Solid-State Structure and Conformation of the Nootropic Agent 4-Hydroxy-2-oxo-1-pyrrolidineacetamide : X-Ray and Theoretical Self-Consistant Field Molecular Orbital (SCF-MO) Studies

抄録

The crystal and molecular structure of 4-hydroxy-2-oxo-1-pyrrolidineacetamide was determined by X-ray analysis. The molecular conformation found in the solid was compared with results of theoretical quantum mechanical calculations carried out by using an ab-initio method at the STO-3G level. Crystals (orthorhombic) of the studied nootropic agent were as follows : a=7.162 (6), b=8.852 (3), c=11.340 (8) Å ; Pbc2₁. The five-membered ring deviates from planarity, while the planes of the amide group and of the four atoms N (1)-C (1)-C (2)-C (4) are almost perpendicular in cis arrangement, with the 4-hydroxy group in the axial position. In the crystals, molecules are linked by two intermolecular hydrogen-bonds, namely O (3)…O (2) and N (2)…O (1), which are 2.77 and 2.92 Å long, respectively. Results of theoretical calculations indicate for the free molecule a twisted cis conformation, with the 4-hydroxy goup in the axial position, as the most preferred one. This appears to be determined by the intramolecular hydrogen-bond between the O (1) atom and amide group hydrogen atoms. The relative conformational energies indicate that several conformations about the minimum can be populated in the solution state. The geometry and conformational profile of the pharmacologically active investigated molecule were found to reproduce, with the exception of the puckered conformation of the fivemembered ring, those previously determined for the related analogous nootropic agent 2-oxo-1-pyrrolidineacetamide (piracetam), whose chemical structure differs only in the lack of the 4-hydroxy group in the β-position to the carbonyl group.