Jan Rohlíček

MCE2005 – a new version of a program for fast interactive visualization of electron and similar density maps optimized for small molecules

A new version of MCE is described. This new version supports atom-position generation based on space groups and can display more unit cells around the basic unit cell. The display settings have been improved to allow the colors of the background, atoms and maps to be changed.

Capecitabine from X-ray powder synchrotron data

In the title compound [systematic name 5-deoxy-5-fluoro-N-(pentyloxycarbonyl)cytidine], C15H22FN3O6, the pentyl chain is disordered over two positions with refined occupancies of 0.53 (5) and 0.47 (5). The furan ring assumes an envelope conformation. In the crystal, intermolecular N—H⋯O hydrogen bonds link the molecules into chains propagating along the b axis. The crystal packing exhibits electrostatic interactions between the 5-fluoropyrimidin-2(1H)-one fragments of neighbouring molecules as indicated by short O⋯C [2.875 (3) and 2.961 (3) Å] and F⋯C [2.886 (3) Å] contacts.

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.

Studies on the crystal structure and arrangement of water in sitagliptin l-tartrate hydrates

The hydration/dehydration behavior of four distinct channel hydrates of sitagliptin L-tartrate (SLT) was investigated by thermoanalytical methods, dynamic vapour sorption analysis and variable humidity X-ray powder diffraction. The crystal structures were determined from single crystal and powder X-ray diffraction data. A survey of the forms revealed that SLT hydrates exhibit both stoichiometric and non-stoichiometric features demonstrating that the characterization of channel hydrates can be challenging as their behavior is not inevitably unambiguous. Upon dehydration, the parent hydrates retain their structures, and the lattices do not collapse; isostructural dehydrates are formed. The solved crystal structures of the packing polymorphs SLT phase 1 and phase 2 provide an effective basis to rationalize the observed hydration/dehydration pathways. The structures are dominated by infinite sheets formed by hydrogen tartrate anions, linked by hydrogen bonds. These layers separate the parallel, infinite chains of water molecules. The water molecules stabilize the structures by providing additional hydrogen bonds between the cation and the anion. This interaction substantiates the high affinity of water molecules to the API framework and explains the stoichiometric characteristics observed by solid state analytical methods. On the other hand, their non-stoichiometric character is evidenced by the non-destructive dehydration processes.

Capecitabine from X-ray powder synchrotron data. Corrigendum

Erratum to Acta Cryst. (2009), E65, o1325–o1326.

Alaptide from synchrotron powder diffraction data.

The title compound [systematic name: (8S)-8-methyl-6,9-diazaspiro[4.5]decane-7,10-dione], C9H14N2O2, consists of two connected rings, viz. a piperazine-2,5-dione (DKP) ring and a five-membered ring. The DKP ring adopts a slight boat conformation and the bonded methyl group is in an equatorial position. The five-membered ring is in an envelope conformation. In the crystal structure, intermolecular N—H⋯O hydrogen bonds link molecules into chains running parallel to the c axis.

Methyl-ergometrine maleate from synchrotron powder diffraction data.

The title compound {systematic name: 9,10-didehydro-N-[1-(hydroxymethyl)propyl]-d-lysergamide maleate}, C20H26N3O2 +·C4H3O4 −, contains a large rigid ergolene group. This group consists of an indole plane connected to a six-membered carbon ring adopting an envelope conformation and N-methyltetrahydropyridine where the methyl group is in an equatorial position. In the crystal, intermolecular N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds form an extensive three-dimensional hydrogen-bonding network, which holds the cations and anions together.

Correction: Studies on the crystal structure and arrangement of water in sitagliptin L-tartrate hydrates

Correction for ‘Studies on the crystal structure and arrangement of water in sitagliptin L-tartrate hydrates’ by Eszter Tieger et al., CrystEngComm, 2016, 18, 3819–3831.

CCDC 1495585: Experimental Crystal Structure Determination

Related Article: Eszter Tieger, Violetta Kiss, Gyorgy Pokol, Zoltan Finta, Jan Rohlicek, Eliska Skořepova, Michal Dusek||CrystEngComm|||doi:10.1039/C6CE01834C

Structural characterization of tenofovir disoproxil fumarate Form I using X-ray and electron diffraction and a study of its conversion to related solid forms

Tenofovir disoproxil fumarate (TDF) is an orally delivered pharmaceutical compound used for the treatment of HIV and chronic hepatitis, which acts as an inhibitor of nucleotide reverse transcriptase. There are many solid forms of TDF described in patent literature; two of them we identified in drug products: Form I and Form A. It seems that during formulation the active pharmaceutical ingredient (API) undergoes partial to total conversion of TDF Form I to TDF Form A. The aim of the study was to propose a formulation of tablet containing pure TDF Form I. However, we observed that TDF Form I converted either to TDF Form A or recently described TDF Form I-1. We investigated, when and why did the conversion occur and whether the conversion could be avoided, and how. The influence of pH and possible interaction with excipients were studied. The conditions enabling using wet granulation in technology while preventing the undesired conversion were found. The stabilization was achieved either by replacement of used disintegrants or pH adjustment by acid addition to the current composition of formulation. We also found that TDF Form I underwent the same non-reversible phase transformation to TDF Form I‐1 both upon heating, as well as upon exposure to humidity. The phenomenon was observed by temperature resolved X-ray powder diffraction (XRPD), solid state NMR spectroscopy and DSC. As neither structure of TDF Form I nor of TDF Form I-1 has been determined, we focused on structure solution by combining high quality XRPD, synchrotron single crystal XRD and electron diffraction. We were successful in indexing of the powder of TDF Form I, which was in agreement with the indexing of the microcrystals measured on synchrotron. Moreover, a structure of another tenofovir compound – tenofovir disoproxil phosphate, was successfully determined from single crystal XRD data. Acknowledgment: This work was supported by the Grant Agency of Czech Republic, Grant no. 106/16/10035S and received financial support from specific university research (MSMT No 20/2016). We acknowledge the ESRF for provision of synchrotron radiation facilities and we would like to thank J. Wright for assistance in using beamline ID11. Figure 1. TDF Form I converted either to TDF Form A upon slurrying in water or to recently described TDF Form I-1 upon heating or exposure to water.