Molecular orbital related descriptors

Some of the earliest QSAR studies on CYPs were performed by Basak (257), Murray (258), and Marshall (205). Gao et al. (259) explored the influence of electronic parameters of CYP substrates in 1996. The findings of Basak that electronic terms would cancel out have been proven wrong by many research papers published in the following decades. Tyrakowska et al. (260) indicated via QSARs based on calculated molecular orbital descriptors that the cat (maximum velocity converted per nmol of P450 per min) for CYP catalyzed C4-hydroxylation rates of aniline derivatives of different species (rats, rabbit, mice, and human) are closely related to the highest occupied molecular orbital energy (EHOMo)> r - 0-97. Several reviews published by Lewis et al. (212,216,228,261-265) and Ekins (240) should also be mentioned. 

A physical model usually predisposes to physicochemical descriptors, such as p/Ca, log P or molar volume for the whole molecule, or the equivalent descriptors for substituents on a common molecular framework. But different structures can have the same or similar property values, and we are interested in designing structures. So at some stage we must choose structural descriptors (atom types, substructural fragments, connections, or indices from molecular orbital calculations) or at least relate structure to property in order to design the appropriate structure. 

Gombar, V.K. and Enslein, K. (1990). Quantitative Structure-Activity Relationship (QSAR) Studies Using Electronic Descriptors Calculated from Topological and Molecular Orbital (MO) Methods. Quant.Struct.-Act.Relat, 9, 321-325. 

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. 

Some molecular descriptors related to the charge density matrix have been proposed [Salem, 1966]. Bond index B,y was proposed to measure the multiplicity of bonds between two atoms [Wiberg, 1968]. It is defined between two atoms i and j as the square of the off-diagonal elements of the charge density matrix between atomic orbitals p on the fth atom and v on the j th atom, summed over all such distinct orbitals ... 

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