Switch the click: Ultrafast photochemistry of photoDIBO-OH tracked by time-resolved IR spectroscopy.

Click chemistry refers to selective reactions developed for grafting of bio(macro)molecules in their biological media. Caged click compounds have been employed to spatiotemporally control click reactions. Here, we survey the uncaging of photo-dibenzocyclooctyne-OH (photoDIBO-OH) to its click-chemistry active form DIBO-OH, with particular attention to its conversion timescale and efficiency. Ultraviolet pump-infrared probe experiments reveal a stepwise decarbonylation: first, carbon monoxide (C≡O) is released within 1.8 ps, and then, it converts, within 10 ps, to DIBO-OH. Completion of uncaging is achieved with an efficiency of ∼50%. A successful demonstration of two-photon uncaging of photoDIBO-OH at long wavelength (700 nm) confers enhanced in vivo compatibility and proceeds on the same timescale.

Photochemical mechanism of DEACM uncaging: a combined time-resolved spectroscopic and computational study.

The elementary steps of photocleavage in (coumarin-4-yl)methyl photoremovable protecting groups (PPGs) are elucidated by a combined electronic structure and time-resolved visible pump infrared probe (VIS-pump IR-probe) spectroscopic study. We specifically focus on the [7-(diethylamino)coumarin-4-yl]methyl (DEACM) PPG which has found increasing interest in biological applications over recent years. A series of leaving groups (LGs) are investigated, including azide (DEACM-N3), thiocyanate (DEACM-SCN), carbonate (DEACM-Carb), and a thymine nucleobase (DEACM-T) representing a model system for caged DNA. These systems are found to exhibit vastly different photocleavage time scales, ranging from the subpicosecond scale in the case of DEACM-SCN to ∼35 picoseconds in the case of DEACM-N3 and ∼540 picoseconds in the case of DEACM-Carb. In the case of DEACM-SCN, the appearance of the product is biphasic, with a fast (

Gaussian-based multiconfiguration time-dependent Hartree: A two-layer approach. II. Application to vibrational energy transport in a molecular chain.

We report on first applications of the Two-Layer Gaussian-based Multi-Configuration Time-Dependent Hartree (2L-GMCTDH) method [Römer et al., J. Chem. Phys. 138, 064106 (2013)] for high-dimensional quantum propagation using variational Gaussian basis sets. This method circumvents the limitations of conventional variational Gaussian wavepacket (GWP) methods by introducing a hierarchical wavefunction representation with a fully flexible first layer composed of orthogonal single-particle functions, which are in turn expressed as superpositions of GWPs of fixed width. The method is applied to a model Hamiltonian describing vibrational energy transport through a molecular chain. The model combines bilinear site-to-site couplings with site-local couplings induced by cubic anharmonicities. We report on simulation results for realizations comprising 5 sites with 35 vibrational modes and 18 sites with 90 vibrational modes, which are shown to be in excellent agreement with reference calculations by the Multi-Layer MCTDH method.

Gaussian-based multiconfiguration time-dependent Hartree: A two-layer approach. III. Application to nonadiabatic dynamics in a charge transfer complex.

In this paper, we report on first applications of the Two-Layer Gaussian-based Multi-Configuration Time-Dependent Hartree (2L-GMCTDH) method to nonadiabatic dynamics. Simulations of ultrafast, coherent charge transfer dynamics are performed for a two-state linear vibronic coupling model describing an oligothiophene-fullerene charge transfer complex, for system dimensions ranging from 20 to 100 modes. Different variants of the state-dependent 2L-GMCTDH propagation are assessed, notably single-set and multi-set versions, along with a third hybrid variant. It is shown that the method is suitable to perform accurate and efficient nonadiabatic dynamics simulations in many dimensions.

The aryl hydrocarbon receptor links integrin signaling to the TGF-ß pathway.

Glioblastoma is the most common and aggressive form of intrinsic brain tumor. Transforming growth factor (TGF)-ß represents a central mediator of the malignant phenotype of these tumors by promoting invasiveness and angiogenesis, maintaining tumor cell stemness and inducing profound immunosuppression. Integrins, which are highly expressed in glioma cells, interact with the TGF-ß pathway. Furthermore, a link has been described between activity of the transcription factor aryl hydrocarbon receptor (AhR) and TGF-ß expression. Here we demonstrate that integrin inhibition, using αv, ß3 or ß5 neutralizing antibodies, RNA interference-mediated integrin gene silencing or pharmacological inhibition by the cyclic RGD peptide EMD 121974 (cilengitide) or the non-peptidic molecule GLPG0187, inhibits AhR activity. These effects are independent of cell detachment or cell density. While AhR mRNA expression was not affected by integrin inhibition, AhR total and nuclear protein levels were reduced, suggesting that integrin inhibition-mediated regulation of AhR may occur at a post-transcriptional level. AhR-null astrocytes, AhR-null hepatocytes or glioblastoma cells with a transiently silenced AhR gene showed reduced sensitivity to integrin inhibition-mediated alterations in TGF-ß signaling, indicating that AhR mediates integrin control of the TGF-ß pathway. Accordingly, there was a significant correlation of αv integrin levels with nuclear AhR and pSmad2 levels as determined by immunohistochemistry in human glioblastoma in vivo. In summary, this study identifies a signaling network comprising integrins, AhR and TGF-ß and validates integrin inhibition as a promising strategy not only to inhibit angiogenesis, but also to block AhR- and TGF-ß-controlled features of malignancy in human glioblastoma.

Ultrafast coherent oscillations reveal a reactive mode in the ring-opening reaction of fulgides.

The ultrafast ring-opening reaction of photochromic fulgides proceeds via conical intersections to the ground state isomers involving activation barriers in the excited state. The coherent oscillations observed in the femtosecond transient absorption signal of a methyl-substituted indolylfulgide were analysed in the framework of vibrational wavepackets to expose a dominant low-frequency mode at ∼80 cm(-1). The quantum chemical calculations in the relaxed excited state geometry of this fulgide revealed that the experimentally observed vibrational normal mode has a dominant contribution to the relevant ring-opening reactive coordinate.

Coherent exciton transport driven by torsional dynamics: a quantum dynamical study of phenylene-vinylene type conjugated systems.

We present a quantum dynamical study of exciton transfer across a torsional defect that locally breaks the pi-conjugation in an oligo-(p-phenylene vinylene) (OPV) fragment. A site-based vibronic coupling Hamiltonian is used which is formulated in a comparative fashion (i) for a Frenkel exciton basis, assuming localized electron-hole pairs whose superposition yields a delocalized exciton, and (ii) more accurately, for a Merrifield type exciton basis including spatially separated electron-hole pairs. Starting from a partially delocalized ("spectroscopic unit") initial condition, the observed transfer dynamics is found to involve two characteristic time scales: (i) a very rapid, coherent transient on a 10-100 femtosecond scale, largely determined by Rabi type oscillations modulated by bond-length-alternation modes, and (ii) a slower time scale involving the planarization of the torsional coordinates that determines the onset of a quasi-stationary exciton-polaron state, and in the process leads to a "healing" of the torsional defect within - 500 femtoseconds. The dynamics obtained from the full electron-hole basis vs. Frenkel basis are in good agreement. In the full electron-hole dynamics, the transients are found to involve a rapid expansion and subsequent contraction of the electron-hole coherence size. Quantum dynamical simulations for a minimal six-site model involving 36 states and 22 vibrational modes, were carried out using the multiconfiguration time dependent Hartree (MCTDH) method.

Gaussian-based multiconfiguration time-dependent Hartree: a two-layer approach. I. Theory.

We describe a novel two-layer variant of the Gaussian-based multiconfiguration time-dependent Hartree (G-MCTDH) approach which improves on the performance and convergence properties of quantum propagation based on variationally evolving frozen Gaussians (FGs). While the standard scheme uses factorizable multi-dimensional FGs, the present approach combines these into flexible, MCTDH-like single-particle functions. At the same time, the expensive variational evolution of the Gaussian parameters is reduced to low-dimensional subspaces. As a result, the novel scheme significantly alleviates the current bottleneck to accurate propagation in G-MCTDH and its variational multiconfigurational Gaussian (vMCG) variant. Since the first-layer single-particle functions are chosen to be orthogonal, the present approach can be straightforwardly combined with existing multi-layer MCTDH schemes.

Compact MCTDH wave functions for high-dimensional system-bath quantum dynamics.

We employ a simple multiconfiguration time-dependent Hartree (MCTDH) ansatz tailored to an effective-mode transformation of environmental variables that brings the bath into a linear chain form. In this form, important (primary) degrees of freedom can be easily identified and treated at a high correlation level, whereas secondary modes are left uncorrelated. The resulting approach scales linearly with the bath dimensions and allows us to easily access recurrence times much longer than usually possible, at a very small computational cost. Test calculations for model atom-surface problems show that the system dynamics is correctly reproduced in the relevant time window, and quantitative agreement is attained for energy relaxation and sticking, particularly in non-Markovian environments. These results pave the way for tackling realistic system-bath quantum dynamical problems on the picosecond scale.

Ab initio quantum dynamical study of photoinduced ring opening in furan.

The nonadiabatic photoinduced ring opening occurring in the two lowest excited singlet states of furan is investigated theoretically, using wave-packet propagation techniques. The underlying multidimensional potential energy surfaces (PESs) are obtained from ab initio computations, using the equation-of-motion coupled cluster method restricted to single and double excitations (EOM-CCSD), reported in earlier recent work [E. V. Gromov, A. B. Trofimov, F. Gatti, and H. Köppel, J. Chem. Phys. 133, 164309 (2010)]. Up to five nuclear degrees of freedom are considered in the quantum dynamical treatment. Four of them represent in-plane motion for which the electronic states in question (correlating with the valence (1)B(2)(V) and Rydberg (1)A(2)(3s) states at the C(2v) ground-state molecular configuration) have different symmetries, A(') and A(''), respectively. The fifth mode, representing out-of-plane bending of the oxygen atom against the carbon-atom plane, leads to an interaction of these states, as is crucial for the photoreaction. The nonadiabatic coupling and conical intersection cause an electronic population transfer on the order of ∼10 fs. Its main features, and that of the wave-packet motion, are interpreted in terms of properties of the PES. The lifetime due to the ring-opening process has been estimated to be around 2 ps. The dependence of this estimate on the nuclear degrees of freedom retained in the computations is discussed.

Unraveling a Brownian particle's memory with effective mode chains.

Memory effects in quantum dynamical processes involving structured environments are presently difficult, if not impossible, to investigate using standard approaches. Progress can be made by transforming the environmental variables to a suitable chain representation which effectively performs a Markovian embedding of the dynamics. Here, we show that this effective-mode chain representation provides a unique way of unraveling the memory kernel κ(t) as a function of time. Truncated or Markov-closed chains with n effective modes exactly reproduce κ(t) to the 4nth order in time, up to an irrelevant constant of order κ(0)/n. These favorable convergence properties pave the way for efficient quantum simulations of fast (non-Markovian) processes by reduced dynamical models.

Communication: Universal Markovian reduction of Brownian particle dynamics.

Non-Markovian processes can often be turned Markovian by enlarging the set of variables. Here we show, by an explicit construction, how this can be done for the dynamics of a Brownian particle obeying the generalized Langevin equation. Given an arbitrary bath spectral density J(0), we introduce an orthogonal transformation of the bath variables into effective modes, leading stepwise to a semi-infinite chain with nearest-neighbor interactions. The transformation is uniquely determined by J(0) and defines a sequence {J(n)}(n∈N) of residual spectral densities describing the interaction of the terminal chain mode, at each step, with the remaining bath. We derive a simple one-term recurrence relation for this sequence and show that its limit is the quasi-Ohmic expression provided by the Rubin model of dissipation. Numerical calculations show that, irrespective of the details of J(0), convergence is fast enough to be useful in practice for an effective Ohmic reduction of the dissipative dynamics.

Multimode quantum dynamics using Gaussian wavepackets: The Gaussian-based multiconfiguration time-dependent Hartree (G-MCTDH) method applied to the absorption spectrum of pyrazine.

The Gaussian-based multiconfiguration time-dependent Hartree (G-MCTDH) method is applied to calculate the S(2)(pipi( *)) absorption spectrum of the pyrazine molecule, whose diffuse structure results from the ultrafast nonadiabatic dynamics at the S(2)-S(1) conical intersection. The 24-mode second-order vibronic-coupling model of Raab et al. [J. Chem. Phys. 110, 936 (1999)] is employed, along with 4-mode and 10-mode reduced-dimensional variants of this model. G-MCTDH can be used either as an all-Gaussian approach or else as a hybrid method using a partitioning into primary modes, treated by conventional MCTDH basis functions, and secondary modes described by Gaussian particles. Comparison with standard MCTDH calculations shows that the method converges to the exact result. The variational, nonclassical evolution of the moving Gaussian basis is a key element in obtaining convergence. For high-dimensional systems, convergence is significantly accelerated if the method is employed as a hybrid scheme.

A novel algorithm for non-adiabatic direct dynamics using variational Gaussian wavepackets.

In a recent paper (G. Worth, P. Hunt and M. Robb, J. Phys. Chem. A, 2003, 107, 621), we used surface hopping direct dynamics calculations to study the molecular dynamics of the butatriene radical cation in the X/A manifold, which is coupled by a conical intersection. Here, we present the first direct dynamics calculations using a novel algorithm, again using this ideal test system. The algorithm, which is based on the powerful multi-configuration time-dependent Hartree (MCTDH) wavepacket propagation method, uses a variational basis of coupled frozen Gaussian functions that optimally represent the evolving nuclear wavepacket at all times. Each Gaussian function follows a "quantum trajectory", along which the potential surface is evaluated by quantum chemistry calculations. As far fewer Gaussian functions are needed than classical trajectories in a semi-classical method, the number of quantum chemical calculations is drastically reduced. A crucial point in direct dynamics. To validate the method, initial calculations have been made using an analytic model Hamiltonian, where it is shown to reproduce the main features of the state population transfer with 8-16 basis functions per state. Coupled to the GAUSSIAN quantum chemistry program, the method is then shown to provide a feasible direct dynamics algorithm for the description of this non-adiabatic process.