Microbial Degradation of Disinfectants: Two New Aromatic Degradation Products of Chlorhexidine, Chlorhexidine Aromatic Degradation Product (CHADP)-4 and CHADP-6, Produced by Pseudomonas sp. Strain No. A-3

Abstract

To clarify the degradation pathway of chlorhexidine by a microbe, Pseudomonas sp. Strain No. A-3, the isolation and identification of microbial chlorhexidine degradation products were attempted. Two aromatic degradation products of chlorhexidine, named chlorhexidine aromatic degradation product (CHADP)-4 and CHADP-6, were isolated by column chromatography using Diaion HP-10, and purified by column chromatography using Diaion HP-20SS and Sephadex LH-20. The chemical structures of both compounds were examined by infrared, 1 H NMR, 13 C NMR and fast atom bombardment (FAB) mass spectra studies. Based on the spectroscopic data, CHADP-4 (molecular weight 335) and CHADP-6 (molecular weight 377) were found to be direct degradation products of chlorhexidine and were thought to be cleavage partners of p-chlorophenylurea (CHADP-5) and p-chloraniline (p-CA), respectively. Antimicrobial activity of CHADP-6 are similar to that of chlorhexidine, but antimicrobial activity of CHADP-4 decreased to 1/5-1/10 that of chlorhexidine.

Chemical Interaction of Alexidine and Sodium Hypochlorite

“…Tanaka et al (32,33) reported that the degradation of CHX occurs through the cleavage of molecules along the hexane diamine linker between the aromatic rings at either end of the molecule. Such cleavage results in smaller degradation products, each of which contains an aromatic ring, and can cause PCA formation (26).…”

An In Vitro Spectroscopic Analysis to Determine Whether Para-Chloroaniline Is Produced from Mixing Sodium Hypochlorite and Chlorhexidine

“…It has been previously shown that the degradation of CHX occurs through the cleavage of the molecule along the hexane diamine linker between the aromatic rings at either end of the molecule (19, 20). Such cleavage results in smaller degradation products, each of which contains an aromatic ring.…”

Análise química do precipitado formado na reação entre hipoclorito de sódio e digluconato de clorexidina

“…Figura 2.9 -Identificação na figura de mecanismo de degradação da CLX (Figuras 2.10 e 2.11), peso molecular e estrutura molecular proposta para os compostos intermediários de degradação da clorexidina em PCA, segundo Zong (2011) Figura 2.12 -Estruturas moleculares dos compostos CHCI-B, CHCI-BR e CHCI-D, segundo Uyeda et al (1996) Figura 2.14 -Compostos da degradação da CLX e suas fragmentações em espectrometria de massa, segundo Tanaka et al (2006) …”

“…Foi demonstrado anteriormente que a degradação de CLX ocorre através da quebra da molécula no grupo guanidil ligado aos anéis aromáticos em ambas as extremidades da molécula (Tanaka et al, 2005;Tanaka et al, 2006). Essa quebra resultaria em produtos de degradação menores em massa que a CLX, cada qual contendo um grupo anilina com um átomo de cloro na posição 4.…”

“…Figura 2.13 -Estrutura molecular do CHDI-C, segundo Tanaka et al (2005) Os mesmos autores (Tanaka et al, 2006), realizando separação e análise de compostos semelhantes às descritas anteriormente, também sugerem a existência de mais dois compostos intermediários do mecanismo de degradação da CLX, 55 denominados CHADP-4 e CHADP-6. Eles seriam pares de degradação da PCU e PCA, respectivamente.…”