Complementarity receptor-substrate binding

The binding by cryptand 1 of the nonspherical ammonium eation was observed, but not surprisingly, the receptor-substrate binding complementarity is poor, and therefore. 

Information may be stored in the architecture of the receptor, in its binding sites, and in the ligand layer surrounding the bound substrate such as specified in Table 1. It is read out at the rate of formation and dissociation of the receptor—substrate complex (14). The success of this approach to molecular recognition ties in estabUshing a precise complementarity between the associating partners, ie, optimal information content of a receptor with respect to a given substrate. 

Complementarity. To a first approximation, complementarity should take two forms (Fig. 1). Firstiy, the shape and size of the receptor cavity must complement the form of the substrate. Secondly, there must be a chemical complementarity between the binding groups lining the interior of the cavity and the external chemical features of the substrate (15). 

Dietrich, B., Guilhem, J., Lehn, J.-M., Pascard, C., Sonveaux, E., 11. Molecular recognition in anion coordination chemistry. Structure, binding constants and receptor-substrate complementarity of a series of anion cryptates of a macrobicyclic receptor molecule. Helv. Chlm. Acta 1984, 67, 91-104. 

C-NMR determinations of the relaxation and correlation times of supermolecules (25) have indicated that complementary receptor-substrate pairs display similar molecular motions for both partners [19]. This dynamic fit may be considered to result from the combination of steric fit with dihapto binding. Thus, complementarity between components of a supramolecular species expresses itself in both its structural and dynamic properties. 

Receptors exhibit structural complementarity with their ligand in the same way that enzymes are complementary to their substrate. Often the actual binding of the hormone to its receptor involved just a small portion of both molecules. The peptide ACTH secreted by the pituitary gland contains 39 amino acids, but only about 12 of these near the N-terminal are required to engage the receptor. Furthermore, and as noted in Section 4.4.1, LH, FSH, TSH and hCG all share a common a subunit and their receptors recognize only the [3 unit. 

Linear recognition is displayed by the hexaprotonated form of the ellipsoidal cryptand bis-tren 33, which binds various monoatomic and polyatomic anions and extends the recognition of anionic substrates beyond the spherical halides [3.11, 3.12]. The crystal structures of four such anion cryptates [3.11b] provide a unique series of anion coordination patterns (Fig. 4). The strong and selective binding of the linear, triatomic anion N3" results from its size, shape and site complementarity to the receptor 33-6H+. In the [N3 pyramidal arrays of +N-H "N- hydrogen bonds, each of which binds one of the two terminal nitrogens of N3-. 

Thus, for both the terminal diammonium and dicarboxylate substrates, selective binding by the appropriate receptors describes a linear recognition process based on length complementarity in a ditopic binding mode. Important biological species, such as polyamines, amino acid and peptide diamines, and dicarboxylates [4.18] may also be bound selectively. Recognition is achieved by multiple coordination to metal ions in dinuclear bis-macrocyclic coreceptors that complex selectively complementary bis-imidazole substrates of compatible length [4.21]. 

The spherically shaped cryptophanes are of much interest in particular for their ability to bind derivatives of methane, achieving for instance chiral discrimination of CHFClBr they allow the study of recognition between neutral receptors and substrates, namely the effect of molecular shape and volume complementarity on selectivity [4.39]. The efficient protection of included molecules by the carcerands [4.40] makes possible the generation of highly reactive species such as cyclobutadiene [4.41a] or orthoquinones [4.41b] inside the cavity. Numerous container molecules [A.38] capable of including a variety of guests have been described. A few representative examples of these various types of compounds are shown in structures 59 (cyclophane) 60 (cubic azacyclophane [4.34]), 61a, 61b ([4]- and [6]-calixa-renes), 62 (cavitand), 63 (cryptophane), 64 (carcerand). 

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