Supramolecular synthon polymorphism in modified amino acids. Structural, conformational and energy landscapes of N-benzoyl-2′-hydroxy-3-methylisovaline

Abstract

The title compound, N-benzoyl-2′-hydroxy-3-methylisovaline, representing synthon polymorphism, can be interesting inter alia from the point of view of modern supramolecular biofunctional materials. A novel crystalline phase (1) was successfully synthesized and its solid-state supramolecular architecture was comprehensively compared with the previously reported polymorphic form (2), deposited in the Cambridge Structural Database as Private Communication by Karr & Fronczek. Molecular conformation, qualitative and quantitative analysis of supramolecular interactions, including evaluation of their energies, were investigated by modern experimental and theoretical methods. The geometries of S and R enantiomers were optimized using DFT at the B3LYP-D3/6-311++G(d, p) basis set level of theory. The conformational structure of these stereoisomers in water was studied using the solvation CPCM model. Water has a slight effect on the geometry and relative stability of isomers. Hirhsfeld surface analysis revealed general similarity of interactions in both polymorphs and closely related isovaline derivatives retrieved from the Cambridge Structural Database, dominated by H⋯H, O⋯H/H⋯O and C⋯H/H⋯C intermolecular contacts, contributing to about 95% of the total HS area. Nevertheless, in (2) π … π stacking interactions play significant role in driving the polymorphism formation. The interplay of basic supramolecular synthons and long-range synthon aufbau modules at subsequent levels of the supramolecular architecture is discussed in detail. Overall, the supramolecular assemblies are composed of large synthons in the form of a layer in (1) and pseudohexagonally packed ribbons in (2), sustained by relatively strong H-bonds (alternating catemer-dimer mix) and π … π contacts, respectively. For a thorough and precise interpretation, two methodologies: Gavezzotti implemented in the PIXELC vs. a novel way via energy frameworks construction in the CrystalExplorer were used. It enabled deeper insight into the quantitative evaluation of the molecular pair-wise interactions energetics in the supramolecular structures of both polymorphs, revealing further differences between them.