HYBOT

Before the comparative molecular field analysis (CoMFA), BCUT descriptors, 4D-QSAR, and HYBOT descriptors arc discussed in more detail, some further descriptors are listed briefly. 

The HYBOT descriptors were successfully applied to the prediction of the partition coefficient log P (>i--octanol/water) for small organic componnds with one acceptor group from their calculated polarizabilities and the free energy acceptor factor C, as well as properties like solubility log S, the permeability of drugs (Caco-2, human skin), and for the modeling of biological activities. 

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

O. A. Raevsky, Hydro n Bond Strength Estimation by means of HYBOT. In... 

HYBOT Hydrogen Bond Thermodynamics LCAP Long-chain arylpiperazine... 

Raevsky OA, Skvortsov VS (2002) 3D hydrogen bond thermodynamics (HYBOT) potentials in molecular modelling. J Comput Aided Mol Des 16(1) 1-10... 

From 163 calculated H-bond donor and 195 calculated H-bond acceptor factors, one can get enthalpy and free energy values for 31785 reactions using Eqs. (3) and (4). Later, the number of H-bond factor values was significantly increased. A special program for calculating factor values was created and included in the HYBOT (Hydrogen Bond Thermodynamics) program [28, 29]. The current version, HYBOT-2006, has about 20000 values of H-bond acceptor factors and about 5000... 

Since the beginning of the 1980s, two different approaches to quantify the H-bond contribution to properties at the 2D and 3D levels developed independently. The carefully parameterized methodology of HYBOT allows one to take into account the influence of substituents on H-bond acceptor and donor strengths. Modern procedures based on X-ray data of ligand-macro molecular complexes consider the... 

Use HYBOT s acceptor and donor enthalpy factors to estimate the optimum H-bonding energy via Eq. (3),... 

The solubility of chemicals, drugs or pollutants in water (S ), in octanol (S ), their saturation concentration in air Qii), as well as their partitioning in the corresponding two-phase systems [octanol-water (P /w = Q/Cw), air-water (Pair/w = C IC ) and air-octanol (Paij/ = C /Co)] are important physicochemical parameters in medicinal chemistry and in environmental research. The following correlahons of those properties with HYBOT descriptors have been published recently [54—58] ... 

I 6 H-bonding Parameterization in Quantitative Structure-Activity Relationships i Drug Design Tab. 6.5 Biopharmaceutics classification for 254 Drugs on the basis of HYBOT descriptors. 

Raevsky, 0. A. Hydrogen bond strength estimation by means of HYBOT. In Computer-Assisted Lead Finding and Optimization, Van de Waterbeemd, H., Testa, B., Folkers, G. (eds.), Wiley-VGH, Weinheim, 1997, pp. 357-378. 

Raevsky, 0. A., Grigor ev, V. Ju., Trepalin, S. V. HYBOT (Hydrogen Bond Thermodynamics) program package. Registration by Russian State Patent Agency N 990090 of 25 February 1999. 

Raevsky, 0. A., Schaper, K.-J. Analysis of water solubility data on the basis of HYBOT descriptors. Part 1. Partitioning of volatile chemicals in the water-gas phase system. QSAR Comh. Sci. 2003,... 

Raevsky, O. A., Dearden, J. C. Creation of predictive models of aquatic toxicity of environmental pollutants with different mechanisms of action on the basis of molecular similarity and HYBOT descriptors. SAR QSAR Environ. Res. 2004, 15, 433-448. 

In addition, the calculation of many different ID, 2D and 3D descriptors is possible using a range of commercially available software packages, such as Sybyl, Cerius2, Tsar, Molconn-Z and Hybot. Several new descriptor sets are based on quantification of 3D molecular surface properties, and these have been explored for the prediction of, e.g., Caco-2 permeability and oral absorption. It is pointed out here that a number of these new descriptors are strongly correlated to the more traditional physico-chemical properties. 

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. 

Product of overall H-bond acidity and basicity (Absolv) Molecular polarizability in A3 (HYBOT) [23] also Alpha Overall H-bond basicity (Absolv) also as Sp 1 [8]... 

Largest H-bond acceptor value in molecule (HYBOT) [23] also Ca max... 

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