title: Solid-state tautomeric structure and invariom refinement of a novel and potent HIV integrase inhibitor.
abstract: The conformation and tautomeric structure of (Z)-4-[5-(2,6-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl]-4-hydroxy-2-oxo-N-(2-oxopyrrolidin-1-yl)but-3-enamide, C27H22F3N3O5, in the solid state has been resolved by single-crystal X-ray crystallography. The electron distribution in the molecule was evaluated by refinements with invarioms, aspherical scattering factors by the method of Dittrich et al. [Acta Cryst. (2005), A61, 314-320] that are based on the Hansen-Coppens multipole model [Hansen & Coppens (1978). Acta Cryst. A34, 909-921]. The β-diketo portion of the molecule exists in the enol form. The enol -OH hydrogen forms a strong asymmetric hydrogen bond with the carbonyl O atom on the β-C atom of the chain. Weak intramolecular hydrogen bonds exist between the weakly acidic α-CH hydrogen of the keto-enol group and the pyridinone carbonyl O atom, and also between the hydrazine N-H group and the carbonyl group in the β-position from the hydrazine N-H group. The electrostatic properties of the molecule were derived from the molecular charge density. The molecule is in a lengthened conformation and the rings of the two benzyl groups are nearly orthogonal. Results from a high-field (1)H and (13)C NMR correlation spectroscopy study confirm that the same tautomer exists in solution as in the solid state.
authors: Department of Chemistry, Emory University, Atlanta, GA 30322, USA. jbacsa@emory.edu
authors: John
authors: J
authors: Bacsa
authors: Maurice
authors: M
authors: Okello
authors: Pankaj
authors: P
authors: Singh
authors: Vasu
authors: V
authors: Nair
mesh_terms: D018360:Crystallography, X-Ray; D004583:Electrons; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry*
chemical_list: C580899:(Z)-4-(5-(2,6-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-hydroxy-2-oxo-N-(2-oxopyrrolidin-1-yl)but-3-enamide; D019428:HIV Integrase Inhibitors; D011725:Pyridines; D011759:Pyrrolidines; D012996:Solutions