An NMR and molecular mechanics study of squalene and squalene derivatives

Various squalene derivatives, including squalene, squalene 2,3-epoxide (monoepoxide, SQME), squalene 2,3;22,23-diepoxide (SQDE), 2-aza-2,3-dihydrosqualene (SQN) and 2-aza-2,3-dihydrosqualene N-oxide (SQNO), were studied in chloroform solutions using 1D high-resolution H-1 spectra and C-13 longitudinal relaxation studies, 2D proton NOESY and COSY and 2D proton-carbon HETCOR spectroscopy. A full interpretation of the H-1 and C-13-NMR spectra is presented. Staggered conformations along the C11-C12 bond are favoured and a relatively rigid structure of the central part of the chain is indicated in relaxation and coupling data, while further away from the central part the molecular mobility grows. A detected NOE dipolar interaction between terminal and central parts of the molecule indicates the presence of dynamically folded structures in solution. The proposed model also explains the selective reactivity of the mobile chain endings with respect to the central part which is protected by these moving ends. Different solvents at different concentrations induce some variations in this molecular model with a shortening or a lengthening of the mean path covered by the tail endings. Molecular mechanics and molecular dynamics calculations on the free squalene molecule indicate that the mobility of the chain is almost equivalent in all its isoprenic moieties, and the greater mobility of the chain ends may be ascribed to co-operative movements from the center to the tails. The solvent probably plays an important role in hindering the motion of the central part of the molecule.