Unsaturated Gemini Surfactants with a Semi-Rigid Spacer: Micellization and Antimicrobial Activity

A homologous series of but-2-ene-1,4-bis(N-alkyl-N,N-dimethylammonium bromides) containing C12, C14, C16, and C18 alkyl chains was investigated to determine the influence of hydrophobic-chain length and a semi-rigid unsaturated spacer on aggregation and antimicrobial properties. The critical micelle concentration decreased from the C12 to the C16 derivative, whereas further chain elongation to C18 resulted in an increase in CMC, indicating that micellization is governed not only by hydrophobicity but also by molecular packing effects. Negative standard Gibbs energies confirmed spontaneous micellization. Antimicrobial activity showed the opposite trend: the C12 derivative was the most active compound against all tested microorganisms, with MIC (minimum inhibitory concentration) values as low as 0.06 mM (12-4ene-12 against C. albicans). Increasing alkyl-chain length markedly reduced activity, particularly against Escherichia coli, for which the MIC increased from 0.12 mM for C12 to over 62.5 mM for C18, demonstrating a pronounced cut-off effect. Staphylococcus aureus remained more susceptible to longer-chain homologues than E. coli, while notable activity was also observed against yeast and filamentous fungi. DFT calculations further indicated that spacer unsaturation affects the electronic properties of the molecules. Overall, the results demonstrate a strong relationship between alkyl-chain length, micellization, spacer rigidity, and antimicrobial performance.