Atom-based descriptors

There are several ways in which molecular descriptors can be classified. The majority of descriptors are atom-based rather than field-based. The bulk of this review is focused on a discussion of atom-based descriptors. As the name implies, atom-based descriptors are based on individual atoms, with the description extending outward to incorporate information about the atom s environment. The descriptors are typically generated by analysis of 2D or 3D connection tables, and can include ID, 2D, or 3D information about the molecule. Atom-based descriptors include individual atoms, feature counts, substructural fragments, topological indices, atomic properties, pharmacophores (see Chapters 17 and 18 of this book), and calculated physicochemical properties. 

A particularly good selection of physical properties may be spectra, because they are known to depend strongly on the chemical structure. In fact, different types of spectra carry different kinds of structural information, NMR spectra characterize individual carbon atoms in their molecular environment. They therefore correspond quite closely to fragment-based descriptors, as underlined by the success of approaches to predict NMR spectra by fragment codes (see Section 10.2.3). 

Molnar, L, Keserii, G. M., Papp A., Gulyas, Z., Darvas, F. A neural network based prediction of octanol-water partition coefficients using atomicS fragmental descriptors. Bioorg. Med. Chtm. Lett. 2004, 14, 851-853. 

The importance of methods to predict log P from chemical structure was described in Chapter 14, which is focused on fragment- and atom-based approaches. In this chapter property-based approaches are reviewed, which comprise two main categories (i) methods that use three-dimensional (3D) structure representation and (ii) methods that are based on topological descriptors. 

Table 1 Calculation of some molecular-based descriptors for BOA, DIMBOA and MBOA. Physicochemical descriptor like logP (partition coefficient between octanol and water) constitutional descriptors like the number of a specified atoms or bonds (number of carbons, hydrogens, oxygens, nitrogens, single and aromatic bonds, the total number of atoms and bonds) and molecular weight quantum-mechanical descriptors like HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital).

A polar surface area approximation can be calculated by summing the V, contribution of each polar atom in a molecule. A hydrophobic surface area approximation can be calculated by V) contribution of each hydrophobic atom in a molecule. More generally, for a given binary property Bt (such as is polar or is aromatic or is acceptor ) for each atom i in a molecule, an approximate surface-area based descriptor can be calculated with... 

Surface-area-based descriptors tend to be more useful than simple atom counts because they take connectivity into account (and also, because of the surface integral motivation). For example, surface-area-based descriptors can... 

Nowadays, more than 4000 types of descriptors are known.17 There exist different ways to classify them. With respect to the type of molecular representation used for their calculations—chemical formula, molecular graph, or spatial positions of atoms—one speaks about ID, 2D, and 3D descriptors, respectively. Descriptors can be global (describing the molecule as a whole) and local (only selected parts are considered). One could distinguish information-based descriptors, which tend to code the information stored in molecular structures, and knowledge-based (or semiempir-ical) descriptors issued from the consideration of the mechanism of action. Most of those descriptors can be obtained with the DRAGON, CODESSA PRO, and ISIDA programs. 

Whole Molecule and Atom-Based Topological Descriptors... 

Bodor and Huang correlated the octanol/water partition coefficient, Po/w (unitless) at 298 K for a set of 302 compounds with a set of 58 descriptors to obtain Eq. [49]. These parameters include seven QM based descriptors that were calculated with the AMI method. The dipole moment is p(D) Qo and Qn are the square roots of the sum of the squares of charges on the O and N atoms, respectively. The parameter Qon is the sum of absolute values of charges on the O and N atoms, and ABSQ is the sum of the absolute values of the charges on all atoms. In addition to these QM descriptors, the surface area, A (A ), and the ovality, O, were calculated from the QM-optimized geometry. The ovality is defined by actual area/area as a sphere, O = A/[4ti(3V/ 4ti) ]. The molecular mass, M, and two indicator variables, Ngik and Nq, for alkanes and carbon atoms, respectively, were also employed. 

Netzeva T1 (2004) Whole molecule and atom-based topological descriptors. In Cronin MTD (ed) Predicting chemical toxicity and fate. CRC, Boca Raton FL... 

Other fundamental energy-based descriptors have been defined by traditional computational chemistry. The concept of electronegativity was recognized as a useful basic principle in chemistry more than 150 years ago [Pritchard and Skinner, 1955]. Originally defined by Pauling [Pauling, 1939], electronegativity is the power of an atom in a molecule to attract electrons to itself . 

Warne, M.S., Osbom, D., Lindon, J.C. and Nicholson, J.K. (1999b). Quantitative Stmcture-Toxicity Relationships for Halogenated Substituted-Benzenes to Vibrio fischeri. Using Atom-Based Semi-Empirical Molecular-Orbital Descriptors. Chemosphere, 38,3357-3382. 

The second set of descriptors describes hydrophobic surface properties of a molecule. As with the first set, the second set contains similar partial hydrophobic and partial hydrophilic surface area descriptors (PPHS-%and PNHS-%, respectively), differences in partial surface area descriptors (FPHS-% and FNHS-%), as well as total surface area weighted descriptors (WPHS-x and WNHS-%). In addition, two descriptors assessing the most hydrophobic atom and the most hydrophilic atom on the overall lipophilicity are also described (RPH and RNH). The atom-based fractional log P contributions used for calculations are those of Wildman and Crippen [37] and... 

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