Hydrate inclusion compounds

There are three general classes of hydrate inclusion compounds: the gas hydrates, the per-alkyl onium salt hydrates, and the alkylamine hydrates. The first are clathrates, the second are ionic inclusion compounds, the third are semi-clathrates. Crystallization occurs because the H₂O molecules, like SiO₂, can form three-dimensional four-connected nets. With water alone, these are the ices. In the inclusion hydrates, nets with larger voids are stabilized by including other guest molecules. Anions and hydrogen-bonding functional groups can replace water molecules in these nets, in which case the guest species are cations or hydrophobic moieties of organic molecules. The guest must satisfy two criteria. One is dimensional, to ensure a comfortable fit within the voids. The other is functional. The guest molecules cannot have either a single strong hydrogen-bonding group, such as an amide or a carboxylate, or a number of moderately strong hydrogen-bonding groups, as in a polyol or a carbohydrate.The common topological feature of these nets is the pentagonal dodecahedra: i.e., 5¹²-hedron. These are combined with 5¹²6²-hedra, 5¹²6³-hedra, 5¹²6⁴-hedra and combinations of these polyhedra, to from five known nets. Two of these are the well-known 12 and 17 Å cubic gas hydrate structures,Pm3n, Fd3m; one is tetragonal,P4 ₂/mnm, and two are hexagonal,P6 ₃/mmc andP6/mmm. The clathrate hydrates provide examples of the two cubic and the tetragonal structures. The alkyl onium salt hydrates have distorted versions of thePm3n cubic, the tetragonal, and one of the hexagonal structures. The alkylamine hydrate structures hitherto determined provide examples of distorted versions of the two hexagonal structures.There are also three hydrate inclusion structures, represented by single examples, which do not involve the 5¹²-hedra. These are 4(CH₃)₃CHNH₂·39H₂O which is a clathrate; HPF₆·6H₂O and (CH₃)₄NOH·5H₂O which are ionic-water inclusion hydrates. In the monoclinic 6(CH₃CH₂CH₂NH₂)·105H₂O and the orthorhombic 3(CH₂CH₂)₂NH·26H₂O, the water structure is more complex. The idealization of these nets in terms of the close-packing of semi-regular polyhedra becomes difficult and artificial. There is an approach towards the complexity of the water salt structures found in the crystals of proteins.     

Zeolite inclusion complexes

Zeolites provide the largest and most useful family of porous host crystals, stable in the presence or absence of guest molecules. An account is given of their structural characteristics in terms of intracrystalline channels and cavities of molecular dimensions; their total intracrystalline pore volumes; and the intracrystalline distribution patterns of guest molecules, often present as clusters or filaments. The way in which the shape and size of the molecules relate to the shape and size of the apertures or windows giving access to the cavities, together with other factors such as cation location, then determine molecule sieving behaviour, which is discussed with reference to several types of zeolite sieve. The relation between diffusivity and molecular dimensions is also illustrated. A comparison between zeolites and clathrate host lattices shows that there are strong similarities of several kinds. Zeolites may form inclusion complexes with metals, salts and polar or non-polar molecules, examples of which are briefly considered, together with isotherms for some of these types of complex. An account of equilibrium and its formulation demonstrates the thermodynamic background and illustrates the degree of success which has been obtained in describing isotherms in terms of various models.     

Helical tubulate inclusion compounds

Abstract

The inclusion properties of the first helical tubuland diol hosts 1–5 have been surveyed and are reported. Bicyclic diol 1 forms helical tubulate inclusion compounds with most small solvent molecules, but with certain phenols hydrogen bonded co-crystalline materials are produced instead. Diol 2 yields helical tubulates with larger guest molecules, but if smaller solvents are used then an alternative host system is obtained. This has the guests trapped in ellipsoidal cavities located along constricted canals and is termed the ellipsoidal clathrate type. In some cases both inclusion types can be produced from 2 by varying the experimental conditions. The free volume present in the helical tubuland lattices of 3 and 5 is insufficient for guest inclusion. Diol 4 has the largest void space and can form inclusion compounds with large molecules such as ferrocene and squalene. X-ray crystal structures of representative examples of these compounds are discussed.     

Preparation and properties of cyclodextrin inclusion compounds of organometallic complexes. Ferrocene inclusion compounds

Inclusion compounds of ferrocene(FcH) and its derivatives with cyclodextrins(CDs; -CD, -CD, and -CD) were prepared. CD-ferrocene inclusion compounds were obtained in a crystalline state in high yield. -CD and -CD formed 11 stoichiometric inclusion compounds with ferrocene and its derivatives. -CD formed 21 (CD:guest) complexes with ferrocene and the monosubstituted derivatives, but did not form complexes with 1,1-disubstituted derivatives, -CD-FcH and -CD-FcH complexes are thermally stable and do not liberate ferrocene on heating at 100°C in vacuo. The cyclodextrin inclusion compounds were characterized by¹H-NMR, IR, UV, and CD spectra. A large positive induced Cotton effect was observed in the case of -CD-FcH complex, while the -CD-FcH complex showed a negative spectrum. The binding mode is discussed. -Cyclodextrin was found to form inclusion complexes in ethylene glycol, diethylene glycol, triethylene glycol, methyl cellosolve, ethyl cellosolve, methyl alcohol, and glycerine solutions. -CD also formed complexes in ethylene glycol solution. The binding of ferrocene by -CD is stronger in ethylene glycol than in dimethyl sulfoxide and dimethyl formamide.     

Enrofloxacin inclusion complexes with cyclodextrins

Inclusion complexes using α-, β-, γ-, and hydroxypropyl-β-CD (HP-β-CD) were produced with the antibiotic enrofloxacin, with the aim of increasing its solubility by complexation. Phase solubility diagrams were obtained, to confirm the formation of inclusion complexes, and to determine the solubility enhancement and stability constant of each complex. Enrofloxacin inclusion in β-CD showed the highest value of the complex stability constant (35.56?mmol?L^?1), but the greatest increase in solubility was obtained using HP-β-CD reaching a 1258% increase over enrofloxacin solubility in the absence of CD. The order of highest enrofloxacin solubility achieved was: HP-β-CD?>?α-CD?>?γ-CD?>?β-CD. In addition, formation of complexes was confirmed by differential scanning calorimetry and thermogravimetry, applied to the complexes obtained by the kneading technique. The influence of citric acid, alone or as an adjunct of β-CD, on the solubility of enrofloxacin was also determined. A solution of 15?mmol?L^?1 citric acid dissolved 10?g?L^?1 of enrofloxacin, but a gradual increase in β-CD concentration in the presence of citric acid did not increase the degree of solubilization of enrofloxacin.     

Novel proton-conducting polymer inclusion membranes

The preparation and characterization of new polymer inclusion membranes (PIMs) for proton transport is described. PIMs were prepared with different polymeric cellulose-based compounds and PVC as supports, tris(2-butoxyethyl)phosphate (TBEP) and 2-nitrophenyl octyl ether (NPOE) as plasticizers and dinonylnaphthalenesulfonic acid (DNSA) and dinonylnaphthalenedisulfonic acid (DNDSA) as carriers. The effects of the nature and content of the supports, plasticizers and carriers on membrane proton conductivity was studied using electrochemical impedance spectroscopy (EIS). This technique was also used to evaluate the chemical stability of a CTA–NPOE–DNDSA membrane while its selectivity was monitored with respect to sodium and calcium ions through counter-transport experiments. DSC and TGA techniques were used to determine the thermal stability of these membranes. A PIM based on CTA–DNDSA–NPOE showed the highest proton conductivity (3.5 mS/cm) with no variation of its behavior during 2 months of evaluation. FTIR characterization did not show structural changes of the membrane in this period of time. Thermal analysis indicates that it is stable up to 180 °C. An empirical functional relationship between PIM resistance and composition indicates that increasing plasticizer and carrier concentrations enhances the conductivity of the membranes, while increasing CTA content tends to decrease this property. Transport experiments showed a good selectivity of the CTA–DNDSA–NPOE membrane for protons over calcium or sodium ions.     

Fendiline-β-Cyclodextrin inclusion complex

Fendiline (N-[1-phenylethyl]-3,3-diphenylpropylamine hydrochloride, trade name: Sensit) is a -receptor blocker and a Ca antagonist. It is a viscous oil and even its crystalline hydrochloride is a very hydrophobic and sparingly soluble compound in water.-Cyclodextrin complexes fendiline base in a molar ratio of 21. In aqueous-cyclodextrin solution, the significantly increased solubility and the intensive induced circular dichroism prove the formation of true inclusion complexes with both the base and the hydrochloride. In artificial gastric juice, the solubility of the complexed forms of the fendiline base and its hydrochloride is 40 and 22 times higher, respectively, than that of free drugs. The complexation withCD resulted in a two-threefold increase in the rate constants of diffusion and absorption determined in a Sartorius apparatus.     

Menadione-γ-cyclodextrin inclusion complex

A stable, nonsublimable -cyclodextrin inclusion complex of menadione (Vitamin K₃) of 11.7% menadione content (molar ratio 1:1) was prepared in solution, in suspension, and by kneading. The physicalchemical properties of the complex formed were studied by X-ray diffraction, by thermal analysis (DTG, TG, DSC, TEA), and by chiroptical studies. The biological activity of the complex was tested on baby chickens by prothrombin time determination. Reduced prothrombin times showed an enhanced bioavailability of menadione in complexed form. The stability of vitamin K₃ is greatly improved in pharmaceuticals or in veterinary products prepared with a menadione--CD inclusion complex.     

An incommensurate thiourea inclusion compound

X-Ray diffraction studies reveal that the tunnel inclusion compound formed between 1-tert-butyl-4-iodobenzene and thiourea has an incommensurate relationship between the periodicities of the host and guest substructures along the tunnel axis, representing the first reported case of an incommensurate thiourea inclusion compound.     

Kinetics and mechanism of cyclodextrin inclusion complexation incorporating bidirectional inclusion and formation of orientational isomers

The kinetics of cyclodextrin (CD) inclusion complexation has been usually analyzed in terms of a one-step reaction or a consecutive two-step reaction involving intracomplex structural transformation as a second step. These schemes presume the inclusion of guest molecules through only one side of the CD cavity and the formation of unidirectional CD complexes. However, there has been increasing experimental evidence for the inclusion of guests through both sides of the CD cavity and the formation of orientational isomers for noncentrosymmetric guest molecules. This article presents a novel parallel reaction scheme for CD inclusion complexation, incorporating bidirectional inclusion and the formation of orientational isomers into the scheme. It is shown that the parallel reaction scheme gives the same concentration versus reaction time relationship as the consecutive two-step reaction scheme. The experimental methods for determining the microscopic directional rate constants are presented. The kinetic parameters of the two-step reaction scheme are expressed as functions of the directional rate constants. The ratios of orientational isomers of alpha-CD-based [2]-pseudorotaxanes and the microscopic directional rate constants of the threading and dethreading reactions are estimated from the reported thermodynamic and kinetics data obtained by using either the one-step or two-step reaction scheme. It is shown that the thermodynamic preference of an isomer over the other is mainly due to the slow dethreading rate of the isomer.     

Efficient resolution of naproxen by inclusion crystallization with N-octyl-glucamine and structure characterization of the inclusion complex

(S)-(+)-Naproxen was directly resolved from the racemate with high enantiopurity (>95% e.e.) by inclusion crystallization using N-octyl-d-(−)-glucamine as the chiral host. The crystal structure of the inclusion complex was determined.     

Chromatographic study of the inclusion properties of cyclodextrins: Study of inclusion from the gaseous phase

The ability of cyclodextrins to form inclusion compounds with substances in the gaseous phase was studied chromatographically. Chromatographic measurements enabled the mechanism of the inclusion process to be clarified and have shown that other forces, mainly hydrogen bonding, play a role in the process in addition to the geometric properties of the interacting substances. These facts are expressed in terms of the changes in the chromatographic quantities and of the changes in the thermodynamic characteristics that are derived from the former quantities. The selective properties of cyclodextrins have been utilized in separations of substances that are otherwise separated with difficulty (xylenes, diethylbenzenes, trimethylbenzenes, etc.).     

Gas chromatography on urea-n-hexadecane inclusion compound

Summary The urea-n-hexadecane adduct, as a relatively stable inclusion compound, was studied gas chromatographically in connection with clathrate formation with n-alkanes, branched alkanes as well as with olefins, ketones and n-alcohols. In dependence on the temperature, either the clathrate itself can be used in the GC system, studying the transition phemonena (clathrate decomposition), or its decomposition product, n-hexandecane, be employed as a liquid stationary phase. Analytical usefulness of these phase is also demonstrated.     

Second harmonic generation in inclusion complexes

Second harmonic generation (S.H.G.) in inclusion complexes between dimethyl -cyclodextrin (dimethyl -CD) and nitroaniline derivatives occurs. This is due to the destruction of the centrosymmtric crystal structure in nitroaniline derivatives caused by forming inclusion complexes. S.H.G. intensity of dimethyl -CD complex with N-methyl-nitroaniline is 5.5 times as large as that of urea.     

Optical resolution by inclusion complex formation

Novel optical resolutions of guest compounds by inclusion complex formation with optically active host compound are reviewed. Tertiary acetylenic alcohols, cyanohydrins, and secondary alcohols were resolved by complexation with alkaloids such as brucine or sparteine. Cycloalkanones, 2,3-epoxycyclohexanones, and some other neutral compounds were resolved by complex formation with optically active diacetylenic diol. Mutual optical resolution of bis--naphthol and sulfoxides by complex formation was also reviewed.     

Heat capacity of urea-trioxane inclusion compound

The heat capacity of urea-trioxane inclusion compound was measured by means of adiabatic calorimetry between 15 and 300 K. Three phase transitions were found at 189.90, 200.86, and 242.55 K.