Cycloamyloses

S. M., Okada, G. M., Sheldrick, G. M., Saenger, W., V-Amylose at Atomic Resolution X-Ray Structure of a Cycloamylose with 26 Glucose Residues (Cyclomalto-hexaicosaose). Proc.Nat.Acad.Sci.USA, 1999, 96, 4246. 

The Chemisorption of Benzene R. B. Moves and P. B. Wells The Electronic Theory of Photocatalytic Reactions on Semiconductors Th. Wolkenstein Cycloamyloses as Catalysts David W. Griffiths and Myron L. Bender... 

In accord with the current interest in stereochemistry at phosphorus a number of optical studies on phosphonous derivatives have been carried out. Benschop and his group have achieved a partial resolution of alkyl alkylphosphinates (133) by stereospecific inclusion in cycloamyloses. Optical purities in the range 20—80% were obtained. 

Cycloamylose forms inclusion complexes stereoselectively with the enantiomers of isopropyl methylphosphinate (124) from which it was possible to isolate one enantiomer with an optical purity of 66%. The absolute configuration of menthyl methylphosphinate has been revised to the opposite of that previously assigned. 

For the mechanism of azolide hydrolysis under specific conditions like, for example, in micelles,[24] in the presence of cycloamyloses,[25] or transition metals,[26] see the references noted and the literature cited therein. Thorough investigation of the hydrolysis of azolides is certainly important for studying the reactivity of those compounds in chemical and biochemical systems.[27] On the other hand, from the point of view of synthetic chemistry, interest is centred instead on die potential for chemical transformations e.g., alcoholysis to esters, aminolysis to amides or peptides, acylation of carboxylic acids to anhydrides and of peroxides to peroxycarboxylic acids, as well as certain C-acylations and a variety of other preparative applications. 

Of the many reagents, both heterogeneous and homogeneous, that can facilitate chemical reactions, the cycloamyloses stand out. Reactions can be catalyzed with many species such as hydronium ions, hydroxide ions, general acids, general bases, nucleophiles, and electrophiles. More effective catalysis can sometimes be achieved by combinations of catalytic species as in multiple catalysis, intramolecular catalysis, and catalysis by com-plexation. Only the latter catalysis can show the real attributes of an efficient catalytic system, namely speed and selectivity. In analogy to molecular sieves, selectivity can be attained by stereospecific complexation and speed can be likewise attained if the stereochemistry within the complex is correct. The cycloamyloses, of any simple chemical compound, come the closest to these goals. 

Cycloamyloses are also referred to as eyelodextrins, eycloglucans, or Schardinger dextrins, preceded, in each case, by a Greek letter to denote the number of glucose units (< - for 6, 0- for 7, y- for 8, etc.). 

Because of the conformational restraints imposed on the cycloamyloses by their looped arrangement, it is reasonable to assume that the structural features derived for the crystalline state will be retained in solution. This has been confirmed in recent years by means of a variety of spectroscopic techniques. Nuclear magnetic resonance (Rao and Foster, 1963 Glass,... 

Fig. 1. Schematic diagram of two glucopyranose units of a cycloamylose molecule illustrating details of the o-(l,4) glycosidic linkage and the numbering system employed to describe the glucopyranose rings.

Nuclear magnetic resonance and infrared spectra of the cycloamyloses in aprotic solvents such as dimethyl sulfoxide indicate that intramolecular... 

In summary, although subtle conformational differences between the various cycloamyloses and the effect of intramolecular hydrogen bonds on their solution conformations remain to be accurately resolved, overall structural features have been clearly defined. This is particularly advantageous and, in fact, a prerequisite if the cycloamyloses are to be profitably used as models for enzymatic or other catalytic processes. In subsequent sections of this article, various aspects of binding and catalysis will be explained on the basis of the chemical nature and geometrical dimensions of the cycloamylose cavity which is, in fact, their active site. 

The ability of the cycloamyloses to form insoluble crystalline complexes with relatively simple alcohols was recognized by Villiers (1891) and... 

Within a similar series of reagents, complexing tendency toward the different cycloamyloses can be qualitatively correlated with the size of the reagent. All three cycloamyloses, for example, are effectively precipitated from aqueous solution by benzene, but only cyclooctaamylose is precipitated by anthracene. Similarly, for cycloheptaamylose, bromobenzene is a more effective precipitant than benzene, whereas the reverse is true for cyclohexaamylose. Discriminating precipitants such as these have been incorporated by French and associates (1949) and by Cramer and Henglein (1958) into schemes for the separation of cyclohexa-, cyclohepta-, and cyclooctaamylose. 

A particularly interesting property of the cycloamyloses is their ability to induce stereospecific precipitation. This was first recognized by Cramer and Dietsche (1959a) who were able to effect partial resolution of a series... 

In a series of papers (Cohen and Lach, 1963 Lach and Cohen, 1963 Lach and Chin, 1964a,b Pauli and Lach, 1965 Lach and Pauli, 1966), Lach and co-workers used a similar technique to evaluate the effect of the cycloamyloses on the solubilities of a variety of pharmaceuticals. Plots of the solubility of the pharmaceutical against the concentration of added cycloamylose were usually linear with slopes ranging from 0 to 2.25. In theory, these slopes can be related to the dissociation constants for the cycloamylose-substrate complexes if the stoichiometries of the complexes can be determined (Thoma and Stewart, 1965). This technique, however, is inferior to the spectrophotometric method to be discussed presently. 

Unlike the crystalline cycloamylose complexes, combining ratios of host to guest in solution are usually 1 1. A notable exception is the interaction of the cycloamyloses with long chain aliphatic carboxylic acids. Solubility plots suggest that as many as four cycloheptaamylose molecules may interact with a single molecule of dodecanoic acid (Schlenk and Sand, 1961). In analogy to the crystalline state, cycloamyloses may form channels in solution in order to accomodate extended chains. 

By correlating the observed spectral changes with the concentrations of added cycloamylose, dissociation constants of the cycloamylose-substrate adducts may be calculated (Rossotti and Rossotti, 1961). Values of the dissociation constants determined in this manner for a variety of complexes are presented in Table II. In most cases, stoichiometries of the complexes have been shown to be 1 1 from the presence of distinct isosbestic points in the spectrophotometric titrations. In a few cases, additional spectral perturbations are observed as the cycloamylose concentration is increased, indicating more complex modes of association. Methyl orange, for example,... 

Fig. 4. Schematic illustration of the inclusion of an azo dye within the cycloamylose cavity emphasizing the increased difficulty of insertion or withdrawal of the dye as the size of the R and R groups is increased. 

A final source of evidence for the formation of inclusion complexes in solution has been derived from kinetic measurements. Rate accelerations imposed by the cycloamyloses are competitively inhibited by the addition of small amounts of inert reagents such as cyclohexanol (VanEtten et al., 1967a). Competitive inhibition, a phenomenon frequently observed in enzymatic catalyses, requires a discrete site for which the substrate and the inhibitor can compete. The only discrete site associated with the cycloamyloses is their cavity. 

The conclusions of the preceding discussion can be briefly summarized as follows. The formation of inclusion complexes in both the crystalline state as well as in solution has been convincingly demonstrated by spectral and kinetic techniques. Whereas the crystalline complexes are seldom stoichiometric, the solution complexes are usually formed in a 1 1 ratio. Although the geometries within the inclusion complexes cannot be accurately defined, it is reasonable to assume that an organic substrate is included in such a way to allow maximum contact of the hydrophobic portion of the substrate with the apolar cycloamylose cavity. The hydrophilic portion of the substrate, on the other hand, probably remains near the surface of the complex to allow maximum contact with the solvent and the cycloamylose hydroxyl groups. The implications of inclusion complex formation for specificity and catalysis will be elucidated in subsequent sections of this article. 

Although the fact that the cycloamyloses include a variety of substrates is now universally accepted, the definition of the binding forces remains controversial. Van der Waals-London dispersion forces, hydrogen bonding, and hydrophobic interactions have been frequently proposed to explain the inclusion phenomenon. Although no definitive criteria exist to distinguish among these forces, several qualitative observations can be made. 

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