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Online powder X-ray diffraction, employing a flow-through cell [Hammond et al. Cryst. Growth Des. 2004, 4, 943] and a previously developed chemometric method [Chen et al. Anal. Chem. 2005, 77, 6563], was applied for quantitative analysis of the polymorphic phase transformation from the metastable R-form to the stable β-form of L-glutamic acid (LGA). The process of interconversion was monitored in aqueous slurries, using a jacketed 400 mL magnetically stirred reactor as a function of temperature. Calibration studies revealed that the current detection limits are ca. 0.8 and 0.2 wt%, respectively, for Rand β-forms of LGA as determined for slurries of LGA in methanol and good signal detection can be accomplished using a data acquisition time of 10 s albeit with increased noise levels. Compositions of slurries, in terms of the amounts of the individual solid phases present, were calculated from the areas of individual, discriminating peaks associated with the phases. Analysis of the diffraction peaks arising from the (111) reflection, 2θ ) 18°for the R-form and (102) reflection, 2θ ) 31°for the β-form, was used to obtain the rates of phase interconversion. Phenomenologically, the rate law observed for dissolution of the R-form was -D R ) k dR and the rate law observed for growth of the β-form was D β ) k gβ C β where C β is the concentration of the β-form expressed in weight percent. At 45 °C, the values of the rate constants k dR and k gβ were 18 × 10 -4 wt% s -1 and 3 × 10 -4 s -1 , respectively. Activation energies calculated, using the Arrhenius relationship, were found to be 43.9 kJ/mol with k dR0 calculated to be 25.9 × 10 3 wt% s -1 for the dissolution of R-form and 47.0 kJ/mol with k gβ0 calculated to be 16.2 × 10 3 s -1 for the growth of the β-form. The activation energy calculated from a different, characteristic peak of the β-form at 2θ ) 21°, corresponding to the reflection from (101) planes, was 32.1 kJ/mol suggesting that there might be some texture effects manifested in the flow field of the crystalline slurry. The overall quantitative accuracy of this method together with potential for improvement is also discussed. † This paper was originally intended for publication as part of the special issue on Facets of

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.