Dispersive Optical Activity of (S)-2-Methylaziridine: Intrinsic Properties and Extrinsic Solvation Effects

The dispersive optical activity of conformationally flexible S-2-methylaziridine (S-2-MeAz) has been investigated experimentally under isolated and solvated conditions to elucidate the impacts of large-amplitude (conformational) and small-amplitude (vibrational) nuclear degrees of freedom on intrinsic chiroptical response and the extrinsic perturbations caused by seven distinct solvents. All solution-phase measurements of optical rotatory dispersion (ORD) revealed plain-looking curves of uniformly negative polarity in the near-ultraviolet/visible regions, while their solvent-free counterpart showed evidence of a zero-crossing that would lead to positive rotatory powers for wavelengths ≤350 nm. A variety of quantum-chemical paradigms built upon density-functional (dispersion-corrected B3LYP and cam-B3LYP) and coupled cluster (CCSD) levels of theory were enlisted to explore the structural and response characteristics of stationary points within the ground electronic state of S-2-MeAz. Two stable conformations possessing distinct orientations of the amino (N-H) moiety with respect to the methyl substituent on the aziridine ring were identified, with the C1 (trans or anti) isomer, which is the global-minimum of energy in all media, predicted to have wavelength-resolved positive specific rotations that were 2-3 times smaller in magnitude than the corresponding negative values of the higher-lying C2 (cis or syn) form. The antagonistic chiroptical signatures of these species were merged under the independent-conformer ansatz by using ambient (T = 300 K) population fractions derived from various relative internal-energy (without and with vibrational zero-point offsets) and free-energy metrics. For isolated (vapor-phase) S-2-MeAz molecules, quantitative agreement between theory and experiment was attained by combining ensemble-averaged CCSD calculations of purely electronic optical activity (EOA) evoked from the static equilibrium configurations of C1 and C2 with commensurate harmonic and anharmonic nuclear contributions to vibronically-/vibrationally-induced optical activity (V2OA). Detailed analyses found essentially all 27 modes of each conformer to participate actively without any particular motions of the molecular framework dominating. In contrast, attempts to model condensed-phase behavior based on the conformer structures, energies, and response-properties (viz., EOA) emerging from PCM and SMD implicit-solvation treatments failed to reproduce the overall shapes of observed ORD profiles, thereby suggesting that other neglected factors (e.g., explicit solute-solvent interactions) may be at play.