Electronic spectroscopy of propofol, propofol homomers ad their hydratated clusters
Fecha
2011-10-07Autor
León Ona, Iker
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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.