1. Intrinsic Optical Activity & Environmental Perturbations: Solvation Effects in Chiral Building Blocks
Paul M. Lemler, Clayton L. Craft, & Patrick H. Vaccaro
Department of Chemistry, Yale University
225 Prospect Street New Haven, CT USA

2. Chiral Molecules Possess Intrinsic “Handedness”
Non-Superimposable Mirror Images (no improper rotation axes)
Circular Birefringence (CB) : Non-Resonant Differential Retardation

3. Intrinsic Response Perturbed by Extrinsic Factors
S-(–)-Methyloxirane
Complex Formation
Unexpected Results
Counterintuitive solvents best mimic intrinsic response.
Quantitative calculations demand zero-point corrections.
Chiral Solvent Shell
Wilson, S. M., Wiberg, K. B., Murphy, M. J., and Vaccaro, P. H. Chirality. 20(3-4), (2008).
Mukhopadhyay, P., Zuber, G., Wipf, P., and Beratan, D. N., Angew. Chem. Int. Ed. 46(34), (2007); 7(12), (2006).

4. Cavity Ring-Down Polarimetery

5. Previously Inaccessible Systems
(1S,2S)-(−)-1-Phenylpropylene oxide (PPO)
(R)-(+)-α-Methylbenzylamine (αMBA)
Conformationally Rigid
Conformationally Flexible
Methyl (2S)-Glycidate (MGly)
(S)-(−)-Glycidol (Gly)
B3LYP/apVTZ

6. M odel Solvation Models Explicit Implicit
P olarizable
C ontinuum
M odel
Solute-solvent system modeled as a supramolecular complex
Accurate treatment of solute-solvent interaction in first solvation shell
Poor description of long-range interactions and electrostatic polarization
Computationally expensive with cost rising dramatically with size of system
Solvent modeled as a continuum dielectric (ε) that surrounds the solute cavity
Neglects important first-shell effects in cybotactic region
Accurate description of long-range electrostatic solute-solvent interactions
Computationally expedient owing to the reduction in effective degrees of freedom

7. Summary and Conclusions
Cavity Ring-Down Polarimetry (CRDP) affords a sensitive means for interrogating dispersive (CB) optical activity under rarefied conditions.
Modification of sample vessel has enabled hitherto inaccessible families of chiral molecules with new chemical functionalities to be investigated: αMBA and PPO.
Solvation can influence optical activity in pronounced and counterintuitive ways, modifying both magnitude and sign of the response evoked from rigid molecules.
Conformational flexibility can modify optical activity grossly, leading to structural isomers that often possess antagonistic physicochemical and chiroptical properties.
Additional theoretical & experimental work is needed to understand solution-phase chiroptical response, especially for cases where specific solute-solvent interactions or chiral imprinting of solvation shells plays an important role.
Supported by
U.S. National Science Foundation