Molecular mechanics and molecular shape. Part 4. Size, shape, and steric parameters

Abstract

To deal with steric effects of substituents on reaction rates, t w o types of descriptor are proposed. Shape is characterised by the ratio (G) of the substituent's surface area to its volume. Bulk is characterised by the volume ( V a ) of the portion of the substituent that is within 0.3 nm of the reaction centre. For alkyl substituents, rate constants for several series of reactions (including the classical series, acid hydrolysis of the esters RC0,Et) correlate fairly well with Va and G. Taft's steric parameters (E,) correlate less well.Values of €s for hetero-substituents are found to be contaminated by non-steric factors. It is possible to construe whether the contaminant acts to hinder or t o enhance reaction.

Re-examination of Steric Substituent Constants by Molecular Mechanics

“…As pointed out in relation to our Ω s , the logarithm of the solid angle of the space open to the access of reagent should be a best steric constant in LFER. From this point of view, log 10 (4π−S') should be as good a steric constant as our log 10 (1 −Ω s ). As given in the last row of Table 3, it is very closely correlated with our isotropic Ω s…”

“…Geometrical parameter S (or S') [10] which was defined on the basis of the solid angle (in steradian)…”

“…If we assume that a light source is placed at the reaction-center-atom (X) and if the shadow of the substituent group (R) is projected on the surrounding sphere (its radius R s = 0.4nm), the proportion of the shadow area can be a measure of the steric hindrance effect caused by R. As easily understood from the definition of Ω s , (1 − Ω s ) should be proportional to the frequency factor of the Arrhenius equation and, hence, log 10 (1 − Ω s ) should be used in the LFER equations. As a complex substituent group has more than one unequal conformer, Ω s was defined as the population-weighted sum of normalized solid angles of shadow area over these conformers.…”

“…Meyer [10] assumed that the steric effect can be evaluated by the combination of shape descriptor G and bulkiness descriptor V a both estimated on the basis of van der Waals molecules. G is calculated as the ratio of surface area of substituent to its volume, and V a is the volume of substituent within 0.3 nm from the reaction center.…”

Investigation of Novel Cinchona Alkaloid-based Zwitterionic Chiral Stationary Phases in Cation- and Zwitterion-Exchange Modes

“…Meyer, the steric effect of a substituent on the reaction rate is characterized by the size-descriptor V a [94] . The data in Figure 20.…”