Synthesis And Biological Evaluation Of Schiff Base Metal Complexes With O,N,O-tridentate Ligands As Urease Inhibitors

Crystal engineering is considered an important option in designing new urease inhibition.It not only find a relation between crystal structure and required properties such as a higherdissolution rate, a requested melting temperature, lower toxicity, less hygroscopic, bettercompressibility, and many others, it is also important to be able to learn how to producedesirable structures. The transition metal complexes of Schiff base have become an importantpart of chemistry as it together with the coordination versatility of the inorganic along withthe functional variety of the organic, and they are of interest since their applications inbiological activities, antifertility and enzymatic activity. In particular, Cu（Ⅱ） complexes,which are stable and relatively lipophilic, are far-famed for their significant pharmaceuticalproperties.In this paper, fifteen new copper（Ⅱ） complexes,[Cu（L¹）（DMF）]（1）,[Cu（L¹）（CH₃OH）]（2）,[Cu（L²）]_n（3）,[Cu（L²）（Cl）]·（CH₃OH）（4）,[Cu（L²）（Br）]·（CH₃OH）（5）,[Cu（L²）（Br）（DMF）]（6）,[Cu（L³）（CH₃OH）]（7）,[Cu（L⁴）（Cl）]₂（8）,[Cu（L⁵）（Cl）]（9）,[Cu（L⁶）（NO₃）（DMF）]（10）,[Cu（L⁷）（Py）]₂·2（CH₃OH）（11）,[Cu（L8）（H2O）]₂（12）,[Cu（L）（Cl）]₂（13）,[Cu（L）（Br）]₂（14） and [Cu（L）（SCN）]₂（15）, where Lnbehave as O,N,O-donor tridentateSchiff base ligands, were synthesized and structurally characterized. X-ray crystal structuresof all complexes reveal that complexes8,11,12,13,14and15were new dimeric copper（Ⅱ）complexes, and the copper centers possess the slightly distorted square pyramidal geometries.The inhibitory activity of all complexes was tested in vitro against jack bean urease. It wasfound that complexes10,13,14,15,11,7,12,2and9showed urease inhibitory potential（IC50:3.00～54.00μM）. Molecular docking analysis was simulated using the AutoDockprogram to gain an understanding of their inhibitory activity. The interactional energies ofdimeric copper（Ⅱ） complexes were calculated in the gas phase using density functional theory（DFT） methods, which can be explained in terms of dissociative capability of the dimericcopper（Ⅱ） complexes.