Electronic spectroscopy of propofol, propofol homomers ad their hydratated clusters

Abstract

As several works suggest, the action of anaesthetics takes place through direct interaction with membrane receptors. They can interrupt the transmission of the electrical signal along the neuron´s axon by blocking the ion channels or they can dock in the pre/post synaptic receptors, blocking the communication between neurons. In the latter, the action is directly related to that of neurotransmitters, as they bind to the same kind of receptors. Mutagenic studies have already probed the existence of several key amino acids in their respective receptors and thus, the anaesthetic-receptor interaction can be modeled by studying separately the non-covalent interactions between specific residues of the amino acids conforming the active site and the anaesthetic. There are three main goals in this thesis: first, characterization of the noncovalent interactions that take place between propofol and the residues of the amino acids conforming the active site, i.e. propofol-phenol and propofol-isopropanol have been characterized using a variety of gas-phase spectroscopic techniques. The results obtained shed some light on some of the particularities observed by X-Ray experiments. Second, the solvation of propofol by water was extensively studied. The whole process of transport and docking of anaesthetics relies in the changes on the Gibb’s free energy, which favors the propofol-active site interaction over propofol solvation by the extracellular medium. Therefore, a deep knowledge on the interactions between both propofol and the extracellular medium (water) is required. Consequently, a complete study of propofol with up to nine water molecules, propofol·W1-9, was done. Third, in order to understand the competition between dispersive forces and hydrogen bond, propofol self-aggregation process was studied (up to propofol6, being one of the greater systems ever explorer by the use of supersonic expansions). Such systems are mainly governed by dispersive forces. In addition, solvation of propofol homomers has also been characterized, introducing water molecules into the previous system: propofol2·W1-7, propofol3·W1 and propofol4·W1. Such study has led to unexpected results in both systems, as for the former, formation of nano-micelles was observed, while the latter allows exploring the solvation process of such nano-micelles.