Distribution of zwitter-ionic tryptophan between the micelles of 1-dodecyl-3-methyl imidazolium and aqueous medium from molecular dynamic simulation

Ionic liquids that form micelles have great potential as drug carriers and separating agents for bioactive substances. For such applications, a key issue is the distribution of the target substance between the micelle and its environment. We perform MD simulations to study solubilization of zwitter-ionic tryptophan in micelles of 1-dodecyl-3-methylimidazolium bromide. We found that the distribution of tryptophan depends strongly on the degree of counterion binding. A decrease in binding of bromide counterions leads to a substantial increase of the distribution coefficient. A dense layer of counterions at the micellar surface impedes the solubilization of the zwitter-ionic tryptophan but at the same time the presence of such a dense layer obstructs the washout of the solubilized tryptophan molecules from the micelle. Based on our simulation data, we conclude that an increase of the distribution coefficient of tryptophan between the micelle and water may be achieved by several means: by introducing counterions that bind weakly to the micelle (bulky ions whose charge is not strongly localized) and/or by employing micelle-forming ionic liquids with shorter alkyl chains to diminish the degree of counterion binding.