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Exploring microsolvation of the anesthetic propofol
Iker Leon1, Emilio J Cocinero, Judith Millán
1Dpto. de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, Leioa, Spain.
Physical Chemistry Chemical Physics : PCCP
|February 24, 2012
Summary
Researchers studied propofol, a general anesthetic, and its interaction with water using advanced spectroscopy and calculations. They identified multiple propofol-water structures, explaining its mobility in biological sites.
Area of Science:
- Physical Chemistry
- Computational Chemistry
- Molecular Spectroscopy
Background:
- Propofol (2,6-diisopropylphenol) is a widely used intravenous anesthetic agent.
- Understanding its molecular interactions is crucial for pharmacology and drug design.
Purpose of the Study:
- To elucidate the molecular structure of propofol and its complexes with water.
- To investigate the influence of water on propofol's hydrogen bonding capabilities.
Main Methods:
- Combined spectroscopic techniques: 1- and 2-color REMPI, UV/UV hole burning, IRIDS.
- Performed under cooled and isolated conditions.
- Supported by high-level ab initio calculations.
Main Results:
- Identified four isomers for bare propofol.
- Detected three isomers for monohydrated propofol and two for propofol·(H2O)2.
- Isopropyl groups hinder but do not eliminate OH solvation, weakening propofol-water hydrogen bonds.
Conclusions:
- The reduced hydrogen bond strength explains propofol's high mobility within the GABA(A) receptor.
- Propofol's limited hydrogen bonding with tyrosine residues in the GABA(A) active site is supported by these findings.
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