Anna Portell

New polymorphic hydrogen bonding donor-acceptor system with two temperature coincident solid-solid transitions†

The polymorphism study of dibenzylsquaramide reveals the appearance of two forms sharing a solid–solid transition at the same temperature towards the highest melting polymorph.

Ziprasidone malate, a new trimorphic salt with improved aqueous solubility

A new salt of ziprasidone with high aqueous solubility has been discovered as a result of a salt screening and it has been found to exist in three anhydrous polymorphic forms. One of these forms shows the highest aqueous solubility ever reported for ziprasidone salts in combination with a high kinetic stability, becoming a good candidate for further pharmaceutical development.

Cooperative induction in double H-bonding donor/acceptor compounds: Chains vs. ribbons

Two different types of monodimensional crystalline aggregates formed by squaramides, chains and ribbons, have been studied both in the solid state and ab initio with four model compounds. Although ribbons are a priori possible, only covalently forced syn conformations have been observed. Cooperative induction is postulated to explain the preference for chains instead of ribbons in squaramide crystals.

Experimental and theoretical study of weak intermolecular interactions in crystalline tertiary squaramides

We report the X-ray solid state structures of two tertiary squaramides, i.e. 3-(diethylamino)-4-ethoxy-cyclobutene-1,2-dione (1) and bis-3,4-(diethylamino)-cyclobutene-1,2-dione (2). Compound 1 forms electrostatically compressed dimers in the solid state. Moreover, compound 2 exhibits a remarkable solid state architecture resembling a lipid bilayer. This supramolecular assembly has been analyzed using high level DFT calculations and Baders theory of “atoms-in-molecules”. The antiparallel CO⋯CO interactions of the cyclobutenedione rings and hydrophobic interactions involving the ethyl chains are crucial for the formation of the bilayer assembly in the solid state.

A cocrystal is the key intermediates for the production of a new polymorph of Vorinostat

A new kinetically stable polymorph of Vorinostat has been discovered as a result of a polymorph screening, however an impurity is always formed in its preparation by crystallization. The interaction of Vorinostat with ammonia yields a new cocrystal which transforms easily through thermal desorption into the new polymorph with a high degree of purity.

Crystal structure solution of an elusive polymorph of Dibenzylsquaramide

The crystal structure of the third polymorph of dibenzylsquaramide (Portell, A. et al., 2009), (fig. 1) has been determined from laboratory X-ray powder diffraction data by means of direct space methods using the computing program FOX. (Favre-Nicolin and Cerný, 2002) The structure resolution has not been straightforward due to several difficulties on the indexing process and in the space group assignment. The asymmetric unit contains two different conformers, which has implied an additional difficulty during the Rietveld (Rietveld, 1969) refinement. All these issues together with particular structural features of disquaramides are discussed.

A combined crystallographic and theoretical study of weak intermolecular interactions in crystalline squaric acid esters and amides

We report the synthesis and X-ray solid state structures of five squaric acid derivatives, i.e. a zwitterionic compound, namely 3-hydroxy-4-(2-pyridin-2-yl-ethylamino)cyclobut-3-ene-1,2-dione (1), a squaramide monoester, 3-ethoxy-4-(2-pyridin-2-yl-ethylamino)cyclobut-3-ene-1,2-dione (2), two differently solvated (EtOH and DMSO/water) disquaramides 3,4-bis((4-hydroxyphenethyl)amino)cyclobut-3-ene-1,2-dione (3 and 4, respectively), and a mixed hydrogen squarate and disquarate 2-(2-aminoethyl)pyridinium salt (5). All compounds form interesting supramolecular assemblies in the solid state that have been analyzed using high level DFT calculations and Baders theory of “atoms-in-molecules”. An intricate combination of ion-pair and H-bonding interactions along with π–π stacking and anion–π contacts of the cyclobutenedione rings is crucial for the formation of the supramolecular assemblies in the solid state.

Polymorphism in secondary squaramides: on the importance of π-interactions involving the four membered ring

We report the X-ray solid state structures of four new squaric acid derivatives, i.e. three polymorphs of 3,4-bis((2-(dimethylamino)ethyl)amino)cyclobut-3-ene-1,2-dione (1a–c) and a co-crystal of compound 1 and resorcinol (2). All structures form interesting supramolecular assemblies in the solid state which have been analyzed using high level DFT calculations and molecular electrostatic potential (MEP) surface calculations. A combination of H-bonding and π–π stacking interactions of the cyclobutenedione rings are crucial for the formation of the supramolecular assemblies in the solid state. Moreover, unusual antiparallel CO⋯CO interactions observed in the X-ray structure of one of the polymorphs of 1 and the lp–π interactions between one oxygen atom of resorcinol and the squaramide ring in 2 have been characterized using Baders theory of “atoms-in-molecules” (AIM).