Using Activation Energies to Elucidate Mechanisms of Water Dynamics Piskulich, Zeke A; Laage, Damien; Thompson, Ward H
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
11/2021, Volume:
125, Issue:
46
Journal Article
Peer reviewed
Open access
Recent advances in the calculation of activation energies are shedding new light on the dynamical time scales of liquid water. In this Perspective, we examine how activation energies elucidate the ...central, but not singular, role of the exchange of hydrogen-bond (H-bond) partners that rearrange the H-bond network of water. The contributions of other motions to dynamical time scales and their associated activation energies are discussed along with one case, vibrational spectral diffusion, where H-bond exchanges are not mechanistically significant. Nascent progress on outstanding challenges, including descriptions of non-Arrhenius effects and activation volumes, are detailed along with some directions for future investigations.
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The reorientation dynamics of water confined within nanoscale, hydrophilic silica pores are investigated using molecular dynamics simulations. The effect of surface hydrogen-bonding and electrostatic ...interactions are examined by comparing with both a silica pore with no charges (representing hydrophobic confinement) and bulk water. The OH reorientation in water is found to slow significantly in hydrophilic confinement compared to bulk water, and is well-described by a power-law decay extending beyond one nanosecond. In contrast, the dynamics of water in the hydrophobic pore are more modestly affected. A two-state model, commonly used to interpret confined liquid properties, is tested by analysis of the position-dependence of the water dynamics. While the two-state model provides a good fit of the orientational decay, our molecular-level analysis evidences that it relies on an over-simplified picture of water dynamics. In contrast with the two-state model assumptions, the interface dynamics is markedly heterogeneous, especially in the hydrophilic pore and there is no single interfacial state with a common dynamics.
Understanding the structure of proteins is key to unraveling their function in biological processes. Thus, significant attention has been paid to the calculation of conformational free energies. In ...this paper, we demonstrate a simple extension of fluctuation theory that permits the calculation of the temperature derivative of the conformational free energy, and hence the internal energy and entropy, from single-temperature simulations. The method further enables the decomposition into the contribution of different interactions present in the system to the internal energy surface. We illustrate the method for the canonical test system of alanine dipeptide in aqueous solution, for which we examine the free energy as a function of two dihedral angles. This system, like many, is most effectively treated using accelerated sampling methods and we show how the present approach is compatible with an important class of these, those that introduce a bias potential, by implementing it within metadynamics.
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Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We ...examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale GCS score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if plasma miRNAs could identify TBI patients within the first 24 h post-injury. Receiver operating characteristic curve analysis indicated that miR-16, miR-92a, and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity), compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.
The self-diffusion of water molecules plays a key part in a broad range of essential processes in biochemistry, medical imaging, material science, and engineering. However, its molecular mechanism ...and the role played by the water hydrogen-bond network rearrangements are not known. Here we combine molecular dynamics simulations and analytic modeling to determine the molecular mechanism of water diffusion. We establish a quantitative connection between the water diffusion coefficient and hydrogen-bond jump exchanges, and identify the features that determine the underlying energetic barrier. We thus provide a unified framework to understand the coupling between translational, rotational, and hydrogen-bond dynamics in liquid water. It explains why these different dynamics do not necessarily exhibit identical temperature dependences although they all result from the same hydrogen-bond exchange events. The consequences for the understanding of water diffusion in supercooled conditions and for water transport in complex aqueous systems, including ionic, biological, and confined solutions, are discussed.
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The ability to generate patient‐specific cells through induced pluripotent stem cell (iPSC) technology has encouraged development of three‐dimensional extracellular matrix (ECM) scaffolds as ...bioactive substrates for cell differentiation with the long‐range goal of bioengineering organs for transplantation. Perfusion decellularization uses the vasculature to remove resident cells, leaving an intact ECM template wherein new cells grow; however, a rigorous evaluative framework assessing ECM structural and biochemical quality is lacking. To address this, we developed histologic scoring systems to quantify fundamental characteristics of decellularized rodent kidneys: ECM structure (tubules, vessels, glomeruli) and cell removal. We also assessed growth factor retention—indicating matrix biofunctionality. These scoring systems evaluated three strategies developed to decellularize kidneys (1% Triton X‐100, 1% Triton X‐100/0.1% sodium dodecyl sulfate (SDS) and 0.02% Trypsin‐0.05% EGTA/1% Triton X‐100). Triton and Triton/SDS preserved renal microarchitecture and retained matrix‐bound basic fibroblast growth factor and vascular endothelial growth factor. Trypsin caused structural deterioration and growth factor loss. Triton/SDS‐decellularized scaffolds maintained 3 h of leak‐free blood flow in a rodent transplantation model and supported repopulation with human iPSC‐derived endothelial cells and tubular epithelial cells ex vivo. Taken together, we identify an optimal Triton/SDS‐based decellularization strategy that produces a biomatrix that may ultimately serve as a rodent model for kidney bioengineering.
The authors validate an optimal detergent‐based protocol for decellularization of rodent whole‐kidney scaffolds, showing that decellularized scaffolds retain an intact vasculature that can be transplanted or re‐endothelialized, wand that the scaffold supports proliferation and tubule formation by human renal cortical tubular epithelial cells.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It is now generally accepted that the hydrated electron occupies a cavity in water, but the size of the cavity and the arrangements of the solvating water molecules have not been fully characterized. ...Here, we use the Kirkwood–Buff (KB) approach to examine how the partial molar volume (V M ) provides insight into these issues. The KB method relates V M to an integral of the electron-water radial distribution function, a key measure of the hydrated electron structure. We have applied it to three widely used pseudopotentials, and the results show that V M is a sensitive measure of the fidelity of hydrated electron descriptions. Thus, the measured V M places constraints on the hydrated electron structure that are important in developing and evaluating the model descriptions. Importantly, we find that V M does not reflect only the cavity size (and thus should not be used to infer the cavity radius) but is strongly dependent on the extended solvation structure.
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Many questions remain about the reactions of the hydrated electron despite decades of study. Of particular note is that they do not appear to follow the Marcus theory of electron transfer reactions, ...a feature that is yet to be explained. To investigate these issues, we used ab initio molecular dynamics (AIMD) simulations to investigate one of the better studied reactions, the hydrated electron reduction of CO2. The rate constant for the hydrated electron–CO2 reaction complex to react to form CO2 – is for the first time estimated from AIMD simulations. Results at 298 and 373 K show the rate constant is insensitive to temperature, consistent with the low measured activation energy for the reaction, and the implications of this behavior are examined. The sampling provided by the simulations yields insight into the reaction mechanism. The reaction is found to involve both solvent reorganization and changes in the carbon dioxide structure. The latter leads to significant vibrational excitation of the bending and symmetric stretch vibrations in the CO2 – product, indicating the reaction is vibrationally nonadiabatic. The former is estimated from the calculation of an approximate collective solvent coordinate and the free energy in this coordinate is determined. These results indicate that AIMD simulations can reasonably estimate hydrated electron reaction activation energies and provide new insight into the mechanism that can help illuminate the features of this unusual chemistry.
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Many questions remain about the reactions of the hydrated electron despite decades of study. Of particular note is that they do not appear to follow the Marcus theory of electron transfer reactions, ...a feature that is yet to be explained. To investigate these issues, we used
molecular dynamics (AIMD) simulations to investigate one of the better studied reactions, the hydrated electron reduction of CO
. The rate constant for the hydrated electron-CO
reaction complex to react to form CO
is for the first time estimated from AIMD simulations. Results at 298 and 373 K show the rate constant is insensitive to temperature, consistent with the low measured activation energy for the reaction, and the implications of this behavior are examined. The sampling provided by the simulations yields insight into the reaction mechanism. The reaction is found to involve both solvent reorganization and changes in the carbon dioxide structure. The latter leads to significant vibrational excitation of the bending and symmetric stretch vibrations in the CO
product, indicating the reaction is vibrationally nonadiabatic. The former is estimated from the calculation of an approximate collective solvent coordinate and the free energy in this coordinate is determined. These results indicate that AIMD simulations can reasonably estimate hydrated electron reaction activation energies and provide new insight into the mechanism that can help illuminate the features of this unusual chemistry.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
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