Molecular fragment and substituent effect studies of styrene derivatives by electron density shape analysis

Antal, Zoltán (2014) Molecular fragment and substituent effect studies of styrene derivatives by electron density shape analysis. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

The research work leading to the content of this thesis and to the related publications represents a novel way to analyze and characterize some aspects of the most fundamental interactions within molecules, namely through-space and through-bond interactions, which are also relevant to substituent effects. The approach and the results give quantum chemical justification for some components of the associated fundamental phenomena which are often difficult or even impossible to examine separately by experimental means. The results are obtained using well-established, thoroughly tested and verified methods of electron density shape analysis approaches, based on input electron densities obtained by various established quantum chemistry computational methods, such as Hartree-Fock, Density Functional, and Møller-Plesset methodologies. The shape analysis methods, applicable to both complete molecules and locally to molecular fragments such as functional groups, are based on two fundamental theorems of quantum chemistry: the Hohenberg-Kohn theorem and the Holographic Electron Density theorem. The first of these theorems establishes that the molecular electron density must contain all molecular properties, whereas the second of these theorems gives justification that even small molecular fragments, such as a vinyl group in our studies, can be used as a “fingerprint”, fully representing all the unique intramolecular interactions within each molecule. As a consequence of these theorems, the electron density shape analysis methods, when applied to the complete electron density cloud of a target molecule, or locally to that of a molecular fragment, yield shape information which can, in principle, give highly detailed theoretical information about all molecular properties, hence, providing a suitable basis for establishing correlations with experimentally available data about various measured chemical properties. In earlier studies, such shape analysis approaches have been used in various applied fields of chemistry, such as pharmacology and toxicology. The present study describes the use of a series of small molecules, specifically, substituted styrenes for the analysis and shape correlations involving through-bond and through-space correlations. As a consequence of their specific structural features, the chosen molecules appear as ideal candidates to study both effects separately. In spite of their specificity, the results provide some general conclusions which are likely to contribute to a better understanding of far more complex phenomena, such as some of the components contributing to the complex folding pattern of globular proteins and more general interaction problems in the emerging field of molecular design. Even in these latter fields, these two types of interactions, through-space and through-bond, play significant roles as well. The presence of aromatic rings in these styrene derivatives is very useful as through-bond transmitting media whilst the distance between the studied molecular fragments obtained after removing the ring is also nearly optimal to be used in through-space interaction studies. The structural specificities of the model molecules have played an important role in all three publications constituting the main chapters of this thesis. Therefore, there is a strong emphasis on the effect transmitting capabilities of the aromatic ring in all 3 of these papers.

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