Studies of conformational isomerization have typically occurred in one of two size regimes. At one extreme are cases where isomerization occurs on a potential energy surface with two conformational minima (e.g., cis/trans isomerization or H-atom tunneling) that are connected by a single transition state along a well-defined reaction coordinate. In such circumstances, detailed state-to-state studies are often possible that probe the energy barrier and reaction dynamics in significant detail. In the other extreme are large macromolecules such as proteins that have potential energy landscapes that are staggeringly complex, so that the nature of the unfolded ‘reactant’ and folded ‘product’, the pathway(s) that connect them, and the timescales over which reaction occur are difficult to define, determine, or control. Furthermore, state-specific descriptions of the dynamics of folding in this macromolecule limit are clearly beyond our present grasp, whether experimentally or by calculation. The wide gulf in terminology, methodology, and goals for studies of conformational isomerization conducted in the two extremes of small and large constitutes a ‘complexity gap’, which is currently of significant proportions.

Between these two extremes lies an interesting size regime in which the full set of conformational minima can still be enumerated, but yet the complexity of the potential energy surface is sufficient to raise issues that may carry through to much larger systems. Our group has utilized the powerful methods at our disposal to take (admittedly small) steps into this complexity gap, studying the single-conformation spectroscopy and conformational isomerization dynamics of molecules possessing a range of types and degrees of conformational complexity. Molecules at the entrance to the complexity gap are large enough to possess many flexible degrees of freedom, but small enough to still benefit from conformation-selective and state-selective studies of the conformational dynamics. A long-term goal of our work has been to develop general rules connecting key features of the potential energy landscapes of the molecules to the time-scales, pathways, and product yields formed in the isomerization process. We also try to evaluate whether there are circumstances in large molecules in which conformation- and mode-specific excitation (for example, involving excitation of a single oscillator in a weakly coupled branch of the molecule) could lead to non-statistical product yields.

A prerequisite to success in this endeavor is a quantitative knowledge of the structures and energetics of key stationary points (minima and barriers) of the potential energy surface on which isomerization occurs. The same kinds of double resonance schemes that are so useful for the studies of molecular clusters also apply to conformational isomers; however, these studies have the additional challenge that mass selection cannot distinguish the isomers. A first step, then, is to determine the number, relative populations, spectroscopic signatures, and conformational assignments of the molecules of interest. This has been a major thrust of our research efforts in the past five years. We are studying a range of molecules with either possess some particular biological relevance (e.g., serotonin or melatonin), or have unique conformational properties (e.g., aromatic molecules with two independent, flexible side chains, multiple ultraviolet chromophores, or macrocyclic receptor sites) or unique folding properties (β-peptides, α/β- peptides, γ-peptides).

The results of the conformation-specific spectroscopy then serve as a foundation for hole-filling or population transfer studies of the conformational isomerization dynamics. SEP excitation has the advantage that it can be used to place a well-defined amount of energy in a single conformation and vary that energy from well below the lowest barriers to isomerization up through these barriers. By selectively exciting conformation X upstream in the supersonic expansion, and selectively detecting conformation Y downstream, one can record the gains in population that occur during the X(E)→Y isomerization. Determining barrier heights to isomerization then amounts to tuning the internal energy E given to conformation X, and looking for the onset of formation of product Y. A set of such spectra in the molecule tryptamine are shown to the right, where the numbers on the spectra indicate the energy thresholds for isomerization in cm^-1 for the A→(B-F) pairs. These studies effectively use spectroscopy to determine barrier heights on the potential energy surface.

In principle, these methods are applicable in any circumstance where more than one distinct isomer is connected by a barrier reachable by laser excitation. For instance, we have recently used the method to study the laser-initiated shuttling of a single water molecule between two H-bonding sites on the same solute molecule (trans-formanilide, TFA). This unusual ‘reaction’ must be occurring in bulk solution, but cannot be studied in the presence of the other solvent molecules that surround the solute. However, both forms of the complex (NH bound and C=O bound) are observed in the supersonic expansion, and SEP-population transfer spectroscopy was used to shuttle the water molecule in either direction (NH→C=O and C=O→N-H).

More generally, we are presently engaged in a concerted push to widen the range of systems studied by these methods. We have recently developed a mass-resolved version of infrared population transfer spectroscopy, which we are using to study the conformation-specific product yields following photodissociative loss of a water molecule from biomolecule-(H₂O) complexes with different H₂O binding sites and different initial biomolecular conformation.