Femtosecond proton transfer in urea solutions probed by X-ray spectroscopy.

Proton transfer is one of the most fundamental events in aqueous-phase chemistry and an emblematic case of coupled ultrafast electronic and structural dynamics1,2. Disentangling electronic and nuclear dynamics on the femtosecond timescales remains a formidable challenge, especially in the liquid phase, the natural environment of biochemical processes. Here we exploit the unique features of table-top water-window X-ray absorption spectroscopy3-6 to reveal femtosecond proton-transfer dynamics in ionized urea dimers in aqueous solution. Harnessing the element specificity and the site selectivity of X-ray absorption spectroscopy with the aid of ab initio quantum-mechanical and molecular-mechanics calculations, we show how, in addition to the proton transfer, the subsequent rearrangement of the urea dimer and the associated change of the electronic structure can be identified with site selectivity. These results establish the considerable potential of flat-jet, table-top X-ray absorption spectroscopy7,8 in elucidating solution-phase ultrafast dynamics in biomolecular systems.

Control of the Two-photon Visual Process in ex vivo Retinas and in Living Mice.

Palcewska et al. first demonstrated near infrared (NIR) visual response in human volunteers upon two-photon absorption (TPA), in a seminal work of 2014, and assessed the process in terms of wavelength- and power-dependence on murine ex-vivo retinas. In the present study, ex-vivo electroretinography (ERG) is further developed to perform a complete characterization of the effect of NIR pulse duration, energy, and focal spot size on the response. The same set of measurements is successively tested on living mice. We discuss how the nonlinear intensity dependence of the photon absorption process is transferred to the amplitude of the visual response acquired by ERG. Finally, we show that the manipulation of the spectral phase of NIR pulses can be translated to predictable change in the two-photon induced response under physiological excitation conditions.

Multiorder Nonlinear Mixing in Metal Oxide Nanoparticles.

Whereas most of the reports on the nonlinear properties of micro- and nanostructures address the generation of distinct signals, such as second or third harmonic, here we demonstrate that the novel generation of dual output lasers recently developed for microscopy can readily increase the accessible parameter space and enable the simultaneous excitation and detection of multiple emission orders such as several harmonics and signals stemming from various sum and difference frequency mixing processes. This rich response, which in our case features 10 distinct emissions and encompasses the whole spectral range from the deep ultraviolet to the short-wave infrared region, is demonstrated using various nonlinear oxide nanomaterials while being characterized and simulated temporally and spectrally. Notably, we show that the response is conserved when the particles are embedded in biological media opening the way to novel biolabeling and phototriggering strategies.

Photoresponsive Nanocarriers Based on Lithium Niobate Nanoparticles for Harmonic Imaging and On-Demand Release of Anticancer Chemotherapeutics.

Nanoparticle-based drug delivery systems have the potential for increasing the efficiency of chemotherapeutics by enhancing the drug accumulation at specific target sites, thereby reducing adverse side effects and mitigating patient acquired resistance. In particular, photo-responsive nanomaterials have attracted much interest due to their ability to release molecular cargos on demand upon light irradiation. In some settings, they can also provide complementary information by optical imaging on the (sub)cellular scale. We herein present a system based on lithium niobate harmonic nanoparticles (LNO HNPs) for the decoupled multi-harmonic cell imaging and near-infrared light-triggered delivery of an erlotinib derivative (ELA) for the treatment of epidermal growth factor receptor (EGFR)-overexpressing carcinomas. The ELA cargo was covalently conjugated to the surface of silica-coated LNO HNPs through a coumarinyl photo-cleavable linker, achieving a surface loading of the active molecule of 27 nmol/mg NPs. The resulting nanoconjugates (LNO-CM-ELA NPs) were successfully imaged upon pulsed laser excitation at 1250 nm in EGFR-overexpressing human prostate cancer cells DU145 by detecting the second harmonic emission at 625 nm, in the tissue transparency window. Tuning the laser at 790 nm resulted in the uncaging of the ELA cargo as a result of the second harmonic emission of the inorganic HNP core at 395 nm. This protocol induced a significant growth inhibition in DU145 cells, which was only observed upon specific irradiation at 790 nm, highlighting the promising capabilities of LNO-CM-ELA NPs for theranostic applications.

Ultrafast pulse shaping modulates perceived visual brightness in living animals.

Vision is usually assumed to be sensitive to the light intensity and spectrum but not to its spectral phase. However, experiments performed on retinal proteins in solution showed that the first step of vision consists in an ultrafast photoisomerization that can be coherently controlled by shaping the phase of femtosecond laser pulses, especially in the multiphoton interaction regime. The link between these experiments in solution and the biological process allowing vision was not demonstrated. Here, we measure the electric signals fired from the retina of living mice upon femtosecond multipulse and single-pulse light stimulation. Our results show that the electrophysiological signaling is sensitive to the manipulation of the light excitation on a femtosecond time scale. The mechanism relies on multiple interactions with the light pulses close to the conical intersection, like pump-dump (photoisomerization interruption) and pump-repump (reverse isomerization) processes. This interpretation is supported both experimentally and by dynamics simulations.

Two-Photon-Triggered Photorelease of Caged Compounds from Multifunctional Harmonic Nanoparticles.

The design of stimuli-responsive nanocarriers has raised much attention to achieve higher local concentration of therapeutics and mitigate the appearance of drug resistance. The combination of imaging properties and controlled photorelease of active molecules within the same nanoconjugate has a great potential for theranostic applications. In this study, a system for NIR light-triggered release of molecular cargos induced by the second harmonic emission from bismuth ferrite harmonic nanoparticles (BFO HNPs) is presented. Silica-coated BFO HNPs were covalently conjugated to a photocaging tether based on coumarin (CM) and l-tryptophan (Trp) as a model molecular cargo. Upon femtosecond pulsed irradiation at 790 nm, Trp was efficiently released from the NP surface in response to the harmonic emission of the nanomaterial at 395 nm. The emitted signal induced the photocleavage of the CM-Trp carbamate linkage resulting in the release of Trp, which was monitored and quantified by ultrahigh performance liquid chromatography-mass spectrometry (UHPLC-MS). While a small fraction of the uncaging process could be attributed to the nonlinear absorption of CM derivatives, the main trigger responsible for Trp release was established as the second harmonic signal from BFO HNPs. This strategy may provide a new way for the application of functionalized HNPs in dual imaging delivery theranostic protocols.

Erratum: Publisher's Note: "Implications of short time scale dynamics on long time processes" (Struct. Dyn. 4, 061507 (2017)].

[This corrects the article DOI: 10.1063/1.4996448.].

Implications of short time scale dynamics on long time processes.

This review provides a comprehensive overview of the structural dynamics in topical gas- and condensed-phase systems on multiple length and time scales. Starting from vibrationally induced dissociation of small molecules in the gas phase, the question of vibrational and internal energy redistribution through conformational dynamics is further developed by considering coupled electron/proton transfer in a model peptide over many orders of magnitude. The influence of the surrounding solvent is probed for electron transfer to the solvent in hydrated I-. Next, the dynamics of a modified PDZ domain over many time scales is analyzed following activation of a photoswitch. The hydration dynamics around halogenated amino acid side chains and their structural dynamics in proteins are relevant for iodinated TyrB26 insulin. Binding of nitric oxide to myoglobin is a process for which experimental and computational analyses have converged to a common view which connects rebinding time scales and the underlying dynamics. Finally, rhodopsin is a paradigmatic system for multiple length- and time-scale processes for which experimental and computational methods provide valuable insights into the functional dynamics. The systems discussed here highlight that for a comprehensive understanding of how structure, flexibility, energetics, and dynamics contribute to functional dynamics, experimental studies in multiple wavelength regions and computational studies including quantum, classical, and more coarse grained levels are required.

Discriminating Bio-aerosols from Non-Bio-aerosols in Real-Time by Pump-Probe Spectroscopy.

The optical identification of bioaerosols in the atmosphere and its discrimination against combustion related particles is a major issue for real-time, field compatible instruments. In the present paper, we show that by embedding advanced pump-probe depletion spectroscopy schemes in a portable instrument, it is possible to discriminate amino acid containing airborne particles (bacteria, humic particles, etc.) from poly-cyclic aromatic hydrocarbon containing combustion particles (Diesel droplets, soot, vehicle exhausts) with high selectivity. Our real-time, multi-modal device provides, in addition to the pump-probe depletion information, fluorescence spectra (over 32 channels), fluorescence lifetime and Mie scattering patterns of each individually flowing particle in the probed air.