Unraveling the effects of co-crystallization on the UV/Vis absorption spectra of an N-salicylideneaniline derivative:A computational RI-CC2 investigation

This work aims at unraveling the effects of co-crystallization on the optical properties of an N-salicylideneaniline-derived molecular switch transforming between an enol and a keto form. This is achieved by way of a two-step multi-scale method where (i) the molecular geometry and unit cell parameters are optimized using a periodic boundary conditions density functional theory method and (ii) the optical properties are computed for a selection of clusters embedded in an array of point-charges that reproduce the crystal field electronic potential. The optical properties (vertical excitation energies and oscillator strengths) are obtained at the RI-CC2/def2-TZVPD level of approximation. This method allows us to decompose the effects of co-crystallization into (i) indirect effects, the geometry changes of the chromophore due to crystal packing with the coformer, and (ii) direct ones, the polarization due to the interacting coformer and to the crystal field. For the former effects, variations of a crucial torsion angle lead to modification of the p-conjugation and therefore to the decrease or increase of the excitation energies. About the latter, they are antagonistic: (i) the coformer is not directly involved in the excitations but its polarization decreases the excitation energies while (ii) the crystal field has the opposite effect. For the co-crystals with succinic and fumaric acids, combining these direct and indirect effects leads to a hypsochromic shift of the first absorption band with respect to the reference crystal, in agreement with experimental data

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

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

Characterization of PECVD Silicon Nitride Photonic Components at 532 and 900 nm Wavelength

Low temperature PECVD silicon nitride photonic waveguides have been fabricated by both electron beam lithography and 200 mm DUV lithography. Propagation losses and bend losses were both measured at 532 and 900 nm wavelength, revealing sub 1dB/cm propagation losses for cladded waveguides at both wavelengths for single mode operation. Without cladding, propagation losses were measured to be in the 1-3 dB range for 532 nm and remain below 1 dB/cm for 900 nm for single mode waveguides. Bend losses were measured for 532 nm and were well below 0.1 dB per 90 degree bend for radii larger than 10 mu m

Phosphorus compounds in conceptual, organic, and organometallic chemistry : a theoretical approach

Dans cette thèse, nous étudions l'interaction qui s'exerce entre les groupements fonctionnels phosphorés et le restant de la molécule. Par une étude théorique fondamentale de ces groupes dans des composés organiques et organométalliques, nous obtenons une description générale de leur comportement. Nous parvenons ainsi à déterminer l'importance de l'atome de phosphore dans ces composés. Pour arriver à comprendre le comportement des composés phosphorés, nous étudions non seulement les propriétés structurales, énergétiques et électroniques, grandeurs directement accessibles, mais également les concepts chimiques importants qui peuvent en être extraits, comme l'électronégativité, la dureté, la fonction de Fukui. Ces concepts ne peuvent mener à des interprétations intéressantes que s'ils sont correctement compris. En conséquence, une première partie de la thèse a une orientation conceptuelle et a pour objectif d'obtenir des valeurs correctes d'électronégativité de groupes. En utilisant un modèle approprié pour décrire l'environnement moléculaire, des électronégativités de 'Group In Molecules' peuvent être obtenues. Ces éléctronegativités tiennent implicitement compte de l'effet de l'environnement moléculaire. En étudiant ces électronégativités ainsi que d'autres concepts liés aux groupements phosphorés dans les composés organiques et organométalliques, nous parvenons à proposer une description générale de l'influence de ces groupements sur les composés étudiés. Nous en déduisons que les groupements phosphorés peuvent être vus comme des espèces à caractère ionique fort, interagissant par polarisation avec leur environnement moléculaire et aussi, lorsque des orbitales de type « donneur électronique » sont accessibles, par rétro donation. En d'autres mots, ces groupements présentent un caractère sigma donneur / pi accepteur.In this thesis, we describe how phosphorus-containing groups interact with the remainder of the molecule on a fundamental level. By a theoretical study of these groups in organic as well as organometallic compounds, we are able to obtain a general description of their behavior towards the studied organic as well as metallic centers and of the importance of the central phosphorus atom. To achieve a full understanding of phosphorus compounds we not only study the directly accessible structural, energetic, and electronic properties, but also the chemically relevant concepts that can be extracted from these latter, such as electronegativity, hardness, Fukui function. These concepts can only be expected to give valuable insights if they are correctly understood. A first part of this thesis therefore has a conceptual orientation, aiming to compute accurate group electronegativity values. By taking an appropriate model of the molecular environment, accurate 'Group In Molecule' electronegativities are determined, which account for the effect of the molecular environment. By studying these and other concepts of the phosphorus groups in organophosphorus as well as organometallic compounds, we are able to give a general description of these groups in the studied compounds. They can be seen as electropositive, highly ionic species interacting with the molecular skeleton through polarization and, if appropriate donor orbitals are present, also through back-bonding. To summarize, these groups have sigma donor / pi acceptor character.Doctorat en sciences (sciences chimiques) (CHIM 3)--UCL, 200

Negative hyperconjugation in phosphorus stabilized carbanions.

The electronic Fukui function is used to give qualitative electronic proof on the existence of back-bonding from the carbon lone pair toward the sigma* P-Y and P-O orbitals in phosphorus stabilized carbanions. NBO analyses are used to investigate the energetic, electronic, and structural impacts of this negative hyperconjugation interaction. The observed energetic stabilization can indeed be attributed to the electronic delocalization of the lone pair toward the antibonding orbitals. This delocalization is furthermore responsible for the shorter P-C bonds, longer P-Y (P-O) bonds, and wider Y-P-Y angles observed for the anionic compounds compared to their neutral counterparts. From the electronic NBO analysis it becomes clear that phosphorus containing functional groups are best described as sigma donor/pi acceptors

Innovative chiral resolution using enantiospecific co-crystallization in solution

A large number of active pharmaceutical ingredients (API) are chiral. Most of them are synthesized as racemic mixtures, and a chiral resolution step is introduced somewhere along the production process. In this study, we have used the specific hydrogen bonding interactions present in co-crystals to develop a new resolution technique. As these interactions are strongly direction dependent, we highlighted that an enantiopure API only forms a co-crystal with one of two enantiomers of a chiral co-crystal former (or co-former). Unlike salts, a diastereomeric pair cannot be obtained. This enantiospecific behavior of co-crystal candidates suggests that a racemic mixture of this candidate can be resolved through a co-crystallization in solution, which hitherto has not been observed yet. As a study system, we chose (RS)-2-(2-oxopyrrolidin-1-yl) butanamide, as the S-enantiomer is an API and no viable salts of this compound have been identified. The only known resolution technique for this compound is, therefore, based on chiral chromatography. Because of enantiospecific interactions with an S-mandelic acid coformer, we were able to selectively co-crystallize the S-enantiomer in acetonitrile. This enantiospecific co-crystallization in solution has been thermodynamically verified, by construction of ternary phase diagrams at different temperatures. Initial results not only validate our innovative resolution technique through co-crystallization but also furthermore already showed high efficiency, as 70% of the S-enantiomer could be separated from the racemic mixture in a single co-crystallization step. © 2012 American Chemical Society