Diastereomeric salts of ( S , S )-sertraline, (Srt), with l - and d -tartaric acids have been prepared and their physical–chemical properties have been analyzed. Single-crystals of these salts have ...been grown and characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, hot-stage microscopy, and solubility measurements. The Srt + conformation proved to be critical for chiral discrimination. The l and d -tartrate anions are bound to the Srt + cation resulting in the formation of non-isostructural phases. The Srt salt with l -tartaric acid (Srt– l -Ta) is anhydrous ( C 2, Z ′ = 1) while that with d -tartaric acid (Srt– d -Ta) crystallizes as a hydrate in which water molecules bridge the cation to the anion ( P 2 1 2 1 2 1 , Z ′ = 1). Despite being formed by different synthons, the 3D arrangement of both salts displays structures by alternating hydrophilic and hydrophobic zones. In Srt– l -Ta, the anions are self-assembled by OH⋯COOH H-bonds to form a polar domain that attaches Srt + cations via NH⋯COO − ones. In hydrate Srt– l -Ta, the polar zone is due to the hydrated assembly of anions that surround the Srt + cations H-bonded through the N + H⋯H 2 O motif. The diastereomeric salt pair has different calculated densities and similar thermal stability (both degrade at 200 °C), but they differ significantly in solubility. The Srt– d -Ta salt is 1.6 times less soluble than the Srt– l -Ta one. Due to these features, these Srt salts have demonstrated the potential for the crystallization-based resolution of tartaric acid.
This study aims to identify, classify, quantify the ingested microplastic by marine teleost fish, in order to analyze the relationship between microplastic and trophic guilds. Food items of 214 ...individuals of Opisthonema oglinum, Bagre marinus, Cathorops spixii, Sciades herzbergii, Chloroscombrus chrysurus, Conodon nobilis, Haemulopsis corvinaeformis were analyzed. The species were classified according to their trophic guilds (zoobenthivorous or opportunistic/omnivorous). All species ingested microplastic and contamination occurred independently of the trophic guild. Of the sampled fish, 55% were contaminated by microplastic. The most consumed categories were blue (28%) and transparent filaments (20%). Raman spectroscopy measurements detected that most sampled filament corresponds to blue synthetic fiber (polyester). This study can contribute by filling gaps in knowledge regarding sandy beach impacts, which are environments so highly threatened by human activities around the world and are neglected in terms of use and conservation plans.
•All species have ingested microplastic.•Microplastic contamination occurred regardless of trophic guild.•The species that most ingested microplastic was Cathrops spixii.•The most recorded microplastic in fish stomach content was the blue filament.
Benznidazole, the primary drug used in Chagas’ disease treatment, has known side effects, which may limit its widespread use. Its low solubility could negatively interfere in the bioavailability, ...even accentuating the toxic effects. Cocrystals have been extensively used to modify and optimize physicochemical properties, but, as single-component raw materials, they are susceptible to the phenomenon of polymorphism. In this work, we report a trimorphic cocrystal containing a 1:1 ratio of benznidazole and salicylic acid. The crystalline structures of three polymorphs were elucidated by single-crystal X-ray diffraction. Moreover, several isostructural solvates were also synthesized and analyzed. The same carboxylic acid-imidazole supramolecular heterosynthon is present in the four forms, but the main structural feature is an extended column based on amide–amide hydrogen bonds. On the basis of the crystalline structures, the trimorphic system was classified as conformational and packing polymorphism. Furthermore, the dissolution profiles of the stable forms were determined and showed a significant solubility improvement over the raw material.
In this paper, novel mixed Tutton salts with the chemical formulas K2Mn0.03Ni0.97(SO4)2(H2O)6 and K2Mn0.18Cu0.82(SO4)2(H2O)6 were synthesized and studied as compounds for thermochemical heat storage ...potential. The crystallographic structures of single crystals were determined by X-ray diffraction. Additionally, a comprehensive computational study, based on density functional theory (DFT) calculations and Hirshfeld surface analysis, was performed to calculate structural, electronic, and thermodynamic properties of the coordination complexes MII(H2O)62+ (MII = Mn, Ni, and Cu), as well as to investigate intermolecular interactions and voids in the framework. The axial compressions relative to octahedral coordination geometry observed in the crystal structures were correlated and elucidated using DFT investigations regarding Jahn–Teller effects arising from complexes with different spin multiplicities. The spatial distributions of the frontier molecular orbital and spin densities, as well as energy gaps, provided further insights into the stability of these complexes. Thermogravimetry, differential thermal analysis, and differential scanning calorimetry techniques were also applied to identify the thermal stability and physicochemical properties of the mixed crystals. Values of dehydration enthalpy and storage energy density per volume were also estimated. The two mixed sulfate hydrates reported here have low dehydration temperatures and high energy densities. Both have promising thermal properties for residential heat storage systems, superior to the Tutton salts previously reported.
With the purpose of enhancing the biopharmaceutical properties of the furosemide, a pharmaceutical salt was obtained and characterized by combining the drug and triethanolamine. The solid system was ...prepared using different techniques such as kneading, grinding, and slow evaporation. It was characterizated by X-ray powder diffraction, solid-state nuclear magnetic resonance, infrared and Raman spectroscopy, thermal analysis, and scanning electron microscopy. The results showed that the same pharmaceutical compound in solid state was obtained through the different preparation techniques. The crystalline structure was fully elucidated by single-crystal X-ray diffraction. The salt formation was confirmed by two-dimensional nuclear magnetic resonance experiments, which revealed the transference of the OH proton of the drug to triethanolamine. Besides, the solubility studies demonstrated an increase in the drug solubility attributed not only to a pH change but also to a soluble salt formation in solution. In addition, the combination of the drug with triethanolamine produces an enhancement of the chemical photostability, whereas the physical photostability and the hygroscopicity status were not modified. Finally, this new solid form of furosemide constitutes an interesting strategy to improve the biopharmaceutical properties and stability of furosemide, with potential application in pharmaceutical formulations.
5-Fluorocytosine (5-FC) was crystallized with complementary dicarboxylic acids, aiming to achieve a controlled synthesis of structures based on the ΔpK a rule proposed in the salt–cocrystal continuum ...study and to provide structural information helpful in the comprehension of its supramolecularity. Although 5-FC tends to be basic, pK a = 3.26, only three salts are reported. In this way, new 5-FC salts were obtained, the fumaric, maleic and oxalic ones, all crystallizing in the monoclinic space group P21/c. In the 5-FC oxalate and fumarate cases, the acid molecules are placed on an inversion center in a fashion that each half molecule exhibits one terminal donor–acceptor site, leading to the constitution of a 5-FC–acid–5-FC heterodimer. Such a heterodimer is observed in only one donor–acceptor site of the maleate of 5-FC, whose acid molecule exhibits a closed chain architecture. Infrared and Raman spectra recorded for the three compounds complement the salt characterization on the basis of the extent of proton transfer. Thermal analysis evidence that the salt formation decreases the melting point of the new compounds, ranking this molecule as a coformer candidate to improve the physical properties of other drugs.
Febuxostat (FXT) is a urate-lowering drug and xanthine oxidase inhibitor which is used for the treatment of hyperuricemia and gout caused by increased levels of uric acid in the blood ...(hyperuricemia). The present study aims to provide deeper knowledge of the structural, vibrational spectroscopic and physiochemical properties of FXT based on monomeric and dimeric model with the aid of combination of experimental and computational methods. The conformational analysis of form Q has been done to predict the possible structure of unknown form A. Vibrational spectra of form A and Q has been compared to get an idea of hydrogen bonding interactions of form A. A computational study of FXT has been executed at different level (B3LYP, M06-2X, WB97XD) of theory and 6–31 G (d, p) basis set for dimeric model to elucidate the nature of intermolecular hydrogen bond. The red shift observed in the stretching modes of OH, CO groups and blue shift in stretching mode of CN group in experimental as well as in theoretical spectra explains the involvement of these groups in intermolecular hydrogen bonding. NBO analysis shows that change in electron density (ED) in the lone pair orbital to σ* antibonding orbital (LP1 (N39) → σ* (O3-H38)) with maximum value of E(2) energy confirms the presence of hydrogen bond (N39⋯H38-O3) leading to dimer formation. Study of topological parameters was executed for dimer using Bader's atoms in molecules (AIM) theory predicting the partially covalent nature of hydrogen bonds present in the molecule. The study of molecular electrostatic potential surface (MEPS) map ascertains that the CO, CN group are prone to electrophilic attack and OH group is active towards nucleophilic attack. The lower energy band gap and higher value of softness of dimeric model of FXT indicates its more reactivity, polarisability than monomeric model. The local reactivity descriptors predict the order of reactive sites towards electrophilic, nucleophilic and radical attack. An investigation made to determine the ligand protein interaction of FXT through docking with different molecular targets reveals the inhibitive as well as antibacterial nature of FXT.
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•Molecular structure of monomeric and dimeric model of FXT has been investigated using FT-IR and FT- Raman spectroscopy and quantum chemical calculations.•Molecular structure of polymorph A has been predicted using Vibrational spectroscopy and conformational analysis.•Natural bond orbital (NBO) analysis supported by QTAIM approach has been done to explain the nature and strength of interactions leading to dimeric model and responsible for the stabilization of the molecule.•The chemical reactivity descriptors calculated for both dimeric model predict higher reactivity of FXT in comparison to monomeric model.•The molecular docking simulation has been done to reveal the inhibitive and antibacterial nature of FXT.
The current study was aimed at investigating the febuxostat-salicylic acid (FXT-SAA) eutectic system using two polymorphs of FXT, form Q and form A. FXT, a BCS class II drug and SAA, the ...water-soluble co-former, were used to formulate the FXT-SAA eutectic system. The formed system was further confirmed using a binary phase diagram and powder X-ray diffraction (PXRD) analysis. Differential scanning calorimetry (DSC) depicted the formation of the FXT-SAA eutectic system, as indicated by the depression of the melting point (observed at 132 °C) compared with the melting points of the individual components, i.e. , FXT (208 °C for form A and 206 °C for Form Q) and SAA (160 °C). Raman and Infrared spectroscopy (IR) were used to confirm the intermolecular interactions between FXT and SAA with both forms of FXT. A novel approach was used to investigate the probable hydrogen bonding interactions in the FXT : SAA (1 : 1) eutectic system of FXT form Q. Dimers formed between the same molecules represented cohesive interactions, whereas those formed between different molecules represented adhesive interactions. The vibrational modes of dimers of FXT and SAA are closer to the experimental eutectic system than the modes of the simulated eutectic system (FXT-SAA), suggesting that the interactions in the eutectic system are predominantly cohesive. The results are in accordance with the reported theory for eutectic systems. The approach was found to be an add-on for existing methods to confirm eutectic formation in the given system. Additionally, the molecular electrostatic potential (MEP) surface predicted the negative and positive potential sites that participate in the inter-molecular hydrogen bonding.
The effect of pressure on the α and β polymorphs of a derivative of Blatter’s radical, 3-phenyl-1-(pyrid-2-yl)-1,4-dihydrobenzoe1,2,4triazin-4-yl, has been investigated using single-crystal X-ray ...diffraction to maximum pressures of 5.76 and 7.42 GPa, respectively. The most compressible crystallographic direction in both structures lies parallel to π-stacking interactions, which semiempirical Pixel calculations indicate are also the strongest interactions present. The mechanism of compression in perpendicular directions is determined by void distributions. Discontinuities in the vibrational frequencies observed in Raman spectra measured between ambient pressure and ∼5.5 GPa show that both polymorphs undergo phase transitions, the α phase at 0.8 GPa and the β phase at 2.1 GPa. The structural signatures of the transitions, which signal the onset of compression of initially more rigid intermolecular contacts, were identified from the trends in the occupied and unoccupied volumes of the unit cell with pressure and in the case of the β phase by deviations from an ideal model of compression defined by Birch–Murnaghan equations of state.
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•Novel systems of furosemide with oligosaccharides and arginine were obtained.•The ternary systems were characterized.•The oligosaccharides stabilized the solid state and improvement ...the solubility.•The systems are useful tools to optimize biopharmaceutical properties of furosemide.
Furosemide is the most commonly prescribed diuretic drug in spite of its suboptimal biopharmaceutical properties. In this work, the addition of different amino-acids was studied with the aim of selecting an enhancer of the furosemide solubility. The best results were obtained with arginine. Also, binary (furosemide:arginine) and ternary (furosemide:arginine:β-cyclodextrin and furosemide:arginine:maltodextrin) systems were prepared by the kneading method and they were compared with their corresponding physical mixtures. These new systems were characterized by Fourier transform infrared and Raman spectroscopy, X-ray powder diffractometry, scanning electron microscopy, thermogravimetric analysis, and differential scanning calorimetry. In addition, dissolution studies were performed in simulated gastric fluid. The best results in relation to improving biopharmaceutical properties were obtained with a binary combination of furosemide and arginine, demonstrating that this system could result in a suitable candidate for the development of a promising pharmaceutical formulation of the drug.
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