Quantification of Non-Covalent Interactions on the Basis of the Thermodynamic Hydrogen Bond Parameters

Abstract

This paper describes how empirical free energy and/or enthalpy values for hydrogen binding strength are derived from thousands of corresponding measurements between H-bond donors and acceptors, mostly in carbon tetrachloride, and how they can be used to construct common scales or factor values (increments) also for other reactions involving electron donor and acceptor ability of functions. The corresponding databases and programs (HYBOT) allow one to predict thermodynamic values for experimentally unknown equilibria, including also ionophore complexes with crown ethers or cryptands. Applications in QSAR involve the prediction of lipophilicity from any structure on the basis of only two variables, e.g. 234 systems are described this way with a correlation coefficient r = 0·96. Similarly, permeabilities and some biological properties such as narcotic activities of chemicals and anti-HIV-1 activity of some porphyrins are evaluated.

Quantitative Estimation of Drug Absorption in Humans for Passively Transported Compounds on the Basis of Their Physico-chemical Parameters

“…Because the results of absorption studies are usually reported as percentages (or fractions) that can never be less than 0% (0.00) and never more than 100% (1.00), sigmoid and other non linear regression models are important physical models to consider [6, 13, 21±23]. H-bond parameters are calculated by HYBOT on the basis of a multiplicative approach, and are related to the free energy of H-bonding (DG) by the following equation [11]:…”

“…Some new descriptors employed were: the sum of absolute values of partial atomic charges for all atoms in the molecule (Sjqj), the sum of Hbond factor values for all acceptor substructures in the molecule (SC a ), the sum of H-bond factor values for all donor atoms in a molecule (SC d ), and sum of absolute values of H-bond factors for all acceptors and all donors in a molecule (SC ad ). Considering the molecular charge as indicated in Table 1 all descriptors were calculated by the program package HYBOTyHYBOT-PLUS-98 [18] which is based on methods described in several articles: H-bond descriptors [11], partial atomic charges [19] and polarizability [20]. Also for the ®rst training set, experimental partition coef®cients [17] in the system octanol-water at pH 7.4 (log D) were studied.…”

Calculation of Molecular Lipophilicity: State-of-the-Art and Comparison of LogP Methods on more than 96,000 Compounds

“…(18) but the best results were obtained using polarizability. The second term reflects intermolecular interactions during the solvation process and was calculated via Hydrogen Bond Thermodynamics (HYBOT) 86. Thus, the terms in Eq.…”

A New Nonlinear Equation for the Tissue/Blood Partition Coefficients of Neutral Compounds

“…Other physicochemical descriptors employed were: the sum of all positive partial atomic charges for all atoms in the molecule (Σ Q + ) as a descriptor of polarity, the sum of H‐bond factor values for all acceptor substructures in the molecule (ΣCa) and the sum of H‐bond factor values for all donor atoms in a molecule (ΣCd), and the maximum H‐bond acceptor descriptor in a molecule (Ca max ). All descriptors were calculated by the program package HYBOT/HYBOT‐PLUS‐98,4 which is the base on the methods described in several articles, such as H‐bond descriptors,13 partial atomic charges,14 and polarizability 15…”