Molecular descriptor area-weighted surface charge

TTie structural features are represented by molecular descriptors, which are numeric quantities related directly to the molecular structure rather than physicochemical properties. Examples of such descriptors include molecular weight, molecular connectivity indexes, molecular complexity (degree of substitution), atom counts and valencies, charge, molecular polarizability, moments of inertia, and surface area and volume. Once a set of descriptors has been developed and tested to remove interdependent/collinear variables, a linear regression equation is developed to correlate these variables with the retention parameter of interest, e.g., retention index, retention volume, or partition coefficient The final equation includes only those descriptors that ate statistically significant and provide the best fit to the data. For more details on QSRR and the development and use of molecular descriptors, the reader is referred to the literature [188,195,198,200-202 and references therein]. 

QuaSAR descriptors [QuaSAR - Chemical Computing Group, Inc., 2007] include several types of traditional molecular descriptors Kier-Hall —> connectivity indices, —> structural keys. Estate indices, descriptors of physico-chemical properties (such as log P, molecular weight and molar refractivity), 3D molecular features (such as potential energy descriptors, surface area, volume and —> shape descriptors, conformation dependent partial charge descriptors), and some pharmacophore-based descriptors. 

Delgado reports a QSPR model [49] for the prediction of log(l/S) for a set of 50 chlorinated hydrocarbons including chlorinated benzenes, dibenzo-p-dioxins and PCBs. The model involves only two molecular descriptors, one geometry-dependent descriptor and one charged partial surface area (CPSA) descriptor. The geometric descriptor is the area of the shadow of the molecule projected on a plane defined by the X and Y axes XY shadow) the CPSA descriptor is the surface weighted atomic partial negative surface area (WNSA-3). The model has a squared correlation coefficient of 0.97 and standard deviation of 0.45 log units. 

For each molecule in these struetures, 131 molecular descriptors were calculated. These included simple atom, bond and group eounts, hydrogen bond donor and acceptor counts, topological indices, a variety of partitioned and charge weighted surface areas and deseriptors of molecular size, shape, polarity... 

CSA2h index -> charged partial surface area descriptors (O HDCA index) cube root molecular weight -> molecular weight cycle cyclic path - graph cycle matrices (C)... 

Computationally derived descriptors (e.g., molecular weight, size, shape, polarity, electrostatic interactions, charge, lipophilicity, hydrogen bonding capacity, polar surface area). 

Among the several CODESSA descriptors, implemented in the homonymous software CODESSA (Comprehensive DEscriptors for Structural and Statistical Analysis) [Katritzky and Gordeeva, 1993 CODESSA- Katritzky, Lobanov et al., 1996 Katritzky, Lobanov et al, 1996], are molecular weight, molecular volume, —> count descriptors, —> topological indices, charge descriptors, shadow indices, charged partial surface area descriptors, quantum-chemical descriptors, and —> electric polarization descriptors. 

The descriptor uses readily calculable physicochemical properties from the topological structure. The descriptors used in this study were atomic weight, hydropho-bicity, molecular refractivity, atomic charge, polar surface area, hydrogen bond acceptors, and hydrogen bond donors. The authors note that Martin et al. [32] applied a similar approach for the design of diverse combinatorial libraries. 

---