title: Conformational analysis of L-prolines in water.
abstract: The results of the ring conformational analysis of L-proline, N-acetyl-L-proline, and trans-4-hydroxy-L-proline by NMR combined with calculations using density functional theory (DFT) and molecular dynamics (MD) are reported. Accurate values of 1H-1H J-couplings in water and other solvents have been determined. Using a two-site equilibrium model, the Cgamma-endo conformer of L-proline in water has been identified as intermediate between gammaTdelta [twist(Cgamma-endo, Cdelta-exo)] and gammaE [envelope(Cgamma-endo)] and the Cgamma-exo conformer as betaTgamma. Both conformers were equally populated at room temperature. The N-acetyl [cis-rotamer gammaTbeta(80%)/gammaE(20%) and trans-rotamer gammaTbeta(61%)/gammaE(39%)] and 4-hydroxy (gammaEpsilon) derivatives showed significant changes in both the population and the geometries of the preferred ring conformers. The combination of NMR predicted populations with the DFT B3LYP/6-311+G(2d,p)/IEFPCM calculations proved successful, resulting in fairly accurate predictions of J-couplings. Simulations using MD were mostly in favor of the two-site equilibrium model between Cgamma-endo and Cgamma-exo conformers, similar to that used for the analysis of NMR J-couplings. Various force fields examined for MD simulations failed to reproduce the ring conformational geometries and populations of L-proline in water accurately, while significantly better agreement with NMR was found for trans-N-acetyl-L-proline using GROMOS and AMBER force fields.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom. a.e.aliev@ucl.ac.uk
authors.forename: Abil E
authors.initials: AE
authors.lastname: Aliev
authors.forename: Denis
authors.initials: D
authors.lastname: Courtier-Murias
mesh_terms: D003198:Computer Simulation; D003460:Crystallization; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011392:Proline / Q000737:chemistry*; D011522:Protons; D014867:Water / Q000737:chemistry*
chemical_list: D011522:Protons; D014867:Water; D011392:Proline