The nonresonant optical activity of two highly flexible aliphatic amines, (2R)-3-methyl-2-butanamine (R-MBA) and (2R)-(3,3)-dimethyl-2-butanamine (R-DMBA), has been probed under isolated and solvated conditions to examine the roles of conformational isomerism and to explore the influence of extrinsic perturbations. The optical rotatory dispersion (ORD) measured in six solvents presented uniformly negative rotatory powers over the 320-590 nm region, with the long-wavelength magnitude of chiroptical response growing nearly monotonically as the dielectric constant of the surroundings diminished. The intrinsic specific optical rotation, (in deg dm-1 [g/mL]-1 ), extracted for ambient vapor-phase samples of R-MBA [-11.031(98) and -2.29 (11)] and R-DMBA [-9.434 (72) and -1.350 (48)] at 355 and 633 nm were best reproduced by counterintuitive solvents of high polarity (yet low polarizability) like acetonitrile and methanol. Attempts to interpret observed spectral signatures quantitatively relied on the linear-response frameworks of density-functional theory (B3LYP, cam-B3LYP, and dispersion-corrected analogs) and coupled-cluster theory (CCSD), with variants of the polarizable continuum model (PCM) deployed to account for the effects of implicit solvation. Building on the identification of several low-lying equilibrium geometries (nine for R-MBA and three for R-DMBA), ensemble-averaged ORD profiles were calculated at T = 300 K by means of the independent-conformer ansatz, which enabled response properties predicted for the optimized structure of each isomer to be combined through Boltzmann-weighted population fractions derived from corresponding relative internal-energy or free-energy values, the latter of which stemmed from composite CBS-APNO and G4 analyses. Although reasonable accord between theory and experiment was realized for the isolated (vapor-phase) species, the solution-phase results were less satisfactory and tended to degrade progressively as the solvent polarity increased. These trends were attributed to solvent-mediated changes in structural parameters and energy metrics for the transition states that separate and putatively isolate the equilibrium conformations supported by the ground electronic potential-energy surface, with the resulting displacement of barrier locations and/or decrease of barrier heights compromising the underlying premise of the independent-conformer ansatz.
Keywords: computational prediction of optical activity; conformational flexibility; dispersive optical activity; intrinsic chiroptical response; optical rotatory dispersion; solvation effects.
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