Computational and synthetic studies of arene- arene interactions

Interactions of stacked aromatics have proven applicable in various biological and chemical systems. Arene-arene interactions have been investigated through experimental approaches in various systems as well as through theoretical studies of simplified arene-arene systems, which are used to further elucidate the specific nature of these interactions on a molecular level. Nucleic acid intercalation is a classic biological example of non-covalent stacked interactions of aromatics. However, ambiguity still remains in terms of how intercalation, as well as non-covalent interactions of aromatics in general, functions on a basic, molecular level. This work is aimed at determining the key intermolecular components that dictate favorable interactions of aromatics.;To computationally evaluate arene-arene interactions, an extensive study of benzene-substituted benzene dimers in a parallel face-to-face conformation was employed and it was found that, while dispersion dominates in these systems, electrostatics are key to predicting binding energies. In a continuation of this study, a series of electron-rich and electron-deficient aromatic systems were evaluated via studies of substituted benzene-hexamethylbenzene and substituted benzene-hexafluorobenzene dimers, respectively. Symmetry-Adapted Perturbation Theory (SAPT) calculations have afforded decomposition of computationally obtained binding energies of these aromatic systems into their energetic components, thus allowing detailed analysis of relative energetic contributions. Substituent effects have been analyzed using Hammett electronic parameters as well as specific energetic components as revealed through SAPT energy decomposition studies. Naphthalimides have long been investigated for their intercalative abilities. A series of substituted naphthalimides were synthesized and intercalated into sequences of DNA and RNA and an experimental melting temperature was obtained. Two-parameter QSAR analyses were performed to generate a theoretical melting temperature value, all yielding adequate statistical data. Upon further investigation, it was found that the parameter coefficient standard deviations in each two-parameter QSAR equation were very large, larger than the respective coefficients. To address the shortcomings of the two-parameter QSAR models, a one-parameter QSAR analysis was performed utilizing a novel arene-arene stacking parameter developed from SAPT energy decomposition studies of computationally-determined benzene-substituted benzene dimer binding energies. The QSAR analysis using the stacking parameter yielded statistics that are significantly better than the two-parameter equations.