Randall H. Goldsmith

Understanding quantum interference in coherent molecular conduction.

Theory and experiment examining electron transfer through molecules bound to electrodes are increasingly focused on quantities that are conceptually far removed from current chemical understanding. This presents challenges both for the design of interesting molecules for these devices and for the interpretation of experimental data by traditional chemical mechanisms. Here, the concept of electronic coupling from theories of intramolecular electron transfer is extended and applied in the scattering theory (Landauer) formalism. This yields a simple sum over independent channels, that is then used to interpret and explain the unusual features of junction transport through cross-conjugated molecules and the differences among benzene rings substituted at the ortho, meta, or para positions.

Quantum interference in acyclic systems: Conductance of cross-conjugated molecules

We calculate that significant quantum interference effects can be observed in elastic electron transport through acyclic molecules. Interference features are evident in the transmission characteristics calculated for cross-conjugated molecules; significantly, these effects dominate the experimentally observable conduction range. The unusual transport characteristics of these molecules are highlighted through comparison with linearly conjugated and nonconjugated systems. The cross-conjugated molecules presented here show a large dynamic range in conductance. These findings represent a new motif for electron transfer through molecules that exhibit both very high and very low tunneling conductance states accessible at low bias without nuclear motion. In designing single molecule electronic components, a large dynamic range allows a high on/off ratio, a parameter of fundamental importance for switches, transistors, and sensors.

Probing Single Biomolecules in Solution Using the Anti-Brownian Electrokinetic (ABEL) Trap

Single-molecule fluorescence measurements allow researchers to study asynchronous dynamics and expose molecule-to-molecule structural and behavioral diversity, which contributes to the understanding of biological macromolecules. To provide measurements that are most consistent with the native environment of biomolecules, researchers would like to conduct these measurements in the solution phase if possible. However, diffusion typically limits the observation time to approximately 1 ms in many solution-phase single-molecule assays. Although surface immobilization is widely used to address this problem, this process can perturb the system being studied and contribute to the observed heterogeneity. Combining the technical capabilities of high-sensitivity single-molecule fluorescence microscopy, real-time feedback control and electrokinetic flow in a microfluidic chamber, we have developed a device called the anti-Brownian electrokinetic (ABEL) trap to significantly prolong the observation time of single biomolecules in solution. We have applied the ABEL trap method to explore the photodynamics and enzymatic properties of a variety of biomolecules in aqueous solution and present four examples: the photosynthetic antenna allophycocyanin, the chaperonin enzyme TRiC, a G protein-coupled receptor protein, and the blue nitrite reductase redox enzyme. These examples illustrate the breadth and depth of information which we can extract in studies of single biomolecules with the ABEL trap. When confined in the ABEL trap, the photosynthetic antenna protein allophycocyanin exhibits rich dynamics both in its emission brightness and its excited state lifetime. As each molecule discontinuously converts from one emission/lifetime level to another in a primarily correlated way, it undergoes a series of state changes. We studied the ATP binding stoichiometry of the multi-subunit chaperonin enzyme TRiC in the ABEL trap by counting the number of hydrolyzed Cy3-ATP using stepwise photobleaching. Unlike ensemble measurements, the observed ATP number distributions depart from the standard cooperativity models. Single copies of detergent-stabilized G protein-coupled receptor proteins labeled with a reporter fluorophore also show discontinuous changes in emission brightness and lifetime, but the various states visited by the single molecules are broadly distributed. As an agonist binds, the distributions shift slightly toward a more rigid conformation of the protein. By recording the emission of a reporter fluorophore which is quenched by reduction of a nearby type I Cu center, we probed the enzymatic cycle of the redox enzyme nitrate reductase. We determined the rate constants of a model of the underlying kinetics through an analysis of the dwell times of the high/low intensity levels of the fluorophore versus nitrite concentration.

Redox cycling and kinetic analysis of single molecules of solution-phase nitrite reductase

Single-molecule measurements are a valuable tool for revealing details of enzyme mechanisms by enabling observation of unsynchronized behavior. However, this approach often requires immobilizing the enzyme on a substrate, a process which may alter enzyme behavior. We apply a microfluidic trapping device to allow, for the first time, prolonged solution-phase measurement of single enzymes in solution. Individual redox events are observed for single molecules of a blue nitrite reductase and are used to extract the microscopic kinetic parameters of the proposed catalytic cycle. Changes in parameters as a function of substrate concentration are consistent with a random sequential substrate binding mechanism.

Unexpectedly Similar Charge Transfer Rates through Benzo-Annulated Bicyclo[2.2.2]octanes

A 4-(pyrrolidin-1-yl)phenyl electron donor and 10-cyanoanthracen-9-yl electron acceptor are attached via alkyne linkages to the bridgehead carbon atoms of bicyclo[2.2.2]octane and all three benzo-annulated bicyclo[2.2.2]octanes. The sigma-system of bicyclo[2.2.2]octane provides a scaffold having nearly constant bridge geometry on which to append multiple, weakly interacting benzo pi-bridges, so that the effect of incrementally increasing numbers of pi-bridges on electron transfer rates can be studied. Surprisingly, photoinduced charge transfer rates measured by transient absorption spectroscopy in toluene show no benefit from increasing the number of bridge pi-systems, suggesting dominant transport through the sigma-system. Even more surprisingly, the significant changes in hybridization undergone by the sigma-system as a result of benzo-annulation also appear to have no effect on the charge transfer rates. Natural Bond Orbital analysis is applied to both sigma- and pi-communication pathways. The transient absorption spectra obtained in 2-methyltetrahydrofuran (MTHF) show small differences between the benzo-annulated molecules that are attributed to changes in solvation. All charge transfer rates increase significantly upon cooling the MTHF solutions to their glassy state. This behavior is rationalized using combined molecular dynamics/electronic structure trajectories.

Photothermal Microscopy of Nonluminescent Single Particles Enabled by Optical Microresonators.

A powerful new paradigm for single-particle microscopy on nonluminescent targets is reported using ultrahigh-quality factor optical microresonators as the critical detecting element. The approach is photothermal in nature as the microresonators are used to detect heat dissipated from individual photoexcited nano-objects. The method potentially satisfies an outstanding need for single-particle microscopy on nonluminescent objects of increasingly smaller absorption cross section. Simultaneously, our approach couples the sensitivity of label-free detection using optical microresonators with a means of deriving chemical information on the target species, a significant benefit. As a demonstration, individual nonphotoluminescent multiwalled carbon nanotubes are spatially mapped, and the per-atom absorption cross section is determined. Finite-element simulations are employed to model the relevant thermal processes and elucidate the sensing mechanism. Finally, a direct pathway to the extension of this new technique to molecules is laid out, leading to a potent new method of performing measurements on individual molecules.

Challenges in Distinguishing Superexchange and Hopping Mechanisms of Intramolecular Charge Transfer through Fluorene Oligomers

The temperature dependence of intramolecular charge separation in a series of donor-bridge-acceptor molecules having phenothiazine (PTZ) donors, 2,7-oligofluorene FL(n) (n = 1-4) bridges, and perylene-3,4:9,10-bis(dicarboximide) (PDI) acceptors was studied. Photoexcitation of PDI to its lowest excited singlet state results in oxidation of PTZ via the FL(n) bridge. In toluene, the temperature dependence of the charge separation rate constants for PTZ-FL(n)-PDI, (n = 1-4) is relatively weak and is successfully described by the semiclassical Marcus equation. The activation energies for charge separation suggest that bridge charge carrier injection is not the rate limiting step. The difficulty of using temperature and length dependence to differentiate hopping and superexchange is discussed, with difficulties in the latter topic explored via an extension of a kinetic model proposed by Bixon and Jortner.

Single-Molecule Investigation of Initiation Dynamics of an Organometallic Catalyst.

The action of molecular catalysts comprises multiple microscopic kinetic steps whose nature is of central importance in determining catalyst activity and selectivity. Single-molecule microscopy enables the direct examination of these steps, including elucidation of molecule-to-molecule variability. Such molecular diversity is particularly important for the behavior of molecular catalysts supported at surfaces. We present the first combined investigation of the initiation dynamics of an operational palladium cross-coupling catalyst at the bulk and single-molecule levels, including under turnover conditions. Base-initiated kinetics reveal highly heterogeneous behavior indicative of diverse catalyst population. Unexpectedly, this distribution becomes more heterogeneous at increasing base concentration. We model this behavior with a two-step saturation mechanism and identify specific microscopic steps where chemical variability must exist in order to yield observed behavior. Critically, we reveal how structural diversity at a surface translates into heterogeneity in catalyst behavior, while demonstrating how single-molecule experiments can contribute to understanding of molecular catalysts.

Chip-Scale Fabrication of High-Q All-Glass Toroidal Microresonators for Single-Particle Label-Free Imaging.

Whispering-gallery-mode microresonators enable materials for single-molecule label-free detection and imaging because of their high sensitivity to their micro-environment. However, fabrication and materials challenges prevent scalability and limit functionality. All-glass on-chip microresonators significantly reduce these difficulties. Construction of all-glass toroidal microresonators with high quality factor and low mode volume is reported and these are used as platforms for label-free single-particle imaging.

Photothermal mapping and free-space laser tuning of toroidal optical microcavities

We report a tuning method for ultrahigh-quality factor toroidal optical microcavities capable of rapid modulation and resonance position control over multiple decades. A free-space laser is focused onto the resonators silicon support pillar, rapidly heating the mode-containing silica. Microcavity photothermal response is spatially mapped. Resonance shift varies inversely with pillar diameter, reaching 1.5 × 105 fm/mW at 2 μm diameter, allowing switching with 1 μW control power. Larger pillar resonators can be modulated at high speeds (>4 kHz). Heat flow simulations accurately model observed shifts. This versatile approach fulfills an outstanding need for fast, flexible control over toroid resonances.