Calculated Hydrogen-Bonding Descriptors

Poorly absorbed compounds have been identified as those with a PSA 140 A2, but considerably more scatter was found around the sigmoidal curve observed for a smaller set of compounds [78]. This is partly due to the fact that many compounds do not show only simple passive diffusion, but are also affected by active carriers, efflux mechanisms involving P-glycoprotein (P-gp) and other transporter proteins, as well as gut wall metabolism. A further refinement in the PSA approach is expected to come from taking into account the strength of the hydrogen bonds, which in principle already is the basis of the HYBOT approach described below. 

---

Osterberg and Norinder [35] analyzed the improvement in the prediction of drug transport processes by the combination of the hydrogen-bonding descriptors and calculated log P. Two data sets were used. The calculated static PSA and the experimental log BB values for 70 compounds (data set 1) were taken from the work of Clark. The calculated dynamic PSA and the experimental log... 

Molecular descriptors are usually classified into several classes by a mixed taxonomy based on different points of view. For example, descriptors are often distinguished by their physico-chemical meaning such as - electronic descriptors, - steric descriptors, lipophilicity descriptors, -> hydrogen-bonding descriptors, - shape descriptors, charge descriptors, - electric polarization descriptors, - reactivity descriptors, moreover, on the basis of the specific mathematical tool used for the calculation of the molecular descriptors, - autocorrelation descriptors, -> eigenvalue-based descriptors, -> determinant-based descriptors, - Wiener-type indices, - Schultz-type indices can be distinguished. 

HYBOT-Plus (hydrogen bonding thermodynamics, calculation of local and molecular physicochemical descriptors) http //www.timtec.net/soJiware/hybot-plus.htm... 

MolSurf parameters [33] are descriptors derived from quantum mechanical calculations. These descriptors are computed at a surface of constant electron density, with which a very fine description of the properties of a molecule at the Van der Waals surface can be obtained. They describe various electrostatic properties such as hydrogen-bonding strengths and polarizability, as well as Lewis base and acid strengths. MolSurf parameters are computed using the following protocol. 

Osterberg and Norinder [42] further analyzed a subset of the ATPase data published by Litman et al. [39]. The ATPase activity values were correlated by multivariate statistics with calculated descriptors (MolSurf descriptors) related to physicochemical properties suchaslipophilicity, polarity, polarizability and hydrogen bonding. After exclusion of one outlier and large molecules such as valinomycin, gramicidin S and so on, which were not handled by the MolSurf software, only 21 compounds were included in the study. Two models were derived model 1, based on... 

Kaznessis et al. [24] used Monte Carlo simulations on a data set of 85 molecules collected from various sources, to calculate physically significant descriptors such as solvent accessible surface area (SASA), solute dipole, number of hydrogen-bond acceptors (HBAC) and donors (HBDN), molecular volume (MVOL), and the hydrophilic, hydrophobic, and amphiphilic components of SASA and related them with BBB permeability using the MLR method. After removing nine strong outliers, the following relationship was developed (Eq. 37) ... 

---