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We report the crystal structure of the anhydrous form of Oxyma-B, a relevant racemization suppressor for peptide synthesis, solved by direct space methodologies with X-Ray Powder Diffraction data. The structure had remained elusive since only monohydrate crystals are readily obtained from slow crystal growth experiments. An extensive combined experimental and computational study has allowed us to obtain deeper insight into the solid-state landscape of Oxyma-B and its tendency for hydration. The singular network of H-bonds and energetically relevant O⋯π interactions formed by the two symmetrically independent molecules of anhydrous Oxyma-B has been analysed by using the quantum theory of "atoms-in-molecules" (QTAIM) and the noncovalent interaction plot (NCIplot). [ABSTRACT FROM AUTHOR]

We report the discovery of new cocrystals of bosentan, a drug used in the treatment of pulmonary artery hypertension, with succinic acid, resorcinol, and 4-hydroxybenzoic acid through a combined virtual/experimental cocrystal screening. The X-ray structure of the bosentan/succinic acid cocrystal shows a network of H-bonds involving both components, which have been studied energetically using DFT calculations. The succinic acid molecules interact with one of the pyrazine rings of bosentan establishing an energetically significant lp⋯π interaction. Moreover, they form homodimers stabilized by antiparallel CO⋯CO interactions. This set of interactions has been rationalized using molecular electrostatic potential (MEP) surfaces, the quantum theory of "atoms-in-molecules" (QTAIM), and the noncovalent interaction plot (NCIplot). [ABSTRACT FROM AUTHOR]

This work reports a combined computational and experimental analysis of the crystal structure of the cancer drug tipiracil hydrochloride in the form of a methanol solvate–hydrate (4 : 1 : 3, molar ratio). The crystal structure shows a complex network of H-bonds with static discrete disorder in two out of the three symmetry-independent solvent molecules, which has been studied by means of DVS and TGA techniques. MEP surface calculations shows a region of positive potential (σ-hole) along the C–Cl bond, which induces the formation of Cl⋯O contacts that are relevant in the crystal packing. The hydrogen and halogen bonding assemblies were further analyzed using density functional theory (DFT), the quantum theory of "atom-in-molecules" (QTAIM) and the noncovalent interaction plot (NCIplot). [ABSTRACT FROM AUTHOR]

We present the discovery of a late appearing polymorph of the nutraceutical pterostilbene and analyzed computationally the intermolecular interactions observed in its crystal structure to explain its higher stability with respect to previously known forms. [ABSTRACT FROM AUTHOR]

A cocrystal screening conducted with solid solutions of three phytosterols (β-sitosterol, campesterol and stigmasterol) and a set of coformers with strong hydrogen bond donors reveals that multicomponent solid solutions are preferentially formed instead of pure cocrystals and are much enriched with β-sitosterol with respect to stigmasterol, a natural product with cytotoxicity concerns. [ABSTRACT FROM AUTHOR]

Herein we report the experimental observation (X-ray characterization) of two different binding modes in H-bonded anion–anion complexes (anion = citrate) in N-(1-(2-phenylethyl)-4-piperidinylium)-N-phenyl-propanamide-citrate (fentanyl citrate). High level DFT calculations indicate that both types of anion–anion complexes (one with two and the other with four H-bonds) are thermodynamically unstable but kinetically stable with respect to the isolated anions with activation barriers as high as 14 kcal mol−1. [ABSTRACT FROM AUTHOR]

Herein we report the X-ray characterization of four sildenafil solvates where the conformation of the pyrazolo[3,4-d]pyrimidine and phenyl rings depends on the solvent. It conditions the formation of an apparently innocent intramolecular H-bond that has a remarkable influence on the solid state architecture of the sildenafil solvates. DFT calculations indicate that a delicate balance between the energies of H-bonding and π–π (or lp–π) interactions are crucial. [ABSTRACT FROM AUTHOR]

Cocrystals have been identified as a method for ensuring the delivery of poorly soluble drugs. Development of cocrystal phases presents many challenges, with the in vivo drug delivery benefits difficult to predict robustly. Additional to this, many of the benefits seen in the literature do not use formulation strategies which are representative of the clinical dosage form. Zafirlukast has been shown to possess poor development properties. It is poorly soluble and difficult to manufacture. Here we present a case study highlighting the benefits of cocrystals in this context, outlining the discovery, formulation and improved pharmacokinetics of mixed stoichiometry cocrystals of zafirlukast. This case study outlines methods, which could be broadly applied to other drug molecules, for determination of the properties of cocrystals through a suite of in vitro experiments that display a predictive pathway from physical form discovery to enhanced in vivo activity in animal models. [ABSTRACT FROM AUTHOR]

The appearance of six new polymorphic forms of (S)-triphenylglycol and the kinetically dependent transformation observed by DSC by means of quenching from the melt are reported.