Charge-weighted descriptor

The comparison between the method-specific trends for the partial positive and negative surface areas (PPSA-1, PNSA-1) as well as their total charge weighted and atomic charge weighted counterparts (PPSA-2, PNSA-2 PPSA-3, PNSA-3) is summarized in terms of R2 values in Table 6.7 together with respective results for the three PPSA descriptors confined to heavy atoms (PPSA-1Z, PPSA-2Z, PPSA-3Z) and to hydrogen (PPSA-1H, PPSA-2H, PPSA-3H). 

The so-called Jurs descriptors are 3D surface descriptions related to various total and fractional defined surfaces. They can be divided into to two parts one electronic [35] and one hydrophobic [36]. The former set of descriptors is generated from partial positive and negative surface areas, total charge as well as atomic positively and negatively charged weighted surface areas, and various differential and fractional charged partial surface areas of the molecule (see Table 14.3). 

FIGU RE 6.33 3D view of a charge-weighted 2D RDF descriptor for a progestagen derivative encoded with effective atom polarizability (a) in the second dimension (128 x 40 5120 components). 

The third model (QSAR 25) developed using the hvdrogen bond descriptor FCPSA (a charge-weighted analog of FPSA [91]), first moment of inertia (J ) and the Balaban topological index (/, a measure of molecular... 

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... 

These first components of the autocorrelation coefficient of the seven physicochemical properties were put together with the other 15 descriptors, providing 22 descriptors. Pairwise correlation analysis was then performed a descriptor was eliminated if the correlation coefficient was equal or higher than 0.90, and four descriptors (molecular weight, the number of carbon atoms, and the first component of the 2D autocorrelation coefficient for the atomic polarizability and n-charge) were removed. This left 18 descriptors. 

Some simple global descriptors are molecular weight, number of atoms present in a molecule (e.g., number of chlorine atoms), number of double bonds, etc. Other descriptors represent the ramification of the molecule. Certain descriptors take into consideration the electronic charge on a certain atom, or its polarity. 

Molecules with a large molecular weight or size are confined to the transcellular route and its requirements related to the hydrophobicity of the molecule. The transcellular pathway has been evaluated for many years and is thought to be the main route of absorption of many drugs, both with respect to carrier-mediated transport and passive diffusion. The most well-known requirement for the passive part of this route is hydrophobicity, and a relationship between permeability coefficients across cell monolayers such as the Caco-2 versus log P and log D 7.4 or 6.5 have been established [102, 117]. However, this relationship appears to be nonlinear and reaches a plateau at around log P of 2, while higher lipophilicities result in reduced permeability [102, 117, 118]. Because of this, much more attention has recently been paid towards molecular descriptors other than lipophilicity [86, 119-125] (see section 5.5.6.). The relative contribution between the para-cellular and transcellular components has also been evaluated using Caco-2 cells, and for a variety of compounds with different charges [110, 112] and sizes [112] (see Section 5.4.5). 

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