Chemical recognition mechanisms

Weinstein, H., R. Osman, and J. P. Green. 1979. The Molecular Basis of Structure-Activity Relationships Quantum Chemical Recognition Mechanisms in Drug-Receptor Interactions. In Computer-Assisted Drug Design. E. C. Olson and R. E. Christofferson, eds. American Chemical Society, Washington, D.C. 

The Molecular Basis of Structure-Activity Relationships Quantum Chemical Recognition Mechanisms in Drug-Receptor Interactions... 

The need for an overall and combined chemical structure and data search system became clear to us some time ago, and resulted in the decision to build CHIRBASE, a molecular-oriented factual database. The concept utilized in this database approach is related to the importance of molecular interactions in chiral recognition mechanisms. Solely a chemical information system permits the recognition of the molecular key fingerprints given by the new compound among thousands of fingerprints of known compounds available in a database. 

Besides, information on intermolecular interactions has been derived in these studies from complexation-induced shifts (CIS). The chemical shift is an indicator for the shielding of a nucleus and thus for the electronic state of a specific proton. Since the electronic environment may change on complexation, CIS can be used to monitor where host-guest contacts may take place. If these interactions occur stereoselectively, the CIS will be different for the two guest enantiomers (AS distinct from 0) giving possibly some insight into the chiral recognition mechanism. 

Different classifications for the chiral CSPs have been described. They are based on the chemical structure of the chiral selectors and on the chiral recognition mechanism involved. In this chapter we will use a classification based mainly on the chemical structure of the selectors. The selectors are classified in three groups (i) CSPs with low-molecular-weight selectors, such as Pirkle type CSPs, ionic and ligand exchange CSPs, (ii) CSPs with macrocyclic selectors, such as CDs, crown-ethers and macrocyclic antibiotics, and (iii) CSPs with macromolecular selectors, such as polysaccharides, synthetic polymers, molecular imprinted polymers and proteins. These different types of CSPs, frequently used for the analysis of chiral pharmaceuticals, are discussed in more detail later. 

Fig. 1 Chemical interaction mechanisms, basic components of the optical sensor instrumentation and their operation. Mechanisms direct measurement of chemical compounds that exhibit spectroscopic properties (1 A) and measurement of light originating from a chemical or a biological reaction in chemiluminescent or bioluminescent phenomena (IB) 2 optodes based on the interaction of indicators and labels with light, which are immobilized in a support and sensors that modify the intrinsic physical or chemical properties of a waveguide (refractive index, phase, etc.) as a result of the presence of the analyte (3A), a recognition element (35), an intermediate analyte (3C) or an indicator (3D)...

Figure 5.6 Chiral stationary phases classification according to chiral recognition mechanisms and chemical structures. (From Reference 256.)...

Approximately 70 chiral stationary phases (CSPs) have been marketed since 1981 [256]. A classification scheme has been proposed for the numerous commercially available CSPs which takes into account chiral recognition mechanism and chemical structure (Figure 5.6). 

Membranes used for separation are thin selective barriers. They may be selective on the basis of size and shape, chemical properties, or electrical charge of the materials to be separated. As discussed in previous sections, membranes that are microporous control separation predominantly by size discrimination, charge interaction, or a combination of both, while nonporous membranes rely on preferential sorption and molecular diffusion of individual species. This permeation selectivity may, in turn, originate from chemical similarity, specific complexation, and/or ionic interaction between the permeants and the membrane material, or specific recognition mechanisms such as bioaffinity. 

Thus, protein adsorption and cell adhesion occur for various reasons and in different appearances. When surfaces of living systems are involved, specific recognition mechanisms undoubtedly play crucial roles. Nevertheless, since we are dealing with a rather general phenomenon, it is likely that these specific interactions are superimposed on a generic interaction mechanism. Bioadhesion and adsorption is very complicated from a physical chemical point of view. Interfacial tensions, wetting and electrical properties of the surfaces are prominently involved. 

This device employs single-stranded poly(adenylic acid) [poly(A)] as the chemical recognition agent. This species selectively recognizes its complementary polymer, poly(U), through hybridization to form a double-stranded nucleic acid. The poly(A) is immobilized onto the activated surface of a quartz piezoelectric crystal, which is a mass-sensitive transducer. Electric dipoles are generated in anisotropic materials (such as quartz crystals) subjected to mechanical stress, and these materials will... 

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