Membrane permeabilization and perturbation induced by alkyl- biguanidium salts

Alkylbiguanidium salts show membrane perturbing properties toward simple phospholipid bilayer (liposomes) and complex phospholipid membranes (bacterial membranes). Compared to metformin and phenformin, alkylbiguanidium salts induce a more significant permeabilization of the phospholipid membranes, leading to highly selective H⁺/OH⁻ ion transport and subsequent depolarization of the membrane. Although alkylbiguanidium salts with shorter C₆ and C₈ chains are too hydrophilic to be inserted into the membrane and perturb it, those with C₁₀, C₁₂, C₁₄, and C₁₆ alkyl chains show high membrane permeabilization and depolarization activity. In addition, the C₁₀, C₁₂, and C₁₄ compounds possess interesting antimicrobial activity, and, at concentrations close to their minimal inhibitory concentrations, they show low hemolytic activity and toxicity.