Article pubs.acs.org/crystal
Polymorphism Arising from Differing Rates of Compression of Liquids Published as part of the Crystal Growth & Design Mikhail Antipin Memorial virtual special issue. Joe Ridout,† Louise S. Price,‡ Judith A. K. Howard,† and Michael R. Probert*,§ †
Department of Chemistry, Durham University, South Road, Durham DH1 3LE, United Kingdom Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom § School of Chemistry, Bedson Building, Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom ‡
S Supporting Information *
ABSTRACT: Crystallization of 2-fluorophenylacetylene at room temperature using high pressure yields three different polymorphs. These have distinct supramolecular assemblies despite the only variation in the crystallization protocol employed being the rate of compression.
■
INTRODUCTION Polymorphism, the multiplicity of crystal structures of given chemical composition, is of critical importance in many fields, ranging from structural biology to materials chemistry.1 In particular, polymorphism is of the utmost importance to the pharmaceutical industry, as the physical properties of different drug polymorphs may differ widely, and each form may be patentable in its own right.2 In some cases where multiple polymorphs of a material are to be found, each polymorph is only stable under a given range of temperature and pressure, i.e., the system is under thermodynamic control. However, it is also possible for kinetic factors to control the supramolecular assembly of a material, potentially leading to metastable crystallization.3 Herein, we investigate the importance of kinetic control on a given high-pressure crystallization. The ability to crystallize liquids under high pressure as an alternative to cooling has been known for many years.4−9 Often the same polymorph is crystallized as from cooling.10,11 However, it is also common for the two crystallization procedures to yield different polymorphs.12 Examples include water ices,13 acetone,14 benzene,9 phenol,15 1,2-dichloromethane,16 chlorotrimethylsilane,17 1-bromo-2,4,6-trifluorobenzene,18 and 4-fluorophenol.19 A potential variable in high-pressure crystallization is the presence of ruby, used to measure the pressure in the sample chamber or metal debris, from the gasket used to hold the liquid in place, which could potentially template a particular © 2014 American Chemical Society
polymorph. Other variables include whether the material was crystallized by direct compression or by decompression of a glass, whether temperature control accompanied compression,20 the purity of the starting material,21 and the rate of compression of the liquid. Both CH···F and CH···π interactions represent the weakest end of the hydrogen bond spectrum, as shown by database and theoretical studies.22−29 However, the tendency of these close contacts toward linearity indicates a significant electrostatic contribution to the total energy of the system. The interplay of these weak CH···X interactions at high pressure is a relatively unexplored area with only a few examples where the role of fluorine could be considered to have importance in driving a given form.30−34 Therefore, compounds containing only C, H, and F represent an interesting probe to explore the directional nature of weak interactions under the application of pressure. We have previously investigated the high-pressure crystal structures of monofluorotoluenes,21 but research in this field is currently sparse. Herein, we examine the kinetic control of the high-pressure crystallization of 2-fluorophenylacetylene (2FPA). 2FPA had previously been characterized as dimorphic by in situ cryocrystallization.35 The hydrogen bonding network of polymorph I, which was crystallized through quenching of Received: March 6, 2014 Revised: May 12, 2014 Published: May 19, 2014 3384
dx.doi.org/10.1021/cg500331u | Cryst. Growth Des. 2014, 14, 3384−3391
Crystal Growth & Design
Article
from an empirical isotropic atom−atom potential, with parameters for all atomic types taken from the work of Williams.60,61 The clustering of duplicate structures was completed following a comparison of each of the reduced unit cells, in order to finalize the crystal energy landscape of 2FPA. Experimentally observed polymorphs have been highlighted on the landscape, shown in Figure 9. More accurate estimates of the lattice energies62 were provided by electronic structure calculations on certain crystal structures using a plane wave DFT-D approach using the Castep63 code with the PBE functional and the Tkatchenko-Scheffler (TS) dispersion correction64 with full optimization of cell dimensions and coordinates, using a kpoint spacing of 0.07 and a cutoff of 500 eV with an external pressure of 0.55 GPa.
the hot (353 K) liquid in N2 (liq), comprises a mixture of relatively long CH···F and CH···π chains. This polymorph has disorder relating to the position of the fluorine atom, with refined occupancies of 0.72 and 0.28 for two positions. Fully ordered polymorph II, crystallized using cooling rates of 1000 K h−1 is characterized by more directional CH···F hydrogen bonds. However, in addition to hydrogen bonding, the presence of π···π interactions is also possible. These were observed in polymorph I but not in II.35 The polymorphism reported for 2FPA prompted us to investigate the crystal energy landscape using crystal structure prediction calculations. Crystal structure prediction has been used for over a decade to help understand and predict polymorphism in molecular systems.36−46 We have used this technique to attempt to understand the observed polymorphism and to investigate if other polymorphs are likely to be accessible experimentally. The presence of two known polymorphs of 2FPA possessing an interesting balance of intermolecular interactions represents an ideal system to explore kinetic control using high-pressure crystallization. The molecular structure of 2FPA is shown in Figure 1.
■
RESULTS X-ray Crystallography. On initial high-pressure crystallization of 2FPA it was apparent from unit cell measurements that polymorph I had been formed. After repeating the crystallization procedure, single crystals of polymorph II and a new form, polymorph III, were also formed (nonconcomitantly). Table 1 lists the crystallographic data for the three polymorphs of 2FPA.
Table 1. Crystallographic Data (2FPA) Polymorph I Empirical formula Formula weight T (K) Habit Size P (kbar) Crystal system Space group a (Å) b (Å) c (Å) β (deg) Z V (Å3) Dcalc (g cm−3) μ (mm−1) Unique reflns Observed reflns Completeness % θmax R1 [I > 2σ] wR2 [all] Goodness-of-fit
Figure 1. Molecular structure of 2FPA.
■
METHOD
X-ray Crystallography. 2FPA was crystallized in situ by isothermal freezing and subsequent pressure cycling in a diamond anvil cell (DAC). A stainless steel gasket was used, with a sample chamber of radius 0.3 mm and depth 0.1 mm. Ruby R1 fluorescence was used to determine the pressure inside the DAC chamber.47 Data were collected at the minimum possible pressure for the crystal to be stable with respect to the liquid phase and to fill the sample chamber. All diffraction data were collected at the XIPHOS diffraction facility at Durham University,48 utilizing an Incoatec Ag IμS system.49 The program ECLIPSE50 was used to generate data files masking areas of the diffraction pattern occluded by the body of the diamond anvil cell. The Bruker Apex251 software suite was used to collect and examine the data. SAINT52 and SADABS53 were used for integration, cell refinement, and scaling, respectively. The Olex254 interface to the SHELX suite of programs55 was used to carry out structural solution and least-squares refinements. Computation. The molecular geometry of 2FPA was calculated using an ab initio optimization of the HF/6-31G(d,p) wave function using GAUSSIAN03.56 Densely packed Z′ = 1 crystal structures in common coordination types and space groups were obtained by MOLPAK57 using a rigid pseudo-hard-sphere model. The lattice energies of the most dense structures from each coordination type were minimized using DMACRYS without the addition of external pressure.58 The electrostatic contribution to the lattice energy was calculated from distributed multipole analysis59 of the HF/6-31G(d,p) charge density. The repulsion−dispersion contribution was evaluated
Polymorph II
Polymorph III
C8F1H5 120.13 ambient (292 K) cylinder 0.25 × 0.25 × 0.10 mm3 5.7 (2) 5.3 (2) 5.7 (2) orthorhombic monoclinic monoclinic Pna21 P21 P21 7.578 (6) 7.031 (4) 3.9343 (7) 13.024 (14) 5.924 (4) 5.9336 (10) 6.171 (5) 7.441 (5) 12.962 (4) 90 103.563 (17) 98.467 (9) 4 2 2 609.1 (10) 301.3 (3) 299.29 (12) 1.310 1.324 1.333 0.059 0.060 0.059 444 1021 848 231 489 353 52.0 47.9 41.6 14.33 19.18 17.99 0.0426 0.0424 0.0346 0.1033 0.0895 0.0630 1.1196 1.1550 1.1810
Following isolation and characterization of the three polymorphs, an examination of the kinetic conditions under which each polymorph was formed was undertaken. As variation of the cooling rate of 2FPA yields different polymorphs,35 varying the rate of compression was expected to be the cause of the observed polymorphism. Polymorph II was formed through slow compression near the phase boundary; this was achieved by minor increases in pressure applied every 15 min until crystallization occurred. Polymorphs I and III were both formed by very rapid compression (
