Average Local Ionization Energies of Molecules

Since the positions of the Is,min are the locations, on the average, of the most easily removed electrons, these should also be the sites that are most reactive toward electrophilic attack. This has been fully confirmed for a group of monosubstituted benzene derivatives [10,21]. The Is,min correctly predict the ortho/para- or meta- directing tendencies of the substituents, even the rather unusual NH3+, which is a metal para director [22]. Furthermore, the magnitudes of the Is,min relative to that of unsubstituted benzene correctly indicate whether each substituent activates or deactivates the aromatic ring toward electrophiles. These analyses have been extended to other aromatic systems, including azines and azine N-oxides [18,23,24]. 

The demonstrated effectiveness of Is,min in relation to interactions with electrophiles encouraged us to investigate whether it may correlate with pKa, since H+ is certainly an electrophile. A possible complication is that pKa refers to aqueous solution, and our calculations are for single molecules, taking no explicit account of solvent effects. Our approach was to seek 

A property that has long been used for interpreting and predicting molecular reactivity [38-40] is the electrostatic potential V(r) that is created in the space around a molecule by its nuclei and electrons. V(r) is given rigorously by eq. (6), 

These observations emphasize what we feel is a key difference between the roles of Vs,min (or Vmin) and Is,min- The former reflects electrostatic factors, whereas the latter is related to charge transfer and polarization. Thus hydrogen bonding, a non-covalent interaction, is described well in terms of the electrostatic potential [19,27,46], while pKa, which involves charge transfer, requires Is,min- The two properties complement each other Vs,min determines the initial approach of the electrophile and Is,min its subsequent charge-sharing interaction, if any. 

Our present view is that the interaction with H , and presumably other electrophiles as well, may involve two phases the initial attraction that brings the H into the vicinity of the molecule or anion, and possibly (but not necessarily) some subsequent degree of charge transfer or polarization. The first step is determined by Vs,min °r Vmin, the second (to whatever extent it occurs) by Is,min- In general, therefore, Vs,min (or Vmin) and s,min play complementary roles in some cases, however, one or the other may be a greatly dominating factor and may suffice for a quantitative representation of the interaction. 

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