Isoquinoline-based Werner clathrates with xylene isomers: aromatic interactions vs. molecular flexibility.

The crystal structures of the Werner clathrates Ni(NCS)2(isoquinoline)4 (H) with para-xylene (px), meta-xylene (mx) and ortho-xylene (ox) have been elucidated. The kinetics of thermal decomposition of the three inclusion compounds were performed using the isothermal technique of Flynn and Wall. Selectivity of H for the xylene isomers was determined for both the liquid and vapour phase binary mixtures of the xylenes. The chosen ligand has a larger aromatic system to improve the possible π interactions between H and the selected guests. The planarity of the isoquinoline ligand causes H rigidity and its selectivity was compared to a related Werner complex containing the more flexible 4-phenylpyridine.

Separation of xylenes by enclathration.

The isomers of xylene have been separated by enclathration using three host compounds: 9,9'-bianthryl (H1), 9,9'-spirobifluorene (H2) and trans-2,3-dibenzoylspiro[cyclopropane-1,9-fluorene] (H3). The structures of each host with a single xylene isomer have been elucidated and, for H1, the relative lattice energies of the clathrates with ortho- and para-xylene have been evaluated.

One hydrogen bond does not a separation make, or does it? Resolution of amines by diacetoneketogulonic acid.

Diacetoneketogulonic acid was used to separate primary amines from their racemic modifications and the selectivity of the acid was rationalized by lattice energy calculations and analyzing the weak interactions around the captured amines.

Enhanced enantioselectivity of 3-methylcyclohexanone by mixed diol host compounds.

3-Methylcyclohexanone is only partially resolved by crystallisation with a chiral diol host compound (ee 40%), but when recrystallised from an equimolar mixture of the chiral diol host and a similar but achiral host we obtain complete resolution. The latter host acts as a nucleation inhibitor and the enhanced resolution is attributed to kinetic effects.

Quininium mandelates--a systematic study of chiral discrimination in crystals of diastereomeric salts.

The selectivity profile for the resolution of mandelic acid by quinine is dominated by structures comprising (QUIN(+))(MAND(-)) salts with Z' = 3 which contain (R)-, (R)- and (S)-mandelate anions.

Inclusion of chlorophenols by 4,4'-(cyclohexane-1,1-diyl)diphenol: structures and kinetics of decomposition.

The structures of the inclusion compounds 4,4'-(cyclohexane-1,1-diyl)diphenol-3-chlorophenol (1/1) and 4,4'-(cyclohexane-1,1-diyl)diphenol-4-chlorophenol (1/1), both C(18)H(20)O(2).C(6)H(5)ClO, are isostructural with respect to the host molecule and are stabilized by extensive host-host, host-guest and guest-host hydrogen bonding. The packing is characterized by layers of host and guest molecules. The kinetics of thermal decomposition follow the R2 contracting-area model, kt = [1 - (1 - alpha)1/2], and yield activation energies of 105 (8) and 96 (8) kJ mol(-1), respectively.

Solid-state chemistry of ambroxol theophylline-7-acetate.

Ambroxol theophylline-7-acetate (ACE) is the salt obtained by reaction of equimolar amounts of ambroxol (AMB), a drug showing mucolytic and expectorant properties, and theophylline-7-acetic acid (TAA), a xanthine derivative with specific bronchodilator activity. ACE is used for the treatment of bronchial and pulmonary diseases (bronchitis, asthma, emphysema, chronic obstructive disease). Recrystallization experiments of ACE resulted in the isolation of two polymorphs (monotropically related) and four solvated forms. X-ray diffractometry, DSC, TGA, and HSM techniques were used to investigate the forms that are obtained by thermal desolvation of the solvates. The phase diagram of the TAA-AMB binary system was constructed by performing thermal analyses on mixtures of TAA-AMB and of each component plus the interaction compound (TAA-ACE and ACE-AMB). The Schroeder-Van Laar equation proved to be a very useful tool for checking the consistency between the experimental data and the theoretical model related to the general system, showing complete miscibility in the liquid phase and complete immiscibility in the solid phase.

Clathrates with mixed guests.

Investigation of the selectivities of two diol organic hosts for pairs of small organic guests gave interesting results which could be correlated with the crystal structures of the inclusion compounds containing mixtures of the two guests; these structures were compared with those of the single guest inclusion compounds.

Two salts of di-p-toluoyltartaric acid with aromatic amines.

The structures of bis[(R)-(+)-1-phenylethylammonium] (2R,3R)-(-)-2,3-di-p-toluoyloxybutanedioate methanol disolvate monohydrate, 2C8H12N(+).C20H16O8(2-).2CH4O.H2O, (I), and bis(benzylammonium) (2R,3R)-(-)-2,3-di-p-toluoyloxybutanedioate dihydrate, 2C7H10N+.C20H16O8(2-).2H2O, (II), exhibit extensive hydrogen bonding, with (N-)H...O and (O-)H...O distances in the ranges 2.716 (2)-2.929 (3) and 2.687 (2)-2.767 (2) angstroms, respectively, in (I), and 2.673 (2)-2.888 (2) and 2.785 (2)-2.931 (2) angstroms, respectively, in (II). The amine groups are protonated and the carboxylate groups of the tartrate anions are fully deprotonated. The conformation of the toluoyltartrate anion and its molecular parameters are similar in both structures.

Inclusion of volatile guests by a tetrapedal host: structure and kinetics.

The host compound tetra(3-hydroxy-3,3-diphenyl-2-propynyl)ethene, TET, forms inclusion compounds with acetone, dimethyl sulfoxide, dioxane and pyridine. All the structures were successfully solved in the triclinic space group P1[combining macron]. We found variable host : guest ratios for the acetone (TET.ACE, H : G = 1 : 4), dimethyl sulfoxide (TET.DMSO, H : G = 1 : 4) and pyridine compounds (TET.PYR, H : G = 1 : 5). Solutions of the host compound and dioxane formed TET.2DIOX, H : G = 1 : 2 when left to crystallise at room temperature, whereas TET.4DIOX, H : G = 1 : 4 was formed during crystal growth at low temperature. We have correlated the structures with their thermal stabilities and kinetics of desolvation.

Xanthenol clathrates: structure, thermal stability, guest exchange and kinetics of desolvation.

A series of clathrates comprising the xanthenol host, 9-(4-methoxyphenyl)-9H-xanthen-9-ol, with a variety of aromatic guests displays similar structures in the space group P(-1). We have elucidated the structures of the inclusion compounds H x 1/2G, where H is 9-(4-methoxyphenyl)-9H-xanthen-9-ol and G is benzene, o-, m- and p-xylene. The structures are isostructural with respect to the host and display consistent (Host)-OH...O-(Host) hydrogen bonding. The guests lie on a centre of inversion and with the exception of the symmetrical guests, benzene and p-xylene, are disordered. An interesting case arises with m-xylene, which is ordered at low temperature (113 K) with both the host and guest molecules in general positions. At a higher temperature (283 K) the inclusion compound with m-xylene fits the series. We have correlated the structures with their thermal stabilities, guest exchange and kinetics of desolvation.

Desorption kinetics of a xanthenol-dioxane clathrate.

The host xanthenol compound forms a 1:1 clathrate with dioxane, namely 9-(1-naphthyl)-9H-xanthen-9-ol-1,4-dioxane, C23H16O2.C4H8O2. The structure of this clathrate is reported, along with a study of the kinetics of desolvation and the determination of an activation energy. The guest molecules are stabilized by O(host)-H...O(guest) hydrogen bonds [O-H = 0.968 (2) A, O...O = 2.7532 (13) A and O-H...O = 151.9 (4) degrees].

Inclusion by a fluorenyl host with volatile guests: structures, thermal stability and kinetics.

The structures of the inclusion compounds formed by the host H = 9,9'-(biphenyl-4,4'-diyl)bis(fluoren-9-ol) with N,N-dimethylacetamide (H.2DMA and H.4DMA), 1,4-dioxane (H.3DIOX), methyl ethyl ketone (H.2MEK), as well as that of the apohost have been elucidated. The compounds were characterised by thermal analysis and solid state NMR, and the kinetics of desorption of H.4DMA, H.2DMA and H.3DIOX have been examined.

Inclusion of quinolines by binaphthol: structures and selectivity.

The enclathration selectivity of the host compound 2,2'-dihydroxyl-1,1'-binaphthyl, BINAP, towards the guests quinoline (Q), 2-methylquinoline (2MeQ), 6-methylquinoline (6MeQ) and 8-methylquinoline (8MeQ) were established by competition experiments as: BINAP.2(2MeQ) > BINAP.2Q > BINAP.2(8MeQ) > BINAP.2.5(6MeQ). The crystal structures of the inclusion compounds were elucidated and are all stabilised by (host)O-H...N(guest) hydrogen bonds. Thermal analysis yields the same sequence with respect to the relative stabilities. pH Control was employed to dramatically modify the selectivity profile of the pair of 2-methylquinoline (2MeQ) and 8-methylquinoline (8MeQ).

Physicochemical aspects of host-guest compounds.

The macro properties of crystalline inclusion compounds depend on their structures. Their thermal stabilities are a function of the strength and the directionality of the various nonbonded interactions occurring in the host-guest assembly. Their lattice energies, as measured by the method of atom-atom potentials, correlate with the thermodynamics of the guest-release reactions and the selectivity that a given host displays for a particular guest. The kinetics of solid-host:vapor-guest reactions and of guest exchange are important in our understanding of catalytic processes. Crystal engineering, in which materials of predetermined properties may be synthesized, is still at the empirical stage.

Crystallization of two forms of a cyclodextrin inclusion complex containing a common organic guest.

The isolation and structural elucidation by single crystal X-ray diffraction of triclinic and monoclinic modifications of an inclusion complex of beta-cyclodextrin with the same guest, methylparaben, are reported.

Weak hydrogen bonding as a basis for concentration-dependent guest selectivity by a cyclophane host.

Crystalline inclusion complexes between the cyclophane 1 and three isomers of picoline and lutidine were grown and their properties and structures were studied by X-ray analysis, thermal gravimetry (TG), and differential scanning calorimetry (DSC). In competition experiments, the cyclophane host, which by itself is only able to form weak Cbond;H.acceptor hydrogen bonds, is able to discriminate between the different picoline or lutidine isomers, although in some cases a strong concentration dependence of the preferred isomer is observed. In the three-component experiments, inclusion of 4-picoline is strongly favored when X(4-picoline)>0.35-0.39. Very similar results were obtained in the lutidine series. The fact that 2,4-lutidine is favored when X(2,4-lutidine)>0.2 indicates that the host prefers the isomer with the methyl group in 4-position relative to the nitrogen atom. The selectivities observed can be explained based on the assignment of the inclusion complexes to different adduct classes. In the case of the picoline isomers, the preference of 4-picoline was in good agreement with the calculated lattice energies for this series. The present work also shows that caution is advisable when deducing selectivity of crystalline inclusion compounds from guest competition experiments.

Inclusion compounds of a diol host with xylidines: controlled stoichiometries.

The diol host, 1,1'-bis-(4-hydroxyphenyl)cyclohexane (DHPC) and a number of xylidine isomers as guests formed a series of inclusion compounds that gave rise to various host:guest ratios controlled by crystallization temperatures. For the host DHPC with a particular xylidine isomer, the number of guests included generally decreases as the crystallization temperature increases. The crystal structures of these host-guest compounds were elucidated using single-crystal X-ray diffraction. Their thermal stabilities were characterized by TG and DSC analysis. The selectivity of enclathration by the host was measured by carrying out a series of competition experiments. The kinetics of guest decomposition were studied using isothermal and non-isothermal methods and reconciled with the crystal structures.