Nonamorphism in flufenamic acid and a new record for a polymorphic compound with solved structures

The unprecedented polymorphism of the non-steroidal anti-inflammatory drug (NSAID) flufenamic acid (FFA) is described here. Nine polymorphs were accessed through the use of polymer-induced heteronucleation (PIHn) and solid-solid transformation at low temperature. Structural elucidation of six of these forms, in addition to the two previously known forms, makes FFA indisputably octamorphic. Although the structure of at least one other form of FFA remains elusive, the occurrence of most of these polymorphs under one crystallization condition through PIHn illustrates that a fine interplay exists among the kinetic factors that lead to phase selection in this NSAID.     

Direct evidence for distinct colour origins in ROY polymorphs

ROY is one of the most well-studied families of crystal structures owing to it being the most polymorphic organic material on record. The various red, orange, and yellow colours of its crystal structures are widely-believed to originate from molecular conformation, though the orange needle (ON) polymorph is thought to be an exception. We report high-pressure, single-crystal X-ray measurements which provide direct experimental evidence that the colour origin in ON is intermolecular, revealing that the molecule undergoes minimal deformation but still exhibits a pronounced, reversible, pale orange → dark red colour change between ambient pressure and 4.18 GPa. Our experimental data are rationalised with band structures, calculated using an accurate hybrid DFT approach, where we are able to account for the variation in colour for five polymorphs of ROY. We highlight the outlier behaviour of ON which shows marked π⋯π stacking interactions that are directly modified through application of pressure. Band structure calculations confirm these intermolecular interactions as the origin of the colour change.

Alternative colour origins in ROY polymorphs are conclusively determined for the first time, using high-pressure diffraction and hybrid DFT.     

How many more polymorphs of ROY remain undiscovered

With 12 crystal forms, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecabonitrile (a.k.a. ROY) holds the current record for the largest number of fully characterized organic crystal polymorphs. Four of these polymorph structures have been reported since 2019, raising the question of how many more ROY polymorphs await future discovery. Employing crystal structure prediction and accurate energy rankings derived from conformational energy-corrected density functional theory, this study presents the first crystal energy landscape for ROY that agrees well with experiment. The lattice energies suggest that the seven most stable ROY polymorphs (and nine of the twelve lowest-energy forms) on the Z′ = 1 landscape have already been discovered experimentally. Discovering any new polymorphs at ambient pressure will likely require specialized crystallization techniques capable of trapping metastable forms. At pressures above 10 GPa, however, a new crystal form is predicted to become enthalpically more stable than all known polymorphs, suggesting that further high-pressure experiments on ROY may be warranted. This work highlights the value of high-accuracy crystal structure prediction for solid-form screening and demonstrates how pragmatic conformational energy corrections can overcome the limitations of conventional density functionals for conformational polymorphs.

Crystal structure prediction suggests that the low-energy polymorphs of ROY have already been found, but a new high-pressure form is predicted.     

Febantel: looking for new polymorphs

The aim of this work was to search for new polymorphic forms of febantel, an anthelminthic drug of great present interest for the veterinary industry. Solvent-based recrystallization, thermal and mechanical treatments and spray drying were chosen to discover new solid forms. The solids obtained were physicochemically characterized by thermal techniques (DSC and TG), FTIR spectroscopy, laboratory and synchrotron X-ray powder diffraction and scanning electron microscopy. Our work leads to obtain a new solid form never described in the literature. In particular, the new polymorph was obtained by the anti-solvent method and the crystallization from isopropanol. The experimental conditions of crystallization favorable to the formation of the highest amount of the new solid phase were selected. The new phase shows a thermal, spectroscopic and diffractometric behavior unique. Furthermore, the preliminary structure investigation suggests two possible crystal systems: an orthorhombic or a monoclinic one, with really comparable lattice parameters and cell volume. Measurements put into evidence that the new phase is a metastable polymorph that is in monotropic relationship with the stable and known form.

     

New polymorphs of curcumin

Two new crystalline polymorphs and an amorphous phase of the active curcuminoid ingredient in turmeric are reported. Curcumin polymorph 2 has higher dissolution rate and better solubility than the known polymorph 1.     

New polymorphs of isonicotinamide and nicotinamide

For each of the well-known co-crystal formers, isonicotinamide and nicotinamide, a new polymorph, obtained during attempted co-crystallisation experiments, has been fully characterized and its stability relationship with previously reported forms established.     

Structure of coexisting liquid phases of supercooled water: analogy with ice polymorphs

The structural changes occurring in supercooled liquid water upon moving from one coexisting liquid phase to the other have been investigated by computer simulation using a polarizable interaction potential model. The obtained results favorably compare with recent neutron scattering data of high and low density water. In order to assess the physical origin of the observed structural changes, computer simulation of several ice polymorphs has also been carried out. Our results show that there is a strict analogy between the structure of various disordered (supercooled) and ordered (ice) phases of water, suggesting that the occurrence of several different phases of supercooled water is rooted in the same physical origin that is responsible for ice polymorphism.     

Hydrothermal synthesis and structures of two zero-dimensional zinc phosphate polymorphs

Two polymorphs of zero-dimensional zinc phosphate with the formula, ⁰_∞[Zn(2,2′-bipy)(H₂PO₄)₂], have been synthesized employing hydrothermal technique and their structure determined by single crystal X-ray diffraction. Both the structures consists of ZnO₃N₂ distorted trigonal-bipyramidal and PO₂(OH)₂ tetrahedral units linked through their vertices giving rise to a zero-dimensional molecular zinc phosphate. The structures are stabilized by extensive hydrogen bond interactions between zero-dimensional monomers. The structures display subtle differences in their packing created by hydrogen bond interactions. Crystal data: polymorph I, triclinic, space group (No. 2), , , , α=67.32(3)°, β=81.67(3)°, γ=69.29(3)°, , Z=2; polymorph II, triclinic, space group (No. 2), , , , α=97.37(2)°, β=100.54(2)°, γ=100.98(2)°, , Z=2.     

Two new copper azido polymorphs: structures, magnetic properties, and effects of "noninnocent" reagents in hydrothermal methods

Two new 3D copper(II) azido isomers, [Cu(N3)(nic)]infinity (1 and 2) (nic = nicotinate), have been synthesized and characterized. To the best of our knowledge, 1 is the first metal azido complex showing rutile-type topology, while 2 is a chiral compound obtained by spontaneous resolution upon crystallization.     

Crystal structures of two polymorphs of Ca3[Al2N4

Green transparent single crystals of alpha-Ca3[Al2N4] (monoclinic, P2(1)/c, No. 14, a = 957.2(3) pm, b = 580.2(3) pm, c = 956.3(5) pm, beta = 111.62(3) degrees; Z = 4) were obtained from reactions of mixtures of the representative metals with nitrogen above temperatures of 1000 degrees C. beta-Ca3[Al2N4] (monoclinic, C2/c, No. 15, a = 1060.6(2) pm, b = 826.0(2) pm, c = 551.7(1) pm, beta = 92.1(1) degrees; Z = 4) was formed as a byproduct of a reaction of calcium with alumina under nitrogen at T = 930 degrees C in form of colorless crystals. The crystal structures of the two polymorphs contain edge- and corner-sharing AlN4 tetrahedra, leading to different layered anionic partial structures: infinity 2[AlN2/2N2/3)2(AlNN2/2N1/3)6/3(12-)] in the alpha-phase and infinity 2[Al2N2N4/2(6-)] in the beta-polymorph.     

Bismuth borates: two new polymorphs of BiB3O6

Two new polymorphs of BiB3O6 were identified at low temperatures using boric acid as a flux. Unlike alpha-BiB3O6, which crystallizes in a noncentrosymmetric space group and, thus, shows exceptional nonlinear optical (NLO) properties, beta-BiB3O6 (I) and gamma-BiB3O6 (II) crystallize in the centrosymmetric space group P2(1)/n with the following lattice parameters: a = 14.1664(1), b = 6.7514(1), c = 4.4290(1) angstroms, beta = 102.125(1) degrees for I; and a = 8.4992(1), b = 11.7093(1), c = 4.2596(1) angstroms, beta = 121.141(1) degrees for II. However, from the structural point of view, the three polymorphs of BiB3O6 are closely related. The structure of beta-BiB3O6 (I) contains a 2-dimensional borate layer, which could be considered to be an intralayered additive product of alpha-BiB3O6. On the other hand, the 3-dimensional borate framework in gamma-BiB3O6 (II) could be considered to be an interlayered additive product of beta-BiB3O6 (I). According to the synthesis experiments and calculated density, it is proposed that compounds I and II should be the low-temperature (high-pressure) polymorphs of BiB3O6.     

Rational design and HT techniques allow the synthesis of new IWR zeolite polymorphs

By combining a rational design of structure directing agents and high throughput and data mining techniques, it has been possible to obtain Ge-free ITQ-24 as pure silica as well as borosilicate polymorphs up to a Si/TIII ratio of 10. Al can be exchanged by B giving strong acid materials. Also, the availability of the pure silica material allows one to determine more precisely the crystal symmetry. This work opens the possibility to synthesize the Ge-free polymorphs of a large number of new germanosilicate structures reported in the last five years. This certainly will increase their possibilities for industrial application.     

Room-temperature ferroelectric and ferroelastic orders coexisting in a new tetrafluoroborate-based perovskite

The coexistence of multiferroic orders has attracted increasing attention for its potential applications in multiple-state memory, switches, and computing, but it is still challenging to design single-phase crystalline materials hosting multiferroic orders at above room temperature. By utilizing versatile ABX₃-type perovskites as a structural model, we judiciously introduced a polar organic cation with easily changeable conformations into a tetrafluoroborate-based perovskite system, and successfully obtained an unprecedented molecular perovskite, (homopiperazine-1,4-diium)[K(BF₄)₃], hosting both ferroelectricity and ferroelasticity at above room temperature. By using the combined techniques of variable-temperature single-crystal X-ray structural analyses, differential scanning calorimetry, and dielectric, second harmonic generation, and piezoresponse force microscopy measurements, we demonstrated the domain structures for ferroelectric and ferroelastic orders, and furthermore disclosed how the delicate interplay between stepwise changed dynamics of organic cations and cooperative deformation of the inorganic framework induces ferroelectric and ferroelastic phase transitions at 311 K and 455 K, respectively. This instance, together with the underlying mechanism of ferroic transitions, provides important clues for designing advanced multiferroic materials based on organic–inorganic hybrid crystals.

An unprecedented tetrafluoroborate-based perovskite reveals the coexistence of ferroelastic and ferroelectric transitions arising from delicate interplay between stepwise frozen organic cations and cooperative deformation of the framework.     

Synthesis and crystal structures of two polymorphs of sulfathiazole:pyridine (1:1) adducts

The paper summarizes recent results on crystallization and characterization of two polymorphs of the sulfathiazole:pyridine (1:1) adducts with substantially different space groups (P4₁ and P2₁/c) and packing. Intermolecular interactions in the adducts are compared. These two forms were obtained from solutions containing different ratios of n-propanol, not participating directly in crystallization but obviously controlling the polymorphism, and pyridine. The adducts are also formed by the contact of pure solid sulfathiazole (different polymorphs) with pyridine vapor. In air, the adducts decompose giving initially the metastable polymorph I of sulfathiazole, and then the stable sulfathiazole-III.

CdWO4 polymorphs: Selective preparation, electronic structures, and photocatalytic activities

This work explored the selective synthesis of polymorphs of CdWO₄ in either tetragonal or monoclinic phase by optimizing the experimental parameters. Systematic characterization indicated that both polymorphs possessed similar spherical morphologies but different structural building blocks. Electronic structures calculations for both polymorphs demonstrated the same constructions of conduction band or valence band, while the conduction band widths of both polymorphs were quite different. Both CdWO₄ polymorphs exhibited good photocatalytic activity for degradation of methyl orange under UV light irradiation. When comparing to some other well-known tungstate oxide materials, the photocatalytic activity was found to follow such a consequence, monoclinic CdWO₄≈monoclinic ZnWO₄>tetragonal CdWO₄>tetragonal CaWO₄. The specific photocatalytic activity of monoclinic CdWO₄ was even higher than that of commercial TiO₂ photocatalyst (Degussa P25). The increased activity from the tetragonal CdWO₄ to the monoclinic was consistent with the trend of the decreased symmetry, and this could be explained in terms of the geometric structures and electronic structures for both polymorphs.     

Naphthylimido-substituted hexamolybdate: preparation, crystal structures, solvent effects, and optical properties of three polymorphs

[(n-C4H9)4N]2[Mo6O18(N-1-C10H(6)-2-CH3)] (1) has been prepared by the reaction of 1-amino-2-methylnaphthalene hydrochloride with [(n-C4H9)4N]4[alpha-Mo8O26] in the presence of 1,3-dicyclohexylcarbodiimide. Three solvent-free crystalline phases are isolated from the mixed solvents of acetone and acetic ether. The X-ray single-crystal structures of the three phases have been determined, showing the packing and supramolecular assembly characters (pseudohigher symmetry, helical chains, and pi-pi stacking) by which the effect of solvent polarity and crystallization speed on polymorphism in organic-inorganic hybrids has been demonstrated.     

New hierarchical titania-based structures for photocatalysis

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Characterization of complicated new polymorphs of chlorothalonil by X-ray diffraction and computer crystal structure prediction

A simultaneous experimental and computational search for polymorphs of chlorothalonil (2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile) has been conducted, leading to the first characterization of forms 2 and 3. The crystal structure prediction study, using a specifically developed anisotropic atom-atom potential for chlorothalonil, gave as the global minimum in the lattice energy a structure that was readily refined against powder diffraction data to the known form 1 (P2(1)/a). The structure of form 2 was solved and refined from powder diffraction data, giving a disordered structure in the Rm (166) space group (Z = 3). It could also be refined against a P1 ordered model, starting from a low-energy hypothetical sheet structure found in the computational search. This shows that the disorder could be associated with the stacking of ordered sheets. The disordered structure for form 2 was later confirmed by single-crystal X-ray diffraction. The structure of form 3, determined from single-crystal diffraction, contains three independent molecules in the asymmetric unit in P2(1) (4) (Z = 6). Powder diffraction showed that this single-herringbone structure was similar to two low-energy structures found in the search. Further analysis confirmed that form 3 has a similar lattice energy and contains elements from both these predicted structures, which can be considered as good approximations to the form 3 structure.     

Framework stability of nanoporous inorganic structures upon template extraction and calcination: a theoretical study of gallophosphate polymorphs

A systematic computational study of gallophosphates was undertaken. First, lattice energy minimization calculations using a formal-charge shell model potential have been carried out on a series of hypothetical gallium phosphates derived from their metallogallophosphate, aluminophosphate, or aluminosilicate analogues through atomic substitution. The minimized structures show the typical features in terms of bond angles and distances as expected in zeolitic gallophosphates. Second, the crystal structures of several gallophosphates in their calcined forms have been predicted, using for each compound lattice energy minimization and an initial model derived from its as-synthesized templated form. All the modified structures thus have the same GaPO(4) composition. The lattice energies of all the simulated gallophosphate structures were compared to that of GaPO(4)-quartz as a reference structure. Interestingly, among all predicted calcined structures, various zeolitic topologies were found. The study of the energetics of these zeotypic structures showed a linear dependence of lattice energy upon density. Strikingly, a few simulated structures showed unrealistic structural features, such as important framework distortions, often associated with the occurrence of a hexameric unit in the original as-synthesized structures. Also, those gallophosphates with structural faults were found in the upper part of the energy/density plot. To address the validity of our force field calculations in these special cases, first principles calculations were undertaken on ULM-4, chosen as a typical representative structure. Indeed, the qualitative agreement found between our results and those obtained with the nonlocal density functional theory demonstrates the robustness of our force field. Further minimization also showed that the inclusion of polarizability is crucial for yielding results comparable with those obtained using first principles methods.     

Molecular docking revealed the binding of nucleotide/side inhibitors to Zika viral polymerase solved structures

A new Zika virus (ZIKV) outbreak started in 2015. According to the World Health Organization, 84 countries confirmed ZIKV infection. RNA-dependent RNA polymerase (RdRp) was an appealing target for drug designers during the last two decades. Through molecular docking, we screened 16 nucleotide/side inhibitors against ZIKV RdRp. While the mode of interaction with ZIKV is different from that in the hepatitis C virus (HCV), nucleotide/side inhibitors in this study (mostly anti-HCV) showed promising binding affinities (?6.2 to ?9.7 kcal/mol calculated by AutoDock Vina) to ZIKV RdRp. Setrobuvir, YAK and, to a lesser extent, IDX-184 reveal promising results compared to other inhibitors in terms of binding ZIKV RdRp. These candidates would be powerful anti-ZIKV drugs.