Experimental Charge Density Analysis of the Anti-inflammatory Drug Meloxicam [sodium 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide Monohydrate]

The charge density analysis of meloxicam sodium monohydrate [sodium 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide monohydrate] was performed with high-resolution X-ray diffraction data measured at low temperature (90 K). The experimental results were compared with those derived from the corresponding periodic theoretical calculations at the B3LYP/6-31G** level of theory. The multipolar charge-density analysis highlights the regions of meloxicam which are the most electronegative. These regions correspond to those forming short electrostatic interactions with the Na+ cation. The molecular conformation in the crystal is maintained by a strong intramolecular N−H…O=C hydrogen bond. The Na+ cation interacts with as much as five neighboring oxygen atoms. The strong hydrogen bonds N/O−H…O/N, the Na…O short contacts and hydrophobic aromatic stacking between the two aromatic cycles constitute the most represented and enriched contact types and act as the driving force in the crystal packing formation. The crystal packing presents several meloxicam anion dimers but also one Na+…Na+ repulsive interactions which are largely compensated by the electrostatic favorable attractions between anions and cations. This work is licensed under a Creative Commons Attribution 4.0 International License

A Novel Catalytic Route to Polymerizable Bicyclic Cyclic Carbonate Monomers from Carbon Dioxide

A new catalytic route has been developed for the coupling of epoxides and CO(2) affording polymerizable six‐membered bicyclic carbonates. Cyclic epoxides equipped with a β‐positioned OH group can be transformed into structurally diverse bicyclic cyclic carbonates in good yields and with high selectivity. Key to the chemo‐selectivity is the difference between the reactivity of syn‐ and anti‐configured epoxy alcohols, with the latter leading to six‐membered ring carbonate formation in the presence of a binary Al(III) aminotriphenolate complex/DIPEA catalyst. X‐ray analyses show that the conversion of the syn‐configured substrate evolves via a standard double inversion pathway providing a five‐membered carbonate product, whereas the anti‐isomer allows for activation of the oxirane unit of the substrate opposite to the pendent alcohol. The potential use of these bicyclic products is shown in ring‐opening polymerization offering access to rigid polycarbonates with improved thermal resistance

Partially Covalent Two-Electron/Multicentric Bonding between Semiquinone Radicals

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Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography

Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification owing to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural L-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale

High resolution X-ray single crystal diffraction

Aquesta tesi doctoral descriu l'ús de dades d'alta resolució de difracció de raigs X de monocristall per a la obtenció de mapes experimentals detallats de distribució de densitat de càrrega. Aquests mapes serveixen per evidenciar experimentalment l'existència d'interaccions intra- i inter-moleculars febles dins de l'estructura del vidre. Els mapes de densitat de càrrega s'obtenen mitjançant un refinament multipolar de l'estructura cristal·lina. En concret, aquest treball se centra en evidenciar experimentalment les interaccions atractives no covalent recentment descrites teòricament i que donen lloc a la formació d'enllaços de tipus "sigma i pi hole". Els termes enllaços de Triel, tetrel, pnictogen i chalcogen van ser recentment introduïts per referir-se a aquestes interaccions en funció del grup (14, 15 i 16) al qual pertany l'àtom implicat com a centre electrofílic. el fet que aquestes interaccions siguin molt febles fa necessari l'obtenció de mapes de densitat electrònica molt precisos. També s'han utilitzat aquests mapes de densitat electrònica per determinar experimental el moment quadrupolar i el potencial electrostàtic molecular d'una sèrie d'anells de fenil amb diferents substituents. Les dades experimentals obtingudes d'aquesta manera han servit per validar els resultats de càlculs teòrics.Esta tesis doctoral describe el uso de datos de alta resolución de difracción de rayos X de monocristal para la obtención de mapas experimentales detallados de distribución de densidad de carga. Estos mapas sirven para evidenciar experimentalmente la existencia de interacciones intra- e inter-moleculares débiles dentro de la estructura del cristal. Los mapas de densidad de carga se obtienen mediante un refinamiento multipolar de la estructura cristalina. En concreto, este trabajo se centra en evidenciar experimentalmente las interacciones atractivas no covalente recientemente descritas teóricamente y que dan lugar a la formación de enlaces de tipo "sigma y pi hole". Los términos enlaces de Triel, tetrel, pnictogen y chalcogen fueron recientemente introducidos para referirse a estas interacciones en función del grupo (14, 15 y 16) al que pertenece el átomo implicado como centro electrofílico. El hecho de que estas interacciones sean muy débiles hace necesario la obtención de mapas de densidad electrónica muy precisos. También se han utilizado estos mapas de densidad electrónica para determinar experimental el momento cuadrupolar y el potencial electrostático molecular de una serie de anillos de fenilo con diferentes sustituyentes. Los datos experimentales obtenidos de esta forma han servido para validar los resultados de cálculos teóricos.radiación de molibdeno para asignar la configuración absoluta de una serie de moléculas orgánicas. Las moléculas medidas fueron seleccionadas teniendo en cuenta que el elemento más pesado de su composición química fuera el oxígeno. Es bien conocido que la dispersión anómala de este tipo de compuestos es muy débil y dificulta la asignación de configuración absoluta mediante esta técnica. El resultados de este trabajo demuestran que la metodología empleada es muy efectivo para poder asignar inequívocamente la configuración absoluta correcta en este tipo de moléculas. This thesis uses high resolution single crystal X-ray diffraction data in order to obtain experimental detailed charge density distribution maps that can exhibit intra and intermolecular interactions. The charge density maps are obtained through the multipolar refinement. Particularly, this work focuses in lasts classified non-covalent attractive interactions due to sigma and pi holes, triel, tetrel, pnictogen and chalcogen bonds. The weakness of these interactions make necessary very accurate and precise maps. In the same manner, in this works they have been determined the quadrupolar moment and the molecular electrostatic potential of a series of phenyl rings substituted with different chemical groups. The experimental data obtained in this way have been used to validate theoretical predictions. Eventually in this work, high resolution single crystal X-ray diffraction data using molybdenum radiation has been employed to assign the absolute configuration of a series of organic molecules. The measured molecules were selected containing oxygen as heaviest atom since the anomalous dispersion of these kind of compounds is very weak. The use of high resolution data has been proved to be effective in order to unequivocally assign the correct absolute configuration in this kind of molecules

Guest Exchange Mechanisms in Mono-Metallic Pd(II)/Pt(II)-Cages Based on a Tetra-Pyridyl Calix[4]pyrrole Ligand

Planar pyridyl N-oxides are encapsulated in mono-metallic Pd(II)/Pt(II)-cages based on a tetra-pyridyl calix[4]pyrrole ligand. The exchange dynamics of the cage complexes are slow on both the NMR chemical shift and EXSY timescales, but encapsulation of the guests by the cages is fast on the human timescale. A “french doors” mechanism, involving the rotation of the meso-phenyl walls of the cages, allows the passage of the planar guests. The encapsulation of quinuclidine N-oxide, a sterically more demanding guest, is slower than pyridyl N-oxides in the Pd(II)-cage, and does not take place in the Pt(II)-counterpart. A modification of the encapsulation mechanism for the quinuclidine N-oxide is postulated that requires the partial dissociation of the Pd(II)-cage. The substrate binding selectivity featured by the cages is related to their different guest uptake/release mechanisms

A Mono-Metallic Pd(II)-Cage Featuring Two Different Polar Binding Sites

The tetra-α isomer of a super aryl-extended tetra-pyridyl calix[4]pyrrole self-assembles into a mono-metallic Pd(II)-cage featuring two different and converging polar binding sites. Mono- and di-topic polar guests are bound reversibly in the cage. A mechanism for guest exchange in the cage complexes is proposed

Nature of Noncovalent Carbon-Bonding Interactions Derived from Experimental Charge-Density Analysis

In an effort to better understand the nature of noncovalent carbon-bonding interactions, we undertook accurate high-resolution X-ray diffraction analysis of single crystals of 1,1,2,2-tetracyanocyclopropane. We selected this compound to study the fundamental characteristics of carbon-bonding interactions, because it provides accessible sigma holes. The study required extremely accurate experimental diffraction data, because the interaction of interest is weak. The electron-density distribution around the carbon nuclei, as shown by the experimental maps of the electrophilic bowl defined by a (CN)(2)CC(CN)(2) unit, was assigned as the origin of the interaction. This fact was also evidenced by plotting the (2)(r) distribution. Taken together, the obtained results clearly indicate that noncovalent carbon bonding can be explained as an interaction between confronted oppositely polarized regions. The interaction is, thus electrophilic-nucleophilic (electrostatic) in nature and unambiguously considered as attractive. &nbsp;</p