Synthesis and Columnar Organization of Partially Fluorinated Dehydrobenz[18]annulenes

Two diamond-shaped and partially fluorinated dehydrobenz[18]annulene macrocycles have been synthesized through a one-pot synthesis relying on fourfold Sonogashira coupling. Single crystal structures of the prepared macrocycles show continuous columnar stacks of these molecules that are mediated by the fluoroarene–alkyne, arene–alkyne, fluoroarene–fluoroarene, and alkyne–alkyne [π···π] interactions instead of the expected fluoroarene–arene [π···π] interaction.

Localising individual atoms of tryptophan side chains in the metallo-<i>β</i>-lactamase IMP-1 by pseudocontact shifts from paramagnetic lanthanoid tags at multiple sites

The metallo-β-lactamase IMP-1 features a flexible loop near the active site that assumes different conformations in single crystal structures, which may assist in substrate binding and enzymatic activity. To probe the position of this loop, we labelled the tryptophan residues of IMP-1 with 7-13C-indole and the protein with lanthanoid tags at three different sites. The magnetic susceptibility anisotropy (Δχ) tensors were determined by measuring pseudocontact shifts (PCSs) of backbone amide protons. The Δχ tensors were subsequently used to identify the atomic coordinates of the tryptophan side chains in the protein. The PCSs were sufficient to determine the location of Trp28, which is in the active site loop targeted by our experiments, with high accuracy. Its average atomic coordinates showed barely significant changes in response to the inhibitor captopril. It was found that localisation spaces could be defined with better accuracy by including only the PCSs of a single paramagnetic lanthanoid ion for each tag and tagging site. The effect was attributed to the shallow angle with which PCS isosurfaces tend to intersect if generated by tags and tagging sites that are identical except for the paramagnetic lanthanoid ion.

Cocrystallization of Febuxostat with Pyridine Coformers: Crystal Structural and Physicochemical Properties Analysis

Drug cocrystals and salts have promising applications for modulating the physicochemical properties and solubility of pharmaceuticals. In this study, a cocrystal and two salts of febuxostat (FEB) with pyridine nitrogen coformers, including 4, 4′-bipyridine (BIP), 3-aminopyridine (3AP) and 4-hydroxypyridine (4HP), were designed to improve the solubility of FEB. The single-crystal structures were elucidated, and their physical and chemical properties were investigated by IR, PXRD, and DSC. In addition, drug-related properties, including the solubility and powder dissolution rate were assessed. The solubility and powder dissolution studies showed that the FEB-BIP cocrystal and FEB-3AP salt have superior dissolution compared to FEB.

Synthesis, Crystal Structures and Urease Inhibition of 4-Bromo-N’-(1-(pyridin-2-yl)ethylidene)benzohydrazide and Its Dinuclear Copper(II) Complex

A new dinuclear copper(II) complex [Cu2(μ-Br)2L2] · 0.5 MeOH with the benzohydrazone ligand 4-bromo-N’-(1-(pyridin-2-yl)ethylidene)benzohydrazide (HL) has been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopic studies. Single crystal structures of the complex and the benzohydrazone compound were studied. The Cu atoms in the complex are coordinated by two benzohydrazone ligands and two Br bridging groups, forming square pyramidal coordination. The complex has good inhibitory activity on Jack bean urease, with IC50 value of 1.38 μmol L-1.

Two Unexpected Temperature-Induced Supermolecular Isomers from Multi-Topic Carboxylic Acid: Hydrogen Bonding Layer or Helix Tube

Under ambient conditions or 160 °C, two supramolecular isomers, namely [(H4PTTA)(H2O)2(DMF)] and [(H4PTTA)(H2O)3]··Guest (1-L and 1-H, H4PTTA = N-phenyl-N′-phenyl bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxdiimide tetra-carboxylic acid, Guest = DMF and H2O), were obtained through the reaction of H4PTTA in a mixture of H2O and dimethylformamide. The single crystal structures reveal the temperature-dependent supramolecular isomerism derived from the torsion of semi-rigid of H4PTTA. The 1-L prepared at room temperature is a hydrogen bond based achiral layer, while the hydrothermal synthesized 1-H is isomer resulted in an H-bond-based chiral tubes-packed supramolecular framework.

Polymorphism in Griseofulvin: New Story of an Old Drug with Polyethylene Glycol

Griseofulvin (GSF) is an antifungal drug that has been clinically used for six decades. Here, we present a rich polymorphism of GSF crystallizing from GSF dispersions with polyethylene glycol (PEG), including five true polymorphs (Forms I-V) and one inclusion complex (IC). Two new polymorphs were reported for the first time, denoted Forms IV and V. Single-crystal structures of new polymorphs and a GSF-PEG IC were determined by X-ray crystallography using single crystals cultivated by microdroplet melt crystallization. A comprehensive solid form landscape of GSF is established to describe phase conversions between polymorphs. Enhancement in molecular mobility by PEG is suggested to be the reason for the nucleation of two new polymorphs, while the small geographic radius of PEG is attributed to the formation of a GSF-PEG IC increasing the density and lowering the Gibbs free energy of the system. This work expands our understanding of the complicated crystallization behavior of GSF in dispersions with PEG and emphasizes the importance of polymorphism control during the manufacturing and storage of PEG-based solid dispersions to achieve reproducible and consistent pharmaceutical performance. The results also suggest that polymer addition is an alternative strategy that cannot be neglected in polymorphism screening.

Charge–Transfer Fluorescence and Room-Temperature Phosphorescence from a Bisamide-Based Derivative

The development of organic luminescent materials with bimodal emissions of both fluorescence and room-temperature phosphorescent (RTP) remains a challenge. The investigation of the relationship between fluorescence and RTP performance is especially rare. In this work, we obtained an organic luminescent molecule, 1,4-phenylenebis((9H-carbazol-9-yl)methanone) (PBCM), which exhibits bimodal emissions of cyan fluorescence and yellow RTP in its crystalline state through adopting an electron donor–acceptor–donor (D–A–D) structure. The charge–transfer (CT) effects in the bimodal luminescent properties of PBCM, as well as the single-crystal structures and thermal properties, were investigated. It was found that the CT effect in the singlet states effectively reduces the ∆Est and promotes the ISC processes, resulting in an efficient phosphorescence of PBCM at room temperature. In addition, many strong intermolecular interactions are formed between the donor and acceptor parts of adjacent molecules, leading to the rigid configurations and compact packing of molecules in crystals, which was also confirmed to facilitate the efficient bimodal emissions of PBCM.

Localising individual atoms of tryptophan side chains in the metallo-β-lactamase IMP-1 by pseudocontact shifts from paramagnetic lanthanoid tags at multiple sites

The metallo-β-lactamase IMP-1 features a flexible loop near the active site that assumes different conformations in single crystal structures, which may assist in substrate binding and enzymatic activity. To probe the position of this loop, we labelled the tryptophan residues of IMP-1 with 7-13C-indole and the protein with lanthanoid tags at three different sites. The magnetic susceptibility anisotropy (Δχ) tensors were determined by measuring pseudocontact shifts (PCS) of backbone amide protons. The Δχ tensors were subsequently used to identify the atomic coordinates of the tryptophan side chains in the protein. The PCSs were sufficient to determine the location of Trp28, which is located in the active site loop targeted by our experiments, with high accuracy. Its average atomic coordinates showed barely significant changes in response to the inhibitor captopril. It was found that localisation spaces could be defined with better accuracy by including only the PCSs of a single paramagnetic lanthanoid ion for each tag and tagging site. The effect was attributed to the shallow angle with which PCS isosurfaces tend to intersect if generated by tags and tagging sites that are identical except for the paramagnetic lanthanoid ion.

Selected solid-state behaviour of three di-tert-butyl-substituted N-salicylideneaniline derivatives: temperature-induced phase transitions and chromic behaviour

The synthesis, single-crystal structures and chromic behaviour of three related Schiff bases, namely, (E)-2,4-di-tert-butyl-6-{[(4-fluorophenyl)imino]methyl}phenol, C21H26FNO, 1, (E)-2,4-di-tert-butyl-6-{[(4-chlorophenyl)imino]methyl}phenol, C21H26ClNO, 2, and (E)-6-{[(4-bromophenyl)imino]methyl}-2,4-di-tert-butylphenol, C21H26BrNO, 3, are reported. Two polymorphs of 1 were obtained, which were found to have different photochromic properties. Schiff bases 2 and 3 were found to be isostructural and underwent a phase transition upon cooling which was attributed to the dynamic disorder in one of the tert-butyl groups resolving at low temperature. All of the structures were found to exist in the enol rather than the keto form based on the C—O(H) and imine C=N bond lengths, and contained an intramolecular O—H...N hydrogen bond alongside weaker intermolecular C—H...O contacts.