Steric fits

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

The theory of hydrophobic interaction [70-72] indicates that hydrophobic residues tend to associate with one another so as to minimize the surface area exposed to the aqueous phase and thereby to release a maximum number of structured water molecules. Therefore, the steric fit between the hydrophobic groups may be an important factor for the hydrophobic association. It is reasonable to consider that aromatic hydrophobic groups may undergo tighter hydrophobic self-association because planar aromatic rings would sterically fit with each other to favor the release of structured water. 

Cavity Shapes Steric Fit of Host-Guest Compounds.103... 

Fig. 32. Packing relations and steric fit of the 26 acetic acid (1 1) clathrate (isomorphous with the corresponding propionic acid clathrate of 26)1U- (a) Stereoscopic packing illustration acetic acid (shown in stick style) forms dimers in the tunnel running along the c crystal axis of the 26 host matrix (space filling representation, O atoms shaded), (b) Electron density contours in the plane of the acetic acid dimer sa First contour (solid line) is at 0.4 eA" while subsequent ones are with arbitrary spacings of either 0.5 and 1 eA 3. Density of the enclosing walls comes from C and H atoms of host molecules.

A further example of the steric fit and thus the conditions of the second rank interactions between host and guest is illustrated by the channel structure of the acid inclusions of 26 (see inclusion compound with acetic acid, Fig. 32a). The tunnel has a mostly hydrophobic character being made up mainly from the aromatic portions of the roof-shaped host molecule. We must note that this arrangement applies possibly for the acetic acid clathrate of 1 as well. 

A theoretical analysis is presented for the binding of the four dia-stereoisomers of benzo[a]pyrene diol epoxides (BPDEs) to N2(g), N6(a), 06(G) and NU(c). Molecular models for binding and stereoselectivity involving intercalation, intercalative covalently and externally bound forms are presented. Molecular mechanics calculations provide the energetics which suggest possible structures for the formation of each of the principal DNA-BPDE complexes. Stereographic projections are used to illustrate the molecular structures and steric fits. The results of previous calculations on intercalation and adduct formation of BPDE l(+) in kinked DNA (37) are summarized and extended to include the four diastereoisomers l( ) and II( ). The theoretical model is consistent with the observed experimental data. 

One could plunge into the steric problems posed by the mechanism of protein synthesis on the ribosome 25 26)> or consider the steric fit of the hormone insulin to its acceptor in the cell membrane 27>. Or one could delve into the beautiful intricacy of terpenoid, squalene and steroid metabolism, or get lost in double bond formation, or in the steric problems posed by the branched chain fatty acids and their derivatives 28-34). 

One of the groups of theories about the origin of the genetic code states that the code has to be the way it is, and is therefore universal, for stereochemical" reasons. In other words, phenylalanine, f. ex. must be represented by the triplets UUU and UUC because phenylalanine is somehow stereochemically related to these two codons 52,53,56,57) This seems likely, since steric fit is an essential property of the processes of replication, transcription and translation. That doesn t mean that one has conclusive evidence for such a statement. It only means that the theoreticians are groping in such a direction. 

The stereospecificity of hydrogen transfer for estradiol-17 and estradiol-17(3 dehydrogenases has been examined by George et a/.84>. These enzymes are both present in chicken liver, and have substrates which differ only in the chirality of their substituents at C—17. Both of these enzymes were shown to use the 4-pro-S or 4B proton of the NADPH. Since the steroid is a bulky substrate, the authors argue that the steric fit between pyridine nucleotide and steroid cannot be as important as the role played by the enzyme in directing the fit. This paper contains an interesting summary of other recent work on the stereospecificity of pyridine nucleotide dependent-steroid dehydrogenases. 

It will be seen below that various types of information may be stored in a molecule thus, complementarity amounts to a sort of generalized "lock and key relationship not limited to steric fit of L and S, but extending over other molecular features. 

A. Balaban, A. Chiriac, J. Motoc, Z. Simon (1980). Steric Fit in Quantitative Structure-Activity Relations. Berlin Springer. 

Although the idea of the steric fit of substrate to enzyme was a powerful one, in detail it presented some problems. One of these, the notion that the enzyme should fit the transition state better than it fits the substrate, has already been mentioned. The most severe of the problems, however, was illustrated with the chemistry of phosphorylase. Why was the enzyme specific for the transfer of glucose from glycogen Why did it not catalyze the... 

Balaban, A. T. et al. Steric Fit in QSAR, Lecture Notes in Chemistry vol. 15, Springer, Berlin 1980... 

The wider the substituents are in the direction B4, the lower the activity. The activity is also related parabolically to the substituent length. The steric fit with the target site is thus supposed to be critical for activity. The compounds such as m-F,... 

The optimum B4 value for N4-substituents, 4.5 A coincides very well not only with that for N substituents of adenylate cytokinins, 5.2 A, shown in the previous section, but also with the value of 4.7 A observed for another class of compounds, N4-substituted 4-amino-2-methylpyrrolo[2,3-d]pyrimidines (24)47) which show either cytokinin or anticytokinin activity depending upon the structure of N4-substituents. These results in combination may help to think of the size of structure which should sterically fit well the cytokinin receptor cavity. 

Adsorption chromatography is a powerful means of separating cis and trans isomers of unsaturated compounds, the separation mechanism being attributed to a steric fitting of solute molecules with the discrete adsorption sites. This is illustrated in the isocratic separation of six geometric isomers of vitamin A obtained by photolysis of all-fran.v-retinol (109). 

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