Taft's E, parameter ie employed to correlate structure-activity relationships in phenoxyethylcyclopropylamine monoamine oxidase inhibitors and diphenhydramine antihistamines. New E, values for the halogens and certain other functions have been calculated from van der Waals radii using an extension of the approach suggested by Charton.The usefulness3 of thermodynamically derived substituent constants for computer-based assaults on biochemical structure-activity problems continues to receive more at'tent'ion. While considerable experience has accrued in t'he use of Hammett, consta'nts ( u , u-, u+) from homogeneous organic reaction^,^^^ the use of hydrophobic parameters (log P , 7 r ) 3 , 6~7 has been less thoroughly studied. Still less underst'ood are paramet,ers for steric effects. Taft's E, parameter4 and t,he modified form, E,", suggested by Hancock, et a1.,8 although not extensively studied in homogeneous organic reactions, are beginning t.0 prove of useg in biochemical systems quite different from that in which t'hey were derived. How far E, corist,ant,s and other st'eric parameters such as Exner's molar volume values (JIV) may be of use in medicinal chemical studies remains to be seen. Our initial successesg with E, have prompted this further study. E, constants have been defined by Taft, using the hydrolysis of aliphatic esters as the model reaction or the hydrolysis of ortho-substitut'ed benzoic esters (ESo) for ortho substituents in aromatic systems. The two groups have been related through the methyl group of value 0.00.Recently, Chartonlo has reexamined E, and shown that Taft's observat,ion t,hat, E, parallels group radii can be expressed in quantitative terms. Charton pointed out that for a symmetrical top-t,ype function such as CF3, one can use either a maximum (r,(max)) or a minimum (rv(min)) van der Waals radius to estimate the st'eric action of the F atoms on neighboring atoms.The value of r,(min) refers to the junction point of the two F atoms. In his correlations he used y,(min). We have used an average (r,(av)) of the two values given by Chartonlo to calculate E
