Selective Nucleation and Discovery of Organic Polymorphs through Epitaxy with Single Crystal Substrates

Crystallization of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (1), previously found to produce six conformational polymorphs from solution, on single-crystal pimelic acid (PA) substrates results in selective and oriented growth of the metastable “YN” (yellow needle) polymorph on the (101)PA faces of the substrate. Though the freshly cleaved substrate crystals expose (101)PA and (111)PA faces, which are both decorated with [101̄]PA ledges that could serve as nucleation sites, crystal growth of YN occurs on only (101)PA. Goniometry measurements performed with an atomic force microscope reveal that the (001)YN plane contacts (101)PA with a crystal orientation [100]YN||[010]PA and [010]YN||[101̄]PA. A geometric lattice analysis using a newly developed program dubbed GRACE (geometric real-space analysis of crystal epitaxy) indicates that this interfacial configuration arises from optimal two-dimensional epitaxy and that among the six polymorphs of 1, only the YN polymorph, in the observed orientation, achieves reasonable epitaxial match to (101)PA. The geometric analysis also reveals that none of the polymorphs, including YN, can achieve comparable epitaxial match with (111)PA, consistent with the absence of nucleation on this crystal face. In contrast, sublimation of 1 on cleaved succinic acid (SA) substrates, which expose large (010)SA faces decorated with steps along [101̄]SA, affords growth of several polymorphs, each with multiple orientations, as well as oriented crystals of a new metastable polymorph on the (010)SA surfaces. The lack of polymorphic selectivity on (010)SA can be explained by the geometric lattice analysis, which reveals low-grade epitaxial matches between (010)SA and several polymorphs of 1 but no inherent selectivity toward a single polymorph. These observations demonstrate the sensitivity of crystal nucleation to substrate surface structure, the potential of crystalline substrates for selective nucleation and discovery of polymorphs, and the utility of geometric lattice modeling for screening of substrate libraries for controlling polymorphism

Salting Benzenes^†

Simple salt crystals, such as potassium sulfate or barium acetate, were grown in the presence of a variety of aromatic molecules, especially aniline derivatives, bearing sulfonate or carboxylate substituents. We call this process salting, borrowing the term from Michl and co-workers who coined it in a related context (Kirkor, E.; Gebicki, J.; Phillips, D. R.; Michl, J. J. Am. Chem. Soc. 1986, 108, 7106−7107). Particular growth sectors of the resultant crystals were luminescent, and the emitted light was highly polarized indicating that the benzene derivatives were oriented inside of the salt lattices. These results are presented in the context of a generalization of single crystal matrix isolation; isomorphous matching of hosts and guests need not be a constraint. We show by polarization spectroscopy and magnetic resonance that different faces of the crystals will entrap molecules in different conformations otherwise separated by small energies in solution. Metastable triplet states are remarkably long-lived at room temperature in salt matrixes. The mechanisms of benzene derivative incorporation depend highly on secondary surface structures that are imaged by differential interference contrast microscopy. Luminescent molecules identify these features by lighting-up particular substructures and as such serve as probes of crystal growth mechanisms. We show how patterns of light in crystals are used to assign absolute growth directions. We conclude by arguing that the results herein can be extended to a limitless range of guests, while encouraging the use of salts as matrixes for the study of organic compounds

Single-Crystal Matrix Isolation of Biopolymers

Single-Crystal Matrix Isolation of Biopolymer

Thermochemistry and Conformational Polymorphism of a Hexamorphic Crystal System

5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile has been crystallized as six solvent-free polymorphs, which differ in the mode of packing and in molecular conformation. The conformational difference results principally from the thiophene torsion relative to the o-nitroaniline fragment, which leads to different crystal colors (red, orange, and yellow). Thermodynamic stability relationships between polymorphs have been determined from solid-state conversions and calorimetric data of melting and eutectic melting. Vibrational spectroscopy and ab initio calculations showed that most conformers in solution feature perpendicularly arranged thiophene and o-nitroaniline fragments, although a minor population of more planar conformers also exist. Crystallization has a stabilizing effect for more planar and higher dipole conformers over perpendicular ones by 3−6 kJ/mol. The only exception to this pattern is the one polymorph containing weak intermolecular hydrogen bonds