An ab initio study of intramolecular hydrogen bondings in alpha-hydroxy ketomethylene dipeptide isostere

Ab initio calculations of the representative a-hydroxy ketomethylene dipept ide isostere (2S,5S)-5-amino-2-hydroxy-4-oxohexanoic acid (1) are described . All calculations including full geometry optimizations were performed at the MP2/6-31G* level. In the gas phase, 12 low-energy conformers are locate d by minimizing geometries assembled from stable molecular fragments. Among these conformers, six structurally similar conformers, in which the 2-hydr oxyl group forms hydrogen bondings with both the O atom of the 4-carbonyl g roup in 1,3-fashion and the O atom of 1-carboxylic acid in 1,2-fashion simu ltaneously, are found to be particularly stable. Thus, the conformational p reference of I appears to be governed by arrangements and strength of intra molecular hydrogen bondings. To examine conformational natures of 1 in solu tions more accurately, we corrected the thermochemical properties and carri ed out self-consistent reaction field calculations. Going from the gas phas e to solutions, the basic features of the conformational preferences in 1 a lso appear to be maintained in solutions including a highly polar aqueous m edium, despite slight changes in the population of each conformer.