Steric matching

The X-ray crystallographic analysis of the unsymmetrical BisP shows a strong distortion of the five-membered chelation ring as compared to that of symmetric BisP [32]. The large difference in the steric repulsions between the bulky substituent borne on one phosphorus atom and the neighboring atoms on the one hand and the other (different) bulky substituent borne on the other phosphorus atom and the same neighboring atoms on the other hand is believed to be responsible for better steric matching with some substrates. 

Kinetic analysis revealed that this reaction is pseudo-first order in dienophile at low conversions (200). At higher conversions, the rate deviates from a linear relationship, suggestive of product inhibition. Indeed, addition of product to the reaction at the start resulted in a decrease in rate by 18%. A number of competitive inhibitors were identified in this study. Particularly interesting was the observation that the matched chiral dienophile product was less effective as an inhibitor than the mismatched product. The authors suggest that the sterically matched complex (where the ligand bulk and imide chirality is on the same side of the complex) is thermodynamically less stable than the mismatched complex. 

Scheme 4.13 Self-sorting within amphiphilic peptides driven by steric matching and electrostatic effects.

Schnarr, N. A. Kennan, A. J. Peptide tic-tac-toe Heterotrimeric coiled-coil specificity from steric matching of multiple hydrophobic side chains. J. Am. 

III. THE IMPORTANCE OE THE ELECTROSTATIC AND STERIC MATCH BETWEEN DRUG AND RECEPTOR... 

III. The Importance of the Electrostatic and Steric Match Between Drug and Receptor... 

What determines Basically, it depends on two factors. One is the electrostatic match between drug and receptor, which is primarily a function of electron density. The other is the steric match between drug and receptor, which is... 

Dispersion or London forces are the universal forces responsible for attractive interactions between nonpolar molecules. Their occurrence is due to the fact that any atom will, at any given instant, be likely to possess a finite dipole moment as a result of the movement of electrons around the nuclei. Such fluctuating dipoles tend to induce opposite dipoles in adjacent molecules, thus resulting in a net attractive force. Although the individual interactions between pairs of atoms are relatively weak, the total contribution to binding from dispersion forces can be very significant if there is a close fit between drug and receptor. The quality of the steric match is thus the dominant factor in nonpolar interactions. 

As for van der Waals forces, hydrophobic interactions are individually weak (0.1 to 0.2 kJ moF for every square angstrom of solvent-accessible hydrocarbon surface ), but the total contribution of hydrophobic bonds to drug-receptor interactions is substantial. Similarly, the overall strength of the hydrophobic interaction between two molecules is very dependent on the quality of the steric match between the two molecules. If this is not sufficiently close to squeeze all of the solvent from the interface, a substantial entropy penalty must be paid for each of the trapped water molecules. 

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