Hydrogen bonding heterogeneity correlates with protein folding transition state passage time as revealed by data sonification.

Protein-protein and protein-water hydrogen bonding interactions play essential roles in the way a protein passes through the transition state during folding or unfolding, but the large number of these interactions in molecular dynamics (MD) simulations makes them difficult to analyze. Here, we introduce a state space representation and associated "rarity" measure to identify and quantify transition state passage (transit) events. Applying this representation to a long MD simulation trajectory that captured multiple folding and unfolding events of the GTT WW domain, a small protein often used as a model for the folding process, we identified three transition categories: Highway (faster), Meander (slower), and Ambiguous (intermediate). We developed data sonification and visualization tools to analyze hydrogen bond dynamics before, during, and after these transition events. By means of these tools, we were able to identify characteristic hydrogen bonding patterns associated with "Highway" versus "Meander" versus "Ambiguous" transitions and to design algorithms that can identify these same folding pathways and critical protein-water interactions directly from the data. Highly cooperative hydrogen bonding can either slow down or speed up transit. Furthermore, an analysis of protein-water hydrogen bond dynamics at the surface of WW domain shows an increase in hydrogen bond lifetime from folded to unfolded conformations with Ambiguous transitions as an outlier. In summary, hydrogen bond dynamics provide a direct window into the heterogeneity of transits, which can vary widely in duration (by a factor of 10) due to a complex energy landscape.

Trimethylamine-N-oxide depletes urea in a peptide solvation shell.

Trimethylamine-N-oxide (TMAO) and urea are metabolites that are used by some marine animals to maintain their cell volume in a saline environment. Urea is a well-known denaturant, and TMAO is a protective osmolyte that counteracts urea-induced protein denaturation. TMAO also has a general protein-protective effect, for example, it counters pressure-induced protein denaturation in deep-sea fish. These opposing effects on protein stability have been linked to the spatial relationship of TMAO, urea, and protein molecules. It is generally accepted that urea-induced denaturation proceeds through the accumulation of urea at the protein surface and their subsequent interaction. In contrast, it has been suggested that TMAO's protein-stabilizing effects stem from its exclusion from the protein surface, and its ability to deplete urea from protein surfaces; however, these spatial relationships are uncertain. We used neutron diffraction, coupled with structural refinement modeling, to study the spatial associations of TMAO and urea with the tripeptide derivative glycine-proline-glycinamide in aqueous urea, aqueous TMAO, and aqueous urea-TMAO (in the mole ratio 1:2 TMAO:urea). We found that TMAO depleted urea from the peptide's surface and that while TMAO was not excluded from the tripeptide's surface, strong atomic interactions between the peptide and TMAO were limited to hydrogen bond donating peptide groups. We found that the repartition of urea, by TMAO, was associated with preferential TMAO-urea bonding and enhanced urea-water hydrogen bonding, thereby anchoring urea in the bulk solution and depleting urea from the peptide surface.

The electrochemistry of stable sulfur isotopes versus lithium.

Sulfur in nature consists of two abundant stable isotopes, with two more neutrons in the heavy one (34S) than in the light one (32S). The two isotopes show similar physicochemical properties and are usually considered an integral system for chemical research in various fields. In this work, a model study based on a Li-S battery was performed to reveal the variation between the electrochemical properties of the two S isotopes. Provided with the same octatomic ring structure, the cyclo-34S8 molecules form stronger S-S bonds than cyclo-32S8 and are more prone to react with Li. The soluble Li polysulfides generated by the Li-34S conversion reaction show a stronger cation-solvent interaction yet a weaker cation-anion interaction than the 32S-based counterparts, which facilitates quick solvation of polysulfides yet hinders their migration from the cathode to the anode. Consequently, the Li-34S cell shows improved cathode reaction kinetics at the solid-liquid interface and inhibited shuttle of polysulfides through the electrolyte so that it demonstrates better cycling performance than the Li-32S cell. Based on the varied shuttle kinetics of the isotopic-S-based polysulfides, an electrochemical separation method for 34S/32S isotope is proposed, which enables a notably higher separation factor than the conventional separation methods via chemical exchange or distillation and brings opportunities to low-cost manufacture, utilization, and research of heavy chalcogen isotopes.

Enhancing ion selectivity by tuning solvation abilities of covalent-organic-framework membranes.

Understanding the molecular-level mechanisms involved in transmembrane ion selectivity is essential for optimizing membrane separation performance. In this study, we reveal our observations regarding the transmembrane behavior of Li+ and Mg2+ ions as a response to the changing pore solvation abilities of the covalent-organic-framework (COF) membranes. These abilities were manipulated by adjusting the lengths of the oligoether segments attached to the pore channels. Through comparative experiments, we were able to unravel the relationships between pore solvation ability and various ion transport properties, such as partitioning, conduction, and selectivity. We also emphasize the significance of the competition between Li+ and Mg2+ with the solvating segments in modulating selectivity. We found that increasing the length of the oligoether chain facilitated ion transport; however, it was the COF membrane with oligoether chains containing two ethylene oxide units that exhibited the most pronounced discrepancy in transmembrane energy barrier between Li+ and Mg2+, resulting in the highest separation factor among all the evaluated membranes. Remarkably, under electro-driven binary-salt conditions, this specific COF membrane achieved an exceptional Li+/Mg2+ selectivity of up to 1352, making it one of the most effective membranes available for Li+/Mg2+ separation. The insights gained from this study significantly contribute to advancing our understanding of selective ion transport within confined nanospaces and provide valuable design principles for developing highly selective COF membranes.

Regulation of anion-Na+ coordination chemistry in electrolyte solvates for low-temperature sodium-ion batteries.

High-performance sodium storage at low temperature is urgent with the increasingly stringent demand for energy storage systems. However, the aggravated capacity loss is induced by the sluggish interfacial kinetics, which originates from the interfacial Na+ desolvation. Herein, all-fluorinated anions with ultrahigh electron donicity, trifluoroacetate (TFA-), are introduced into the diglyme (G2)-based electrolyte for the anion-reinforced solvates in a wide temperature range. The unique solvation structure with TFA- anions and decreased G2 molecules occupying the inner sheath accelerates desolvation of Na+ to exhibit decreased desolvation energy from 4.16 to 3.49 kJ mol-1 and 24.74 to 16.55 kJ mol-1 beyond and below -20 °C, respectively, compared with that in 1.0 M NaPF6-G2. These enable the cell of Na||Na3V2(PO4)3 to deliver 60.2% of its room-temperature capacity and high capacity retention of 99.2% after 100 cycles at -40 °C. This work highlights regulation of solvation chemistry for highly stable sodium-ion batteries at low temperature.

Unveil the origin of voltage oscillation for sodium-ion batteries operating at -40 °C.

Voltage oscillation at subzero in sodium-ion batteries (SIBs) has been a common but overlooked scenario, almost yet to be understood. For example, the phenomenon seriously deteriorates the performance of Na3V2(PO4)3 (NVP) cathode in PC (propylene carbonate)/EC (ethylene carbonate)-based electrolyte at -20 °C. Here, the correlation between voltage oscillation, structural evolution, and electrolytes has been revealed based on theoretical calculations, in-/ex-situ techniques, and cross-experiments. It is found that the local phase transition of the Na3V2(PO4)3 (NVP) cathode in PC/EC-based electrolyte at -20 °C should be responsible for the oscillatory phenomenon. Furthermore, the low exchange current density originating from the high desolvation energy barrier in NVP-PC/EC system also aggravates the local phase transformation, resulting in severe voltage oscillation. By introducing the diglyme solvent with lower Na-solvent binding energy, the voltage oscillation of the NVP can be eliminated effectively at subzero. As a result, the high capacity retentions of 98.3% at -20 °C and 75.3% at -40 °C are achieved. The finding provides insight into the abnormal SIBs degradation and brings the voltage oscillation behavior of rechargeable batteries into the limelight.

Toward a quantitative interfacial description of solvation for Li metal battery operation under extreme conditions.

The future application of Li metal batteries (LMBs) at scale demands electrolytes that endow improved performance under fast-charging and low-temperature operating conditions. Recent works indicate that desolvation kinetics of Li+ plays a crucial role in enabling such behavior. However, the modulation of this process has typically been achieved through inducing qualitative degrees of ion pairing into the system. In this work, we find that a more quantitative control of the ion pairing is crucial to minimizing the desolvation penalty at the electrified interface and thus the reversibility of the Li metal anode under kinetic strain. This effect is demonstrated in localized electrolytes based on strongly and weakly bound ether solvents that allow for the deconvolution of solvation chemistry and structure. Unexpectedly, we find that maximum degrees of ion pairing are suboptimal for ultralow temperature and high-rate operation and that reversibility is substantially improved via slight local dilution away from the saturation point. Further, we find that at the optimum degree of ion pairing for each system, weakly bound solvents still produce superior behavior. The impact of these structure and chemistry effects on charge transfer are then explicitly resolved via experimental and computational analyses. Lastly, we demonstrate that the locally optimized diethyl ether-based localized-high-concentration electrolytes supports kinetic strained operating conditions, including cycling down to -60 °C and 20-min fast charging in LMB full cells. This work demonstrates that explicit, quantitative optimization of the Li+ solvation state is necessary for developing LMB electrolytes capable of low-temperature and high-rate operation.

Rotational dive into the water clusters on a simple sugar substrate.

Most biomolecular activity takes place in aqueous environments, and it is strongly influenced by the surrounding water molecules. The hydrogen bond networks that these water molecules form are likewise influenced by their interactions with the solutes, and thus, it is crucial to understand this reciprocal process. Glycoaldehyde (Gly), often considered the smallest sugar, represents a good template to explore the steps of solvation and determine how the organic molecule shapes the structure and hydrogen bond network of the solvating water cluster. Here, we report a broadband rotational spectroscopy study on the stepwise hydration of Gly with up to six water molecules. We reveal the preferred hydrogen bond networks formed when water molecules start to form three-dimensional (3D) topologies around an organic molecule. We observe that water self-aggregation prevails even in these early stages of microsolvation. These hydrogen bond networks manifest themselves through the insertion of the small sugar monomer in the pure water cluster in a way in which the oxygen atom framework and hydrogen bond network resemble those of the smallest three-dimensional pure water clusters. Of particular interest is the identification, in both the pentahydrate and hexahydrate, of the previously observed prismatic pure water heptamer motif. Our results show that some specific hydrogen bond networks are preferred and survive the solvation of a small organic molecule, mimicking those of pure water clusters. A many-body decomposition analysis of the interaction energy is also performed to rationalize the strength of a particular hydrogen bond, and it successfully confirms the experimental findings.

Regulating the reduction reaction pathways via manipulating the solvation shell and donor number of the solvent in Li-CO2 chemistry.

Transforming CO2 into valuable chemicals is an inevitable trend in our current society. Among the viable end-uses of CO2, fixing CO2 as carbon or carbonates via Li-CO2 chemistry could be an efficient approach, and promising achievements have been obtained in catalyst design in the past. Even so, the critical role of anions/solvents in the formation of a robust solid electrolyte interphase (SEI) layer on cathodes and the solvation structure have never been investigated. Herein, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in two common solvents with various donor numbers (DN) have been introduced as ideal examples. The results indicate that the cells in dimethyl sulfoxide (DMSO)-based electrolytes with high DN possess a low proportion of solvent-separated ion pairs and contact ion pairs in electrolyte configuration, which are responsible for fast ion diffusion, high ionic conductivity, and small polarization. The 3 M DMSO cell delivered the lowest polarization of 1.3 V compared to all the tetraethylene glycol dimethyl ether (TEGDME)-based cells (about 1.7 V). In addition, the coordination of the O in the TFSI- anion to the central solvated Li+ ion was located at around 2 Å in the concentrated DMSO-based electrolytes, indicating that TFSI- anions could access the primary solvation sheath to form an LiF-rich SEI layer. This deeper understanding of the electrolyte solvent property for SEI formation and buried interface side reactions provides beneficial clues for future Li-CO2 battery development and electrolyte design.

Solvent selection criteria for temperature-resilient lithium-sulfur batteries.

All-climate temperature operation capability and increased energy density have been recognized as two crucial targets, but they are rarely achieved together in rechargeable lithium (Li) batteries. Herein, we demonstrate an electrolyte system by using monodentate dibutyl ether with both low melting and high boiling points as the sole solvent. Its weak solvation endows an aggregate solvation structure and low solubility toward polysulfide species in a relatively low electrolyte concentration (2 mol L-1). These features were found to be vital in avoiding dendrite growth and enabling Li metal Coulombic efficiencies of 99.0%, 98.2%, and 98.7% at 23 °C, -40 °C, and 50 °C, respectively. Pouch cells employing thin Li metal (50 µm) and high-loading sulfurized polyacrylonitrile (3.3 mAh cm-2) cathodes (negative-to-positive capacity ratio = 2) output 87.5% and 115.9% of their room temperature capacity at -40 °C and 50 °C, respectively. This work provides solvent-based design criteria for a wide temperature range Li-sulfur pouch cells.

Coupling dual metal active sites and low-solvation architecture toward high-performance aqueous ammonium-ion batteries.

Aqueous rechargeable ammonium-ion batteries (AIBs) possess the characteristics of safety, low cost, environmental friendliness, and fast diffusion kinetics. However, their energy density is often limited due to the low specific capacity of cathode materials and narrow electrochemical stability windows of electrolytes. Herein, high-performance aqueous AIBs were designed by coupling Fe-substituted manganese-based Prussian blue analog (FeMnHCF) cathodes and highly concentrated NH4CF3SO3 electrolytes. In FeMnHCF, Mn3+/Mn2+-N redox reaction at high potential was introduced, and two metal active redox species of Mn and Fe were achieved. To match such FeMnHCF cathodes, highly concentrated NH4CF3SO3 electrolyte was further developed, where NH4+ ion displays low-solvation structure because of the increased coordination number of CF3SO3- anions. Furthermore, the water molecules are confined by NH4+ and CF3SO3- ions in their solvation sheath, leading to weak interaction between water molecules and thus effectively extending the voltage window of electrolyte. Consequently, the FeMnHCF electrodes present high reversibility during the charge/discharge process. Moreover, owing to a small amount of free water in concentrated electrolyte, the dissolution of FeMnHCF is also inhibited. As a result, the assembled aqueous AIBs exhibit enhanced energy density, excellent rate capability, and stable cycling behavior. This work provides a creative route to construct high-performance aqueous AIBs.

Unraveling the Hydrolysis Mechanism of LiPF6 in Electrolyte of Lithium Ion Batteries.

Lithium hexafluorophosphate (LiPF6) has been the dominant conducting salt in lithium-ion battery (LIB) electrolytes for decades; however, it is extremely unstable in even trace water (ppm level). Interestingly, in pure water, PF6- does not undergo hydrolysis. Hereby, we present a fresh understanding of the mechanism involved in PF6- hydrolysis through theoretical and experimental explorations. In water, PF6- is found to be solvated by water, and this solvation greatly improved its hydrolytic stability; while in the electrolyte, it is forced to "float" due to the dissociation of its counterbalance ions. Its hydrolytic susceptibility arises from insufficient solvation-induced charge accumulation and high activity in electrophilic reactions with acidic species. Tuning the solvation environment, even by counterintuitively adding more water, could suppress PF6- hydrolysis. The undesired solvation of PF6- anions was attributed to the perennial LIB electrolyte system, and our findings are expected to inspire new thoughts regarding its design.

Superior Li+ Kinetics by "Low-Activity-Solvent" Engineering for Stable Lithium Metal Batteries.

The structure of solvated Li+ has a significant influence on the electrolyte/electrode interphase (EEI) components and desolvation energy barrier, which are two key factors in determining the Li+ diffusion kinetics in lithium metal batteries. Herein, the "solvent activity" concept is proposed to quantitatively describe the correlation between the electrolyte elements and the structure of solvated Li+. Through fitting the correlation of the electrode potential and solvent concentration, we suggest a "low-activity-solvent" electrolyte (LASE) system for deriving a stable inorganic-rich EEI. Nano LiF particles, as a model, were used to capture free solvent molecules for the formation of a LASE system. This advanced LASE not only exhibits outstanding antidendrite growth behavior but also delivers an impressive performance in Li/LiNi0.8Co0.1Mn0.1O2 cells (a capacity of 169 mAh g-1 after 250 cycles at 0.5 C).

Low-Temperature and Fast-Charging Lithium Metal Batteries Enabled by Solvent-Solvent Interaction Mediated Electrolyte.

Lithium metal batteries utilizing lithium metal as the anode can achieve a greater energy density. However, it remains challenging to improve low-temperature performance and fast-charging features. Herein, we introduce an electrolyte solvation chemistry strategy to regulate the properties of ethylene carbonate (EC)-based electrolytes through intermolecular interactions, utilizing weakly solvated fluoroethylene carbonate (FEC) to replace EC, and incorporating the low-melting-point solvent 1,2-difluorobenzene (2FB) as a diluent. We identified that the intermolecular interaction between 2FB and solvent can facilitate Li+ desolvation and lower the freezing point of the electrolyte effectively. The resulting electrolyte enables the LiNi0.8Co0.1Mn0.1O2||Li cell to operate at -30 °C for more than 100 cycles while delivering a high capacity of 154 mAh g-1 at 5.0C. We present a solvation structure and interfacial model to analyze the behavior of the formulated electrolyte composition, establishing a relationship with cell performance and also providing insights for the electrolyte design under extreme conditions.

An All-Climate Nonaqueous Hydrogen Gas-Proton Battery.

Rechargeable hydrogen gas batteries, driven by hydrogen evolution and oxidation reactions (HER/HOR), are emerging grid-scale energy storage technologies owing to their low cost and superb cycle life. However, compared with aqueous electrolytes, the HER/HOR activities in nonaqueous electrolytes have rarely been studied. Here, for the first time, we develop a nonaqueous proton electrolyte (NAPE) for a high-performance hydrogen gas-proton battery for all-climate energy storage applications. The advanced nonaqueous hydrogen gas-proton battery (NAHPB) assembled with a representative V2(PO4)3 cathode and H2 anode in a NAPE exhibits a high discharge capacity of 165 mAh g-1 at 1 C at room temperature. It also efficiently operates under all-climate conditions (from -30 to +70 °C) with an excellent electrochemical performance. Our findings offer a new direction for designing nonaqueous proton batteries in a wide temperature range.

Resolving binding pathways and solvation thermodynamics of plant hormone receptors.

Plant hormones are small molecules that regulate plant growth, development, and responses to biotic and abiotic stresses. They are specifically recognized by the binding site of their receptors. In this work, we resolved the binding pathways for eight classes of phytohormones (auxin, jasmonate, gibberellin, strigolactone, brassinosteroid, cytokinin, salicylic acid, and abscisic acid) to their canonical receptors using extensive molecular dynamics simulations. Furthermore, we investigated the role of water displacement and reorganization at the binding site of the plant receptors through inhomogeneous solvation theory. Our findings predict that displacement of water molecules by phytohormones contributes to free energy of binding via entropy gain and is associated with significant free energy barriers for most systems analyzed. Also, our results indicate that displacement of unfavorable water molecules in the binding site can be exploited in rational agrochemical design. Overall, this study uncovers the mechanism of ligand binding and the role of water molecules in plant hormone perception, which creates new avenues for agrochemical design to target plant growth and development.

Thermodynamic consequences of stapling side-chains on a peptide ligand using a lactam-bridge: A theoretical study on anti-angiogenic peptides targeting VEGF.

Peptides are promising therapeutic agents for various biological targets due to their high efficacy and low toxicity, and the design of peptide ligands with high binding affinity to the target of interest is of utmost importance in peptide-based drug design. Introducing a conformational constraint to a flexible peptide ligand using a side-chain lactam-bridge is a convenient and efficient method to improve its binding affinity to the target. However, in general, such a small structural modification to a flexible ligand made with the intent of lowering the configurational entropic penalty for binding may have unintended consequences in different components of the binding enthalpy and entropy, including the configurational entropy component, which are still not clearly understood. Toward probing this, we examine different components of the binding enthalpy and entropy as well as the underlying structure and dynamics, for a side-chain lactam-bridged peptide inhibitor and its flexible analog forming complexes with vascular endothelial growth factor (VEGF), using all-atom molecular dynamics simulations. It is found that introducing a side-chain lactam-bridge constraint into the flexible peptide analog led to a gain in configurational entropy change but losses in solvation entropy, solute internal energy, and solvation energy changes upon binding, pinpointing the opportunities and challenges in drug design. The present study features an interplay between configurational and solvation entropy changes, as well as the one between binding enthalpy and entropy, in ligand-target binding upon imposing a conformational constraint into a flexible ligand.

Computed versus experimental energy barriers in solution: Influence of the type of the density functional approximation.

Mechanistic investigations at the density functional theory level of organic and organometallic reactions in solution are now broadly accessible and routinely implemented to complement experimental investigations. The selection of an appropriate functional among the plethora of developed ones is the first challenge on the way to reliable energy barrier calculations. To provide guidelines for the choice of an initial and reliable computational level, the performances of commonly used non-empirical (PBE, PBE0, PBE0-DH) and empirical density functionals (BLYP, B3LYP, B2PLYP) were evaluated relative to experimental activation enthalpies. Most reactivity databases to assess density functional performances are primarily based on high level calculations, here a set of experimental activation enthalpies of organic and organometallic reactions performed in solution were selected from the literature. As a general trend, the non-empirical functionals outperform the empirical ones. The most accurate energy barriers are obtained with hybrid PBE0 and double-hybrid PBE0-DH density functionals, both providing similar performance. Regardless of the functional under consideration, the addition of the GD3-BJ empirical dispersion correction does not enhance the accuracy of computed energy barriers.

Soft-sphere continuum solvation models for nonaqueous solvents.

Solvation effects profoundly influence the characteristics and behavior of chemical systems in liquid solutions. The interaction between solute and solvent molecules intricately impacts solubility, reactivity, stability, and various chemical processes. Continuum solvation models gained prominence in quantum chemistry by implicitly capturing these interactions and enabling efficient investigations of diverse chemical systems in solution. In comparison, continuum solvation models in condensed matter simulation are very recent. Among these, the self-consistent continuum solvation (SCCS) and the soft-sphere continuum solvation models (SSCS) have been among the first to be successfully parameterized and extended to model periodic systems in aqueous solutions and electrolytes. As most continuum approaches, these models depend on a number of parameters that are linked to experimental or theoretical properties of the solvent, or that can be tuned based on reference data. Here, we present a systematic parameterization of the SSCS model for over 100 nonaqueous solvents. We validate the model's efficacy across diverse solvent environments by leveraging experimental solvation-free energies and partition coefficients from comprehensive databases. The average root means square error over all the solvents was calculated as 0.85 kcal/mol which is below the chemical accuracy (1 kcal/mol). Similarly to what has been reported by Hille et al. (J. Chem. Phys. 2019, 150, 041710.) for the SCCS model, a single-parameter model accurately reproduces experimental solvation energies, showcasing the transferability and predictive power of these continuum approaches. Our findings underscore the potential for a unified approach to predict solvation properties, paving the way for enhanced computational studies across various chemical environments.

Conformational energies of biomolecules in solution: Extending the MPCONF196 benchmark with explicit water molecules.

A prerequisite for the computational prediction of molecular properties like conformational energies of biomolecules is a reliable, robust, and computationally affordable method usually selected according to its performance for relevant benchmark sets. However, most of these sets comprise molecules in the gas phase and do not cover interactions with a solvent, even though biomolecules typically occur in aqueous solution. To address this issue, we introduce a with explicit water molecules solvated version of a gas-phase benchmark set containing 196 conformers of 13 peptides and other relevant macrocycles, namely MPCONF196 [J. Rezác et al., JCTC 2018, 14, 1254-1266], and provide very accurate PNO-LCCSD(T)-F12b/AVQZ' reference values. The novel solvMPCONF196 benchmark set features two additional challenges beyond the description of conformers in the gas phase: conformer-water and water-water interactions. The overall best performing method for this set is the double hybrid revDSDPBEP86-D4/def2-QZVPP yielding conformational energies of almost coupled cluster quality. Furthermore, some (meta-)GGAs and hybrid functionals like B97M-V and ω B97M-D with a large basis set reproduce the coupled cluster reference with an MAD below 1 kcal mol - 1 . If more efficient methods are required, the composite DFT-method r 2 SCAN-3c (MAD of 1.2 kcal mol - 1 ) is a good alternative, and when conformational energies of polypeptides or macrocycles with more than 500-1000 atoms are in the focus, the semi-empirical GFN2-xTB or the MMFF94 force field (for very large systems) are recommended.