Combining two antitubercular drugs, clofazimine and 4-aminosalicylic acid, in order to improve clofazimine aqueous solubility and 4-aminosalicylic acid thermal stability

Four forms of a salt combining two antitubercular drugs, clofazimine and 4-aminosalicylic acid, are reported and the crystal structure of two of these forms are described. TG/DSC analysis of all four forms demonstrate an increase in the temperature at which degradation (upon decarboxylation) occurs in comparison to pure 4-aminosalicylic acid. Water solubility evaluation indicates a significant increase of the amount of clofazimine detected in water (10.26 ± 0.52 mg/mL for form I, 12.27 ± 0.32 mg/mL for form II, 7.15 ± 0.43 mg/mL for form III and 8.50 ± 1.24 mg/mL for form IV) in comparison to pure clofazimine (0.20 ± 0.03 mg/mL

Secondary ion mass spectrometry, a powerful tool for revealing ink formulations and animal skins in medieval manuscripts

XRD diffractograms, ToF-SIMS MS and ATR-FTIR spectrometry spectra, recorded on inks on historical parchments (pigments, inked areas). ToF-SIMS and ATR-FTIR spectra from non-inked areas of the parchments. See the read-me file for complete description of the files and structure, and the main manuscript for the methodology. The PCA algorithm code is also provided. Article abstract : Book production by medieval scriptoria have gained growing interest in recent studies. In this context, identifying ink compositions and parchment animal species from illuminated manuscripts is of great importance. Here, we introduce time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a non-invasive tool to identify both inks and animal skins in manuscripts, at the same time. For this purpose, both positive and negative ion spectra in inked and non-inked areas were recorded. Chemical compositions of pigments (decoration) or black inks (text) were determined by searching for characteristic ion mass peaks. Animal skins were identified by data processing of raw ToF-SIMS spectra using Principal Component Analysis (PCA). In illuminated manuscripts from 15th c. to 16th c., malachite (green), azurite (blue), cinnabar (red) inorganic pigments, as well as iron-gall black ink, were identified. Carbon black and indigo (blue) organic pigments were also identified. Animal skins were identified in modern parchments of known animal species by a two-steps PCA procedure. We believe the proposed method will find extensive application in material studies of medieval manuscripts, as it is non-invasive, highly sensitive and able to identify both inks and animal skins at the same time, even from traces of pigments and tiny scanned areas.In-house PCA algorithm requires python. ToF-SIMS raw data require SurfaceLab software. ATR-FTIR raw data (.0) can be read with free-licence software (Fityk). XRD diffractograms are directly exported in .txt from .xyz files. Funding provided by: Namur Institute of Structured Matter, University of NamurCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100023393Award Number:Analytical and data processing methods can be found in the manuscript

Synthesis of a Bimetallic Dodecaborate LiNaB_(12)H_(12)with Outstanding Superionic Conductivity

Metal dodecaborates M_2/_nB_(12)H_(12) (n denotes the valence of the metal M), containing icosahedral polyatomic anion [B_(12)H_(12)]^(2−), have been attracting increasing interest as potential energy materials, especially in the context of hydrogen storage and superionic conductivity. M_2/_nB_(12)H_(12) are commonly formed as dehydrogenation intermediates from metal borohydrides M(BH_4)_n, like LiBH_4 and Mg(BH_4)_2, which are well-known as potential high-density hydrogen storage materials. The strong B−B bond in the icosahedral [B_(12)H_(12)]^(2−), however, is regarded to be the key factor that prevents the rehydrogenation of dodecaborates. In order to elucidate the mechanism as well as to provide effective solutions to this problem, a novel solvent-free synthesis route of anhydrous M_2/nB_(12)H_(12) (here M means Li, Na, and K) has been developed. Thermal stability and transformations of the anhydrous single phase Li_2B_(12)H_(12) suggested the formation of the high temperature polymorph of Li_2B_(12)H_(12) during the dehydrogenation of LiBH_4, while concurrently emphasized the importance of further investigation on the decomposition mechanism of metal borohydrides and metal dodecaborates. The high stability of icosahedral [B_(12)H_(12)]^(2−), on the other hand, favors its potential application as solid electrolyte. Recently, Na^+ conductivity of Na_2B_(12)H_(12) was reported to be 0.1 S/cm above its order−disorder phase transition at ∼529 K, which is comparable to that of a polycrystalline β”-Al_2O_3 (0.24 S/cm at 573 K) solid state Na-electrolyte. Mechanistic understanding on the diffusion behavior of cation and further improvement of ionic conductivity at a lower temperature, however, are important in order to facilitate the practical application of metal dodecaborates as superionic conductors

Exploring polymorphism and stoichiometric diversity in naproxen/proline cocrystals

We present naproxen/proline cocrystals discovered when combining enantiopure and racemic naproxen and proline. Using liquid-assisted grinding as the main method to explore the variety of crystal forms in this system, we found 17 cocrystals, of which the structures of only four of them were previously known. The naproxen/proline system exhibited multiple polymorphs of 1 : 1 stoichiometry as well as more rare cocrystals with 1 : 2 and 2 : 3 stoichiometries, two cocrystal hydrates and one cocrystal solvate. In situ ball-milling, used to monitor liquid-assisted grinding reactions, revealed that the solvent dictates the reaction intermediates even if the final reaction product stays the same. Synchrotron X-ray diffraction data collected in situ upon heating allowed us to monitor directly the phase changes upon heating and gave access to pure diffraction patterns of several cocrystals, thus enabling their structure determination from powder X-ray diffraction data; this method also confirmed the formation of a conglomerate in the RS-naproxen/DL-proline system. Proline in cocrystals kept its ability to form charge-assisted head-to-tail N–H⋯O hydrogen bonds, typical of pure crystalline amino acids, thus increasing the percentage of strong charge-assisted interactions in the structure and consequently providing some of the cocrystals with higher melting points as compared to pure naproxen. The majority of drugs are chiral, and hence, these data are of importance to the pharmaceutical industry as they provide insight into the challenges of chiral cocrystallization

Tribenzoatobismuth(III): a new ­polymorph

A new polymorph (β) was obtained for an active pharmaceutical ingredient, bis­muth tribenzoate, [Bi(C6H5CO2)3]. The new β-polymorph is 1.05 times denser than the previously known polymorph [Rae et al. (1998 ▶). Acta Cryst. B54, 438–442]. In the β-polymorph, the Bi atom is linked with three benzoate anions, each of them acting as a bidentate ligand, and these assemblies with C 3 point symmetry can be considered as ‘mol­ecules’. The structure of the β-polymorph has no polymeric chains, in contrast to the previously known polymorph. The ‘mol­ecules’ in the β-polymorph are stacked along [001], so that the phenyl rings of the neighbouring mol­ecules are parallel to each other. Based on the pronounced difference in the crystal structures, one can suppose that two polymorphs should differ in the dissolution kinetics and bioavailability