Block site-selective complexation

A unique strength of solid-state NMR is its ability to probe molecular dynamics with site selectivity.9132 In this section, we present some specific examples that illustrate the considerable insight into dynamic processes provided by advanced solid-state NMR experiments applicable to as-synthesized samples, i.e., without the requirement for isotopic labeling. These examples focus on well-defined processes that are fast as compared to the time scale of the H DQ MAS experiment, this being on the order of 10-6 to 10 4 s. In addition, it should be noted that the extraction of dipolar couplings by following the buildup of DQC in a H DQ MAS experiment has been shown to provide insight into the complex dynamic processes in polymer melts,172 block copolymers,173 and elastomers.174... 

It should be clear from this discussion that the working, active, and selective catalyst is a complex, multicomponent chemical system. This system is finely tuned and buffered to carry out desirable chemical reactions with high turnover frequency and to block the reaction paths for other thermodynamically equally feasible but unwanted reactions. Thus, an iron catalyst or a platinum catalyst is composed not only of iron or platinum but of several other constituents as well to ensure the necessary surface structure and oxidation state of surface atoms for optimum catalytic behavior. Additives are often used to block sites. 

The binding sites of most enzymes and receptors are highly stereoselective in recognition and reaction with optical isomers (J, 2 ), which applies to natural substrates and synthetic drugs as well. The principle of enantiomer selectivity of enzymes and binding sites in general exists by virtue of the difference of free enthalpy in the interaction of two optical antipodes with the active site of an enzyme. As a consequence the active site by itself must be chiral because only formation of a diasteromeric association complex between substrate and active site can result in such an enthalpy difference. The building blocks of enzymes and receptors, the L-amino acid residues, therefore ultimately represent the basis of nature s enantiomer selectivity. 

Several potent anti-estrogens also have a potential to be used as 17/f-HSD inhibitors because some of them have a dual site of inhibitory action they block both the estrogen receptor (anti-estrogen effect) and estrogen formation (inhibitory effect on 17/f-HSD). Despite the complexity of a dually active agent, such inhibitors have interesting properties suitable for their potential use in the treatment of estrogen-sensitive diseases, but their potency and selectivity for 17/1-HSDl have to be improved [98]. 

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