Jan Čejka

Characterizing Crystal Disorder of Trospium Chloride: A Comprehensive,13C CP/MAS NMR, DSC, FTIR, and XRPD Study

Analysis of C cross-polarization magic angle spinning (CP/MAS) nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray powder diffraction data of trospium chloride (TCl) products crystallized from different mixtures of water-ethanol [φ(EtOH) = 0.5-1.0] at various temperatures (0°C, 20°C) and initial concentrations (saturated solution, 30%-50% excess of solvent) revealed extensive structural variability of TCl. Although (13) C CP/MAS NMR spectra indicated broad variety of structural phases arising from molecular disorder, temperature-modulated DSC identified presence of two distinct components in the products. FTIR spectra revealed alterations in the hydrogen bonding network (ionic hydrogen bond formation), whereas the X-ray diffraction reflected unchanged unit cell parameters. These results were explained by a two-component character of TCl products in which a dominant polymorphic form is accompanied by partly separated nanocrystalline domains of a secondary phase that does not provide clear Bragg reflections. These phases slightly differ in the degree of molecular disorder, in the quality of crystal lattice and hydrogen bonding network. It is also demonstrated that, for the quality control of such complex products, (13) C CP/MAS NMR spectroscopy combined with factor analysis (FA) can satisfactorily be used for categorizing the individual samples: FA of (13) C CP/MAS NMR spectra found clear relationships between the extent of molecular disorder and crystallization conditions.

Preparation of new trifluoromethyl substituted tri- and tetracyclic heterocycles with Peganin skeleton from a methyl 3,3,3-trifluoropyruvate / 2-aminobenzylamine adduct

Abstract Addition of 2-aminobenzylamine to methyl trifluoropyruvate afforded methyl 2-((2-aminobenzyl)amino)-3,3,3-trifluoro-2-hydroxypropionate, which reacted with various ketones to give new fluorinated tricyclic and tetracyclic heterocycles with the skeleton of the alkaloid Peganin.

CrystalCMP: an easy-to-use tool for fast comparison of molecular packing

A new approach is introduced for the comparison of molecular packing and the identification of identical crystal structure motifs. It has been tested on data sets for the solid forms of benzamide, cabergoline and trospium. In this approach, the packing similarity is calculated using a simple formula involving the distances between molecular centres and the relative orientations of molecular entities inside a finite molecular cluster. The approach is independent of the atomic labelling, the unit-cell parameters, the space group setting and the number of molecules in the asymmetric part of the unit cell. Owing to its low sensitivity to volume changes, this approach allows the comparison of various solid forms (such as polymorphs, hydrates, solvates, co-crystals or salts) of identical or similar molecular compounds. The method is also suitable for identifying similar results from direct space methods, which are often used in powder diffraction.

calix-Tris-Tröger's bases – a new cavitand family

The first members of a new cavitand family, represented by calix-shaped tris Trögers base diastereoisomers, are prepared via step-by-step synthesis as well as one-pot mixed troegeration.