title: Alpha-ketoamides and alpha-ketocarbonyls: conformational analysis and development of all-atom OPLS force field.
abstract: The molecular structures and barriers for the internal rotation around the OC-CO single bond in four alpha-ketoamides and eight alpha-ketocarbonyls have been determined from the MP3/aug-cc-pVDZ and MP2/aug-cc-pVDZ calculations. Alpha-ketocarbonyls with non-bulky substituents adopt planar conformations with two carbonyl oxygens in s-trans arrangement. The s-cis conformation is significantly less stable due to the electrostatic repulsion between the two carbonyl groups. Primary and secondary alpha-ketoamides are planar when the substituent at the carbonyl carbon is hydrogen or methyl group but tertiary alpha-ketoamides adopt a conformation where the OC-CO unit is significantly bent. Based on current ab initio structural data, a set of OPLS-AA force field parameters has been derived. These parameters can be used for the modeling of a variety of alpha-ketoamide or alpha-ketocarbonyl containing drugs such as novel protease inhibitors or neuroregenerative polyketides.
authors.affiliation: Department of Chemistry and Biochemistry, University of California-Santa Barbara, 93106, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kahn
authors.forename: T C
authors.initials: TC
authors.lastname: Bruice
mesh_terms: D000577:Amides / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D007659:Ketones / Q000737:chemistry*; D018942:Macrolides / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry*
chemical_list: D000577:Amides; D007659:Ketones; D018942:Macrolides; D011480:Protease Inhibitors