Nikoletta B. Báthori

Testing the limits of synthon engineering: salts of salicylic and sulfosalicylic acid with nucleobases and derivatives

Synthon engineering concepts were tested by using nucleobases and derivatives, namely adenine, cytosine, benzimidazole and fluorocytosine when crystallized with salicylic acid and 5-sulfosalicylic acid. These bases were selected to investigate how the hydrogen bond donor and acceptor groups would influence the crystal structure. Salicylic acid was selected to investigate N–H⋯O hydrogen bonding and synthon formation, while its derivative, 5-sulfosalicylic acid, was selected to see how the sulfonate group would enhance or disrupt these features. Each of the seven complexes obtained was characterized by single crystal X-ray diffraction, which showed that acid–base pairing favored salt formation. All the salicylic acid complexes adopt similar hetero supramolecular synthons, while 5-sulfosalicylic acid forms more complex structures with more than one type of synthon present. Crystal formation using cytosine or fluorocytosine did not result in the predicted synthon formation. This unexpected outcome highlights the current limitations of synthon engineering.

Melting point–solubility–structure correlations in multicomponent crystals containing fumaric or adipic acid

This study investigates the relationships between the supramolecular structure and the solubility and melting point of six multicomponent crystals involving fumaric acid (FUM series) and adipic acid (ADI series). The crystals were prepared by solvent evaporation and fully characterised by thermal and diffraction techniques. In each series the melting points of the multicomponent crystals are lower than the relevant carboxylic acid and they show partial correlation with their aqueous solubilities. With the aid of Hirshfeld surface analysis, the relationships between solubility, melting point and the supramolecular structure are discussed.

Selectivity of amides by host–guest inclusion

The mechanism of selectivity by enclathration of four amides, N-methylformamide (NMF), dimethylformamide (DMF), N-methylacetamide (NMA) and dimethylacetamide (DMA), has been investigated by employing a bulky, flexible host. We measured the two-component selectivity curves for a mixture of amides, whose proportions in the crystals were determined by 1H NMR spectroscopy. The crystal structures of the single guest inclusion compounds were elucidated and analyzed. The subtle changes in the torsional flexibility of the host were correlated to the selectivity. The packing factor, which represents the occupied vs. available space by the guest in the crystal structures correlates with the measured selectivities.

Are gamma amino acids promising tools of crystal engineering? – Multicomponent crystals of baclofen

Baclofen, (RS)-4-amino-3-(4-chlorophenyl)butanoic acid, is a slightly water soluble hydrophobic γ-amino acid and primarily used as a muscle relaxant. The crystal structure, thermal analysis and powder X-ray analysis of the multicomponent crystals formed between baclofen and selected monocarboxylic acids (benzoic acid, p-toluic acid and 1-hydroxy-2-naphthoic acid), dicarboxylic acids (oxalic acid and maleic acid) and p-toluene sulfonic acid are presented. Conformation and protonation properties of the baclofen moiety are discussed. Hirshfeld surface analysis is used to analyse the specific intermolecular interactions in the presented structures, and their percentage appearance is correlated with the melting points of the multicomponent crystals.

Solid-state isolation of a unique, small-molecule, supra-heterodimer of large hexameric assemblies of C-methylcalix[4]resorcinarene

The well-known host molecule C-methylcalix[4]resorcinarene is shown to exist in two unique hexameric arrangements within the same crystal. These two hexameric assemblies are linked via a water molecule into a supra-heterodimer.

Werner clathrate formation with polyaromatic hydrocarbons: comparison of different crystallisation methods

The single crystal structures of the Werner host, bis-isothiocyanato tetrakis-vinylpyridine nickel(II), H, with seven polyaromatic hydrocarbons (PAHs), indene (IND), naphthalene (NAP), azulene (AZU), fluorene (FLU), anthracene (ANT), phenanthrene (PHE) and pyrene (PYR) have been elucidated. The isomorphous and isostructural behaviours of these structures were scrutinised. The inclusion compounds can be formed using a variety of crystallisation methods such as solution crystallisation, grinding, slurrying and co-melting. Grinding allowed determination of rate constants of formation for the host with NAP at room temperature and with AZU at 35 °C. The kinetics of thermal decomposition of the inclusion compounds using non-isothermal methods permitted the establishment of the activation energies of the decomposition reactions with NAP and IND. Product formation in an ambient water slurry was successful with guests NAP and AZU showing low solubility at room temperature; for PHE, PYR and FLU this occurred only after longer stirring at a higher temperature (50 °C) at which the guests had low levels of solubility and for ANT no successful slurrying results were reached.

Salts of (+)-deoxycholic acid with amines: structure, thermal stability, kinetics of salt formation, decomposition and chiral resolution

(+)-Deoxycholic acid forms salts with 1-propylamine, di-n-butylamine, sec-butylamine and 3-methyl-2-butylamine. The salts were characterised using thermal analysis and single crystal X-ray diffraction. The chiral discrimination of (+)-deoxycholic acid for racemic sec-butylamine and racemic 3-methyl-2-butylamine was studied and correlated with the structural and thermal results. A mixture of (+)-deoxycholic acid and racemic sec-butylamine yielded crystals of (R)-2-butylammonium deoxycholate. (+)-Deoxycholic acid was exposed to vapours of propylamine and racemic sec-butylamine and the kinetics of absorption were determined. The kinetics of decomposition of powdered samples obtained from (+)-deoxycholic acid with di-n-butylamine and racemic sec-butylamine were investigated. Crystallisation of (+)-deoxycholic acid with racemic 3-methyl-2-butylamine resulted in crystals of (S)-3-methyl-2-butylammonium deoxycholate.

Inclusion of 1,4-bis(diphenylhydroxymethyl)benzene with amides: structure and selectivity

The host compound 1,4-bis(diphenylhydroxymethyl)benzene is shown to include a series of amides: N,N-dimethylacetamide (DMA), N,N-dimethylformamide (DMF), N-methylacetamide (NMA) and N-methylformamide (NMF). The resultant inclusion compounds were characterised using thermal analysis and single crystal X-ray diffraction. A kinetic experiment was performed on the DMF clathrate and the activation energy determined. The host selectivity for the amides was studied through competition experiments.

Solid state structures of p-cresol revisited

The two previously reported solid state forms of p-cresol are revisited and detailed structural analysis, thermal analysis, lattice energy calculations and variable temperature powder X-ray diffraction are presented. A possible mechanism for the transformation from form II to form I is proposed.

Resolution of (±)-Citronellic Acid with (–)-Cinchonidine: The Crystal Structure of the Cinchonidinium-( S )-citronellate Diastereomeric Salt

AbstractA successful optical resolution of the racemic modification of citronellic acid was carried out by using (–)-cinchonidine, one of the cinchona alkaloids. The resultant crystals contain the protonated cinchonidinium cation and the (S)-(–)-citronellate anion in 1:1 ratio.Graphical AbstractA successful optical resolution of the racemic modification of citronellic acid was carried out by using (–)-cinchonidine, one of the cinchona alkaloids. The resultant crystals contain the protonated cinchonidinium cation and the (S)-(–)-citronellate anion in 1:1 ratio.