Rotational investigation of volatile anesthetics: Conformational equilibrium, molecular structure, and complex hyperfine interactions of methoxyflurane

The volatile anesthetic methoxyflurane was investigated in the 2-8 GHz region by chirp-excitation Fourier-transform broadband microwave spectroscopy. The presence of two conformers-gauche-trans (C1) and trans-trans (Cs)-each containing two quadrupolar chlorine nuclei and one methyl internal rotor, results in a very dense spectrum with complex rotational hyperfine effects, where contributions from nuclear quadrupole interactions and internal rotation couple to the overall molecular rotation. For the spectrally more complicated C1-conformer, additional impulse-excitation cavity measurements were carried out in the region of 10-21 GHz. To the best of our knowledge, there is no published code that can handle two quadrupolar nuclei in a non-coplanar orientation with respect to the internal rotor, so we developed our own codes interfacing with Pickett's SPFIT rovibrational fitting program to allow for a near-experimental accuracy fit of the relatively abundant isotopologues, comprising all isotopologue combinations of the 35Cl and 37Cl nuclei. Furthermore, the Hartwig-Herbers' XIAM-NQ code was later extended to treat a second quadrupolar nucleus, and global fits with this new code XIAM-2NQ were validated against SPFIT results. The relative transition intensities of the two conformers were used to estimate the relative room-temperature population as N(Cs)/N(C1) = 0.88 ± 0.30 corresponding to a difference in the Gibbs free energy of -1.4 ± 1.1 kJ/mol. A computational characterization using density functional theory [CAM-B3LYP-D3 (BJ)] complemented the experimental results. This work completes the rotational investigations on the conformational and structural panorama of the most important halogenated inhalational anesthetics, potentially enabling their monitoring through rotational spectroscopic fingerprints.