Molecular aromaticity constant

Atkinson (1987) developed very reliable fragment additivity SARs for estimating kHO(air) from molecular structure using more than 400 compounds in the database (Chapter 14 describes procedures for using these SARs). SARs for HO are based on the premise that rate constants for each of the several different classes of reactions of HO with organic compounds — abstraction of H- atom (kH), addition to double, triple or aromatic bonds (kE), and reaction with S or N atoms (kA) — can be estimated separately and then summed to give the total molecular rate constant, kHO ... 

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). 

Structure elucidation does not necessarily require the complete analysis of all multiplets in complicated spectra. If the coupling constants are known, the characteristic fine structure of the single multiplet almost always leads to identification of a molecular fragment and, in the case of alkenes and aromatic or heteroaromatic compounds, it may even lead to the elucidation of the complete substitution pattern. 

As a final example we consider noncovalent molecular complex formation with the macrocyclic ligand a-cyclodextrin, a natural product consisting of six a-D-glucose units linked 1-4 to form a torus whose cavity is capable of including molecules the size of an aromatic ring. Table 4-3 gives some rate constants for this reaction, where L represents the cyclodextrin and S is the substrate ... 

The link between UpophiUcity and point charges is given by intermolecular electrostatic interactions (Sections 12.1.1.2, 12.1.3 and 12.1.4 address this topic) and ionization constants. The mathematical relationships between Upophilicity descriptors and pKjS are discussed in detail in Chapter 3 by Alex Avdeef. Here, we recall how pKj values are related to the molecular electron flow by taking the difference between the pfCj of aromatic and aUphatic amines as an example. The pfCa of a basic compound depends on the equilibrium shown in Fig. 12.2(A). A chemical effect produces the stabilization or destabiUzation of one of the two forms, the free energy difference (AG) decreases or increases and, consequently. 

It is now common to use Viscosity Gravity Constant (VGC) as the criterion for choice of a processing oil. The VGC represents the overall average aromaticity of an oil independent of its molecular weight. 

Chen, J.W., Kong, L.R., Zhu, C.M., Huang, Q.G., Wang, L.S. (1996) Correlation between photolysis rate constants of polycyclic aromatic hydrocarbons and frontier molecular orbital energy. Chemosphere 33, 1143-1150. 

Aromaticity varies with change of state because of the influence of the molecular environment on the interactions that determine aromaticity quantitatively, particularly in nonsymmetrical heterocycles. Comparative calculations of aromaticity indices for molecules in the gas phase and in condensed media with dielectric constants > 1, with or without hydrogen-bonding, showed coherent results for a set of nitrogen heterocycles, including imidazole, pyrrole, pyrazole, 1//-1,2,4-triazole, and benzimidazole. The... 

TABLE 13. Apparent stability constants of molecular complexes between 2-hydroxypyridine and some aromatic nitro derivatives in hen/enevA at 25 °C125. Reproduced by permission of societa chimica Italiana from Reference 125... 

The study of molecular complexation was then extended to other aromatic nitro derivatives125. Although, as was described before, one of the more frequent methods of studying the formation of molecular complexes is by UV-visible spectrophotometry, the author did not observe detectable differences in the UV-visible absorbance spectra between the 2-hydroxypyridine-l-fluoro-2,4-dinitrobenzene (FDNB) mixtures and the sum of their separate components. The author observed that the signals of the 1II NMR spectra of FDNB in apolar solvents were shifted downward by the addition of 2-hydroxypyridine from solutions where [2-hydroxypyridine] [FDNB] he calculated the apparent stability constants, which are shown in Table 13. 

One of the major difficulties in Forlani s proposal of the molecular complex substrate-catalyst mechanism, to explain the fourth-order kinetics, is the assumption that this complex needs an additional molecule of amine to decompose to products. The formation of molecular complexes between dinitrohalobenzenes and certain amines (especially aromatic amines) has been widely studied, and their involvement in SwAr reaction has been discussed in Section II.E. The equilibrium constants for the formation of those complexes were calculated in several cases, and they were included in the kinetic expressions when pertinent. But in all cases, the complex was assumed to be in the reaction pathway, and no need of an additional amine molecule was invoked by the several authors who studied those reactions. 

A set of n = 209 polycyclic aromatic compounds (PAC) was used in this example. The chemical structures have been drawn manually by a structure editor software approximate 3D-structures including all H-atoms have been made by software Corina (Corina 2004), and software Dragon, version 5.3 (Dragon 2004), has been applied to compute 1630 molecular descriptors. These descriptors cover a great diversity of chemical structures and therefore many descriptors are irrelevant for a selected class of compounds as the PACs in this example. By a simple variable selection, descriptors which are constant or almost constant (all but a maximum of five values constant), and descriptors with a correlation coefficient >0.95 to another descriptor have been eliminated. The resulting m = 467 descriptors have been used as x-variables. The y-variable to be modeled is the Lee retention index (Lee et al. 1979) which is based on the reference values 200, 300, 400, and 500 for the compounds naphthalene, phenanthrene, chrysene, and picene, respectively. 

Lipophilicity in particular, as reflected in partition coefficients between aqueous and non-aqueous media most commonly water (or aqueous buffer) and Z-octanol,has received much attention [105,141,152,153,176,199,232,233]. Logic )W for the octanol-water system has been shown to be approximately additive and constitutive, and hence, schemes for its a priori calculation from molecular structure have been devised using either substituent tt values or substructural fragment constants [289, 299]. The approximate nature of any partition coefficient has been frequently emphasized and, indeed, some of the structural features that cause unreliability have been identified and accommodated. Other complications such as steric effects, conformational effects, and substitution at the active positions of hetero-aromatic rings have been observed but cannot as yet be accounted for completely and systematically. Theoretical statistical and topological methods to approach some of these problems have been reported [116-119,175,289,300]. The observations of linear relationships among partition coefficients between water and various organic solvents have been extended and qualified to include other dose-response relationships [120-122,160,161,299-302]. 

---