Molecular descriptor topological descriptors

Huang, Q.G., Song, W.L. and Wang, L.S. (1997). Quantitative Relationship Between the Physio-chemical Characteristics as well as Genotoxicity of Organic Polluttants and Molecular Autocorrelation Topological Descriptors. Chemosphere, 35,2849-2855. 

There was a time when one could use only a few molecular descriptors, which were simple topological indices. The 1990s brought myriads of new descriptors [11]. Now it is difficult even to have an idea of how many molecular desaiptors are at one s disposal. Therefore, the crucial problem is the choice of the optimal subset among those available. 

Some further topological descriptors are the Kier-Hall connectivity indices [13] and the electrotopological state index (or -state index) [14]. A comprehensive overview of topological molecular desaiptors is given by Todeschini and Consonni [15]. 

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 proper representation of the molecular structure is crucial for the prediction of spectra. Fragment-based methods, topological descriptors, physicochemical descriptors, and 3D descriptors have been used for this endeavor. 

Molecular descriptors must then be computed. Any numerical value that describes the molecule could be used. Many descriptors are obtained from molecular mechanics or semiempirical calculations. Energies, population analysis, and vibrational frequency analysis with its associated thermodynamic quantities are often obtained this way. Ah initio results can be used reliably, but are often avoided due to the large amount of computation necessary. The largest percentage of descriptors are easily determined values, such as molecular weights, topological indexes, moments of inertia, and so on. Table 30.1 lists some of the descriptors that have been found to be useful in previous studies. These are discussed in more detail in the review articles listed in the bibliography. 

CODESSA can compute or import over 500 molecular descriptors. These can be categorized into constitutional, topological, geometric, electrostatic, quantum chemical, and thermodynamic descriptors. There are automated procedures that will omit missing or bad descriptors. Alternatively, the user can manually define any subset of structures or descriptors to be used. 

A common feature of the various methods that we have developed for the calculation of electronic effects in organic molecules is that they start from fundamental atomic data such as atomic ionization potentials and electron affinities, or atomic polarizability parameters. These atomic data are combined according to specific physical models, to calculate molecular descriptors which take account of the network of bonds. In other words, the constitution of a molecule (the topology) determines the way the procedures (algorithms) walk through the molecule. Again, as previously mentioned, the calculations are performed on the entire molecule. 

Three classes of calculated molecular descriptors, viz., topological and substruc-tural descriptors, geometrical (3-D) indices, and quantum chemical (QC) indices, have been extensively used in QSAR studies pertaining to drug discovery and environmental toxicology [8-12],... 

Flexible optimal descriptors have been defined as specific modifications of adjacency matrix, by means of utilization of nonzero diagonal elements (Randic and Basak, 1999, 2001 Randic and Pompe, 2001a, b). These nonzero values of matrix elements change vertex degrees and consequently the values of molecular descriptors. As a rule, these modifications are aimed to change topological indices. The values of these diagonal elements must provide minimum standard error of estimation for predictive model (that is based on the flexible descriptor) of property/activity of interest. 

We can also look at other literature datasets to gain an idea of how similar our compounds are to compounds for which QMPRPlus gives very good predictions. We have looked at four simple descriptors molecular weight, topological polar surface area [40], chemical complexity [41], and rotatable bond count, using John Bradshaw s... 

To overcome this weakness, we are developing a quantitative structure-activity strategy that is conceptually applicable to all chemicals. To be applicable, at least three criteria are necessary. First, we must be able to calculate the descriptors or Independent variables directly from the chemical structure and, presumably, at a reasonable cost. Second, the ability to calculate the variables should be possible for any chemical. Finally, and most importantly, the variables must be related to a parameter of Interest so that the variables can be used to predict or classify the activity or behavior of the chemical (j ) One important area of research is the development of new variables or descriptors that quantitatively describe the structure of a chemical. The development of these indices has progressed into the mathematical areas of graph theory and topology and a large number of potentially valuable molecular descriptors have been described (7-9). Our objective is not concerned with the development of new descriptors, but alternatively to explore the potential applications of a group of descriptors known as molecular connectivity indices (10). 

---