REORIENTATIONAL DYNAMICS AND INTERNAL MOBILITY OF THE MIXED AGONIST-ANTAGONIST OPIOID NARCOTIC CYCLAZOCINE BY C-13 NMR RELAXATION-TIMES

The motional behaviour of the mixed agonist-antagonist opioid narcotic cyclazocine ylmethyl-2'-hydroxy-5,9-dimethyl-6,7-benzomorphan) as a c ationic species (CLZH+) was analysed by C-13 NMR spin-lattice relaxati on times (T1). Both AM1 and MM2 theoretical calculations were performe d to predict the preferred conformations and torsional energetics of C LZH+ in the vapour phase. The analysis of the experimental T1 data (in aqueous solution) was performed by using an analytical model to descr ibe the overall and internal motions of the molecule. The best fit of the relaxation times allowed the detection, in the liquid phase, of ef fective solute-solvent interactions and the fully anisotropic diffusiv e process of the molecule. The motional parameters obtained indicated an increased rotational anisotropy of CLZH+ on passing from the gas ph ase to the solution state. Different activation energies arising from separate solvation effects were found for the motion of the 10-Me and 11-Me groups. The fitted energies and transition energies matrix relat ive to the internal motion of the N-cyclopropylmethyl group indicated that the preferred conformational states are not isolated and that the overall and internal motions are of the same order of magnitude.