Mimicking anesthetic–receptor interactions in jets: the propofol–isopropanol cluster

Abstract

The interaction of the general anesthetic propofol with an individual residue of threonine in the membrane receptors has been modeled in the gas phase by examining the adduct of propofol with the isopropanol side-chain. We determined the structural preferences of the cluster using a combination of mass-resolved laser spectroscopy and quantum mechanical calculations. The first electronic transition of propofol-isopropanol was recorded with vibrational resolution using resonant two-photon ionization (R2PI) and ion dip IR spectroscopy. The spectra obtained were compared with density-functional calculations (DFT) using the M06-2X functional in order to obtain the cluster's structure. Three isomers have been detected. The results suggest that propofol acts as a Brønsted acid, donating a proton to the isopropanol molecule in a conformation that resembles that of propofol-water, but displaced towards the aromatic ring, due to the interaction with the aliphatic side of isopropanol. The higher affinity of propofol for isopropanol compared to water may correlate with the biological role of propofol at the protein binding site. On the other hand, propofol shows a similar affinity for isopropanol and phenol, which could explain the mobility that propofol experiences inside the GABAA cavity.

The evolution towards cyclic structures in the aggregation of aromatic alcohols: the dimer, trimer and tetramer of 2-phenylethanol

“…15–17 Following these previous works on small and simple dimers, we are engaged in the study of more complex aggregates, characterized by a larger molecular size and different competing interactions. We use a multi-methodological approach, which combines broadband microwave spectroscopy for small-scale systems (dimers–trimers) with laser spectroscopy for the largest clusters (up to nonamers), as exemplified with the propofol homo 18 and heteroclusters 19–21 or the aniline 22 homoaggregates. The extension of the molecular size is challenging because of the growing spectral congestion and computational difficulties, but permits following the emergence of molecular-scale patterns, such as nanomicelles.…”

Spatial separation of 2-propanol monomer and its ionization-fragmentation pathways

“…The dipole-moment components are µ a = 0, µ b = 1.40 D, µ c = 0.73 D for the trans [7] and µ a = 1.114 D, µ b = 0.737 D, µ c = 0.813 D for the gauche conformer, respectively [8]. Their energy difference is smaller than 1 kJ/mol and the isomerization barrier corresponding to rotation of the hydroxyl moiety is low [16]. The gauche conformer is more stable than the trans conformer and there is a strong conformational relaxation of 2-propanol monomer from trans to gauche [44].…”

“…Supersonic molecular beam is a valuable tool for molecular spectroscopy and the studies of molecular dynamics and reactions [11][12][13]. For instance, this was exploited in studies of the hydrogen bonding in 2-propanol [14] and its hydrogen-bonded complexes [15,16]. Generally, the supersonic expansion provides beams of molecules at low rotational temperatures.…”

Tracing Photoinduced Hydrogen Migration in Alcohol Dications from Time-Resolved Molecular-Frame Photoelectron Angular Distributions

“…59−61 Propagations were performed with a time step of Δt = 0.1 fs and a fictitious electron mass of μ = 0.1 amu, ensuring adiabaticity in the simulations. For ethanol, propanol, and isopropanol, the different structural isomers existing at room temperature were considered, 62,63 namely the gauche and trans conformers for ethanol, 64−66 the gauche and trans conformers for 2-propanol, 67,68 PA-MFPAD Calculations. To calculate the electronic continuum states that are necessary to obtain PA-MFPADs, we have used the multiple-scattering method of ref 71.…”