Jérémie Léonard

Water-Soluble, Donor–Acceptor Biphenyl Derivatives in the 2-(o-Nitrophenyl)propyl Series: Highly Efficient Two-Photon Uncaging of the Neurotransmitter γ-Aminobutyric Acid at λ=800 nm†

By using two-photon (TP)[1] photoreleasable neurotransmitters like glutamate (Glu) or γ-aminobutyric acid (GABA), neuronal processes can be activated or inhibited with high temporal and spatial control (with around one micron three-dimensional precision) with reduced photodamage to cells or organs, and with deeper penetration of the light beam into living tissue compared to that of UV photoactivation.[2]

An artificial molecular switch that mimics the visual pigment and completes its photocycle in picoseconds

Single molecules that act as light-energy transducers (e.g., converting the energy of a photon into atomic-level mechanical motion) are examples of minimal molecular devices. Here, we focus on a molecular switch designed by merging a conformationally locked diarylidene skeleton with a retinal-like Schiff base and capable of mimicking, in solution, different aspects of the transduction of the visual pigment Rhodopsin. Complementary ab initio multiconfigurational quantum chemistry-based computations and time-resolved spectroscopy are used to follow the light-induced isomerization of the switch in methanol. The results show that, similar to rhodopsin, the isomerization occurs on a 0.3-ps time scale and is followed by <10-ps cooling and solvation. The entire (2-photon-powered) switch cycle was traced by following the evolution of its infrared spectrum. These measurements indicate that a full cycle can be completed within 20 ps.

Polariton dynamics under strong light-molecule coupling.

We present a comprehensive experimental study of the photophysical properties of a molecule-cavity system under strong coupling conditions, using steady-state and femtosecond time-resolved emission and absorption techniques to selectively excite the lower and upper polaritons as well as the reservoir of uncoupled molecules. Our results demonstrate the complex decay routes in such hybrid systems and that, contrary to expectations, the lower polariton is intrinsically long-lived.

Live-Cell One- and Two-Photon Uncaging of a Far-Red Emitting Acridinone Fluorophore

Total synthesis and photophysical properties of PENB-DDAO, a photoactivatable 1,3-dichloro-9,9-dimethyl-9H-acridin-2(7)-one (DDAO) derivative of a far-red emitting fluorophore, are described. The photoremovable group of the DDAO phenolic function comprises a donor/acceptor biphenyl platform which allows an efficient (> or = 95%) and rapid (< 15 micros time-range) release of the fluorescent signal and displays remarkable two-photon uncaging cross sections (delta(a) x Phi(u) = 3.7 GM at 740 nm). PENB-DDAO is cell permeable as demonstrated by the triggering of cytoplasmic red fluorescent signal in HeLa cells after one-photon irradiation (lambda(exc) around 360 nm) or by the generation of a red fluorescent signal in a delineated area of a single cell after two-photon photoactivation (lambda(exc) = 770 nm).

Photolabile Glutamate Protecting Group with High One- and Two-Photon Uncaging Efficiencies

A π‐extended [2‐(2‐nitrophenyl)propoxy]carbonyl (NPPOC) derivative has been prepared as an efficient UV and near‐IR photolabile protecting group for glutamate. This glutamate cage compound exhibits efficient photorelease upon one‐photon excitation (εΦ=990 M−1 cm−1 at 315 nm). In addition, it also shows efficient photorelease in activation of glutamate receptors in electrophysiological recordings. Combined with a high two‐photon uncaging cross‐section (δΦ=0.45 GM at 800 nm), its overall properties make this new cage—3‐(2‐propyl)‐4′‐methoxy‐4‐nitrobiphenyl (PMNB)—for glutamate a very promising tool for two‐photon neuronal studies.

Mechanistic origin of the vibrational coherence accompanying the photoreaction of biomimetic molecular switches.

The coherent photoisomerization of a chromophore in condensed phase is a rare process in which light energy is funneled into specific molecular vibrations during electronic relaxation from the excited to the ground state. In this work, we employed ultrafast spectroscopy and computational methods to investigate the molecular origin of the coherent motion accompanying the photoisomerization of indanylidene-pyrroline (IP) molecular switches. UV/Vis femtosecond transient absorption gave evidence for an excited- and ground-state vibrational wave packet, which appears as a general feature of the IP compounds investigated. In close resemblance to the coherent photoisomerization of rhodopsin, the sudden onset of a far-red-detuned and rapidly blue-shifting photoproduct signature indicated that the population arriving on the electronic ground state after nonadiabatic decay through the conical intersection (CI) is still very focused in the form of a vibrational wave packet. Semiclassical trajectories were employed to investigate the reaction mechanism. Their analysis showed that coupled double-bond twisting and ring inversions, already populated during the excited-state reactive motion, induced periodic changes in π-conjugation that modulate the ground-state absorption after the non-adiabatic decay. This prediction further supports that the observed ground-state oscillation results from the reactive motion, which is in line with a biomimetic, coherent photoisomerization scenario. The IP compounds thus appear as a model system to investigate the mechanism of mode-selective photomechanical energy transduction. The presented mechanism opens new perspectives for energy transduction at the molecular level, with applications to the design of efficient molecular devices.

Functional electric field changes in photoactivated proteins revealed by ultrafast Stark spectroscopy of the Trp residues

Ultrafast transient absorption spectroscopy of wild-type bacteriorhodopsin (WT bR) and 2 tryptophan mutants (W86F and W182F) is performed with visible light excitation (pump) and UV probe. The aim is to investigate the photoinduced change in the charge distribution with 50-fs time resolution by probing the effects on the tryptophan absorption bands. A systematic, quantitative comparison of the transient absorption of the 3 samples is carried out. The main result is the absence in the W86F mutant of a transient induced absorption band observed at ≈300–310 nm in WT bR and W182F. A simple model describing the dipolar interaction of the retinal moiety with the 2 tryptophan residues of interest allows us to reproduce the dominant features of the transient signals observed in the 3 samples at ultrashort pump-probe delays. In particular, we show that Trp86 undergoes a significant Stark shift induced by the transient retinal dipole moment. The corresponding transient signal can be isolated by direct subtraction of experimental data obtained for WT bR and W86F. It shows an instantaneous rise, followed by a decay over ≈500 fs corresponding to the isomerization time. Interestingly, it does not decay back to zero, thus revealing a change in the local electrostatic environment that remains long after isomerization, in the K intermediate state of the protein cycle. The comparison of WT bR and W86F also leads to a revised interpretation of the overall transient UV absorption of bR.

Directionality of Double-Bond Photoisomerization Dynamics Induced by a Single Stereogenic Center

In light-driven single-molecule rotary motors, the photoisomerization of a double bond converts light energy into the rotation of a moiety (the rotor) with respect to another (the stator). However, at the level of a molecular population, an effective rotary motion can only be achieved if a large majority of the rotors rotate in the same, specific direction. Here we present a quantitative investigation of the directionality (clockwise vs counterclockwise) induced by a single stereogenic center placed in allylic position with respect to the reactive double bond of a model of the biomimetic indanylidene-pyrrolinium framework. By computing ensembles of nonadiabatic trajectories at 300 K, we predict that the photoisomerization is >70% unidirectional for the Z → E and E → Z conversions. Most importantly, we show that such directionality, resulting from the asymmetry of the excited state force field, can still be observed in the presence of a small (ca. 2°) pretwist or helicity of the reactive double bond. This questions the validity of the conjecture that a significant double-bond pretwist (e.g., >10°) in the ground state equilibrium structure of synthetic or natural rotary motors would be required for unidirectional motion.

Ultrafast photo-induced reaction dynamics in bacteriorhodopsin and its Trp mutants

This review paper presents the recent advances made in observing and understanding the ultrafast photo-reaction dynamics in retinal proteins, in particular bacteriorhodopsin (bR), with a special emphasis on the retinal–protein interactions and the mechanisms of protein activation on a sub-picosecond timescale. We review our latest results obtained on wild-type (wt) bR, and on two tryptophan mutants W86F and W182F, obtained by femtosecond pump–probe experiments. It was shown that light-induced charge translocations and modifications of the protein electrostatics can be monitored by the near-UV differential absorption of Trp86, which experiences a linear intra-protein Stark effect. In the same spectral region, non-exponential wavepacket-like dynamics was found for the formation of the 13-cis retinal isomer in wt-bR. The present paper highlights how this finding is underpinned by the experiments on the mutants. New results are presented regarding the reaction dynamics in the Trp mutants, studied in the vis/near-IR by transient absorption. Interestingly, W86F displays a faster excited state decay and photoproduct formation than wt-bR. This is tentatively attributed to an all-trans/13-cis ground state mixture known to occur in the light-adapted state in this special mutant, due to increased conformational flexibility of the retinal chromophore.

Ultrafast broadband laser spectroscopy reveals energy and charge transfer in novel donor-acceptor triads for photovoltaic applications

Triggered by the quest for new organic materials and micro-structures for photovoltaic applications, a novel class of donor-acceptor-donor (DAD) triads extended with siloxane chains has been synthesized in our labs. Because of the siloxane chains, the molecules self-organize into a smectic liquid crystal phase, resulting in a stacking of the DAD cores.We report here a preliminary study of the ultrafast dynamics of energy and charge transfer studied by femtosecond broadband transient absorption experiments on isolated triads in chloroform.