Soft Antimicrobial Agents:  Synthesis and Activity of Labile Environmentally Friendly Long Chain Quaternary Ammonium Compounds

Abstract

A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized. These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group. They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks. However, their chemical stability has to be adequate in order for them to have antimicrobial effects. Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability. Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log. The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C.

Quantitative Structure-Activity Relation Study of Quaternary Ammonium Compounds in Pathogen Control: Computational Methods for the Discovery of Food Antimicrobials

“…Three sections of data were collected via literature searches (1) a model building set, (2) a validation set, and (3) a prediction set of compounds [27][28][29]. The model building set was based on known QACs with data on the MIC of these compounds against E. coli.…”

Synthesis and Biological Activity of Azine Heterocycle Functionalized Quaternary Phosphonium salts

“…Quaternary ammonium compounds are actively prevented the growth bacterial growth against both Gram-positive and Gram-negative bacteria, as well as against other pathogenic species of fungi and protozoa [1]. It has been found that quarternary phosphonium salts also showed beneficial antibacterial activity [2,3].…”

“…Quaternary ammonium compounds are actively prevented the growth bacterial growth against both Gram-positive and Gram-negative bacteria, as well as against other pathogenic species of fungi and protozoa [1]. It has been found that quarternary phosphonium salts also showed beneficial antibacterial activity [2,3].Microbial protection is mainly dependent on long alkyl chains which are attached with the phosphonium salts. These can be enhanced strongly by the molecular structure, correlation between antimicrobial activity and molecular structure [4].…”

N, N, N-triethyl Ammonium L-Phenylalanine Esters as Potential Antimicrobial Agents

“…Therefore, there is a need to develop more QUATS with antimicrobial activities. Quaternary ammonium compounds, in general, have toxic effects toward mammalian cells [9]. In humans and animals they are considered too toxic for systemic applications, but acceptable for topical applications.…”