Three-point binding modes

This three point binding mode implies that the chirality of the helix determines the asymmetric induction of the epoxidation and not the chirality of the or-carbon atoms of the peptide catalyst. " Natural enzymes show related arrangements of three NHs as binding motif for fully or partially negatively charged entities. The oxy-anion hole in serine esterase is known to use a similar H-bonding motif as proposed in this model. ... 

These mechanistic investigations are supported by theoretical studies on the model compound [(PH3)3RhH] and they confirm the formation of a formate unit coordinating in a -binding mode in the presence of three phosphine ligands [47]. Recent ab initio calculations pointed out that the -formate unit is the most stable coordination mode in complexes, but the species incorporating the -bonded formate seems to be the more reactive intermediate [48]. 

Fig. 17.1 Interaction capacities of the natural R +)-epinephrine and its S(-)-antipode. In simply assuming that the natural R(+)-epinephrine establishes a three point interaction with its receptor (A) the combination of the donor-acceptor interaction, the hydrogen bond and the ionic interaction will be able to generate energies in the order 12 to 17 kcal mole that corresponds to binding constants of 10 to 10 The less active isomer, S(+)-epinephrine, may establish only a two point contact (B). The loss of the hydrogen bond interaction equals to approximately 3 kcal mole this isomer should therefore possess an approximately 100-fold lesser affinity. The experience confirms this estimate. If we consider less abstract models it becomes apparent that the less potent enantiomer is also able to develop three intermolecular bonds to the receptor, provided that it approaches the receptor in a different manner. However, the probability of this alternative binding mode to trigger the same biological response is close to null.

In critical articles, it has been pointed out that the choice of the methods to determine the binding mode must be made with caution and that only a combination of selected methods provides sufficient information to determine the binding mode [117-119]. Thus, for a detailed analysis of criteria for intercalation, Long and Barton divided the aforementioned experimental techniques into three groups (Table 1) [118] ... 

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