Enhanced antibacterial activity of new “composite” biocides with both N-chloramine and quaternary ammonium moieties

Abstract

Combining both N-chloramine and quaternary ammonium moieties in one molecule results in a new biocide with better antibacterial activity.

Synthesis of Gemini‐QA N‐Chloramine Biocides for Antibacterial Applications

“…Obvious chemical shift change was observed on 1 H NMR spectra once precursors 8 a ‐ 11 a were transformed into N ‐chloramines 8–11 via chlorination, which well conformed to our previous reports . For instance, the signal of CH 3 ‐ and ‐CH 2 ‐ (adjacent to the imide N ) of 8 a shifted downfield from 1.36 ppm to 1.43 ppm and 3.55 ppm to 3.63 ppm respectively (Figure ), which probably was due to the electron‐withdrawing effect of the newly produced N ‐Cl bond.…”

“…On the contrary, a natural barrier might be offered by the lipopolysaccharide outer membrane of E. coli during the membrane penetration process of N ‐chloramines. Such antibacterial trend is also consistent with previous studies that E. coli usually is more resistant compared with S. aureus . Of course, collaboration with medical institutes to challenge these Gemini‐QA N ‐chloramines against drug resistant pathogens is also under consideration currently.…”

“…It was proposed that higher positive charge density of Gemini‐cationic heads leads to more facilitated adsorption on negatively charged bacteria cell, resulting in superior bactericidal efficacy. However, given our previous study that QA N ‐chloramine 1 , 6 and 7 hold the same level biocidal efficacy, the increased charge density of 8 may hardly account for its enhanced antibacterial efficacy. The prominent bactericidal capacity of N ‐chloramine 8 was probably due to the “team effort” contact killing of the Gemini‐QA architecture that could be regarded as the symmetric combination of two QA N ‐chloramine units (Figure ).…”

“…and 0.5 equiv. QA units per N ‐Cl unit respectively, displayed almost the same level antibacterial efficacy in contrast to N ‐chloramine 1 . This finding indicated that biocidal activity of the “composite” N ‐chloramines may mainly rely on the N ‐chloramine scaffold, and the molecular positive charge density may not play a predominant role on bactericidal activity at this point.…”

“…As the cationic QA moiety was proved to enhance contact killing of N ‐chloramine scaffold, more derivatives of N ‐chloramine 1 have been synthesized to seek even higher antibacterial efficacy as well as to expand the cationic N ‐chloramine library . Not surprisingly, antibacterial synergistic effect was observed for biocide 5 [ 16] which consists of an N ‐chloramine unit and a dodecyl chain tethered QA unit.…”