Three-point attachment model

In a nonchiral environment, the enantiomers of a racemate possess the same physical and chemical properties. But in the early 1930s, Easson and Stedman introduced a three-point attachment model that laid the basis for the initial understanding of stereochemical differences in pharmacological activity [13]. The authors described the differences in the bioaffinity of the enantiomers to a common site on an enzyme or receptor surface, with the receptor or enzyme needing to possess three nonequivalent binding sites to discriminate between the enantiomers. The enantiomer that interacts simultaneously with all three sites is called the eutomer (active enantiomer), whereas the other, which binds to fewer than three sites at the same time, is called the distomer (inactive enantiomer) [14]. 

Figure 15 Deformation of the surface for chiral recognition, (a) A three-point attachment model for enantioresolution on the surface (b) a surface with a shallow dip (c) a surface with a steep dip and (d) a channel in the extreme case, caused by deformation.

Ogston [20,21], seemingly unaware of the Easson-Stedman model, proposed a similar three-point attachment model to rationalize the observed stereoselectivity in the enzymatic transformation of symmetrical prochiral substrates, e.g., citrate and aminomalonate (Fig. 3) [22]. Similarly, Dalgleish [23], also unaware of the Easson-Stedman model [17], rationalized his observations concerning the resolution of the enantiomers of a number of amino acids on paper chromatography by a three-point attachment. In a subsequent telephone conversation with Bentley [24], Dalgleish stated that he was terribly impressed by the Ogston hypothesis. It is therefore... 

Inspired by Easson and Stedman s work, Dalgliesh established the three-point attachment model in 1952 to elucidate the chromatographic separation of D-/L-amino acids in cellulose paper chromatography [22]. The Dalgliesh s model was later improved by Lochmuller and Souter [23]. According to this three-point attachment model, it is necessary to have at least three attractive interactions, or two attractive and one repulsive (steric) interaction between the receptor and one of the... 

Figure 17.10 Original three-point attachment model for...

Fig. 2. Illustration of the three-point attachment between citric acid and enzyme. The areas on the left-hand side of the diagram represent the enzyme surface. It is asssumed that combination between enzyme and substrate can occur where the patterns of enzsme model and substrate model match. There is only one position in which the citric acid molecule can be placed on the enz3me if a three-point attachment takes place. ...

The concept of the three-point fit was proposed in 1933 [11]. In this model, stereochemical differences in pharmacological activities were due to the differential binding of enantiomers to a common site on a receptor surface. The three-point interaction model was revisited by Ogston [12]. However, the often-quoted paper is the one from Dalgliesh [13], who invoked a three-point interaction to explain the enantioselective separation of amino acids on cellulose paper. The three-point interaction rule differs from the three-point attachment rule as was pointed out by Davankov [14], who states that the condition for a chiral selector to recognize the enantiomers is that at least three configuration-dependent active points of the selector molecule should interact with three complementary... 

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. 

Tensile moduli were measured from standard dog-bone samples (2.0 mm thickness, 4.7 mm width, and 22.0 mm gauge length) in a Model 1122 Instron. Flexural modulus was determined using a testing apparatus which consists of two aluminium/steel pieces attached to the Instron which is fitted with a tensile load cell. This device effectively performs an inverted three-point bend the two side bars remain stationary above the sample as the central bar below the sample moves upward. Flexural samples measured ca. 52.0 x 1.7 x 13.1 mm and were tested using a 25.4 mm span (distance between the two side bars). Crosshead speed (CHS) for both flexural and tensile testing was 1.0 mm/min. 

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