The combination of racemic praziquantel, (RS)-PZQ, with aliphatic dicarboxylic acids of the homologous series HOOC−(CH 2 ) n −COOH (with n = 0−8) and the unsaturated analogues of succinic acid as cocrystal formers via liquid-assisted grinding provided a total of nine 1:1 and 2:1 cocrystals with oxalic acid, malonic acid, succinic acid (two polymorphic phases), maleic acid, fumaric acid, glutaric acid, adipic acid, and pimelic acid. The cocrystalline phases were identified first by XRPD analysis and then structurally characterized by IR spectroscopy and, as far as possible, by single-crystal X-ray diffraction analysis. Crystals suitable for XRD analysis were obtained for seven cocrystals and, additionally, for (RS)-PZQ. The analysis of the supramolecular interactions in the crystal structures has shown that the dominant hydrogen bonding patterns within the cocrystals are heterodimeric motifs formed through O−H•••O hydrogen bonds between PZQ and the dicarboxylic acids, which mostly contain additionally at least one secondary C−H•••O contact. In all crystal structures, the PZQ molecules are connected with each other through cyclic homodimeric hydrogen bonding interactions formed mainly through C−H•••O, but also through C−H•••π contacts, giving overall 1D, 2D or 3D hydrogen bonded networks. The crystallographic study also allowed us to establish that there are two main rotational conformers for PZQ, which differ in the configuration of the CO groups in the piperazinone−cyclohexylcarbonyl segment. In the crystal structure of (RS)-PZQ, all four independent molecules in the asymmetric unit have the syn-conformation, which in the hemihydrates, viz. (R)-PZQ•0.5H 2 O and (S)-PZQ•0.5H 2 O, and all cocrystals except for one are switched to the anti-antagonist.

His research interests focus on chemical reactivity in aggregates, such as micelles and liposomes, the hydrolysis of phosphates and phosphonates (especially as related to the decontamination of chemical warfare agents), and the physical organic chemistry of reactive organic intermediates, particularly carbenes and carbocations. His nonscientific publications include articles on Sherlock Holmes and the literature of baseball. Professor Moss is married to Dr. Sandra Moss, M.D. They have two sons, Kenneth and Daniel.

Praziquantel (PZQ) is an important chiral active pharmaceutical ingredient for the treatment of gastrointestinal parasites, which is commercially available only in the form of its racemate. In this article, on the basis of co-crystallization experiments a convenient two-step protocol for the chiral resolution of RS-PZQ is described. Screening experiments with RS-PZQ using the liquid-assisted grinding technique revealed the formation of a diastereomeric co-crystal pair with L-malic acid (L-MA) of the compositions R-PZA:L-MA and S-PZQ:L-MA. Both co-crystals have been examined by single-crystal X-ray diffraction analysis, revealing similar unit cell parameters but differences in the supramolecular organization. Particularly the analysis of the hydrogen bonding patterns indicated overall stronger intermolecular interactions in the case of R-PZA:L-MA, which was confirmed by thermogravimetric−differential scanning calorimetry analysis giving a substantial difference in the melting point when compared to S-PZA:L-MA. After synthesis of R-and S-PZQ in enantiomerically pure form for the selective preparation of both R-PZA:L-MA and S-PZQ:L-MA, comparative solubilization experiments were carried out. Since significant variations in the solubility were found in some solvents, a procedure could be established allowing for the separation of R-PZA:L-MA by fractional crystallization. In a subsequent reaction step, the biologically active enantiomer R-PZQ was liberated from the co-crystal in the form of its hemihydrate by stirring with water. Comparison of the intrinsic dissolution rates for RS-PZQ, R-PZA•0.5H 2 O, and R-PZA:L-MA indicated that the co-crystalline phase exhibits a significantly larger rate constant than praziquantel in its enantiomerically pure form or as a racemate.

A series of 2:1 fluorinated arylboronic ester adducts with 4,4′-bipyridine sustained by N→B dative bonds have been synthesized. The degree of fluorination in the arylboronic esters derived from catechol is shown to modulate the molecular conformation of the coordinated boronic ester moieties and the intermolecular interactions by means of C−H•••F and F•••F contacts that sustain the crystal lattices. The adduct derived from the catechol ester of 2,4-difluorophenylboronic acid was chosen to examine the formation of inclusion complexes with a large number of aromatic guests, affording solvates, cocrystals, and a cocrystal solvate. Six different crystal structure types with 1:1, 1:2, and 1:2:2 N→B adduct−guest ratios were observed, whose supramolecular organization is strongly influenced by the formation of sandwich-type complexes between the host and guest molecules. The host−guest interactions involve π•••π interactions with the bipyridine linkers and additional contacts with the catecholate and Baryl F substituents, indicating a large flexibility of the N→B adducts to adapt to the guest stereochemistry. The versatility of the crystallization system was employed to isolate o-xylene from an equimolar mixture of o-, m-, and p-xylene.

[reaction: see text] A free porphyrin coupled on 2-deoxy-D-ribose was synthesized and incorporated into DNA via phosphoramidite chemistry. Substitution at the ends of a 5'-modified self-complementary duplex was found to be thermally and thermodynamically stabilizing. The porphyrin moiety strongly intercalates in the duplex when located near the center, and retains its fluorescence properties in DNA.