Síntese de miméticos da urease de Canavalia ensiformis e avaliação mecanística da decomposição da ureia

Abstract

Urease is a metalloenzyme found in many different organisms, which is also associated to virulence factors, such as pielonefritis. Hence, the study of urease inhibitors is necessary to control its activity. For a better design of urease inhibitors it is necessary to understand its hydrolysis mechanism and enzyme biomimetics arise as a simple alternative to study some aspects of enzymes. In this work, four urease mimics were designs, synthesized, characterized and evaluated in urea´s hydrolysis. These mimetic compounds were based on dinuclear nickel complexes using new bis-triazole ligands, which were designed to render a similar environment than ureases´s active site. All characterizations (Mass Spectrometry, Elemental Analysis, Thermogravimetric, Infrared, UV-Vis, Cyclic Voltammetry, Electrochemical Spectrum, Magnetic Analysis), converge to the proposed structures for each mimetic. It was observed that all complexes could form ammonia from urea, exhibiting decay in ammonia concentration over reaction time, suggesting that ammonia was being lost by volatilization or coordination. The reaction intermediate was determined by 15N NMR, observing the appearance of a peak at 244 ppm that can be attributed to the isocyanate, characteristic of an elimination mechanism. It was also possible to detect the active species of the complex in the reaction, which is the aquo complex, suggesting that the mechanism occurs via the external sphere, since urea is not coordinated in solution to the complex. This mechanism differs from proposed mechanisms for urease and other mimetic complexes, but the reaction intermediate is in agreement with the mechanism of other mimetic complexes.