A Combined Experimental and Computational Study of Halogen and Hydrogen Bonding in Molecular Salts of 5-Bromocytosine

Although natural or artificial modified pyrimidine nucleobases represent important molecules with valuable properties as constituents of DNA and RNA, no systematic analyses of the structural aspects of bromo derivatives of cytosine have appeared so far in the literature. In view of the biochemical and pharmaceutical relevance of these compounds, six different crystals containing proton-transfer derivatives of 5-bromocytosine are prepared and analyzed in the solid-state by single crystal X-ray diffraction. All six compounds are organic salts, with proton transfer occurring to the Nimino atom of the pyridine ring. Experimental results are then complemented with Hirshfeld surface analysis to quantitively evaluate the contribution of different intermolecular interactions in the crystal packing. Furthermore, theoretical calculations, based on different arrangements of molecules extracted from the crystal structure determinations, are carried out to analyze the formation mechanism of halogen bonds (XBs) in these compounds and provide insights into the nature and strength of the observed interactions. The results show that the supramolecular architectures of the six molecular salts involve extensive classical intermolecular hydrogen bonds. However, in all but one proton-transfer adducts, weak to moderate XBs are revealed by C–Br…O short contacts between the bromine atom in the fifth position, which acts as XB donor (electron acceptor). Moreover, the lone pair electrons of the oxygen atom of adjacent pyrimidine nucleobases and/or counterions or water molecules, which acts as XB acceptor (electron donor).

From pipemidic acid molecular salts to metal complexes and BioMOFs using mechanochemistry

Mechanochemistry has proven to be an excellent sustainable, efficient and fast tool for the discovery of new crystal forms of old drugs.

Molecular salts of quinine. A crystal engineering route to enhance the aqueous solubility

The anti-malarial drug quinine (QUN) has poor aqueous solubility and belongs to Biopharmaceutical Classification System (BCS) Class-II. We report 12 novel molecular salts of QUN with α,ω-aliphatic dicarboxylic acids, and...

2-Chloro-4-nitrobenzoic acid as a coformer with pharmaceutical cocrystals and molecular salts

A series of five binary complexes, i.e. three cocrystals and two molecular salts, using 2-chloro-4-nitrobenzoic acid as a coformer have been produced with five commonly available compounds, some of pharmaceutical relevance, namely, 2-chloro-4-nitrobenzoic acid–isonicotinamide (1/1), C7H4ClNO4·C6H6N2O, 2-chloro-4-nitrobenzoic acid–3,3-diethylpyridine-2,4(1H,3H)-dione (2/1), 2C7H4ClNO4·C9H13NO2, 2-chloro-4-nitrobenzoic acid–pyrrolidin-2-one (1/1), C7H4ClNO4·C4H7NO, 2-carboxypiperidinium 2-chloro-4-nitrobenzoate, C6H12NO2 −·C7H3ClNO4 −, and (2-hydroxyethyl)ammonium 2-chloro-4-nitrobenzoate, C2H8NO+·C7H3ClNO4 −. The coformer falls under the classification of a `generally regarded as safe' compound. All five complexes make use of a number of different heteromeric hydrogen-bonded interactions. Intermolecular potentials were evaluated using the CSD-Materials module.

Swelling of polyacrylamide-based hydrogel in aqueous solutions of low-molecular salts

The swelling kinetics of cross-linked polyacrylamide was studied depending on the composition of the external solution. It was shown that the polymer gel swelling during the transition from water to a potassium or sodium chloride solution and vice versa sharply decreases, then gradually increases. The swelling of gel in a solution of sodium chloride is higher than that of potassium chloride. In the equilibrium swollen gel, the concentration of salts in the gel phase is higher than in the external solution and increases with the transition from potassium chloride to sodium chloride.

Different packing motifs in the crystal structures of three molecular salts containing the 2-amino-5-carboxyanilinium cation: C7H9N2O2 +·Cl−, C7H9N2O2 +·Br− and C7H9N2O2 +·NO3 −·H2O

The syntheses and crystal structures of three molecular salts of protonated 3,4-diaminobenzoic acid, viz. 2-amino-5-carboxyanilinium chloride, C7H9N2O2 +·Cl−, (I), 2-amino-5-carboxyanilinium bromide, C7H9N2O2 +·Br−, (II), and 2-amino-5-carboxyanilinium nitrate monohydrate, C7H9N2O2 +·NO3 −·H2O, (III), are described. The cation is protonated at the meta-N atom (with respect to the carboxy group) in each case. In the crystal of (I), carboxylic acid inversion dimers linked by pairwise O—H...O hydrogen bonds are seen and each N—H group forms a hydrogen bond to a chloride ion to result in (100) undulating layers of chloride ions bridged by the inversion dimers into a three-dimensional network. The extended structure of (II) features O—H...Br, N—H...Br and N—H...O hydrogen bonds: the last of these generates C(7) chains of cations. Overall, the packing in (II) features undulating (100) sheets of bromide ions alternating with the organic cations. Intermolecular interactions in the crystal of (III) include O—H...O, O—H...(O,O), N—H...O, N—H...N and O—H...N links. The cations are linked into (001) sheets, and the nitrate ions and water molecules form undulating chains. Taken together, alternating (001) slabs of organic cations plus anions/water molecules result. Hirshfeld surfaces and fingerprint plots were generated to give further insight into the intermolecular interactions in these structures. The crystal used for the data collection of (II) was twinned by rotation about [100] in reciprocal space in a 0.4896 (15):0.5104 (15) ratio.