Superdelocalizabilities nucleophilic

The drug designer must consider the susceptibility to, and consequences of, the principal Phase 1 metabolic reactions hydrolysis, reduction and oxidation. Susceptibility to oxidation can be calculated using semi-empirical molecular orbital theory. Ease of oxidation is reflected by the energy of the HOMO, and the probable site of oxidation can be predicted from calculation of the electrophilic superdelocalizability. Likewise, ease of reduction is related to LUMO energy, and probable site to nucleophilic superdelocalizability (Loew and Burt, 1990). 

QnH,L = electron density in the HOMO or LEMO, respectively, of atom N SN = total nucleophilic superdelocalizability... 

An electronic parameter that often correlates with metabolic rates is the electrophilic (or nucleophilic) superdelocalizability. This quantity is a reactivity index formulated by Fukui and colleagues as an orbital-weighted electron density.145 The total electrophilic superdelocalizability, 2SE, summed over all atoms in a molecule, exhibits a parallelism with the hydrophobic parameter, log P, in several series of compounds such as PAHs and aliphatic amines, where it is probably approximating molecular volume. 

If the transition states are mainly controlled by the frontier orbital, the nucleophilic superdelocalizability is calculated on the lowest unoccupied molecular orbital (LUMO). 

The maximum nucleophilic superdelocalizability among all the atoms in a molecule is a molecular descriptor defined as ... 

The total nucleophilic superdelocalizability is the sum over all of the atoms of the nucleophilic superdelocalizability, i.e. 

The average nucleophilic superdelocalizability is derived from the total nucleophilic superdelocalizability as ... 

A variety of molecular descriptors have been defined and used proceeding from frontier molecular orbital theory (FMO) of chemical reactivity [42]. This theory is based on the concept of the superdelocalizability, an index characterizing the affinity of occupied and unoccupied orbitals in chemical reactions. A distinction has been made between the electrophilic and the nucleophilic superdelocalizability (or acceptor and donor superdelocalizability), respectively. The former describes the interaction of... 

He also suggested the use of tt net charge, 7r-electrophilic and nucleophilic superdelocalizabilities, and energy level differences to interpret drug-receptor interactions. When this approach was applied to selected cholinesterase inhibitors, he obtained very good correlations... 

An example of a QSERR study is by Carotti [39]. It involves the resolution of sulfoxides, 20, on a it-acid CSP containing (S,S)-N,N -(3,5-dinitrobenzoyl)-frans-1,2-diaminocyclohexane (DACH-DNB), 19a. After establishing capacity factors, k s and k R for the first and second eluted enantiomers, respectively, as well as determining the separation factors, a, the authors began their computational studies. They used a variety of electronic descriptors for the analytes including electrophilic superdelocalizabilities (S omo) and nucleophilic superdelocalizabilities of various key analyte atoms... 

Using a more conventional interpretation of molecular properties as derived from quantum mechanical calculations, Reddy and Locke calculated log Poet for 90 herbicides. Their equation included terms for the van der Waals volume, dipole moment, superdelocalizability of the highest occupied molecular orbital (5homo). and nucleophilic superdelocalizability (5n). The regression equation had an SE of 0.705 and an of 0.67. 

Site-specific reactivity indices are arrived at by considering electronic information at specific locations in the molecule. The electrophilic and nucleophilic superdelocalizabilities at atom i are energy-weighted atomic electron densities. The electrophilic superdelocalizability roughly measures the availability of electrons at atom i nucleophilic superdelocalizability measures the availability of room on atom i for additional electron density. While these indices are atomic in nature, they may be classified as whole molecule descriptors if atom i is a fixed position in a series of congeners, or if the maximum superdelocalizability among all the atoms is chosen. 

Nucleophilic superdelocalizability CS - measure of electron-donating ability of atom r... 

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