Electronic descriptor

The use of a Hammett substituent constants in QSAR analyses has been prominent since the early studies by Hansch and Fujita (1964) in medicinal chemistry. The electron-withdrawing/releasing potency of substituents on an aromatic system has been formalized by the Hammett equation (Hammett, 1940). The relative reactivities among homologous series of compounds under defined conditions - for example, the logarithms of the rate and equilibrium constants for the hydrolysis of substituted benzoic acid esters (rate constant k) and the ionization constants (K) of the corresponding acids, were found to be linearly related  

The index x denotes the respective substituent in the m- or p-position of the benzene ring p and c represent the slope and the intercept of the function, respectively. Subtracting the analogous equation for the non-substituted ester and the corresponding acid with x = hydrogen (h) yields 

For the purpose of characterizing chemicals for designing and selecting training sets for QSAR analyses, a values can be retrieved from tabulations (e.g. Perrin, Dempsey and Serjeant, 1981 Hansch, Leo and Taft, 1991). If several substituents are present on a parent structure, the sum of the corresponding cr values is used. Especially for c -substituents, specific (rvalues for the given chemical class have to be used. 

The second application of a values for QS ARs in environmental sciences is for the estimation of values. In contrast to the substituent constants, the latter represent properties of the entire molecules and are used to quantify the degree of dissociation at a given (e.g. ambient) pH. In this way, like log values may appear in two ways as an endpoint by itself in hazard-assessment schemes and as a chemical descriptor to account for environmental conditions affecting chemical properties. For a large number of chemicals, values are available in the literature and may also be retrieved from databases. If such are not available and experimental determinations are not feasible, estimates may be obtained from a compound class-specific Hammett equation for aromatic substances or a Taft equation for aliphatic acids  

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Reactions belonging to the same reaction type are projected into coherent areas on the Kohonen map this shows that the assignment of reaction types by a chemist is also perceived by the Kohonen network on the basis of the electronic descriptors. This attests to the power of this approach. 

Several research groups have built models using theoretical desaiptors calculated only from the molecular structure. This approach has been proven to be particularly successful for the prediction of solubility without the need for descriptors of experimental data. Thus, it is also suitable for virtual data screening and library design. The descriptors include 2D (two-dimensional, or topological) descriptors, and 3D (three-dimensional, or geometric) descriptors, as well as electronic descriptors. 

A classical Hansch approach and an artificial neural networks approach were applied to a training set of 32 substituted phenylpiperazines characterized by their affinity for the 5-HTiA-R and the generic arAR [91]. The study was aimed at evaluating the structural requirements for the 5-HTiA/ai selectivity. Each chemical structure was described by six physicochemical parameters and three indicator variables. As electronic descriptors, the field and resonance constants of Swain and Lupton were used. Furthermore, the vdW volumes were employed as steric parameters. The hydrophobic effects exerted by the ortho- and meta-substituents were measured by using the Hansch 7t-ortho and n-meta constants [91]. The resulting models provided a significant correlation of electronic, steric and hydro-phobic parameters with the biological affinities. Moreover, it was inferred that the... 

Electronic descriptors were calculated for the ab initio optimized (RHG/STO-3G) structures. In addition, logP as a measure of hydrophobicity and different topological indices were also calculated as additional descriptors. A nonlinear model was constructed using ANN with back propagation. Genetic algorithm (GA) was used as a feature selection method. The best ANN model was utilized to predict the log BB of 23 external molecules. The RMSE of the test set was only... 

There are also various hybrid descriptors. For example, elec-trotopological descriptors are a hybrid of topological and electronic descriptors. 

Recent progress in computational hardware and the development of efficient algorithms have assisted the routine development of molecular quantum-mechanical calculations. New semiempirical methods calculate realistic quantum-chemical molecular quantities in a relatively short computational time frame. Quantum-chemical calculations are thus an attractive source for molecular descriptors that can express all of the electronic and geometric properties of molecules and their interactions. Quantum-chemical methods can be applied to QSARs by direct derivation of electronic descriptors from the molecular wave function. 

Molecular polarity-related (electronic) descriptors Dipole moments... 

These are - electronic descriptors defined in terms of atomic charges and used to describe electronic aspects both of the whole molecule and of particular regions, such as atoms, bonds, and molecular fragments. Charge descriptors are ealculated by - computational chemistry and therefore can be considered among - quantum-chemical descriptors [Lowe, 1978 Streitweiser, 1961],... 

An electronic descriptor defined as the maximum excess charge differenee for a pair of atoms in the moleeule [Kaliszan et al., 1985 Osmialowski et al., 1985], i.e. caleulated from the difference between the atomic maximum positive eharge Qmax and the atom-ie maximum negative charge Qmax in a molecule ... 

A molecular electronic descriptor defined as [Katritzky et al., 1996b] ... 

Local or global molecular descriptors related to the electronic distribution in the molecule they are fundamental to many chemical reactions, physico-chemical properties, and ligand-macromolecule interactions. The theory of electronic density is based on a quantum-mechanical approach however, - electronegativity and charges, which are not physical observables, are also important quantities for the definition of several electronic descriptors. 

Many quantum-chemical descriptors are derived from the charge distribution in a molecule or the electron density of specified atoms or molecular regions, and from conformational energy values such as the Joshi electronic descriptors. Moreover, several -> charge descriptors and -> electric polarization descriptors are obtained from atomic charge estimations. 

Electronic information is combined with shape and steric information to characterize molecules in - charged partial surface area descriptors. Other approaches, different from those closely related to quantum-chemistry, refer to electronic descriptors, such as - electronic substituent constants, - electrotopological state indices, -> topological charge indices. - Reactivity indices and - resonance indices are also related to electronic descriptors. 

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