Electronic structure of thiazides studied by ³⁵Cl‐NQR spectroscopy and DFT calculations

Abstract

NQR frequencies were determined for the 35 Cl isotope in a few benzodithiazine derivatives, chlorothiazide (CTZ), hydrochlorothiazide (HCTZ), althiazide (ATZ), trichloromethiazide (TCTZ), benzthiazide (BTZ) and furosemide (FSE), at liquid nitrogen and room temperatures. It was found that changes of the substituent at C-3 are transferred through a system of coupled rings on to the chlorine atom at C-6. The substituents occurring in thiazides can be ordered according to increasing electron-acceptor properties as -CH 2 SCH 2 Ph < -CH 2 SCH 2 CH CH 2 < -CHCl 2 . At the liquid nitrogen temperature -CH 2 SCH 2 Ph and -CH 2 SCH 2 CH CH 2 are electron donors, and CHCl 2 is an electron acceptor, whereas at room temperature -CH 2 SCH 2 Ph is an electron donor and -CH 2 SCH 2 CH CH 2 and -CHCl 2 are electron acceptors. The character of the substituent properties is preserved irrespective of whether the system is aromatic or aliphatic. The NQR frequencies and substituents properties are well reproduced by the DFT B3LYP/6-311+G(2d,p) method. The topological properties of the Laplacian of the electron density were analysed within the AIM (atoms in molecules) approach. The changes in the electron density at C-3 are correlated with the biological activity of the compounds studied.

Temperature Variation of Ultralow Frequency Modes and Mean Square Displacements in Solid Lasamide (Diuretic Drug) Studied by 35Cl-NQR, X-ray and DFT/QTAIM

“…Cl(1) in the p -position relative to the carboxyl group in the benzene ring forces the conformation of the sulphonamide group via S···O van der Waals contact of length 3.4 Å, while Cl(2) in the o -position links molecules in layers via intermolecular van der Waals N···Cl and Cl···O contacts. The assignment of two NQR frequencies to chlorine atoms, the one of the higher frequency to Cl(2) (R C–Cl(2) = 1.732 Å) and the one of the lower frequency to Cl(1) (R C–Cl(1) = 1.728 Å), was made on the basis of a comparison with the experimental data for 4-chlorobenzoic acid, 2-chlorobenzoic acid, 2,4-dichlorobenzoic acid, , 2-chlorobenzenesulphonamide, 4-chlorobenzene-sulphonamide, monochlorobenzene, , 1,3-dichlorobenzene and furosemide . The above assignment was also confirmed by B3LYP/6-311++G­(d,p) computations performed assuming the monomer and tetramer constructed on the basis of crystalline structure (Table ).…”

Potential of Nuclear Quadrupole Resonance in Pharmaceutical Analysis

“…For furosemide, 35 Cl signals have been detected at 77 K; only one frequency is reported, at 36.759 MHz, which appears to correspond to the line at 36.266 MHz at room temperature, an indication of the temperature effects for this nucleus to which we have already referred. Notably, this line has a very short spin−lattice relaxation of 2 ms at room temperature, a value not untypical of the higher frequencies observed for 35 Cl nuclei in organic compounds.…”