Isoenergetic Polymorphism: The Puzzle of Tolazamide as a Case Study.

In the present case study of tolazamide we illustrate how many seemingly contradictory results that have been obtained from experimental observations and theoretical calculations can finally start forming a consistent picture: a "puzzle put together". For many years, tolazamide was considered to have no polymorphs. This made this drug substance unique among the large family of sulfonylureas, which was known to be significantly more prone to polymorphism than many other organic compounds. The present work employs a broad and in-depth analysis that includes the use of optical microscopy, single-crystal and powder X-ray diffraction, IR and Raman spectroscopies, DSC, semiempirical PIXEL calculations and DFT of three polymorphs of tolazamide. This case study shows how the polymorphs of a molecular crystal can be overlooked even if discovered serendipitously on one of numerous crystallizations, and how very different molecular packings can be practically isoenergetic but still crystallize quite selectively and transform one into another irreversibly upon heating.

Low-temperature phase transition in glycine-glutaric acid co-crystals studied by single-crystal X-ray diffraction, Raman spectroscopy and differential scanning calorimetry.

The occurrence of a first-order reversible phase transition in glycine-glutaric acid co-crystals at 220-230 K has been confirmed by three different techniques - single-crystal X-ray diffraction, polarized Raman spectroscopy and differential scanning calorimetry. The most interesting feature of this phase transition is that every second glutaric acid molecule changes its conformation, and this fact results in the space-group symmetry change from P2(1)/c to P1. The topology of the hydrogen-bonded motifs remains almost the same and hydrogen bonds do not switch to other atoms, although the hydrogen bond lengths do change and some of the bonds become inequivalent.

From geology to biology: an interdisciplinary course in crystal growth.

This contribution shares experience of teaching an interdisciplinary university course in crystal growth with examples ranging from geology to biology. This is an attempt to combine teaching the basics of the classical and non-classical theories of crystallization with impressive examples of crystals growing around us and in the human body, as well as demonstration of the common phenomena in the growth of minerals in nature, crystalline materials in industry and the laboratory, and biomimetic and stimulus-responsive crystals. Lectures are supported by laboratory exercises. Students can also perform an individual research project and present an oral contribution at a mini-conference. Examples of the topics considered in the course are given, and an extensive list of references to papers and web resources is provided, which may be useful to those who want to implement anything from the authors' experience.

Glycinium semi-malonate and a glutaric acid-glycine cocrystal: new structures with short O-H...O hydrogen bonds.

Glycinium semi-malonate, C(2)H(6)NO(2)(+)·C(3)H(3)O(4)(-), (I), and glutaric acid-glycine (1/1), C(2)H(5)NO(2)·C(5)H(8)O(4), (II), are new examples of two-component crystal structures containing glycine and carboxylic acids. (II) is the first example of a glycine cocrystal which cannot be classified as a salt, as glutaric acid remains completely protonated. In the structure of (I), there are chains formed exclusively by glycinium cations, or exclusively by malonate anions, and these chains are linked with each other. Two types of very short O-H...O hydrogen bonds are present in the structure of (I), one linking glycinium cations with malonate anions, and the other linking malonate anions with each other. In contrast to (I), no direct linkages between molecules of the same type can be found in (II); all the hydrogen-bonded chains are heteromolecular, with molecules of neutral glutaric acid alternating with glycine zwitterions, linked by two types of short O-H...O hydrogen bonds.

Concomitant cocrystal and salt: no interconversion in the solid state.

A cocrystal and a molecular salt of ß-alanine and DL-tartaric acid, C3H8NO2+·C4H4O6-, of the same chemical composition, were studied over a wide temperature range by single-crystal and powder X-ray diffraction. Neither the interconversion between the two phases nor any polymorphic transitions were observed in the temperature range from 100 K to the melting points. This contrasts with the solvent-mediated phase transition from the salt to the cocrystal in a slurry that has been documented earlier.

Completing the picture of tolazamide polymorphism under extreme conditions: a low-temperature study.

We present the results of an experimental and computational study of structural changes in two polymorphs of tolazamide {systematic name: 1-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide}, C14H21N3O3S, on cooling to 100 K and reverse heating. No phase transitions occurred in this temperature range. The anisotropy of the thermal expansion was different for the two polymorphs and differed from that reported previously for the hydrostatic compression. The changes in different intermolecular contacts responsible for the strain anisotropy were analysed. Relative shortening of the contacts was related directly to their initial length and reversely to the steric density around them. Increasing steric density is likely to be the driving force for the conformational ordering of the azepane ring under compression.

New 1:1 and 2:1 salts in the `DL-norvaline-maleic acid' system as an example of assembling various crystal structures from similar supramolecular building blocks.

Molecular salts and cocrystals of amino acids have potential applications as molecular materials with nonlinear optical, ferroelectric, piezoelectric, and other various target physical properties. The wide choice of amino acids and coformers makes it possible to design various crystal structures. The amino acid-maleic acid system provides a perfect example of a rich variety of crystal structures with different stoichiometries, symmetries and packing motifs built from the molecular building blocks, which are either exactly the same, or differ merely by protonation or as optical isomers. The present paper reports the crystal structures of two new salts of the DL-norvaline-maleic acid system with 1:1 and 2:1 stoichiometries, namely DL-norvalinium hydrogen maleate, C5H12NO2+·C4H3O4-, (I), and DL-norvalinium hydrogen maleate-DL-norvaline, C5H12NO2+·C4H3O4-·C5H11NO2, (II). These are the first examples of molecular salts of DL-norvaline with an organic anion. The crystal structure of (I) has the same C22(12) structure-forming motif which is common for hydrogen maleates of amino acids. The structure of (II) has dimeric cations. Of special interest is that the single crystals of (I) which are originally formed on crystallization from aqueous solution transform into single crystals of (II) if stored in the mother liquor for several hours.

Crystallographic education in the 21st century.

There are many methods that can be used to incorporate concepts of crystallography into the learning experiences of students, whether they are in elementary school, at university or part of the public at large. It is not always critical that those who teach crystallography have immediate access to diffraction equipment to be able to introduce the concepts of symmetry, packing or molecular structure in an age- and audience-appropriate manner. Crystallography can be used as a tool for teaching general chemistry concepts as well as general research techniques without ever having a student determine a crystal structure. Thus, methods for younger students to perform crystal growth experiments of simple inorganic salts, organic compounds and even metals are presented. For settings where crystallographic instrumentation is accessible (proximally or remotely), students can be involved in all steps of the process, from crystal growth, to data collection, through structure solution and refinement, to final publication. Several approaches based on the presentations in the MS92 Microsymposium at the IUCr 23rd Congress and General Assembly are reported. The topics cover methods for introducing crystallography to undergraduate students as part of a core chemistry curriculum; a successful short-course workshop intended to bootstrap researchers who rely on crystallography for their work; and efforts to bring crystallography to secondary school children and non-science majors. In addition to these workshops, demonstrations and long-format courses, open-format crystallographic databases and three-dimensional printed models as tools that can be used to excite target audiences and inspire them to pursue a deeper understanding of crystallography are described.