2-in-1 Phase Space Sampling for Calculating the Absorption Spectrum of the Hydrated Electron.

The investigation of vibrational effects on absorption spectrum calculations often employs Wigner sampling or thermal sampling. While Wigner sampling incorporates zero-point energy, it may not be suitable for flexible systems. Thermal sampling is applicable to anharmonic systems yet treats nuclei classically. The application of generalized smoothed trajectory analysis (GSTA) as a postprocessing method allows for the incorporation of nuclear quantum effects (NQEs), combining the advantages of both sampling methods. We demonstrate this approach in computing the absorption spectrum of a hydrated electron. Theoretical exploration of the hydrated electron and its embryonic forms, such as water cluster anions, poses a significant challenge due to the diffusivity of the excess electron and the continuous motion of water molecules. In many previous studies, the wave nature of atomic nuclei is often neglected, despite the substantial impact of NQEs on thermodynamic and spectroscopic properties, particularly for hydrogen atoms. In our studies, we examine these NQEs for the excess electrons in various water systems. We obtained structures from mixed classical-quantum simulations for water cluster anions and the hydrated electron by incorporating the quantum effects of atomic nuclei with the filtration of the classical trajectories. Absorption spectra were determined at different theoretical levels. Our results indicate significant NQEs, red shift, and broadening of the spectra for hydrated electron systems. This study demonstrates the applicability of GSTA to complex systems, providing insights into NQEs on energetic and structural properties.

Prediction of Redox Power for Photocatalysts: Synergistic Combination of DFT and Machine Learning.

The accurate prediction of excited state properties is a key element of rational photocatalyst design. This involves the prediction of ground and excited state redox potentials, for which an accurate description of electronic structures is needed. Even with highly sophisticated computational approaches, however, a number of difficulties arise from the complexity of excited state redox potentials, as they require the calculation of the corresponding ground state redox potentials and the estimation of the 0-0 transition energies (E0,0). In this study, we have systematically evaluated the performance of DFT methods for these quantities on a set of 37 organic photocatalysts representing 9 different chromophore scaffolds. We have found that the ground state redox potentials can be predicted with reasonable accuracy that can be further improved by rationally minimizing the systematic underestimations. The challenging part is to obtain E0,0, as calculating it directly is highly demanding and its accuracy depends strongly on the DFT functional employed. We have found that approximating E0,0 with appropriately scaled vertical absorption energies offers the best compromise between accuracy and computational effort. An even more accurate and cost-effective approach, however, is to predict E0,0 with machine learning and avoid the use of DFT for excited state calculations. Indeed, the best excited state redox potential predictions are achieved with the combination of M062X for ground state redox potentials and machine learning (ML) for E0,0. With this protocol, the excited state redox potential windows of the photocatalyst frameworks could be adequately predicted. This shows the potential of combining DFT with ML in the computational design of photocatalysts with preferred photochemical properties.

N-Alkylated Pyridoxal Derivatives as Negative Electrolyte Materials for Aqueous Organic Flow Batteries: Computational Screening.

N-functionalized pyridinium frameworks derived from the three major vitamers of vitamin B6, pyridoxal, pyridoxamine and pyridoxine, have been screened computationally for consideration as negative electrode materials in aqueous organic flow batteries. A molecular database including the structure and the one-electron standard reduction potential of related pyridinium derivatives has been generated using a computational protocol that combines semiempirical and DFT quantum chemical methods. The predicted reduction potentials span a broad range for the investigated pyridinium frameworks, but pyridoxal derivatives, particularly those involving electron withdrawing substituents, have potentials compatible with the electrochemical stability window of aqueous electrolytes. The stability of radicals formed upon one-electron reduction has been analyzed by a new computational tool proposed recently for large-scale computational screening.

Carboxylate Catalyzed Isomerization of ß,γ-Unsaturated N-Acetylcysteamine Thioesters.

We demonstrate herein the capacity of simple carboxylate salts - tetrametylammonium and tetramethylguanidinium pivalate - to act as catalysts in the isomerization of ß,γ-unsaturated thioesters to α,ß-unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect (k1H /k1D =1.065±0.026) with a ß,γ-deuterated substrate. Computational analysis of the mechanism provides a similar value (k1H /k1D =1.05) with a mechanism where γ-reprotonation of the enolate intermediate is rate determining.

Two Faces of the Two-Phase Thermodynamic Model.

The quantum harmonic model and the two-phase thermodynamic method (2PT) are widely used to obtain quantum-corrected properties such as isobaric heat capacities or molar entropies. 2PT heat capacities were calculated inconsistently in the literature. For water, the classical heat capacity was also considered, but for organic liquids, it was omitted. We reanalyzed the performance of different quantum corrections on the heat capacities of common organic solvents against experimental data. We have pointed out serious flaws in previous 2PT studies. The vibrational density of states was calculated incorrectly causing a 39% relative error in diffusion coefficients and 45% error in the 2PT heat capacities. The wrong conversion of isobaric and isochoric heat capacities also caused about 40% error but in the other direction. We have introduced the concept of anharmonic correction (AC), which is simply the deviation of the classical heat capacity from that of the harmonic oscillator model. This anharmonic contribution is around +30 to 40 J/(mol K) for water depending on the water model and -8 to -10 J/(mol K) for hydrocarbons and halocarbons. AC is unrealistically large, +40 J/(K mol) for alcohols and amines, indicating some deficiency of the OPLS force field. The accuracy of the computations was also assessed with the determination of the self-diffusion coefficients.

Multiscale Modeling of Electronic Spectra Including Nuclear Quantum Effects.

Theoretical prediction of electronic absorption spectra without input from experiments is no easy feat, as it requires addressing all of the factors that affect line shapes. In practice, however, the methodologies are limited to treat these ingredients only to a certain extent. Here, we present a multiscale protocol that addresses the temperature, solvent, and nuclear quantum effects as well as anharmonicity and the reconstruction of the final spectra from individual transitions. First, quantum mechanics/molecular mechanics (QM/MM) molecular dynamics is conducted to obtain trajectories of solute-solvent configurations, from which the corresponding quantum-corrected ensembles are generated through the generalized smoothed trajectory analysis (GSTA). The optical spectra of the ensembles are then produced by calculating vertical transitions using time-dependent density-functional theory (TDDFT) with implicit solvation. To obtain the final spectral shapes, the stick spectra from TDDFT are convoluted with Gaussian kernels where the half-widths are determined by a statistically motivated strategy. We have tested our method by calculating the UV-vis spectra of a recently discovered acridine photocatalyst in two redox states. Vibronic progressions and broadenings due to the finite lifetime of the excited states are not included in the methodology yet. Nuclear quantization affects the relative peak intensities and widths, which is necessary to reproduce the experimental spectrum. We have also found that using only the optimized geometry of each molecule works surprisingly well if a proper empirical broadening factor is applied. This is explained by the rigidity of the conjugated chromophore moieties of the selected molecules, which are mainly responsible for the excitations in the spectra. In contrast, we have also shown that other parts of the molecules are flexible enough to feature anharmonicities that impair the use of other techniques such as Wigner sampling.

Air-stable 18-electron adducts of Schrock catalysts with tuned stability constants for spontaneous release of the active species.

Schrock alkylidenes are highly versatile, very active olefin metathesis catalysts, but their pronounced sensitivity to air still hinders their applications. Converting them into more robust but inactive 18-electron adducts was suggested previously to facilitate their handling. Generating the active species from the inactive adducts, however, required a high-temperature Lewis acid treatment and resulted in an insoluble by-product, limiting the practicality of the methodology. Herein, we introduce an approach to circumvent the inconvenient, costly, and environmentally taxing activation process. We show that 18-electron adducts of W- and Mo-based Schrock catalysts with finite stability constants (typically K = 200-15,000 M-1) can readily be prepared and isolated in excellent yields. The adducts display enhanced air-stability in the solid state, and in solution they dissociate spontaneously, hence liberating the active alkylidenes without chemical assistance.

Nuclear Quantum Effects from the Analysis of Smoothed Trajectories: Pilot Study for Water.

Nuclear quantum effects have significant contributions to thermodynamic quantities and structural properties; furthermore, very expensive methods are necessary for their accurate computation. In most calculations, these effects, for instance, zero-point energies, are simply neglected or only taken into account within the quantum harmonic oscillator approximation. Herein, we present a new method, Generalized Smoothed Trajectory Analysis, to determine nuclear quantum effects from molecular dynamics simulations. The broad applicability is demonstrated with the examples of a harmonic oscillator and different states of water. Ab initio molecular dynamics simulations have been performed for ideal gas up to the temperature of 5000 K. Classical molecular dynamics have been carried out for hexagonal ice, liquid water, and vapor at atmospheric pressure. With respect to the experimental heat capacity, our method outperforms previous calculations in the literature in a wide temperature range at lower computational cost than other alternatives. Dynamic and structural nuclear quantum effects of water are also discussed.

Stereocontrol in Diphenylprolinol Silyl Ether Catalyzed Michael Additions: Steric Shielding or Curtin-Hammett Scenario?

The enantioselectivity of amine-catalyzed reactions of aldehydes with electrophiles is often explained by simple steric arguments emphasizing the role of the bulky group of the catalyst that prevents the approach of the electrophile from the more hindered side. This standard steric shielding model has recently been challenged by the discovery of stable downstream intermediates, which appear to be involved in the rate-determining step of the catalytic cycle. The alternative model, referred to as the Curtin-Hammett scenario of stereocontrol, assumes that the enantioselectivity is related to the stability and reactivity of downstream intermediates. In our present computational study, we examine the two key processes of the catalytic Michael reaction between propanal and ß-nitrostyrene that are relevant to the proposed stereoselectivity models, namely the C-C bond formation and the protonation steps. The free energy profiles obtained for the pathways leading to the enantiomeric products suggest that the rate- and stereodetermining steps are not identical as implied by the previous models. The stereoselectivity can be primarily controlled by C-C bond formation even though the reaction rate is dictated by the protonation step. This kinetic scheme is consistent with all observations of experimental mechanistic studies including those of mass spectrometric back reaction screening experiments, which reveal a mismatch between the stereoselectivity of the back and the forward reactions.

Development of a True Transition State Force Field from Quantum Mechanical Calculations.

Transition state force fields (TSFF) treated the TS structure as an artificial minimum on the potential energy surface in the past decades. The necessary parameters were developed either manually or by the Quantum-to-molecular mechanics method (Q2MM). In contrast with these approaches, here we propose to model the TS structures as genuine saddle points at the molecular mechanics level. Different methods were tested on small model systems of general chemical reactions such as protonation, nucleophilic attack, and substitution, and the new procedure led to more accurate models than the Q2MM-type parametrization. To demonstrate the practicality of our approach, transferrable parameters have been developed for Mo-catalyzed olefin metathesis using quantum mechanical properties as reference data. Based on the proposed strategy, any force field can be extended with true transition state force field (TTSFF) parameters, and they can be readily applied in several molecular mechanics programs as well.

A Catalyst Designed for the Enantioselective Construction of Methyl- and Alkyl-Substituted Tertiary Stereocenters.

Tertiary methyl-substituted stereocenters are present in numerous biologically active natural products. Reported herein is a catalytic enantioselective method for accessing these chiral building blocks using the Mukaiyama-Michael reaction between silyl ketene thioacetals and acrolein. To enable remote enantioface control on the nucleophile, a new iminium catalyst, optimized by three-parameter tuning and by identifying substituent effects on enantioselectivity, was designed. The catalytic process allows rapid access to chiral thioesters, amides, aldehydes, and ketones bearing an α-methyl stereocenter with excellent enantioselectivities, and allowed rapid access to the C4-C13 segment of (-)-bistramide A. DFT calculations rationalized the observed sense and level of enantioselectivity.

Cross-dehydrogenative couplings between indoles and ß-keto esters: ligand-assisted ligand tautomerization and dehydrogenation via a proton-assisted electron transfer to Pd(II).

Cross-dehydrogenative coupling reactions between ß-ketoesters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of ß-ketoesters and indoles. The mechanism of the reaction between a prototypical ß-ketoester, ethyl 2-oxocyclopentanonecarboxylate, and N-methylindole has been studied experimentally by monitoring the temporal course of the reaction by (1)H NMR, kinetic isotope effect studies, and control experiments. DFT calculations have been carried out using a dispersion-corrected range-separated hybrid functional (ωB97X-D) to explore the basic elementary steps of the catalytic cycle. The experimental results indicate that the reaction proceeds via two catalytic cycles. Cycle A, the dehydrogenation cycle, produces an enone intermediate. The dehydrogenation is assisted by N-methylindole, which acts as a ligand for Pd(II). The computational studies agree with this conclusion, and identify the turnover-limiting step of the dehydrogenation step, which involves a change in the coordination mode of the ß-keto ester ligand from an O,O'-chelate to an α-C-bound Pd enolate. This ligand tautomerization event is assisted by the π-bound indole ligand. Subsequent scission of the ß'-C-H bond takes place via a proton-assisted electron transfer mechanism, where Pd(II) acts as an electron sink and the trifluoroacetate ligand acts as a proton acceptor, to produce the Pd(0) complex of the enone intermediate. The coupling is completed in cycle B, where the enone is coupled with indole. Pd(TFA)2 and TFA-catalyzed pathways were examined experimentally and computationally for this cycle, and both were found to be viable routes for the coupling step.

A frustrated-Lewis-pair approach to catalytic reduction of alkynes to cis-alkenes.

Frustrated Lewis pairs are compounds containing both Lewis acidic and Lewis basic moieties, where the formation of an adduct is prevented by steric hindrance. They are therefore highly reactive, and have been shown to be capable of heterolysis of molecular hydrogen, a property that has led to their use in hydrogenation reactions of polarized multiple bonds. Here, we describe a general approach to the hydrogenation of alkynes to cis-alkenes under mild conditions using the unique ansa-aminohydroborane as a catalyst. Our approach combines several reactions as the elementary steps of the catalytic cycle: hydroboration (substrate binding), heterolytic hydrogen splitting (typical frustrated-Lewis-pair reactivity) and facile intramolecular protodeborylation (product release). The mechanism is verified by experimental and computational studies.

Dihydrooxazine oxides as key intermediates in organocatalytic Michael additions of aldehydes to nitroalkenes.

Pause and play: dihydrooxazine oxides are stable intermediates that are protonated directly, without the intermediacy of the zwitterions, in organocatalytic Michael additions of aldehydes and nitroalkenes (see scheme, R=alkyl). Protonation of these species explains both the role of the acid co-catalyst in these reactions, and the observed stereochemistry when the reaction is conducted with α-alkylnitroalkenes.

Cooperative assistance in bifunctional organocatalysis: enantioselective Mannich reactions with aliphatic and aromatic imines.

Hold them tight: Guided by X-ray structures, bifunctional thiourea catalysts containing an activating intramolecular hydrogen bond were redesigned. The new catalysts were used to effect a highly enantioselective Mannich reaction between malonates and both aliphatic and aromatic imines (see scheme; Boc=tert-butoxycarbonyl).

Comment on "Does the hydrated electron occupy a cavity?".

Larsen et al. (Reports, 2 July 2010, p. 65) challenged the long-standing model of the solvent geometry surrounding a free electron in water using molecular dynamics simulations based on a newly derived electron-water pseudopotential. We illustrate that, in contrast to the model they used, the true electron-water interaction is repulsive in the region relevant to the reported extended electron distribution, consistent with the cavity model.

Response of observables for cold anionic water clusters to cluster thermal history.

We have used mixed quantum classical molecular dynamics simulations to explore the role of structural relaxation when binding an excess electron to neutral water clusters. The structural and spectral properties of the water cluster anions were investigated as a function of the size (n = 45 and 104), nominal temperature (T(nom) = 50, 100, and 150 K), and preparation method of the parent neutral clusters. In particular, we consider two different protocols for preparing the initial neutral clusters, which differ markedly in their thermal history. In the first, warm equilibrium neutral clusters are gradually quenched to increasingly lower temperature. In the second, neutral clusters are formed spontaneously at approximately 0 K and then warmed to the same target temperatures, yielding inherently metastable, nonequilibrium structures. Electron attachment to these alternative sets of clusters shows that below a critical temperature (approximately 200 K), the metastable water clusters bind a surface state excess electron significantly more strongly than the quenched, equilibrium clusters. The structural analysis indicates that these cluster anions with larger vertical detachment energies (VDEs) more frequently stabilize the electron by double-acceptor-type water molecules and exhibit a weak temperature dependence of the VDE compared with the quenched clusters. These results suggest that the alternative classes of cluster anions seen experimentally may reflect differences in the thermal history of such clusters.

Interior- and surface-bound excess electron states in large water cluster anions.

We present the results of mixed quantum/classical simulations on relaxed thermal nanoscale water cluster anions, (H(2)O)(n)(-), with n=200, 500, 1000, and 8000. By using initial equilibration with constraints, we investigate stable/metastable negatively charged water clusters with both surface-bound and interior-bound excess electron states. Characterization of these states is performed in terms of geometrical parameters, energetics, and optical absorption spectroscopy of the clusters. The calculations provide data characterizing these states in the gap between previously published calculations and experiments on smaller clusters and the limiting cases of either an excess electron in bulk water or an excess electron at an infinite water/air interface. The present results are in general agreement with previous simulations and provide a consistent picture of the evolution of the physical properties of water cluster anions with size over the entire size range, including results for vertical detachment energies and absorption spectra that would signify their presence. In particular, the difference in size dependence between surface-bound and interior-bound state absorption spectra is dramatic, while for detachment energies the dependence is qualitatively the same.

Excess electron relaxation dynamics at water/air interfaces.

We have performed mixed quantum-classical molecular dynamics simulations of the relaxation of a ground state excess electron at interfaces of different phases of water with air. The investigated systems included ambient water/air, supercooled water/air, Ih ice/air, and amorphous solid water/air interfaces. The present work explores the possible connections of the examined interfacial systems to finite size cluster anions and the three-dimensional infinite, fully hydrated electron. Localization site analyses indicate that in the absence of nuclear relaxation the electron localizes in a shallow potential trap on the interface in all examined systems in a diffuse, surface-bound (SB) state. With relaxation, the weakly bound electron undergoes an ultrafast localization and stabilization on the surface with the concomitant collapse of its radius. In the case of the ambient liquid interface the electron slowly (on the 10 ps time scale) diffuses into the bulk to form an interior-bound state. In each other case, the excess electron persists on the interface in SB states. The relaxation dynamics occur through distinct SB structures which are easily distinguishable by their energetics, geometries, and interactions with the surrounding water bath. The systems exhibiting the most stable SB excess electron states (supercooled water/air and Ih ice/air interfaces) are identified by their characteristic hydrogen-bonding motifs which are found to contain double acceptor-type water molecules in the close vicinity of the electron. These surface states correlate reasonably with those extrapolated to infinite size from simulated water cluster anions.