Abstract
A vibrational assignment of the anaesthetic sevoflurane, (CF(3))(2)CHOCH(2)F, is proposed and its interaction with the aromatic model compound benzene is studied using vibrational spectroscopy of supersonic jet expansions and of cryosolutions in liquid xenon. Ab initio calculations, at the MP2/cc-pVDZ and MP2/aug-cc-pVDZ levels, predict two isomers for the 1 : 1 complex, one in which the near-cis, gauche conformer of sevoflurane is hydrogen bonded through its isopropyl-hydrogen atom, the other in which the same conformer is bonded through a bifurcated hydrogen bond with the fluoromethyl hydrogen atoms. From the experiments it is shown that the two isomers are formed, however with a strong population dominance of the isopropyl-bonded species, both in the jet and liquid phase spectra. The experimental complexation enthalpy in liquid xenon, ΔH(o)(LXe), of this species equals -10.9(2) kJ mol(-1), as derived from the temperature dependent behaviour of the cryosolution spectra. Theoretical complexation enthalpies in liquid xenon were obtained by combining the complete basis set extrapolated complexation energies at the MP2/aug-cc-pVXZ (X = D,T) level with corrections derived from statistical thermodynamics and Monte Carlo Free Energy Perturbation calculations, resulting in a complexation enthalpy of -11.2(3) kJ mol(-1) for the isopropyl-bonded complex, in very good agreement with the experimental value, and of -11.4(4) kJ mol(-1), for the fluoromethyl-bonded complex. The Monte Carlo calculations show that the solvation entropy of the isopropyl-bonded species is considerably higher than that of the fluoromethyl-bonded complex, which assists in explaining its dominance in the liquid phase spectra.
Highlights
The working principle of anaesthetics has been in the focus of vigorous research for many decades, always with the intention of improving and understanding their remarkable medical applications
View Article Online survive at the higher temperatures of the solutions in liquid xenon (LXe), where they can be studied under conditions of thermodynamic equilibrium, allowing the stoichiometry and complexation enthalpy to be determined
At the MP2/cc-pVDZ level we have identified three pairs of equivalent conformers that, as was the case with the previous investigation,[29] differ in the values of t1 and t2
Summary
The working principle of anaesthetics has been in the focus of vigorous research for many decades, always with the intention of improving and understanding their remarkable medical applications. The investigations have shown that they selectively interact with membrane proteins.[1] Model systems for these, i.e. reference proteins with designed binding locations, have been developed and have been intensively studied with X-ray methods and spectroscopic techniques such as infrared and Raman, fluorescence and high resolution NMR.[2,3,4]. We have concentrated on sevoflurane, (CF3)2CHOCH2F, one of the prevalent anaesthetics,[7,8,9] and its interactions, in view of the above, with the ultimate aromatic model compound benzene, using supersonic jet and cryosolutions infrared and Raman spectroscopic techniques. The supersonic jet experiments allow the study of weakly bonded complexes, amplifying their concentration due to the low temperatures, without the complications of solvent influences. Survive at the higher temperatures of the solutions in liquid xenon (LXe), where they can be studied under conditions of thermodynamic equilibrium, allowing the stoichiometry and complexation enthalpy to be determined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
