Physicochemical Solubility of and Biological Sensitivity to Long-Chain Alcohols Determine the Cutoff Chain Length in Biological Activity.

The cutoff phenomenon associated with the effectiveness of long-chain alcohols in the induction of anesthesia is also observed for various antimicrobial activities, although the mechanism has remained unknown for over eight decades. The minimum inhibitory concentrations at 25°C for budding yeast growth exponentially decreased with increasing chain length of -alcohols (C-C), whereas alcohols ≥C lost the inhibitory effect. Thus, growth inhibition by alcohols obeys the Meyer-Overton correlation up to C and exhibits a cutoff phenomenon. The densities of alcohols are low, and the melting point and hydrophobicity increase with chain length. C and C inhibited yeast growth at 39.8°C, above their melting points. Alcohols ≤C inhibited thermophilic bacterial growth at 50°C, whereas C inhibited it at 67.5°C, above their melting points. Thus, the high melting points of long-chain alcohols contribute to the cutoff phenomenon. C did not effectively inhibit yeast growth in a static culture at 39.8°C, in contrast to a shaking culture, in which the low density-dependent concentration gradient was eliminated. The duration of the transient growth inhibition of yeast by C was prolonged by sonication, which prevented hydrophobic aggregation. Therefore, a nonuniform distribution owing to low density and high hydrophobicity contributes to the cutoff. C inhibited the growth at 25°C of the mutant, defective in multidrug efflux pumps, whereas C did not inhibit the growth of yeast overexpressing , indicating that the sensitivity to long-chain alcohols contributed to the cutoff. A balance between the physicochemical solubility of and the biological sensitivity to long-chain alcohols determines the cutoff chain length.