Case Studies in Solvation of Bioactive Molecules
1994; American Chemical Society; Linguagem: Inglês
10.1021/bk-1994-0568.ch018
ISSN1947-5918
AutoresCarol A. Venanzi, Ronald A. Buono, Victor B. Luzhkov, Randy J. Zauhar, Thomas J. Venanzi,
Tópico(s)Free Radicals and Antioxidants
ResumoMolecular dynamics and the Lagevin Dipole, Induced Polarization Charge Boundary Element, and Self-Consistent Reaction Field static solvation models are shown to agree in their prediction of the relative solvation energy of conformers of amiloride. This is important since NMR experiments were unable to distinguish between the conformers in solution. Molecular dynamics simulation also showed that the protonated form of amiloride tends to remain planar on the average due to a high OCCN torsional barrier. This lends support to the hypothesis that amiloride most likely binds to DNA in a planar conformation. The Langevin Dipole model is also used with the AM1 semiempirical quantum mechanical method to compare the reaction paths for acetate phenol cleavage by hydroxide ion and by cyclodextrin. The results show that acylation at the 3'-hydroxyl of cyclodextrin is favored over the 2'-position by about 10 kcal/mol and that cyclodextrin lowers the activation energy barrier for acylation by about 10 kcal/mol compared to attack by hydroxide ion.
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