The creation of salts is a frequently used approach to modify physicochemical properties of active pharmaceutical ingredients. This work prepares a collection of sulfathiazole salts to probe the influence of counterion structure on crystal packing.
Six new multi-component crystals between 4-phenylpyridine and substituted benzoic acids (3-nitrobenzoic acid, 3,5-dinitrobenzoic acid, gallic acid, 4-aminobenozic acid, salicylic acid and 2-aminobenzoic acid) were created and characterized crystallographically to investigate the influence of chemical and structural factors on the hydrogen location between the two components. While the expected intermolecular interactions are formed between the acid and pyridine group in most cases, the gallic acid structure is anomalous forming an unexpected salt with pyridine to hydroxyl interactions. Calculations of the hydrogen bonding motifs indicate that the level of proton transfer (e.g. salt versus co-crystal formation) is not solely a function of the dimer geometry but influenced by the local crystallographic environment. Analysis of the crystal structures indicates the strength of the hydrogen bonding into this motif alters the expected protonation state from chemical considerations.
Tephrochronology (the dating of sedimentary sequences using volcanic ash layers) is an important tool for the dating and correlation of sedimentary sequences containing archives and proxies of past environmental change. In addition, tephra layers provide valuable information on the frequency and nature of ash fallout from volcanic activity. Successful tephrochronology is usually reliant on the correct geochemical identification of the tephra which has, until now, been based primarily on the analysis of major element oxide composition of glass shards using electron probe microanalysis (EPMA). However, it is often impossible to differentiate key tephra layers using EPMA alone. For example, the Hekla AD 1947 and 1510 tephras (which are found as visible layers in Iceland and also as ‘crypto-tephra’ microscopic layers in NW Europe) are currently indistinguishable using EPMA. Therefore, other stratigraphic or chronological information is needed for their reliable identification. Raman spectroscopy is commonly used in chemistry, since vibrational information is specific to the chemical bonds and symmetry of molecules, and can provide a fingerprint by which these can be identified. Here, we demonstrate how Raman spectroscopy can be used for the successful discrimination of mineral species in tephra through the analysis of individual glass shards. In this study, we obtained spectra from minerals within the glass shards – we analysed the microlites and intratelluric mineral phases that can definitely be attributed to the tephra shards and the glass itself. Phenocrysts were not analysed as they could be sourced locally from near-site erosion. Raman spectroscopy can therefore be considered a valuable tool for both proximal and distal tephrochronology because of its non-destructive nature and can be used to discriminate Hekla 1510 from Hekla 1947.
Cocrystals have been increasingly recognized as an attractive alternative delivery form for solid drug products. In this work, Raman spectroscopy, X-ray powder diffraction/X-ray crystallography, and differential scanning calorimetry have been used to study the phenomenon of cocrystal formation in stoichiometric mixtures of citric acid with paracetamol. Raman spectroscopy was particularly useful for the characterization of the products and was used to determine the nature of the interactions in the cocrystals. It was observed that little change in the vibrational modes associated with the phenyl groups of the respective reactants took place upon cocrystal formation but changes in intensities of the vibrational modes associated with the amide and the carboxylic acid groups were observed upon cocrystal formation. Several new vibrational bands were identified in the cocrystal which were not manifest in the raw material and could be used as diagnostic features of cocrystal formation. An understanding of the effects of cocrystal formation on the vibrational modes was obtained by the complete assignment of the spectra of the starting materials and of the cocrystal component. The results show that the cocrystals was obtained in a 2 : 1 molar ratio of paracetamol to citric acid. The asymmetric unit of the crystal contains two paracetamol molecules hydrogen-bonded to the citric acid; one of these acts as a phenolic-OH hydrogen bond donor to the carbonyl of a carboxylic acid arm of citric acid. In contrast, the other phenolic-OH acts as a hydrogen bond acceptor from the quaternary C–OH of citric acid.
Ternary crystalline complexes consisting of both salts and ionic co-crystals have been created through the crystallisation of the binary co-crystal 3,5-dinitrobenzoic acid–4-(dimethylamino)benzoic acid with group 1 or ammonium cations. The size and charge density of the cation can be used to adjust the protonation level and local geometry of the acid pair. The selectivity and coordination geometry of the chaperone cation may be further adjusted by the inclusion of a crown ether to reduce the number and location of potential binding sites.
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