Marcin Podsiadło

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.

1,1-Dichloroethane: A Molecular Crystal Structure without van der Waals Contacts?

Isochoric and isobaric freezing of 1,1-dichloroethane, CH3CHCl2, mp=176.19 K, yielded the orthorhombic structure, space group Pnma, with the fully ordered molecules, in the staggered conformation, located on mirror planes. The CH3CHCl2 ambient-pressure (0.1 MPa) structures were determined at 160 and 100 K, whereas the 295 K high-pressure structures were determined at 0.59 and 1.51 GPa. At 0.1 MPa, all intermolecular distances are considerably longer than the sums of the van der Waals radii, and only a pressure of about 1.5 GPa squeezed the Cl...Cl and Cl...H contacts to distances commensurate with these sums. The exceptionally large difference between the melting points of isomeric 1,1- and 1,2-dichloroethane can be rationalized in terms of their molecular-packing efficiency. It has been shown that the location of atoms in molecules affects their intermolecular interactions, and hence their van der Waals radii are the function of molecular structures.

In-situ high-pressure crystallization and compression of halogen contacts in dichloromethane

The structure of dichloromethane, CH2Cl2, crystallized in situ in a diamond-anvil cell, has been determined by single-crystal X-ray diffraction at 1.33 and 1.63 GPa. The pressure-frozen crystal was determined to be orthorhombic, with the space group Pbcn, and isostructural with the low-temperature phase at 0.1 MPa. The CH2Cl2 molecules are located on one set of crystallographic twofold axes. The characteristics determined for the CH2Cl2 crystal (compression of the close intermolecular contacts, molecular association and the crystal habit of dichloromethane) suggest that the crystal cohesion forces are dominated by H...Cl interactions rather than by Cl...Cl attractions.

Halogen⋯halogen contra C–H⋯halogen interactions

Pressure affects the competition between C–H⋯X hydrogen bonds and X⋯X halogen⋯halogen interactions. In bromomethane, CH3Br, pressure changes the molecular arrangement of the two solid-state phases of this compound: low-pressure phase α is dominated by halogen⋯halogen interactions, whereas above 1.5 GPa the β phase is governed by C–H⋯halogen bonds. The CH3Br phase α is isostructural with solid CH3I of orthorhombic space group Pnma, while CH3Br phase β is polar, isostructural with CH3Cl and CH3CN crystals, of orthorhombic space group Cmc21. The crystal structures of CH3Cl (b.p. = 249.1 K) and CH3Br (b.p. = 276.7 K) have been determined by high pressure single-crystal X-ray diffraction up to 4.38 GPa and 2.85 GPa, respectively. In CH3Br, pressure of 1.5 GPa enforces the close packing and opposite electrostatic-potential matching between molecular surfaces in contact. The interweaved C–H⋯X bonded diamondoid networks of β-CH3X are similar to those of acetonitrile, H2O ice VII and solidified X2 halogens. The phase diagrams of CH3Br and CH3Cl have been constructed.

Molecular interactions in crystalline dibromomethane and diiodomethane, and the stabilities of their high-pressure and low-temperature phases

Dibromomethane, CH2Br2, and diiodomethane, CH2I2, have been in situ pressure-crystallized in a diamond-anvil cell and their structures determined by single-crystal X-ray diffraction at 0.61 and 0.16 GPa, respectively. The pressure-frozen CH2Br2 crystal is isostructural with its C2/c phase obtained by cooling. CH2I2 is known to form several phases at low temperature, one of which is isostructural with CH2Br2. However, pressure freezing leads to the polar Fmm2 phase. The formation of the polar CH2I2 structure at 0.16 GPa has been rationalized by the electrostatic and anisotropic van der Waals interactions of the I atoms. No ferroelectric behaviour of the Fmm2 polar phase II of CH2I2 has been determined. The diffraction, calorimetric and dielectric constant studies reveal considerable temperature hysteresis of transformations between the CH2I2 phases, as well as metastable regions strongly dependent on the sample shape and history.

Isobaric and isochoric freezing of CH2BrCl and isostructural relations between CH2Cl2, CH2Br2 and CH2BrCl

Bromochloromethane, CH(2)BrCl, has been temperature-frozen and in situ pressure-frozen and the structure determined by X-ray diffraction at low temperatures of 170 and 100 K at ambient pressure (0.10 MPa), and at high pressures of 1.04 and 1.72 GPa at room temperature (295 K). CH(2)BrCl exhibits a remarkable polymorphism: at low temperature it crystallizes in the monoclinic space group C2/c (phase I), isostructural to the crystals of CH(2)Br(2). The pressure-frozen crystal of CH(2)BrCl is orthorhombic, space group Pbcn, and is isostructural to the crystal of CH(2)Cl(2). In both phases I and II the Br and Cl atoms are substitutionally disordered. The freezing temperatures and pressures of simple dihalomethanes have been correlated to their molecular weight and halogen... halogen distances. Calculated electrostatic potential surfaces have been related to the different crystal packing of dihalomethanes investigated.

Competing patterns of weak directional forces in pressure-frozen CH2ClI and CH2I2.

Isostructural relations and phase transitions of dihalomethanes have been rationalized by the competing patterns of CH...halogen hydrogen bonds and halogen...halogen interactions, the common weak directional interactions in soft organic matter. Pressure-frozen chloroiodomethane, CH(2)ClI, at 295 K and 0.72 GPa forms centrosymmetric phase III, which at ca. 400 K and 1.6 GPa disproportionates into CH(2)Cl(2) and CH(2)I(2). The directional character of intermolecular contacts between halogen atoms results from the characteristic anisotropic charge distribution on molecular surface.

Isostructural relations in dihalomethanes and disproportionation of bromoiodomethane

The directional character of halogen⋯halogen forces has been evidenced by specific structural features of bromoiodomethane crystals, CH2BrI. The crystals were in-situ grown in isobaric conditions in a glass capillary and in isothermal and isochoric conditions in a diamond-anvil cell, and the structures have been determined by single-crystal X-ray diffraction at 0.10 MPa/220 K, 0.10 MPa/100 K, 0.54 GPa/295 K. The freezing point for isothermal compression at 295 K is 0.47 GPa. At 0.80 GPa/490 K CH2BrI disproportionates to CH2I2 and CH2Br2. The ambient-pressure/low-temperature and 0.54 GPa/ambient-temperature CH2BrI crystals are monoclinic, space-groupC2/c, isostructural with CH2Br2, CH2I2 and CH2BrCl phases. High-pressure structure of CH2I2, determined at 0.80 GPa/295 K, is orthorhombic, space-group Fmm2. Crystals of CH2Br2, CH2BrI and CH2I2 are 2-dimensionally isostructural. The polar arrangement of molecular sheets in CH2I2 is favoured by CH⋯I hydrogen bonds, which are absent in the centrosymmetric CH2BrI structure. The temperature at which CH2BrI disproportionates into CH2Br2 and CH2I2 is raised by pressure, as this process requires that CH2BrI be liquid.

Chemistry of density: extension and structural origin of Carnelley's rule in chloroethanes

Low-density liquids and solids, with all intermolecular contacts longer than the sum of van der Waals radii, are formed by all ethanes chlorinated at one locant: CH2ClCH3, CHCl2CH3 and CCl3CH3. The concepts of molecular symmetry described by Carnelley and that of point groups have been compared. Carnelleys rule, when applied to liquid and solid chloroethanes clearly reveals the density dependence on the presence of intermolecular Cl⋯Cl and H⋯Cl short contacts, or their absence due to steric hindrances of overcrowded substituents. At 2.62 GPa, CH2ClCH3 freezes directly into phase II, with molecules arranged into layers with short Cl⋯Cl, H⋯Cl and H⋯H contacts. Only for CH2ClCH3, both the low-density phase at low temperature and closely-packed phase above 2.62 GPa have been observed.

Density, freezing and molecular aggregation in pyridazine, pyridine and benzene

Molecular aggregation of pyridazine (C4H4N2) and pyridine (C5H5N) has been compared with that of benzene (C6H6) in its phases I and II. The crystal structures of pyridazine and pyridine, in situ crystallized in a diamond-anvil cell, have been determined by single-crystal X-ray diffraction at 0.27 and 0.61 GPa (C4H4N2) and 1.23 GPa (C5H5N). The isochoric and isothermal freezing of pyridazine yielded monoclinic crystals, space-group P21/n, of the same symmetry as those obtained by isobaric freezing at 0.1 MPa below 100 K. At 295 K pyridine froze at 1.23 GPa in orthorhombic space-group Pna21. The compressibility measurement of both compounds have been performed at 295 K up to ca. 2 GPa and confirmed their freezing pressure of 0.19 GPa for pyridazine and 0.53 GPa for pyridine. The interactions governing the molecular arrangement in the series of pyridazine, pyridine and benzene structures, gradually change from C–H⋯N to C–H⋯π hydrogen bonds. High pressure also favours the C–H⋯N interactions over the C–H⋯π bonds in pyridine, but benzene remains more stable than pyridazine and pyridine. The phase diagram of pyridine has been outlined up to 2.0 GPa. A pyridine–methanol 3 : 1 co-crystal has been obtained at 1.80 GPa/295 K.