Comparison of the Crystal Chemistry, the Process Conditions for Crystallization and the Relative Structural Stability of Two Polymorphic Forms of N^G-monomethyl-l-arginine Hydrochloride

Abstract

Crystal structures of two conformational polymorphs (FormA and Form D) of N G -monomethyl-L-arginine hydrochloride, a drug developed to treat septic shock, are presented. Form A is orthorhombic in a tetra-molecular unit cell and Form D is monoclinic in a bimolecular unit cell (space groups P2 1 2 1 2 1 and P2 1 , respectively). The two forms display differences in the conformation of the terminal N-methyl group, which is cis in Form D and trans in Form A. Structural energy calculations demonstrate that Form D has a lower lattice energy compared to Form A (-134.7 and -128.8 kcal/mol, respectively). This is supported by solution stability studies where the potential for solution-mediated phase transformation was investigated and Form D is found to be the more stable polymorphic structure at room temperature. The melting behavior of forms A and D indicates a monotropic phase transformation relationship between the two polymorphic forms albeit their melting points (215.7 and 203.7 °C for forms A and D, respectively) would be more consistent with enantiotropic behavior. Solution-mediated phase transformation is thought to be the likely mechanism for monotropic phase interconversion between the two polymorphs. Graph set analysis of the hydrogen bond patterns for both forms reveals the respective first-order graph sets to consist solely of chain motifs involving only the cation moieties. The overall hydrogen bond patterns for both forms were also found to exhibit characteristic packing motifs around the chloride counterion associated with it acting as a hydrogen bond acceptor, bonding to donor groups from three different molecular cations. In this respect, Form A hydrogen bonds with two donor groups towards the carboxylic end and one towards the N-methyl end of the molecular cation and Form D hydrogen bonds with two donor groups towards the N-methyl end and one towards the carboxylic end. With the presence of a high number of hydrogen bond donors and acceptors, the potential for the formation of other packing motifs and associated polymorphic forms is reviewed.

Synthesis, single crystal growth, characterization and comparison of two new enone shifted chalcones and their NLO behaviour

“…2 Strong intra molecular strength contributes to a good output in SHG, 9b which attracts a great deal of attention due to their large optical nonlinearities. 15 Recently, it has been observed that among many organic compounds reported for their second harmonic generation, chalcone derivatives have displayed excellent blue light transmittance, large first order hyperpolarizability with high damage threshold and good crystallizability. 13 Among the many known organic NLO materials, some chalcone materials exhibited extremely high and fast nonlinearity 1,2,16,17 and established a preference to crystallize in non-centrosymmetric structures.…”