HYBOT descriptor

Interactions between hydrogen-bond donor and acceptor groups in different molecules play a pivotal role in many chemical and biological problems. Hydrogen bonds can be studied with quantum chemical calculations and empirical methods. 

AG and AH can be expressed as a multiplicative function of hydrogen bonding in different polar and nonpolar solvents by means of enthalpy acceptor factors E - enthalpy donor factors free energy acceptor factors Q, and free energy donor factors Q (Eqs. (32) and (33), where kj, 2- 3 [kcal/mol] are regression coefficients). 

Based on known ocpcrimontal AG values, and Q, were estimated. The system phenol-HMPA in CCI4. was chosen as the reference standard the H-boud free energy factors C, and Q were set at -2.50 (phenol) and 4,00 (HMPA) respectively. 

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. 

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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 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., 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. 

The relationship between individual components appears to indicate that the first and second SaSA dimensions can be related to the first and third ALMOND dimensions, with an emphasis on the first component. The first SaSA component is dominated by size-related descriptors, e.g., the total number of heavy atoms, MW, CMR, and polarizability. These properties explain approximately 60% of the first ALMOND component, suggesting that large internode distances and high internode interaction energies dominate this component. The third ALMOND component has a weaker relationship (25%) to hydrophobicity descriptors such as CLOGP, ELogP, nonpolar surface area, and the number of nonpolar atoms [123]. Only the fourth ALMOND component appears to be related (under 25%) with hydrogen-bond-related, e.g., HYBOT descriptors, whereas the second, fifth, and sixth ALMOND... 

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

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. 

Nevertheless, Absolv gave us five additional parameters to work with. What is more, we used ALOGP, the predicted octanol/water partition coefficient also calculated by Absolv. We combined these descriptors with CLOGP, CMR and those from HYBOT. Forward step-wise regression gave Eq. (7) ... 

The sum of hydrogen bonding donor and acceptor related E-state descriptors are well correlated with the corresponding HYBOT parameters, with r2-values of 0.8-0.95 [38]. This gives the E-state descriptors a link to experimental values, which is positive but not necessary for the purpose of generating useful models with good statistical quality for, in this case, intestinal absorption. 

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