Exploring microsolvation of the anesthetic propofol

Propofol (2,6-diisopropylphenol) is a broadly used general anesthetic. By combining spectroscopic techniques such as 1- and 2-color REMPI, UV/UV hole burning, infrared ion-dip spectroscopy (IRIDS) obtained under cooled and isolated conditions with high-level ab initio calculations, detailed information on the molecular structure of propofol and on its interactions with water can be obtained. Four isomers are found for the bare propofol, while only three are detected for the monohydrated species and two for propofol·(H(2)O)(2). The isopropyl groups do not completely block the OH solvation site, but reduce considerably the strength of the hydrogen bonds between propofol and water. Such results may explain the high mobility of propofol in the GABA(A) active site, where it cannot form a strong hydrogen bond with the tyrosine residue.