Evaluation of degradation mechanism of chlorhexidine by means of Density Functional Theory calculations. (December 2017) - Salvador, Michele Aparecida
Graphical abstract: Highlights: Computational simulations to elucidate the degradation mechanism of chlorhexidine. Electronic properties and thermodynamic parameters involved in the different pathways. Besides p -chloroaniline, other products are viable. Abstract: Chlorhexidine (CHD), a germicidal drug, has degradation products that can be hemotoxic and carcinogenic. However, there is no consensus in literature about the degradation pathway. In order to shed light on that mechanism, we have employed Density Functional Theory to study reactants, in different protonation states, products and intermediates involved in the different pathways. Based on free energy values comparison and frontier molecular orbital analysis, we have obtained the most stable structures in each protonation state. CHD in saturated form has HOMO localized in one p -chloroaniline, and, due to molecule's symmetry, HOMO-1 has contributions from the other side of the molecule, but mainly from the biguanide portion of the molecule, instead of from the p -chloroaniline. For the saturated form, we have studied two possible degradation pathways, starting from the monoprotonated structure, and three pathways starting from the neutral structure. We found out that the mechanisms proposed in literature, whose pathways lead to p- chloroaniline (PCA) formation in a smaller number of steps, are more likely than the mechanisms with more intermediate steps or pathways that do not predict PCA formation. Also, based on free energy results, we have found that the formation of another sub-product (PBG-AU) is favorable as well.