Conformational Stability and Thermal Pathways of Relaxation in Triclosan (Antibacterial/Excipient/Contaminant) in Solid-State: Combined Spectroscopic (H-1 NMR) and Computational (Periodic DFT) Study

摘要

The mechanism of molecular dynamics in the antibacterial/antifungal agent, triclosan (5-chloro-2-(2',4'-dichlorophenoxy)-phenol), in solid state was studied by H-1 NMR spectroscopy and periodic density functional theory (DFT) calculations. Temperature dependencies of the proton spin lattice relaxation time (T-1) in the ranges 86-293 and 90-250 K (at 15 and 24.667 MHz, respectively) and the second moment (M-2) of the H-1 NMR resonant line in the range 103-300 K were measured. Two minima in the temperature dependence of T-1 revealed a classical Arrhenius governed activation processes. The low temperature shallow minimum T-1(T) of 71 s at 115 K, 15 MHz, which shifts with frequency, was assigned to classical hindered jumps of hydroxyl group around OC axis and with respect to a 5-chloro-2-phenol ring. The activation energy of this motion estimated on the basis of the fit of the theoretical model to the experimental points is 9.68 kJ/mol. The pointed high temperature minimum T-1(T) of 59 s at 190 K, 15 MHz, which also shifts with frequency, was assigned to the small angle librations by Theta(lib)=+/- 9 degrees between two positions of equilibrium differing in energy by 7.42 kJ/mol. The activation energy of this motion estimated on the basis of the fit of the theoretical model to the experimental points is 31.1 kJ/mol. Both motions result in a negligible reduction in the H-1 NMR line second moment, thus the second moment delivers an irrelevant description of the molecular motions in triclosan.