Mechanism of preferential enrichment,an unusual enantiomeric resolution phenomenon caused by polymorphic transition during crystallization of mixed crystals composed of two enantiomers

The mechanism of Preferential Enrichment, an unusual enantiomeric resolution phenomenon observed upon recrystallization of a series of racemic crystals which are classified as a racemic mixed crystal with fairly ordered arrangement of the two enantiomers, has been studied. On the basis of the existence of polymorphs and the occurrence of the resulting polymorphic transition during crystallization from solution, the mechanism has been accounted for in terms of (1) a preferential homochiral molecular association to form one-dimensional chain structures in the supersaturated solution of the racemate or nonracemic sample with a low ee value, (2) a kinetic formation of a metastable crystalline phase retaining the homochiral chain structures in a process of nucleation, (3) a polymorphic transition from the metastable phase to a stable one followed by enantioselective liberation of the excess R (or S) enantiomers from the transformed crystal into solution at the beginning of crystal growth to result in a slight enrichment (up to 10% ee) of the opposite S (or R) enantiomer in the deposited crystals, together with an enantiomeric enrichment of the R (or S) enantiomer in the mother liquor, and (4) a chiral discrimination by the once formed S (or R)-rich stable crystalline phase in a process of the subsequent crystal growth, leading to a considerable enantiomeric enrichment of the R (or S) enantiomer up to 100% ee in the mother liquor. The processes (3) and (4) are considered to be directly responsible for an enrichment of one enantiomer in the mother liquor. The association mode of the two enantiomers in solution has been investigated by means of (i) the solubility measurement and (ii) the number-averaged molecular weight measurement in solution by vapor pressure osmometry, together with (iii) the molecular dynamics simulation of oligomer models. The polymorphic transition during crystallization has been observed visually and by means of the in situ FTIR technique and DSC measurement. Both metastable and stable crystals have been obtained, and their crystal structures have been elucidated by X-ray crystallographic analysis of their single crystals.     

Crystals of Benzamide,the First Polymorphous Molecular Compound,Are Helicoidal

The growth of spontaneously twisted crystals is a common but poorly understood phenomenon. An analysis of the formation of twisted crystals of a metastable benzamide polymorph (form II ) crystallizing from highly supersaturated aqueous and ethanol solutions is given here. Benzamide, the first polymorphic molecular crystal reported (1832), would have been the first helicoidal crystal observed had the original authors undertaken an analysis by light microscopy. Polymorphism and twisting frequently concur as they are both associated with high thermodynamic driving forces for crystallization. Optical and electron microscopies as well as electron and powder X-ray diffraction reveal a complex lamellar structure of benzamide form II needle-like crystals. The internal stress produced by the overgrowth of lamellae is shown to be able to create a twist moment that is responsible for the observed non-classical morphologies.     

Physico-chemical characterization of an active pharmaceutical ingredient

The physico-chemical properties and polymorphism of a new active pharmaceutical ingredient entity has been analyzed and the gain of knowledge during the chemical development of the substance is described. Initial crystallization revealed an anhydrous crystal form with good crystallinity and a single, sharp DSC melting peak at 171°C and a straightforward development of this crystal form seemed possible. However, during polymorphism screening, new crystalline forms were detected that were often analyzed as mixtures of crystal forms. The process of characterization and identification of the different crystalline forms and its thermodynamical relationship has been supported by a combination of experimental and computational work including determination of the three-dimensional structures of the crystal forms. The crystal structure of one polymorphic form was solved by single crystal X-ray structure analysis. Unfortunately, Mod B resisted in formation of suitable single crystals, but its structure could be solved by high resolution powder diffraction data analysis using synchrotron radiation. Calculation of the theoretical X-ray powder diffraction pattern from three dimensional crystal coordinates allowed an unambiguous identification of the different crystalline forms. Two polymorphic crystal forms of the API-CG3, named Mod A and Mod B, are enantiotropic whereas Mod B is the most stable polymorph at room temperature up to about 50°C and Mod A at temperatures above 50°C. The mechanism of the solid-solid transition can be explained by analyzing the molecular packing information gained from the single crystal structures. A third crystalline form with the highest melting peak turned out to be not a polymorphic or pseudopolymorphic crystal modification of our API-CG3 but a chemically different substance. This revised version was published online in July 2006 with corrections to the Cover Date.     

Crystals of Benzamide,the First Polymorphous Molecular Compound,Are Helicoidal

The growth of spontaneously twisted crystals is a common but poorly understood phenomenon. An analysis of the formation of twisted crystals of a metastable benzamide polymorph (form II ) crystallizing from highly supersaturated aqueous and ethanol solutions is given here. Benzamide, the first polymorphic molecular crystal reported (1832), would have been the first helicoidal crystal observed had the original authors undertaken an analysis by light microscopy. Polymorphism and twisting frequently concur as they are both associated with high thermodynamic driving forces for crystallization. Optical and electron microscopies as well as electron and powder X‐ray diffraction reveal a complex lamellar structure of benzamide form II needle‐like crystals. The internal stress produced by the overgrowth of lamellae is shown to be able to create a twist moment that is responsible for the observed non‐classical morphologies.     

Complexation-mediated crystallization. Crystallization of sodium acetate trihydrate needles from cyclohexane solution

The phenomenon of complexation-mediated crystallization is introduced and proposed as a new means for the preparation of novel forms of materials. Attempted crystallization of complexes of salts with crown ethers often results in the precipitation of the uncomplexed salt rather than the complex. In this study, a solution of the 15-crown-5 complex of sodium acetate in cyclohexane precipitated uncomplexed sodium acetate trihydrate as single crystals. The crystal morphology (long needles) of this crystalline sodium acetate stands in sharp contrast to the hexagonal plates known to form from aqueous solution. X-ray diffraction analysis revealed that sodium acetate as crystallized from cyclohexane solution adopted a crystal lattice identical to that in sodium acetate crystallized from aqueous solution. Possible origins of the change in crystal morphology are discussed.     

Polymorphism and solvatomorphism of bicalutamide

Single crystals of the crystallosolvate [bicalutamide + DMSO] with 1:1 stoichiometry were grown, and their structures were solved by X-ray diffraction methods. Polymorphic modifications I and II, the amorphous state, and the DMSO crystallosolvate of bicalutamide were prepared and thermochemistry of fusion processes was studied by DSC technique. The temperature dependence of the saturated vapor pressure of polymorphic form I was obtained and the thermodynamic characteristics of the sublimation process including the crystal lattice energy were calculated. The solution enthalpies of the forms under consideration and the crystallosolvate were acquired by the solution calorimetry procedure. The phase transition enthalpies estimated for form I, form II, and the amorphous state followed the rank order: form I— > form II, form I— > amorphous state, and form II— > amorphous state. The crystal lattice energy of polymorphic form II was determined using the results of sublimation and solution calorimetric experiments. The difference between the crystal lattice energy of the crystallosolvate and unsolvated phases was observed. The dissolution kinetics of forms I, II, the amorphous state, and DMSO solvate in water were investigated.     

Effect of doping an organic molecule ligand on TGS single crystals

Good quality single crystals of thiourea-doped triglycinesulphate (TuTGS) a new semiorganic nonlinear optical (NLO) crystal has been successfully grown from aqueous solution by slow evaporation method. The solubilities under various solvents in different proportions have been studied. The structural characterization of the grown crystals was carried out by X-ray diffraction. The grown crystals were subjected to FTIR and Raman analyses for vibrational assignments. The optical absorption coefficient alpha was analysed and interpreted to be allowed in the direct transition. The values of allowed direct energy gap (Eg) for undoped and doped crystals were calculated. It was found that Eg values were decreased with organic molecule doping. The powder technique of Kurtz and Perry confirm the NLO property of the grown crystal.     

弛豫基铁电单晶0.91Pb(Zn1/3Nb2/3)O3-0.09PbTiO3的制备与 性能研究

用改进的Bridgman法,在加入助熔剂的条件下,生长出最大尺寸为φ30×25mm^3的铌锌酸铅-钛酸铅固溶体单晶[0.91Pb(Zn1/3Nb2/3)O3-0.09PbTiO3]。无宏观缺陷的晶片的典型尺寸为20×15mm^2。晶体的单晶性及其结构用X射线衍射法加以研究。所得晶体用Laue衍射法定向,取(001)晶片进行性能表征。研究了材料的介电性能,并用偏光显微镜观察了(001)晶片的电畴结构。结果表明,室温下材料的介电常数较大,为2500～5000。随着温度的升高,材料发生四方铁电相—立方顺电相的相变,相变温度为190℃左右。单晶的介电温谱呈现明显的频率色钐现象,同时,介电常数最大值的温度tm随着频率的升高而降低,观察到了电畴结构的不均匀与孪生现象。     

热处理对聚己二酸丁二醋多晶结构和降解行为的影响

通过熔融结晶并结合退火处理方法得到多晶结构的聚己二酸丁二酯(PBA)及具有不同热历史的热力学稳定的a晶型,采用广角X射线衍射仪(WAXD)、原子力显微镜(AFM)和差示扫描量热仪(DSC)研究了PBA的多晶结构、晶体尺寸和结晶形貌,跟踪了退火处理PBA的生物降解行为.结果表明,分子链在相同晶格排列中围绕c轴空间取向的不...     

Influence of nucleating agent on the formation and enzymatic degradation of poly(butylene adipate) polymorphic crystals

The effects of nucleating agent multimethyl-benzilidene sorbitol (TM6) on crystallization and morphology of poly(butylene adipate) (PBA) with polymorphic crystal structures were studied by means of differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD) and polarized optical micrographs (POM). In addition to the heterogeneous nucleation, TM6 changes the formation conditions of PBA polymorphic crystals. The addition of TM6 is favorable for the formation of PBA α-form crystals, resulting in the morphological changes from spherulites to interpenetrated fibrils. The influences of TM6 on enzymatic degradation of PBA were studied in terms of the morphological change and weight loss. The results indicate that the α-form crystals induced by TM6 show much slower degradation rate. This work provides an efficient method to control the polymorphic crystal structure and further to regulate the biodegradation rate of polymer materials through modulating the homogeneous and heterogeneous nucleation modes by adding nucleating agents.     

Epitaxial crystallization of polyesters on inorganic and organic substrates

A series of low-molecular-weight linear polyesters were epitaxially crystallized from dilute solution and the melt on a variety of organic and inorganic substrates. The rod-like polyester crystals which were formed assumed general orientations in alignment with substrate geometry. This yielded monodirectional orientation of these crystals on one of the organic substrates, and bidirectional orientation on the other surfaces. Heterogeneous nucleation on the organic substrates, trioxane and naphthalene, induced the growth of much larger epitaxial crystals than have previously been observed on inorganic substrates. Those polyesters, with a high percentage of methylene units per chain repeat, crystallized in an unusual polymorphic form when in contact with the organic substrates. Polymorphic transformation to the normal form was not possible under thermal treatment or with increased crystal thickness. The expected relationship between dipolar alignment in the polymer crystal and this polymorphism was established.     

Evaluation of solvents’ effect on solubility,intermolecular interaction energies and habit of ascorbic acid crystals

Solubility of active pharmaceutical ingredient (API) in solvents is very important for drug development and manufacturing. Solubility data may provide further information such as thermochemical properties and intermolecular interactions that may lead to a better understanding of the formation of API crystals. In this study, solubility of ascorbic acid was determined by gravimetric method in four different commonly used polar protic solvents: water, methanol, ethanol and 2-propanol. The solubility of ascorbic acid crystal was also predicted using Conductor-like Screening Model – Realistic Solvent (COSMO-RS) approach. In this computational analysis, the generated ΔG values are based on the solubilities that were experimentally obtained to simulate the intermolecular forces. The intermolecular interaction data from COSMO-RS provide an insight into the relationship between the intermolecular interactions and its crystal habit across four different polar protic solvents. The habit of the crystals was then determined using light microscopy and scanning electron microscopy techniques, while the polymorphic form of the crystals was identified by X-ray powder diffraction and single X-ray diffraction techniques. The solubility and characterization data showed that the solvents with high polarity increased the solubility of ascorbic acid. The data also showed that different solvent polarity influenced the crystal habit, but did not change the crystal structure to form a new polymorph.     

Study on melting and polymorphic behavior of poly(decamethylene terephthalamide)

This work describes the melting and polymorphic behavior of poly(decamethylene terephthalamide) (PA 10T). Both solution‐crystallized (SC) and melt‐crystallized (MC) PA 10T show double melting endotherms in DSC. The SC crystal form melts at 260–300°C giving the first melting endotherm, and meanwhile undergoes a polymorphic transition forming the MC crystal form. The subsequent melting of the MC crystal form gives the second melting endotherm at 300–325°C. This irreversible polymorphic transition is confirmed by variable‐temperature WAXD and IR. Dynamic mechanical thermal analysis (DMTA) shows a glass transition temperature (T_g) at 127°C and the presence of an α′ transition at 203°C (0.1 and 1 Hz). This transition could be confirmed by DSC and variable‐temperature WAXD experiments. The α′ transition correlates with a reversible thermal process and a sudden change in intersheet spacing. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 465–472     

LiCoO(2) Concaved Cuboctahedrons from Symmetry-Controlled Topological Reactions

Morphology control of functional materials is generally performed by controlling the growth rates on selected orientations or faces. Here, we control particle morphology by "crystal templating": by choosing appropriate precursor crystals and reaction conditions, we demonstrate that a material with rhombohedral symmetry-namely the layered, positive electrode material, LiCoO(2)-can grow to form a quadruple-twinned crystal with overall cubic symmetry. The twinned crystals show an unusual, concaved-cuboctahedron morphology, with uniform particle sizes of 0.5-2 μm. On the basis of a range of synthetic and analytical experiments, including solid-state NMR, X-ray powder diffraction analysis and HRTEM, we propose that these twinned crystals form via selective dissolution and an ion-exchange reaction accompanied by oxidation of a parent crystal of CoO, a material with cubic symmetry. This template crystal serves to nucleate the growth of four LiCoO(2) twin crystals and to convert a highly anisotropic, layered material into a pseudo-3-dimensional, isotropic material.     

Temperature-dependent spin crossover in neuronal nitric oxide synthase bound with the heme-coordinating thioether inhibitors

A series of L-arginine analogue nitric oxide synthase inhibitors with a thioether tail have been shown to form an Fe-S thioether interaction as evidenced by continuous electron density between the Fe and S atoms. Even so, the Fe-S thioether interaction was found to be far less important for inhibitor binding than the hydrophobic interactions between the alkyl group in the thioether tail and surrounding protein (Martell et al. J. Am. Chem. Soc. 2010 , 132 , 798). However, among the few thioether inhibitors that showed Fe-S thioether interaction in crystal structures, variations in spin state (high-spin or low-spin) were observed dependent upon the heme iron oxidation state and temperature. Since modern synchrotron X-ray data collection is typically carried out at cryogenic temperatures, we reasoned that some of the discrepancies between cryo-crystal structures and room-temperature UV-visible spectroscopy could be the result of temperature-dependent spin-state changes. We, therefore, have characterized some of these neuronal nitric oxide synthase (nNOS)-thioether inhibitor complexes in both crystal and solution using EPR and UV-visible absorption spectrometry as a function of temperature and the heme iron redox state. We found that some thioether inhibitors switch from high to low spin at lower temperatures similar to the "spin crossover" phenomenon observed in many transition metal complexes.     

不同初始结构间规聚丙烯纤维熔融过程中的结晶转变行为

通过熔融纺丝及随后的热处理制备了具有不同初始结构的间规聚丙烯纤维(sPP).采用差示扫描量热仪(DSC)和变温广角X-射线衍射仪详细研究了sPP纤维在升温过程中的结构转变和熔融行为.结果表明,不同初始结构sPP纤维的晶型不同,卷绕纤维和退火处理纤维以Ⅰ型和Ⅱ型晶型为主,牵伸纤维介晶相占优;升高温度导致Ⅰ型和Ⅱ型两种晶型直接熔融,没有出现Ⅱ型向Ⅰ型的晶型转变;初始结构为介晶相的纤维在升温过程中部分介晶相直接转变为Ⅱ型晶型,还有一部分介晶相直接熔融,并在随后的升温过程中,形成Ⅰ型晶型.sPP纤维的多重熔融行为与其初始结构和纤维制备条件密切相关.     

Bistability in Fc-PTM crystals: the role of intermolecular electrostatic interactions

Fc-PTM is a valence tautomeric radical, where the ferrocene (Fc) group, a good electron donor, is linked by an ethylenic spacer to a perchlorotriphenylmethyl radical (PTM(*)), a good electron acceptor. In solution this compound exists mainly in the neutral Fc-PTM(*) form which can be photoexcited through an intramolecular electron transfer to the zwitterionic Fc(+*)-PTM(-) form. By contrast, in crystals of Fc-PTM at room temperature both the neutral and the zwitterionic forms coexist, pointing to a true bistability phenomenon. We rationalize these findings accounting for the role of intermolecular electrostatic interactions in Fc-PTM crystals. In fact the energy of the zwitterionic Fc(+*)-PTM(-) form is lowered in the crystal by attractive electrostatic intermolecular interactions and the cooperative nature of these interactions explains the observed coexistence of neutral Fc-PTM(*) and zwitterionic Fc(+*)-PTM(-) species. The temperature evolution of Mossbauer spectra of Fc-PTM is quantitatively reproduced adopting a bottom-up modeling strategy that combines a molecular model, derived from optical spectra of Fc-PTM in solution, with a model for intermolecular electrostatic interactions, supported by quantum-chemical calculations. Fc-PTM then offers the first experimental demonstration of bistability induced by electrostatic interactions in crystals of valence tautomeric donor-acceptor molecules.     

Spectral, optical, and thermal studies of pure and Zn(II)-doped l-histidine hydrochloride monohydrate (LHHC) crystals

The influence of doping the transition metal Zn(II) on the growth, spectral, optical, and thermal properties of l-histidine hydrochloride monohydrate (LHHC) crystals grown by slow solvent evaporation method has been investigated. Structural characterizations of the grown crystals were carried out by single crystal X-ray diffraction analysis and it shows slight structural changes as a result of doping. The FT-IR spectral study reveals the presence of various functional groups and confirms the slight distortion of the structure of the crystals due to doping. The energy dispersive X-ray analysis reveals the incorporation of Zn(II) in the crystalline matrix of LHHC crystal. The UV?CVis spectral study was carried out to analyze the optical transmittance of the grown crystals and found that the transmittance is very high in the visible and UV regions for both pure and doped crystals. The second harmonic generation (SHG) for the grown crystals was confirmed by Nd:YAG laser. The scanning electron microscopy reveals the presence of defect centers and crystal voids. The thermal stability and purity of the grown crystals were analyzed by thermogravimetry, differential thermal analysis, and differential scanning calorimetry techniques.     

Polymorphs with Remarkably Distinct Physical and/or Chemical Properties

Polymorphism in crystals is known since 1822 and the credit goes to Mitscherlich who realized the existence of different crystal structures of the same compound while working with some arsenate and phosphate salts. Later on, this phenomenon was observed also in organic crystals. With the advent of different technologies, especially the easy availability of single crystal XRD instruments, polymorphism in crystals has become a common phenomenon. Almost 37 % of compounds (single component) are polymorphic to date. As the energies of the different polymorphic forms are very close to each other, small changes in crystallization conditions might lead to different polymorphic structures. As a result, sometimes it is difficult to control polymorphism. For this reason, it is considered to be a nuisance to crystal engineering. It has been realized that the property of a material depends not only on the molecular structure but also on its crystal structure. Therefore, it is not only of interest to academia but also has widespread applications in the materials science as well as pharmaceutical industries. In this review, we have discussed polymorphism which causes significant changes in materials properties in different fields of solid-state science, such as electrical, magnetic, SHG, thermal expansion, mechanical, luminescence, color, and pharmaceutical. Therefore, this review will interest researchers from supramolecular chemistry, materials science as well as medicinal chemistry.     

Mesogen-jacketed Liquid Crystal Polymers With Mesogens of Aromatic Amide Structure

The synthesis and property of a new series of "mesogen-jacketed liquid crystal polymers" are reported. These polymers have aromatic amide structures as the mesogenic groups and are represented by poly-2,5-bis(4-methoxy- benzamido)styrene. The preliminary study on properties shows that the polymers have very high glass transition temperatures as well as very low critical concentrations for the formation of the lyotropic liquid crystal phase. The results indicate a high degree of chain rigidity. However, the liquid crystalline order of molecular organization in bulk samples disappears upon heating to the glass transition temperature as revealed by polarizing microscopy and by X-ray diffractometer. Therefore, the liquid crystalline order of these polymers forms only through solution but not through heating. This behavior is different from that of the previously studied poly-2,5-bis[(4-methoxybenzoyl)oxy]styrene and its homologs. The latter polymers are liquid crystals both lyotropically and thermotropically. © 1997 John Wiley & Sons, Ltd.