Stability and molecular dynamics of solid lasamide (API of diuretic and antivirial drugs) studied by 1H NMR spectroscopy and DFT methods

Temperature dependence of the relaxation time T, (in the ranges: 10-200 K at 24.667 MHz; 105-460 K at 90 MHz) and the second moment of the NMR line for protons M-2 (in the range: 130-400 K, 24.667 MHz) in a polycrystalline sample of 2,4-dichloro-5-sulfamoyl-benzoic acid (lasamide) an Active Pharmaceutical Ingredient of both diuretic and antiviral drugs have been measured. The results have revealed two activation processes: the concerted proton transfer in inter-molecular double hydrogen bonds (the low-temperature T-1 minimum at about 92 K; the activation energy 5.02 kJ/mol) and the jumps of the -NH2 group (the high-temperature, 2 GS(2) reduction of the second moment; the activation energy 48 kJ/mol). The low-temperature flattening of the T-1 dependence stretched up to the helium temperatures indicating the incoherent tunnelling in the proton transfer dynamics. (C) 2009 Elsevier B.V. All rights reserved.