¹H and ¹³C NMR studies of the self‐association of chlorpromazine hydrochloride in aqueous solution

Abstract

The 'H NMR spectrum of chlorpromazine hydrochloride was fully assigned at 400 MHz Similarly, the "C NMR spectrum was assigned unambiguously using two-dimensional NMR. Measurements of chemical shift as a function of concentration in D,O showed appreciable changes of shift of both protons and carbons which were apparent even at solution concentrations two orders of magnitude lower than the critical micelle concentration (CMC). The relative magnitude of the shifts of the aromatic protons and carbons on dilution below the CMC were compatible with vertical stacking of the molecules in an off-set manner such that maximum overlap of the chlorinated rings occurred. Proton chemical shift data were interpreted using a stepwise association model to quantify the extent of association in the pre-CMC region.

NMR detects molecular interactions of graphene with aromatic and aliphatic hydrocarbons in water

“…CPZ showed a 'vertical' stacking of the molecules in an offset manner: with the positively-charged alkyl side-chains located on the opposite sides of the stack and with the maximum overlap of the chlorinated rings; in agreement with earlier work, recognizing the V-shaped phenothiazine ring system of CPZ [66]. DAA and PyY seemed to form partly-overlapping aggregates, interacting mainly in the hydrophobic regions of their structures, free of polar heteroatoms (N and O, respectively) and substituting groups (-NH 2 and -N-(CH3) 2 , respectively).…”

Self-association of Verapamil in Aqueous Electrolyte Solution

“…Upfield shifts on increase of concentra- tion were larger in the case of the aromatic protons (Table 2) indicative of an intermolecular ring current effect as the two phenyl ring systems associate to form the micelle core (12,13). Similar upfield shifts of the aromatic protons have been noted, for example, for the micellization of ω-phenylalkyltrimethylammonium bromides (14, 15) and sodium ω-phenyl decanoate (16) and are also characteristic of compounds that exhibit a stacking mode of association such as nucleotides (17), dyes (18,19), phenothiazine drugs (20), and penicillins (21,22). Protons 2 and 4 corresponding to methyl groups adjacent to the phenyl ring undergo smaller upfield shifts, while proton 3 situated on the alkyl chain shows a small downfield shift.…”

Self-association of cromolyn sodium in aqueous solution characterized by nuclear magnetic resonance spectroscopy

“…The increased shielding of ring nuclei upon self-association may be attributed primarily to an inter-molecular ring current effect; similar shifts have been reported for phenothiazine drugs exhibiting a stacking mode of self-association. 17 The concentration-dependent spectral shifts and changes in coupling strength observed for the methylene and methine protons arise primarily from conformational changes in the alkyl chain linkage between the two ring units.…”