Early research efforts have focused on understanding and exploiting the high sensitivity of second harmonic generation (SHG) and sum-frequency generation (SFG) measurements to chirality.  Whereas absorbance circular dichroism (CD) and optical rotary dispersion (ORD) are subtle effects relative to the analogous achiral properties of absorption and refraction, the chiral responses in second harmonic generation and sum-frequency generation are on the same order of magnitude as the achiral responses. Furthermore, this chiral-specific response often originates from a single molecular monolayer in a diffraction-limited spot size, corresponding to a conservative detection limit of ~106 molecules required for chiral analysis. 

We have developed a general and self-consistent approach for simplifying the molecular interpretations of broad classes of nonlinear optical and multi-photon processes (J. Phys. Chem. A 2005; J. Phys. Chem. B. 2004). These developments have engendered new, intuitive visualization methods for depicting the molecular tensor with full quantitative rigor (J. Phys. Chem. B, 2005, J. Comput. Chem. 2007, Acc. Chem. Res. 2007).  In brief, standard sum-over-states expressions for the tensors describing NLO or multi-photon phenomena derived from time-dependent perturbation theory were shown to be intuitively and concisely represented by simple direct products of lower-order effects without requiring any additional assumptions or approximations. This approach is very general, providing a simple method for interpreting the overall magnitudes and polarization dependences of broad classes of nonlinear optical and multi-photon process, including SHG, SFG, coherent anti-Stokes Raman spectroscopy, higher harmonic generation, hyper-Raman spectroscopy, multi-photon absorption, etc. In the specific case of electronically resonant SHG and SFG, the molecular tensor was rigorously shown for the first time to be given by the simple product of the tensor for two-photon absorption and the transition moment for stimulated emission.

The exquisite sensitivity of polarization-dependent SHG and SFG measurements to chirality have fueled the need for the development of general predictive tools at both the molecular level (J. Phys. Chem. B 2006; Chem. Phys. Lett. 2004) and in the laboratory frame (ChemPhysChem 2004; J. Am. Chem. Soc. 2003; Phys. Rev. B. 2002; J. Chem. Phys. 2002).  Within the molecular frame, a simple perturbation theory approach was developed for quantitatively predicting the second-order NLO properties of systems containing coupled chromophores. The predictions of the model are consistent with previous experimental measurements and provide a simple context for interpreting the NLO properties of dimeric and polymeric systems.   At the macroscopic level, it was demonstrated both experimentally (J. Am. Chem. Soc. 2003, J. Am. Chem. Soc. 2006) and theoretically (Phys. Rev. B. 2002; J. Chem. Phys. 2002, J. Am. Chem. Soc. 2006) that orientational effects alone can yield large chiral effects in SHG and SFG measurements of surface assemblies.  In brief, chirality within the sterics driving surface packing generally leads to asymmetric orientation of the chromophore planes. This structural origin of chirality is analogous to that arising in a propeller, in which the blades themselves are not required to be chiral in order to generate a chiral macrostructure. Unlike chiral effects in absorbance CD, coupling between the achiral chromophores is not required for the generation of chiral-specific surface measurements. Experimental measurements of achiral chromophores assembled at chiral-templated interfaces have confirmed that these orientational effects can be quite large. Most significantly, the experimentally measured magnitudes, signs, and trends for the chiral and achiral nonlinear optical properties of bacteriorhodopsin Langmuir-Blodgett films were quantitatively predicted through molecular modeling calculations using the known structure and orientation of the retinal chromophore with no adjustable parameters (J. Am. Chem. Soc. 2006). The intrinsic chirality of the retinal chromophore was calculated to be insignificant, confirming that the macroscopic chiral responses arose exclusively from simple orientational effects.