Structural studies of crystalline forms of triamterene with carboxylic acid, GRAS and API molecules.

Pharmaceutical salt solvates (dimethyl sulfoxide, DMSO) of the drug triamterene with the coformers acetic, succinic, adipic, pimelic, azelaic and nicotinic acid and ibuprofen are prepared by liquid-assisted grinding and solvent-evaporative crystallization. The modified ΔpKa rule as proposed by Cruz-Cabeza [(2012 ▸). CrystEngComm, 14, 6362-6365] is in close agreement with the results of this study. All adducts were characterized by X-ray diffraction and thermal analytical techniques, including single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermal gravimetric analysis. Hydrogen-bonded motifs combined to form a variety of extended tapes and sheets. Analysis of the crystal structures showed that all adducts existed as salt solvates and contained the amino-pyridinium-carboxyl-ate heterodimer, except for the solvate containing triamterene, ibuprofen and DMSO, as a result of the presence of a strong and stable hemitriamterenium duplex. A search of the Cambridge Structural Database (CSD 5.36, Version 1.18) to determine the frequency of occurrence of the putative supramolecular synthons found in this study showed good agreement with previous work.

Using crystallography, topology and graph set analysis for the description of the hydrogen bond network of triamterene: a rational approach to solid form selection.

This study has demonstrated the use of crystallography, topology and graph set analysis in the description and classification of the complex hydrogen bonded network of triamterene. The aim is to give a brief overview of the methodology used to discuss the crystal structure of triamterene with a view to extending the study to include the solvates, cocrystals and salts of this compound. Graphical abstract One of the structurally significant dimers (supramolecular synthons) of triamterene identified by this study.

The ecstasy and the agony; compression studies of 3,4-methylenedioxymethamphetamine (MDMA).

MDMA (3,4-methylenedioxymethamphetamine) is a Class A substance that is usually found in a tableted form. It is only observed in one orthorhombic polymorph under ambient conditions. It shows slight positional disorder around the methlyenedioxy ring which persists during compression up to 6.66 GPa. The crystal quality deteriorates above 6.66 GPa where the hydrostatic limit of the pressure-transmitting medium is exceeded. The structure undergoes anisotropic compression with the a-axis compressing the greatest (12% cf. 4 and 10% for the b- and c-axes, respectively). This is due to the pattern of the hydrogen bonding which acts like a spring and allows the compression along this direction.

Ultrasound-assisted construction of halogen-bonded nanosized cocrystals that exhibit thermosensitive luminescence.

Multi-component organic nanocrystals that are comprised of two or more supramolecular building blocks can be used to extend the design and assembly scope of solid molecular materials. Herein, we report the use of ultrasonication to prepare halogen-bonded stilbene-based nano-cocrystals that exhibit different photoemission properties, including one- and two-phonon emission and fluorescence lifetimes, relative to those of macrodimensional crystals. The structural transformation from nano-cocrystals into nanocrystals upon heating results in a luminescence red-shift from greenish blue to yellow. The temperature-dependent ratiometric luminescence may allow such nano-cocrystals to be used as fluorescent sensors and thermosensitive materials.

Pharmaceutical cocrystals and poorly soluble drugs.

In recent years cocrystal formation has emerged as a viable strategy towards improving the solubility and bioavailability of poorly soluble drugs. In this review the success of numerous pharmaceutical cocrystals for the improvement of the solubility and dissolution rates of poorly soluble drugs is demonstrated using various examples taken from the literature. The role of crystal engineering principles in the selection of appropriate coformers and the nature of the supramolecular synthons present within the crystals are described. Evidence for improved animal pharmacokinetic data is given for several systems. A summary is provided of our current understanding of the relationship between cocrystal structure and solution phase interactions on solubility as well as those factors that influence overall cocrystal thermodynamic stability.

Quantifying homo- and heteromolecular hydrogen bonds as a guide for adduct formation.

An investigation into the predictability of molecular adduct formation is presented by using the approach of hydrogen bond propensity. Along with the predictions, crystallisation reactions (1a-1j) were carried out between the anti-malarial drug pyrimethamine (1) and the acids oxalic (a), malonic (b), acetylenedicarboxylic (c), adipic (d), pimelic (e), suberic (f), azelaic acids (g), as well as hexachlorobenzene (h), 1,4-diiodobenzene (i), and 1,4-diiodotetrafluorobenzene (j); seven (1a to 1g) of these successfully formed salts. Five of these seven salts were found to be either hydrated or solvated. Hydrogen bond propensity calculations predict that hydrogen bonds between 1 and acids a-g are more likely to form rather than the H bonds involved in self-association, providing a rationale for the observation of the seven new salts. In contrast, propensity of hydrogen bonds between 1 and h-j is much smaller as compared to other bonds predicted for self-association/solvate formation, in agreement with the observed unsuccessful reactions.

A cocrystal strategy to tune the luminescent properties of stilbene-type organic solid-state materials.

The one- and two-photon luminescence of stilbene-type solid-state materials can be tuned and controlled from blue to yellow color by a supramolecular cocrystal method.

pK(a)-directed host-guest assemblies: rational analysis of molecular adducts of 2,4-diamino-6-methyl-1,3,5-triazine with various aliphatic dicarboxylic acids.

Molecular adducts of 2,4-diamino-6-methyl-1,3,5-triazine (1) have been prepared with various aliphatic dicarboxylic acids. The molecular complexes (1 a-1 i) thus formed by co-crystallizing 1 with oxalic, malonic, succinic, fumaric, acetylene dicarboxylic, glutaric, thiodiglycolic, diglycolic, and adipic acids have been found to give two types of host-guest assemblies that have voids or channels in a three-dimensional arrangement. The different types of host-guest arrangement appear to result from differences in the acidity of the dicarboxylic acids, that is, acids with pK(a)<3.0 give host networks that consist of 1 and the corresponding acid with water or solvent molecules of crystallization present as guests, whereas acids with pK(a)>3.0 exist as guests in voids in a host network formed by 1. The former arrangement is observed in adducts 1 a, 1 b, 1 e, and 1 h and the latter arrangement is found in adducts 1 c, 1 d, 1 f, 1 g, and 1 i.