Solvent Effect on Optical Rotation: A Case Study of Methyloxirane in Water

Abstract

A long-standing challenge in molecular stereochemistry is to assess the contributions of the solvent surrounding chiral organic molecules. The observed specific rotation angles and optical rotatory dispersion (ORD) spectra are strongly influenced by solvent-solute interactions. For example, (S)-methyloxirane has a positive optical rotation (OR) in water and a negative OR in benzene.[1] The vapor phase and condensed phase optical rotations of chiral molecules are also known to differ in large and nonintuitive ways.[2a] Access to experimental gas phase optical rotation data [2] and to modern linear-response OR calculations [3] provides the tools needed to analyze and predict the contributions of solute-solvent interactions to OR. Wilson et al. recently reported the OR for a series of organic molecules in the vapor phase using cavity ring-down polarimetry.[2b] These authors compared the solution and vapor phase OR to assess the influence of the condensed phase environment on ORD. They concluded: 1) for flexible solute molecules, solvent stabilization of individual conformers can influence the optical rotation strongly; 2) solvation of rigid molecules like methyloxirane causes changes in the static and dynamic distribution of molecular electron densities; and 3) surprisingly, OR under solvent-free conditions can resemble OR measured in a highly polar solvent. We find that, for methyloxirane in high-polarity solvents such as water, it is essential to include explicit solutesolvent interactions in the theoretical analysis to describe the observed ORD spectrum.Recently, coupled-cluster (CC) and time dependent density functional theory (TD-DFT) methods have been used to predict OR.[3l] However, the substantially greater computational efficiency of TD-DFT methods has led to their favored use in current OR calculations. The solvent dependence of OR for chiral molecules has been computed using TD-DFT and an implicit continuum solvent model. Kongsted et al. recently used CC methods combined with a continuum solvent description to calculate the influence of solvent on the OR of (S)-methyloxirane.[3j,k] The authors concluded that continuum models do not reproduce the experimentally observed solvent shifts in the ORD spectra as a function of solvent. Moreover, implicit solvent models do not predict the sign change in the ORD spectrum of methyloxirane in aqueous solution at wavelengths longer than 400 nm. Accordingly, the inclusion of explicit solvent effects appears to be essential for further progress. Here, we show that ORD calculations using explicit solvent models, combined with continuum models, such as the conductor-like screening model (COSMO), [4] can capture the sign and relative magnitude of the ORD spectrum of methyloxirane in water. More importantly, explicit solvent studies allow elucidation of the solvent contributions to the observed OR spectrum. Comparison of the total computed OR (solute + solvent) with the OR computed for the solvent shell (solvent with the chiral solute removed from the electronic structur...

Gas phase optical rotation calculated from coupled cluster theory with zero‐point vibrational corrections from density functional theory

“…A promising, if computationally expensive, alternative is to combine molecular dynamics (MD) simulation with quantum chemical sampling of the solute and explicit solvent molecules. [40][41][42] In an attempt to keep the computational cost of the MD-based approach at a minimum, Kundrat and Autschbach 43,44 have shown that a simple point charge representation of the solvent molecules (water) may be used to simulate explicit solvent effects in the quantum chemical sampling. As noted by these authors, the MD-based scheme may also be used as an alternative to Boltzmann averaging to account for conformational effects.…”

Hydration of a Chiral Molecule: The Propylene Oxide⋅⋅⋅(Water)2 Cluster in the Gas Phase

“…[5] It would be of great interest to follow the solvation process by sequentially solvating PO with more water molecules to conclusively establish the trend.…”

“…Subsequent theoretical simulations showed that, interestingly, the optical rotation response in an aqueous environment is dominated by that of the binary PO···water complex rather than of the PO monomer itself. [5] In addition, a tentative conclusion that the water molecules bind preferentially to PO in the anti rather than in the syn position was drawn, by comparing the simulations with the experimental results. [4,5] Here, anti or syn refers to the side of PO that is opposite to or the same as the methyl group, respectively.…”

“…In particular, syn PO···H 2 O was found to be strongly preferred over the anti conformer experimentally, [7] whereas the theoretical modeling predicted anti to be a preferred binding position in an aqueous solution. [5] This motivated us to carry out further gas-phase studies of PO sequentially solvated by a few water molecules to bridge this gap. In this work, we report the rotational spectroscopic and high-level ab initio studies of the PO···(H 2 O) 2 ternary cluster.…”

Induzierte Chiralität in achiralen Lösungsmitteln – mysteriöse Solvenseffekte, aufgeklärt mit theoretischen Methoden

“…b) Qualitative Situation für Methyloxiran (nach den Daten aus Lit. [9,11] oder eine ¾nderung des Aggregationsverhaltens des chiralen Moleküls.…”