Dissociation constant molecular properties

Theoretical and structural studies have been briefly reviewed as late as 1979 (79AHC(25)147) (discussed were the aromaticity, basicity, thermodynamic properties, molecular dimensions and tautomeric properties ) and also in the early 1960s (63ahC(2)365, 62hC(17)1, p. 117). Significant new data have not been added but refinements in the data have been recorded. Tables on electron density, density, refractive indexes, molar refractivity, surface data and dissociation constants of isoxazole and its derivatives have been compiled (62HC(17)l,p. 177). Short reviews on all aspects of the physical properties as applied to isoxazoles have appeared in the series Physical Methods in Heterocyclic Chemistry (1963-1976, vols. 1-6). 

The major differences between behavior profiles of organic chemicals in the environment are attributable to their physical-chemical properties. The key properties are recognized as solubility in water, vapor pressure, the three partition coefficients between air, water and octanol, dissociation constant in water (when relevant) and susceptibility to degradation or transformation reactions. Other essential molecular descriptors are molar mass and molar volume, with properties such as critical temperature and pressure and molecular area being occasionally useful for specific purposes. A useful source of information and estimation methods on these properties is the handbook by Boethling and Mackay (2000). 

Two of its three adjustable parameters, De and re correspond to directly measurable molecular properties of bond dissociation energy and equilibrium interatomic distance respectively. The third parameter, a, is related to the force constants commonly used in spectroscopic analyses. A standard procedure [147] to obtain experimental potential energy curves is to calculate from spectroscopic data the constants ke, g, and j that appear in the expression... 

A second important tool stems from improved computational quantiun mechanical methods, particularly DFT, which are now capable of predicting the molecular properties of small- to medium-size organic structures (< about 30 first row atoms) with a precision approaching that of experiment. Good quahty computed electronic energies, coupled with improved force constants (and hence good vibrational analyses), enable molecular bond dissociation... 

Physico-chemical properties constitute the most important class of experimental measurements, also playing a fundamental role as - molecular descriptors both for their availability as well as their interpretability. Examples of physico-chemical measurable quantities are refractive indices, molar refractivities, parachors, densities, solubilities, partition coefficients, dipole moments, chemical shifts, retention times, spectroscopic signals, rate constants, equilibrium constants, vapor pressures, boiling and melting points, acid dissociation constants, etc. [Lyman et al, 1982 Reid et al, 1988 Horvath, 1992 Baum, 1998]. 

Many physico-chemical properties and biological acitivities seem to fall within the domain of additive properties. Examples of constantive properties are local molecular properties, such as dissociation energy for a localized bond or ionization potential. Characteristic multiplicative properties are wave functions, Kekul6 structure counts and probabilities. The derivative properties are associated to the correspnding multiplicative property P. 

Methods other than thermodynamic cycles are often used to calculate acid dissociation constants. Previous publications implement the theoretical relationship between pKa and structural property [6], bond valence methods and bond lengths [33], pKa correlations with highest occupied molecular orbital (HOMO) energies and frontier molecular orbitals [34], and artificial neural networks [35] to predict pKa values. In addition much work has been done using physical properties as quantitative structure-activity relationship (QSAR) descriptors, and regression equations with such descriptors to yield accurate pKa values for specific classes of molecules [36-47]. The correlation of pKas to various molecular properties, however, is often restricted to specific classes of compounds, and it is... 

Following the approach of Tanford (1961), it is useful to examine the ionization of a hypothetical diprotic acid (HA-BH). Thermodynamically, the acid-base properties of this acid are completely described by two acid dissociation constants ( fi and K2). However, at the molecular level, it is clearly more appropriate to define four dissociation constants as depicted in Equation (2) ... 

Indeed, on the basis of the cyclase assay, amitriptyline is one of the most potent H2-antagonists presently available (KD 0.05 /iM) [ 181, 193]. The dissociation constants for many of the antidepressants are sufficiently low to suggest that the activation of adenylate cyclase by histamine may be inhibited by therapeutically effective concentrations of these compounds [81, 193]. This biochemical action of the tricyclic and tetracyclic antidepressants may thus represent part of the molecular basis of clinical antidepressant activity [193]. It should also be noted that most tricyclic and tetracyclic antidepressants are much more potent inhibitors of H,-receptor responses [67, 120] than they are of the H2-cyclase response, and this property of these compounds may mediate the sedative actions of these drugs [71, 73, 75]. 

Fig. 8. Separation of an overall binding or dissociation event into two steps. The intrinsic binding step is characterized by rate constants kon and kofS, which are determined by receptor and ligand molecular properties. The transport step is characterized by rate constant k+ and is influenced by diffusion and geometric considerations. The state in which receptor and ligand are close enough to bind but have not yet done so is sometimes termed the encounter complex.

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