Hydrophobic forces, substrate bound

The chemistry of interest when cyclodextrin or its derivatives are used as enzyme mimics involves two features. First of all, the substrate binds into the cavity of the cyclodextrin as the result of hydrophobic or lyophobic (4) forces. Then the bound substrate undergoes a reaction, which may involve the cyclodextrin as a reagent or as a catalyst. The speed of this reaction is promoted generally by the proximity induced by binding, and in addition the reactions are often selective because of geometric constraints in the transition state. This selectivity may involve the selective reaction of one potential substrate relative to another, selective production of one regiochemical isomer compared with another, or selective production of one stereoisomer relative to another. This last area, selective stereochemistry and asymmetric synthesis, is still one of the most neglected areas of cyclodextrin chemistry. 

In the preceding section we discussed the properties of zinc(II) as an ion. These properties are, of course, important in understanding its role in biological catalysis, but it would be too simplistic to believe that reactivity can be understood solely on this basis. Catalysis occurs in cavities whose surfaces are constituted by protein residues. Catalytic zinc is bound to a water molecule, which often is H-bonded to other residues in the cavity and/or to other water molecules. The structure of the water molecules in the cavity cannot be the same as the structure of bulk water. Furthermore, the substrate interacts with the cavity residues through either hydrophilic (H-bonds or electric charges) or hydrophobic (London dispersive forces) interactions. As a result, the overall thermodynamics of the reaction pathway is quite different from that expected in bulk solutions. Examples of the importance of the above interactions will be given in this chapter. 

This internal cavity which is highly hydrophobic can accommodate a wide range of guest molecules, ranging from polar compounds such as alcohols, acids, amines, and small inorganic anions to apolar compounds such as aliphatic and aromatic hydrocarbons. In all cases, the guest is bound at least partially, within the cavity of the CD. The driving forces for the inclusion complexation of CD with substrates are attributed to several factors such as van der Waals forces, hydrophobic interactions, electronic effects, and steric factors. ... 

The specific binding between enzymes and substrates is thought to be based on structural and electrostatic complementarity. A substrate is firmly held in the active site by an assortment of weak forces contributed by hydrophobic, hydrophilic, H-bonding, and/or electrostatic interactions. The bound substrate is poised next to an acidic, basic, or nucleophilic group(s) of amino acid(s) that usually serve as catalytic residues. 

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