Ewa Patyk

High-Pressure (+)-Sucrose Polymorph†

With the exponential rise in interest in the fundamental, commercial, and intellectual-property importance of crystal forms, the late Walter McCrone s provocative statement regarding the propensity for the formation of polymorphs is often cited: “It is at least this author s opinion that every compound has different polymorphic forms and that, in general, the number of forms known for each compound is proportional to the time and money spent in research on that compound.” (italics in original). In response to McCrone, the lack of evidence for more than one crystal form of two very common, indeed paradigmatic and often crystallized compounds, sucrose and naphthalene, has been frequently cited. Sucrose (saccharose, (+)-C12H22O11), common table sugar, is a particularly poignant example because of the well-known difficulty in inducing industrial-scale crystallizations and the countless variety of conditions and number of times it has been crystallized merely for human consumption. Virtually all of these crystallizations have been carried out under ambient pressure, which represents but a small region of phase space. About ten years ago, with the development of relatively straightforward techniques to explore phase space at pressures above ambient, we undertook a search for a highpressure form of sucrose. A second form was elusive for a number of years, and although the search eventually proved successful, as reported herein, the preparation and characterization of the high-pressure form of sucrose required overcoming a number of experimental difficulties and in the end proved to be remarkably different from the ubiquitous common form sucrose I. Although unstable at ambient conditions, sucrose II provides new information about this compound and all sugars in general. Sugars, in their variety of mono-, di-, and polysaccharides, are the main carriers for energy transport and storage in biological systems and the primary building blocks in living tissue. World-wide production of the disaccharide (+)-sucrose exceeds that of all other manufactured organic compounds. The molecule has considerable conformational freedom and many hydrogen-bonding functionalities (Figure 1), which might suggest the possibility or even tendency for the existence of multiple crystal forms, although there are no published statistics on such correlations between hydrogenbonding functionality, molecular flexibility, and the tendency to crystallize in multiple crystal forms. Nevertheless, as for many other widely studied monoand disaccharides, only a few cases of polymorphs were reported, for example for b-dallose. Cellulose, the most abundant polymer on Earth, and starch are also known for structural transformations and polymorphs. However, their macromolecular amorphous and microcrystalline composition allows for the determination of only average structural features. The structures of ribose anomers were revealed only recently. The sucrose crystals were shown to be stable between 20 K and 373 K, when sucrose starts to decompose. So, there are scarcely any data on the polymorphism of sugars, and no direct observation of their phase transitions have been reported. This information is essential for understanding the interplay between properties of sugars with the conformational flexibility and intermolecular interactions. Sucrose is uniquely suitable for investigating the structure–property relations at varied thermodynamic conditions. Our study reveals an extraordinary molecular flexibility combined with transforming hydrogen-bond types and patterns in sucrose I and II. The types and patterns of hydrogen bonds are characteristic Figure 1. Structural formula of sucrose, with hydrogen bonds and their transformations coded in colors described in the legend. A four-digit ORTEP code of symmetry transformations has been used for specifying intermolecular H bonds; the explicit transformation codes have been listed in Table S7 in the Supporting Information. For clarity, only the hydrogen bonds involving the H-donor atom in the molecule have been indicated. All O···O contacts and OH···O bonds, separately in phase I and II, are shown in Figure S5 in the Supporting Information. Letters “g” and “f” in atomic labels denote the glucose and fructose moieties, respectively.

Isothermal and isochoric crystallization of highly hygroscopic pyridine N-oxide of aqueous solution

Highly hygroscopic pyridine N-oxide, C5H5NO, dissolves in water absorbed from atmospheric air, but it crystallizes in the neat form of the aqueous solution under high pressure. The crystals grown at high-pressure isochoric conditions are of the same phase as that obtained from anhydrous crystallization at ambient pressure. This feature can be employed for retrieving compounds highly soluble in water from their aqueous solutions. The crystal structure is strongly stabilized by CH...O contacts. The crystal compression and thermal expansion as well as three shortest H...O distances comply with the inverse-relationship rule of pressure and temperature changes.

Conformational and H-Bonding Preferences for Facile Racemate Crystallization of Ribose

Recalcitrant crystallization and syrup formation are frequent features of natural sugars. This is the case of D-ribose, yielding low-quality crystals of mixed α- and β-pyranose anomers. However, large crystals of DL-ribose can be grown easily. The crystal structures of stable D-ribose forms I and II as well as DL-form II have been analyzed in terms of their compatibility with the molecular aggregation. The comparison of the potential energy of all conformers and their OH···O hydrogen-bonding patterns is consistent with the preferential racemate crystallization in terms of departures from the optimized isolated ribose molecule and its directional interactions. This analysis is aimed at rationalizing the interplay between the molecular structure and spontaneous crystallization of chiral compounds.