On the Importance of σ-/π-Hole Interactions in Chemistry and Biochemistry

Resumen

This PhD. thesis is devoted to the study of “unconventional” noncovalent interactions, particularly σ-/π-hole interactions. The inner structure is composed by a State of the art (Chapter 1) which gives a general overview of this “non-classical” noncovalent chemistry, followed by three main chapters (Chapters 2 to 4), each one devoted to the analysis of a particular interaction. These chapters are: Tetrel bonding Interactions (2), Pnicogen bonding Interactions (3) and finally Aerogen bonding Interactions (4). Chapter 1 collects a detailed introduction to focalize the main subject of this research, particularly on σ- and π-hole interactions, which are the main goal of this investigation. Their physical nature is explained as well as several experimental examples in order to put onto scene the vast potential of this family of interactions in fields such as supramolecular chemistry, molecular sensing and biological systems. Chapters 2 to 4 are divided into a number of sections, involving several papers derived from our research. In these sections, the reader will find the same distribution for his/her comfort. First, an Introduction part where the background about the main issue is detailed, including previous results related with the topic. The second part gathers the Computational methodology used, followed by the Results and discussion section. Finally, the main Conclusions derived from our investigation are highlighted. Chapter 2 is divided into four sections. First, the "rediscovery" of the tetrel bonding interaction, a term coined by our research group to describe the σ-hole interaction established between tetrel bearing compounds and electron-rich entities. Second, the role of sp3 carbon atoms to act as tetrel bond donors in ArCX3 (X = H and F) compounds is analyzed using a combination of the CSD (Cambridge Structural Database) as a useful source of experimental data and high level ab initio calculations. Finally, the last part of this chapter is devoted to study the impact of tetrel bonding interactions in two different fields; atmospheric chemistry and biological systems. Chapter 3 is divided into four sections. First, the directionality of -hole pnicogen bonding interactions involving the sp2 nitrogen atom present in -NO2 group is analyzed using the CSD (Cambridge Structural Database) and high level ab initio calculations. Second, the ability of the NO3− to behave as a Lewis acid when placed in the appropiate chemical context and establish -hole antielectrostatic interactions with electron-rich guests is studied using both CSD and PDB (Protein Data Bank) databases. Finally, the study of the interaction between sp3 pnicogen atoms and aromatic rings is analysed using the PDB (Protein Data Bank) database to support the results retrieved from ab initio calculations. These particular interactions are key in the mechanism of action of drugs used in the treatment of Leishmaniasis disease. Chapter 4 is divided into three sections. First, aerogen bonding interactions involving Xe(VI) and Xe(IV) compounds are analysed and characterized as a novel supramolecular force involving the σ-hole of the aerogen atom and electron-rich entities. In addition, π-hole bonding interactions involving Xe(IV) compounds are also described focusing on two derivatives; XeF4 and Xe(OTeF5)4. Finally, the last section of the chapter is focused on the ability of Xe(VI) and Xe(IV) compounds to interact with aromatic moieties, thus establishing aerogen- interactions. Finally, Chapter 5 assembles the main conclusions derived from this thesis.