Data-Driven Path Collective Variables.

Identifying optimal collective variables to model transformations using atomic-scale simulations is a long-standing challenge. We propose a new method for the generation, optimization, and comparison of collective variables that can be thought of as a data-driven generalization of the path collective variable concept. It consists of a kernel ridge regression of the committor probability, which encodes a transformation's progress. The resulting collective variable is one-dimensional, interpretable, and differentiable, making it appropriate for enhanced sampling simulations requiring biasing. We demonstrate the validity of the method on two different applications: a precipitation model and the association of Li+ and F- in water. For the former, we show that global descriptors such as the permutation invariant vector allow reaching an accuracy far from the one achieved via simpler, more intuitive variables. For the latter, we show that information correlated with the transformation mechanism is contained in the first solvation shell only and that inertial effects prevent the derivation of optimal collective variables from the atomic positions only.

Free energy calculations and unbiased molecular dynamics targeting the liquid-liquid transition in water no man's land.

The existence of a first-order phase transition between a low-density liquid (LDL) and a high-density liquid (HDL) form of supercooled water has been a central and highly debated issue of physics and chemistry for the last three decades. We present a computational study that allows us to determine the free-energy landscapes of supercooled water over a wide range of pressure and temperature conditions using the TIP4P/2005 force field. Our approach combines topology-based structural transformation coordinates, state-of-the-art free-energy calculation methods, and extensive unbiased molecular dynamics. All our diverse simulations cannot detect any barrier within the investigated timescales and system size, for a discontinuous transition between the LDL and HDL forms throughout the so-called "no man's land," until the onset of the solid, non-diffusive amorphous forms.

Critical Assessment of Data-Driven versus Heuristic Reaction Coordinates in Solution Chemistry.

Reaction coordinates are an essential ingredient of theoretical studies of rare events in chemistry and physics because they carry information about reaction mechanism and allow the computation of free-energy landscapes and kinetic rates. We present a critical assessment of the merits and disadvantages of heuristic reaction coordinates, largely employed today, with respect to coordinates optimized on the basis of reliable transition-path sampling data. We take as a test bed multinanosecond ab initio molecular dynamics simulations of chloride SN2 substitution on methyl chloride in explicit water. The computational protocol we devise allows the unsupervised optimization of agnostic coordinates able to account for solute and solvent contributions, yielding a free-energy reconstruction of quality comparable to the best heuristic coordinates without requiring chemical intuition.

Combining Machine Learning Approaches and Accurate Ab Initio Enhanced Sampling Methods for Prebiotic Chemical Reactions in Solution.

The study of the thermodynamics, kinetics, and microscopic mechanisms of chemical reactions in solution requires the use of advanced free-energy methods for predictions to be quantitative. This task is however a formidable one for atomistic simulation methods, as the cost of quantum-based ab initio approaches, to obtain statistically meaningful samplings of the relevant chemical spaces and networks, becomes exceedingly heavy. In this work, we critically assess the optimal structure and minimal size of an ab initio training set able to lead to accurate free-energy profiles sampled with neural network potentials. The results allow one to propose an ab initio protocol where the ad hoc inclusion of a machine-learning (ML)-based task can significantly increase the computational efficiency, while keeping the ab initio accuracy and, at the same time, avoiding some of the notorious extrapolation risks in typical atomistic ML approaches. We focus on two representative, and computationally challenging, reaction steps of the classic Strecker-cyanohydrin mechanism for glycine synthesis in water solution, where the main precursors are formaldehyde and hydrogen cyanide. We demonstrate that indistinguishable ab initio quality results are obtained, thanks to the ML subprotocol, at about 1 order of magnitude less of computational load.

Carbon Dioxide under Earth Mantle Conditions: From a Molecular Liquid through a Reactive Fluid to Polymeric Regimes.

In both its gaseous and condensed forms, carbon dioxide has an ever-increasing impact on Earth's chemistry and human life and activities. However, many aspects of its high-pressure phase diagram remain unclear. In this work, we present a complete structural characterization of carbon dioxide fluids under geological conditions using extensive ab initio molecular dynamics simulations throughout a wide pressure and temperature range, corresponding to Earth's lower mantle. We identify and describe four different disordered regimes, including two polymeric forms and two molecular ones, all within the geothermal conditions of the lower mantle. At pressures below 40 GPa, we find that the molecular liquid becomes very reactive above 2000 K: the C-O double bond routinely breaks, resulting in small and transient chains composed of CO2 units and frequently leading to an exchange of oxygen atoms between molecules. At higher pressures, in addition to the polymeric fluid previously reported at 3000 K, we find a polymeric system with glass-like behavior at lower temperatures, suggesting a complex interplay between kinetics and stability.

Step by Step Strecker Amino Acid Synthesis from Ab Initio Prebiotic Chemistry.

The amino acids synthesis from elementary precursors in abiotic conditions is traditionally described according to the Strecker reaction, thoroughly invoked to justify the observation of amino acids in extraterrestrial samples and their emergence in the primordial Earth. To this day, however, a quantitative microscopic description of the mechanism, thermodynamics, and kinetics of the multistep Strecker reaction is still lacking. In the present work we tackle this study by adopting a state-of-the-art ab initio computational approach, combining an efficient scheme of exploration of the relevant chemical networks with a rigorous determination of the underlying free energy and transition states. We determine the step-by-step chemical pathway from "Strecker precursors" to glycine in solution and calculate the corresponding full free energy landscape. Our results agree well with the scarce available experimental data and complete them, thus providing the first end-to-end study of this complex reaction, a crucial bottleneck for the emergence of life.

Ab Initio Molecular Dynamics Study of Methanol-Water Mixtures under External Electric Fields.

Intense electric fields applied on H-bonded systems are able to induce molecular dissociations, proton transfers, and complex chemical reactions. Nevertheless, the effects induced in heterogeneous molecular systems such as methanol-water mixtures are still elusive. Here we report on a series of state-of-the-art ab initio molecular dynamics simulations of liquid methanol-water mixtures at different molar ratios exposed to static electric fields. If, on the one hand, the presence of water increases the proton conductivity of methanol-water mixtures, on the other, it hinders the typical enhancement of the chemical reactivity induced by electric fields. In particular, a sudden increase of the protonic conductivity is recorded when the amount of water exceeds that of methanol in the mixtures, suggesting that important structural changes of the H-bond network occur. By contrast, the field-induced multifaceted chemistry leading to the synthesis of e.g., hydrogen, dimethyl ether, formaldehyde, and methane observed in neat methanol, in 75:25, and equimolar methanol-water mixtures, completely disappears in samples containing an excess of water and in pure water. The presence of water strongly inhibits the chemical reactivity of methanol.

Prebiotic chemistry and origins of life research with atomistic computer simulations.

Research in origins of life is an intrinsically multi-disciplinary field, aimed at finding answers to the formidably complex problem of understanding the emergence of life from the modern versions of Charles Darwin's celebrated "primordial soup". In the last few years, thanks to the increasing computational power and the development of sophisticated theoretical and numerical methods, several computational chemistry and physics groups have invested this field, providing new microscopic insights on fundamental prebiotic chemistry phenomena possibly occurring in the early Earth and outer space. This review presents the most successful and powerful approaches in computational chemistry, and the main results thus obtained in prebiotic chemistry and origins of life. The aim of this work is both to describe the state-of-the-art in computational prebiotic chemistry, possibly useful both to theorists and experimentalists in origins of life research, and to suggest future directions and new perspectives offered by modern simulation tools.

On the link between polyamorphism and liquid-liquid transition: The case of salty water.

We investigate a LiCl:6D2O water solution in the deep undercooled regime as a function of pressure by neutron diffraction, small angle neutron scattering, and molecular dynamics simulations. We probe the structure of the undercooled liquid and the existence of density fluctuations in the system along isotherms just above the observed first-order-like polymorphic transition in the solid between a high density amorphous (s-HDA) and a very high density amorphous (s-VHDA) form [L. E. Bove et al., Phys. Rev. Lett. 106, 125701 (2011)]. We observe a continuous pressure evolution of the structure factor of the liquid and the absence of density fluctuations when crossing the continuation line of the s-HDA and s-VHDA boundary. These results indicate that no liquid-liquid transition is observed in the system in correspondence with the solid polyamorphism.

Synthesis of RNA Nucleotides in Plausible Prebiotic Conditions from ab Initio Computer Simulations.

Understanding the mechanism of spontaneous formation of ribonucleotides under realistic prebiotic conditions is a key open issue of origins-of-life research. In cells, de novo and salvage nucleotide enzymatic synthesis combines 5-phospho-α-d-ribose-1-diphosphate (α-PRPP) and nucleobases. Interestingly, these reactants are also known as prebiotically plausible compounds. Combining ab initio molecular dynamics simulations with recently developed reaction exploration and enhanced sampling methods, we show that nucleobases and α-PRPP should spontaneously combine, under mild hydrothermal conditions, with an exothermic reaction and a facile mechanism, forming both purine and pyrimidine ribonucleotides. Surprisingly, this mechanism is very similar to the biological one and yields ribonucleotides with the same anomeric carbon chirality as in biological systems. Mass spectrometry experiments performed on solutions of adenine and PRPP in similar conditions support the formation of AMP. These results suggest that natural selection might have optimized, through enzymes, a pre-existing ribonucleotide formation mechanism, carrying it forward to modern life forms.

Synthesis of (d)-erythrose from glycolaldehyde aqueous solutions under electric field.

The formation of the first C-C bonds from formaldehyde represents the rate-limiting step of the formose reaction. However, the free-energy surface associated with such a process has never been determined in condensed phase. By means of ab initio molecular dynamics and metadynamics techniques here we report on the free-energy landscape underlying the synthesis of glycolaldehyde from a formaldehyde aqueous solution. Moreover, numerical samples of formaldehyde (both neat and in water solution) and of glycolaldehyde (both neat and in aqueous solution) have been exposed to intense electric fields. The application of electrostatic gradients strongly prevents the formaldehyde umpolung and catalyzes the formation of C-O-bonded polymers in formaldehyde-containing samples. However, when the field is applied on glycolaldehyde aqueous solutions, new C-C bonds are formed and (d)-erythrose is synthesized. This way, a numerical Miller-like experiment led to the formation of a prebiotically relevant (d)-tetrose from ubiquitarious molecules such as glycolaldehyde and water.

Hydrothermal Decomposition of Amino Acids and Origins of Prebiotic Meteoritic Organic Compounds.

The organic compounds found in carbonaceous chondrite meteorites provide insight into primordial solar system chemistry. Evaluating the formation and decomposition mechanisms of meteoritic amino acids may aid our understanding of the origins of life and homochirality on Earth. The amino acid glycine is widespread in meteorites and other extraterrestrial environments; other amino acids, such as isovaline, are found with enantiomeric excesses in some meteorites. The relationship between meteoritic amino acids and other compounds with similar molecular structures, such as aliphatic monoamines and monocarboxylic acids is unclear; experimental results evaluating the decomposition of amino acids have produced inconclusive results about the preferred pathways, reaction intermediates, and if the conditions applied may be compatible with those occurring inside meteoritic parent bodies. In this work, we performed extensive tandem metadynamics, umbrella sampling, and committor analysis to simulate the neutral mild hydrothermal decomposition mechanisms of glycine and isovaline and put them into context for the origins of meteoritic organic compounds. Our ab initio simulations aimed to determine free energy profiles and decomposition pathways for glycine and isovaline. We found that under our modeled conditions, methylammonium, glycolic acid, and sec-butylamine are the most likely decomposition products. These results suggest that meteoritic aliphatic monocarboxylic acids are not produced from decomposition of meteoritic amino acids. Our results also indicate that the decomposition of L-isovaline prefers an enantioselective pathway resulting in the production of (S)-sec-butylamine.

Novel electrochemical route to cleaner fuel dimethyl ether.

Methanol, the simplest alcohol, and dimethyl ether, the simplest ether, are central compounds in the search for alternative "green" combustion fuels. In fact, they are generally considered as the cornerstones of the envisaged "Methanol Economy" scenario, as they are able to efficiently produce energy in an environmentally friendly manner. However, despite a massive amount of research in this field, the synthesis of dimethyl ether from liquid methanol has never so far been reported. Here we present a computational study, based on ab initio Molecular Dynamics, which suggests a novel synthesis route to methanol dehydration - leading thus to the dimethyl ether synthesis - through the application of strong electric fields. Besides proving the impressive catalytic effects afforded by the field, our calculations indicate that the obtained dimethyl ether is stable and that it can be progressively accumulated thanks to the peculiar chemical pathways characterising the methanol reaction network under electric field. These results suggest that the experimental synthesis of dimethyl ether from liquid methanol could be achieved, possibly in the proximity of field emitter tips.

One-step electric-field driven methane and formaldehyde synthesis from liquid methanol.

The reaction pathways connecting methanol to methane and formaldehyde are among the most emblematic in chemistry because of their outstanding interest in the fields of energy, synthesis, and bio- and geo-chemistry. Despite of its fundamental nature, the one-pot synthesis of formaldehyde and methane stemming from methanol has never been reported before. Here we present a study, based on ab initio molecular dynamics and free-energy methods, in which the simultaneous oxidation and reduction (i.e., the disproportionation) of liquid methanol into methane and formaldehyde has been achieved at ambient temperature through the application of a static electric field. Because strong electric fields can be generated in the proximity of field emitter tips, this finding shows that the challenge of experimentally disproportionating methanol into formaldehyde and methane could be attempted. We show that the methanol "solvent" molecules play a major role in this process and that the chemical pathway connecting methanol to the detected products in the bulk liquid phase is very different from its reproduced gas-phase counterpart. Finally, we demonstrate that switching on an external electric field drastically modifies the reaction network of methanol, lowering some activation barriers, stabilizing the methane and formaldehyde products, and opening otherwise difficult-to-achieve chemical routes.

Prebiotic synthesis of nucleic acids and their building blocks at the atomic level - merging models and mechanisms from advanced computations and experiments.

The origin of life on Earth is one of the most fascinating questions of contemporary science. Extensive research in the past decades furnished diverse experimental proposals for the emergence of first informational polymers that could form the basis of the early terrestrial life. Side by side with the experiments, the fast development of modern computational chemistry methods during the last 20 years facilitated the use of in silico modelling tools to complement the experiments. Modern computations can provide unique atomic-level insights into the structural and electronic aspects as well as the energetics of key prebiotic chemical reactions. Many of these insights are not directly obtainable from the experimental techniques and the computations are thus becoming indispensable for proper interpretation of many experiments and for qualified predictions. This review illustrates the synergy between experiment and theory in the origin of life research focusing on the prebiotic synthesis of various nucleic acid building blocks and on the self-assembly of nucleotides leading to the first functional oligonucleotides.

Liquid methanol under a static electric field.

We report on an ab initio molecular dynamics study of liquid methanol under the effect of a static electric field. We found that the hydrogen-bond structure of methanol is more robust and persistent for field intensities below the molecular dissociation threshold whose value (≈0.31 V/Å) turns out to be moderately larger than the corresponding estimate obtained for liquid water. A sustained ionic current, with ohmic current-voltage behavior, flows in this material for field intensities above 0.36 V/Å, as is also the case of water, but the resulting ionic conductivity (≈0.40 S cm(-1)) is at least one order of magnitude lower than that of water, a circumstance that evidences a lower efficiency of proton transfer processes. We surmise that this study may be relevant for the understanding of the properties and functioning of technological materials which exploit ionic conduction, such as direct-methanol fuel cells and Nafion membranes.

Effect of electric field orientation on the mechanical and electrical properties of water ices: an ab-initio study.

We present a first-principles study of the properties of ordinary hexagonal ice (phase I(h)) and of its proton-ordered version (phase XI) under the action of static electric fields. We compute the mechanical response to the field in addition to the ionic current-voltage diagrams; we also analyze several other microscopic aspects of the proton transfer mechanism, with particular emphasis on the role played by the oxygen sublattice in driving molecular dissociation. We further study the topological aspects of the mechanical and electrical responses by orienting the external field along two different crystalline directions in both ice samples. At variance with ice Ih, ice XI displays an anisotropic behavior in the range of explored field intensities. In fact, when the direction of the field coincides with the ferroelectric axis, sustained molecular dissociation and proton transfer events are both observed just beyond a given field intensity; instead, the two processes exhibit different activation thresholds when the field is oriented along another symmetry axis. The underlying mechanism of molecular dissociation appears to be the same in solid and liquid water independently of the direction of the field.