A density functional theory study of the free-radical scavenging activity of aminoguanidine. Comparison with its reactive carbonyl compound and metal scavenging activities

Since protein glycation is related to several human diseases, it is very important to develop molecules that can inhibit its effects. This work adds the reaction of Aminoguanidine (AG) with the methoxy (OCH3) and hydroperoxyl (OOH) radicals at the UM05-2X-SMD/6-311+G(d,p) level of theory in water and pentyl ethanoate to simulate the physiological aqueous and lipidic environments. At physiological pH, AG is an effective OCH3 and a moderate OOH scavenger in nonpolar solvents (where AG is predominantly neutral), acting exclusively by hydrogen-atom transfer. However, reactions in a polar solvent (where AG is predominantly cationic) have smaller rate constants. Therefore, the ability of AG to scavenge free radicals seems to depend on the polarity of the environment. Taken together, the results reported herein and in previous works suggest that the scavenging of reactive carbonyl species is the main mechanism of action of aminoguanidine in the context of protein glycation inhibition.