Jennifer Lynn Herek

Quantum control of energy flow in light harvesting

Coherent light sources have been widely used in control schemes that exploit quantum interference effects to direct the outcome of photochemical processes. The adaptive shaping of laser pulses is a particularly powerful tool in this context: experimental output as feedback in an iterative learning loop refines the applied laser field to render it best suited to constraints set by the experimenter. This approach has been experimentally implemented to control a variety of processes, but the extent to which coherent excitation can also be used to direct the dynamics of complex molecular systems in a condensed-phase environment remains unclear. Here we report feedback-optimized coherent control over the energy-flow pathways in the light-harvesting antenna complex LH2 from Rhodopseudomonas acidophila, a photosynthetic purple bacterium. We show that phases imprinted by the light field mediate the branching ratio of energy transfer between intra- and intermolecular channels in the complexs donor–acceptor system. This result illustrates that molecular complexity need not prevent coherent control, which can thus be extended to probe and affect biological functions.

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

Fluorescence imaging is currently attracting much interest as a method for intraoperative tumor detection, but most current tracers lack tumor specificity. Therefore, this technique can be further improved by tumor-specific detection. With tumor-targeted antibodies bound to a radioactive label, tumor-specific SPECT or PET is feasible in the clinical setting. The aim of the present study was to apply antibody-based tumor detection to intraoperative optical imaging, using preclinical in vivo mouse models. Methods: Anti–vascular endothelial growth factor (VEGF) antibody bevacizumab and anti–human epidermal growth factor receptor (HER) 2 antibody trastuzumab were labeled with the near-infrared (NIR) fluorescence dye IRDye 800CW. Tumor uptake of the fluorescent tracers and their 89Zr-labeled radioactive counterparts for PET was determined in human xenograft–bearing athymic mice during 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. Intraoperative imaging of fluorescent VEGF- or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneal dissemination tumor models. Results: Tumor-to-background ratios, with fluorescent imaging, were 1.93 ± 0.40 for bevacizumab and 2.92 ± 0.29 for trastuzumab on day 6 after tracer injection. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneal dissemination tumor models. These results were supported by standard histology, immunohistochemistry, and fluorescence microscopy analyses. Conclusion: NIR fluorescence–labeled antibodies targeting VEGF or HER2 can be used for highly specific and sensitive detection of tumor lesions in vivo. These preclinical findings encourage future clinical studies with NIR fluorescence–labeled tumor-specific antibodies for intraoperative-guided surgery in cancer patients.

Revisiting the optical properties of the FMO protein

We review the optical properties of the FMO complex as found by spectroscopic studies of the Qy band over the last two decades. This article emphasizes the different methods used, both experimental and theoretical, to elucidate the excitonic structure and dynamics of this pigment–protein complex.

Chemical Imaging of Oral Solid Dosage Forms and Changes upon Dissolution Using Coherent Anti-Stokes Raman Scattering Microscopy

Dissolution testing is a crucial part of pharmaceutical dosage form investigations and is generally performed by analyzing the concentration of the released drug in a defined volume of flowing dissolution medium. As solid-state properties of the components affect dissolution behavior to a large and sometimes even unpredictable extent there is a strong need for monitoring and especially visualizing solid-state properties during dissolution testing. In this study coherent anti-Stokes Raman scattering (CARS) microscopy was used to visualize the solid-state properties of lipid-based oral dosage forms containing the model drug theophylline anhydrate during dissolution in real time. The drug release from the dosage form matrix was monitored with a spatial resolution of about 1.5 microm. In addition, as theophylline anhydrate tends to form the less soluble monohydrate during dissolution, CARS microscopy allowed the solid-state transformation of the drug to be spatially visualized. The results obtained by CARS microscopy revealed that the method used to combine lipid and active ingredient into a sustained release dosage form can influence the physicochemical behavior of the drug during dissolution. In this case, formation of theophylline monohydrate on the surface was visualized during dissolution with tablets compressed from powdered mixtures but not with solid lipid extrudates.

Pump-probe and pump-deplete-probe spectroscopies on carotenoids with N=9–15 conjugated bonds

A series of all-trans-carotenoids with N=9, 13, and 15 conjugated bonds has been studied by pump-probe and pump-deplete-probe spectroscopies to obtain a systematic analysis of the energy flow between the different electronic states. The ultrafast dynamics in the carotenoids are initialized by excitation to the S2 state and subsequently manipulated by an additional depletion pulse in the near-IR spectral range. The changes in the dynamics after depletion of the excited state population allowed differentiation of the excited state absorption into two components, a major one corresponding to the well known S1 state and the small contribution on the red wing of the S0-S2 absorption band originating from the hot ground state. We found no evidence for an additional electronically excited state, usually called S*. Instead, a deactivation mechanism that includes the hot ground state supports the observed results nicely in the framework of a simple three state model (S2, S1, and S0).

Photoswitchable Sexithiophene-Based Molecular Wires

Photochromic sexithiophenes were prepared by oxidative electrochemical coupling of terthiophenes. The redox properties in the open state are typical of sexithiophenes. Ring closure of both photochromic units leads to a decrease in the energy of the LUMO orbitals with little affect on the energy of the HOMO orbitals. The photochemical tuning of the conjugation of a molecular wire is achieved by combining dithienylethene units with a sexithiophene.

Controlling the efficiency of an artificial light-harvesting complex.

Adaptive femtosecond pulse shaping in an evolutionary learning loop is applied to a bioinspired dyad molecule that closely mimics the early-time photophysics of the light-harvesting complex 2 (LH2) photosynthetic antenna complex. Control over the branching ratio between the two competing pathways for energy flow, internal conversion (IC) and energy transfer (ET), is realized. We show that by pulse shaping it is possible to increase independently the relative yield of both channels, ET and IC. The optimization results are analyzed by using Fourier analysis, which gives direct insight to the mechanism featuring quantum interference of a low-frequency mode. The results from the closed-loop experiments are repeatable and robust and demonstrate the power of coherent control experiments as a spectroscopic tool (i.e., quantum-control spectroscopy) capable of revealing functionally relevant molecular properties that are hidden from conventional techniques.

Background free CARS imaging by phase sensitive heterodyne CARS

In this article we show that heterodyne CARS, based on a controlled and stable phase-preserving chain, can be used to measure amplitude and phase information of molecular vibration modes. The technique is validated by a comparison of the imaginary part of the heterodyne CARS spectrum to the spontaneous Raman spectrum of polyethylene. The detection of the phase allows for rejection of the non-resonant background from the data. The resulting improvement of the signal to noise ratio is shown by measurements on a sample containing lipid.

Extraction of optical Bloch modes in a photonic-crystal waveguide

We perform phase-sensitive near-field scanning optical microscopy on photonic-crystal waveguides. The observed intricate field patterns are analyzed by spatial Fourier transformations, revealing several guided transverse electric (TE) and transverse magnetic (TM) like modes. Using the reconstruction algorithm proposed by Ha et al. [Opt. Lett. 34, 3776 (2009)], we decompose the measured two-dimensional field pattern in a superposition of propagating Bloch modes. This opens new possibilities to study specific modes in near-field measurements. We apply the method to study the transverse behavior of a guided TE-like mode, where the mode extends deeper in the surrounding photonic crystal when the band edge is approached

In vitro self-assembly of the light harvesting pigment-protein LH2 revealed by ultrafast spectroscopy and electron microscopy

Controlled ensemble formation of protein-surfactant systems provides a fundamental concept for the realization of nanoscale devices with self-organizing capability. In this context, spectroscopic monitoring of pigment-containing proteins yields detailed structural information. Here we have studied the association behavior of the bacterial light-harvesting protein LH2 from Rhodobacter spheroides in an n,n-dimethyldodecylamine-n-oxide/water environment. Time-resolved studies of the excitation annihilation yielded information about aggregate sizes and packing of the protein complexes therein. The results are compared to transmission electron microscopy images of instantaneously frozen samples. Our data indicate the manifestation of different phases, which are discussed with respect to the thermodynamic equilibrium in ternary protein-surfactant-water systems. Accordingly, by varying the concentration the formation of different types of aggregates can be controlled. Conditions for the appearance of isolated LH2 complexes are defined.