A series of quaternary ammonium compounds that are esters of betaine and fatty alcohols with hydrocarbon chain lengths of 10 to 18 carbon atoms were tested with respect to antimicrobial activities and rates of hydrolysis. When the tetradecyl derivative was tested against some selected microorganisms, the killing effect was comparable to that of the stable quaternary ammonium compound cetyltrimethylammonium bromide. At higher pH values, both the antimicrobial effect and the rate of hydrolysis of the esters increased. However, whereas at pH 6 greater than 99.99% killing of Salmonella typhimurium was achieved with 5 ,ug/ml in 3 min, the rate of hydrolysis was less than 20% in 18 h. At pH 7, a similar killing effect was achieved in 2 min and 50% hydrolysis occurred in ca. 5 h. Thus, it is possible to exploit the rapid microbicidal effect of the compounds before they hydrolyze. The rate of hydrolysis was reduced by the presence of salt. The bactericidal effect of the betaine esters increased with the length of the hydrocarbon chain of the fatty alcohol moiety up to 18 carbon atoms. Since the hydrolysis products are normal human metabolites, the hydrolysis property may extend the use of these quaternary ammonium compounds as disinfectants and antiseptics for food and body surfaces.The membrane-disruptive and antimicrobial activities of cationic surfactants are well recognized. These agents are often active against a broad range of bacteria and other cells and can also inactive certain viruses (16,29). Because of their high affinity for biological membranes, these agents show a low selectivity and can be damaging to a variety of mammalian cells (17,23,24).Since the time needed to kill microorganisms with cationic surfactants is usually short, it could be expected that side effects in the host might be decreased by the use of substances that are subject to hydrolytic degradation. However, the lifetime of the compounds must be sufficiently long to allow proper inactivation of the undesired microorganisms. The products obtained in the degradation steps should also be significantly less toxic than the original compound and should ideally constitute normal metabolites of the host.To explore the possible use of degradable cationic surfactants, we studied a series of amphiphilic betaine esters (Fig. 1). Although the increased rate of base-catalyzed hydrolysis of lower esters of this structure has been investigated and is understood to be caused by an inductive effect from the positive charge (5, 26), this property does not seem to have been considered in connection with biological (10,27) or recent surface chemical (4, 25) studies of compounds of this type. In the present paper, we describe the synthesis of some esters between betaine (trimethylglycine) and long-chain fatty alcohols, their antimicrobial activities, and their rates of hydrolysis.
MATERIALS AND METHODSCompounds investigated. The betaine esters were obtained as chlorides by chloroacetylation of the corresponding longchain alcohol, principally as described by Ho...