Basic Principles of Molecular Recognition

Native enzymes show remarkably sharp substrate specificities. Actually, an enzyme can sometimes distinguish a slight difference of shapes between its specific and nonspecific guests, even if the electronic states of both are almost the same. The term molecular recognition is used to describe such ability of the molecule (enzyme). Inclusion compounds are supersimplified, but very appropriate systems for elucidation of the nature of the molecular recognition, since interactions between the inclusion host and a substrate are not more complicated than can be measured or even calculated. In this section, we will survey the recent results on the crystal structures of the inclusion compounds, and based on the information, the probable driving force for the inclusion is discussed in detail. 

Cyclo- dextrin Guest Chemical composition Space group Ref. 

Since the first X-ray analysis of the complex of a-cyclodextrin with potassium acetate was reported by Hyble et al. (8), the various types of cyclodextrin complexes have been studied by X-ray crystallography as shown in Table I. In contrast with cyclodextrin, only two examples of X-ray analyses of cyclo-phanes as inclusion hosts are known, which are also shown in Table I. 

Interplanar Angles and Diameters Characterizing Empty Cyclodextrin 

Empty ft- (11) and y-cyclodextrins (12) also take normal torus shapes, as revealed by X-ray crystallography, and no significant deformations are observed for these two cyclodextrins when they bind guest molecules. It is noteworthy that all empty cyclodextrins include water molecules in their cavities as shown in Table IV and Fig. 4. Since no water molecules were observed in inclusion complexes of cyclodextrins with organic guest molecules, it is evident that the expulsion of these water molecules in the cyclodextrin cavities is one of the important factors for formation of the inclusion complexes. 

---

In the first chapter I shall describe basic principles of molecular recognition of monomers and polymers by cyclodextrins (G. Wenz, in Volume 222, Chapter 1) and try to provide an overview of inclusion polymers with cyclodextrins. The following chapters are more specialized. They are about functional cyclodextrin polyrotaxanes for drug delivery (N. Yui, R. Katoono, A. Yamashita, in Volume 222, Chapter 2), cyclodextrin inclusion polymers forming hydrogels (J. Li,... 

The synthesis of new molecular cavities is of interest for a variety of reasons. Investigations on the influence of cavity size and conformation on complexation abilities renders information on fundamental principles of molecular recognition which are basic for the life sciences. The ability to construct hosts for selective complexation is a prerequisite for the design of artificial catalysts for various reactions. 

Moyer, B. A. (1996) Basic Principles of Extraction and Liquid-Liquid Systems Employing Crown Ethers and Related Metal-Ion Receptors, in Atwood, J. L., Davies, J. E. D., McNicol, D. D., Vogtle, F., Lehn, J.-M. (eds.), Molecular Recognition Receptors for Cationic Guests, Pergamon, New York, pp 325-365 and references cited therein. 

In order to address the characteristics of biological models, we have to first define the basic principles of biological systems that a supramolecular model may mimic. Among the most important are selective molecular recognition of a molecular entity selective and highly accelerated modification of a substrate (typieal role of enzymes) compartmentalization and selective translocation of chemical species across boundaries (typieal role of biomembranes) harvesting and transformation of energy and self-replication. 

I would like to thank all the authors, as well as all those who have facilitated this volume, and I hope that readers will find answers to key questions concerning basic principles and related evolutional approaches that have been used in Constitutional Dynamic Chemistry (CDC). The most revolutionary consequences may reflect the fascinating possibilities offered by selection, evolution, amplification, molecular recognition, and replication processes. This volume is not a comprehensive treatise, but is a timely objective snapshot of the CDC field from which the reader can get a broader insight into this and hopefully a future source of inspiration. 

The two examples mentioned above illustrated basic principles how protein phosphorylation serves specific biological purposes. Although different kinases might be involved in diverse pathways, the molecular mechanism for the regulation of protein function by phosphorylation is similar By changing protein structure, phosphorylation can turn on/off the catalytic activity of a protein, or create/mask recognition motif for binding by other molecules. 

The kajk-and-key principle formulaled by Emil Fischer as early as Ihc end of the I9i h century has still not lost any of its significance for the life sciences. The basic aspects of ligand-protein interaction may be summarized under the term molecular recognition and concern the specificity as well as stability of ligand binding. 

As described in previous chapters, MIPs prepared by modern protocols are robust materials capable of highly specific molecular recognition. Since specific molecular recognition is the hallmark of enzyme catalysis, it is apparent that MIPs are potentially suited for catalytic applications. And indeed, investigations have shown that catalytic MIPs can be produced and successively more active and selective MIP catalysts were presented over the last years. In the following, the basic ideas and principles of catalytic MIPs are described using selected examples from the literature. For supplementary reading on this topic, review articles by Wulff (1), Whitcombe et al. [2] and Davis et al. [3] are recommended. 

---