Orbital steering concept

Having compared these data with the geometry of the molecules calculated by the molecular mechanics method, the same authors concluded that in XXXVIIIc optimal orientation is achieved of the nucleo philic group OH with respect to carbonyl, namely, the angle of approach of 98°, while even insignificant deviations ( 10°) from it appreciably inhibit the reaction. The requirement for such refined adjustment of the reaction site became known as the orbital steering concept provoking lively discussion [118,119]. 

Furthermore, the postulate of a strongly preferred orientation for the nucleophilic attack corroborated the concepts invoked at the time to understand the high kinetic accelerations of enzymic or intramolecular reactions, such as Koshland s concept of orbital steering in enzyme catalysis [46]. Finally, the hypothesis offered grounds for attractive interpretations of a puzzling pattern of regioselectivity in the reactions of imides and cyclic anhydrides [47,48]. 

So far in this chapter, the chemical biology reader has been introduced to examples of biocatalysts, kinetics assays, steady state kinetic analysis as a means to probe basic mechanisms and pre-steady-state kinetic analysis as a means to measure rates of on-catalyst events. In order to complete this survey of biocatalysis, we now need to consider those factors that make biocatalysis possible. In other words, how do biocatalysts achieve the catalytic rate enhancements that they do This is a simple question but in reality needs to be answered in many different ways according to the biocatalyst concerned. For certain, there are general principles that underpin the operation of all biocatalysts, but there again other principles are employed more selectively. Several classical theories of catalysis have been developed over time, which include the concepts of intramolecular catalysis, orbital steering , general acid-base catalysis, electrophilic catalysis and nucleophilic catalysis. Such classical theories are useful starting points in our quest to understand how biocatalysts are able to effect biocatalysis with such efficiency. 

Since the intramolecular reactivity often achieves the highest limits of the enzyme reaction rates and even rivals them [9,10], a special attention has been paid to studying its sources. A variety of useful rules and concepts, such as entropy and stereopopulation control, orbital steering, propinquity, and spatiotemporal hypotheses, have been evolved and their scope and limitations critically reviewed [11-13]. While differing from one another in their terms and emphases, they are common in reflecting in their essence a general principle of steric fitness of initial and transition state structures of fast intramolecular reactions. 

This section is devoted to this question through the presentation of a relatively new concept in organic chemistry, stereoelectronic control, exploited by P. Deslongchamps from the University of Sherbrooke (114,115). It uses the properties of proper orbital orientation in the breakdown of tetrahedral intermediates in hydrolytic reactions. This concept is quite different from Koshland s orbital steering hypothesis where proper orbital alignment is invoked for the formation of a tetrahedral intermediate. Here we are interested by the process that follows the cleavage of the tetrahedral intermediate in the hydrolysis of esters and amides. 

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