High-Pressure Polymorphs of Molecular Solids: When Are They Formed, and When Are They Not? Some Examples of the Role of Kinetic Control Elena Boldyreva*
CRYSTAL GROWTH & DESIGN 2007 VOL. 7, NO. 9 1662-1668
REC-008 NoVosibirsk State UniVersity, Institute of Solid State Chemistry and Mechanochemistry Siberian Branch of the Russian Academy of Sciences, Kutateladze, 18, NoVosibirsk 630128 Russia ReceiVed January 29, 2007; ReVised Manuscript ReceiVed June 18, 2007
W This paper contains enhanced objects available on the Internet at http://pubs.acs.org/crystal. ABSTRACT: A few examples of the kinetic control of the formation of new polymorphs at high pressure are discussed. Crystallization of liquids, crystallization from solutions, and solid-state polymorphic transformations are considered. Introduction Control of polymorphism and polymorph prediction are the key problems of solid-state science. Apart from obvious practical importance, the ability to generate a desirable three-dimensional pattern from the available “building blocks” (synthones, structureforming units) is a challenge, and a test, to see whether we can really understand the factors that determine the formation of various crystal structures, their stability, and transformations. Quite a lot has been achieved in this field in the last century. The vast information on the topic is summarized in so many books and papers that they cannot be referred to in this contribution. As entry points, one could recommend a now classical monograph1 and recent books.2-4 The most typical techniques of controlling the growth of a desirable polymorph are based on the variations of the solvent, temperature conditions, the saturation of the solution, addition of impurities, surfactants, or templates, modification of the viscosity of the solution, use of electric/magnetic fields, etc. A relatively recent trend is to vary pressure conditions. This includes (i) crystallization of liquids at high pressures, (ii) crystallization from solutions at high pressures, and (iii) pressure-induced solid-state polymorphic transformations. Although the first experiments in these directions date back to the beginning of the 20th century, and many valuable examples can be found in the now classical books by Bridgman5,6 or by Vereshchagin and Kabalkina,7 most of the work on the high-pressure polymorphism of organic and molecular compounds was done only rather recently (see refs 8-22 as entry points). The field is still in its infancy compared to other disciplines, and a real understanding of the crystallization and/or phase transformations of molecular crystals at high pressures is lacking. There is substantial evidence that in many cases the process is controlled by kinetic rather than by thermodynamic factors. Crystallization of Pure Liquids at High Pressures. Crystallization of liquids at high pressure is known as an alternative to crystallization on cooling since the times of Bridgman.5,6 Later, many examples were published in papers by several groups.23-47 Sometimes, the same polymorph is formed as a result of the crystallization on cooling and with increasing pressure; examples are 1,2-dichloromethane37 and carbon disulfide.36 More often, the high-pressure and the low-temperature polymorphs differ. One of the examples is water: ambientpressure and high-pressure ices differ significantly in the * To whom correspondence should be addressed. E-mail: boldyrev@ nsu.ru.
structures and properties.42 Acetone,29 acetic acid,30 alcohols,27,30,31 benzene,23-26,41 chlorotrimethylsilane,39 1,2-dichloroethane,37 sulfuric acid,33 phenol,32 2-chlorophenol and 4-fluorophenol40 are further examples of compounds, liquid at ambient conditions, which also give different polymorphs on cooling and with increasing pressure. The low-temperature and the high-pressure forms may differ in the conformations of molecules, but, more often, the main structural difference is related to the orientation of the molecules with respect to each other and to the structure of hydrogen-bonded networks, or the type of carbonyl-carbonyl, or halogen-halogen, or π-π interactions. Sometimes, a low-temperature structure is disordered, and a high-pressure one is completely ordered. This holds, for example, for 1,3-cyclohexanedione.43 A comparison of the low-temperature and the high-pressure structures is helpful to estimate the relative energies of different noncovalent interactions, to study the conformational flexibility, and the factors determining the crystallization of a selected polymorph. In many cases, the structures formed are thermodynamically stable at the given P-T conditions, and phase diagrams can be used to predict reliably the formation of a given polymorph. However, some phases can be crystallized only following a special procedure, combining compression to a high pressure with a subsequent decompression to a lower value, at which crystallization eventually occurs. In many cases, the sample is recycled many times, combining compression with slight heating and subsequent cooling, to get a single-crystalline sample, for which the structure can be solved more easily. It is possible that for some highly polymorphic compounds a procedure involving only “pure” compression without temperature variation at all would give other forms than compression combined with temperature variations (either cooling or heating). At the present time, there is no experimental evidence to substantiate this hypothesis. This highlights the difficulty of pinpointing the effects of kinetic factors. Other kinetic factors (such as the rate of compression or the effects of “over pressurization”, the presence of impurities, the lack or presence of smooth surfaces in the gasket or even the presence of ruby) might also affect nucleation and crystal growth, and in this way could also influence high-pressure polymorphism of liquid compounds. Supersaturation, overcooling, seeding, impurities, and the presence of rough surfaces are well-known to be important for nucleation at ambient pressure. Crystallization at High Pressures from Solutions. Another possibility to obtain high-pressure polymorphs is to crystallize compounds, which are solid at ambient conditions, from their
10.1021/cg070098u CCC: $37.00 © 2007 American Chemical Society Published on Web 08/04/2007
High-Pressure Polymorphs of Molecular Solids
solutions, using the decrease in the solubility with increasing pressure, similar to how compounds are crystallized on cooling, using evaporation or antisolvent techniques. Crystallization at high pressure has been known since a very long time, but its systematic application for obtaining new polymorphs and solvates has started a few years ago.48-51 Some of them were never observed at ambient conditions before, also those forms, which turned out to be quenchable to ambient pressure. This is a vast field of research, not just because of the practical interest of obtaining new forms of pharmaceuticals or new molecular materials. It is very promising for understanding thermodynamic versus kinetic factors governing crystal growth and polymorph formation. Sometimes, high-pressure crystallization from a solution gives the polymorph, which is thermodynamically stable at these conditions. Paracetamol II (Pbca) provides such an example. At ambient pressure, paracetamol I (P21/n) is the stable form at any temperature, although, once obtained, paracetamol II can be preserved for an indefinitely long time, and even survive until melting, if the presence of even traces of water/alcohol is excluded.52 Paracetamol II was obtained from paracetamol I at high pressure (see more details in the next section)53 and was later shown to be the thermodynamically preferable phase at high pressures.54 Direct crystallization of paracetamol from ethanol solution at 1.1 GPa gave paracetamol II.49 In other cases, high-pressure crystallization from a solution gives metastable forms and is strongly affected by such “nonthermodynamic parameters” as the details of the compression procedure (e.g., first compressed, than decompressed to a lower, but still nonambient, pressure) or the rate of compression/ decompression. Crystallization may be sensitive to the solvent and to the concentration of the solution. Piracetam provides one such example, giving different forms on crystallization from different solvents and from the solutions of different concentrations in the same solvent.55,56,102 Thus, piracetam II recrystallizes from methanol at 0.1 GPa to give form III, from water at 0.4 GPa (6 M solution) to give form IV, which transforms either to form II or to form V, when depressurized to ambient pressure. Recrystallization from diluted aqueous solutions gives various hydrates, which can also dehydrate giving various polymorphs, depending on temperature, pressure, and the rate of their change.55,56 High pressure adds a new dimension to the old problems of the solvent-mediated polymorphic transformations, solvent effect on crystallization, templating effects in crystallization, crystallization and quenching of metastable polymorphs varying supersaturation, viscosity of solutions, etc. An additional difficulty is that the structure of solution can be pressure-dependent. It is well-known that mixtures of liquids can be more stable with respect to high-pressure solidification (giving either glassy or crystalline states). This phenomenon is widely used, for example, when EtOH is added to MeOH to prepare a pressuretransmitting liquid to reach higher pressures57 or when a small amount of water is added as the third component to increase the pressure of solidification even more.58 A solid dissolved in a liquid can also affect the structure of this liquid and its response to increasing pressure. For example, additives of amino acids, and some other small molecules, are known to increase the stability of water to solidification under pressure. This is considered as one of the mechanisms of stabilizing secondary structures of biopolymers with respect to pressure by introducing selected additives to the solution.59 Interestingly, the presence of water can influence the pressure-induced crystallization of the dissolved organic compounds as well.55,56
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Pressure-Induced Solid-State Polymorphic Transformations. Many papers deal with the pressure-induced polymorphic transformations in molecular solids (see refs 5-22, 53, 55, 6065 as examples). Sometimes, the high-pressure polymorph is the same as the low-temperature form; in other cases, this is not so. High-pressure polymorphs may have the same space group symmetry, as the original ambient-pressure form and even be isostructural with it (isosymmetric phase transitions), and in this case only a direct optical observation of the interface66-68 and a set of structure refinements at several pressures, showing if the cell parameters and volume changes with pressure are continuous or not,14-19,47,64,69-74 can help to distinguish between a phase transition and an anisotropic structural distortion of the same phase. The dynamics of hydrogen bonds, their squeezing and stretching, can play an important role in pressure-induced phase transformations and in the formation of the high-pressure polymorphs. Distortion of hydrogen bonds can be accompanied by the changes in the conformations of molecular rings, by the rotation of molecular fragments, or of molecules as a whole, by dynamic or static disordering of molecules and their moieties.8-22,60-65,69,75 More often than not, the transformations give metastable forms, and not the thermodynamically preferable one. The following facts can indicate the kinetically and not thermodynamically controlled transformations: (1) Different forms are obtained at the same conditions from different starting polymorphs. (2) Different forms are obtained on compression, and on decompression; transformations are not reversible. (3) Effect of pressure is different for single crystals and for powder samples. (4) The transformation is characterized by a pronounced induction period, a hysteresis, is incomplete, or is extended in a wide pressure range. (5) Different forms are observed depending on how rapid compression and decompression were and on how long the sample was held at a selected pressure. (6) The transformation is sensitive to the choice of the pressure-transmitting liquid (in which the sample is emerged in hydrostatic loading experiments) and to the presence of even traces of a liquid in a slurry. This can be illustrated by several examples: polymorphs of glycine (1-6), polymorphs of paracetamol (2-6), L-serine (3, 4), β-alanine (5), piracetam (1, 2, 6), CBr4 (2), L-cysteine (2, 3), pentaerythritol (3), chlorpropamide (6), indomethacine (6), etc. Three polymorphs of glycine, which can be crystallized at ambient conditions (often concomitantly) and which are very close in their thermodynamic stability,76-78 show a remarkably different stability with respect to increasing pressure. With increasing pressure, the R-polymorph is preserved at least up to 23 GPa (the highest pressure achieved in experiments),79 the β-polymorph undergoes a reversible single-crystal to singlecrystal polymorphic transformation at 0.76 GPa,67,80 the γ-polymorph is preserved up to 3.5 GPa, and then an extended polymorphic transformation starts, which is accompanied by the fragmentation of the single crystals into powder.80-84 The polymorphs of glycine convert easily into each other at ambient pressure in the presence of various gases such as water or NH3, or on recrystallization in solution, temperature changes or storage also induce transformations between the R-, β-, and γ-forms.77,78 Interestingly, the pressure-induced transformations of the β- and γ-polymorphs give two new polymorphs that were never before observed at ambient conditions: β-glycine gives
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Boldyreva
Figure 1. Schematic presentation of transitions between polymorphs of glycine.67,79,81-84 Notation in brackets was suggested later in ref 80.
β′-glycine with the structure related to that of the β-form, and γ-glycine transforms into the δ-glycine.67,80-84 On decompression, β′-glycine transforms back to the β-form without a hysteresis,67 whereas the δ-polymorph is preserved until 0.6 GPa (what is below even the β-β′ phase transition point) and then transforms into one more polymorph, the ζ-glycine, which cannot be accessed in another way.84 Recently, we have observed a transformation of γ-glycine into the δ-form at 0.8 GPa already (instead of 3.5 GPa or higher!), when a powder sample was kept at this pressure for several hours, and fluorinert was used as a pressure-transmitting liquid.85 Obviously enough, such a series of transformations cannot be described in terms of an equilibrium phase P-T diagram since different polymorphs of glycine are formed at the same pressure-temperature conditions, depending on the starting form. Instead of a phase diagram, one should use a schematic diagram, like the ones used when describing the formation of nonequilibrium forms on crystallization (Figure 1). When this paper was already under revision, similar observations were published for piracetam: different forms were obtained, depending on the starting form and on the compression-decompression procedure.56 For CBr4,4,5 for some low-dimensional organic conductors based on charge-transfer salts of bis(ethylenedithio)-tetra-thia-fulvalene and its analogues,86 for sodium oxalate,64 and for L-cysteine,87 new polymorphs were obtained on decompression, which could not be observed when increasing the pressure. The pressureinduced solid-state transformation of paracetamol I to paracetamol II was also observed not when increasing the pressure but on decompression: pressure first increased in one step to 1.6 GPa, then steadily up to 4.5 GPa, and after that it decreased slowly down to 1.3 GPa, and only at 1.3 GPa a sudden irreversible partial transition I f II was observed. When pressure was increased again, the concentration of form II increased, but the I f II transition was never complete.53 This polymorphic transition can illustrate one more peculiar effect: it was observed only when a powder sample was compressed, single crystals
of paracetamol I preserving their crystal structure and just being anisotropically compressed at least up to 5 GPa.70 A similar effect was described for pentaerythritol.61 For sodium oxalate, a sharp phase transition with the interface rapidly propagating through a crystal was observed by optical microscopy.66 When the same transition was monitored by X-ray powder diffraction, the low-pressure and the high-pressure phases could be observed simultaneously in a rather wide pressure range.64 An even more complicated situation was observed for L-serine. Sharp phase transitions I f II and II f III were detected in the single crystals of L-serine by optical microscopy and Raman spectroscopy68 and by single-crystal X-ray diffraction at about 5 GPa71,72 and at about 8 GPa.72,75 For single crystals of L-serine, the phase transitions I f II and II f III were observed reproducibly at the same pressures. During the I f II and the reverse II f I phase transitions in L-serine single crystals, an interface propagated rapidly (
