Molecular descriptors, used

Based on the experience with tertiary phosphines, the importance of the steric properties of NHC hgands in determining chemical behaviour has been immediately recognised. The main practical problem, however, is that NHC hgands substantiaUy present a local symmetry axis, whereas phosphines present a local symmetry axis. This imphes that the well-accepted molecular descriptor used to quantify steric properties in phosphines, the Tohnan cone angle [78], cannot be applied to NHC ligands. 

The molecular descriptors used for KoW, solubility in water and vapor pressure can potentially be applied to KoA. 

What are common molecular descriptors used to correlate rates of oxidative or reductive transformations of structurally related compounds ... 

The octanol/water coefficient (log P) is the standard molecular descriptor used to provide the chemical property of the hydrophobicity of a molecule. Compounds with high partition coefficients usually have very low aqueous solubility. This will decrease the chance of attack by hydroxyl radicals and lead to a lower rate constant. Nevertheless, the linear relationships with log P do not reproduce similar trends of several chemical classes such as alkane and phenol. They could be either positive or negative linear relationships. Alkene (R2 < 0.67), benzene (R2 < 0.78), carboxylic acid (R2 < 0.74), and halide (R2 < 0.55) classes do not provide significant correlations. 

Gini, G., Lorenzini, M., Benfenati, E., Grasso, P., and Bruschi, M., Predictive carcinogenicity a model for aromatic compounds, with nitrogen-containing substituents, based on molecular descriptors using artificial neural network, J. Chem. Inf. Comput. Sci., 39, 1076-1080, 1999. 

On the basis of the origin of molecular descriptors used in calculations, QSAR methods can be divided into three groups. One group is based on a relatively small number (usually many times smaller than the number of compounds in a data set) of physicochemical properties and parameters describing,for example, hydrophobic, steric, and electrostatic effects. Usually, these descriptors are used as independent variables in multiple regression approaches (18) Jn the literature, these methods are typically referred to as Hansch analysis (8).These types of descriptors and corresponding linear optimization methods used in traditional QSAR analyses are discussed extensively in the chapter by Celassie (7) and therefore is not reviewed here. 

Figure 10 Theoretical (a) and practical (b) representation of QSARs. Panel b describes a QSAR for the methanotrophic oxidation (activity of methane monooxygenase) of 6>r /i6>(Ci2)-substituted biphenyls. The structural backbone was biphenyl, and the substituents considered included all halogens, methyl-, methoxy-, hydroxyl-, nitro-, and amino-moieties (Lindner et al, 2003). The molecular descriptors used in (b) are (charge on the ortho-csubon), (Taft s steric parameter), and log ow...

It should be noted that some invariance properties such as invariance to atom numbering and roto-translations are mandatory for molecular descriptors used in QSAR/ QSPR modelling in several cases, chemical invariance is required, particularly when dealing with a series of compounds with different substituents moreover, conformational invariance is closely dependent on the considered problem. 

Dimov, N., Osman, A., Mekenyan, O. and Papazova, D. (1994). Selection of Molecular Descriptors Used in Quantitative Structure Gas Chromatographic Retention Relationships. 1. Application to Alkylbenzenes and Naphthalenes. Anal.Chim.Acta, 298,303-317. 

Joshi, R.K., Meister, Th., Scapozza, L. and Ha, T.-K. (1993). Development of New Molecular Descriptors Using Conformational Energies from Quantum Calculations and Their Application in QSAR Analysis. In Trends in QSAR and Molecular Modelling 92 (Wermuth, C.G., ed.), ESCQM, Leiden (The Netherlands), pp. 362-363. 

DT Does not make any assumption of the type of relationship between target property and molecular descriptors Models are easy to interpret Fast classification speed Multi-class classification May have over fitting when training set is small and number of molecular descriptors is large Ranks molecular descriptors using information gain which may not be the best for some problems... 

Figure 23.2 Molecular descriptors used in environmental QSAR.

Examples of count descriptors are reported by Feher and Schmidt [Feher and Schmidt, 2003]. Moreover, count descriptors are usually the basic molecular descriptors used to generate property filters. Examples of count descriptors used for property filters are those proposed by [Zheng, Luo et al., 2005] which are listed in Table C8. 

PASS was trained on more than 30000 compounds that reveal more than 500 kinds of different biological activities. The molecular descriptors used by PASS are MNA descriptors. 

There is a large variety of molecular descriptors used to address drug-likeness they range from constitutional and counting descriptors to topological descriptors, from physico-chemical properties to pharmacophore description, from thermodynamic considerations to the synthetic accessibility, from presence of functional groups to ADME/Tox properties. 

Failure of the congenericity principle has been recognized as one of the major problems for producing reliable QSAR models, unless the presence of the so-called activity cliffs is accounted for. The activity cliff was defined as the ratio of the difference in activity of two compounds to their distance in a given chemical space [Maggiora, 2006]. Activity cliffs arise when very similar compounds, whose similarity is measured by the set of molecular descriptors used to define the chemical space, possess very different activities. The presence of activity difFs leads to some important implications for QSAR modeling ... 

Any set of molecular descriptors used to represent molecules in a fixed and ordered sequence was called basis of descriptors [Randic, 1992c Randic and Trinaj Stic, 1993a Baskin, Skvortsova et al., 1995]. Abasis of descriptors can be defined (a) selecting a class of homogeneous naturally ordered descriptors ( path counts, connectivity indices, 3D-MoRSE descriptors, EVA descriptors, Burden eigenvalues, etc.) (b) by using a few ad hoc selected descriptors such as one —> lipophilicity descriptor, one steric descriptor and one —> electronic descriptor, as used in classical QSAR. 

Taraviras, S.L., Ivanciuc, O. and Cabrol-Bass, D. (2000) Identification of groupings of graph theoretical molecular descriptors using a hybrid cluster analysis approach. /. Chem. Inf. Comput. Sci., 40, 1128-1146. 

Quantitative structure-activity relationships QSAR. The QSAR approach pioneered by Hansch and co-workers relates biological data of congeneric structures to physical properties such as hydrophobicity, electronic, and steric effects using linear regression techniques to estimate the relative importance of each of those effects contributing to the biological effect. The molecular descriptors used can be 1-D or 3-D (3D-QSAR). A statistically sound QSAR regression equation can be used for lead optimization. 

A number of approaches to QSAR are based on the ideas of pattern recognition theories (PRT). Using PRT, some classification rules are worked out, by means of which the molecules under consideration are divided into the classes of active and inactive compounds. Most important in these PRT approaches are the methods for describing molecules. Indeed, the better the description of the molecule in terms of parameters that represent its activity, the better the pattern recognition and separation of molecules into active and inactive classes. Therefore the QSAR methods differ mainly in the molecular descriptors used. 

Figure 11. Several of the molecular descriptors used in a QSERR study of 1,4-benzodiazepine analogs on a human serum albumin-based HPLC chiral stationary phase.

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