Naphthalene, aromaticity molecular model

When molecular orbital calculations are carried out for naphthalene using the model shown in Fig. 14.16, the results of the calculations correlate well with our experimental knowledge of naphthalene. The calculations indicate that delocalization of the 10 electrons over the two rings produces a structure with considerably lower energy than that calculated for any individual Kekule structure. Naphthalene, consequently, has a substantial resonance energy. Based on what we know about benzene, moreover, naphthalene s tendency to react by substitution rather than addition and to show other properties associated with aromatic compounds is understandable. 

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. 

Preliminary information useful in prodrug design has been obtained with amino acids attached to model aromatic amines. Thus, N-(naphthalen-2-yl) amides of amino acids (6.1, R=side chain of amino acid, R =H) proved to be of interest as test compounds to monitor peptidase activity such as ami-nopeptidase M (membrane alanyl aminopeptidase, microsomal aminopepti-dase, EC 3.4.11.2) [16][17], In the presence of purified rabbit kidney aminopeptidase M or human cerebrospinal fluid (CSF) aminopeptidase activity, the rate of hydrolysis decreased in the order Ala-> Leu->Arg->Glu-2-naphthyl-amide. Ala-2-naphthylamide, in particular, proved to be a good test compound, as its rate of hydrolysis was influenced by experimental conditions (preparation, inhibitors, etc.), as was the hydrolysis of a number of low-molecular-weight opioid peptides and circulating vasoactive peptides. 

Type III PKSs are small, homodimeric enzymes which can be found in both plants and a wide array of microbes. They generally construct fairly low molecular weight 1-2 ring aromatic molecules.36 Examples include plant chalcone and stilbene synthases and the S. coelicolor gene tetrahydroxy naphthalene synthase (THNS), each of which has been structurally characterised by X-ray diffraction. These enzymes are often easy to express het-erologously in E. coli and much work has been done to understand their complicated enzymology as a model for the larger, more complex Type I and II systems.2... 

---