Research Overview
Identification and characterization of transient intermediates is crucial for developing detailed molecular-level knowledge of chemical reaction mechanisms – insight that is required to fully understand important biological processes like photosynthesis, energy storage and transfer, and for the rational development of novel synthetic catalysts. However, key reaction intermediates and their dynamics are often too short-lived or technically challenging to capture and interrogate directly with current methods. Next‑generation methods are required to isolate and probe elusive reaction intermediates and transition‑state species with atomistic detail.
Our research program seeks to develop novel experimental techniques which will allow for the capture and direct interrogation of reaction intermediates by combining the high sensitivity and selectivity of mass spectrometry, the high-frequency resolution of gas‑phase ion spectroscopies, and the time resolution of ultrafast spectroscopies in a single experiment.
The versatility of mass spectrometric techniques allows for the careful control and manipulation of the chemical system of interest in a composition-selective manner, allowing for the isolation of well-defined chemical architectures. Cryogenic cooling (10 K) of these isolated systems in an ion trap allows us to obtain highly resolved optical spectra, yielding unambiguous structural identification. The time evolution of the spectroscopic transitions with ultrafast resolution will help us characterize the time-evolving shape of the reactive potential energy surface (PES). This data will provide the basis for clear mechanistic interpretation of fast chemical reactions and how the surrounding chemical environment actively dictates the reaction dynamics and underlying shape of the PES.
Specifically, we are interested in studying catalytic processes driven by proton-coupled electron transfer (PCET), which are ubiquitous throughout chemistry and biology. Our focus will include two forefront problems where clear mechanistic details are vitally needed: (1) The role of tyrosine and tryptophan in biological PCET, in particular, the nature and dynamics of TyrOH•+ and TrpNH•+ radical cation species which are proposed key intermediates across numerous catalytic proton transport pathways. (2) Capturing intermediates generated during the activation of small molecules by organometallic catalysts, specifically, how solvent waters around the active site and ligand composition in water oxidation catalysts drive the formation of the proposed high-valent metal-oxo intermediates.
Capturing Proton-Coupled Electron Transfer (PCET) Processes in Biological Model Systems
Due to the confined environments encountered in biological systems, proton transport (PT) processes are often mediated through water amino acid side chains. Of particular importance are the roles of the aromatic amino acids Tyr and Trp, which are readily oxidized to form radical intermediates that play critical roles in charge transport reactions across many biological processes including in the oxygen-evolving complex of Photosystem II, ribonucleotide reductase, cytochrome c oxidase, and photolyase. To further complicate matters, proposed PCET mechanisms and observed dynamics vary dramatically from system to system due to differences in local chemical environments. The critical questions that must be answered, therefore, do not simply revolve around addressing the type of mechanism (e.g., concerted vs. step-wise mechanisms), but also in understanding how these pathways are dictated by the local environment (e.g., proton donor-acceptor distances, amino acid charge states, role of water/solvent).
We will first study Tyr and Trp model complexes, such as the Ru(bpy)32+-Tyr/Trp complexes shown here which have been extensively studied in solution. Solution-phase studies, however, have focused on the electronic transitions and have only inferred about the proton transfer coordinate. By triggering PCET with an actinic UV/Vis pump, we will be able to directly monitor the proton transfer coordinate using time and frequency-resolved IR spectroscopies on the by probing the key TyrO-H and TrpN-H stretches. Crucially, actinic excitation in a controlled gas-phase environment will allow for the generation and capture of the critical radical cation intermediates as Tyr and Trp oxidize upon electron transfer to the metal center. Transient IR pump-IR probe experiments (UV/Vis-IR-IR) will be crucial to recover how the PT PES evolves in real time during PCET reactions.
The crucial advantage of our approach is the ability to perform detailed, systematic studies of PCET dynamics in a controlled fashion. By having complete control over the chemical environment (proton donor-acceptor distance, oxidative potential of the metal center, addition of solvent water one molecule at time, H/D exchange and kinetic isotope effects, temperature dependence,…) we will be able to develop a more unified molecular-level description of PCET mechanisms.
Generation and Capture of Reactive Intermediates Relevant to Small Molecule Catalysis
Activation of small molecules using homogenous organometallic catalysts has rapidly grown into a new frontier of modern chemical research. PCET is often invoked as crucial steps in the proposed catalytic cycles and is now being exploited in the design of catalysts for organic synthesis. However, reactive intermediates in catalytic reactions are usually too short-lived to capture using standard solution-phase techniques, leading to proposed reaction mechanisms that are often highly debated. In order to better design and optimize organometallic catalysts, more intimate knowledge of the reaction mechanisms is required, in particular, the unambiguous identity of the short‑lived intermediates and how PCET drives the formation of these species. The application of our experimental approach provides a potential new method to activate isolated catalysts, allowing for the generation and ultrafast spectroscopic interrogation of the critical short‑lived intermediates formed through PCET.
An ultrafast actinic UV/Vis pump will be used to activate the system of interest, such as the protypical RuII(bpy)3(H2O)2+ water oxidation catalyst. After actinic excitation, we will monitor the spectral dynamics of the water OH stretches as electron transfer from water to Ru begins to weaken the O‑H bonds and strengthen the Ru-O bond. The important variation here will be the ability to complex the bound water with a controlled amount of solvent water molecules. The sequential addition of water will reveal how solvent molecules influence the dynamics and mechanism of intermediate formation one molecule at a time. The vibrational transitions, and thus intermediate structures, will unambiguously be assigned based on the high-resolution IR spectra that will be recorded as outlined schematically in the accompanying figure. A key observation will be how many solvent waters will be required to stabilize the RuIII-OH intermediate and allow for the irreversible PT to the water solvent cluster. Critical insight will be gained by monitoring how the H-bond structure of the solvent network changes upon accommodation of the transferring proton, as this rearrangement will be crucial for promoting long‑range PT away from the metal complex. Here, UV/Vis‑IR‑IR measurements will again be critical to establish the changes in the PES during the PT process, in particular how the solvent dynamics dictate changes to the PT barrier height during the transfer process.
Also of great importance are the roles of the organic ligands and how their electronic properties influence the performance of the catalyst. A systematic study of how the ultrafast PT spectral dynamics evolve as different electron donating or withdrawing substituents (methyl, ethyl, hydroxyl, nitro, etc.) are added to the bipyridine ligands or as the ligands are changed altogether will help establish how the overall electronic structure determines the rate of the critical first PT step in the catalytic cycle. This is a crucial piece of information that is necessary for the rational design of improved catalysts.
PCET mechanisms and the crucial active role of solvent around the metal-ligand active site are proposed to occur in other small molecule catalysts such as those for CO2 reduction and CH bond activation. Our experimental methods can therefore be readily applied to other catalytic systems.
