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The ab initio molecular dynamics method is extended to treat exchange of electrons between molecules and a reservoir at fixed chemical potential. The method is based on a rigorously grand-canonical density functional approach using separate potential energy surfaces for each oxidation state. It is shown that the resulting discontinuous dependency of excess charge on chemical potential is consistent with the statistical thermodynamics of equilibrium gas-phase reactions. The method is illustrated by an application to the adiabatic redox dynamics of an aniline molecule.

We present a model Hamiltonian to study the nonadiabatic dynamics of photoexcited [Cu(dmp)2]+, (dmp = 2,9-dimethyl-1,10-phenanthroline). The relevant normal modes, identified by the magnitude of the first order coupling constants, correspond closely to those observed experimentally. The potential energy surfaces (PES) and nonadiabatic couplings for these modes are computed and provide a first interpretation of the nonadiabatic relaxation mechanism. The Hamiltonian incorporates both the low lying singlet and triplet states, which will make it possible to follow the dynamics from the photoexcitation event to the initial stages of intersystem crossing.

G protein coupled receptors (GPCRs) are a large family of integral membrane proteins involved in many signal transduction pathways. The recently crystallized structures of two engineered adrenergic receptors (ARs)[1,2] and of ligand-free opsin bound to a G-protein peptide[3] have opened new avenues for the understanding of the molecular mechanisms of action of GPCRs, but they also generated some controversy on the proposed mechanism of GPCR activation.To understand the molecular details of GPCR activation, we carried out submicrosecond molecular dynamics simulations of wild type β1AR and β2AR and of rhodopsin dimer in explicit lipid bilayer under physiological conditions.Our simulations showed that the equilibrated structures of ARs recover all the previously suggested features of inactive GPCRs, including formation of a crucial salt bridge between the cytoplasmatic moieties of helices III and VI (“ionic-lock”) that is absent in the crystal structures[4].We found that cooperation between a number of highly conserved residues is a key component in the early steps of the activation mechanism of diffusible ligand class A GPCRs and that “ionic-lock” formation in ARs is directly correlated with the protonation state of a highly conserved aspartic acid, even though the two sites are located more than 20A away from each other[5].Additionally, following the real time evolution of the rhodopsin dimer up to microseconds after photoexcitation, we propose a tandem mechanism for signal transduction where one monomer is responsible for light detection while the other one serves as G-protein coupling site[6]. This interface-mediated pathway suggests oligomerization-aided signal transduction as a crucial biological mechanism to enhance activation of GPCRs.[1] Cherezov et al, Science, 2007.[2] Warne et al, Nature, 2008.[3] Scheerer et al. Nature, 2008.[4] Vanni et al. Biochemistry, 2009.[5] Vanni et al. Submitted.[6] Neri et al. Submitted.

The implementation of local control theory using nonadiabatic molecular dynamics within the framework of linear-response time-dependent density functional theory is discussed. The method is applied to study the photoexcitation of lithium fluoride, for which we demonstrate that this approach can efficiently generate a pulse, on-the-fly, able to control the population transfer between two selected electronic states. Analysis of the computed control pulse yields insights into the photophysics of the process identifying the relevant frequencies associated to the curvature of the initial and final state potential energy curves and their energy differences. The limitations inherent to the use of the trajectory surface hopping approach are also discussed.

We present a Wavelet transform analysis for the X-ray absorption spectra of molecules. In contrast to the traditionally used Fourier transform approach, this analysis yields a 2D correlation plot in both R- and k-space. As a consequence, it is possible to distinguish between different scattering pathways at the same distance from the absorbing atom and between the contributions of single and multiple scattering events, making an unambiguous assignment of the fine structure oscillations for complex systems possible. We apply this to two previously studied transition metal complexes, namely iron hexacyanide in both its ferric and ferrous form, and a rhenium diimine complex, [ReX(CO)(3)(bpy)], where X = Br, Cl, or ethyl pyridine (Etpy). Our results demonstrate the potential advantages of using this approach and they highlight the importance of multiple scattering, and specifically the focusing phenomenon to the extended X-ray absorption fine structure (EXAFS) spectra of these complexes. We also shed light on the low sensitivity of the EXAFS spectrum to the Re-X scattering pathway. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4772766]

The advent of x-ray free electron lasers offers new opportunities for x-ray scattering (XRS) studies of ultrafast molecular dynamics in liquids, which have so far been limited to the 100 ps resolution of synchrotrons. In particular, anisotropic XRS induced by photoselection, using a linearly polarized pump pulse, can enhance the contrast of the signal from excited molecules against the diffuse background and allows the probing of their vibrational and rotational dynamics. Here, we present a computational approach for calculating transient scattering intensities, based on molecular dynamics simulations. This is applied to the study of the excited state dynamics of molecular iodine dissolved in n-hexane. We report that at short times the transient XRS patterns reflect the evolving vibrational and rotational dynamics of I-2, even when the disordered solvent environment is included. We then use these simulations to derive the anticipated signal-to-noise ratio for a large class of model diatomic systems in solution, indicating that an S/N >= 1 will be possible from single-shot experiments in weakly scattering solvents.

We investigate the dynamics of a core-ionized molecule in liquid water by performing first-principles density functional theory (DFT)-based simulations. We observe that molecular dissociation is reached within the lifetime of the induced vacancy. Our findings show that at least one of the intramolecular hydrogens migrates from the core- ionized molecule to one molecule of the first solvation shell.

We have investigated the mechanism of proton transfer in the lowest photoexcited state of 7-hydroxyquinoline.(NH3)3 using TDDFT based molecular dynamics. We observe a concerted mechanism according to which all protons are transferred simultaneously in a fast process (approximately 100 fs) that amounts to the net transport of one proton from the oxygen to the nitrogen of 7-hydroxyquinoline. In addition, the observed proton transfer pathway involves all three ammonia molecules and not only two as previously proposed. These differences arise from dynamical effects that occur at finite temperature. Our simulations provide a detailed time-resolved description of the proton transfer reaction mechanism for a prototypical molecular cluster and thus help to shed further light on the nature of this important and ubiquitous process.

Biased Born-Oppenheimer molecular dynamics simulations are performed to compute redox potential and free energy curves for the redox half reaction Ag(+)-->Ag(2+)+e(-) in aqueous solution. The potential energy surfaces of reactant and product state are linearly coupled and the system transferred from the reduced state to the oxidized state by variation of the coupling parameter from 0 to 1. The redox potential is obtained by thermodynamic integration of the average ionization energy of Ag(+). Diabatic free energy curves of reduced (R) and oxidized (O) states are obtained to good statistical accuracy by reweighting and combining the set of biased distributions of the ionization energy. The diabatic free energy curves of Ag(+) and Ag(2+) are parabolic over a wide range of the reaction coordinate in agreement with the linear response assumption that underlies Marcus theory. However, we observe deviations from parabolic behavior in the equilibrium region of Ag(+) and find different values for the reorganization free energy of R (1.4 eV) and O (0.9 eV). The computed reorganization free energy of Ag(2+) is in good agreement with the experimental estimate of 0.9-1.2 eV obtained from photoelectron spectroscopy. As suggested by our calculations, the moderate deviation from linear response behavior found for Ag(+) is likely related to the highly fluxional solvation shell of this ion, which exhibits water exchange reactions on the picosecond time scale of the present molecular dynamics simulation. [on SciFinder (R)]

The thermochemistry of the RuO(4)(2-)+MnO(4)(-)--RuO(4)(-)+MnO(4)(2-) redox reaction in aqueous solution is studied by separate density-functional-based ab initio molecular-dynamics simulations of the component half reactions RuO(4)(2-)--RuO(4)(-)+e(-) and MnO(4)(2-)--MnO(4)(-)+e(-). We compare the results of a recently developed grand-canonical method for the computation of oxidation free energies to the predictions by the energy-gap relations of the Marcus theory that can be assumed to apply to these reactions. The calculated redox potentials are in good agreement. The subtraction of the half-reaction free energies gives an estimate of the free energy of the full reaction. The result obtained from the grand-canonical method is -0.4 eV, while the application of the Marcus theory gives -0.3 eV. These should be compared to the experimental value of 0.0 eV. Size effects, in response to increasing the number of water molecules in the periodic model system from 30 to 48, are found to be small ( approximately 0.1 eV). The link to the Marcus theory also has enabled us to compute reorganization free energies for oxidation. For both the MnO(4)(2-) and RuO(4)(2-) redox reactions we find the same reorganization free energy of 0.8 eV (1.0 eV in the larger system). The results for the free energies and further analysis of solvation and electronic structure confirm that these two tetrahedral oxoanions show very similar behavior in solution in spite of the central transition-metal atoms occupying a different row and column in the periodic table.

Controlling selectivity of reactions is an ongoing quest in chemistry. In this work, we demonstrate reversible and selective bond formation and dissociation promoted by tip-induced reduction-oxidation reactions on a surface. Molecular rearrangements leading to different constitutional isomers are selected by the polarity and magnitude of applied voltage pulses from the tip of a combined scanning tunneling and atomic force microscope. Characterization of voltage dependence of the reactions and determination of reaction rates demonstrate selectivity in constitutional isomerization reactions and provide insight into the underlying mechanisms. With support of density functional theory calculations, we find that the energy landscape of the isomers in different charge states is important to rationalize the selectivity. Tip-induced selective single-molecule reactions increase our understanding of redox chemistry and could lead to novel molecular machines.

Proteins have a complex free-energy landscape because of their rich topology and the nature of their nonbonded interaction potential. This has important consequences because the roughness of the landscape affects the ease with which a chain folds and also determines the dynamic behavior of the folded structure, thus influencing its functional and stability properties. A detailed description of the free-energy landscape is therefore of paramount importance for a quantitative understanding of the relationships between structure, dynamics, stability, and functional behavior of proteins. The free-energy landscape of a protein is a high-dimensional hypersurface, difficult to rationalize. Therefore, achieving its detailed graphical representation in a way that goes beyond the familiar funnel-like free-energy model is still a big challenge. We describe here an approach based on global structural parameters that allows a two-dimensional representation of the free-energy landscape from simulated atomic trajectories. As shown in this and in the accompanying article, our representation of the landscape, combined with other conformational analyses, provides valuable information on its roughness and on how atomic trajectories evolve with time.

The photophysical and photochemical properties of 5-benzyluracil and 5,6-benzyluracil, the latter produced by photocyclization of the former through irradiation with femtosecond UV laser pulses, are investigated both experimentally and theoretically. The absorption spectra of the two molecules are compared, and the principal electronic transitions involved are discussed, with particular emphasis on the perturbation induced on the two chromophore species (uracil and benzene) by their proximity. The photoproduct formation for different irradiation times was verified with high-performance liquid chromatography and nuclear magnetic resonance measurements. The steady-state fluorescence demonstrates that the fluorescence is a distinctive physical observable for detection and selective identification of 5- and 5,6-benzyluracil. The principal electronic decay paths of the two molecules, obtained through TDDFT calculations, explain the features observed in the emission spectra and the photoreactivity of 5-benzyluracil. The order of magnitude of the lifetime of the excited states is derived with steady-state fluorescence anisotropy measurements and rationalized with the help of the computational findings. Finally, the spectroscopic data collected are used to derive the photocyclization and fluorescence quantum yields. In obtaining a global picture of the photophysical and photochemical properties of the two molecules, our findings demonstrates that the use of 5-benzyluracil as a model system to study the proximity relations of a DNA base with a close-lying aromatic amino acid is valid at a local level since the main characteristics of the decay processes from the excited states of the uracil/thymine molecules remain almost unchanged in 5-benzyluracil, the main perturbation arising from the presence of the close-lying aromatic group.

Many-body Green's functions encode all the properties and excitations of interacting electrons. While these are challenging to be evaluated accurately on a classical computer, recent efforts have been directed towards finding quantum algorithms that may provide a quantum advantage for this task, exploiting architectures that will become available in the near future. In this work we introduce a novel near-term quantum algorithm for computing one-particle Green's functions via their Lehmann representation. The method is based on a generalization of the quantum equation of motion algorithm that gives access to the charged excitations of the system. We demonstrate the validity of the present proposal by computing the Green's function of a two-site Fermi-Hubbard model on a IBM quantum processor.

Limited searching in the conformational space is one of the major obstacles for investigating protein dynamics by numerical approaches. For this reason, classical all-atom molecular dynamics (MD) simulations of proteins tend to be confined to local energy minima, particularly when the bulk solvent is treated explicitly. To overcome this problem, we have developed a novel replica exchange protocol that uses modified force-field parameters to treat interparticle nonbonded potentials within the protein and between protein and solvent atoms, leaving unperturbed those relative to solvent-solvent interactions. We have tested the new protocol on the 18-residue-long tip of the P domain of calreticulin in an explicit solvent. With only eight replicas, we have been able to considerably enhance the conformational space sampled during a 100 ns simulation, compared to as many parallel classical molecular dynamics simulations of the same length or to a single one lasting 450 ns. A direct comparison between the various simulations has been possible thanks to the implementation of the weighted histogram analysis method, by which conformations simulated with modified force-field parameters can be assigned different weights. Interatom, inter-residue distances in the structural ensembles obtained with our novel replica exchange approach and by classical MD simulations compare equally well with those derived from NMR data. Rare events, such as unfolding and refolding, occur with reasonable statistical frequency. Visiting of conformations characterized by very small Boltzmann weights is also possible. Despite their low probability, such regions of the conformational space may play an important role in the search for local potential-energy minima and in dynamically controlled functions.

To assess the effect of an 8-oxoguanine (8OG) defect base on the vertical ionization energies (VIEs) and electron affinities (VEAs) of DNA, density functional theory calculations were carried out for native and defect DNA bases and nucleotides, as well as for larger fragments containing one or multiple pairs. Absolute values of VIE and VEA under implicit solvation did not converge as a function of model size even up to the largest systems taken into consideration (3 base pairs/2 nucleotide pairs). Nonetheless, a consistent trend was observed for the relative difference in the VIE of native and damaged DNA showing that the defect was lowering the VIE by -0.1 eV for the largest fragments. This strongly suggests that the presence of 8OG makes the DNA more easily oxidizable and is in line with experimental evidence that a defect region can act as a sink of oxidative damage. In contrast, relative differences in VEA were very small and varied inconsistently around 0.01 eV. This seems to indicate that insertion of 8OG has a negligible effect on the electron capturing properties of DNA. Similar conclusions can be drawn by the adiabatic IEs and EAs computed for some of the larger fragments. Analysis of the hole and excess electron distributions was consistent with the above trends. The findings presented here support the possibility that a mechanism based on hole transport through DNA may be efficiently employed by the cell for the detection of defect bases.

We rationalize the chemoselectivity of the monofunctional ruthenium anticancer compound [(η(6)-arene)Ru(II)(en)(OH2)](2+) (en=ethylenediamine; arene=benzene 1, p-cymene 2) toward guanine, using static DFT (BP86) and MP2 calculations together with Car-Parrinello molecular dynamics. The calculated binding energies for the three investigated nucleobases (G, A, C) decreases in the order G(N7) ≫ C(O2) ∼ C(N3) > A(N7) > G(O6) > OH2. The G(N7) complex is the most stable product due to a hydrogen bond of its O6 with one of the H2N-amine groups of en, while the corresponding NH2-H2N(en) interaction in the adenine complex is repulsive. A very low rotational barrier of 0.17 kcal/mol (BP86) and 0.64 kcal/mol (MP2) was calculated for the arene rotation in [(η(6)-C6H6)Ru(en)(Cl)](+) (3) allowing complexes containing arenes with bulky side chains like p-cymene to minimize steric interactions with, e.g., DNA by simple arene rotation. All [(η(6)-arene)Ru(en)(L)](2+) compounds exist in two stable conformers obtained for different diamine dihedral angle (NCCN) orientation, which, in the case of asymmetric ligands L, differ by up to ∼2.8 kcal/mol. Car-Parrinello dynamics reveal a chelating transition state for the interconversion between N7 and O6 binding of guanine to [(η(6)-arene)Ru(en)](2+).

We present a static and picosecond X-ray absorption study at the Cu K-edge of bis(2,9-dimethyl-1,10-phenanthroline)copper(I) ([Cu(dmp)(2)](+); dmp = 2,9-dimethyl-1,10-phenanthroline) dissolved in acetonitrile and dichloromethane. The steady-state photoluminescence spectra in dichloromethane and acetonitrile are also presented and show a shift to longer wavelengths for the latter, which points to a stronger stabilization of the excited complex. The fine structure features of the static and transient X-ray spectra allow an unambiguous assignment of the electronic and geometric structure of the molecule in both its ground and excited (MLCT)-M-3 states. Importantly, the transient spectra are remarkably similar for both solvents, and the spectral changes can be rationalized using the optimized ground- and excited-state structures of the complex. The proposed assignment of the lifetime shortening of the excited state in donor solvents (acetonitrile) to a metal-centered exciplex is not corroborated here. Molecular dynamics simulations confirm the lack of complexation; however, in both solvents the molecules come close to the metal but undergo rapid exchange with the bulk. The shortening of the lifetime of the title complex and nine additional related complexes can be rationalized by the decrease in the (MLCT)-M-3 energy. Deviations from this trend may be explained by means of the effects of the dihedral angle between the ligand planes, the solvent, and the (MLCT)-M-3-(MLCT)-M-1 energy gap.

To improve their efficiency beyond the state-of-the-art, D-pi-A dyes must display increased spectral breadth and account for the physical limitations observed in the dye. sensitized solar cells. In particular, they should be designed to control the electron-transfer processes that ensure efficient dye-regeneration and prevent undesired electron recombination. In this article, the electronic and steric properties of a fluorene donor are engineered to meet all these requirements. This elegant donor is featured along with a cyclopentadithiophene bridge and a cyanoacrylic acid acceptor in JF419. A thorough comparison with Y123 and C218 demonstrates the relevance of the design. Relative to conventional donors, the fluorene construct described here enhances the light harvesting properties, because of its exceptional electron donating character. The functionalities used to induce the electronic push through the D-pi-A structure also provide the dye with favorable steric properties. Indeed, the substitution around the fluorene core adequately insulates the TiO2 surface from the electrolyte, which prevents back-recombination and prolongs the electron lifetime in the semiconductor. Furthermore, compared to analogous dyes, JF419 maintains nearly quantitative regeneration efficiency, despite the lower regeneration driving force. The root of this observation is contributed to a significantly more delocalized hole in the photo-oxidized JF419(center dot+), which is highlighted through transient absorption spectroscopy and quantum chemical calculations. The design principles established are relevant to the development of more comprehensive sensitizers, as evidenced by the 10.3% efficiency obtained in cobalt-based liquid dye-sensitized solar cells.

A mixed quantum-classical method aimed at the study of nonadiabatic dynamics in the presence of external electromagnetic fields is developed within the framework of time-dependent density functional theory. To this end, we use a trajectory-based description of the quantum nature of the nuclear degrees of freedom according to Tully's fewest switches trajectories surface hopping, where both the nonadiabatic coupling elements between the different potential energy surfaces, and the coupling with the external field are given as functionals of the ground-state electron density or, equivalently, of the corresponding Kohn-Sham orbitals. The method is applied to the study of the photodissociation dynamics of some simple molecules in gas phase.

The combination of time-dependent density functional theory (TDDFT) for the description of excited states with a hybrid quantum mechanics/molecular mechanics (QM/MM) approach enables the study of photochemical processes in complex environments. Here, we present a short overview of recent applications of TDDFT/MM approaches to a variety of systems including studies of the optical properties of prototypical organic and inorganic molecules in gas phase and solution, photoinduced electron transfer reactions in donor-bridge-acceptor complexes, and in situ investigations of the molecular mechanisms of photoactive proteins. The application of TDDFT/MM techniques to a wide range of systems enables an assessment of the current performance and limitations of these methods for the characterization of photochemical processes in complex systems.

CONSPECTUS: Recent developments in nonadiabatic dynamics enabled ab inito simulations of complex ultrafast processes in the condensed phase. These advances have opened new avenues in the study of many photophysical and photochemical reactions triggered by the absorption of electromagnetic radiation. In particular, theoretical investigations can be combined with the most sophisticated femtosecond experimental techniques to guide the interpretation of measured time-resolved observables. At the same time, the availability of experimental data at high (spatial and time) resolution offers a unique opportunity for the benchmarking and the improvement of those theoretical models used to describe complex molecular systems in their natural environment. The established synergy between theory and experiments can produce a better understanding of new ultrafast physical and chemical processes at atomistic scale resolution. Furthermore, reliable ab inito molecular dynamics simulations can already be successfully employed as predictive tools to guide new experiments as well as the design of novel and better performing materials. In this paper, I will give a concise account on the state of the art of molecular dynamics simulations of complex molecular systems in their excited states. The principal aim of this approach is the description of a given system of interest under the most realistic ambient conditions including all environmental effects that influence experiments, for instance, the interaction with the solvent and with external time-dependent electric fields, temperature, and pressure. To this end, time-dependent density functional theory (TDDFT) is among the most efficient and accurate methods for the representation of the electronic dynamics, while trajectory surface hopping gives a valuable representation of the nuclear quantum dynamics in the excited states (including nonadiabatic effects). Concerning the environment and its effects on the dynamics, the quantum mechanics/molecular mechanics (QM/MM) approach has the advantage of providing an atomistic (even though approximated) description of the solvent molecules, which is crucial for the characterization of all ultrafast relaxation phenomena that depend on the geometrical arrangement at the interface between a molecule and the solvent, for example, the hydrogen bond network. After a short description of the TDDFT-based implementation of Ehrenfest and trajectory surface hopping dynamics, I will present applications in different domains of molecular chemistry and physics: the analysis and the understanding of (time-resolved) X-ray absorption spectra, the interpretation of the ultrafast relaxation dynamics of photoexcited dyes in solution, and the design of specific laser pulses (capable of inducing desired chemical reactions) using local control theory.

Light-driven reactions constitute an important class of processes in physics, chemistry, and biology. The development of accurate and efficient computational tools for the study of excited states dynamics has thus become of primary importance. Recently, we have developed a non-adiabatic ab initio molecular dynamics (AIMD) method, which combines Tully's surface hopping with TDDFT. Here, we investigate some fundamental aspects of this AIMD scheme that deal with the accuracy of TDDFT potential energy surfaces in regions of strong coupling and with the associated intensity of the non-adiabatic couplings (NACs). Of particular interest is the coupling between the ground and the first excited singlet state, which constitute a potential pitfall for all non-adiabatic AND based on TDDFT. To this end, we have investigated the excited state dynamics of protonated formaldimine (CH2NH2+) with particular emphasis on the analysis of the NAC strengths in regions of the configurational space close to surface hopping points and conical intersections. A good agreement of the structural and dynamical properties is found with respect to state averaged multiconfiguration self consistent field results. (C) 2009 Elsevier B.V. All rights reserved.

Understanding the binding mode of agonists to adrenergic receptors is crucial to enabling improved rational design of new therapeutic agents. However, so far the high conformational flexibility of G protein-coupled receptors has been an obstacle to obtaining structural information on agonist binding at atomic resolution. In this study, we report microsecond classical molecular dynamics simulations of β1 and β2 adrenergic receptors bound to the full agonist isoprenaline and in their unliganded form. These simulations show a novel agonist binding mode that differs from the one found for antagonists in the crystal structures and from the docking poses reported by in silico docking studies performed on rigid receptors. Internal water molecules contribute to the stabilization of novel interactions between ligand and receptor, both at the interface of helices V and VI with the catechol group of isoprenaline as well as at the interface of helices III and VII with the ethanolamine moiety of the ligand. Despite the fact that the characteristic N-C-C-OH motif is identical in the co-crystallized ligands and in the full agonist isoprenaline, the interaction network between this group and the anchor site formed by Asp(3.32) and Asn(7.39) is substantially different between agonists and inverse agonists/antagonists due to two water molecules that enter the cavity and contribute to the stabilization of a novel network of interactions. These new binding poses, together with observed conformational changes in the extracellular loops, suggest possible determinants of receptor specificity., Author Summary G-protein coupled receptors are the largest family of membrane proteins in the human genome and they constitute the largest class of drug targets. Amongst them, beta adrenergic receptors are involved in the regulation of muscular and vascular tone and are thus molecular targets for the treatment of various diseases including hypertension, heart failure and asthma. The function of these receptors is regulated via the binding of endogenous or exogenous ligands that can either lead to activation (agonists) or inactivation (inverse agonists/antagonists). However, structure determination of these receptors has been very elusive, and the few atomic resolution structures that are available so far have only been obtained in the presence of inverse agonists or antagonists. In order to study the binding mode of agonists inside the binding pocket, we employ all-atom molecular dynamics. This facilitates the study of the details of the interaction between agonist and receptor in full atomistic detail. We find that agonists binding to beta adrenergic receptors require the formation of a highly structured hydrogen bond network that is further stabilized by the presence of internal water molecules. The observed local rearrangements also help provide insights into the molecular origin of the differences between agonist and inverse agonist binding.

On-the-fly excited state molecular dynamics is a valuable method for studying non-equilibrium processes in excited states and is beginning to emerge as a mature approach much like its ground state counterparts. In contrast to quantum wavepacket dynamics methods, it negates the need for modelling potential energy surfaces, which usually confine nuclear motion within a reduced number of vibrational modes. In addition, on-the-fly molecular dynamics techniques are easily combined with the atomistic description of the solvents (through the QM/MM approach) making it possible to explicitly address the effect of the environment. Herein, we study the nonadiabatic relaxation of photoexcited [Cu(dmp)(2)](+) (dmp = 2,9-dimethyl- 1,10-phenanthroline) using QM/MM Trajectory Surface Hopping (TSH). We show that the decay of the initially excited singlet state into the lowest singlet (S-1) state occurs within 100 fs, in agreement with previous experiments, and is slightly influenced by the solvent. Using a principal component analysis (PCA), we also identify the dominant normal modes activated during the excited state decay, which are then used to design the vibronic Hamiltonian for quantum wavepacket dynamics simulations.

Microbial production of desired compounds provides an efficient framework for the development of renewable energy resources. To be competitive to traditional chemistry, one requirement is to utilize the full capacity of the microorganism to produce target compounds with high yields and turnover rates. We use integrated computational methods to generate and quantify the performance of novel biosynthetic routes that contain highly optimized catalysts. Engineering a novel reaction pathway entails addressing feasibility on multiple levels, which involves handling the complexity of large-scale biochemical networks while respecting the critical chemical phenomena at the atomistic scale. To pursue this multi-layer challenge, our strategy merges knowledge-based metabolic engineering methods with computational chemistry methods. By bridging multiple disciplines, we provide an integral computational framework that could accelerate the discovery and implementation of novel biosynthetic production routes. Using this approach, we have identified and optimized a novel biosynthetic route for the production of 3HP from pyruvate.

A series of tris-heteroleptic iridium complexes of the form [Ir(CN-1)(CN-2)(acac)] combining 2-phenyl pyridine (ppy), 2-(2,4-difluorophenyl)pyridine (dFppy), 1-phenylpyrazole (ppz), and 1-(2,4-difluorophenyl)pyrazole (dFppz) as the CAN ligands have been synthesized and fully characterized by NMR, X-ray crystallography, UV-vis absorption and emission spectroscopy, and electrochemical methods. It is shown that "static properties" (e.g., absorption and emission spectra and redox potentials) are primarily dictated by the overall architecture of the complex, while "dynamic properties" (e.g., excited-state lifetime and radiative and nonradiative rate constants) are, in addition, sensitive to the specific positioning of the substituents. As a result, the two complexes [Ir(dFppy)(ppz)(acac)] and [Ir(ppy) (dFppz) (acac)] have the same emission maxima and redox potentials, but their radiative and nonradiative rate constants differ significantly by a factor Then acetylacetonate (acac) was replaced by picolinate (pic), and two pairs of diastereoisomers were obtained. As expected, the use of pic as the ancillary ligand results in blue-shifted emission, stabilization of the oxidation potential, and improvement of the photoluminescence quantum yield, and only minor differences in the optoelectronic properties are found between the two diastereoisomers of each pair.

Understanding radiation-induced defect formation in carbon materials is crucial for nuclear technology and for the manufacturing of nanostructures with desired properties. Using first principles molecular dynamics, we perform a systematic study of the non-equilibrium processes of radiation damage in graphite. Our study reveals a rich variety of defect structures (vacancies, interstitials, intimate interstitial-vacancy pairs, and in-plane topological defects) with formation energies of 5--15 eV. We clarify the mechanisms underlying their creation and find unexpected preferences for particular structures. Possibilities of controlled defect-assisted engineering of nanostructures are analyzed. In particular, we conclude that the selective creation of two distinct low-energy intimate Frenkel pair defects can be achieved by using a 90--110 keV electron beam irradiation., Comment: 5 pages, 4 figures

We have coupled hybrid quantum mechanics (density functional theory; Car–Parrinello)/molecular mechanics molecular dynamics simulations to a grand-canonical scheme, to calculate the in situ redox potential of the Cu 2+ + e − → Cu + half reaction in azurin from Pseudomonas aeruginosa . An accurate description at atomistic level of the environment surrounding the metal-binding site and finite-temperature fluctuations of the protein structure are both essential for a correct quantitative description of the electronic properties of this system. We report a redox potential shift with respect to copper in water of 0.2 eV (experimental 0.16 eV) and a reorganization free energy λ = 0.76 eV (experimental 0.6–0.8 eV). The electrostatic field of the protein plays a crucial role in fine tuning the redox potential and determining the structure of the solvent. The inner-sphere contribution to the reorganization energy is negligible. The overall small value is mainly due to solvent rearrangement at the protein surface.

The L-3 X-ray absorption spectrum of aqueous iodide is reported, and its EXAFS is compared to theoretical spectra reconstructed from the radial distribution function of the iodide hydration obtained from classical, hybrid Quantum Mechanics Molecular Mechanics, (QM/MM) and full quantum (density functional theory, DFT) molecular dynamics simulations. Since EXAFS is mainly sensitive to short distances around the iodide ion, it is a direct probe of the local solvation structure. The comparison shows that QM/MM simulations deliver a satisfactory description of the EXAFS signal, while nonpolarizable classical simulations are somewhat less satisfactory and DFT-based simulations perform poorly. We also identify a weak anisotropy of the water solvation shell around iodide, which may be of importance in electron photoejection experiments. (C) 2010 Elsevier B.V. All rights reserved.

Within the framework of Kohn-Sham density functional theory, interaction energies of hydrogen bonded and pi-pi stacked supramolecular complexes of aromatic heterocycles, nucleobase pairs, and complexes of nucleobases with the anti-cancer agent ellipticine as well as its derivatives are evaluated. Dispersion-corrected atom-centered potentials (DCACPs) are employed together with a generalized gradient approximation to the exchange correlation functional. For all systems presented, the DCACP calculations are in very good agreement with available post Hartree-Fock quantum chemical results. Estimates of 3-body contributions (15% of the respective interaction energy) and deformation energies (5-15% of the interaction energy) are given. Based on our results, we predict a strongly bound interaction energy profile for the ellipticine intercalation process with a stabilization of nearly 40 kcal/mol (deformation energy not taken into account) when fully intercalated. The frontier orbitals of the intercalator-nucleobase complex and the corresponding non-intercalated nucleobases are investigated and show significant changes upon intercalation. The results not only offer some insights into the systems investigated but also suggest that DCACPs can serve as an effective way to achieve higher accuracy in density functional theory without incurring an unaffordable computational overhead, paving ways for more realistic studies on biomolecular complexes in the condensed phase.

We present a detailed study of the excited state properties of 5-benzyluracil (5BU) in the gas phase and in implicit solvent using different electronic structure approaches ranging from time-dependent density functional theory in the linear response regime (LR-TDDFT) to a set of different wave-function-based methods for excited states, namely perturbed coupled cluster (CC2), algebraic diagrammatic construction method to second order (ADC(2)), and perturbed configuration interaction (CIS(D)). 5BU has been used to investigate DNA base-amino acid interactions. In particular, it served as a model of protein-DNA photoinduced cross-linking. While LR-TDDFT is computationally the most efficient first-principles approach for static and dynamic simulations of this bichromophoric system, its accuracy is difficult to assess due to the presence of excited states with charge transfer character. In this work, the performance of different exchange correlation functionals is compared against accurate benchmarks obtained either from high level wave-function-based methods or directly from experimental absorption spectra. Our investigation shows that accurate results for the excitation energies can be obtained using the hybrid meta-GGA functional M06. In view of dynamical studies of the relaxation of 5BU after photoexcitation, we also show that the PBE functional, while failing in the Franck-Condon region, provides qualitatively good results for the characterisation of a possible photocyclization path.

Investigations of blue phosphorescent organic light emitting diodes (OLEDs) based on [Ir(2-(2,4-difluorophenyl)pyridine)(2)(picolinate)] (FIrPic) have pointed to the cleavage of the picolinate as a possible reason for device instability. We reproduced the loss of picolinate and acetylacetonate ancillary ligands in solution by the addition of Bronsted or Lewis acids. When hydrochloric acid is added to a solution of a [Ir(C(∧)N)(2)(X(∧)O)] complex (C(∧)N = 2-phenylpyridine (ppy) or 2-(2,4-difluorophenyl)pyridine (diFppy) and X(∧)O = picolinate (pic) or acetylacetonate (acac)), the cleavage of the ancillary ligand results in the direct formation of the chloro-bridged iridium(III) dimer [{Ir(C(∧)N)(2)(μ-Cl)}(2)]. When triflic acid or boron trifluoride are used, a source of chloride (here tetrabutylammonium chloride) is added to obtain the same chloro-bridged iridium(III) dimer. Then, we advantageously used this degradation reaction for the efficient synthesis of tris-heteroleptic cyclometalated iridium(III) complexes [Ir(C(∧)N(1))(C(∧)N(2))(L)], a family of cyclometalated complexes otherwise challenging to prepare. We used an iridium(I) complex, [{Ir(COD)(μ-Cl)}(2)], and a stoichiometric amount of two different C(∧)N ligands (C(∧)N(1) = ppy; C(∧)N(2) = diFppy) as starting materials for the swift preparation of the chloro-bridged iridium(III) dimers. After reacting the mixture with acetylacetonate and subsequent purification, the tris-heteroleptic complex [Ir(ppy)(diFppy)(acac)] could be isolated with good yield from the crude containing as well the bis-heteroleptic complexes [Ir(ppy)(2)(acac)] and [Ir(diFppy)(2)(acac)]. Reaction of the tris-heteroleptic acac complex with hydrochloric acid gives pure heteroleptic chloro-bridged iridium dimer [{Ir(ppy)(diFppy)(μ-Cl)}(2)], which can be used as starting material for the preparation of a new tris-heteroleptic iridium(III) complex based on these two C(∧)N ligands. Finally, we use DFT/LR-TDDFT to rationalize the impact of the two different C(∧)N ligands on the observed photophysical and electrochemical properties.

In this work we assess the performance of different dispersion-corrected density functional theory (DFT) approaches (M06, M06-2X, DFT-D3, and DCACP) in reproducing high-level wave function based benchmark calculations on the weakly bound halogen dimers X2···X2 and X2···Ar (for X = F, Cl, Br, and I), as well as the prototype halogen bonded complexes H3CX···OCH2 (X = Cl, Br, I). In spite of the generally good performance of all tested methods for weakly bound systems, their performance for halogen-containing compounds varies largely. We find maximum errors in the energies with respect to the CCSD(T) reference values of 0.13 kcal/mol for DCACP, 0.22 kcal/mol for M06-2X, 0.47 kcal/mol for BLYP-D3, and 0.77 kcal/mol for M06. The root-mean-square deviations are 0.13 kcal/mol for DCACP and M06-2X, 0.44 kcal/mol for M06, and 0.51 kcal/mol for BLYP-D3.

The ground state electronic structure of oxidized azurin from Pseudomonas aeruginosa and its optical response have been investigated by combining hybrid quantum mechanics/molecular mechanics simulations with time-dependent density functional theory. In agreement with experiment, we find that the unpaired electron spin density is mainly localized on the copper ion. The vertical absorption spectrum in the visible range is well reproduced, with the central band centered around 2.1 eV. The anisotropic dipolar field due to the extended alpha-helix polarizes the metal binding site and is responsible for a shift of the absorption bands by +/-0.1-0.2 eV. At 300 K, the bond distances of the copper binding site undergo large fluctuations (approximately 0.3 A). It is crucial to take these thermal fluctuations into account for a faithful description of the optical properties.

The reaction of the anticancer compound [(eta(6)-benzene)Ru(en)(OH(2))](2+) (1) toward the nucleobases guanine, adenine, and cytosine is studied computationally using DFT/BP86 calculations. The aqua leaving group of such compounds is known to undergo ligand exchange reactions with nucleophilic centers in DNA and preferentially with the N7 atom of guanine, N7(G). Our results show that an H-bonded reactant adduct with nucleobases is formed via either the aqua ligand (cis adduct) or the en (ethylenediamine) ligand (trans adduct) of 1. All studied nucleobases favor an H-bonded cis adduct. Only guanine forms also a trans reactant adduct in the gas phase. The guanine N7 and O6 atoms in this trans adduct are situated in an ideal position to form each a strong H-bond to both amino groups of the en ligand of 1. A docking study shows that this unique recognition pattern is also plausible for the interaction with double stranded DNA. For the reaction of 1 with guanine, we identified three different reaction pathways: (i) A cis (G)N7-Ru-OH(2) transition state (TS). (ii) A direct trans reaction pathway. (iii) A 2-step trans mechanism. The activation energies for the cis pathway are smaller than for the trans pathways. The ultimately formed Ru-N7(G) product is characterized by a thermally stable H-bond between the O6(G) and a diamine-NH(2) hydrogen.

In this note, we show that the development for the calculation of nonadiabatic coupling vectors in the framework of TDDFT introduced by the authors in the series of recent publications [E. Tapavicza et al., Phys. Rev. Lett.98, 023001 (2007); I. Tavernelli et al., J. Chem. Phys.130, 124107 (2009)] is rigorous and fully equivalent to the one proposed by Sugino and co-workers [C. P. Hu et al., J. Chem. Phys.127, 064103 (2007)]. Specific applications of our formulation are also discussed.

International audience; Coulombic explosion of uracil: Ionizing radiation is used in cancer therapy to induce molecular damage in cells. Ab initio molecular dynamics were used to probe the early dissociation processes and ensuing chemical reactions following selective ionization of either uracil or the surrounding water molecules (see scheme; C gray, N blue, O red, H white).

The advent of x-ray free electron lasers is providing new opportunities for probing the ultrafast excited state dynamics using structurally sensitive techniques. Herein we use excited state wavepacket dynamics of a prototypical Cu(I)-phenanthroline complex, [Cu(dmp)(2)](+) (dmp = 2, 9-dimethyl-1, 10-phenanthroline) to investigate how femtosecond vibrational and electronic relaxation is translated into transient x-ray absorption and emission. Using realistic experimental parameters we also derive the anticipated signal strengths for these transient features. This indicates that although recording a signal capturing the strongest transient (i.e. excited state-ground state) changes will be possible for all cases, only with x-ray absorption near-edge structure and extended x-ray absorption fine structure will it be possible to resolve the fine details associated with the wavepacket dynamics within realistic experimental acquisition times.

The description at atomic level of protein folding is an ambitious goal in biophysics, particularly because of the difficulty in obtaining structural information on unfolded states. Computer simulations can contribute in achieving this goal. Here we report the results of a 10-ns comparative simulation on bovine ribonuclease A and its S-protein, obtained by removal from the native molecule of the first 20 residues, the so-called S-peptide. The atomic trajectories have been analyzed by standard procedures and by applying concepts previously developed for disordered systems. Furthermore, we used a novel approach, described in the preceding paper, to represent graphically the energy landscape of the simulated systems. Relative to RNase-A, the S-protein, while largely maintaining its structural organization, displays an increased structural flexibility, it gains ergodicity and its core loses order, thus indicating that the removal of the S-peptide from ribonuclease A triggers the transition to a folding intermediate with reduced compactness. This finding also has biochemical relevance since the S-protein is recognized as not properly folded by the machinery responsible for the control of the folding quality in the endoplasmic reticulum.

In this work, we develop a method to design control pulses for fixed-frequency superconducting qubits coupled via tunable couplers based on local control theory, an approach commonly employed to steer chemical reactions. Local control theory provides an algorithm for the monotonic population transfer from a selected initial state to a desired final state of a quantum system through the on-the-fly shaping of an external pulse. The method, which only requires a unique forward time-propagation of the system wavefunction, can serve as starting point for additional refinements that lead to new pulses with improved properties. Among others, we propose an algorithm for the design of pulses that can transfer population in a reversible manner between given initial and final states of coupled fixed-frequency superconducting qubits.