The structure-dependent effects of newly synthesised cationic gemini surfactants against yeast cells

The mechanism of action of cationic gemini surfactants, namely dimethyl{{3-[N-(3-{N-[3-(dimethylammonium)propyl]alkylamido}propyl}dodecylamido}propyl}}ammonium dibromides (2xCnBrG3, n = 12, 14), dimethyl carbonates (2xCnMeCO3G3, n = 12), and dimethyl{{3-[N-(3-{N-[3-(dimethylamine)propyl]alkylamido}propyl}dodecylamido}propyl}}amine dihydrochlorides (2xCnHClG3, n = 12, 14), was investigated in Saccharomyces cerevisiae cells. Studies indicated the influence of the chemical structure of these compounds on their activity. The tested cationic gemini surfactants increased K⁺ ion leakage from yeast cells. Moreover, these compounds elevated the intracellular content of both saturated and unsaturated fatty acids, as well as sterols (ergosterol, zymosterol, lanosterol). Especially, compounds 2xC14BrG3 and 2xC14HClG3 increased these membrane sterols content by a factor of two and five, respectively. The studied gemini quaternary ammonium salts (QAS) inhibited the activity of plasma membrane and mitochondrial H⁺-ATPase and reduced phenylalanine uptake under repressive and derepressive conditions of Gap1 permease. Additionally, the surfactants increased oxidative stress levels in yeast cells. The tested surfactants also completely inhibited oxygen uptake by S. cerevisiae. It was also observed that gemini QAS induce morphological changes in yeast cells. To sum up, the compounds with 12-carbon alkyl chains showed stronger effects than 14-carbon compounds. Short chains incorporate more easily into membranes, which results in greater activity at lower concentrations.