Solid-state tautomeric structure and invariom refinement of a novel and potent HIV integrase inhibitor

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 ¹H and ¹³C NMR correlation spectroscopy study confirm that the same tautomer exists in solution as in the solid state.

Determination of the electron density in methyl (±)-(1S,2S,3R)-2-methyl-1,3-di­phenyl­cyclo­propane­carboxyl­ate using refinements with X-ray scattering factors from wavefunction calculations of the whole mol­ecule

The electron density in the title substituted cyclo­propane has been determined by refining single-crystal X-ray data using scattering factors derived from quantum mechanical calculations. Topological analysis of the electron densities in the three cyclo­propane C-C bonds was carried out and shows the effects of substitution on these C-C bonds.