The crystal structures of 4-(3,4-dimethoxyphenylethylamino)-methylidene-2,3,4,10-tetrahydro-1H-pyrido[2,1-b]-quinazolin-10-one (1) and 4-(3,4-methylene-dioxyphenylethylamino)-methylidene-2,3,4,10-tetrahydro-1H-pyrido[2,1-b]-quina-zolin-10-one hydrochloride (2) were studied by single crystal X-ray diffraction. Their molecular and crystal structures are described in the context of intra- and inter-molecular interactions and of stereoisomerism. The crystallographic study established mixed E, Z configuration about the C4=C12 bond for (1) and E configuration about the C4=C12 bond for (2). For molecular crystals, Hirshfeld surface analyses may provide insight into intermolecular interactions, and energy framework analyses allow one to quantify different contributions to the overall energy. These analyses were performed to pinpoint intermolecular interactions in (1) and (2). According to our results, the molecules are associated with intra- and intermolecular hydrogen bonds, C-H···π and π-stacking interactions. The three-dimensional Hirshfeld surface analyses and two-dimensional fingerprint plots revealed that the structures are dominated by H···H, H···C/C···H and H···O/O···H contacts. The intermolecular energy analysis confirmed a significant contribution of dispersion to the stabilization of molecular packings in (1) and (2). Full article

The search for mononuclear lanthanoid-based single-ion magnets (SIMs) has increased the interest in some coordination environments with low coordination numbers, in combination with an axial symmetry, as they could maximize the anisotropy of complexes of oblate lanthanoid ions, such as dysprosium(III). In this sense, the pentagonal–bipyramid geometry can have ground-state doublets with perfect axiality, and therefore such complexes can be good candidates for SIMs. In our particular case, we have used a well-known open planar pentadentate chelating Schiff base ligand as 2,6-bis(1-salicyloylhydrazonoethyl)pyridine) (H₄daps) for the synthesis of air-stable pentagonal–bipyramidal Ln^III complexes (these being Ln: Dy and Er, oblate and prolate, respectively), in order to compare their structures. Thus, the reaction of H₄daps with (CH₃)₄NOH·5H₂O and the corresponding LnCl₃·hexahydrate has yielded heptacoordinate [(CH₃)₄N][Ln^III(H₂daps)Cl₂] complexes, where the tetramethylammonium cation is acting as the counterion of pentagonal–bipyramidal Ln^III complexes, which are bearing two chloride atoms in apical positions. As both complexes could be crystallized as single crystals, we can compare their crystal structures, as well as with some other related complexes in the literature, which contain different counterions, trying to see their influence on other properties of the compounds, such as their magnetic behavior. Full article

New quaternary thallium-containing chalcogenides Tl₂M^IIM^IV₃X₈ and Tl₂M^IIM^IVX₄ were synthesized, and their crystal structure was determined by XRD. Three Tl₂M^IIM^IV₃X₈ chalcogenides crystallize in orthorhombic symmetry (S.G. P2₁2₁2₁; Tl₂CdGe₃Se₈ lattice parameters a = 0.76023(9), b = 1.2071(2), c = 1.7474(2) nm), eight isostructural Tl₂B^IID^IVX₄ compounds crystallize in tetragonal symmetry, S.G. I-42m. These compounds form in the quasi-ternary systems Tl₂X–M^IIX–M^IVX₂ (X–S, Se, Te) at the component ratio 1:1:1 and 1:1:3 at the sections Tl₂M^IVX₃–B^IIX and Tl₂M^IIM^IVX₄–M^IVX₂, respectively. The composition of the Tl₂CdGe₃Se₈ compound was additionally confirmed by SEM and EDS. Full article

Quaternary semiconductor materials of the Pb₄Ga₄GeS(Se)₁₂ composition have attracted the attention of researchers due to their possible use as active elements of optoelectronics and nonlinear optics. The Pb₄Ga₄GeS(Se)₁₂ phases belong to the solid solution ranges of the Pb₃Ga₂GeS(Se)₈ compounds which form in the quasi-ternary systems PbS(Se)−Ga₂S(Se)₃−GeS(Se)₂ at the cross of the PbGa₂S(Se)₄−Pb₂GeS(Se)₄ and PbS(Se)−PbGa₂GeS(Se)₆ sections. The quaternary sulfide melts congruently at 943 K. The crystallization of the Pb₄Ga₄GeSe₁₂ phase is associated with the ternary peritectic process L_p + PbSe ↔ PbGa₂S₄ + Pb₃Ga₂GeSe₈ at 868 K. For the single crystal studies, Pb₄Ga₄GeS(Se)₁₂ were pre-synthesized by co-melting high-purity elements. The X-ray diffraction results confirm that these compounds possess non-centrosymmetric crystal structure (tetragonal symmetry, space group P–42₁c). The crystals were grown by the vertical Bridgman method in a two-zone furnace. The starting composition was stoichiometric for Pb₄Ga₄GeS₁₂, and the solution-melt method was used for the selenide Pb₄Ga₄GeSe₁₂. The obtained value of the bandgap energy for the Pb₄Ga₄GeS₁₂ and Pb₄Ga₄GeSe₁₂ crystals is 1.86 and 2.28 eV, respectively. Experimental measurements of the spectral distribution of photoconductivity for the Pb₄Ga₄GeS₁₂ and Pb₄Ga₄GeSe₁₂ crystals exhibit the presence of two spectral maxima. The first lies in the region of 570 (2.17 eV) and 680 nm (1.82 eV), respectively, and matches the optical bandgap estimates well. The locations of the admixture maxima at about 1030 (1.20 eV) and 1340 nm (0.92 eV), respectively, agree satisfactorily with the calculated energy positions of the defects vs. and V_Se. Full article

The genes for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) encode the proteins responsible for enzyme activity. Additional gene products, PRiMA and ColQ, anchor AChE and BChE proteins into membranes. Soluble AChE and BChE tetramers are composed of four identical subunits plus one polyproline-rich peptide. Dilution does not release the polyproline-rich peptide from tetramers. However, protein denaturation, for example, heating in a boiling water bath, dissociates the polyproline-rich peptide. Using mass spectrometry to sequence peptides released from soluble AChE and BChE tetramers, we find sequences that correspond to proline-rich regions from a variety of proteins. A typical peptide sequence contains 20 consecutive prolines in a 23-residue peptide, LPPPPPPPPPPPPPPPPPPPPLP. There is no single, common consensus sequence, i.e., no specific gene appears to be responsible for the polyproline-rich peptides found in soluble AChE and BChE tetramers. We propose that during metabolic turnover, protein fragments containing polyproline-rich sequences are scavenged by AChE and BChE dimers, to make stable AChE and BChE tetramers. The 40-residue, alpha-helical C-terminus of AChE or BChE is the tetramerization domain that binds the polyproline-rich peptide. Four parallel alpha helices wrap around a single antiparallel polyproline peptide to lock the tetramer in place. This organization was established by classical X-ray crystallography for isolated C-termini in complex with a proline-rich peptide. The organization was confirmed for intact, tetrameric human BChE using cryoelectron microscopy. When 40 amino acids are deleted from the carboxy terminus, monomeric enzymes are created that retain full enzymatic activity. Full article

Bioactive glasses 70SiO₂–(30-x)CaO–xZnO (x = 1, 3, 5 mol.%) were prepared by the acid-free hydrothermal method in keeping with green chemical technology. The synthetic glasses were investigated by TG-DSC, BET, XRD, and SEM–EDX methods. All synthetic glasses present mesoporous structures consisting of aggregates of nanoparticles. The bioactivity of synthetic glasses was confirmed through the formation of the hydroxyapatite phase after an in vitro experiment in simulated body fluid (SBF) solution. The effect of Zn addition is shown through the decrease in the bioactivity of synthetic glasses. Additionally, the inductively coupled plasma optical emission spectrometry (ICP-OES) analysis indicates that the Zn ions were released from the glassy networks during in vitro experiments, and they act as Zn(OH)₂ suspended precipitation to inhibit the apatite deposition. The in vitro experiment in cell culture matter was performed for SaOS₂ and Eahy929 cells. The results confirm the biocompatibility of synthetic glasses and the role of Zn addition in the proliferation of living cells. Full article

Currently, one of the key challenges in the pharmaceutical industry is the transformation of traditional batch production methods into robust continuous processes with the intention of reducing manufacturing costs and time and improving product quality. Crystallization is by far the most important purification technology in Pharma, as more than 80% of the active pharmaceutical ingredients (API) require at least one crystallization step. A successful crystallization process requires tight control over crystal size, shape and polymorphic purity. A rigorous and systematic methodology is presented to design and optimize multistage combined cooling and antisolvent continuous (mixed-suspension, mixed-product removal- MSMPR) crystallizers. The crystallization of acetylsalicylic acid (API) in ethanol (solvent) and water (anti-solvent) is used as a case study. A predictable and validated mathematical model of the system, which consists of a one-dimensional population balance model, was used to develop several optimizations strategies. Firstly, the attainable region of the mean particle size was determined for both minimum and maximum attainable crystal size. The method helped identify the most suitable number of stages and total residence time or volume for a cascade of continuous crystallizers. This was followed by a steady state optimization which helped determine the optimal operating temperatures and antisolvent flowrates. To minimize the startup time, a series of dynamic optimization strategies were implemented, assuming starting from empty vessels. The optimal dynamic profiles of the temperature and antisolvent flow rate, at different crystallization steps, were identified using a systematic and rigorous approach allowing a reduction in the startup time by 31%. Full article

As mathematical tools that can be commonly used for indexing analyses from different types of experimental patterns, we have recently developed (i) rules on forbidden hkl’s that can be used even when the space group and setting are unknown, (ii) an algorithm for error-stable Bravais lattice determination, (iii) generalization of the de Wolff figure of merit for powder diffraction (1D data) to data in higher-dimensions such as Kikuchi patterns (2D data) by electron backscatter diffraction (EBSD). In particular, (ii) could be used in a variety of situations, not just for indexing. It is explained how (i)–(iii) are used in the mathematical framework of our indexing algorithms. Full article

The d1Dplot and d2Dplot computer programs have been developed as user-friendly tools for the inspection and processing of 1D and 2D X-ray diffraction (XRD) data, respectively. d1Dplot provides general tools for data processing and includes the ability to generate comprehensive 2D plots of multiple patterns to easily follow transformation processes. d2Dplot is a full package for 2D XRD data. Besides general processing tools, it includes specific data analysis routines for the application of the through-the-substrate methodology [Rius et al. IUCrJ 2015, 2, 452–463]. Both programs allow the creation of a user compound database for the identification of crystalline phases. The software can be downloaded from the ALBA Synchrotron Light Source website and can be used free of charge for non-commercial and academic purposes. Full article

Many liquid crystal devices are driven by electric fields. Ions, typically present in molecular liquid crystal materials in minute quantities, can compromise the performance of mesogenic materials (in the simplest case, through a well-known screening effect). Even highly purified liquid crystals can be contaminated with ions during their production and handling. Therefore, measurements of the concentration of ions have become an important part of the material characterization of liquid crystals. Interestingly, even a brief analysis of existing publications can reveal a quite broad variability of the values of the concentration of ions measured by different research groups for the same liquid crystals. This reflects the complexity of ion generation mechanisms in liquid crystal materials and their dependence on numerous factors. In this paper, an overview of ion generation mechanisms in liquid crystals and modern ion measurement techniques is followed by the discussion of frequently overlooked factors affecting the measured values of the ion concentration. Ion-generating and ion-capturing properties of the alignment layers (or substrates) of liquid crystal cells are considered and used to evaluate a true concentration of ions in liquid crystals. In addition, practical recommendations aimed at improving the measurements of the ion density in liquid crystals are also discussed. Full article

Stony monuments must continuously be safeguarded from damage caused over time, in particular from the detrimental effects of weathering. One of the new environmentally-friendly (nano) materials for stone reinforcement, particularly suitable for marble and calcareous (limestone, sandstone) artifacts, is Ca₁₀(PO₄)₆(OH)₂ hydroxyapatite (HAp), which has a considerably lower dissolution rate and solubility compared to CaCO₃ calcite (the building block of marble materials): thus, HAp has been proposed for the protection of calcareous monuments against acidic rain corrosion. Promising results have been obtained, but further optimization is necessary as the treated layer is often incomplete, cracked and/or porous. Several parameters need to be optimized, in this way a homogeneous layer can be obtained, and consequently the formation of metastable can be avoided, soluble phases instead of HAp. These include: the pH of the starting solution; the effect of organic and inorganic additions in particular, that of ethanol, which is known to adsorb calcite, thus possibly favoring the growth of the HAp layer. The formation of HAp nanoparticles and their application on stony substrates has been investigated by means of a multi-methodological approach based on scanning electron microscopy, x-ray diffraction, small- and/or wide-angle x-ray scattering, Fourier-transform infrared spectroscopy, and finally, in situ measurements of laser-induced breakdown spectroscopy and acid attack preliminary tests on stony substrates. Full article

In this work, we are the first to identify and report pharmaceutically effective cocrystals of the poorly soluble drug Modafinil (MOD) using a crystal engineering approach. A multi-component system of MOD with nicotinic acid (NIC) as the coformer at a 1:1 molar ratio was prepared to simultaneously improve the solubility, dissolution and bioavailability by applying a liquid assistant grinding technique. Nicotinic acid as a potential coformer for cocrystal preparation was predicted using a novel approach of the Hansen Solubility Parameter (HSP) group contribution method. Various evaluation parameters pertaining to confirm cocrystal formation, such as Fourier transformer infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and field emission scanning electron microscopy (FESEM) were carried out. Further effects of precipitation inhibitor Hydroxypropyl methyl cellulose (HPMC) on in-vivo bioavailability enhancement were also studied. MOD-NIC cocrystals formation was confirmed by integrating the results of instrumental techniques. Aqueous solubility and in-vivo pharmacokinetic study proved 5.96 and 1.88 times higher bioavailability, respectively, in the case of prepared cocrystals compared to MOD alone, whereas bioavailability further increased by 2.72 times when these cocrystals were administered in the presence of precipitation inhibitor. Hence, solid state manipulation was successful for preparing modafinil cocrystals as a potential method for illustrating several properties. The concept of cocrystals coupled with precipitation inhibitors significantly enhanced the bioavailability of modafinil. Full article

Cyclometallated compounds have been extensively studied, in particular those with palladium and platinum. This is because of their possible applications in medicinal chemistry, as anticancer or antimicrobial agents; in some cases, with similar results as cisplatin, carboplatin or oxaliplatin. What is also remarkable is their use as homogeneous catalysts, for example, in cross coupling reactions such as Suzuki–Miyaura or Mizoroki–Heck. Herein, we report the synthesis of different thiosemicarbazone ligands, which will be reacted with a palladium or platinum salt, to give the corresponding cyclometallated compounds; in addition, their reactivity with bis(diphenylphosphino)methane (dppm) will be studied. Characterization has been carried out by elemental analysis, IR spectroscopy, ¹H and ³¹P NMR spectroscopy. Additionally, 1c has been studied by X-ray diffraction. Full article

The design and synthesis of pharmaceutical cocrystals have received great interest in the recent years. Cocrystallization of drug substances offers a tremendous opportunity for the development of new drug products with superior physical and pharmacological properties such as solubility, stability, hydroscopicity, dissolution rates and bioavailability. This short review summarizes this highly topical field, covering why the topic is of interest in pharmaceutical formulation, the definitions and practical scope of cocrystals, cocrystal preparation and characterization, a comparison of different (traditional and novel) methods for cocrystal formation and the implications for regulatory control and intellectual property protection. Traditionally, cocrystals can be prepared by solvent evaporation method, grinding, and slurry method, but every method has its limitations for certain conditions. The current trend for cocrystal formation uses sophisticated methods such as the hot melt extrusion method, spray-drying method, supercritical fluid technology and the newest method: laser irradiation. The purpose of the development of a new method is not only to overcome the limitation of traditional cocrystallization methods, but also to generate simpler steps and a continuous process for the production of the cocrystal product. This article provides a brief explanation of each method that can be used to generate pharmaceutical cocrystals as well as evaluation of cocrystals. This article also covers how the developing field of cocrystallization may impact the pharmaceutical intellectual property landscape. Full article