Double Life of Methanol: Experimental Studies and Nonequilibrium Molecular-Dynamics Simulation of Methanol Effects on Methane-Hydrate Nucleation.

We have investigated systematically and statistically methanol-concentration effects on methane-hydrate nucleation using both experiment and restrained molecular-dynamics simulation, employing simple observables to achieve an initially homogeneous methane-supersaturated solution particularly favorable for nucleation realization in reasonable simulation times. We observe the pronounced "bifurcated" character of the nucleation rate upon methanol concentration in both experiments and simulation, with promotion at low concentrations and switching to industrially familiar inhibition at higher concentrations. Higher methanol concentrations suppress hydrate growth by in-lattice methanol incorporation, resulting in the formation of "defects", increasing the energy of the nucleus. At low concentrations, on the contrary, the detrimental effect of defects is more than compensated for by the beneficial contribution of CH3 in easing methane incorporation in the cages or replacing it altogether.

Controlling hydrogen release from remaining-intact Clathrate hydrates by electromagnetic fields: molecular engineering via microsecond non-equilibrium molecular dynamics.

In view of the recently-predicted hydrogen release from type-II (sII) clathrate hydrates in the general 140-180 K temperature range [J. Phys. Chem. C, 125, 8430-8439 (2021)], we have investigated in the present study, by means of microsecond-long non-equilibrium molecular-dynamics simulation, the effect of externally-applied electric fields (both static and alternating) on manipulating and accelerating this H2-escape process. In particular, we have found that judiciously-selected electromagnetic fields, in the microwave frequency range, serve to enhance dramatically this H2-release rate - crucially, without any breakup of the hydrate lattice itself. Of those studied, we have found that 10 GHz serves as the optimal frequency to maximise hydrogen release, owing to promotion of H2-H2 molecular collisions inside doubly-occupied 51264 cages in the sII structure and optimal field-period overlap with intra-cage tetrahedral-site hopping and opportunities for inter-cage passage via hexagonal cage faces. This study opens up the vista of "field engineering" for exquisite kinetic control of large, Grid-(terawatt hour)-scale hydrogen-storage systems.

Investigation of Dipolar Response of the Hydrated Hen-Egg White Lysozyme Complex under Externally Applied Electric Fields: Insights from Non-equilibrium Molecular Dynamics.

Given its ubiquitous presence in the environment of bio-macromolecules, water is well known to play a fundamental part in biological activity, often as a regulating agent. In parallel, with increasing attention focused on the potential damage of microwave-frequency radiation exposure to human health, the effects of extraneous electric and electromagnetic (e/m) fields on water shells surrounding proteins, and, indeed, biomolecules themselves, are becoming a particularly pertinent issue. In this study, non-equilibrium molecular dynamics simulations of hydrated hen-egg white lysozyme have been performed in both the absence and presence of external electric fields of varying intensity (0.005-0.02 V/Å) and frequency (static, i.e., zero-frequency, together with oscillating fields of 2.45-100 GHz). By comparing the effect of different electric-field conditions on both the protein's and surrounding hydration layer's dipole moments and their underlying relaxation dynamics, clear and evident non-thermal field effects were observed on the dipolar response of both the protein and hydration layer. This occurred primarily as a consequence of the protein's dipolar alignment with the external field and increased with the growth of field intensity. In addition, it was found that the lag time of dipolar response to the applied field itself, for both the protein and the first hydration sub-shell (i.e., directly adsorbed layer), under oscillating fields is longer than that in both the second hydration sub-layer and bulk water, owing to strong direct protein-water adsorption. In that respect, we also probe and discuss the effect of protein-water hydrogen bonds, dissecting the subtleties of "bio-water" dipolar response.

Effects of Externally Applied Electric Fields on the Manipulation of Solvated-Chignolin Folding: Static- versus Alternating-Field Dichotomy at Play.

The interaction between a protein and external electric field (EF) can alter its structure and dynamical behavior, which has a potential impact on the biological function of proteins and cause uncertain health consequences. Conversely, the application of EFs of judiciously selected intensity and frequency can help to treat disease, and optimization of this requires a greater understanding of EF-induced effects underpinning basic protein biophysics. In the present study, chignolin─an artificial protein sufficiently small to undergo fast-folding events and transitions─was selected as an ideal prototype to investigate how, and to what extent, externally applied electric fields may manipulate or influence protein-folding phenomena. Nonequilibrium molecular dynamics (NEMD) simulations have been performed of solvated chignolin to determine the distribution of folding states and their underlying transition dynamics, in the absence and presence of externally applied electric fields (both static and alternating); a key focus has been to ascertain how folding pathways are altered in an athermal sense by external fields. Compared to zero-field conditions, a dramatically different─indeed, bifurcated─behavior of chignolin-folding processes emerges between static- and alternating-field scenarios, especially vis-à-vis incipient stages of hydrophobic-core formation: in alternating fields, fold-state populations diversified, with an attendant acceleration of state-hopping folding kinetics, featuring the concomitant emergence of a new, quasi-stable structure compared to the native structure, in field-shifted energy landscapes.

Phenylethanoid glycosides as a possible COVID-19 protease inhibitor: a virtual screening approach.

From the beginning of pandemic, more than 240 million people have been infected with a death rate higher than 2%. Indeed, the current exit strategy involving the spreading of vaccines must be combined with progress in effective treatment development. This scenario is sadly supported by the vaccine's immune activation time and the inequalities in the global immunization schedule. Bringing the crises under control means providing the world population with accessible and impactful new therapeutics. We screened a natural product library that contains a unique collection of 2370 natural products into the binding site of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). According to the docking score and to the interaction at the active site, three phenylethanoid glycosides (forsythiaside A, isoacteoside, and verbascoside) were selected. In order to provide better insight into the atomistic interaction and test the impact of the three selected compounds at the binding site, we resorted to a half microsecond-long molecular dynamics simulation. As a result, we are showing that forsythiaside A is the most stable molecule and it is likely to possess the highest inhibitory effect against SARS-CoV-2 Mpro. Phenylethanoid glycosides also have been reported to have both protease and kinase activity. This kinase inhibitory activity is very beneficial in fighting viruses inside the body as kinases are required for viral entry, metabolism, and/or reproduction. The dual activity (kinase/protease) of phenylethanoid glycosides makes them very promising anit-COVID-19 agents.

The Importance of Precursors and Modification Groups of Aerogels in CO2 Capture.

The rapid growth of CO2 emissions in the atmosphere has attracted great attention due to the influence of the greenhouse effect. Aerogels' application for capturing CO2 is quite promising owing to their numerous advantages, such as high porosity (~95%); these are predominantly mesoporous (20-50 nm) materials with very high surface area (>800 m2∙g-1). To increase the CO2 level of aerogels' uptake capacity and selectivity, active materials have been investigated, such as potassium carbonate, K2CO3, amines, and ionic-liquid amino-acid moieties loaded onto the surface of aerogels. The flexibility of the composition and surface chemistry of aerogels can be modified intentionally-indeed, manipulated-for CO2 capture. Up to now, most research has focused mainly on the synthesis of amine-modified silica aerogels and the evaluation of their CO2-sorption properties. However, there is no comprehensive study focusing on the effect of different types of aerogels and modification groups on the adsorption of CO2. In this review, we present, in broad terms, the use of different precursors, as well as modification of synthesis parameters. The present review aims to consider which kind of precursors and modification groups can serve as potentially attractive molecular-design characteristics in promising materials for capturing CO2.

Hydrogen and Deuterium Molecular Escape from Clathrate Hydrates: "Leaky" Microsecond-Molecular-Dynamics Predictions.

It is predicted herewith that the leakage of both hydrogen (H2) and deuterium (D2) from sII clathrate hydrates, borne of guest chemical-potential equalization driving enhanced nonequilibrium intercage hopping, should be observable experimentally. To this end, we have designed simulations to realize and study this process by microsecond molecular dynamics within the temperature range of 150-180 K-for which the hydrate lattice was found to be stable. In this pursuit, we considered initial large-cage (51264) guest occupancies of 1-4, with single occupation of 512 cavities. Examining transient, nonequilibrium intercage hopping, we present a lattice-escape activation energy for the four nominal large-cage occupancies (1-4), by fitting to the hydrate-leakage rate. The intercage hopping of H2 and D2 was studied using Markov-chain models and expressed at different temperatures and large-cage occupancies. The free energy of guest "binding" in the large and small cages was also computed for all of the occupancies. Toward equilibrium, following the majority of H2/D2 escape via leakage, the percentage of occupancies was calculated for both H2 and D2 for all of the systems for all initial nominal large-cage occupancies; here, not unexpectedly, double occupancies occurred more favorably in large cages and single occupancies dominated in small cages.

Magnetic-Field Manipulation of Naturally Occurring Microbial Chiral Peptides to Regulate Gas-Hydrate Formation.

Clathrate hydrates are nonstoichiometric crystalline inclusion compounds, wherein a water host lattice entraps small guest molecules in cavities, with methane hydrates being the most widespread in nature. Recent studies have shown that proteins and polypeptides produced by micro-organisms can accelerate methane-hydrate formation. However, the role of magnetic fields and chirality in such phenomena is heretofore unclear. Here, we find prima facie evidence of differently oriented magnetic fields of varying strength showing intricate control on the hydrate-formation kinetics by R and S versions of a prototypical aromatic peptide derived from a naturally occurring, hydrate-promoting source. We also discuss the wider implications of these results on chirality in the biosphere and hydrates in the environment.

Kinetic study on electro-nucleation of water in a heterogeneous propane nano-bubble system to form polycrystalline ice Ic.

Elucidating the underlying mechanisms of water solidification in heterogeneous systems is crucially important for a panoply of applications; gaining such an understanding has also proven to be very challenging to the community. Indeed, one such example lies in clarifying the thermodynamics and kinetics of electro-crystallization in heterogeneous systems, such as micro- and nano-bubble systems. Here, we employ non-equilibrium molecular dynamics of water in heterogeneous environments experiencing direct contact with a propane gas phase at various temperatures in externally applied static electric fields, elucidating significant external-field effects in inducing poly-crystalline cubic-ice formation. This is in stark contrast with recent work on homogeneous cubic-ice electro-nucleation to produce largely fault-free single crystals. We explore the kinetics of heterogeneous cubic-ice electro-nucleation under different field intensities and thermal conditions and provide an overview of time-dependent dynamics of evolution of polycrystallinity.

Experimental and theoretical study for miR-155 detection through resveratrol interaction with nucleic acids using magnetic core-shell nanoparticles.

A novel electrochemical nanobiosensor for the detection of miR-155 (as breast cancer biomarker) is introduced . Fe3O4NPs@Ag core-shell nanoparticles were synthesized and their shape and characteristics were confirmed by scanning electron microscope (SEM) imaging, Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) methods. Synthesized nanoparticles were applied onto the magnetic bar carbon paste electrode and then the amine-modified anti-miR-155 (single-stranded probes) was applied on the modified electrode surface and upon hybridization with target miR-155, resveratrol (RSV) was eventually applied as an electrochemical label on the double-strand oligonucleotide. Differential pulse voltammetry (DPV) of the oxidation peak of RSV was assumed as the final signal by sweeping potential from 0 to 0.6 V (vs. Ag/AgCl). The fabrication process was optimized through a series of experiments and the optimized process was confirmed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The linear range of the fabricated nanobiosensor was 0.5 fM to 1.0 nM and the detection limit was 0.15 fM. The nanobiosensor was able to pass reproducibility and specificity tests using different types of mismatched target sequences.Spiked real samples of human serum were used to confirm that the nanobiosensor enables detection of miR-155 without any significant interferences from other moieties and molecules. Finally, the molecular dynamics simulation of the RSV interaction with single- and double-stranded oligonucleotide was performed and confirmed the preferential binding of RSV to double-stranded DNA; therefore, it can be used as the electrochemical label of DNA and/or miRNA hybridization-based biosensors. Graphical abstract.

Engineering Peptides to Catalyze and Control Stabilization of Gas Hydrates: Learning From Nature.

Clathrate hydrates are nonstoichiometric crystalline inclusion compounds. Water acts as a "host lattice" and traps small guest molecules in stable cavities. One example, methane hydrates, are especially prevalent in situ at the seafloor. Although microorganism-produced proteins and polypeptides, including marine methylotroph porin proteins, can accelerate methane hydrate formation under conditions simulating their natural occurrence at the seafloor, the role that particular peptide sequences play in biocatalytic hydrate kinetics enhancement is unclear, especially the underlying molecular-level mechanisms. Here, we reveal the peptide-focused regulation of microorganisms' role in managing marine hydrates via an approximation mechanism of enzymatic catalysis accelerating hydrate formation. Aside from control of hydrate kinetics per se, we speculate that this peptide-centric mechanistic understanding could lead to a re-evaluation of the extent and geological importance of bioregulation of methane turnover in the biosphere.

Massive generation of metastable bulk nanobubbles in water by external electric fields.

Nanobubbles (NBs) are nanoscopic gaseous domains than can exist on solid surfaces or in bulk liquids. They have attracted substantial attention due to their long-time (meta)stability and a high potential for real-world applications. Using an approach not previously investigated, we exploit surface-electrostatic NB formation and stabilization via application of external electric fields in gas-liquid systems, with the marked result of massively increased gas uptake into the liquid in NB form. The de facto gas solubility enhancement (over many months) ranges from 2.5-fold for oxygen to 30-fold for methane vis-à-vis respective Henry's law values for gas solubility; the more hydrophobic the gas, the more spectacular the increase. Molecular dynamics simulations reveal that the origin of NBs' movement lies in dielectrophoresis, while substantial NB stabilization arises from a surface-polarization interaction.

Acoustic-propagation properties of methane clathrate hydrates from non-equilibrium molecular dynamics.

Given methane hydrates' importance in marine sediments, as well as the widespread use of seabed acoustic-signaling methods in oil and gas exploration, the elastic characterization of these materials is particularly relevant. A greater understanding of the properties governing phonon, sound, and acoustic propagation would help to better classify methane-hydrate deposits, aiding in their discovery. Recently, we have published a new nonequilibrium molecular-dynamics (NEMD) methodology to recreate longitudinal and transverse perturbations, observing their propagation through a crystalline lattice by various metrics, to study the underlying S- and P-wave velocities (achieving excellent agreement with experiment) [Melgar et al., J. Phys. Chem. 122(5), 3006-3013 (2018); ibid.150, 084101 (2019)]. Here, we apply these NEMD methods to methane-clathrate systems to study acoustic-propagation characteristics, as well as the lattice elastic behavior. In so doing, we determine S- and P-wave velocities in excellent accord with experiment; we also ascertain the allowable magnitude range of acoustic perturbation and establish a threshold for lattice breakup and hydrate decomposition. Interestingly, upon dissociation, we observe the formation of methane nanobubbles, which agrees with previous studies on the microscopic fundamentals of hydrate dissociation by various means.

Multi-parameter optimization of the capacitance of Carbon Xerogel catalyzed by NaOH for application in supercapacitors and capacitive deionization systems.

Carbon Xerogel is an economic choice of material for electrodes with applications in Electric Double Layer Capacitors (EDLCs) and Capacitive DeIonization systems (CDI, particularly for desalination). The objective here is to optimize Carbon Xerogel's performance, specifically its capacitance, through multi-parameter optimization using Response Surface Methodology (RSM). We choose NaOH as the catalyst and select as the optimization parameters (i) the pH of the initial Resorcinol-Formaldehyde-Catalyst (RFC) solution, (ii) Reactants to Liquid mass ratio (R/L) of the RFC solution, and (iii) the Pyrolysis Temperature (PT). For a selected range of these three parameters, we obtain an optimum capacitance of Carbon Xerogel equal to 37.6 F/g with optimized parameters PT = 800, R/L = 30% and pH = 5.7. Through comparing Carbon Xerogel samples synthesized with Na2CO3 versus NaOH as the catalyst, we show that the capacitance not only depends on the pH of the initial RFC solution, but also is a strong function of the catalyst material.

Non-equilibrium molecular-dynamics study of electromagnetic-field-induced propane-hydrate dissociation.

Non-equilibrium molecular-dynamics simulations have been performed for dissolution of planar propane-hydrate/water interfaces in externally-applied electromagnetic (e/m) fields in the microwave to far infrared range (∼2.45-200 GHz) at electric-field intensities up to 2.0 V/nm and at roughly 20 K over/under temperatures vis-à-vis the zero-field propane-hydrate melting point. Upon e/m-field application, there is a field-frequency threshold above which the dissociation rate drops significantly, with a plateau therein for larger-frequencies. It was found that higher intensity and lower frequency facilitates dissociation. Except in the presence of a thermal driving-force, the 10 GHz frequency shows more substantial rate-enhancement effect vis-à-vis static electric fields or, indeed, lower-frequency e/m fields.

Pressure-Induced Densification of Ice Ih under Triaxial Mechanical Compression: Dissociation versus Retention of Crystallinity for Intermediate States in Atomistic and Coarse-Grained Water Models.

Molecular-dynamics (MD) simulation of triaxially pressurized ice Ih up to 30 kbar at 240 K (with sudden mechanical pressurization from its ambient-pressure structure) has been carried out with both the single-particle mW and atomistic TIP4P-Ice water potentials on systems of up to ∼1 million molecules, for times of the order of 100 ns. It was found that the TIP4P-Ice systems adopted a high-density liquid state above ∼7 kbar, while densification of the mW systems retained essentially crystalline order, owing to a failure for the tetrahedral network to break down appreciably from its ice Ih lattice structure. Both are intermediate states adopted along the path toward respective thermodynamically stable states (and with pressure removal show reversion to Ih for mW and to supercooled liquid for TIP4P-Ice), similar to recent ice electro-freezing simulations in "No Man's Land". Densification kinetics showed faster mW-system adaptation.

Molecular-dynamics study of propane-hydrate dissociation: Fluctuation-dissipation and non-equilibrium analysis.

Equilibrium and non-equilibrium molecular-dynamics (MD) simulations have been performed to investigate thermal-driven break-up of planar propane-hydrate interfaces in contact with liquid water over the 260-320 K range. Two types of hydrate-surface water-lattice molecular termination were adopted, at the hydrate edge with water, for comparison: a 001-direct surface cleavage and one with completed cages. Statistically significant differences in melting temperatures and initial break-up rates were observed between both interface types. Dissociation rates were observed to be strongly dependent on temperature, with higher rates at larger over-temperatures vis-à-vis melting. A simple coupled mass and heat transfer model, developed previously, was applied to fit the observed dissociation profiles, and this helps us to identify clearly two distinct hydrate-decomposition régimes; following a highly temperature-dependent break-up phase, a second well-defined stage is essentially independent of temperature, in which the remaining nanoscale, de facto two-dimensional system's lattice framework is intrinsically unstable. Further equilibrium MD-analysis of the two-phase systems at their melting point, with consideration of the relaxation times gleaned from the auto-correlation functions of fluctuations in a number of enclathrated guest molecules, led to statistically significant differences between the two surface-termination cases; a consistent correlation emerged in both cases between the underlying, non-equilibrium, thermal-driven dissociation rates sampled directly from melting with that from an equilibrium-MD fluctuation-dissipation approach.

Human aquaporin 4 gating dynamics under axially oriented electric-field impulses: A non-equilibrium molecular-dynamics study.

Human aquaporin 4 has been studied using non-equilibrium molecular dynamics simulations in the absence and presence of pulses of external electric fields. The pulses were 100 ns in duration and 0.005-0.015 V/Å in intensity acting along the pores' axes. Water diffusivity and the dipolar response of various residues of interest within the pores have been studied. Results show relatively little change in levels of water permeability per se within aquaporin channels during axially oriented field impulses, although care must be taken with regard to statistical certainty. However, the spatial variation of water permeability vis-à-vis electric-field intensity within the milieu of the channels, as revealed by heterogeneity in diffusivity-map gradients, indicates the possibility of somewhat enhanced diffusivity, owing to several residues being affected substantially by external fields, particularly for HIS 201 and 95 and ILE 93. This has the effect of increasing slightly intra-pore water diffusivity in the "pore-mouths" locale, albeit rendering it more spatially uniform overall vis-à-vis zero-field conditions (via manipulation of the selectivity filter).