Solid‐State Characterization of 2‐[(2,6‐Dichlorophenyl)amino]‐Benzaldehyde: An Experimental and Theoretical Investigation

The solid‐state properties of 2‐[(2,6‐dichlorophenyl)amino]‐benzaldehyde (DCABA ) were investigated. Unlike its precursor diclofenac acid, for which three polymorphs are currently known, only one crystalline form of DCABA was found. It was further characterized by other spectroscopic and spectrometric methods including IR , Raman, and UV –vis spectroscopy and powder X‐ray diffraction (PXRD ). The thermal behavior of the crystalline form was studied by differential scanning calorimetry (DSC ). Theoretical studies, including Hirshfeld surface analysis and conformational energy searches, were performed to provide insight into the factors contributing to the stability of the crystal and to assess the possibility of additional polymorphs. The full characterization of this compound can help fast and accurate identification of DCABA both in dosage forms and in the environment.     

Desmotropy,Polymorphism, and Solid‐State Proton Transfer: Four Solid Forms of an Aromatic o‐Hydroxy Schiff Base

The Schiff base derived from salicylaldehyde and 2‐amino‐3‐hydroxypyridine affords a diversity of solid forms, two polymorphic pairs of the enol‐imino ( D1 a and D1 b ) and keto‐amino ( D2 a and D2 b ) desmotropes. The isolated phases, identified by IR spectroscopy, X‐ray crystallography, and ¹³C cross‐polarization/magnetic angle spinning (CP/MAS) NMR spectroscopy, display essentially planar molecular conformations characterized by strong intramolecular hydrogen bonds of the O? H???N ( D1 ) or N? H???O ( D2 ) type. A change in the position of the proton within this O???H???N system is accompanied by substantially different molecular conformations and, subsequently, by divergent supramolecular architectures. The appearance and interconversion conditions for each of the four phases have been established on the basis of a number of solution and solvent‐free experiments, and evaluated against the results of computational studies. Solid phases readily convert into the most stable form ( D1 a ) upon exposure to methanol vapor, heating, or by mechanical treatment, and these transformations are accompanied by a change in the color of the sample. The course of thermally induced transformations has been monitored in detail by means of temperature‐resolved powder X‐ray diffraction and infrared spectroscopy. Upon dissolution, all forms equilibrate immediately, as confirmed by NMR and UV/Vis spectroscopy in several solvents, with the equilibrium shifted far towards the enol tautomer. This study reveals the significance of peripheral groups in the stabilization of metastable tautomers in the solid state.     

Conformational Polymorphism in N‐(4′‐methoxyphenyl)‐ 3‐bromothiobenzamide

Three conformational polymorphs of N‐(4′‐methoxyphenyl)‐3‐bromothiobenzamide, yellow α, orange β, and yellow γ, have been identified by single‐crystal X‐ray diffraction. The properties and structure of the polymorphs were examined with FT Raman, FTIR (ATR), and UV/Vis spectroscopy, as well as differential scanning calorimetry. Computational data on rotational barriers in the isolated gas‐phase molecule indicate that the molecular conformation found in the α form is energetically preferred, but only by around 2 kJ mol^?1 over the γ conformation. The planar molecular structure found in the β form is destabilized by 10–14 kJ mol^?1, depending on the calculation method. However, experimental evidence suggests that the β polymorph is the most stable crystalline phase at room temperature. This is attributed to the relative planarity of this structure, which allows more and stronger intermolecular interactions, that is, more energetically effective packing. Calculated electronic‐absorption maxima were in agreement with experimental spectra.     

The Rich Tautomeric Behavior of Campestarenes

Campestarenes are a new family of Schiff‐base macrocycles that form selectively in a one‐step synthesis. These macrocycles with five‐fold symmetry show solvent‐dependent tautomerization and dimerization or aggregation. In this paper, we have prepared new soluble campestarenes that do not aggregate. The initial single‐crystal X‐ray diffraction study of a campestarene reveals that these macrocycles are nearly flat. The tautomeric behavior of the campestarenes has been extensively studied by variable‐temperature, multinuclear NMR spectroscopy, UV/Vis spectroscopy, and IR spectroscopy. In polar solvents, such as DMF, the molecules exist predominantly in their keto‐enamine form, but the enol‐imine tautomer is dominant in non‐polar solvents. A detailed computational study of the tautomeric forms of campestarenes provides a theoretical basis for their behavior and corroborates the experimental data. The results of this study give the first comprehensive understanding of the electronic and spectroscopic properties of these pentagonal macrocycles.     

Ionic solid-state dimers and polymers derived from imidazolium dicarboxylic acids

A series of imidazolium dicarboxylic acids have been prepared from the reaction of the 1,3‐bis(carboxymethyl)imidazolium zwitterion with the Brønsted acids HX (X=F, Br, Cl, ClO₄). The structures of these acids have been established in the solid state by single‐crystal X‐ray diffraction, which revealed that the cations and anions form strong hydrogen bonds through O? H???X interactions, leading to the formation of dimeric and polymeric networks. These acids react with elemental zinc and cobalt to form stable polymeric coordination complexes, some of which have also been characterised by X‐ray diffraction.     

A High‐Pressure Polymorph of Phosphorus Nitride Imide

Phosphorus nitride imide, PN(NH), is of great scientific importance because it is isosteric with silica (SiO₂). Accordingly, a varied structural diversity could be expected. However, only one polymorph of PN(NH) has been reported thus far. Herein, we report on the synthesis and structural investigation of the first high‐pressure polymorph of phosphorus nitride imide, β‐PN(NH); the compound has been synthesized using the multianvil technique. By adding catalytic amounts of NH₄Cl as a mineralizer, it became possible to grow single crystals of β‐PN(NH), which allowed the first complete structural elucidation of a highly condensed phosphorus nitride from single‐crystal X‐ray diffraction data. The structure was confirmed by FTIR and ³¹P and ¹H solid‐state NMR spectroscopy. We are confident that high‐pressure/high‐temperature reactions could lead to new polymorphs of PN(NH) containing five‐fold‐ or even six‐fold‐coordinated phosphorus atoms and thus rivalling or even surpassing the structural variety of SiO₂.     

Crystalline structure of polyamide 12 as revealed by solid‐state 13C NMR and synchrotron WAXS and SAXS

The crystalline structure of polyamide‐12 (PA12) was studied by solid‐state ¹³C nuclear magnetic resonance (NMR) as well as by synchrotron wide‐ and small‐angle X‐ray scattering (WAXS and SAXS). Isotropic and oriented PA12 showed different NMR spectra ascribed to γ‐ and γ′‐crystalline modifications, respectively. On the basis of the position of the first diffraction peak, the isotropic γ‐form and the oriented γ′‐form were shown to be with hexagonal crystalline lattice at room temperature. When heated, the two PA12 polymorphs demonstrated different behaviors. Above 140 °C, the isotropic γ‐PA12 partially transformed into α‐modification. No such transition was observed with the oriented γ′‐PA12 phase even after annealing at temperatures close to melting. A γ′–γ transition was observed here only after isotropization by melting point. Various structural parameters were extracted from the WAXS and SAXS patterns and analyzed as a function of temperature and orientation: the degree of crystallinity, the d‐spacings, the Bragg's long spacings, the average thicknesses of the crystalline (l_c) and amorphous (l_a) phases, and the linear crystallinity x_cl within the lamellar stacks. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3720–3733, 2005     

Polymorphism of N,N'-diacetylbiuret studied by solid-state 13C and 15N NMR spectroscopy, DFT calculations, and X-ray diffraction

The molecular configuration and crystal structure of solid polycrystalline N,N′′‐diacetylbiuret (DAB), a potential nitrogen‐rich fertilizer, have been analyzed by a combination of solid‐ and liquid‐state NMR spectroscopy, X‐ray diffraction, and DFT calculations. Initially a pure NMR study (“NMR crystallography”) was performed as available single crystals of DAB were not suitable for X‐ray diffraction. Solid‐state ¹³C NMR spectra revealed the unexpected existence of two polymorphic modifications (α‐ and β‐DAB) obtained from different chemical procedures. Several NMR techniques were applied for a thorough characterization of the molecular system, revealing chemical shift anisotropy (CSA) tensors of selected nuclei in the solid state, chemical shifts in the liquid state, and molecular dynamics in the solid state. Dynamic NMR spectroscopy of DAB in solution revealed exchange between two different configurations, which raised the question, is there a correlation between the two different configurations found in solution and the two polymorphic modifications found in the solid state? By using this knowledge, a new crystallization protocol was devised which led to the growth of single crystals suitable for X‐ray diffraction. The X‐ray data showed that the same symmetric configuration is present in both polymorphic modifications, but the packing patterns in the crystals are different. In both cases hydrogen bonds lead to the formation of planes of DAB molecules. Additional symmetry elements, a two‐fold screw in the case of α‐DAB and a c‐glide plane in the case of β‐DAB, lead to a more symmetric (α‐DAB) or asymmetric (β‐DAB) intermolecular hydrogen‐bonding pattern for each molecule.     

Tautomeric polymorphism of the neuroactive inhibitor kynurenic acid

Kynurenic acid (KYN; systematic name: 4‐hydroxyquinoline‐2‐carboxylic acid, C₁₀H₇NO₃) displays a therapeutic effect in the treatment of some neurological diseases and is used as a broad‐spectrum neuroprotective agent. However, it is understudied with respect to its solid‐state chemistry and only one crystal form (α‐KYN·H₂O) has been reported up to now. Therefore, an attempt to synthesize alternative solid‐state forms of KYN was undertaken and six new species were obtained: five solvates and one salt. One of them is a new polymorph, β‐KYN·H₂O, of the already known KYN monohydrate. All crystal species were further studied by single‐crystal and powder X‐ray diffraction, thermal and spectroscopic methods. In addition to the above methods, differential scanning calorimetry (DSC), in‐situ variable‐temperature powder X‐ray diffraction and Raman microscopy were applied to characterize the phase behaviour of the new forms. All the compounds display a zwitterionic form of KYN and two different enol–keto tautomers are observed depending on the crystallization solvent used.     

Two tautomeric forms of 2‐amino‐5,6‐dimethylpyrimidin‐4‐one

Derivatives of 4‐hydroxypyrimidine are an important class of biomolecules. These compounds can undergo keto–enol tautomerization in solution, though a search of the Cambridge Structural Database shows a strong bias toward the 3H‐keto tautomer in the solid state. Recrystallization of 2‐amino‐5,6‐dimethyl‐4‐hydroxypyrimidine, C₆H₉N₃O, from aqueous solution yielded triclinic crystals of the 1H‐keto tautomer, denoted form (I). Though not apparent in the X‐ray data, the IR spectrum suggests that small amounts of the 4‐hydroxy tautomer are also present in the crystal. Monoclinic crystals of form (II), comprised of a 1:1 ratio of both the 1H‐keto and the 3H‐keto tautomers, were obtained from aqueous solutions containing uric acid. Forms (I) and (II) exhibit one‐dimensional and three‐dimensional hydrogen‐bonding motifs, respectively.     

Ba3V2S4O3: A Mott Insulating Frustrated Quasi‐One‐Dimensional S=1 Magnet

Through a solid‐state reaction, a practically phase pure powder of Ba₃V₂S₄O₃ was obtained. The crystal structure was confirmed by X‐ray single‐crystal and synchrotron X‐ray powder diffraction (P6₃, a=10.1620(2), c=5.93212(1) Å). X‐ray absorption spectroscopy, in conjunction with multiplet calculations, clearly describes the vanadium in charge‐disproportionated V^IIIS₆ and V^VSO₃ coordinations. The compound is shown to be a strongly correlated Mott insulator, which contradicts previous predictions. Magnetic and specific heat measurements suggest dominant antiferromagnetic spin interactions concomitant with a weak residual ferromagnetic component, and that intrinsic geometric frustration prevents long‐range order from evolving.     

Luminescence Color‐Tuning through Polymorph Doping: Preparation of a White‐Emitting Solid from a Single Gold(I)–Isocyanide Complex by Simple Precipitation

We report the luminescent color tuning of a new complex, 2‐benzothiophenyl(4‐methoxyphenyl isocyanide)gold(I) ( 1 ), by using a new “polymorph doping” approach. The slow crystallization of the complex 1 afforded three different pure polymorphic crystals with blue, green, and orange emission under UV‐light irradiation. The crystal structures of pure polymorphs of 1 were investigated in detail by means of single‐crystal X‐ray analyses. Theoretical calculations based on the single‐crystal structures provided qualitative explanation of the difference in the excited energy‐levels of the three polymorphs of 1 . In sharp contrast, the rapid precipitation of 1 , with the optimized conditions reproducibly afforded homogeneous powder materials showing solid‐state white‐emission with Commission Internationale de l’Éclairage (CIE) 1931 chromaticity coordinates of (0.33, 0.35), which is similar to pure white. New “polymorphic doping” has been revealed to be critical to this white emission through spectroscopic and X‐ray diffraction analyses. The coexistence of the multiple polymorphs of 1 within the homogeneous powder materials and the ideal mixing of multiple luminescent colors gave its white emission accompanied with energy transfer from the predominant green‐emitting polymorph to the minor orange‐emitting polymorph.     

Solid‐State Form Screen of Cardiosulfa and Its Analogues

Cardiosulfa is a biologically active sulfonamide molecule that was recently shown to induce abnormal heart development in zebrafish embryos through activation of the aryl hydrocarbon receptor (AhR). The present report is a systematic study of solid‐state forms of cardiosulfa and its biologically active analogues that belong to the N‐(9‐ethyl‐9H‐carbazol‐3‐yl)benzene sulfonamide skeleton. Cardiosulfa (molecule 1 ; R¹=NO₂, R²=H, R³=CF₃), molecule 2 (H, H, CF₃), molecule 3 (CF₃, H, H), molecule 4 (NO₂, H, H), molecule 5 (H, CF₃, H), and molecule 6 (H, H, H) were synthesized and subjected to a polymorph search and solid‐state form characterization by X‐ray diffraction, differential scanning calorimetry (DSC), variable‐temperature powder X‐ray diffraction (VT‐PXRD), FTIR, and solid‐state (ss) NMR spectroscopy. Molecule 1 was obtained in a single‐crystalline modification that is sustained by N? H???π and C? H???O interactions but devoid of strong intermolecular N? H???O hydrogen bonds. Molecule 2 displayed a N? H???O catemer C(4) chain in form I, whereas a second polymorph was characterized by PXRD. The dimorphs of molecule 3 contain N? H???π and C? H???O interactions but no N? H???O bonds. Molecule 4 is trimorphic with N? H???O catemer in form I, and N? H???π and C? H???O interactions in form II, and a third polymorph was characterized by PXRD. Both polymorphs of molecule 5 contain the N? H???O catemer C(4) chain, whereas the sulfonamide N? H???O dimer synthon R₂²(8) was observed in polymorphs of 6 . Differences in the strong and weak hydrogen‐bond motifs were correlated with the substituent groups, and the solubility and dissolution rates were correlated with the conformation in the crystal structure of 1 , 2 , 3 , 4 , 5 , 6 . Higher solubility compounds, such as 2 (10.5 mg mL^?1) and 5 (4.4 mg mL^?1), adopt a twisted confirmation, whereas less‐soluble 1 (0.9 mg mL^?1) is nearly planar. This study provides practical guides for functional‐group modification of drug lead compounds for solubility optimization.     

Cu(OAc)2.H2O与1-苯基-3-甲基-4-苯甲酰基吡唑啉酮-5(HPMBP)的固相配位化学反应

在低加热条件下(<100℃), 研究了Cu(OAc)2.H2O与1-苯基-3-甲基-4-苯甲酰基吡唑啉酮-5-(HPMBP)两种异构体(烯醇式与酮式)的固相配位化学反应, 结果表明两种异构体与Cu(OAc)2.H2O固相化学反应活性并不相同。通过IR, UV测定, 发现酮式异构体在与Cu(OAc)2.H2O的固相反应过程中, 其自身经过了一个由酮式到烯醇式的固相异构化。     

Predicting the tautomeric equilibrium of acetylacetone in solution. I. The right answer for the wrong reason?

This study investigates how the various components (method, basis set, and treatment of solvent effects) of a theoretical approach influence the relative energies between keto and enol forms of acetylacetone, which is an important model system to study the solvent effects on chemical equilibria from experiment and theory. The computations show that the most popular density functional theory (DFT) approaches, such as B3LYP overestimate the stability of the enol form with respect to the keto form by ～10 kJ mol^?1, whereas the very promising SCS‐MP2 approach is underestimating it. MP2 calculations indicate that in particular the basis set size is crucial. The Dunning Huzinaga double ζ basis (D95z(d,p)) used in previous studies overestimates the stability of the keto form considerably as does the popular split‐valence plus polarization (SVP) basis. Bulk properties of the solvent included by continuum approaches strongly stabilize the keto form, but they are not sufficient to reproduce the reversal in stabilities measured by low‐temperature nuclear magnetic resonance experiments in freonic solvents. Enthalpic and entropic effects further stabilize the keto form, however, the reversal is only obtained if also molecular effects are taken into account. Such molecular effects seem to influence only the energy difference between the keto and the enol forms. Trends arising due to variation in the dielectric constant of the solvent result from bulk properties of the solvent, i.e., are already nicely described by continuum approaches. As such this study delivers a deep insight into the abilities of various approaches to describe solvent effects on chemical equilibria. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

Keto/enol tautomerism in phenylpyruvic acids: structure of the o-nitrophenylpyruvic acid

The synthesis of a tautomeric keto/enol mixture of o-nitrophenylpyruvic acid followed the acid hydrolysis of the azlactone of o-nitrobenzaldehyde was carried out. The structures of the two tautomeric forms were assigned by NMR spectroscopy. X-ray diffraction of a single crystal revealed that the crystalline form corresponds to the keto tautomer. Quantum mechanics calculations in the gas phase confirmed the experimental findings in solution.     

Coordination Polymer Flexibility Leads to Polymorphism and Enables a Crystalline Solid–Vapour Reaction: A Multi‐technique Mechanistic Study

Despite an absence of conventional porosity, the 1D coordination polymer [Ag₄(O₂C(CF₂)₂CF₃)₄(TMP)₃] ( 1 ; TMP=tetramethylpyrazine) can absorb small alcohols from the vapour phase, which insert into Ag?O bonds to yield coordination polymers [Ag₄(O₂C(CF₂)₂CF₃)₄(TMP)₃(ROH)₂] ( 1‐ROH ; R=Me, Et, iPr). The reactions are reversible single‐crystal‐to‐single‐crystal transformations. Vapour‐solid equilibria have been examined by gas‐phase IR spectroscopy (K=5.68(9)×10^?5 (MeOH), 9.5(3)×10^?6 (EtOH), 6.14(5)×10^?5 (iPrOH) at 295 K, 1 bar). Thermal analyses (TGA, DSC) have enabled quantitative comparison of two‐step reactions 1‐ROH → 1 → 2 , in which 2 is the 2D coordination polymer [Ag₄(O₂C(CF₂)₂CF₃)₄(TMP)₂] formed by loss of TMP ligands exclusively from singly‐bridging sites. Four polymorphic forms of 1 ( 1‐A^LT , 1‐A^HT , 1‐B^LT and 1‐B^HT ; HT=high temperature, LT=low temperature) have been identified crystallographically. In situ powder X‐ray diffraction (PXRD) studies of the 1‐ROH → 1 → 2 transformations indicate the role of the HT polymorphs in these reactions. The structural relationship between polymorphs, involving changes in conformation of perfluoroalkyl chains and a change in orientation of entire polymers (A versus B forms), suggests a mechanism for the observed reactions and a pathway for guest transport within the fluorous layers. Consistent with this pathway, optical microscopy and AFM studies on single crystals of 1‐MeOH / 1‐A^HT show that cracks parallel to the layers of interdigitated perfluoroalkyl chains develop during the MeOH release/uptake process.     

A High‐Pressure Polymorph of Phosphorus Oxonitride with the Coesite Structure

The chemical and physical properties of phosphorus oxonitride (PON) closely resemble those of silica, to which it is isosteric. A new high‐pressure phase of PON is reported herein. This polymorph, synthesized by using the multianvil technique, crystallizes in the coesite structure. This represents the first occurrence of this very dense network structure outside of SiO₂. Phase‐pure coesite PON (coe‐PON) can be synthesized in bulk at pressures above 15 GPa. This compound was thoroughly characterized by means of powder X‐ray diffraction, DFT calculations, and FTIR and MAS NMR spectroscopy, as well as temperature‐dependent diffraction. These results represent a major step towards the exploration of the phase diagram of PON at very high pressures and the possibly synthesis of a stishovite‐type PON containing hexacoordinate phosphorus.     

Bismuth Tri‐ and Tetraarylcarboxylates: Crystal Structures,In Situ X‐ray Diffraction,Intermediates and Luminescence

A systematic investigation of the systems Bi³⁺/carboxylic acid/HNO₃ for the tri‐ and tetracarboxylic acids pyromellitic acid (H₄Pyr), trimellitic acid (H₃Tri) and trimesic acid (H₃BTC) acid led to the discovery of five new bismuth carboxylates. Structural characterisation allowed the influence of the linker geometry and the Bi³⁺:linker molar ratio in the starting solution on the crystal structure to be determined. The crystallisation of three selected compounds was investigated by in situ energy‐dispersive X‐ray diffraction. Three new crystalline intermediates were observed within minutes, and two of them could be isolated by quenching of the reaction mixture. Their crystal structures were determined from laboratory and synchrotron X‐ray powder diffraction data and allowed a possible reaction pathway to be established. In depth characterisation of the luminescence properties of the three bismuth pyromellate compounds was carried out. Fluorescence and phosphorescence could be assigned to (mainly) ligand‐ and metal‐based transitions. The polymorphs of Bi(HPyr) exhibit different luminescence properties, although their structures are very similar. Surprisingly, doping of the three host structures with Eu³⁺ and Tb³⁺ ions was only successful for one of the polymorphs.     

Hierarchical Organization of Ferrocene–Peptides

Hierarchical self‐assembly of disubstituted ferrocene (Fc)–peptide conjugates that possess Gly‐Val‐Phe and Gly‐Val‐Phe‐Phe peptide substituents leads to the formation of nano‐ and micro‐sized assemblies. Hydrogen‐bonding and hydrophobic interactions provide directionality to the assembly patterns. The self‐assembling behavior of these compounds was studied in solution by using ¹H NMR and circular dichroism (CD) spectroscopies. In the solid state, attenuated total reflectance (ATR) FTIR spectroscopy, single‐crystal X‐ray diffraction (XRD), powder X‐ray diffraction (PXRD), and scanning electron microscopy (SEM) methods were used. Spontaneous self‐assembly of Fc–peptides through intra‐ and intermolecular hydrogen‐bonding interactions induces supramolecular assemblies, which further associate and give rise to fibers, large fibrous crystals, and twisted ropes. In the case of Fc[CO‐Gly‐Val‐Phe‐OMe]₂ ( 1 ), molecules initially interact to form pleated sheets that undergo association into long fibers that form bundles and rectangular crystalline cuboids. Molecular offsets and defects, such as screw dislocations and solvent effects that occur during crystal growth, induce the formation of helical arrangements, ultimately leading to large twisted ropes. By contrast, the Fc–tetrapeptide conjugate Fc[CO‐Gly‐Val‐Phe‐Phe‐OMe]₂ ( 2 ) forms a network of nanofibers at the supramolecular level, presumably due to the additional hydrogen‐bonding and hydrophobic interactions that stem from the additional Phe residues.