Why 1-NH and 3-NH Protons of d-Biotin Exhibit Different Activities in Aqueous Solution

Abstract

Quantum chemical calculations, combined with the molecular dynamics results, have been employed to explain why the 1- and 3-NH protons of biotin exhibit different activities in aqueous solution. They suggested that the relative proportion of the three different conformations of biotin in the solution was responsible for different activities of the two amide protons of biotin. The relative activity of the two amide protons calculated by theoretical work here is 6, which is in good agreement with the experimental data, which is 5, reinforcing the viewpoint that biotin jumps between the three conformations in aqueous solution and the relative proportion of extended, semifolded, and folded biotin in water is 24:3.6:1. The method for computing the relative activity of the two amide protons of biotin in water here may be used to predict the relative activity in other solutions. The behavior of biotin in aqueous solution may be helpful for better understanding the unusual strong biotin-(strept)avidin binding.