Inclusion compounds occurrence

In the next section we consider some general questions about the occurrence, properties and experimental investigation of helical canal inclusion compounds, in relation to inclusion compounds with different topologies. In subsequent sections we describe the properties of specific systems. 

In 1979 the bieyclic diol exo-2,ejco-6-dihydroxy-2,6-dimethylbicyclo[3.3.1]nonane (i) was prepared and observed to co-crystallise with various solvents, including ethyl acetate, chloroform, toluene, dioxane, and acetone. A crystal structure determination of the ethyl acetate compound revealed the occurrence of a helical canal host structure, containing ethyl acetate as guest (with 3 1 diol ethyl acetate stoichiometry), and that spontaneous resolution had occurred on crystallisation of the multimolecular inclusion compound 6>. 

Hydrogen-bonding patterns in crystal structures of the cydodextrins and the simpler carbohydrates differ. The infinite, homodromic chains are common both in the low molecular-weight carbohydrates and in the cydodextrins. The principal difference lies in the frequency of occurrence of the homodromic and antidromic cycles, which are common in the cyclodextrin crystal structures and rare in the mono-, di-, and trisaccharides. The cyclic patterns are the rule in the clathrate hydrates and in the ices. From this point of view, the hydrogen-bonding patterns of the hydrated cydodextrins lie between those of the simpler hydrated carbohydrates and those of the hydrate inclusion compounds, discussed in Part IV, Chapter 21. 

The real occurrence of polymerization inside the channels was demonstrated in several ways. It does not occur, at least for a number of monomers, when there is a simple mixture of host and monomer without the formation of a clathrate or when the monomer is placed in the presence of solid substances unable to form inclusion compounds. Even in cases when polymerization does take place the structure of the polymer formed outside the channels differs from that obtained in proper conditions. The reaction rate is very temperature and pressure dependent and has a sheirp drop-off point beyond which reaction ceases. The boundaur y conditions for polymerization correspond to those which delimit the field of thermodynamic stability of the monomeric clathrate, determined by vapor pressure measurements or by DSC. This coincidence enables us to state that the two phenomena, monomer inclusion and polymerization, are strictly related. In addition, in some typical cases a structural change from monomer to polymer was directly observed inside the channels by X-ray analysis. 

Inclusion compounds allow the realization of copolymerization in the crystal state (1-6). This is a further difference with respect to typical solid state reactions. Both block- and statistical copolymers can be obtained the former involves a two-step process, with subsequent inclusion and polymerization of two different monomers (21) the latter requires the simultaneous inclusion of two guests. This phenomenon has a much wider occurrence than thought at first, especially when a not very selective host such as PHTP is used. Research with this host started with mixtures of 2-methylpentadiene and 4-methylpentadiene, two almost exactly superimposable molecules (22), but was successfully extended to very dissimilar monomers, such as butadiene and 2,3-dimethylbutadiene. 

The purpose of this review is to assemble and assess currently available information about structural modification of urea/thiourea inclusion compounds. We concentrate here on the structural aspects of new inclusion compounds with urea/thiourea/selenourea-anion host lattices, most of which were prepared and structurally analyzed in our laboratory. The versatility of urea or thiourea as a key component in the construction of novel anionic host lattices is clearly demonstrated by occurrence of many new types of linkage modes. The results show that co-molecular aggregates of urea or thiourea with other neutral molecules or anionic moieties can be considered as fundamental building blocks for the constructions of various types of novel host lattices. Comments on structure-property relationship for these inclusion compounds are made wherever appropriate. 

Our studies on the generation of novel urea, thiourea, and selenourea-anion inclusion compounds have shown that novel anionic host lattices can be constructed from urea derivatives and many types of anions as building blocks. The versatility of urea, thiourea, or selenourea as a key component in the construction of novel host lattices is clearly demonstrated by the occurrence of many new types of linkage modes, which include various discrete units, chains or ribbons, and composite ribbons with corresponding anions. These motifs are shown in Tables 14, IS, and 16, respectively. 

The geometry of the interaction of a pair of phenyl rings can be viewed more generally in terms of the angle between the ring planes and the offset of the centroid of one ring from the normal to the other [83b]. Scatter plots of the experimental values of these two attributes (from crystal structures) reveal the more and the less attractive geometries [84]. The occurrence, characteristics and importance of aryl-aryl interactions have been assessed for proteins [84a, 84c, 85, 86], nucleic acids [83b] and inclusion compounds [87]. 

Amylose. A component (20-30%) of starch surrounded by amylopectin. A. is a linear a-l,4-glucan, Mr 50000-200000 (see figure at starch). Crystalline A. occurs in various polymorphic forms (A, B, C, and V-A.), that differ in conformation and crystal packing. A. is soluble in water and gives the characteristic blue color with iodine-potassium iodide solution (Lugol s solution) (formation of inclusion compounds, traces of iodide ions are necessary for occurrence of the blue color, formation of I5 ions I -1 I I -1). Because of its predominately unbranched structure, A. can be degraded to oligosaccharides both by a- and by /S-amylase. The screw-like (helical) conformation also allows the formation of inclusion compounds with alcohols. 

Numerous instances of isostructurality among Hofmann clathrates. M(NH3)2M (CN)4 2G, are known, the high frequency of occurrence probably owing to the fact that this family of inclusion compounds has been studied extensively over a long period. In addition, isostructurality can manifest itself in different ways, e.g., with either M. M fixed and guest G variable or with M, M variable and a common guest. An example in the former category... 

The occurrence of an isostructural series of inclusion compounds is informative, indicating the structural integrity of a particular type of host array but also reflecting a degree of flexibility to accommodate small to moderate structural modifications in the guest. This information can be carried over to the design of analogous host systems. 

The first step in the generation of the database of molecular properties in cocrystals was the retrieval of co-crystal structures from the CSD. Co-crystals were defined as organic structures containing at least two eharge neutral nonsolvent molecules with different structural formulas. To avoid possible statistical bias by the frequent occurrence of some eommonly used eo-formers e.g., urea, 4,4 -bipyridine, see Table 1 in ref. 7), struetures with these moleeules were excluded. Initial survey of the data showed that inelusion eompounds, which consist of a large and a small molecule, form a distinet group in the data set. Co-crystals of molecules with more than 30 and with less than six nonhydrogen atoms were thus removed and the analysis foeused on eo-erystals other than inclusion compounds. The final data set eontained 710 struetures. 

Changes of phase that take place in the solid state as a consequence of a change in temperature are, of course, a common occurrence. For inclusion compounds such changes may be catastrophic inasmuch as they may result in the expulsion of the guest molecule. In Figure 8 are shown the results for the 1 2 complex [22] formed between CH2CI2 and (3-methylpyridine)4Fe(SeCN)2. 

In general, polymorphs of a given compound have different physicochemical properties, such as melting point, solubility and density, so that the occurrence of polymorphism has important formulation, biopharmaceutical and chemical process implications. In addition to polymorphs, solvates (inclusion of the solvent of crystallization), hydrates (inclusion of water of crystallization) and amorphous forms (where no long-range order exists) may also exist. Figure 3.8 shows an example of the polymorphism of estrone (Busetta et al. 1973). 

In addition, the occurrence of picene derivatives as well as similar polynuclear aromatic systems (White, 1983) in the solvent extracts of coal might be cited as evidence for the inclusion of sterane-type materials in the precursor material to coal. This does assume that the skeletal structure remains intact throughout the maturation process and that there has been no degradation or even formation of new skeletal systems. Indeed, the biosynthesis of aromatic compounds is well documented, including the synthesis of aromatic species from nonaromatic precursors (Weiss and Edwards, 1980 Lee et al., 1981). 

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