Microscopic Medium Effects and Deviant Points

Free energy correlations often exhibit scatter plots where the deviations from a linear regression fall outside experimental error. These deviations may be attributable to differences in microscopic environment between the standard equilibrium and the reaction being studied and are called microscopic medium effects. 

The reaction of 3- and 4-substituted pyridines with an V-phosphoryl-isoquinolinium ion (isq-POj , Equation 22) is a good example of the influence of such microscopic medium effects. 

The cause of the scatter is the non-systematic influence of the substituent on the microscopic environment of the transition structure. The linear free energy relationship between product state XpyH (Equation 22) and the transition structure (Xpy. .. PO32 . . . isq) will be modulated by second-order non-systematic variation because the microscopic environment of the reaction centre in the standard (XpyH ) differs slightly from that (Xpy-PO ) in the reaction under investigation giving rise to specific substituent effects. These effects are mostly small. An unusually dramatic intervention of the microscopic medium effect may be found in Myron Bender s extremely scattered Hammett dependence of the reaction of cyclodextrins with substituted phenyl acetates.22 The cyclodextrin reagent complexes the substrate and interacts 

Microscopic medium effects are usually regarded as small and the question of which data points to include in the linear correlation is best dealt with by inspection. The minimum deviation between observed and predicted rate constants is generally accepted to be between one and two orders of magnitude if a different mechanism is to be assigned. 

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