Investigating pnictogen bonds: impact on molecular interactions and NMR parameters

Abstract

The nature of non-covalent interactions has been the subject of intense debate in recent literature, questioning the predominance of the purely electrostatic model in favor of a significant orbital contribution. In this context, this thesis investigated the nature of pnictogen bonds (PnB) and their impact on two highly relevant real systems: the inhibition of the enzyme acetylcholinesterase (AChE) by organophosphorus compounds and the design of molecules for quantum computing via Nuclear Magnetic Resonance (NMR). Using Density Functional Theory (DFT) combined with topological analysis and energy decomposition tools (AIM, NBO, and EDA), it was demonstrated that interactions involving phosphorus (and selenium) atoms have an orbital component that is decisive for their physicochemical properties. In the biological system, the formation of the PnB bond between chemical warfare agents (such as Sarin and VX) and the active site of AChE proved crucial to the inhibition mechanism, suggesting new avenues for the development of more efficient antidotes. In the technological field, the modulation of intramolecular P···P and P···Se interactions in naphthalene derivatives has allowed the fine tuning of NMR parameters (chemical shift and coupling constant), enabling the rational design of molecular qubits that satisfy DiVincenzo's criteria. The results unify the understanding of these interactions, proposing that manipulating the covalent character in non-covalent bonds is a powerful strategy for both medicinal chemistry and quantum materials engineering.