H-1 AND C-13 NMR-STUDIES OF THE SELF-ASSOCIATION OF CHLORPROMAZINE HYDROCHLORIDE IN AQUEOUS-SOLUTION

The H-1 NMR spectrum of chlorpromazine hydrochloride was fully assigne d at 400 MHz. Similarly, the C-13 NMR spectrum was assigned unambiguou sly using two-dimensional NMR. Measurements of chemical shift as a fun ction of concentration in D2O showed appreciable changes of shift of b oth protons and carbons which were apparent even at solution concentra tions two orders of magnitude lower than the critical micelle concentr ation (CMC). The relative magnitude of the shifts of the aromatic prot ons and carbons on dilution below the CMC were compatible with vertica l stacking of the molecules in an off-set manner such that maximum ove rlap of the chlorinated rings occurred. Proton chemical shift data wer e interpreted using a stepwise association model to quantify the exten t of association in the pre-CMC region.