Crystal Polymorphism Research Articles

A density-functional benchmark of vibrational free-energy corrections for molecular crystal polymorphism.

Many crystal structure prediction protocols only concern themselves with the electronic energy of molecular crystals. However, vibrational contributions to the free energy (Fvib) can be significant in determining accurate stability rankings for crystal candidates. While force-field studies have been conducted to gauge the magnitude of these free-energy corrections, highly accurate results from quantum mechanical methods, such as density-functional theory (DFT), are desirable. Here, we introduce the PV17 set of 17 polymorphic pairs of organic molecular crystals, for which plane wave DFT is used to calculate the vibrational free energies and free-energy differences (ΔFvib) between each pair. Our DFT results confirm that the vibrational free-energy corrections are small, having a mean value of 1.0 kJ/mol and a maximum value of 2.3 kJ/mol for the PV17 set. Furthermore, we assess the accuracy of a series of lower-cost DFT, semi-empirical, and force-field models for computing ΔFvib that have been proposed in the literature. It is found that calculating Fvib using the Γ-point frequencies does not provide ΔFvib values of sufficiently high quality. In addition, ΔFvib values calculated using various approximate methods have mean absolute errors relative to our converged DFT results of equivalent or larger magnitude than the vibrational free-energy corrections themselves. Thus, we conclude that, in a crystal structure prediction protocol, it is preferable to forego the inclusion of vibrational free-energy corrections than to estimate them with any of the approximate methods considered here.

The interplay of intra- and intermolecular errors in modeling conformational polymorphs.

Conformational polymorphs of organic molecular crystals represent a challenging test for quantum chemistry because they require careful balancing of the intra- and intermolecular interactions. This study examines 54 molecular conformations from 20 sets of conformational polymorphs, along with the relative lattice energies and 173 dimer interactions taken from six of the polymorph sets. These systems are studied with a variety of van der Waals-inclusive density functionals theory models; dispersion-corrected spin-component-scaled second-order Møller-Plesset perturbation theory (SCS-MP2D); and domain local pair natural orbital coupled cluster singles, doubles, and perturbative triples [DLPNO-CCSD(T)]. We investigate how delocalization error in conventional density functionals impacts monomer conformational energies, systematic errors in the intermolecular interactions, and the nature of error cancellation that occurs in the overall crystal. The density functionals B86bPBE-XDM, PBE-D4, PBE-MBD, PBE0-D4, and PBE0-MBD are found to exhibit sizable one-body and two-body errors vs DLPNO-CCSD(T) benchmarks, and the level of success in predicting the relative polymorph energies relies heavily on error cancellation between different types of intermolecular interactions or between intra- and intermolecular interactions. The SCS-MP2D and, to a lesser extent, ωB97M-V models exhibit smaller errors and rely less on error cancellation. Implications for crystal structure prediction of flexible compounds are discussed. Finally, the one-body and two-body DLPNO-CCSD(T) energies taken from these conformational polymorphs establish the CP1b and CP2b benchmark datasets that could be useful for testing quantum chemistry models in challenging real-world systems with complex interplay between intra- and intermolecular interactions, a number of which are significantly impacted by delocalization error.

Competition between Hydrogen and Anagostic Bonds in Ruthenocene Phases under High Pressure

High pressure favors anagostic bonds CH···Ru, which leads to a new polymorph of ruthenocene RuCp2, where Cp denotes the cyclopentadienyl ring [C5H5]−. Ruthenocene can be isothermally compressed in its ambient-pressure phase α up to 3.9 GPa, when it transforms to the new phase, β. The transition between phases α and β proceeds with an exceptionally wide hysteresis extending between 0.7 and 3.9 GPa. The transition destroys single crystals of RuCp2, but a single crystal of polymorph β can be obtained by high-pressure nucleation (above 3.9 GPa) and its isochoric growth continued above 1.0 GPa. On decompression, phase β transforms back to phase α at 0.7 GPa. The structures of phases α (space group Pnma) and β (space group Pcmb) have been determined by X-ray diffraction in the pressure range from 0.1 MPa up to 3.9 GPa. The eclipsed conformation of α-RuCp2 is retained in phase β, which contrasts with the conformational phase transitions in ferrocene and nickelocene. The lattice dimensions and molecular orientations in ruthenocene polymorphs are clearly related, which leads to the characteristic twinning-like oriented growth of the crystals of concomitant phases.

Insoluble Salt of Memantine with a Unique Fluorescence Phenomenon.

Alzheimer's disease is a chronic disease, and the long-term treatment of chronic diseases has always been a concern. Memantine (Mem) is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. In this study, reactions of memantine (Mem) with pamoic acid (Pam) were carried out to form insoluble salts (Mem-Pam). Four polymorphic forms (Forms I-IV) of Mem-Pam were successfully obtained through polymorphic screening, which were systematically characterized by X-ray powder diffraction (PXRD), thermal analysis (TGA and DSC), single-crystal X-ray diffraction (SXRD), and solid-state fluorescence. Compared with the hydrochloride form, the dissolution and release rates of these four forms are lower. The presence of pamoic acid reduces the release rate of memantine and makes it possible to achieve a sustained release of the drug. Interestingly, because of the presence of memantine, each polymorphic solid crystal of Mem-Pam has unique fluorescence emission. Therefore, memantine and pamoic acid have a synergistic effect on the fluorescence performance and can be expected to be used for real-time monitoring in continuous and controlled release drug delivery systems. In addition, the polymorphic solid crystals also exhibit reversible mechanochromic luminescence under the fumigation of acetonitrile vapor, which has a guiding role in the fluorescence design and synthesis of Pam substances and is expected to be used for information security, visual inspection of organic substances, etc.

The Biotic‐Abiotic Control of Si Burial in Marine Carbonate Systems of the Pre‐Eocene Si Cycle

AbstractThe silicon (Si) cycle in the modern ocean might still be representative of some of the processes that occurred in the Si‐depleted post‐Eocene oceans resulting after the expansion of diatoms. However, silicon‐rich pre‐Eocene seas, where sponges and radiolarians were major Si users before the emergence of diatoms, were radically different from modern ocean scenarios. The spatial and temporal evolution of Si cycling in Earth history is recorded in geological deposits and could be reconstructed by petrographic and mineralogical analyses. The thick successions of carbonate siliceous rocks deposited in marine environments during the Paleozoic and Mesozoic indicate the significant role of Si outflow from the Si cycle via burial in sediments. The aim of this study is to fill an important gap in knowledge concerning the functioning of the main silicon sink in the oceans: burial in sediments. Si outflow from the marine biogeochemical Si cycle occurs via early diagenetic silica crystallization within seabed mud. The mechanisms leading to Si binding in silica minerals are a complex process controlled by abiotic global events, biological activity of silicifiers and geochemical conditions mediated by microbes. This study concentrates on reconstructions of the mechanisms of Si outflow from the Si cycle by silica polymorph crystallization below the seabed surface and was realized through mineralogical and microtextural analyses of the main components of Upper Cretaceous carbonate–siliceous rocks.

Effect of symmetry reduction on the magnetic properties of LnIr[formula omitted]Si[formula omitted] polymorphs

Many tetragonal compounds LnIr2Si2 (Ln = lanthanoid) occur in two polymorphous phases and are therefore well suited to study the relationship between crystal structure and magnetic properties. We have grown GdIr2Si2 single crystals of both polymorphs from a high-temperature indium flux and investigated their anisotropic magnetic properties. The higher symmetric form with the ThCr2Si2 structure (space group I4/mmm) orders antiferromagnetically at TN=87K while for the lower symmetric compound in the CaBe2Ge2 structure (space group P4/nmm) we determined a much lower Néel temperature TN=12K. Our magnetic characterization of the single crystals reveals that for both compounds the magnetic moments are aligned in the a−a plane of the tetragonal lattice, but that the change of the symmetry strongly effects the inplane alignment of the moment orientation. For Ln=Er and Ho, we confirmed the existence of LnIr2Si2 in the space group P4/nmm. The magnetic properties of these lower symmetric compounds are in remarkable difference to their related compounds in the space group I4/mmm.

A Solid-Solid Phase Transformation of Triclabendazole at High Pressures

Triclabendazole is an effective medication to treat fascioliasis and paragonimiasis parasitic infections. We implemented a reliable quantum mechanical method which is density functional theory at the level of ωB97XD/6-31G* along with embedded fragments to elucidate stability and phase transition between two forms of triclabendazole. We calculated crystal structure parameters, volumes, Gibbs free energies, and vibrational spectra of two polymorphic forms of triclabendazole under different pressures and temperatures. We confirmed form I was more stable than form II at atmospheric pressure and room temperature. From high-pressure Gibbs free energy computations, we found a pressure-induced phase transformation between form I (triclinic unit cell) and form II (monoclinic unit cell). The phase transition between forms I and II was found at a pressure and temperature of 5.5 GPa and ≈350 K, respectively. In addition, we also studied the high-pressure polymorphic behavior of two forms of triclabendazole. At the pressure of 5.5 GPa and temperature from ≈350 K to 500 K, form II was more stable than form I. However, at temperatures lower than ≈350 K, form I was more stable than form II. We also studied the effects of pressures on volumes and Raman spectra. To the best of our knowledge, no such research has been conducted to determine the presence of phase transformation between two forms of triclabendazole. This is a case study that can be applied to various polymorphic crystals to study their structures, stabilities, spectra, and phase transformations. This research can assist scientists, chemists, and pharmacologists in selecting the desired polymorph and better drug design.

Effect of Taylor vortex wavelength on polymorphic crystallization of L-histidine

Axial wavelength is a key characteristic parameter of Taylor vortex flows. Thus, in the current study, the effect of Taylor vortex wavelength on the polymorphic nucleation and phase transformation of L-histidine was examined. The vortex wavelength was altered by altering the gap width between the outer and inner cylinders. Further, the vortex velocity was changed by controlling the inner cylinder rotation speed. Owing to the promotion of stable nucleation by the periodic fluid motion, the primary polymorphic fraction of the stable Form A of L-histidine in Taylor vortex flow [Couette–Taylor (CT) crystallizer] was much greater than that in a turbulent eddy flow [mixing tank (MT) crystallizer]. As the vortex wavelength decreased, stable nucleation was promoted, thus increasing the initial polymorphic fraction of the stable Form A. Moreover, the initial polymorphic fraction of the stable Form A increased as the vortex velocity increased. These experimental results are described based on molecular alignment effect of Taylor vortex on stable nucleation. The phase transformation of L-histidine was also strongly influenced by the vortex wavelength and vortex velocity. Hence, the rate of phase transformation in CT crystallizer was approximately ten-fold better than MT crystallizer.

Phase Transformation of a Dual Phase Al–Fe Alloy Prepared by Mechanical Alloying

Abstract A metastable Al90Fe10 (at.%) alloy, composed of a supersaturated solid solution of face-centred cubic (fcc) Al(Fe) and an amorphous phase matrix, was prepared by mechanical alloying of a mixture of Al and Fe elemental blends. The thermally induced microstructural evolution in the dual phase alloy was characterized by X-ray diffraction, transmission electron microscopy, differential scanning calorimetry, and magnetothermal analysis. On continuous heating two stages of solid state phase transformation occurred: (i) a polymorphous crystallization of the amorphous phase to a metastable crystalline Al6Fe that structurally stabilizes over a temperature range of about 200 K, and (ii) a eutectoid decomposition of the crystalline Al6Fe into the equilibrium phases of Al13Fe4 and fcc Al(Fe). Thermodynamic and kinetic analyses of the observed phase transformation processes were given. The formation of the dual phase alloy in the as-milled state and the phase transitions can be illustrated by a hypothetical free energy diagram, implying the dual phase structure facilitates the polymorphous crystallization of Al6Fe.

Isotropic liquid state of triacylglycerols

Over the years, several models of triacylglycerol (TAG) molecular conformations and bulk arrangements in isotropic liquid state have been proposed and are still up for debate. Such organization has a major impact on nucleation and crystal formation. The current research aims to further explore this debate by implementing experimental methods, such as X-ray diffraction and small-angle X-ray scattering coupled with a computational method, such as molecular dynamic simulation. These techniques were used to study tristearin and triolein as models for saturated and unsaturated TAGs, respectively. Four different conformations were suggested for the two TAGs, and the results showed conformation abundancy in the order: trident (Tr) > chair (Ch) > propeller (Pr) > tuning-fork (Tf). The existence of clusters was demonstrated for both TAGs, each of which exhibited a heterogeneous distribution of conformations. The preferability to find a specific pair of conformations next to each other was analyzed and, surprisingly, it was found that Tf will preferably pair only with Tr although Tf is the preferable conformation in most crystal polymorphs. High general conversion rates from any conformation to another, and high specific conversion rates from and to the Tf conformation were calculated. It is proposed that the high conversion rates observed enable the crystallization process, despite the low proportion of Tf molecules, which are in the suitable conformation for the crystal state. The conversion rates in triolein were lower compared with tristearin. This observation was ascribed to the lower simulated temperatures and the higher rigidity of the fatty acid chain induced by the double bond. Overall, the results confirm the formation of specific structures in liquid state, which combine all previously suggested models and further expand the knowledge using experimental and computational tools.

Exploring the role of crystal habit in the Ostwald rule of stages.

The crystallization of calcium carbonate is shown to be dictated by the Ostwald rule of stages (ORS), for high relative initial supersaturations (), under sweet (carbon dioxide saturated) and anoxic (oxygen depleted) solution conditions. Rhombohedral calcite crystals emerge after the sequential crystallization and dissolution of the metastable polymorphs: vaterite (snowflake-shaped) and aragonite (needle-shaped). However, the presence of certain cations, which can form trigonal carbonates (e.g. Fe2+ and Ni2+), in concentrations as low as 1.5 mM, triggers the emergence of calcite crystals, with a star-shaped crystal habit, first. These star-shaped crystals dissolve to yield needle-shaped aragonite crystals, which in turn dissolve to give the rhombohedral calcite crystals. The star-shaped crystals, formed at high SCaCO3, possess higher surface free energy (therefore higher apparent solubility) than their rhombohedral counterparts. This sequence of dissolution and recrystallization demonstrates that the ORS does not only drive the crystal towards its thermodynamically most stable polymorph but also towards its most stable crystal habit.

Physical Properties and Polymorphism of Acrylic Acid-Grafted Poly(1,4-butylene adipate-co-terephthalate)/Organically Modified Layered Double Hydroxide Nanocomposites.

Novel and biodegradable acrylic acid-grafted poly(1,4-butylene adipate-co-terephthalate)/organically modified layered double hydroxide (g-PBAT/m-LDH) nanocomposites were synthesized through the polycondensation and transesterification process, with the covalent linkages between the polymer and the inorganic materials. X-ray diffraction and transmission electron microscopy were used to characterize the structure and morphology of the g-PBAT/m-LDH nanocomposites. The experimental results show that the m-LDH was exfoliated and widely distributed in the g-PBAT matrix. The addition of m-LDH into the g-PBAT extensively improved the storage modulus at −90 °C, when compared to that of the pure g-PBAT matrix. The effects of the minor comonomer of the butylene terephthalate (BT) unit and the addition of m-LDH on the crystallization behavior, and the polymorphic crystals of the g-PBAT at numerous crystallization temperatures, were examined, using a differential scanning calorimeter (DSC). The data indicate that the minor comonomer of the BT unit into g-PBAT can significantly change the starting formation temperatures of the α-form and ꞵ-form crystals, while a change in the starting formation temperatures of the α-form and ꞵ-form crystals using the addition of m-LDH into g-PBAT is not evident.

Retarded Crystallization and Promoted Phase Transition of Freeze-Dried Polybutene-1: Direct Evidence for the Critical Role of Chain Entanglement

Polymorphism and crystal transition are common phenomena of semicrystalline polymers. These two behaviors are known to be controlled by the nucleation and chain mobility of polymers, both of which are constrained by the chain entanglement at the molecular level. However, the role of chain entanglement in polymorphic crystallization and crystal phase transition of polymers has not been well understood. Herein, we use isotactic polybutene-1 (PB-1) as a model polymorphic polymer and present the crucial role of chain entanglement in the polymorphic crystallization kinetics and solid-solid phase transition. A series of less-entangled PB-1 with different entanglement degrees were successfully prepared by freeze-drying the polymer dilute solution. Compared to the bulk sample and re-entangled one, chain disentangling of PB-1 suppressed the crystallization kinetics of form II but significantly increased the phase transition rate and final transition degree from form II to form I. The disentangling-promoted II-I phase transition originated from the reduced nucleation barrier and enhanced chain mobility. This work would advance the in-depth understanding on the formation and transition mechanisms of polymorphic polymer crystals at the molecular level.

Conformational Selectivity and Evolution Affected by the Desolvation Process

The inconsistency between solution chemistry and the crystal structure indicates the potential conformational evolution and rearrangement during the nucleation process. However, the mechanism of how the conformation is selected to form the corresponding polymorph is still not clear due to the complicated crystallization environment. In this work, conformation and polymorph selectivity of three anhydrous forms of gabapentin were investigated. Quantum chemical computation was used to analyze gabapentin conformations in the solution state and explore their transformation pathway. Besides, visual molecular dynamics was adopted to calculate the structural difference of the conformers in solution and crystal states, which was closely related to conformational selectivity. Moreover, the effects of solvent types and the supersaturation on solute–solvent interactions were investigated by Fourier transform infrared spectra and molecular dynamics simulations. Combined with the outcome of rapid cooling experiments, it was found that the solute–solvent interaction may affect the difficulty of desolvation so as to affect the conformational selectivity before nucleation. A special evaporation experiment was designed to obtain the unstable polymorph of gabapentin. Finally, the possible mechanism of selective polymorph crystallization was proposed and analyzed.

RELATIVE LENGTH AS A CLASSIFICATION PARAMETER OF THE CRYSTALLIZATION MODE OF AMORPHOUS FILMS

The possibility of using of the relative length δ0 as a parameter, determining the polymorphous crystallization mode of amorphous films, was considered. Following polymorphous crystallization modes have been identified based on the structural and morphological characteristics. Layer polymorphous crystallization mode, describes the nucleation and growth of a single-crystal layer in the field of the electron-beam impact, for which δ0 is about several thousand (3000…5000). Island polymorphous crystallization mode, describes the nucleation and growth of a polycrystalline layer, for which δ0 is about several hundred (100…1100). Dendrite polymorphous crystallization mode, describes the nucleation and growth of dendrite, for which δ0 is about several thousand (~ 4000).

Crystal polymorphism and crystalline-state photochromism of a rhodium dithionite complex with n-methoxypropyl moieties

The crystalline-state photochromism of 1MPro in the β-crystal was successfully disclosed by time-dependent X-ray diffraction experiments.

Pyridyl substitution at the 2,6-positions of anthracene toward crystal polymorphs with distinct optical characteristics

Via pyridyl substitution at the 2,6-positions of anthracene, we achieved two packing polymorphs with different crystal morphologies and optical characteristics.

Luminescent polymorphic crystals: mechanoresponsive and multicolor-emissive properties

Polymorphic organic crystals that can switch their photophysical properties in response to mechanical stimuli are highlighted.

Synthesis and transformation of calcium carbonate polymorphs with chiral purine nucleotides

Crystallization of CaCO3 polymorphs is controlled using the chiral purine nucleotides adenosine triphosphate (ATP) and guanosine triphosphate (GTP). The effects of ATP and GTP on the transformation of calcite into vaterite are investigated.

Crystal growth and structure of a high temperature polymorph of Sr2TiO4 with tetrahedral Ti-coordination, and transition to the Ruddlesden–Popper tetragonal phase

We have grown single crystals of a new polymorph of Sr2TiO4. It contains titanium in an unusual tetrahedral coordination and transforms to the Ruddlesden–Popper structure with an interesting orientational relationship.