Alternating 1-Phenyl-2,2,2-Trifluoroethanol Conformational Landscape With the Addition of One Water: Conformations and Large Amplitude Motions

Abstract

The 1:1 adduct of 1-phenyl-2,2,2-trifluoroethanol (PhTFE), a chiral fluoroalcohol, with water was investigated using chirped pulse Fourier transform microwave spectroscopy and computational methods. While PhTFE itself was predicted to have three minima, I (gauche+), II (trans), and III (gauche−), only I and II were stable and only I was observed experimentally. A systematic search of the PhTFE···H2O conformational landscape identified 110 stable minima, 14 of which are within a 15 kJ mol–1 energy window. Rotational spectra of the two PhTFE···H2O conformers along with several deuterium and 18O isotopologues were assigned, and the isotopic data were used to verify the corresponding structures. In the two observed monohydrate conformers, one contains PhTFE I where the water subunit is inserted into the existing intramolecular OH···F contact of I, and the binary adduct is stabilized by two intermolecular contacts: OH···OW and HW···F, whereas the other contains PhTFE II where the water subunit interacts with both the alcohol hydrogen and phenyl ring of II, demonstrating that interaction with water sufficiently stabilizes II for its observation in a jet expansion. Interestingly, the predicted electric dipole moment components at the identified minima deviate considerably from the experimental ones. Such deviations were analyzed in terms of dynamic effects associated with the large amplitude motions of the unbound HW. In addition, tunnelling effects associated with the exchange of the bonded and nonbonded HW were also discussed.

Conformations of Steroid Hormones: Infrared and Vibrational Circular Dichroism Spectroscopy

“…The Boltzmann averaged IR and VCD spectra of the three most stable conformers of DHEA were simulated using three different basis sets: cc-pVTZ, 6-31++G(2d,p) and def2-TZVPD. The B3LYP-D3BJ/def2-TZVP has been utilized extensively by the rotational spectroscopic community and the inclusion of an additional set of diffuse functions, i.e., def2-TZVPD, appeared to provide even better performance for conformational geometries and their energy ordering, with little additional computational cost [ 40 ]. It is interesting to compare its performance with the other two basis sets often used by the VCD and ROA community.…”

“…It has been recognized from some previous ab initio MD studies [ 28 ] and DFT VCD solvation studies [ 66 ] that using the spectroscopic properties at the predicted minima may not be enough to reproduce the observed spectral features in solution. More recently, some rotational spectroscopic studies [ 40 , 67 ] demonstrated clearly that the experimental electric dipole components and nuclear quadruple coupling constants could be very different from those predicted at the minima because of large amplitude motions. In addition, the associated VCD simulations showed that the vibrationally average features can be dramatically different from those at the minima [ 40 ].…”

“…More recently, some rotational spectroscopic studies [ 40 , 67 ] demonstrated clearly that the experimental electric dipole components and nuclear quadruple coupling constants could be very different from those predicted at the minima because of large amplitude motions. In addition, the associated VCD simulations showed that the vibrationally average features can be dramatically different from those at the minima [ 40 ]. Following a similar approach described in [ 66 ], we first performed a one-dimensional, relaxed potential energy surface (PES) along the dihedral angle (C19-C21-O2-C49) for 360° with the PCM of DMSO and the result is depicted in Figure S9 .…”

“…The energy barrier separating AcO-DHEA-I and AcO-DHEA-II is quite low (<2.5 kJ mol −1 ). One may expect the compound to undergo a large amplitude motion between I and II in solution and the resulting IR and VCD spectra would have contributions from all geometries in between [ 40 ]. In contrast, AcO-DEHA-III is separated from AcO-DHEA-II and -I by somewhat high barriers of ~20 kJ mol −1 .…”

“…In some cases, these minima turned out to be unstable after zero-point-energy (ZPE) correction, i.e., when the ZPE level is higher than the related conformational conversion transition state. In recent rotational spectroscopic studies of 1-phenyl-2,2,2-trifluoroethanol (PhTFE) [ 39 ] and its complex with a water molecule [ 40 ], PhTFE-W, it was reported that several DFT minima identified do not correspond to true conformers, i.e., they are connected by the so-called large amplitude motions. Furthermore, in those cases, some experimentally observed ground state properties, such as dipole moment components, deviate drastically from those predicated at the minima.…”