallic complex structures were also investigated for their inhibition potential against hCAs. Bouchouit et al, [ 39 ] Alyar and Adem, [ 40 ] and Ul‐Hassan et al [ 41 ] reported some metal complexes with organic structures for hCAs inhibitions. Ghiasi and her co‐workers also investigated the theoretical modeling of the complex structure of CA and ligands.…”

“…Besides organic compounds, some of the organometallic complex structures were also investigated for their inhibition potential against hCAs. Bouchouit et al, [39] Alyar and Adem, [40] and Ul-Hassan et al [41] reported some metal complexes with organic structures for hCAs inhibitions. Ghiasi and her co-workers also investigated the theoretical modeling of the complex structure of CA and ligands.…”