Acid-Base Chemistry of Short Hydrogen Bonds: A Tale of Schrödinger's Cat in Glutamine-Derived Crystals.

Short hydrogen bonds, defined by donor-acceptor distances of less than 2.5 Å, represent a distinct regime in acid-base chemistry where conventional models of hydrogen bonding break down. In an organic crystal formed via a temperature-induced chemical transformation of l-glutamine, we previously identified a short hydrogen bond featuring a double-well potential indicative of an activated proton transfer.

Opportunities and Challenges in Unsupervised Learning: The Case of Aqueous Electrolyte Solutions.

Machine learning has emerged as a powerful tool in atomistic simulations, enabling the identification of complex patterns in molecular systems, limiting human intervention and bias. However, the practical implementation of these methods presents significant technical challenges, particularly in the selection of hyperparameters and in the physical interpretability of machine-learned descriptors. In this work, we systematically investigate these challenges by applying an unsupervised learning protocol to a fundamental problem in physical chemistry, namely, how ions perturb the local structure of water.

Towards a robust approach to infer causality from molecular dynamics simulations.

The ability to distinguish between correlation and causation of variables in molecular systems remains an interesting and open area of investigation. In this work, we probe causality in a molecular system using two independent computational methods that infer the causal direction through the language of information transfer. Specifically, we demonstrate that a molecular dynamics simulation involving a single tryptophan in liquid water displays asymmetric information transfer between specific collective variables, such as solute and solvent coordinates.

Computational investigation of uracil dimers in water and the role of classical potentials.

Nucleobases possess a marked tendency to establish hydrogen bonds - a structural trait at the base of the storage of biological information. It is crucial to understand what is the impact on this intermolecular interaction when free nucleobases are moved to aqueous media. In this work, we present a systematic investigation of the thermodynamics of uracil dimers in explicit water solvent.

Crystallization of L-Cysteine in Heavy Water Induces Intrinsic Fluorescence.

Developing noninvasive techniques that can probe how solvents modulate the nucleation pathways of bioorganic molecules in solution remains an active and open area of research. Herein, we investigate the crystallization of the amino acid L-Cysteine and show that both the structure of the crystal and its intrinsic fluorescence can be drastically altered by the solvent. Crystals formed in heavy water exhibit markedly different intermolecular packing as well as strikingly different monomer conformations compared to those in light water.

Data-Driven Discovery of the Origins of UV Absorption in the Alpha-3C Protein.

Over the past decade, there has been a growing body of experimental work showing that proteins devoid of aromatic and conjugated groups can absorb light in the near-UV beyond 300 nm and emit visible light. Understanding the origins of this phenomenon offers the possibility of designing noninvasive spectroscopic probes for local interactions in biological systems. It was recently found that the synthetic protein αC displays UV-vis absorption between 250 and 800 nm, which was shown to arise from charge-transfer excitations between charged amino acids.

Non-adiabatic Couplings in Surface Hopping with Tight Binding Density Functional Theory: The Case of Molecular Motors.

Nonadiabatic molecular dynamics (NAMD) has become an essential computational technique for studying the photophysical relaxation of molecular systems after light absorption. These phenomena require approximations that go beyond the Born-Oppenheimer approximation, and the accuracy of the results heavily depends on the electronic structure theory employed. Sophisticated electronic methods, however, make these techniques computationally expensive, even for medium size systems.

Revisiting the Enhanced Chemical Reactivity in Water Microdroplets: The Case of a Diels-Alder Reaction.

Often, chemical reactions are markedly accelerated in microdroplets compared with the corresponding bulk phase. While identifying the precise causative factors remains challenging, the interfacial electric field (IEF) and partial solvation are the two widely proposed factors, accounting for the acceleration or turning on of many reactions in microdroplets. In sharp contrast, this combined computational and experimental study demonstrates that these two critical factors have a negligible effect on promoting a model Diels-Alder (DA) reaction between cyclopentadiene and acrylonitrile in water microdroplets.

Dissecting the hydrogen bond network of water: Charge transfer and nuclear quantum effects.

The molecular structure of water is dynamic, with intermolecular hydrogen (H) bond interactions being modified by both electronic charge transfer and nuclear quantum effects (NQEs). Electronic charge transfer and NQEs potentially change under acidic or basic conditions, but such details have not been measured. In this work, we developed correlated vibrational spectroscopy, a symmetry-based method that separates interacting from noninteracting molecules in self- and cross-correlation spectra, giving access to previously inaccessible information.

The Joint Solvation Interaction.

The solvent-induced interactions (SIIs) between flexible solutes can be separated into two distinct components: the solvation-induced conformational effect and the joint solvation interaction (JSI). The JSI quantifies the thermodynamic effect of the solvent simultaneously accommodating the solutes, generalizing the typical notion of the hydrophobic interaction. We present a formal definition of the JSI within the framework of the mixture expansion, demonstrate that this definition is equivalent to the SII between rigid solutes, and propose a method, partially connected molecular dynamics, which allows one to compute the interaction with existing free energy algorithms.

Evidence of ferroelectric features in low-density supercooled water from ab initio deep neural-network simulations.

Over the last decade, an increasing body of evidence has emerged, supporting the existence of a metastable liquid-liquid critical point in supercooled water whereby two distinct liquid phases of different densities coexist. Analyzing long molecular dynamics simulations performed using deep neural-network force fields trained to accurate quantum mechanical data, we demonstrate that the low-density liquid phase displays a strong propensity toward spontaneous polarization, as witnessed by large and long-lived collective dipole fluctuations. Our findings suggest that the dynamical stability of the low-density phase, and hence the transition from high-density to low-density liquid, is triggered by a collective process involving an accumulation of rotational angular jumps, which could ignite large dipole fluctuations.

Exploring the Mechanisms behind Non-aromatic Fluorescence with the Density Functional Tight Binding Method.

Recent experimental findings reveal nonconventional fluorescence emission in biological systems devoid of conjugated bonds or aromatic compounds, termed (NAF). This phenomenon is exclusive to aggregated or solid states and remains absent in monomeric solutions. Previous studies focused on small model systems in vacuum show that the carbonyl stretching mode along with strong interaction of short hydrogen bonds (SHBs) remains the primary vibrational mode explaining NAF in these systems.

Beyond Local Structures in Critical Supercooled Water through Unsupervised Learning.

The presence of a second critical point in water has been a topic of intense investigation for the last few decades. The molecular origins underlying this phenomenon are typically rationalized in terms of the competition between local high-density (HD) and low-density (LD) structures. Their identification often requires designing parameters that are subject to human intervention.

Lessons Learned from Multiobjective Automatic Optimizations of Classical Three-Site Rigid Water Models Using Microscopic and Macroscopic Target Experimental Observables.

The development of accurate water models is of primary importance for molecular simulations. Despite their intrinsic approximations, three-site rigid water models are still ubiquitously used to simulate a variety of molecular systems. Automatic optimization approaches have been recently used to iteratively refine three-site water models to fit macroscopic (average) thermodynamic properties, providing state-of-the-art three-site models that still present some deviations from the liquid water properties.

The carbonyl-lock mechanism underlying non-aromatic fluorescence in biological matter.

Challenging the basis of our chemical intuition, recent experimental evidence reveals the presence of a new type of intrinsic fluorescence in biomolecules that exists even in the absence of aromatic or electronically conjugated chemical compounds. The origin of this phenomenon has remained elusive so far. In the present study, we identify a mechanism underlying this new type of fluorescence in different biological aggregates.

ZundEig: The Structure of the Proton in Liquid Water from Unsupervised Learning.

The structure of the excess proton in liquid water has been the subject of lively debate on both experimental and theoretical fronts for the last century. Fluctuations of the proton are typically interpreted in terms of limiting states referred to as the Eigen and Zundel species. Here, we put these ideas under the microscope, taking advantage of recent advances in unsupervised learning that use local atomic descriptors to characterize environments of acidic water combined with advanced clustering techniques.

Zirconium Coordination Chemistry and Its Role in Optimizing Hydroxymate Chelation: Insights from Molecular Dynamics.

In the past decade, there has been a growth in using Zirconium-89 (Zr) as a radionuclide in nuclear medicine for cancer diagnostic imaging and drug discovery processes. Although one of the most popular chelators for Zr, desferrioxamine (DFO) is typically presented as a hexadentate ligand, our work suggests a different scenario. The coordination structure of the Zr-DFO complex has primarily been informed by DFT-based calculations, which typically ignore temperature and therefore entropic and dynamic solvent effects.

Free energy decompositions illuminate synergistic effects in interfacial binding thermodynamics of mixed surfactant systems.

Recent vibrational sum frequency generation spectroscopic experiments [Sengupta et al., J. Phys.

Examining the origins of observed terahertz modes from an optically pumped atomistic model protein in aqueous solution.

The microscopic origins of terahertz (THz) vibrational modes in biological systems are an active and open area of current research. Recent experiments [Phys Rev X. , 031061 (2018)] have revealed the presence of a pronounced mode at ∼0.

Solvation thermodynamics from cavity shapes of amino acids.

According to common physical chemistry wisdom, the solvent cavities hosting a solute are tightly sewn around it, practically coinciding with its van der Waals surface. Solvation entropy is primarily determined by the surface and the volume of the cavity while enthalpy is determined by the solute-solvent interaction. In this work, we challenge this picture, demonstrating by molecular dynamics simulations that the cavities surrounding the 20 amino acids deviate significantly from the molecular surface.

Water Self-Dissociation is Insensitive to Nanoscale Environments.

Nanoconfinement effects on water dissociation and reactivity remain controversial, despite their importance to understand the aqueous chemistry at interfaces, pores, or aerosols. The pKw in confined environments has been assessed from experiments and simulations in a few specific cases, leading to dissimilar conclusions. Here, with the use of carefully designed ab initio simulations, we demonstrate that the energetics of bulk water dissociation is conserved intact to unexpectedly small length-scales, down to aggregates of only a dozen molecules or pores of widths below 2 nm.

Effect of Quantum Delocalization on Temperature Dependent Double Proton Transfer in Molecular Crystals of Terephthalic Acid.

Double proton transfers (DPTs) are important for several physical processes, both in molecules and in the condensed phase. While these have been widely studied in biological systems, their study in crystalline environments is rare. In this work, using path integral molecular dynamics simulations, we have studied temperature dependent DPT in molecular crystals of terephthalic acid (TPA).

Nonreciprocal forces enable cold-to-hot heat transfer between nanoparticles.

We study the heat transfer between two nanoparticles held at different temperatures that interact through nonreciprocal forces, by combining molecular dynamics simulations with stochastic thermodynamics. Our simulations reveal that it is possible to construct nano refrigerators that generate a net heat transfer from a cold to a hot reservoir at the expense of power exerted by the nonreciprocal forces. Applying concepts from stochastic thermodynamics to a minimal underdamped Langevin model, we derive exact analytical expressions predictions for the fluctuations of work, heat, and efficiency, which reproduce thermodynamic quantities extracted from the molecular dynamics simulations.

Do Machine-Learning Atomic Descriptors and Order Parameters Tell the Same Story? The Case of Liquid Water.

Machine-learning (ML) has become a key workhorse in molecular simulations. Building an ML model in this context involves encoding the information on chemical environments using local atomic descriptors. In this work, we focus on the Smooth Overlap of Atomic Positions (SOAP) and their application in studying the properties of liquid water both in the bulk and at the hydrophobic air-water interface.

The collective burst mechanism of angular jumps in liquid water.

Understanding the microscopic origins of collective reorientational motions in aqueous systems requires techniques that allow us to reach beyond our chemical imagination. Herein, we elucidate a mechanism using a protocol that automatically detects abrupt motions in reorientational dynamics, showing that large angular jumps in liquid water involve highly cooperative orchestrated motions. Our automatized detection of angular fluctuations, unravels a heterogeneity in the type of angular jumps occurring concertedly in the system.