Theoretical descriptors

Wilson, L. Y., Famini, G. R. Using theoretical descriptors in quantitative structure-activity relationships some... 

Haeberlein, M., Brinck, T. Prediction of water-octanol partition coefficients using theoretical descriptors derived from the molecular surface area and the electrostatic potential. J. Chem. Soc. 

The relationship between the herbicidal activity of 1,2,5-oxadiazole iV-oxides and some physicochemical properties potentially related to this bioactivity, such as polarity, molecular volume, proton acceptor ability, lipophilicity, and reduction potential, were studied. The semi-empirical MO method AMI was used to calculate theoretical descriptors such as dipolar moment, molecular volume, Mulliken s charge, and the octanol/water partition coefficients (log Po/w) <2005MOL1197>. 

Randic, M. Graph theoretical descriptors of two-dimensional chirality with possible extension to three-dimensional chirality. J. Chem. Inf. Comput. Sci. 2001, 41, 639-649. 

De Benedetti, P.G., Menziani, M.C., Cocchi, M. and Fanelli, F. (1995) Prototropic molecular forms and theoretical descriptors in QSAR analysis. Journal of Molecular Structure (Theochemj, 333, 1—17. 

M., Fanelli, F. and De Benedetti, P.G. (1992) Molecular modeling and quantitative structure-activity relationship analysis using theoretical descriptors of 1,4-benzodioxan (WB-4101) related compounds al-adrenergic antagonists. Journal of Molecular Structure (Theochem), 276, 327-340. 

Menziani, M.C., De Benedetti, P.G. and Karelson, M. (1998) Theoretical descriptors in quantitative structure-affinity and selectivity relationship study of potent N4-substituted arylpiperazine... 

Besides the counts of fragments or atom types, a lot of theoretical descriptors have been successfully applied in predicting aqueous solubility. Mitchell and Jurs... 

MS-WHIM, new 3D theoretical descriptors derived from molecular surface properties a comparative 3D QSAR study in a series of steroids../. Comput. 

Local (Atomic) and Global (Molecular) Graph-Theoretical Descriptors ... 

Qraph-Theoretical Indices - Boiling Point Relationships Randic et al. [25] have compared several graph-theoretical descriptors and their use in correlation with boiling points of alkanes [25]. Schultz and Schultz [26] reported the following correlation for alkanes (C2-C15) ... 

Famini, G.R., Using Theoretical Descriptors in Quantitative Structure Activity Relationships and Linear Free Energy Relationships, 2003. http //www.NETSCI.ORG/ Science / Compchem / feature08.html. 

Famini, G.R. and Wilson, L.Y. (1999) Using theoretical descriptors in linear free energy relationships characterizing several polarity, acid and basicity scales./. Phys. Org. Chem., 12, 645. 

PapaE, VillaF, GramaticaP (2005) Statistically validated QSARs, based on theoretical descriptors, for modeling aquatic toxicity of organic chemicals in Pimephales promelas (fathead... 

The primary supposition of any toxicological QSAR is that the potency of a compound is dependent upon its molecular structure, which is typically quantified by chemical properties (Schultz et al., 2002). Chemical descriptors include a variety of types, including atom, substituent, and molecular parameters. The most transparent of these are the molecular-based empirical and quantum chemical descriptors. Empirical descriptors are measured descriptors and include physicochemical properties such as hydrophobicity (Dearden, 1990). Quantum chemical properties are theoretical descriptors and include charge and energy values (Karelson et al., 1996). Physicochemical and quantum chemical descriptors are for the most part easily interpretable with regard to how that property may be related to toxicity. The classic example of this, the partitioning of a toxicant between aqueous and lipid phases, has been used as a measure of hydrophobicity for over a century (Livingstone, 2000). 

A subtle distinction can be made between QSARs and the PMs associated with physicochemical tests. The distinction is that while any PM (associated with a physicochemical test) could also be called a QSAR, not all QSARs could also be called PMs. For example, QSARs can also be based on theoretical descriptors (e.g., topological indices) or on experimental properties that are themselves more easily predicted than measured (e.g., the octanol-water partition coefficient). Furthermore, QSARs developed for the prediction of physicochemical and in vitro end points would not be regarded as PMs. 

However, before progressing further, it is important to note that the prefixes cis vs. trans are metric vs. graph theoretic descriptors... 

Identification of Groupings of Graph Theoretical Descriptors Using a Hybrid Cluster Analysis Approach. 

Correlation analysis can employ empirical (experimental) descriptors or theoretical descriptors or both. As introduced earlier, theoretical (computational) descriptors offer several advantages over empirical ones. They are... 

Although the Abraham LSER parameter set produces good correlations for many properties, two questions arise. First, what about compounds for which these empirical parameters have not yet been obtained Second, can a theoretical, structurally based molecular parameter set be calculated that might model the empirical parameters and/or produce good quality correlation equations The first question can be answered by noting that already there are methods " for estimating empirical parameter values of new functional groups and elements. Flowever, theoretical descriptors would be more convenient. The answer to the second question is affirmative indeed, it is the reason for this chapter. 

Nonmodel-based methods use large sets of descriptors and, often, complex methods for regression analysis. The equations from regression analysis have been labeled by Bakken and Jurs as type 1 equations.The equations are similar in form to those used with small descriptor sets. Type 1 equations rely on QM and other theoretical descriptors. 

Octanol Partition Coefficients Using Theoretical Descriptors Derived from Molecular Surface Area and the Electrostatic Potential. 

By a quantitative structure-property relationship (QSPR) analysis of a total of 45 different empirical solvent scales and 350 solvents, the direct calculation of predicted values of solvent parameters for any scale and for any previously unmeasured solvent was possible using the CODESS A program [ie. comprehensive descriptors for structural and statistical analysis) developed by Katritzky et al. [244]. The QSPR models for each of the solvent scales were constructed using only theoretical descriptors, derived solely from the molecular solvent structure. This QSPR study enabled classification of the various solvent polarity scales and ultimately allowed a unified PCA treatment of these scales. This PCA treatment, carried out with 40 solvent scales as variables (each having 40 data points for 40 solvents as objects), allowed a rational classification and grouping... 

In addition to the physicochemical domain, the topological features of selected HIV-1 RT inhibitors, 2-(2,6-dihalophenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones (Fig. 26, Table 16), have been analyzed [182] with the empirical, constitutional, and graph theoretical descriptors from the DRAGON software package [47]. This study has resulted in the identification of several influential descriptors to model the inhibitory activity and the equations shown below represent some models stemming from these descriptors. 

Constructs are generated from theoretical descriptors representing a certain medium. The correlation function for a Debye random medium [8] is... 

Fig. 3 shows the theoretical descriptors S2(r) and p(r) and their recalculations from construct B depicted in Fig. 1. RES A shows high angularity, and the deviation of the computed and the theoretical p(r) at low r reflects the difficulty of constructing the shape of contacting and sUghtly penetrating spheres precisely. However, the principal character of the morphology is recovered. A complete agreement between target and spatial reconstruction was observed at no time [29,30,34,35]. The construction was fairly successful with respect to the geometrical parameters, as the comparison of the data in the third row in Table 1 with the theoretical data in the first row shows.

Mathematics and statistics, graph theory, computational chemistry and molecular modelling techniques enable the definition of a large number of theoretical descriptors characterizing physico-chemical and biological properties, reactivity, shape, steric hindrance, etc. of the whole molecule, molecular fragments and substituents. 

The fundamental difference between theoretical descriptors and experimentally measured ones is that theoretical descriptors contain no statistical error due to experimental noise, which is not the case for experimental measurements. 

However, the assumptions needed to facilitate calculation and numerical approximation are themselves associated with an inherent error, although in most cases the direction, but not the magnitude, of the error is known. Moreover, within a series of related compounds the error term is usually considered to be approximately constant. All kinds of error are absent only for the most simple theoretical descriptors such as count descriptors or for descriptors directly derived from exact mathematical theories such as graph invariants. 

Theoretical descriptors derived from physical and physico-chemical theories show some natural overlap with experimental measurements. Several quantum-chemical descriptors, surface areas and -> volume descriptors are examples of such descriptors also having an experimental counterpart. 

With respect to the experimental measurements, the greatest recognized advantages of the theoretical descriptors are usually (but not always) in terms of cost, time and availability. 

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