Theoretical and experimental conformational analysis of two diastereomeric "Val"-statine derivatives

Toniolo, C.; Valle, G.; Crisma, M.; Bonora, G.M.; Lelj, F.; Cristinziano, P.L.; Barone, V.; Nisato, D.

Peptide Research 3(1): 27-34


ISSN/ISBN: 1040-5704
PMID: 2134045
Document Number: 366518
The preferred conformations and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 5-methylhexanoic acid ("Val"-statine) with (S,S) and (R,S) configurations at the 3-hydroxy and 4-amino carbon atoms, respectively, were determined in solution as well as in the crystal state by infrared absorption, 1H nuclear magnetic resonance and x-ray diffraction. A corollary conformational energy computation study was also carried out. In the crystal state intramolecular H-bonds are absent in both structures. However, the change in chirality of the carbon atom carrying the hydroxy group and the presence of a co-crystallized water molecule in the (S,S) isomer induce partially different backbone and "Val" side chain conformations and divergent intermolecular H-bonding schemes in the two isomers. A marked propensity to self-aggregate is seen in solvents of low polarity. The two isomers, however, are largely solvated in solvents of high polarity. Conformational energy computations indicate that in vacuo both diastereomers exhibit a significant flexibility and the conformers presenting absolute minima are not stabilized by any intramolecular bonding.

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