Fitting concept

For more details on this topic see References 138, 139,148 for more illustrations on the chiral fit concept see also Inclusion compounds. 

The use of the symbol E in 5.1 for the environment had a double objective. It stands there for general environments, and it also stands for the enzyme considered as a very specific environment to the chemical interconversion step [102, 172], In the theory discussed above catalysis is produced if the energy levels of the quantum precursor and successor states are shifted below the energy value corresponding to the same species in a reference surrounding medium. Both the catalytic environment E and the substrates S are molded into complementary surface states to form the complex between the active precursor complex Si and the enzyme structure adapted to it E-Si. In enzyme catalyzed reactions the special productive binding has been confussed with the possible mechanisms to attain it lock-key represents a static view while the induced fit concept... 

The capacity of inositol orthoformate derivatives 124 and 125 for binding to alkali metal ions was studied by electrospray ionization mass spectrometry (ESI-MS) gas-phase measurements <2001JOC8629>. The [5.5.5]-iono-phore 125 n = 3) possessed the highest Li /Na selectivity and the best affinity for Li. The results obtained proved to be in agreement with the size-fit concept. Other factors which influence the complexation are the orientation of the oxygen atoms, which are able to bind to metal, the basicity, and the polarizability of the heteroatoms around the perimeter of the binding cavity. 

The building of a cavity around the guest is an extension of induced fit concept. This is the case with hexokinase enzyme [ 13b] and foldamers [ 13c] that wrap themselves around the guest. 

Hexokinase initially binds glucose, then the hex-okinase-glucose complex binds ATP. How do you explain the purpose of this substrate-binding pattern to a fellow student without using the induced-fit concept ... 

Therefore, another strategy was developed, based on the induced-fit concept, which uses flexible receptors in order to optimize the interactions between the donor atoms and the metal ion. In fact, the coordination environment is built upon complexation thanks to the flexibility introduced into the complexation agent, which is now termed predisposed ligand . These receptors are either large macrocycles able to wrap around the guest or small macrocycles fitted with pendant arms. The latter approach has proved to be very successful, particularly with calixarene (Asfari et al., 2001) and cyclen (1,4,7,10-tetraaza-dodecane) (Lukes et al., 2001) derivatives. 

Scheme 7). Interestingly, the optical purity of the recovered alcohol is dependent on the electron donating ability of the aromatic nuclei in the substrate, possibly indicating that n-n stacking plays a pivotal role in the enantiodifferentiat-ing event. It was also shown that the pyridinium ion derived from 18 and isobutyric anhydride adopts a closed conformation , in contrast to 18, in which the naphthyl moiety is situated over the pyridine ring, thus shielding the si face of the carbonyl group and supporting the induced fit concept.

A schematic depiction of the mechanism at the active site of beta-amylase has been described in terms of an induced-fit concept. This scheme accounts qualitatively for the specificity of the enzyme (the exclusive formation of maltose) the failure to bypass branchpoints and the inhibition by maltose, interior parts of starch chains, and Schardinger dextrins. 

We have already introduced the hole-fit concept for a macrocyclic ligand in Chapter 4 (see Figure 4.38), which effectively means that the most stable complexes form where the internal diameter of the ring cavity matches the size of the entering cation. The effect can be significant for example, the natural antibiotic valinomycin is a macrocycle that binds potassium ion to form a complex 104 times more stable than that formed with the smaller... 

Induced fit D. Koshland Jr. introduced the induced fit concept to explain the conformational adjustment of enzyme and substrate, as an improvement over the more rigid lock-and-key model. Neither model can exclusively explain all... 

If a metaphorical statement can ever reveal how things are , Emil Fischer s static lock-and-key metaphor [31a] ought to be replaced with a dynamic one. This was done by D. E. Koshland s induced-fit concept [31b], which readily produced the self-explanatory hand-and-glove metaphor. Binding of a given effector will bring about a conformational change of the receptor that is favorable for catalytic activity of the formed supermolecule. 

Even if conformational selection is more appropriate to explain special binding events, the well-established induced fit concept is not outdated and keeps its legitimation. Each of both pathways may be pursued in case of conformational selection, the ligand binds selectively to one of the macromolecule s low populated conformations while in case of an induced fit, the ligand binds to the predominating conformation of the macromolecule. Which path is chosen mainly depends on ligand and protein concentration [17]. 

Approaches for fully flexible docking either follow a conformational selection or an induced fit concept (Figure 8.3). Ensemble docking implements the principle of conformational selection and relies on the protein structural change occurring before the ligand binds to the protein. The ensemble of input protein conformations... 

Among the ion-binding behavior mechanisms, cation-71 interaction is an important kind of driving force in molecular recognition. Even here, the induced-fit concept is reportedly an important mechanism for understanding the structures of cation-7i complexes. Yoshida et al. ... 

It was demonstrated that the induced-fit concept of the interaction between an enzyme and a substrate was introduced from biological processes to supramolecular systems for explaining the molecular-binding behavior of artificial receptors, including crown ethers, cyclodextrins. calixarenes, porphyrins, etc. The induced-fit mechanism was utilized to explore the binding behavior of ions and molecules, and was adopted to accurately describe... 

In certain cases, a values of 30 or more have been found, which then correspond to A(AG) values in the range of 2 kcal/mol (8.4 kJ/mol). Generally, such values are obtained owing to very low retention of the first enantiomer eluted. This means that a very enantioselective sorption process is operating in the column, i.e., one of the enantiomers is virtually unbound by the CSP for steric reasons. Such phenomena are not easily explained by the three-point interaction model, but rather indicate the operation of a sort of chiral steric exclusion mechanism, more in line with a steric fit concept involving only one binding interaction. ... 

Coordination chemistry complex stability. The sizes of the hydrophilic cavities of the macrocyclic poly ethers (13) can be compared with the radii of unsolvated ions of alkali metal ions (1,4) (Table 2.1). The predicted Optimal Spatial Fit Concept (circular recognition) between 12-crown-4 (3) and Li" ", 15-crown-5 (16) and Na", 18-crown-6 (15) and is confirmed by experimentally determined thermodynamic stability constants (15) (iCJ, i.e. the better the fit of the guest cation into the cavity of the host the larger Kg. Figure 2.3 clearly demonstrates the relationship between cation radius/cavity radius size and the stability constant of the respective complexes (15). 

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