Triplet State Radical Chemistry: Significance of the Reaction of 3SO2 with HCOOH and HNO3.

The triplet excited states of sulfur dioxide can be accessed in the UV region and have a lifetime large enough that they can react with atmospheric trace gases. In this work, we report high level ab initio calculations for the reaction of the a3B1 and b3A2 excited states of SO2 with weak and strong acidic species such as HCOOH and HNO3, aimed to extend the chemistry reported in previous studies with nonacidic H atoms (water and alkanes). The reactions investigated in this work are very versatile and follow different kinds of mechanisms, namely, proton-coupled electron transfer (pcet) and conventional hydrogen atom transfer (hat) mechanisms. The study provides new insights into a general and very important class of excited-state-promoted reactions, opening up interesting chemical perspectives for technological applications of photoinduced H-transfer reactions. It also reveals that atmospheric triplet chemistry is more significant than previously thought.

Reactivity of Monoethanolamine at the Air-Water Interface and Implications for CO2 Capture.

The development of CO2-capture technologies is key to mitigating climate change due to anthropogenic greenhouse gas emissions. These cover a number of technologies designed to reduce the level of CO2 emitted into the atmosphere or to eliminate CO2 from ambient air. In this context, amine-based sorbents in aqueous solutions are broadly used in most advanced separation techniques currently implemented in industrial applications. It has been reported that the gas/liquid interface plays an important role in the early stages of the capture process, but how the interface influences the chemistry is still a matter of debate. With the help of first-principles molecular dynamics simulations, we show that monoethanolamine (MEA), a prototypical sorbent molecule, has a weak affinity for the air-water interface, where in addition it exhibits a lower nucleophilicity compared to bulk solution. The change in reactivity is due to the combination of structural and electronic factors, namely, the shift of the conformational equilibrium and the stabilization of the N-atom lone pair. Based on these results, strategies for improving the efficiency of alkanolamine sorbents are proposed.

Quantum Chemistry in Solution: Fiftieth Anniversary.

In this perspective, we briefly present the historical context in which, fifty years ago, dielectric continuum models were developed to incorporate solvent effects into quantum mechanical calculations. Since the first self-consistent-field equations including the solvent electrostatic potential (or reaction field) were reported in 1973, continuum models have become extremely popular in the computational chemistry community and are routinely used in a very wide range of applications.

Electrostatics and Chemical Reactivity at the Air-Water Interface.

It has been recently discovered that chemical reactions at aqueous interfaces can be orders of magnitude faster compared to conventional bulk phase reactions, but despite its wide-ranging implications, which extend from atmospheric to synthetic chemistry or technological applications, the phenomenon is still incompletely understood. The role of strong electric fields due to space asymmetry and the accumulation of ions at the interface has been claimed as a possible cause from some experiments, but the reorganization of the solvent around the reactive system should provide even greater additional electrostatic contributions that have not yet been analyzed. In this study, with the help of first-principles molecular dynamics simulations, we go deeper into this issue by a careful assessment of solvation electrostatics at the air-water interface. Our simulations confirm that electrostatic forces can indeed be a key factor in rate acceleration compared to bulk solution. Remarkably, the study reveals that the effect cannot simply be attributed to the magnitude of the local electric field and that the fluctuations of the full electrostatic potential resulting from unique dynamical behavior of the solvation shells at the interface must be accounted for. This finding paves the way for future applications of the phenomenon in organic synthesis, especially for charge transfer or redox reactions in thin films and microdroplets.

Disentangling reaction rate acceleration in microdroplets.

We have investigated the origin of the unexpected, recently discovered phenomenon of reaction rate acceleration in water microdroplets relative to bulk water. Acceleration factors for reactions of atmospheric and synthetic relevance can be dissected into elementary contributions thanks to the original and versatile kinetic model. The microdroplet is partitioned in two sub-volumes, the surface and the interior, operating as interconnected chemical reactors in the fast diffusion regime. Reaction rate acceleration and its dependence on reaction molecularity and microdroplet dimensions are explained by applying transition-state-theory at thermodynamic equilibrium. We also show that our model, in combination with experimental measurements of rate acceleration factors, can be used to obtain chemical kinetics data at the air-water interface, which has been a long-standing challenge for chemists.

Fast Sulfate Formation Initiated by the Spin-Forbidden Excitation of SO2 at the Air-Water Interface.

The multiphase oxidation of SO2 to sulfate in aerosol particles is a key process in atmospheric chemistry. However, there is a large gap between the observed and simulated sulfate concentrations during severe haze events. To fill in the gaps in understanding SO2 oxidation chemistry, a combination of experiments and theoretical calculations provided evidence for the direct, spin-forbidden excitation of SO2 to its triplet states using UVA photons at an air-water interface, followed by reactions with water and O2 that facilitate the rapid formation of sulfate. The estimated reaction energy for the whole process, 3SO2 + H2O + 1/2O2 → HSO4- + H+ (298 K, 1 M), was ΔGr = -107.8 kcal·mol-1. Moreover, calculations revealed that this was a multistep reaction involving submerged, small energy barriers (∼10 kcal·mol-1). These results indicate that photochemical oxidation of SO2 at the air-water interface with solar actinic light may be an important unaccounted source of sulfate aerosols under polluted haze conditions.

Mechanistic Investigation of Lysine-Targeted Covalent Inhibition of PI3Kδ via ONIOM QM:QM Computations.

Phosphoinositide 3-kinase (PI3K) enzymes are important drug targets, especially in oncology, and several inhibitors are currently under investigation in clinical trials for the treatment of lymphocytic leukemia, follicular lymphoma, breast, thyroid, colorectal, and lung cancer. Targeted covalent inhibitors hold significant promise for drug discovery research especially for kinases. Targeting the lysine residues attracts attention as a new strategy in designing targeted covalent inhibitors, since the lysine residue provides several advantages over the traditional cysteine residue. Recently, new highly selective covalent inhibitors of PI3Kδ with activated ester warheads, targeting the conserved Lys779 residue, were reported. Based on the observed kinetics, a covalent inhibition mechanism was proposed, but the atomistic details of the reaction are still not understood. Therefore, in the present work, we have conducted quantum chemical ONIOM M06-2X/6-31+G(d,p):PM6 calculations on the active site cluster structure of PI3Kδ to elucidate the microscopic details of the mechanism of the aminolysis reaction between Lys779 and the ester inhibitors. Our calculations clearly discriminate the noncovalent methyl ester inhibitor and the covalent inhibitors with activated phenolic esters. For the representative p-NO2, p-F, p-H, and p-OCH3 phenolic esters, the Gibbs free energy profiles of alternative mechanistic paths through either Asp782 or Asp911 demonstrate the modulatory role of active site aspartate residues. The most plausible path alters depending on the electron-withdrawing/donating nature of the p-substituted phenolate leaving group. Inhibitors with sufficiently strong electron-withdrawing group prefer direct dissociation of the leaving group from the tetrahedral zwitterion intermediate, while the ones with electron-donating group favor the formation of a neutral tetrahedral intermediate prior to the dissociation. The relative Gibbs free energy barriers of p-NO2 < p-F < p-H < p-OCH3 substituted phenyl esters display the same qualitative trend as the experimentally measured kinact/KI values. Our results provide in depth insight into the mechanism, which can pave the way for optimizing the inhibitor efficiency.

Photosensitization mechanisms at the air-water interface of aqueous aerosols.

Photosensitization reactions are believed to provide a key contribution to the overall oxidation chemistry of the Earth's atmosphere. Generally, these processes take place on the surface of aqueous aerosols, where organic surfactants accumulate and react, either directly or indirectly, with the activated photosensitizer. However, the mechanisms involved in these important interfacial phenomena are still poorly known. This work sheds light on the reaction mechanisms of the photosensitizer imidazole-2-carboxaldehyde through ab initio (QM/MM) molecular dynamics simulations and high-level ab initio calculations. The nature of the lowest excited states of the system (singlets and triplets) is described in detail for the first time in the gas phase, in bulk water, and at the air-water interface, and possible intersystem crossing mechanisms leading to the reactive triplet state are analyzed. Moreover, the reactive triplet state is shown to be unstable at the air-water surface in a pure water aerosol. The combination of this finding with the results obtained for simple surfactant-photosensitizer models, together with experimental data from the literature, suggests that photosensitization reactions assisted by imidazole-2-carboxaldehyde at the surface of aqueous droplets can only occur in the presence of surfactant species, such as fatty acids, that stabilize the photoactivated triplet at the interface. These findings should help the interpretation of field measurements and the design of new laboratory experiments to better understand atmospheric photosensitization processes.

Mechanistic insights into lysine-targeting covalent inhibition through a theoretical study of ester aminolysis.

Development of targeted covalent inhibitors in drug design has a broad and important interest and many efforts are currently being made in this direction. Targeted covalent inhibitors have special relevance in oncology due to the possibilities they offer to overcome the problems of acquired resistance. In recent experiments, lysine-targeting has been envisaged for the irreversible inhibition of the heterodimeric lipid kinase phosphoinositide 3-kinase delta (PI3Kδ). Activated esters have been evaluated and shown to be promising inhibitors of this enzyme, but the reaction mechanisms display specificities that are not yet fully understood. In the present work, we have carried out a theoretical study of the aminolysis reaction of model esters in aqueous solution to gain insights into the corresponding biological processes. We have found that phenolic esters bearing electron-withdrawing groups are particularly reactive. The predicted mechanism involves the formation of a tetrahedral zwitterionic intermediate, which dissociates into an alkoxide and a protonated amide, this charge separation being the driving force for the subsequent proton transfer and final product formation. Structure-reactivity relationships are reported and shown to be a useful tool for evaluating potential inhibitor candidates.

Midair transformations of aerosols.

Spontaneous reactions play an important role in shaping the chemistry of aerosols.

Tight electrostatic regulation of the OH production rate from the photolysis of hydrogen peroxide adsorbed on surfaces.

Recently, experimental and theoretical works have reported evidence indicating that photochemical processes may significantly be accelerated at heterogeneous interfaces, although a complete understanding of the phenomenon is still lacking. We have carried out a theoretical study of interface and surface effects on the photochemistry of hydrogen peroxide (H2O2) using high-level ab initio methods and a variety of models. Hydrogen peroxide is an important oxidant that decomposes in the presence of light, forming two OH radicals. This elementary photochemical process has broad interest and is used in many practical applications. Our calculations show that it can drastically be affected by heterogeneous interfaces. Thus, compared to gas phase, the photochemistry of H2O2 appears to be slowed on the surface of apolar or low-polar surfaces and, in contrast, hugely accelerated on ionic surfaces or the surface of aqueous electrolytes. We give particular attention to the case of the neat air-water interface. The calculated photolysis rate is similar to the gas phase, which stems from the compensation of two opposite effects, the blue shift of the n→σ* absorption band and the increase of the absorption intensity. Nevertheless, due to the high affinity of H2O2 for the air-water interface, the predicted OH production rate is up to five to six orders of magnitude larger. Overall, our results show that the photochemistry of H2O2 in heterogeneous environments is greatly modulated by the nature of the surface, and this finding opens interesting new perspectives for technological and biomedical applications, and possibly in various atmospheres.

Reactivity of Undissociated Molecular Nitric Acid at the Air-Water Interface.

Recent experiments and theoretical calculations have shown that HNO3 may exist in molecular form in aqueous environments, where in principle one would expect this strong acid to be completely dissociated. Much effort has been devoted to understanding this fact, which has huge environmental relevance since nitric acid is a component of acid rain and also contributes to renoxification processes in the atmosphere. Although the importance of heterogeneous processes such as oxidation and photolysis have been evidenced by experiments, most theoretical studies on hydrated molecular HNO3 have focused on the acid dissociation mechanism. In the present work, we carry out calculations at various levels of theory to obtain insight into the properties of molecular nitric acid at the surface of liquid water (the air-water interface). Through multi-nanosecond combined quantum-classical molecular dynamics simulations, we analyze the interface affinity of nitric acid and provide an order of magnitude for its lifetime with regard to acid dissociation, which is close to the value deduced using thermodynamic data in the literature (∼0.3 ns). Moreover, we study the electronic absorption spectrum and calculate the rate constant for the photolytic process HNO3 + hν → NO2 + OH, leading to 2 × 10-6 s-1, about twice the value in the gas phase. Finally, we describe the reaction HNO3 + OH → NO3 + H2O using a cluster model containing 21 water molecules with the help of high-level ab initio calculations. A large number of reaction paths are explored, and our study leads to the conclusion that the most favorable mechanism involves the formation of a pre-reactive complex (HNO3)(OH) from which product are obtained through a coupled proton-electron transfer mechanism that has a free-energy barrier of 6.65 kcal·mol-1. Kinetic calculations predict a rate constant increase by ∼4 orders of magnitude relative to the gas phase, and we conclude that at the air-water interface, a lower limit for the rate constant is k = 1.2 × 10-9 cm3·molecule-1·s-1. The atmospheric significance of all these results is discussed.

The Aqueous Surface as an Efficient Transient Stop for the Reactivity of Gaseous NO2 in Liquid Water.

The heterogeneous reaction of NO2 with water on diverse surfaces is broadly considered as a possible source of atmospheric HONO in dark conditions, but the associated mechanisms are not fully understood. We report data from first-principles simulations showing that the lifetime of the putative reactive NO2 dimer on the surface of pure water droplets is too small to host the whole process. One infers from our results that the hydrolysis of NO2 in clouds must be catalyzed by organic or inorganic species adsorbed on the droplets.

Photoinduced Oxidation Reactions at the Air-Water Interface.

Chemistry on water is a fascinating area of research. The surface of water and the interfaces between water and air or hydrophobic media represent asymmetric environments with unique properties that lead to unexpected solvation effects on chemical and photochemical processes. Indeed, the features of interfacial reactions differ, often drastically, from those of bulk-phase reactions. In this Perspective, we focus on photoinduced oxidation reactions, which have attracted enormous interest in recent years because of their implications in many areas of chemistry, including atmospheric and environmental chemistry, biology, electrochemistry, and solar energy conversion. We have chosen a few representative examples of photoinduced oxidation reactions to focus on in this Perspective. Although most of these examples are taken from the field of atmospheric chemistry, they were selected because of their broad relevance to other areas. First, we outline a series of processes whose photochemistry generates hydroxyl radicals. These OH precursors include reactive oxygen species, reactive nitrogen species, and sulfur dioxide. Second, we discuss processes involving the photooxidation of organic species, either directly or via photosensitization. The photochemistry of pyruvic acid and fatty acid, two examples that demonstrate the complexity and versatility of this kind of chemistry, is described. Finally, we discuss the physicochemical factors that can be invoked to explain the kinetics and thermodynamics of photoinduced oxidation reactions at aqueous interfaces and analyze a number of challenges that need to be addressed in future studies.

Isoprene Reactivity on Water Surfaces from ab†initio QM/MM Molecular Dynamics Simulations.

Isoprene is the most abundant volatile organic compound in the atmosphere after methane. While gas-phase processes have been widely studied, the chemistry of isoprene in aqueous environments is less well known. Nevertheless, some experiments have reported unexpected reactivity at the air-water interface. In this work, we have carried out combined quantum-classical molecular dynamics simulations of isoprene at the air-water interface, as well as ab initio and density functional theory calculations on isoprene-water complexes. We report the first calculation of the thermodynamics of adsorption of isoprene at the water surface, examine how hydration influences its electronic properties and reactivity indices, and estimate the OH-initiated oxidation rate. Our study indicates that isoprene interacts with the water surface mainly through H-π bonding. This primary interaction mode produces strong fluctuations of the π and π* bond stabilities, and therefore of isoprene's chemical potential, nucleophilicity and ionization potential, anticipating significant dynamical effects on its reactivity at the air-water interface. Using data from the literature and free energies reported in our work, we have estimated the rate of the OH-initiated oxidation process at the air-water interface (5.0×1012  molecule cm-3 s-1 ) to be about 7 orders of magnitude larger than the corresponding rate in the gas phase (8.2×105  molecule cm-3 s-1 ). Atmospheric implications of this result are discussed.

Vibrational Sum-Frequency Generation Spectroscopy in the Energy Representation from Dual-Level Molecular Dynamics Simulations.

We report a cost-effective molecular dynamics approach to calculate sum-frequency generation (SFG) vibrational spectra of molecular species at liquid interfaces in the energy representation formalism that brings together the instantaneous normal mode (INM) analysis at free-energy minima (FEM) and the dual-level free-energy perturbation (FEP) methods. This combined FEP-INM-FEM approach allows analyzing SFG spectra in terms of normal mode contributions at very-high ab initio levels, in contrast to standard time-correlation function (TCF)-based methods, from which it can be considered complementary. It is applied here to the study of the CH3-stretching band of methanol at the air-water interface, which has been thoroughly studied in the literature. The SFG band of acetonitrile in the same conditions has also been calculated with the aim of testing the capability of the method to reproduce small chemical shifts. The suitability of the proposed model is demonstrated by comparing the results with TCF data from QM/MM simulations and with experiments. Analysis of these results provides new insights into the strength and orientational dependence of the SFG signal of symmetric and asymmetric stretching vibrations of CH3 groups, which can be of paramount importance to analyze the spectra of more complex systems.

Molecular reactions at aqueous interfaces.

This Review aims to critically analyse the emerging field of chemical reactivity at aqueous interfaces. The subject has evolved rapidly since the discovery of the so-called 'on-water catalysis', alluding to the dramatic acceleration of reactions at the surface of water or at its interface with hydrophobic media. We review critical experimental studies in the fields of atmospheric and synthetic organic chemistry, as well as related research exploring the origins of life, to showcase the importance of this phenomenon. The physico-chemical aspects of these processes, such as the structure, dynamics and thermodynamics of adsorption and solvation processes at aqueous interfaces, are also discussed. We also present the basic theories intended to explain interface catalysis, followed by the results of advanced ab initio molecular-dynamics simulations. Although some topics addressed here have already been the focus of previous reviews, we aim at highlighting their interconnection across diverse disciplines, providing a common perspective that would help us to identify the most fundamental issues still incompletely understood in this fast-moving field.

A New Mechanism of Acid Rain Generation from HOSO at the Air-Water Interface.

The photochemistry of SO2 at the air-water interface of water droplets leads to the formation of HOSO radicals. Using first-principles simulations, we show that HOSO displays an unforeseen strong acidity (pKa = -1) comparable with that of nitric acid and is fully dissociated at the air-water interface. Accordingly, this radical might play an important role in acid rain formation. Potential implications are discussed.

Fast and Accurate Quantum Crystallography: From Small to Large, from Light to Heavy.

The coupling of the crystallographic refinement technique Hirshfeld atom refinement (HAR) with the recently constructed libraries of extremely localized molecular orbitals (ELMOs) gives rise to the new quantum-crystallographic method HAR-ELMO. This method is significantly faster than HAR but as accurate and precise, especially concerning the free refinement of hydrogen atoms from X-ray diffraction data, so that the first fully quantum-crystallographic refinement of a protein is presented here. However, the promise of HAR-ELMO exceeds large molecules and protein crystallography. In fact, it also renders possible electron-density investigations of heavy elements in small molecules and facilitates the detection and isolation of systematic errors from physical effects.