The three-point contact model

Acceptor-donor or hydrophobic interaction between the aromatic ring of adrenaline and an aromatic ring of the receptor protein. 

An ionic bond between the protonated amino group and an aspartic or glutamic carboxyhc group of the receptor. 

The two phenolic hydroxyl groups exchange hydrogen bonds with Ser and Ser ° respectively 

The aromatic ring of adrenaline is stabilized by means of 1T-1T interactions with Phe and Phe  

The cationic head exerts a coulombic interaction with the Asp carboxylate and is located in a hydrophobic pocket made of Trp , Phe , and Trp  

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An Early Three-dimensional Approach the Three-point Contact Model... 

The low energy sweetening properties of aspartame have been discussed on the basis of structural relationships [1, 83] within the context of the three point contact model of the sweet taste receptor. This model involves a hydrogen bond donor, a hydrogen bond acceptor, and a hydrophobic region with specific geometric relationships. The model accounts for the fact that only one of the four diastereomers of aspartylphenylalanyl methyl ester is sweet. 

The three-point contact model Diastereoisomers Stereoselectivity ratios Pfeiffer s rule... 

It is interesting to note that the interaction of a prochiral reactant with a chiral step-kink site and with an adsorbed chiral modifier each fiilfills the three-point contact model required for chiral recognition [102-104]. At a step-kink site, the reactant adsorbed in the pro-(l ) geometry contacts the surface plane, the step, and the kink in a way that is not equivalent to the pro-(S) adsorbate. Similarly, in the modifier-reactant interaction between methyiacetoacetate and pyroglutamate, it is proposed that the reactant has three key points of contact comprising the metal-molecule interaction and two intermolecular H-bonds with the modifier [101]. 

A new approach to stereoselective transfer hydrogenation of imines was the application of chiral phosphoric acid esters as organocatalysts [50-52]. The mechanism is based on the assumption that the imine is protonated by a chiral Bronsted acid, which acts as the catalyst. The resulting diastereomeric iminium ion pairs, which may be stabilized by hydrogen bonding, react with the Hantzsch dihydropyridine at different rates to give an enantiomerically enriched amine and a pyridine derivative [50-52]. The exact mechanism is still under discussion however computational density functional theory (DFT) studies ]53, 54] suggest a three-point contact model. ... 

Steroidal podands similar to 3 are, in fact, quite well-adapted for enantioselective recognition. The three functionalised sites on the steroid nucleus may be modified to give asymmetrical derivatives of general form 10, capable in principle of the three-point contact required for the classical model of enantioselectivity. Whether or not this idealised situation is ever achieved in practice, the chiral, functionalised steroidal a-face appears to provide an excellent environment for enantioselection. 

There are numerous chiral stationary phases available commercially, which is a reflection of how difficult chiral separations can be and there is no universal phase which will separate all types of enantiomeric pair. Perhaps the most versatile phases are the Pirkle phases, which are based on an amino acid linked to aminopropyl silica gel via its carboxyl group and via its amino group to (a-naphthyl)ethylamine in the process of the condensation a substituted urea is generated. There is a range of these type of phases. As can be seen in Figure 12.23, the interactions with phase are complex but are essentially related to the three points of contact model. Figure 12.24 shows the separation of the two pairs of enantiomers (RR, SS, and RS, S,R) present in labetalol (see Ch. 2 p. 36) on Chirex 3020. 

When an asymmetric center is present in a compound, it is thought that the substituents on the chiral carbon atom make a three-point contact with the receptor. Such a fit insures a very specific molecular orientation which can only be obtained for one of the two isomers (Fig. 1.3). A three-point fit of this type was first suggested by Easson and Stedman [23], and the corresponding model proposed by Beckett [24] in the case of (R)-( )-adrenaline [= (R)-( )-epinephrine]. The more active natural (R)-( )-adrenaline establishes contacts with its receptor through the three interactions shown in Fig. 1.3. 

In discussing the appearence of diastereoselectivity in natural systems, the rule of three-point contact is frequently used11). This rule implies that a prochiral substrate becomes a chiral one, when it is fixed on three nonidentical points on the enzyme system. On the other hand, the well-known lock-key model is mainly based on a specific spacial arrangement and does not take into account specific types of bonding to the matrix12). For a discussion of diastereoselectivity in reactions with metal complexes, it seems more appropriate to use such a lock-key model. 

One important finding of this study is that, for the case of full-sphere geometry (Figure 6.11b), the planar diffusion model is not an appropriate approximation. Rather, the microparticle sphere exhibits a region, where the reverse scan current decreases with scan rate, as the geometry favors a convergent diffusion of charge -that is, towards the equatorial point of the three-phase contact. This causes a dilution of the product species near this point at scan rates above the thin layer... 

The three-point attachment rule is largely qualitative and only valid with bimolecular processes (e.g., small Pirkle or ligand-exchange selectors). Another drawback of this model approach is that it cannot be applied to enantiomers with multiple chiral centers. Sundaresan and Abrol [15] proposed a novel chiral recognition model to explain stereoselectivity of substrates with two or three stereo centers requiring a minimum of four or five interaction points. In the same way, Davankov [16] pointed out that much more contact points are realized with chiral cavities of solids. 

IVa represents a physical bond resulting from highly localized intermolecular dispersion forces. It is equal to the sum of the surface free energies of the liquid, 7, and the solid, 72. loss the interfacial free energy, 7,2. It follows that Eq. (2.1) can be related to a model of a liquid drop on a solid shown in Fig. 2.2. Resolution of forces in the horizontal direction at the point A where the three phases are in contact yields Young s equation... 

Fig. 6.77. Calculations done using the statistical mechanical theory of electrolyte solutions. Probability density p(6,r) for molecular orientations of water molecules (tetrahedral symmetry) as a function of distance rfrom a neutral surface (distances are given in units of solvent diameter d = 0.28 nm) (a) 60H OH bond orientation and (b) dipolar orientation, (c) Ice-like arrangement found to dominate the liquid structure of water models at uncharged surfaces. The arrows point from oxygen to hydrogen of the same molecule. The peaks at 180 and 70° in p(0OH,r) for the contact layer correspond to the one hydrogen bond directed into the surface and the three directed to the adjacent solvent layer, respectively, in (c). (Reprinted from G. M. Tome and G. N. Patey, ElectrocNm. Acta 36 1677, copyright 1991, Figs. 1 and 2, with permission from Elsevier Science.

In order to elucidate the mechanism of moisture and water absorption by phenolic foams, Lowe et al." calculated the wall thickness of cells using three simplified models of cell packing 1) spheres with point contacts 2) den packing of cubes without distortion of faces 3) fused cubes with distorted faces. 

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