Evaluation of degradation mechanism of chlorhexidine by means of Density Functional Theory calculations

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.

Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life

“…DCHX followed an Avrami kinetic model, while the CR degradation profile fitted better to a zero-order model. Even though there is no full consensus in the literature about the degradation pathway of DCHX, it seems that DCHX suffers from hydrolysis in aqueous solutions, with the direct formation of PCA being the major pathway in acidic conditions, whereas the indirect formation of PCA via the formation of p-chlorophenylurea is the main pathway in alkaline conditions [12,13]. PCA was not used for quantification purposes as it behaved as an intermediate product that degraded successively into other degradants.…”

Multifunctional Dental Adhesives Formulated with Silane-Coated Magnetic Fe3O4@m-SiO2 Core–Shell Particles to Counteract Adhesive Interfacial Breakdown

“…The particles were also tested via TGA using 10 mg of SiQac@ Fe 3 O 4 @m-SiO 2 and Fe 3 O 4 @m-SiO 2 heated in alumina crucibles from 30 to 800 °C with a heat flow rate of 10 °C/min under an N 2 atmosphere. 70 4.6. In Vitro CHX Release Analysis.…”