Ph.D. thesis Dr. A. Patrícia Bento

On October 27th, 2008, Dr. A. Patrícia Bento successfully defended her Ph.D. thesis entitled
“Nucleophilic Substitution Reactions:
Theoretical Study on the Origin of Reaction Barriers”.
Dr. Patrícia Bento was supervised by copromotor Dr. Matthias Bickelhaupt (promotor Prof. Dr. Evert Jan Baerends). A PDF file of this thesis is available from the Ph.D. Theses section. Contact SCM to obtain a free paper copy in book form (limited availability).

In her thesis one of the most fundamental chemical reactions is studied: the bimolecular nucleophilic substitution or SN2-reaction. This type of reaction plays a central role for example in processes of industrial syntheses of bulk- and fine-chemicals, in academic laboratories in the syntheses of specific reagents and pharmacological active substances as well as in a large number of biological processes. Despite their wide use, there were a number of elementary questions related with SN2 substitutions that needed to be answered. For example, where does the reaction barrier that dictates the speed of SN2-reactions originate from? And how does the height of this barrier exactly depend on the different components of the reacting system? Dr. Bento has succeeded in answering these and other questions in detail by making use of advanced quantum chemical simulation techniques and analysis of the molecular electronic structure. The ADF program was used in predicting that an SN2 barrier originates mainly from steric effects: during an SN2 substitution, the center of nucleophilic attack is sterically crowded and, as the nucleophile approaches it, the repulsion between the substituents increases, giving rise to a destabilization in energy and thus to the formation of an SN2 barrier. In her thesis it has also been shown that these barriers can be modulated by choosing a larger center of nucleophilic attack or by using nucleophiles with greater donor capability. The first predictions based on the new insights have already been successfully confirmed using the ADF program, such as for example the recipe to slow down SN2 reactions at silicon and thereby making it behave more like carbon, by spatially restricting access to the silicon atom. The obtained results have led to a better understanding of SN2-reactions in general. Because of this, chemical and biochemical processes can in the future be designed and optimized in a more rational and thus more efficient manner.