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New salicylic (2-hydroxybenzoic) acid derivatives 1–6 were prepared by conventional heating or microwave irradiation of a mixture consisting of methyl salicylate and the corresponding amino alcohol (2,2′-dihydroxydiethylamine, 2,2′,2″-trihydroxytriethylamine or N-phenyl-2,2′-dihydroxydiethylamine) and metallic sodium as catalyst. For compounds 1, 3, and 5 X-ray structure analysis was performed, as well as molecular mechanics calculations (MMC), to define their conformation in terms of their energy minima. Comparison of crystal and MMC structures for these three compounds (1, 3, and 5) revealed that the intramolecular hydrogen bonds play an important role, stabilizing conformation of the most part of the molecule. The antioxidant activity and cytotoxicity of the synthesized derivatives were evaluated in a series of in vitro tests. The newly synthesized compounds exhibited strong activity against hydroxyl radical, as well as promising lipid peroxidation inhibition. The study showed that the electronic effects of the groups at the N atom are responsible for neutralization of the OH radical, i.e., antioxidant activity. Compounds 1–3 exhibited sub-micromolar cytotoxicity against HeLa S3, whereas compounds 1, 3 and 5 efficiently inhibited the growth of PC3 cells.

Isostructural solvates of the 1:1 molecular complex between the antibacterial drugs tetroxoprim (TXP) and sulfametrole (SMTR) with formulae TXP·SMTR·CH3OH (I), TXP·SMTR·C2H5OH (II) and TXP·SMTR·H2O (III), were investigated to establish their propensity for guest exchange. Separate exposure of powdered (I), (II) and (III) to a saturated atmosphere of each solvent of the complementary solvate pair at ambient temperature resulted in reversible solvent exchange in all cases. DSC and TG were the methods of choice for monitoring the exchange processes since (I)-(III) have distinct onset temperatures of desolvation and characteristic mass losses. Interpretation of the results in terms of the known locations of the solvent molecules in crystals of (I)-(III) led to the conclusion that solvent exchange probably proceeds by a co-operative mechanism involving material transport through channels while the common host framework is maintained.

A methodology has been developed to predict the propensity for hydrogen bonds to form in crystal structures, treating each potential H-bond as a binary response variable, and modelling its likelihood using a set of relevant chemical descriptors [1]. Modelling is tailored to a target using chemically similar known structures, from e.g. the Cambridge Structural Database [2], making it accessible to the complete spectrum of organic structures, including solvates, hydrates and cocrystals. Recent work has developed the approach to predicting inter- and intramolecular H-bonds when either type can occur. By way of a comparison between possible and observed H-bonds, the method has been applied to assess structural stability, which shows much promise in the domain of polymorph screening in the pharmaceutical industry. We will introduce the methodology and illustrate its application using a selection of pharmaceutical compounds, one of which will be Abbott's well-publicised anti-HIV medication ritonavir (Norvir™). Owing to a hidden, more stable form II with much lower bioavailability, ritonavir was temporarily withdrawn from the market with significant financial impact [3]. Our method quickly suggests a real threat of polymorphism in this compound, and strongly supports the relative stability of form II over form I. For all examples, the high predictivity of the method is emphasised.

Direct monitoring of cationic polymerization was accomplished by simultaneous measurement of the average dielectric constant, representing the dipoles, of the conductivity, produced by unpaired ions, and of the temperature, characteristic for reaction rate. The ionogenic equilibria during the living polymerization of isobutylene by 1, 3, 5-tris(2-methoxy-2-propyl)benzen/BCl3 in CH2Cl2 at-25°C were demonstrated. Temperature, resistance and capacitance were measured directly in the reaction mixture by a specially designed instrument.