RT Journal Article
SR Electronic
T1 Molecular Determinants for Drug-Receptor Interactions
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 558
OP 564
VO 20
IS 3
A1 GIULIANO BANDOLI
A1 DORE A. CLEMENTE
A1 ANTONIO GRASSI
A1 GIUSEPPE C. PAPPALARDO
YR 1981
UL http://molpharm.aspetjournals.org/content/20/3/558.abstract
AB The crystal and molecular structure of 2-pyrrolidone-N-acetamide was determined by X-ray analysis. Crystal (monoclinic) data were as follows: a = 16.376(8), b = 6.413(5), c = 6.493(5) Å; b = 92.21(5)°, Z = 4, space group P21/n. The 2-pyrrolidone ring and the amide group are planar, their planes being almost perpendicular (dihedral angle between the normals is 88.2° with the C=O fragment of the amide group directed toward the ring (in a perpendicular trans arrangement). All bond angles and distances were in good agreement with expected standard values. In the crystals, two molecules from a dimer through N(2)(X,Y,Z)----O(2) (1 - X, 1 - Y, 1 - Z) and its symmetrical equivalent, linked by hydrogen bonds of 2.95 Å, with an additional hydrogen bond of 2.93 Å between N(2)(X,Y,Z) and O(1)(X,Y, 1 + Z). The N(1) atom of the ring is not involved in any such interactions. Geometry and conformation of the 2-pyrrolidone ring were reviewed. The results of quantum mechanical calculations, carried out using an ab initio method with an STO-3G basis set indicate for the free molecule a preferred, twisted cis conformation that appears essentially determined by the intramolecular hydrogen bond between the 0(1) atom and the amide group. The shape of the minimum energy zone (wide and shallow) and the small energy difference between the twisted cis conformation and the one found in the crystal suggest that in solution the conformation of the solid is partially retained and that an equilibrium is likely to occur between several energetically preferred conformations.