Hydration effect on molecular conformation of oxyphenonium bromide

The C-H COSY, H-H COSY, and NOESY spectra of 2-[(cyclohexylhydroxyphenylace tyl)oxy]-N N-methylethanaminium bromide (OB), an antiacetylcholine drug, in D2O are recorded, and calculations of molecular mechanics, molecular dynam ics, and molecular hydrophobic and hydrophilic surface areas are carried ou t for the prediction of its solution structure. From the assignments of all protons and carbons of OB, it is established that a pair of the correspond ing protons and carbons of the cyclohexyl group are magnetically nonequival ent with one another. On the basis of quantitative analysis of this nonequi valence by the ring current effect due to the phenyl group and the NOESY sp ectrum, the solution structure of the OB ion is estimated; the cyclohexyl a nd phenyl groups are spatially close to one another because of hydrophobic interactions. The structure that has the largest hydrophilic surface area a nd a very small hydrophobic surface area under the condition of no interato mic collision is very close to this NMR structure. Molecular mechanical cal culations that take into consideration the salvation energy estimated from molecular surface areas would predict a more reasonable conformation of the OB ion in the aqueous solution. The molecular dynamics simulations provide information about the flexibility and conformations of OB; the internal ro tations of the cyclohexyl and phenyl groups are rather restricted and these groups are spatially close to one another. The estimated solution structur e serves for the understanding of the pharmacological action and the intera ction between OB and cyclodextrin.