Haloamines of the Neurotransmitter γ-Aminobutyric Acid (GABA) and Its Ethyl Ester: Mild Oxidants for Reactions in Hydrophobic Microenvironments and Bactericidal Activity

神经递质γ-氨基丁酸(GABA)及其乙酯的卤胺:疏水微环境中反应的温和氧化剂及杀菌活性

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Abstract

N-chlorotaurine (Tau-Cl) is a mild oxidizing haloamine formed from the reaction of hypochlorous acid (HOCl) with taurine (2-amino-ethanesulfonic acid). It is widely used as a topical antiseptic. In this study, we investigated haloamines derived from the neurotransmitter γ-aminobutyric acid, specifically GABA chloramine and bromamine (GABA-Cl, GABA-Br), as well as their halogenated γ-aminobutyric acid ethyl esters (GABAet-Cl, GABAet-Br). Due to their higher hydrophobicity, the esterified haloamines were more potent oxidants in the presence of lyophilic surfactant micelles, demonstrating their greater ability to access hydrophobic environments. By using fluorescent azapentalenes as molecular targets incorporated into sodium dodecyl sulfate (SDS) micelles, the second-order oxidation rate constants (k(2)) resulted in 1.15 × 10(2) and 1.10 × 10(4) M(-1)min(-1) for GABA-Cl and GABAet-Cl, respectively. As expected, due to the presence of a bromine atom, GABAet-Br was even more reactive (4.50 × 10(6) M(-1)min(-1)). The ability of GABAet-Br to access hydrophobic sites was demonstrated by comparing the reaction rate using micelles generated by different surfactants such as SDS (4.5 × 10(6) M(-1)min(-1)), cetyltrimethylammonium chloride (CTAC, 2.5 × 10(4) M(-1)min(-1)), and triton X-100 (TX-100, 3.9 × 10(3) M(-1)min(-1)). GABAet-Cl and GABAet-Br exhibited higher bactericidal activity against Staphylococcus aureus and Escherichia coli, probably due to their increased lipophilicity and improved penetration into microorganisms compared to GABA-Cl and GABA-Br. The enhancement of the oxidation capacity by GABAet-Cl and GABAet-Br represents a new direction in the exploration and application of haloamines as antiseptic agents.

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