Hydro phobic forms of morphine 6-glucosides

NMR spectroscopy of 6-acetylmorphine (6-AM), a chloroform-soluble model com pound for the hydrophilic, highly potent analgesic drug morphine-6-glucoron ide (M6G), in a hydrophobic solvent indicates one hydrogen bonded water mol ecule per molecule of 6-AM. By analysis of nuclear Overhauser enhancements (NOEs) we find a 6-AM dimer in which the monomers are linked by two water m olecules. Molecular modeling studies underscore the stability of such dimer ic structures involving water molecules for 6-AM and point out their more l ipophilic character allowing penetration of the blood-brain barrier. (C) 20 01 Elsevier Science Ltd. All rights reserved.