Two novel polymorphic forms of iron‐chelating agent deferiprone

Thalassemia is a genetic blood disorder requiring life‐long blood transfusions. This process often results in iron overload and can be treated by an iron‐chelating agent, like deferiprone (3‐hydroxy‐1,2‐dimethylpyridin‐4‐one), C₇H₉NO₂, in an oral formulation. The first crystal structure of deferiprone, (Ia), was reported in 1988 [Nelson et al. (1988). Can. J. Chem. 66 , 123–131]. In the present study, two novel polymorphic forms, (Ib) and (Ic), of deferiprone were identified concomitantly with polymorph (Ia) during the crystallization experiments. Polymorph (Ia) was redetermined at low temperature for comparison of the structural features and lattice energy values with polymorphs (Ib) and (Ic). Polymorph (Ia) crystallized in the orthorhombic space group Pbca, whereas both polymorphs (Ib) and (Ic) crystallized in the monoclinic space group P2₁/c. The asymmetric units of (Ia) and (Ib) contain one deferiprone molecule, while polymorph (Ic) has three crystallographically independent molecules (A, B and C). All three polymorphs have similar hydrogen‐bonding features, such as an R₂²(10) dimer formed by O—H…O hydrogen bonds, an R₄³(20) tetramer formed by C—H…O hydrogen bonds and π–π interactions, but the polymorphs differ in their molecular arrangements in the solid state and are classified as packing polymorphs. O—H…O and C—H…O hydrogen bonds lead to the formation of two‐dimensional hydrogen‐bonded parallel sheets which are interlinked by π–π stacking interactions. In the three‐dimensional crystal packing, the deferiprone molecules were aggregated as corrugated sheets in polymorphs (Ia) and (Ic), whereas in polymorph (Ib), they were aggregated as a square‐grid network. The characteristic crystalline peaks of polymorphs (Ia), (Ib) and (Ic) were established through powder X‐ray diffraction analysis. The Rietveld analysis was also performed to estimate the contribution of the polymorphs to the bulk material.     

Two polymorphs of 2,5‐dichloro‐3,6‐bis(dibenzylamino)‐p‐hydroquinone with flexible dibenzylamino groups

We obtained two conformational polymorphs of 2,5‐dichloro‐3,6‐bis(dibenzylamino)‐p‐hydroquinone, C₃₄H₃₀Cl₂N₂O₂. Both polymorphs have an inversion centre at the centre of the hydroquinone ring (Z′ = ), and there are no significant differences between their bond lengths and angles. The most significant structural difference in the molecular conformations was found in the rotation of the phenyl rings of the two crystallographically independent benzyl groups. The crystal structures of the polymorphs were distinguishable with respect to the arrangement of the hydroquinone rings and the packing motif of the phenyl rings that form part of the benzyl groups. The phenyl groups of one polymorph are arranged in a face‐to‐edge motif between adjacent molecules, with intermolecular C—H…π interactions, whereas the phenyl rings in the other polymorph form a lamellar stacking pattern with no significant intermolecular interactions. We suggest that this partial conformational difference in the molecular structures leads to the significant structural differences observed in their molecular arrangements.     

ϵ‐RbCuCl3, a new polymorph of rubidium copper trichloride: synthesis,structure and structural complexity

A novel polymorph of RbCuCl₃ (rubidium copper trichloride), denoted ϵ‐RbCuCl₃, has been prepared by chemical vapour transport (CVT) from a mixture of CuO, CuCl₂, SeO₂ and RbCl. The new polymorph crystallizes in the orthorhombic space group C222₁. The crystal structure is based on an octahedral framework of the 4H perovskite type. The Rb⁺ and Cl⁻ ions form a four‐layer closest‐packing array with an ABCB sequence. The Cu²⁺ cations reside in octahedral cavities with a typical [4 + 2]‐Jahn–Teller‐distorted coordination, forming four short and two long Cu—Cl bonds. ϵ‐RbCuCl₃ is the most structurally complex and most dense among all currently known RbCuCl₃ polymorphs, which allows us to suggest that it is a high‐pressure phase, which is unstable under ambient conditions.     

Crystal structures of two polymorphic forms of DOTAM‐mono‐acid dihydrate

The structural chemistry of 2‐[4,7,10‐tris(carbamoylmethyl)‐1,4,7,10‐tetraazacyclododecan‐1‐yl]acetic acid dihydrate, C₁₆H₃₁N₇O₅·2H₂O, is described. The macrocyclic compound, also known by the abbreviation DOTAM‐mono‐acid, crystallized at room temperature and was isolated concomitantly as two polymorphic forms. The structures of both polymorphs were determined at 90 K. The first polymorph crystallized as a zwitterionic dihydrate [systematic name: 4,7,10‐tris(carbamoylmethyl)‐1‐(carboxylatomethyl)‐1,4,7,10‐tetraazacyclododecan‐1‐ium dihydrate] in the space group P2₁/n, with Z′ = 1. The second polymorph crystallized as a zwitterionic dihydrate in the space group P2₁ at 90 K, with Z′ = 2. The two independent molecules are related by a local center. In each polymorph, the zwitterion is formed between the negatively‐charged carboxylate group and the ring N atom that bears the acetate pendant arm. Extensive inter‐ and intramolecular hydrogen bonding exists in both polymorphic structures. In polymorph 1, an intermolecular hydrogen‐bonding network propagating parallel to the a direction creates an infinite chain. A second hydrogen‐bonding network is observed through a water molecule of hydration in the b direction. Polymorph 2 also has two intermolecular hydrogen‐bonding networks. One propagates parallel to the a direction, while the other propagates in the [10] direction. Increasing the temperature of polymorph 2 yields the same structure at T = 180 K, but the pseudocenter becomes exact at 299 K. The higher‐temperature structure has Z′ = 1 in the space group P2₁/c.     

Reassessment of paracetamol orthorhombic Form III and determination of a novel low‐temperature monoclinic Form III‐m from powder diffraction data

Paracetamol [N‐(4‐hydroxyphenyl)acetamide, C₈H₉NO₂] has several polymorphs, just like many other drugs. The most stable polymorphs, denoted Forms I and II, can be obtained easily and their crystal structures are known. Crystals of the orthorhombic, less stable, room‐temperature Form III are difficult to grow; they need a special recipe to crystallize and suffer from severe preferred orientation. A crystal structure model of Form III has been proposed and solved from a combination of structure prediction and powder X‐ray diffraction (PXRD) [Perrin et al. (2009). Chem. Commun. 22 , 3181–3183]. The final R_wp value of 0.138 and the corresponding considerable residual trace were reasons to check its validity. A new structure determination of Form III using new high‐resolution PXRD data led to a final R_wp value of 0.042 and an improvement of the earlier proposed model. In addition, a reversible phase transition was found at 170–220 K between the orthorhombic Form III and a novel monoclinic Form III‐m. The crystal structure of Form III‐m has been determined and refined from PXRD data to a final R_wp value of 0.059.     

Aqueous Solubility of Organic Compounds for Flow Battery Applications: Symmetry and Counter Ion Design to Avoid Low-Solubility Polymorphs

Flow batteries can play an important role as energy storage media in future electricity grids. Organic compounds, based on abundant elements, are appealing alternatives as redox couples for redox flow batteries. The straightforward scalability, the independence of material sources, and the potentially attractive price motivate researchers to investigate this technological area. Four different benzyl-morpholino hydroquinone derivatives were synthesized as potential redox active species. Compounds bearing central symmetry were shown to be about an order of magnitude less soluble in water than isomers without central symmetry. Counter ions also affected solubility. Perchlorate, chlorate, sulfate and phosphate anions were investigated as counter ions. The formations of different polymorphs was observed, showing that their solubility is not a function of their structure. The kinetics of the transformation can give misleading solubility values according to Ostwald’s rule. The unpredictability of both the kinetics and the thermodynamics of the formation of polymorphs is a danger for new organic compounds designed for flow battery applications.     

Polymorphic Characterization,Pharmacokinetics, and Anti-Inflammatory Activity of Ginsenoside Compound K Polymorphs

Polymorphism exhibits different physicochemical properties, which can impact the bioavailability and bioactivity of solid drugs. This study focused on identifying the polymorphs of ginsenoside compound K (CK) and studying their different behaviors in pharmacokinetics (PK) and pharmacodynamics (PD). Four CK polymorphs (form I, II, III, and IV) from organic solvents were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD). A feasible LC-MS/MS method was exploited to determine the PK parameters. Form II displayed the most exposure, followed by form I, III, and IV. Notably, all forms showed sex dimorphism, and the bioavailability in the female group was about two-fold higher than in the male group. The PD properties were investigated in carrageenan-induced acute paw inflammation, and form II at 20 mg/kg showed significant inhibition of edema by 42.7%. This study clarified the polymorphic, PK, and PD characters of four crystal forms of CK, and the data suggested that form II had the best efficacy for drug development.     

Concomitant polymorphs of 1,3‐bis(3‐fluorophenyl)urea

Hydrogen bonding between urea functionalities is a common structural motif employed in crystal‐engineering studies. Crystallization of 1,3‐bis(3‐fluorophenyl)urea, C₁₃H₁₀F₂N₂O, from many solvents yielded concomitant mixtures of at least two polymorphs. In the monoclinic form, one‐dimensional chains of hydrogen‐bonded urea molecules align in an antiparallel orientation, as is typical of many diphenylureas. In the orthorhombic form, one‐dimensional chains of hydrogen‐bonded urea molecules have a parallel orientation rarely observed in symmetrically substituted diphenylureas.     

Temperature‐Dependent Evolution of Poly(3‐Hexylthiophene) Type‐II Phase in a Blended Thin Film

The structure of P3HT in P3HT:PCBM films is examined on a poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) substrate subjected to cryo‐cooling to low temperature (−143 °C) followed by gradual heating to 50 °C. The behavior of these systems is examined in the absence and presence of an Al electrode on top of the P3HT:PCBM film. At temperatures below −10 °C, only the type‐I phase of P3HT is observed. However, the type‐II phase of P3HT starts to form near −10 °C, in both the presence and absence of the Al layer. In the system without an Al layer, the type‐II phase disappears at 30 °C, but this phase persists to 50 °C in the presence of the Al layer. Concomitant with the formation of the type‐II phase, a 1:3 ordered P3HT type‐II (1/3,0,0) superlattice peak emerged. The type‐II domains tend to form near the Al electrode layer and show a higher degree of alignment than the type‐I crystals.

     

马来酰肼多形态的太赫兹光谱研究

分子的多形态(多晶型)是指化学组成相同但存在不止一种晶体形式的物质.这些多形态广泛存在于自然界中,其中药物的多形态尤其普遍.这些药物多形态虽然具有相同的化学分子组成,但其理化性质却存在差异,最终会导致药物作用功能的不同.近年来,随着太赫兹(THz)辐射源的产生方式成为一种常规技术后,太赫兹时域光谱技术(THz-TDS)...