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Intrinsically disordered proteins (IDPs) play key roles in cellular regulation, including signal transduction, transcription, and cell-cycle control. Accordingly, IDPs can commonly interact with numerous different target proteins, and their interaction networks are expected to be highly regulated. However, many of the underlying regulatory mechanisms have remained unclear. Here, we examine the representative case of the nuclear coactivator binding domain (NCBD) of the large multidomain protein CBP, a hub in transcriptional regulation, and the interaction with several of its binding partners. Single-molecule Förster resonance energy transfer measurements show that phosphorylation of NCBD reduces its binding affinity, with effects that vary depending on the binding partner and the site and number of modifications. The complexity of the interaction is further increased by the dependence of the affinities on peptidyl-prolyl cis/trans isomerization in NCBD. Overall, our results reveal the potential for allosteric regulation on at least three levels: the different affinities of NCBD for its different binding partners, the differential modulation of these affinities by phosphorylation, and the effect of peptidyl-prolyl cis/trans isomerization on binding. [ABSTRACT FROM AUTHOR]

Significant effort has been devoted to benchmarking isotropic hyperfine coupling constants for both wavefunction and density-based approaches in recent years, as accurate theoretical predictions aid the fitting of experimental model Hamiltonians. However, literature examining the predictive quality of a Density Functional Theory (DFT) functional abiding by the Bartlett IP condition is absent. In an attempt to rectify this, we report isotropic hyperfine coupling constant predictions of 24 commonly used DFT functionals on a total of 56 radicals, with the intent of exploring the successes and failures of the Quantum Theory Project (QTP) line of DFT functionals (i.e., CAM-QTP00, CAM-QTP01, CAM-QTP02, and QTP17) for this property. Included in this benchmark study are both small and large organic radicals as well as transition metal complexes, all of which have been studied to some extent in prior work. Subsequent coupled-cluster singles and doubles (CCSD) and CCSD withperturbative triples [CCSD(T)] calculations on small and large organic radicals show modest improvement as compared to prior work and offer an additional avenue for evaluation of DFT functional performance. We find that the QTP17 and CAM-QTP00 functionals consistently underperform, despite being parameterized to satisfy an IP eigenvalue condition primarily focused on inner shell electrons. On the other hand, the CAM-QTP01 functional is the most accurate functional in both organic radical datasets. Furthermore, both CAM-QTP01 and CAM-QTP02 are the most accurate functionals tested on the transition metal dataset. A significant portion of functionals were found to have comparable errors (within 5–15 MHz), but the hybrid class of DFT functionals maintains a consistently optimal balance between accuracy and precision across all datasets. [ABSTRACT FROM AUTHOR]

In this period of intense interest in human immunity, we attempt here to quantify the immune response against pathogen invasion through T-cell population dynamics. Borrowing concepts from equilibrium statistical mechanics, we introduce a new description of the immune response function (IMRF) in terms of fluctuations in the population number of relevant biological cells (effector and regulatory T-cells). We use a coarse-grained chemical reaction network model (CG-CRNM) to calculate the number fluctuations and show that the response function derived as such can, indeed, capture the crossover observed in a T-cell driven immune response. We employ the network model to learn the effect of vitamin-D as an immunomodulator. We solve our CG-CRNM using a stochastic Gillespie algorithm. Depending on the effector T-cell concentration, we can classify immune regulation regimes into three categories: weak, strong, and moderate. The IMRF is found to behave differently in these three regimes. A damped cross-regulatory behavior found in the dynamics of effector and regulatory T-cell concentration in the diseased states correlates well with the same found in a cohort of patients with specific malignancies and autoimmune diseases. Importantly, the crossover from the weakly regulated steady state to the other (the strongly regulated) is accompanied by a divergence-like growth in the fluctuation of both the effector and the regulatory T-cell concentration, characteristic of a dynamic phase transition. We believe such steady-state IMRF analyses could help not only to phase-separate different immune stages but also aid in the valuable connection between autoimmunity, optimal vitamin-D, and consequences of immunosuppressive stress and malignancy. [ABSTRACT FROM AUTHOR]

Rotational transitions of the mono(β)-deuterated vinyl radical, HDC=CH, produced in a supersonic jet expansion by the ArF excimer laser photolysis, were observed by millimeter-wave spectroscopy. The b-type rotational transitions together with the weak a-type transitions were observed only for the lower component of the tunneling doublet, and no tunneling-rotation transitions connecting the lower and upper components were observed, suggesting that state mixing between the two components is negligibly small. The derived molecular constants such as the A rotational constant, Fermi contact interaction constants, and magnetic dipolar interaction constants indicate that the carrier of the observed spectrum is the trans-form of HDC=CH isomers, where the α-proton is located on the opposite side of the β-deuteron. The present conclusion of the trans-form of HDC=CH was also supported by the ab initio calculation in the CCSD(T)/cc-pVTZ level since the trans-form is calculated to be located by 30.04 cm−1 lower than the cis-form due to the difference in the zero point energy. As a result, the tunneling components in the ground state of HDC=CH behave as two different isomers localized at the trans- and cis-wells of the asymmetric double minimum potential. Observed hyperfine constants for HDC=CH were compared with those for H2C=CH to be consistent with each other. [ABSTRACT FROM AUTHOR]

The stochastic drift-diffusion (DrDiff) theory is an approach used to characterize the dynamical properties of simulation data. With new features in transition times analyses, the framework characterized the thermodynamic free-energy profile [F(Q)], the folding time (τf), and transition path time (τTP) by determining the coordinate-dependent drift-velocity [ v (Q)] and diffusion [D(Q)] coefficients from trajectory time traces. In order to explore the DrDiff approach and to tune it with two other methods (Bayesian analysis and fep1D algorithm), a numerical integration of the Langevin equation with known D(Q) and F(Q) was performed and the inputted coefficients were recovered with success by the diffusion models. DrDiff was also applied to investigate the prion protein (PrP) kinetics and thermodynamics by analyzing folding/unfolding simulations. The protein structure-based model, the well-known G o ¯ -model, was employed in a coarse-grained Cα level to generate long constant-temperature time series. PrP was chosen due to recent experimental single-molecule studies in D and τTP that stressed the importance and the difficulty of probing these quantities and the rare transition state events related to prion misfolding and aggregation. The PrP thermodynamic double-well F(Q) profile, the "X" shape of τf(T), and the linear shape of τTP(T) were predicted with v (Q) and D(Q) obtained by the DrDiff algorithm. With the advance of single-molecule techniques, the DrDiff framework might be a useful ally for determining kinetic and thermodynamic properties by analyzing time observables of biomolecular systems. The code is freely available at https://github.com/ronaldolab/DrDiff. [ABSTRACT FROM AUTHOR]

A theoretical stochastic diffusion framework is developed that characterizes the position-dependent diffusion coefficient [D(Q)] and drift velocity [ v (Q)] by analysing single-molecule time traces [Q(t)]. The free-energy landscape [F(Q)] that governs the dynamics is reconstructed with the calculated D and v. There are many computational tools that perform this task in which some are computationaly demanding, difficult to run, and, most of the time, not directly available to the community. This is a first attempt to implement the simplified stochastic diffusion framework that is fast, easy to run in a Python environment, and available to be extended as needed. It does not require adjustable parameters, inference methods, or sampling bias such as Monte Carlo Bayesian estimators or umbrella samplings. The stochastic framework was applied in the protein-like lattice model with Monte Carlo simulations, which accurately predicted the folding rates with the coordinate-dependent D and F plugged into Kramers' theory. The results were compared with two other independently developed methodologies (the Bayesian analysis and fep1D algorithm) presenting a good match, which confirms its validity. This theoretical framework might be useful in determining the free-energy and rates by providing time series only from biological or condensed-phase systems. The code is freely available at https://github.com/ronaldolab/stochastic_diffusion. [ABSTRACT FROM AUTHOR]

We report photodetachment and resonant photoelectron-imaging studies of cryogenically cooled phenoxide (C6H5O−) and thiophenoxide (C6H5S−) anions. In a previous study [H. T. Liu et al. Angew. Chem., Int. Ed. 52, 8976 (2013)], a dipole-bound excited state was observed for C6H5O− at 97 cm−1 below the detachment threshold. Eight resonant photoelectron spectra were obtained via excitations to eight vibrational levels of the dipole-bound state (DBS) followed by autodetachment. Here we present a complete photodetachment spectrum of C6H5O− covering a spectral range 2600 cm−1 above the detachment threshold and revealing nine additional vibrational resonances of the DBS. We also report the first observation of a dipole-bound excited state for C6H5S−, 39 cm−1 below its detachment threshold of 18 982 cm−1. Photodetachment spectroscopy covering a spectral range 1500 cm−1 above the threshold reveals twelve vibrational resonances for the DBS of C6H5S−. By tuning the detachment laser to the vibrational resonances in the DBS of C6H5O− and C6H5S−, we obtain highly non-Franck-Condon resonant photoelectron spectra, as a result of mode-selectivity and the Δv = −1 propensity rule for vibrational autodetachment. Five new fundamental vibrational frequencies are obtained for the ground state of the C6H5O (X2B1) radical. Intramolecular inelastic scattering is observed in some of the resonant photoelectron spectra, leading to the excitation of the Franck-Condon-inactive lowest-frequency bending mode (ν20) of C6H5O. The first excited state of C6H5O (A2B2) is observed to be 0.953 eV above the ground state. Twelve resonant photoelectron spectra are obtained for C6H5S−, allowing the measurements of seven fundamental vibrational frequencies of the C6H5S radical, whereas the non-resonant photoelectron spectrum exhibits only a single Franck-Condon active mode. The current study again demonstrates that the combination of photodetachment spectroscopy and resonant photoelectron spectroscopy is a powerful technique to obtain vibrational information about polar radical species. [ABSTRACT FROM AUTHOR]

We present the slow electron velocity map imaging spectroscopy of cryogenically cooled phenoxide, 1-naphthoxide, and 2-naphthoxide anions. The results allow us to examine the ground state and the lowest energy excited state in the corresponding neutral radicals. Care was taken to minimize autodetachment signals in the photoelectron spectra, allowing for more straightforward comparisons with Franck-Condon analyses. The ground states of these three aromatic oxide radicals all have the unpaired electron residing in a π orbital delocalized throughout the molecule. The electron affinity of 1-naphthoxy is measured to be 2.290(2) eV, while that of 2-naphthoxy is measured to be 2.404(2) eV, both of which are higher than that of the smaller phenoxy molecule at 2.253(1) eV. The first excited states have the unpaired electron residing in a more localized σ orbital, yielding measured term energies for the à state of 1.237(2) eV in 1-naphthoxy and 1.068(1) eV in 2-naphthoxy, while that of phenoxy is lower at 0.952(1) eV. The calculated Franck-Condon spectra generally showed good agreement with the experimental spectra, yielding assignments of the more active vibrations in each electronic state. Significant autodetachment signals arising from dipole bound states near the ground states of all three radicals were observed in our efforts to avoid them, and comparably less autodetachment signals were observed near the excited states. Besides this type of non-Franck-Condon intensities in the photoelectron spectra, we also observed minor features arising due to vibronic coupling in the ground states of all three radicals. [ABSTRACT FROM AUTHOR]

The dynamics of unfolded proteins are important both for the process of protein folding and for the behavior of intrinsically disordered proteins. However, methods for investigating the global chain dynamics of these structurally diverse systems have been limited. A versatile experimental approach is single-molecule spectroscopy in combination with Förster resonance energy transfer and nanosecond fluorescence correlation spectroscopy. The concepts of polymer physics offer a powerful framework both for interpreting the results and for understanding and classifying the properties of unfolded and intrinsically disordered proteins. This information on long-range chain dynamics can be complemented with spectroscopic techniques that probe different length scales and time scales, and integration of these results greatly benefits from recent advances in molecular simulations. This increasing convergence between the experiment, theory, and simulation is thus starting to enable an increasingly detailed view of the dynamics of disordered proteins. [ABSTRACT FROM AUTHOR]

In this paper, we give a full account of our previous work [C. C. Shen et al., J. Chem. Phys. 141, 171103 (2014)] on the study of an ultrafast photoionization-induced proton transfer (PT) reaction in the phenol-ammonia (PhOH-NH3) complex using ultrafast time-resolved ion photofragmentation spectroscopy implemented by the photoionization-photofragmentation pump-probe detection scheme. NeutralPhOH-NH3 complexes prepared in a free jet are photoionized by femtosecond 1 + 1 resonanceenhanced multiphoton ionization via the S1 state. The evolving cations are then probed by delayed pulses that result in ion fragmentation, and the ionic dynamics is followed by measuring the parent-ion depletion as a function of the pump-probe delay time. By comparing with systems in which PT is not feasible and the steady-state ion photofragmentation spectra, we concluded that the observed temporal evolutions of the transient ion photofragmentation spectra are consistent with an intracomplex PT reaction after photoionization from the initial non-PT to the final PT structures. Our experiments revealed that PT in [PhOH-NH3]+ cation proceeds in two distinct steps: an initial impulsive wavepacket motion in ~70 fs followed by a slower relaxation of about 1 ps that stabilizes the system into the final PT configuration. These results indicate that for a barrierless PT system, even though the initial PT motions are impulsive and ultrafast, the time scale to complete the reaction can be much slower and is determined by the rate of energy dissipation into other modes. [ABSTRACT FROM AUTHOR]

Recent single-molecule experiments probed transition paths of biomolecular folding and, in particular, measured the time biomolecules spend while crossing their free energy barriers. A surprising finding from these studies is that the transition barriers crossed by transition paths, as inferred from experimentally observed transition path times, are often lower than the independently determined free energy barriers. Here we explore memory effects leading to anomalous diffusion as a possible origin of this discrepancy. Our analysis of several molecular dynamics trajectories shows that the dynamics of common reaction coordinates used to describe protein folding is subdiffusive, at least at sufficiently short times. We capture this effect using a one-dimensional fractional Brownian motion (FBM) model, in which the system undergoes a subdiffusive process in the presence of a potential of mean force, and show that this model yields much broader distributions of transition path times with stretched exponential long-time tails. Without any adjustable parameters, these distributions agree well with the transition path times computed directly from protein trajectories. We further discuss how the FBM model can be tested experimentally. [ABSTRACT FROM AUTHOR]

Intrinsically disordered proteins (IDPs) are increasingly recognized as a class of molecules that can exert essential biological functions even in the absence of a well-defined three-dimensional structure. Understanding the conformational distributions and dynamics of these highly flexible proteins is thus essential for explaining the molecular mechanisms underlying their function. Single-molecule fluorescence spectroscopy in combination with Förster resonance energy transfer (FRET) is a powerful tool for probing intramolecular distances and the rapid long-range distance dynamics in IDPs. To complement the information from FRET, we combine it with photoinduced electron transfer (PET) quenching to monitor local loop-closure kinetics at the same time and in the same molecule. Here we employed this combination to investigate the intrinsically disordered N-terminal domain of HIV-1 integrase. The results show that both long-range dynamics and loop closure kinetics on the submicrosecond time scale can be obtained reliably from a single set of measurements by the analysis with a comprehensive model of the underlying photon statistics including both FRET and PET.Amore detailed molecular interpretation of the results is enabled by direct comparison with a recent extensive atomistic molecular dynamics simulation of integrase. The simulations are in good agreement with experiment and can explain the deviation from simple models of chain dynamics by the formation of persistent local secondary structure. The results illustrate the power of a close combination of single-molecule spectroscopy and simulations for advancing our understanding of the dynamics and detailed mechanisms in unfolded and intrinsically disordered proteins. [ABSTRACT FROM AUTHOR]

The n-propyl and i-propyl radicals were generated in the gas phase via pyrolysis of n-butyl nitrite [CH3(CH2)3ONO] and i-butyl nitrite [(CH3)2CHCH2ONO], respectively. Nascent radicals were promptly solvated by a beam of He nanodroplets, and the infrared spectra of the radicals were recorded in the CH stretching region. Several previously unreported bands are observed between 2800 and 3150 cm-1. The CH stretching modes observed above 3000 cm-1 are in excellent agreement with CCSD(T) anharmonic frequencies computed using second-order vibrational perturbation theory. However, between 2800 and 3000 cm-1, the spectra of n- and i-propyl radicals become congested and difficult to assign due to the presence of multiple anharmonic resonance polyads. To model the spectrally congested region, Fermi and Darling-Dennison resonances are treated explicitly using "dressed" Hamiltonians and CCSD(T) quartic force fields in the normal mode representation, and the agreement with experiment is less than satisfactory. Computations employing local mode effective Hamiltonians reveal the origin of the spectral congestion to be strong coupling between the high frequency CH stretching modes and the lower frequency CHn bending/scissoring motions. The most significant coupling is between stretches and bends localized on the same CH2/CH3 group. Spectral simulations using the local mode approach are in excellent agreement with experiment. [ABSTRACT FROM AUTHOR]

The changes in the strength of the interaction between the polycyclic aromatic hydrocarbon, coronene, and graphite as a function of the degree of super-hydrogenation of the coronene molecule are investigated using temperature programmed desorption. A decrease in binding energy is observed for increasing degrees of super-hydrogenation, from 1.78 eV with no additional hydrogenation to 1.43 eV for the fully super-hydrogenated molecule. Density functional theory calculations using the optB88-vdW functional suggest that the decrease in binding energy is mostly due to an increased buckling of the molecule rather than the associated decrease in the number of π-electrons. [ABSTRACT FROM AUTHOR]

Even though the interaction of a <1 mT magnetic field with an electron spin is less than a millionth of the thermal energy at room temperature (kBT), it still can have a profound effect on the quantum yields of radical pair reactions. We present a study of the effects of sub-millitesla magnetic fields on the photoreaction of flavin mononucleotide with ascorbic acid. Direct control of the reaction pathway is achieved by varying the rate of electron transfer from ascorbic acid to the photo-excited flavin. At pH 7.0, we verify the theoretical prediction that, apart from a sign change, the form of the magnetic field effect is independent of the initial spin configuration of the radical pair. The data agree well with model calculations based on a Green's function approach that allows multinuclear spin systems to be treated including the diffusive motion of the radicals, their spin-selective recombination reactions, and the effects of the inter-radical exchange interaction. The protonation states of the radicals are uniquely determined from the form of the magnetic field-dependence. At pH 3.0, the effects of two chemically distinct radical pair complexes combine to produce a pronounced response to ~500 μT magnetic fields. These findings are relevant to the magnetic responses of cryptochromes (flavin-containing proteins proposed as magnetoreceptors in birds) and may aid the evaluation of effects of weak magnetic fields on other biologically relevant electron transfer processes. [ABSTRACT FROM AUTHOR]

Femtosecond extreme ultraviolet (XUV) transient absorption spectroscopy based on a high-harmonic generation source is used to study the 266 nm induced A-band photodissociation dynamics of allyl iodide (CH2==CHCH2I). The photolysis of the C-I bond at this wavelength produces iodine atoms both in the ground (2P3/2, I) and spin-orbit excited (2P1/2, I*) states, with the latter as the predominant channel. Using XUV absorption at the iodine N4/5 edge (45-60 eV), the experiments constitute a direct probe of not only the long-lived atomic iodine reaction products but also the fleeting transition state region of the repulsive nIσ* C-I excited states. Specifically, three distinct features are identified in the XUV transient absorption spectrum at 45.3 eV, 47.4 eV, and 48.4 eV (denoted transients A, B, and C, respectively), which arise from the repulsive valence-excited nσ* states and project onto the high-lying core-excited states of the dissociating molecule via excitation of 4d(I) core electrons. Transients A and B originate from 4d(I) → n(I) core-to-valence transitions, whereas transient C is best assigned to a 4d(I) → σ*(C-I) transition. The measured differential absorbance of these new features along with the I/I* branching ratios known from the literature is used to suggest a more definitive assignment, albeit provisional, of the transients to specific dissociative states within the A-band manifold. The transients are found to peak around 55 fs-65 fs and decay completely by 145 fs-185 fs, demonstrating the ability of XUV spectroscopy to map the evolution of reactants into products in real time. The similarity in the energies of transients A and B with analogous features observed in methyl iodide [Attar et al. J. Phys. Chem. Lett. 6, 5072, (2015)] together with the new observation of transient C in the present work provides a more complete picture of the valence electronic structure in the transition state region. The results provide a benchmark for theoretical calculations on the nature of core-excited states in halogenated hydrocarbons, especially in the transition state region along the C-I reaction coordinate. [ABSTRACT FROM AUTHOR]

A numerical method using B-splines is used to solve the linear Boltzmann equation describing the energy relaxation of massive tracer particles moving through a dilute bath gas. The smooth and rough hard sphere and Maxwell molecule models are used with a variety of mass ratios and initial energies to test the capability of the numerical method. Massive tracers are initialized with energies typically found in energy loss experiments in mass spectrometry using biomolecules. The method is also used to examine the applicability of known expressions for the kinetic energy decay from the Fokker-Planck equation for the Rayleigh gas, where we find that results are generally good provided that the initial energy is properly bounded. Otherwise, the energy decay is not constant and a more complex behaviour occurs. The validity of analytical expressions for drag coefficients for spherical particles under specular and diffuse scattering is also tested. We find such expressions are generally good for hard spheres but cannot account, as expected, for the softer repulsive walls of the Maxwell (and real) molecules. Overall, the numerical method performed well even when tracers more than 400 times as massive as the bath were initialized with energies very far from equilibrium. This is a range of applicability beyond many of the standard methods for solving the Boltzmann equation. [ABSTRACT FROM AUTHOR]

A general formalism to compute configurational properties of proteins and other heteropolymers with an arbitrary sequence of charges and non-uniform excluded volume interaction is presented. A variational approach is utilized to predict average distance between any two monomers in the chain. The presented analytical model, for the first time, explicitly incorporates the role of sequence charge distribution to determine relative sizes between two sequences that vary not only in total charge composition but also in charge decoration (even when charge composition is fixed). Furthermore, the formalism is general enough to allow variation in excluded volume interactions between two monomers. Model predictions are benchmarked against the all-atom Monte Carlo studies of Das and Pappu [Proc. Natl. Acad. Sci. U. S. A. 110, 13392 (2013)] for 30 different synthetic sequences of polyampholytes. These sequences possess an equal number of glutamic acid (E) and lysine (K) residues but differ in the patterning within the sequence. Without any fit parameter, the model captures the strong sequence dependence of the simulated values of the radius of gyration with a correlation coefficient of R² = 0.9. The model is then applied to real proteins to compare the unfolded state dimensions of 540 orthologous pairs of thermophilic and mesophilic proteins. The excluded volume parameters are assumed similar under denatured conditions, and only electrostatic effects encoded in the sequence are accounted for. With these assumptions, thermophilic proteins are found--with high statistical significance--to have more compact disordered ensemble compared to their mesophilic counterparts. The method presented here, due to its analytical nature, is capable of making such high throughput analysis of multiple proteins and will have broad applications in proteomic studies as well as in other heteropolymeric systems. [ABSTRACT FROM AUTHOR]

We analyze a model statistical description of the polypeptide chain helix-coil transition, where we take into account the specificity of its primary sequence, as quantified by the phase space volume ratio of the number of all accessible states to the number corresponding to a helical conformation. The resulting transition phase diagram is then juxtaposed with the unusual behavior of the secondary structures in Intrinsically Disordered Proteins (IDPs) and a number of similarities are observed, even if the protein folding is a more complex transition than the helix-coil transition. In fact, the deficit in bulky and hydrophobic amino acids observed in IDPs, translated into larger values of phase space volume, allows us to locate the region in parameter space of the helix-coil transition that would correspond to the secondary structure transformations that are intrinsic to conformational transitions in IDPs and that is characterized by a modified phase diagram when compared to globular proteins. Here, we argue how the nature of this modified phase diagram, obtained from a model of the helix-coil transition in a solvent, would illuminate the turned-out response of IDPs to the changes in the environment conditions that follow straightforwardly from the re-entrant (cold denaturation) branch in their folding phase diagram. [ABSTRACT FROM AUTHOR]

In earlier works, we showed that the entropic effect originating from the translational displacement of water molecules plays the pivotal role in protein folding and denaturation. The two different solvent models, hard-sphere solvent and model water, were employed in theoretical methods wherein the entropic effect was treated as an essential factor. However, there were similarities and differences in the results obtained from the two solvent models. In the present work, to unveil the physical origins of the similarities and differences, we simultaneously consider structural transition, cold denaturation, and pressure denaturation for the same protein by employing the two solvent models and considering three different thermodynamic states for each solvent model. The solvent-entropy change upon protein folding/unfolding is decomposed into the protein-solvent pair (PA) and many-body (MB) correlation components using the integral equation theories. Each component is further decomposed into the excluded-volume (EV) and solvent-accessible surface (SAS) terms by applying the morphometric approach. The four physically insightful constituents, (PA, EV), (PA, SAS), (MB, EV), and (MB, SAS), are thus obtained. Moreover, (MB, SAS) is discussed by dividing it into two factors. This all-inclusive investigation leads to the following results: (1) the protein-water many-body correlation always plays critical roles in a variety of folding/unfolding processes; (2) the hard-sphere solvent model fails when it does not correctly reproduce the protein-water many-body correlation; (3) the hard-sphere solvent model becomes problematic when the dependence of the many-body correlation on the solvent number density and temperature is essential: it is not quite suited to studies on cold and pressure denaturating of a protein; (4) when the temperature and solvent number density are limited to the ambient values, the hard-sphere solvent model is usually successful; and (5) even at the ambient values, however, the many-body correlation plays significant roles in the β-sheet formation and argument of relative stabilities of very similar structures of a protein. These results are argued in detail with respect to the four physically insightful constituents and the two factors mentioned above. The relevance to the absence or presence of hydrogen-bonding properties in the solvent is also discussed in detail. [ABSTRACT FROM AUTHOR]

We perform molecular dynamics simulations to observe the structure and dynamics of SPC/E water in amorphous silica pores and amorphous ice pores with radii slightly larger than 10 À. In addition to atomically rough pores, we construct completely smooth pores such that the potential felt at a given distance from the pore wall is an averaged atomic potential. As compared to rough walls, smooth walls induce stronger distortions of water structure for both silica and ice confinements. On the other hand, unlike the smooth pores, the rough pores strongly slow down water dynamics at the pore wall. The slowdown vanishes when reducing the atomic charges in the wall, i.e., when varying the hydroaffinity, while keeping the surface topology, indicating that it is not a geometric effect. Rather, it is due to the fact that the wall atoms provide a static energy landscape along the surface, e.g., fixed anchor-points for hydrogen bonds, to which the water molecules need to adapt, blocking channels for structural rearrangement. In the smooth pores, water dynamics can be faster than in the bulk liquid not only at the pore wall but also in the pore center. Changes in the tetrahedral order rather than in the local density are identified as the main cause for this change of the dynamical behavior in the center of smooth pores. [ABSTRACT FROM AUTHOR]

The mechanism of cold denaturation in proteins is often incompletely understood due to limitations in accessing the denatured states at extremely low temperatures. Using atomistic molecular dynamics simulations, we have compared early (nanosecond timescale) structural and solvation properties of yeast frataxin (Yfh1) at its temperature of maximum stability, 292 K (Ts), and the experimentally ob-served temperature of complete unfolding, 268 K (Tc). Within the simulated timescales, discernible "global" level structural loss at Tc is correlated with a distinct increase in surface hydration. How-ever, the hydration and the unfolding events do not occur uniformly over the entire protein surface, but are sensitive to local structural propensity and hydrophobicity. Calculated infrared absorption spectra in the amide-I region of the whole protein show a distinct red shift at Tc in comparison to Ts. Domain specific calculations of IR spectra indicate that the red shift primarily arises from the beta strands. This is commensurate with a marked increase in solvent accessible surface area per residue for the beta-sheets at Tc. Detailed analyses of structure and dynamics of hydration water around the hydrophobic residues of the beta-sheets show a more bulk water like behavior at Tc due to preferential disruption of the hydrophobic effects around these domains. Our results indicate that in this protein, the surface exposed beta-sheet domains are more susceptible to cold denaturing con-ditions, in qualitative agreement with solution NMR experimental results. [ABSTRACT FROM AUTHOR]

Photoionization-induced proton transfer (PT) in phenol-ammonia (PhOH-NH3) complex has been studied using ultrafast time-resolved ion photofragmentation spectroscopy. Neutral PhOH-NH3 com-plexes prepared in a free jet are photoionized by femtosecond [1+1] resonance-enhanced multipho- ton ionization via the S1 state, and the subsequent dynamics occurring in the cations is probed by delayed pulses that result in ion fragmentation. The observed temporal evolutions of the photofrag-mentation spectra are consistent with an intracomplex PT reaction. The experiments revealed that PT in [PhOH-NH3]+ cation proceeds in two distinct steps: an initial impulsive wave-packet motion in ∼70 fs followed by a slower relaxation of about 1 ps that stabilizes the system into the final PT configuration. These results indicate that for a barrierless PT system, even though the initial PT motions are impulsive and ultrafast, the reaction may take a much longer time scale to complete. [ABSTRACT FROM AUTHOR]

We present a new formulation of the time-dependent theory of Resonance-Raman spectroscopy (TD-RR). Particular attention has been devoted to the generality of the framework and to the possibility of including different effects (Duschinsky mixing, Herzberg-Teller contributions). Furthermore, the effects of different harmonic models for the intermediate electronic state are also investigated. Thanks to the implementation of the TD-RR procedure within a general-purpose quantum-chemistry program, both solvation and leading anharmonicity effects have been included in an effective way. The reliability and stability of our TD-RR implementation are validated against our previously proposed and well-tested time-independent procedure. Practical applications are illustrated with some closed- and open-shell medium-size molecules (anthracene, phenoxyl radical, benzyl radical) and the simulated spectra are compared to the experimental results. More complex and larger systems, not limited to organic compounds, can be also studied, as shown for the case of Tris(bipyridine)ruthenium(II) chloride. [ABSTRACT FROM AUTHOR]

We perform molecular dynamics simulations to observe the structure and dynamics of water using different water models (TIP3P, TIP4P, TIP5P) at ambient conditions, constrained by planar walls, which are either modeled by smooth potentials or regular atomic lattices, imitating the honeycombstructure of graphene. We implement walls of different hydroaffinity, different lattice constant, and different types of interaction with the water molecules. We find that in the hydrophobic regime the smooth wall generally represents a good abstraction of the atomically rough walls, while in the hydrophilic regime there are noticeable differences in structure and dynamics between all stages of wall roughness. For a small lattice constant however the smooth and the atomically rough wall still share a number of structural and dynamical similarities. Out of the three water models, TIP5P water shows the largest degree of tetrahedral ordering and is often the one that is least perturbed by the presence of the wall. [ABSTRACT FROM AUTHOR]

We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters is estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the 14 model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction ∈hb(AT) for an AT base pair and the ring factor ξ turn out to be the most sensitive parameters. In addition, the stacking interaction ∈st (TA-TA) for an TA-TA nearest neighbor pair of base-pairs is found to be the most sensitive one among all stacking interactions. Moreover, we also establish that the nature of stacking interaction has a deciding effect on the DNA breathing dynamics, not the number of times a particular stacking interaction appears in a sequence. We show that the sensitivity analysis can be used as an effective measure to guide a stochastic optimization technique to find the kinetic rate constants related to the dynamics as opposed to the case where the rate constants are measured using the conventional unbiased way of optimization. [ABSTRACT FROM AUTHOR]

The ethyl radical has been isolated and spectroscopically characterized in 4He nanodroplets. The band origins of the five CH stretch fundamentals are shifted by < 2 cm-1 from those reported for the gas phase species [S. Davis, D. Uy, and D. J. Nesbitt, J. Chem. Phys. 112, 1823 (2000); T. Häber, A. C. Blair, D. J. Nesbitt, and M. D. Schuder, J. Chem. Phys. 124, 054316 (2006)]. The symmetric CH2 stretching band (v1) is rotationally resolved, revealing nuclear spin statistical weights predicted by G12 permutation-inversion group theory. A permanent electric dipole moment of 0.28 (2) D is obtained via the Stark spectrum of the v1 band. The four other CH stretch fundamental bands are significantly broadened in He droplets and lack rotational fine structure. This broadening is attributed to symmetry dependent vibration-to-vibration relaxation facilitated by the He droplet environment. In addition to the five fundamentals, three a1′ overtone/combination bands are observed, and each of these have resolved rotational substructure. These are assigned to the 2v12, v4 + v6, and 2v6 bands through comparisons to anharmonic frequency computations at the CCSD(T)/cc-pVTZ level of theory. [ABSTRACT FROM AUTHOR]

The hyperfine coupling constant of the hydrogen atom has been measured in pressurized liquid water up to 300 °C. The reduced constant Awater/Avacuum is 0.9939 at room temperature, and decreases to a minimum of 0.9918 at 240 °C. The reduced constant then increases at higher temperature. The g-factor is 2.002244(10) at room temperature and decreases to 2.00221(1) at 240 °C. The change in g-factor is proportional to the change in hyperfine coupling. The behavior below 110 °C is in excellent agreement with a previously proposed model in which the H atom is confined to a harmonic solvent cage, and vibrations within the cage mix 'p-type' character into the wavefunction, resulting in Awater/Avacuum < 1. The harmonic model breaks down above 130 °C. We demonstrate that a classical binary collision model using approximate partial molar volume information can recover the observed minima near 240 °C. [ABSTRACT FROM AUTHOR]

By analyzing a set of organic π radicals, we demonstrate that zero-point vibrational corrections give significant contributions to carbon hyperfine coupling constants, in one case even inducing a sign reversal for the coupling constant. We discuss the implications of these findings for the computational analysis of electron paramagnetic spectra based on hyperfine coupling constants evaluated at the equilibrium geometry of radicals. In particular, we note that a dynamical description that involves the nuclear motion is in many cases necessary in order to achieve a semi-quantitatively predictive theory for carbon hyperfine coupling constants. In addition, we discuss the implications of the strong dependence of the carbon hyperfine coupling constants on the zero-point vibrational corrections for the selection of exchange-correlation functionals in density functional theory studies of these constants. [ABSTRACT FROM AUTHOR]

Förster resonance energy transfer (FRET) is a powerful optical technique to determine intra-molecular distances. However, the dye rotational motion and the linker flexibility complicate the relationship between the measured energy transfer efficiency and the distance between the anchoring points of the dyes. In this study, we present a simple model that describes the linker and dye dynamics as diffusion on a sphere. Single-pair energy transfer was treated in the weak excitation limit, photon statistics and scaffold flexibility were ignored, and different time-averaging regimes were considered. Despite the approximations, our model provides new insights for experimental designs and results interpretation in single-molecule FRET. Monte Carlo simulations produced distributions of the inter-dye distance, the dipole orientation factor, κ2, and the transfer efficiency, E, which were in perfect agreement with independently derived theoretical functions. Contrary to common perceptions, our data show that longer linkers will actually restrict the motion of dye dipoles and hence worsen the isotropic 2/3 approximation of κ2. It is also found that the thermal motions of the dye-linker system cause fast and large efficiency fluctuations, as shown by the simulated FRET time-trajectories binned on a microsecond time scale. A fundamental resolution limit of single-molecule FRET measurements emerges around 1-10 μs, which should be considered for the interpretation of data recorded on such fast time scales. [ABSTRACT FROM AUTHOR]

Three solid state formation routes have been proposed in the past to explain the observed abundance of water in space: the hydrogenation reaction channels of atomic oxygen (O + H), molecular oxygen (O2 + H), and ozone (O3 + H). New data are presented here for the third scheme with a focus on the reactions O3 + H, OH + H and OH + H2, which were difficult to quantify in previous studies. A comprehensive set of H/D-atom addition experiments is presented for astronomically relevant temperatures. Starting from the hydrogenation/deuteration of solid O3 ice, we find experimental evidence for H2O/D2O (and H2O2/D2O2) ice formation using reflection absorption infrared spectroscopy. The temperature and H/D-atom flux dependence are studied and this provides information on the mobility of ozone within the ice and possible isotope effects in the reaction scheme. The experiments show that the O3 + H channel takes place through stages that interact with the O and O2 hydrogenation reaction schemes. It is also found that the reaction OH + H2 (OH + H), as an intermediate step, plays a prominent (less efficient) role. The main conclusion is that solid O3 hydrogenation offers a potential reaction channel for the formation of water in space. Moreover, the nondetection of solid ozone in dense molecular clouds is consistent with the astrophysical picture in which O3 + H is an efficient process under interstellar conditions. [ABSTRACT FROM AUTHOR]

The H2C==CD isotopic species of vinyl radical produced in a supersonic jet expansion by ultraviolet laser photolysis was studied by millimeter-wave spectroscopy. Due to the tunneling motion of the α deuteron, the ground state is split into two components, 0+ and 0-. Tunneling-rotation transitions connecting the lower (0+) and upper (0-) components of the tunneling doublet were observed in the frequency region of 184-334 GHz, including three R- and two Q-branch transitions. Three and two pure rotational transitions in the Ka=0 and 1 stacks, respectively, were also observed for each of the 0+ and 0- states in the frequency region of 52-159 GHz. Least-squares analysis of the observed frequencies for the tunneling-rotation and pure rotational transitions with well resolved hyperfine structures yielded a set of precise molecular constants, among which the tunneling splitting in the ground state was determined to be ΔE0=1187.234(17) MHz, which is 1/14 that for H2C==CH. The potential barrier height derived from the observed tunneling splitting by an analysis of the tunneling dynamics using a one-dimensional model is 1545 cm-1, consistent with the value 1568 cm-1 obtained for the normal vinyl. The observed spectrum was found to be perturbed by a hyperfine interaction connecting ortho and para levels. The constant for the interaction, which we call the ortho-para mixing Fermi contact interaction, has been determined to be δaF(β)=68.06(53) MHz. This is believed to be the first definite detection of such an interaction. By this interaction the ortho and para states of H2C==CD are mixed up to about 0.1%. The constant is more than 1000 times larger than spin-rotation interaction constants that cause ortho-para mixing in closed shell molecules and suggests extremely rapid conversion between the ortho and para nuclear spin isomers of H2C==CD. [ABSTRACT FROM AUTHOR]

There has been considerable effort to understand the inherent time scale for conformational reconfiguration of denatured proteins. Even a simple homopolymer, however, exhibits a spectrum of fluctuation time scales rather than a unique characteristic time. Consequently, different time scales may be probed by different measurements. Motivated by recent single-molecule fluorescence resonance energy transfer experiments, here I have studied theoretically how the characteristic time scale exhibited by fluctuations of the distance between two residues within an unfolded polypeptide depends on the choice of the residue pair. This time scale was generally found to become shorter as the sequence separation between the residues is reduced. The maximum reconfiguration time, however, corresponds not to the residues being located at the ends of the chain but rather to each residue residing a short length apart from the ends. Comparison of these findings with recent single-molecule measurements suggests that the latter may bear signatures of transient residual structure. [ABSTRACT FROM AUTHOR]

Fluorescence intensity correlation functions contain information about photophysical and conformational dynamics. We propose and implement a simple procedure to analyze such functions measured in the presence of resonance energy transfer. When there is a separation of time scales and the conformational dynamics is modeled as diffusion in the potential of mean force along the interdye distance, we obtain an analytic expression for the conformational correlation time. This can be used to find the diffusion coefficient describing conformational fluctuations given the photon count rate and equilibrium distribution. [ABSTRACT FROM AUTHOR]

Recent years have seen a number of investigations in which distances within unfolded proteins, polypeptides, and other biopolymers are probed via fluorescence resonance energy transfer, a method that relies on the strong distance dependence of energy transfer between a pair of dyes attached to the molecule of interest. In order to interpret the results of such experiments it is commonly assumed that intramolecular diffusion is negligible during the excited state lifetime. Here we explore the conditions under which this “frozen chain” approximation fails, leading to significantly underestimated donor-acceptor distances, and describe a means of correcting for polymer dynamics in order to estimate these distances more accurately. [ABSTRACT FROM AUTHOR]

Förster resonance energy transfer is an increasingly popular method for studying protein folding at single molecule resolution. By attaching dye molecules to particular residues in a protein molecule and measuring the energy transfer to the acceptor dye on excitation of the donor dye, information about the separation of the dyes can be obtained. Here we use an atomistic coarse-grained molecular model of the protein and dyes to look at the assumption that the dyes rotate freely during the donor decay time. We find that although complete orientational averaging does not always occur, the consequences of this are not extreme. Even in the native state, the errors in efficiency, which result from incorrectly assuming κ2=2/3, are smaller than the typical experimental error of an efficiency measurement. The orientational freedom of the dyes originates both from the dynamics of the linker and dye molecules and also from the movements of the protein chain itself. In the unfolded state, the movements of the protein chain are sufficient to provide complete, or almost complete, orientational averaging within the donor lifetime. Increasing the rigidity of the dyes therefore has only a very small effect on the measured efficiencies in the unfolded state. In the native state the contribution of the linker and dye dynamics to orientational averaging is larger; nevertheless increasing the rigidity still has only a small effect on the measured efficiency. [ABSTRACT FROM AUTHOR]

Pulsed-field-ionization zero-kinetic-energy photoelectron spectra of jet-cooled allyl radical (C3H5) have been recorded following single-photon and resonant multiphoton excitation. Simulations based on an orbital ionization model and rovibronic photoionization selection rules reliably describe the observed intensity distributions in the photoelectron spectra obtained from single-photon excitation from the ground state and resonant multiphoton excitation via the 3s and the 3p Rydberg states. More than 30 transitions to vibrational levels of the cation were identified and assigned on the basis of predictions from ab initio calculations. [ABSTRACT FROM AUTHOR]

The orbital occupation, which is the centerpiece of both self-interaction and several metal-insulator transition analyses, as well as of the local density or generalized gradient approximation with a Hubbard term, is not well defined, in the sense that it is partially ambiguous. A general treatment can be applied to both strongly and weakly correlated systems. When it is applied to an intermediate- and partially filled band within of the host semiconductor gap whose width is less than the semiconductor gap, the original single band can either split as in a Mott transition or not. The former situation is usual and almost always generalized. However the latter also takes place and results from a dilution effect of the self-interaction where a large orbital correlation is reduced if there are other orbital contributions with lower self-interaction in the band. The key is in the choice of the subspace of correlated orbitals. This effect can neither be ignored nor discarded for those systems where there is a substantial mix of states. Examples of these behaviors will be presented and compared to other results. Moreover, the combination of different Hubbard terms acting on different atomic state subspaces can also be used to correct the spurious self-interaction of the bands and the gap underestimation. The relationship between these terms applied to different subspaces of correlated electrons will be presented. [ABSTRACT FROM AUTHOR]

We recorded several rovibronic bands of C6H5O and C6D5O in their à 2B2←X 2B1 transitions in the range 1.14–1.31 μm with the cavity ringdown technique. While the electronic transition is forbidden, several vibronic bands are observed. By comparison of rovibronic contours of observed and simulated bands to determine their types of transition, and by consideration of vibrational wavenumbers of the upper state based on quantum-chemical calculations, we were able to provide vibronic assignments of observed bands and derive several experimental vibrational wavenumbers (given as ν in unit of cm-1 in this paper) for the à 2B2 state, namely, ν12=947, ν13=793, ν14=417, ν15=964, ν16=866, ν17=723, ν18=680, and ν19=499 for C6H5O, and ν12=772, ν13=626, ν14=365, ν15=812, ν17=599, ν18=532, and ν19=436 for C6D5O. Transitions involving vibrationally excited levels of ν20 were also observed; ν20 of the à state is greater by 50 cm-1 than the X state of C6H5O. A weak origin at 7681 cm-1 for the Ã←X transition of C6H5O (7661 cm-1 for C6D5O) with a c-type contour was observed. Observed isotopic ratios of vibrational wavenumbers for the à state of C6H5O to those of C6D5O are in good agreement with the predictions from quantum-chemical calculations at the B3LYP/aug-cc-pVTZ level. [ABSTRACT FROM AUTHOR]

First high-resolution IR spectra of jet-cooled vinyl radical in the C[Single_Bond]H stretch region are reported. Detailed spectral assignments and least squares fits to an A-reduction Watson asymmetric top Hamiltonian yield rotational constants and vibrational origins for three A-type bands, assigned to single quantum excitation of the symmetric CH2 stretch. Two of the observed bands arise definitively from ground state vinyl radical, as rigorously confirmed by combination differences predicted from previous midinfrared CH2 wagging studies of Kanamori et al. [J. Chem. Phys. 92, 197 (1990)] as well as millimeter wave rotation-tunneling studies of Tanaka et al. [J. Chem. Phys. 120, 3604 (2004)]. The two bands reflect transitions out of symmetric (0+) and antisymmetric (0-) tunneling levels of vinyl radical populated at 14 K slit-jet expansion temperatures. The band origins for the lower-lower (0+←0+) and upper-upper (0-←0-) transitions occur at 2901.8603(7) and 2901.9319(4) cm-1, respectively, which indicates an increase in the tunneling splitting and therefore a decrease in the effective tunneling barrier upon CH2 symmetric stretch excitation. The third A-type band with origin at 2897.2264(3) cm-1 exhibits rotational constants quite close to (but at high-resolution distinguishable from) the vinyl radical ground state, consistent with a CH2 symmetric stretch hot band built on one or more quanta of excitation in a low frequency vibration. The observed CH2 symmetric stretch bands are in excellent agreement with anharmonically scaled high level density functional theory (DFT) calculations and redshifted considerably from previous low resolution assignments. Of particular dynamical interest, Boltzmann analysis indicates that the pair of 0+ and 0- tunneling bands exhibits 1:1 nuclear spin statistics for Ka=even:odd states. This differs from the expected 3:1 ratio for feasible exchange of the two methylenic H atoms but is consistent with a 4:4 ratio predicted for interchange between all three H atoms. This suggests the novel dynamical possibility of large amplitude “roaming” of all three H atoms in vinyl radical, promoted by high internal vibrational excitation arising from dissociative electron attachment in the discharge. [ABSTRACT FROM AUTHOR]

We report a pump-probe femtosecond transient absorption spectroscopic study on the electron transfer reaction of CCl4 in liquid ethanol. By direct observations of the presolvated electron and of the reaction transition state CCl4*-, this study provides direct evidence of the resonant dissociative electron transfer (RDET) of the presolvated electron to CCl4. Moreover, the lifetime of CCl4*- in ethanol is directly obtained from the decay kinetics and its measured value is found to be nearly identical to its gas-phase value. Hence, these results also imply that RDET can be an efficient process in an aqueous environment. [ABSTRACT FROM AUTHOR]

The photoinduced hydrogen (or deuterium) detachment reaction of thiophenol (C6H5SH) or thiophenol-d1 (C6H5SD) pumped at 243 nm has been investigated using the H (D) ion velocity map imaging technique. Photodissociation products, corresponding to the two distinct and anisotropic rings observed in the H (or D) ion images, are identified as the two lowest electronic states of phenylthiyl radical (C6H5S·). Ab initio calculations show that the singly occupied molecular orbital of the phenylthiyl radical is localized on the sulfur atom and it is oriented either perpendicular or parallel to the molecular plane for the ground (B1) and the first excited state (B2) species, respectively. The experimental energy separation between these two states is 2600±200 cm-1 in excellent agreement with the authors’ theoretical prediction of 2674 cm-1 at the CASPT2 level. The experimental anisotropy parameter (β) of -1.0±0.05 at the large translational energy of D from the C6H5SD dissociation indicates that the transition dipole moment associated with this optical transition at 243 nm is perpendicular to the dissociating S–D bond, which in turn suggests an ultrafast D+C6H5S·(B1) dissociation channel on a repulsive potential energy surface. The reduced anisotropy parameter of -0.76±0.04 observed at the smaller translational energy of D suggests that the D+C6H5S·(B2) channel may proceed on adiabatic reaction paths resulting from the coupling of the initially excited state to other low-lying electronic states encountered along the reaction coordinate. Detailed high level ab initio calculations adopting multireference wave functions reveal that the C6H5S·(B1) channel may be directly accessed via a 1(nπ,σ*) photoexcitation at 243 nm while the key feature of the photodissociation dynamics of the C6H5S·(B2) channel is the involvement of the 3(nπ,π*)→3(nσ,σ*) profile as well as the spin-orbit induced avoided crossing between the ground and the 3(nπ,σ*) state. The S–D bond dissociation energy of thiophenol-d1 is accurately estimated to be D0=79.6±0.3 kcal/mol. The S–H bond dissociation energy is also estimated to give D0=76.8±0.3 kcal/mol, which is smaller than previously reported ones by at least 2 kcal/mol. The C–H bond of the benzene moiety is found to give rise to the H fragment. Ring opening reactions induced by the π-π*/nπ-π* transitions followed by internal conversion may be responsible for the isotropic broad translational energy distribution of fragments. [ABSTRACT FROM AUTHOR]

Replacement of thymidine in DNA by bromodeoxyuridine (BrdU) has long been known to enhance DNA damage and cell death induced by ionizing/UV radiation, but the mechanism of action of BrdU at the molecular level is poor understood. Using time-resolved femtosecond laser spectroscopy, we obtain the real-time observation of the transition state of the ultrafast electron transfer (ET) reaction of BrdU with the precursor to the hydrated electron, which is a general product in ionizing/UV radiation. The results show that the ET reaction is completed within 0.2 picosecond (ps) after the electronic excitation, leading to the formation of a transition state BrdU*- with a lifetime of ∼1.5 ps that then dissociates into Br- and a high reactive radical dU*. The present results can greatly enhance our understanding not only of the mechanism of BrdU as a radio-/photosensitizer but of the role of prehydrated electrons in electron-initiated processes in biological and environmental systems. [ABSTRACT FROM AUTHOR]