Intermolecular reactivity descriptors

The Fukui function (f(r)) makes an assessment of the tendency towards reactivity of the different local sites of the same molecule and thus serves as an intramolecular reactivity descriptor. The local sofmess (5(r)), on the other hand, compares and correlates the propensity of a pair of interacting molecular neighbors during chemical response and unlike /(r) serves as an intermolecular reactivity descriptor. 

Roy RK, Krishnamurti S, Geerlings P, Pal S (1998) Local softness and hardness based reactivity descriptors for predicting intra- and intermolecular reactivity sequences carbonyl compounds. J Phys Chem A 102(21) 3746-3755... 

Apart from reflecting directly the reactivity between receptor and pharmacological agent, the MO-related descriptors may be related to the intermolecular donor-acceptor interactions responsible for bioavailability of compounds. Once again, the search for analogous correlations for the properties like solubility or distribution coefficients could be useful for determining the mechanism of biological action. 

It can thus be concluded that the differences in the co-crystallisation behaviour of the four steroids are caused by specific intermolecular interactions between the steroid ot-face and aromatic rings. The discrepancy between the observed reactivity and expectations based on molecular descriptors led to the identification of this new mode of molecular recognition. 

While descriptors related to intermolecular interactions are useful for predicting bulk physical properties and certain types of biological activities, they provide little direct information about the reactivities of compounds. This type of information, however, is available through molecular orbital (MO) calculations. The Hiickel molecular orbital (HMO) method haS provided a number of so-called reactivity indices, although any MO technique could be used to calculate these descriptors. 

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