CYCLOHEXADECANONE DERIVATIVE GAMMA-CYCLODEXTRIN COMPLEXES MD SIMULATIONS AND AMSOL CALCULATIONS IN-VACUO AND IN AQUO COMPARED WITH EXPERIMENTAL FINDINGS

The complex formations of cis- and trans-cyclohexadecenone (cis-CHDC a nd trans-CHDC) and cyclohexadecanone (CHDH) with gamma-cyclodextrin (g amma-CD) in the presence of water are investigated. In the experiment [cis-CHDC//gamma-CD] complexes are found to be slightly preferred over [trans-CHDC//gamma-CD] complexes, with an energy difference of less t han 1 kcal/mol. Molecular dynamics (MD) simulations in vacuo showed th at energetically favourable complexes are formed, whereby (contrary to experiment) trans-CHDC has the best complexation energy, followed by cis-CHDC, (their calculated energy difference being less than 3 kcal/m ol) and then cyclohexadecanone (CHDH). MD simulations in aqueous solut ion reveal positive complexation energies for all three compounds of a bout 12 to 25 kcal/mol, i.e., these practically do not exist in aquo, which is in agreement with the experimental observation that about 99% precipitate is formed. AMSOL calculations of the hydration energies s upport the low solubility of all three CHDC derivatives and the high s olubility of gamma-CD. Therefore, the simulations in aquo showed that hydration can play such an important role, that although complexation is possible in vacuo, the complexes are not formed in water. (C) 1998 Elsevier Science Limited.