K. Manoj

Highly efficient chiral resolution of DL-arginine by cocrystal formation followed by recrystallization under preferential-enrichment conditions.

An excellent chiral symmetry-breaking spontaneous enantiomeric resolution phenomenon, denoted preferential enrichment, was observed on recrystallization of the 1:1 cocrystal of dl-arginine and fumaric acid, which is classified as a racemic compound crystal with a high eutectic ee value (>95 %), under non-equilibrium crystallization conditions. On the basis of temperature-controlled video microscopy and in situ time-resolved solid-state (13) C NMR spectroscopic studies on the crystallization process, a new mechanism of phase transition that can induce preferential enrichment is proposed.

Isostructural molecular strings linked via conserved dipolar (ether) O⋯CO short contacts in conformational polymorphs of racemic 2,4-di-O-acetyl-6-O-tosyl-myo-inositol 1,3,5-orthoesters

Conformational dimorphs of racemic 2,4-di-O-acetyl-6-O-tosyl-myo-inositol 1,3,5-orthoformate and its orthoacetate analogue were characterized using single crystal X-ray diffraction, thermal analysis and hot-stage microscopy techniques. In these polymorphs, the tosyl group adopted different conformations due to the rotation about the O–S bond. A significant variation in the torsion angle for the tosyl group (∼56°) was observed for Form II crystal of the orthoformate derivative, which exhibited an intramolecular dipolar SO⋯CO (sulfonyl–carbonyl) short contact. An interesting feature in all conformational polymorphs is the formation of an isostructural string (despite the differences in the orientation of the tosyl group) linked via dipolar (ether) O⋯CO contacts, which is further stitched by other weak interactions to form different layers in their crystal lattice.

Solvent induced crystallization of 1,2,3,4(6),5-penta-O-acetyl-6(4)-O-[(1S)-10-camphor sulfonyl]-myo-inositol diastereomers associated via weak trifurcated C–H⋯O interactions

The title compound produced three different types of solvent inclusion crystals having a conserved dimeric association via trifurcated C–H⋯O interactions between the diastereomers. These ‘dimeric’ units are organized differently to produce three crystal types containing guest molecules. In type I and II, unit translated dimers created voids for guest inclusion, whereas in type III the guest sites were produced by helical association of dimers. Inclusion of dichloromethane gave two different types of crystals; however, we were unable to obtain unsolvated crystals of the title compound.

Preferential Enrichment of DL-Leucine Using Cocrystal Formation With Oxalic Acid Under Nonequilibrium Crystallization Conditions.

By utilizing the preferential enrichment (PE) technique, we achieved an improved enantiomeric resolution of DL-leucine (Leu) using a 1:1 cocrystal (DL-) of DL-Leu and oxalic acid. The crystal structure analysis of DL- indicated the occurrence of a novel type of phase transition and subsequent preferential redissolution of one enantiomer from the resulting crystals into solution.

Crystal engineering of homochiral molecular organization of naproxen in cocrystals and their thermal phase transformation studies

Since the racemic naproxen does not have the desired crystal structure essential to induce preferential enrichment, we used crystal engineering principle to produce the required homochiral R- and S-chains in the solid state. The cocrystal structures of racemic and S-naproxen (NPX) with bipyridine (BPY) and piperazine (PIZ) were determined, which consist of homochiral 1D naproxen chains that are associated by weak non-covalent interactions. Thermal studies of both racemic and S-naproxen–bipyridine cocrystals indicated a monotropic polymorphic transformation upon heating and the new crystalline phase was characterized by DSC, PXRD, hot-stage microscopy, and FT-IR spectroscopy.