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

## TL;DR

This study explores new haloamine compounds derived from GABA that show improved oxidizing power and antibacterial activity in hydrophobic environments.

## Contribution

The study introduces esterified GABA haloamines with enhanced reactivity and bactericidal properties in hydrophobic microenvironments.

## Key findings

- GABAet-Br showed the highest oxidation rate (4.50 × 10⁶ M⁻¹min⁻¹) among the tested haloamines.
- Esterified haloamines demonstrated greater bactericidal activity against S. aureus and E. coli.
- The compounds' reactivity varied with surfactant type, indicating their ability to access hydrophobic sites.

## 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 (k2) resulted in 1.15 × 102 and 1.10 × 104 M−1min−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 × 106 M−1min−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 × 106 M−1min−1), cetyltrimethylammonium chloride (CTAC, 2.5 × 104 M−1min−1), and triton X-100 (TX-100, 3.9 × 103 M−1min−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.