Micellization and other associations of amphiphilic antimicrobial quaternary ammonium salts in aqueous solutions

Micellization and other types of associations of amphiphilic quaternary ammonium salts (QAS) in aqueous solutions are analysed in connection with their cationic surfactant nature and antimicrobial activity. In homologous series of QAS, log CMC decreases linearly with the number of CH2 groups in the alkyl tail (tails) of the quaternary cations, so that with some limitations,--log CMC is a relative measure of hydrophobicity. The concentration of the free monomer quaternary cations of the well ionized QAS (chlorides, bromides) increases up to CMC only, while in the micellar solution above CMC it sharply decreases in conformity with the mass-action micellization model. CMC thus represents the maximal available concentration of the monomer quaternary cations of the well ionized amphiphilic QAS which may account both for the observed decrease of the antimicrobial activity above CMC and, at least in part, also for the cut-off effect of too hydrophobic QAS with low CMC. Admixtures of another electrolyte and some other additives lower CMC and thus diminish the availability of the quaternary cations. Possible differences between micellization of the well ionized QAS and weakly ionized salts of protonable bases with respect to the antimicrobial action are pointed out. Antimicrobial action of QAS can be blocked by ion-pairing and precipitation of quaternary cations with bulky anions, by interaction with other surfactants and sometimes even selectively neutralized by their inclusion complexation with alpha- and beta-cyclodextrins.