Entropy Drives Accelerated Ion Diffusion upon Carbon Dioxide Expansion of Electrolytes.

Carbon dioxide-expanded liquids, organic solvents with high concentrations of soluble carbon dioxide (CO2) at mild pressures, have gained attention as green catalytic media due to their improved properties over traditional solvents. More recently, carbon dioxide-expanded electrolytes (CXEs) have demonstrated improved reaction rates in the electrochemical reduction of CO2, by increasing the rate of delivery of CO2 to the electrode while maintaining facile charge transport. However, recent studies indicate that the limiting behavior of CXEs at higher CO2 pressures is a decline in solution conductivity due to reduced polarity, leading to poorer charge screening and greater ion pairing. In this article, we employ molecular dynamics simulations to investigate the energetic driving forces behind the diffusive properties of an acetonitrile and tetrapropylammonium hexafluorophosphate (TPrAPF6) CXE with increasing CO2 concentration. Our results indicate that entropy drives solvent and electrolyte diffusion with increasing CO2 pressure. The activation energy of ion diffusion increases with higher concentrations of CO2, indicating that increasing the temperature may improve solution conductivity in these systems. This trend in the activation energies is traced to stronger cation-anion Coulombic interactions due to weaker solvent screening at high CO2 concentrations, suggesting that the choice of ion may provide a route to diminish this effect.

Tuning the redox profile of the 6,6'-biazulenic platform through functionalization along its molecular axis.

The E1/2 potential associated with reduction of the linearly-functionalized 6,6'-biazulenic scaffold is accurately correlated to the combined σp Hammett parameters of the substituents over >600 mV range. X-ray crystallographic analysis of the 2,2'-dichloro-substituted derivative revealed unexpectedly short C-Cl bond distances, along with other metric changes, suggesting a non-trivial cycloheptafulvalene-like structural contribution.

A structure-dynamics relationship enables prediction of the water hydrogen bond exchange activation energy from experimental data.

It has long been understood that the structural features of water are determined by hydrogen bonding (H-bonding) and that the exchange of, or "jumps" between, H-bond partners underlies many of the dynamical processes in water. Despite the importance of H-bond exchanges there is, as yet, no direct method for experimentally measuring the timescale of the process or its associated activation energy. Here, we identify and exploit relationships between water's structural and dynamical properties that provide an indirect route for determining the H-bond exchange activation energy from experimental data. Specifically, we show that the enthalpy and entropy determining the radial distribution function in liquid water are linearly correlated with the activation energies for H-bond jumps, OH reorientation, and diffusion. Using temperature-dependent measurements of the radial distribution function from the literature, we demonstrate how these correlations allow us to infer the value of the jump activation energy, Ea,0, from experimental results. This analysis gives Ea,0 = 3.43 kcal mol-1, which is in good agreement with that predicted by the TIP4P/2005 water model. We also illustrate other approaches for estimating this activation energy consistent with these estimates.

Exploring the Unusual Reactivity of the Hydrated Electron with CO2.

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.

Mechanistic Basis of Conductivity in Carbon Dioxide-Expanded Electrolytes: A Joint Experimental-Theoretical Study.

Electrolyte conductivity contributes to the efficiency of devices for electrochemical conversion of carbon dioxide (CO2) into useful chemicals, but the effect of the dissolution of CO2 gas on conductivity has received little attention. Here, we report a joint experimental-theoretical study of the properties of acetonitrile-based CO2-expanded electrolytes (CXEs) that contain high concentrations of CO2 (up to 12 M), achieved by CO2 pressurization. Cyclic voltammetry data and paired simulations show that high concentrations of dissolved CO2 do not impede the kinetics of outer-sphere electron transfer but decrease the solution conductivity at higher pressures. In contrast with conventional behaviors, Jones reactor-based measurements of conductivity show a nonmonotonic dependence on CO2 pressure: a plateau region of constant conductivity up to ca. 4 M CO2 and a region showing reduced conductivity at higher [CO2]. Molecular dynamics simulations reveal that while the intrinsic ionic strength decreases as [CO2] increases, there is a concomitant increase in ionic mobility upon CO2 addition that contributes to stable solution conductivities up to 4 M CO2. Taken together, these results shed light on the mechanisms underpinning electrolyte conductivity in the presence of CO2 and reveal that the dissolution of CO2, although nonpolar by nature, can be leveraged to improve mass transport rates, a result of fundamental and practical significance that could impact the design of next-generation systems for CO2 conversion. Additionally, these results show that conditions in which ample CO2 is available at the electrode surface are achievable without sacrificing the conductivity needed to reach high electrocatalytic currents.

Hypotension during intensive care stay and mortality and morbidity: a systematic review and meta-analysis.

PURPOSE: The aim of this study is to provide a summary of the existing literature on the association between hypotension during intensive care unit (ICU) stay and mortality and morbidity, and to assess whether there is an exposure-severity relationship between hypotension exposure and patient outcomes. METHODS: CENTRAL, Embase, and PubMed were searched up to October 2022 for articles that reported an association between hypotension during ICU stay and at least one of the 11 predefined outcomes. Two independent reviewers extracted the data and assessed the risk of bias. Results were gathered in a summary table and studies designed to investigate the hypotension-outcome relationship were included in the meta-analyses. RESULTS: A total of 122 studies (176,329 patients) were included, with the number of studies varying per outcome between 0 and 82. The majority of articles reported associations in favor of 'no hypotension' for the outcomes mortality and acute kidney injury (AKI), and the strength of the association was related to the severity of hypotension in the majority of studies. Using meta-analysis, a significant association was found between hypotension and mortality (odds ratio: 1.45; 95% confidence interval (CI) 1.12-1.88; based on 13 studies and 34,829 patients), but not for AKI. CONCLUSION: Exposure to hypotension during ICU stay was associated with increased mortality and AKI in the majority of included studies, and associations for both outcomes increased with increasing hypotension severity. The meta-analysis reinforced the descriptive findings regarding mortality but did not yield similar support for AKI.

Empirically Optimized One-Electron Pseudopotential for the Hydrated Electron: A Proof-of-Concept Study.

Mixed quantum-classical molecular dynamics simulations have been important tools for studying the hydrated electron. They generally use a one-electron pseudopotential to describe the interactions of an electron with the water molecules. This approximation shows both the strength and weakness of the approach. On the one hand, it enables extensive statistical sampling and large system sizes that are not possible with more accurate ab initio molecular dynamics methods. On the other hand, there has (justifiably) been much debate about the ability of pseudopotentials to accurately and quantitatively describe the hydrated electron properties. These pseudopotentials have largely been derived by fitting them to ab initio calculations of an electron interacting with a single water molecule. In this paper, we present a proof-of-concept demonstration of an alternative approach in which the pseudopotential parameters are determined by optimizing them to reproduce key experimental properties. Specifically, we develop a new pseudopotential, using the existing TBOpt model as a starting point, which correctly describes the hydrated electron vertical detachment energy and radius of gyration. In addition to these properties, this empirically optimized model displays a significantly modified solvation structure, which improves, for example, the prediction of the partial molar volume.

Relation between the Hydrated Electron Solvation Structure and Its Partial Molar Volume.

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 (VM) provides insight into these issues. The KB method relates VM 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 VM is a sensitive measure of the fidelity of hydrated electron descriptions. Thus, the measured VM places constraints on the hydrated electron structure that are important in developing and evaluating the model descriptions. Importantly, we find that VM 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.

Effects of polarizability and charge transfer on water dynamics and the underlying activation energies.

A large number of force fields have been proposed for describing the behavior of liquid water within classical atomistic simulations, particularly molecular dynamics. In the past two decades, models that incorporate molecular polarizability and even charge transfer have become more prevalent, in attempts to develop more accurate descriptions. These are frequently parameterized to reproduce the measured thermodynamics, phase behavior, and structure of water. On the other hand, the dynamics of water is rarely considered in the construction of these models, despite its importance in their ultimate applications. In this paper, we explore the structure and dynamics of polarizable and charge-transfer water models, with a focus on timescales that directly or indirectly relate to hydrogen bond (H-bond) making and breaking. Moreover, we use the recently developed fluctuation theory for dynamics to determine the temperature dependence of these properties to shed light on the driving forces. This approach provides key insight into the timescale activation energies through a rigorous decomposition into contributions from the different interactions, including polarization and charge transfer. The results show that charge transfer effects have a negligible effect on the activation energies. Furthermore, the same tension between electrostatic and van der Waals interactions that is found in fixed-charge water models also governs the behavior of polarizable models. The models are found to involve significant energy-entropy compensation, pointing to the importance of developing water models that accurately describe the temperature dependence of water structure and dynamics.

A Maxwell relation for dynamical timescales with application to the pressure and temperature dependence of water self-diffusion and shear viscosity.

A Maxwell relation for a reaction rate constant (or other dynamical timescale) obtained under constant pressure, p, and temperature, T, is introduced and discussed. Examination of this relationship in the context of fluctuation theory provides insight into the p and T dependence of the timescale and the underlying molecular origins. This Maxwell relation motivates a suggestion for the general form of the timescale as a function of pressure and temperature. This is illustrated by accurately fitting simulation results and existing experimental data on the self-diffusion coefficient and shear viscosity of liquid water. A key advantage of this approach is that each fitting parameter is physically meaningful.

Effect of the machine learning-derived Hypotension Prediction Index (HPI) combined with diagnostic guidance versus standard care on depth and duration of intraoperative and postoperative hypotension in elective cardiac surgery patients: HYPE-2 - study protocol of a randomised clinical trial.

INTRODUCTION: Hypotension is common during cardiac surgery and often persists postoperatively in the intensive care unit (ICU). Still, treatment is mainly reactive, causing a delay in its management. The Hypotension Prediction Index (HPI) can predict hypotension with high accuracy. Using the HPI combined with a guidance protocol resulted in a significant reduction in the severity of hypotension in four non-cardiac surgery trials. This randomised trial aims to evaluate the effectiveness of the HPI in combination with a diagnostic guidance protocol on reducing the occurrence and severity of hypotension during coronary artery bypass grafting (CABG) surgery and subsequent ICU admission. METHODS AND ANALYSIS: This is a single-centre, randomised clinical trial in adult patients undergoing elective on-pump CABG surgery with a target mean arterial pressure of 65 mm Hg. One hundred and thirty patients will be randomly allocated in a 1:1 ratio to either the intervention or control group. In both groups, a HemoSphere patient monitor with embedded HPI software will be connected to the arterial line. In the intervention group, HPI values of 75 or above will initiate the diagnostic guidance protocol, both intraoperatively and postoperatively in the ICU during mechanical ventilation. In the control group, the HemoSphere patient monitor will be covered and silenced. The primary outcome is the time-weighted average of hypotension during the combined study phases. ETHICS AND DISSEMINATION: The medical research ethics committee and the institutional review board of the Amsterdam UMC, location AMC, the Netherlands, approved the trial protocol (NL76236.018.21). No publication restrictions apply, and the study results will be disseminated through a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NL9449), ClinicalTrials.gov (NCT05821647).

Direct calculation of the temperature dependence of 2D-IR spectra: Urea in water.

A method for directly calculating the temperature derivative of two-dimensional infrared (2D-IR) spectra from simulations at a single temperature is presented. The approach is demonstrated by application to the OD stretching spectrum of isotopically dilute aqueous (HOD in H2O) solutions of urea as a function of concentration. Urea is an important osmolyte because of its ability to denature proteins, which has motivated significant interest in its effect on the structure and dynamics of water. The present results show that the temperature dependence of both the linear IR and 2D-IR spectra, which report on the underlying energetic driving forces, is more sensitive to urea concentration than the spectra themselves. Additional physical insight is provided by calculation of the contributions to the temperature derivative from different interactions, e.g., water-water, water-urea, and urea-urea, present in the system. Finally, it is demonstrated how 2D-IR spectra at other temperatures can be obtained from only room temperature simulations.

Trust as a key measure of quality and safety after the restriction of family contact in Canadian long-term care settings during the COVID-19 pandemic.

Family caregivers in Canadian long-term care homes are estimated to provide 10 h per week of direct care to approximately 30% of residents through roles including mobility support, mealtime assistance, personal care, social interaction, psychological care, care coordination, and advocacy. Despite these contributions, they continue to be viewed as visitors rather than as key participants in the interdependent relationships that support the long-term care sector. Their marginalization was evident during the COVID-19 pandemic, as Canadian public health policy focused on preventing them from entering long-term care, rather than supporting personal risk management, symptom screening, personal protective equipment, and other mechanisms for safe involvement in care. Several iatrogenic resident outcomes have been attributed to this, including decreased cognitive function, decreased mobility, increased incontinence, weight loss, increased depression and anxiety, increased responsive behaviours amongst those living with dementia, and increased delirium. In this commentary article, we argue that family caregiver presence was conflated as a risk when instead, it contributed to unintended harm. We identify nine well-known human social cognitive predispositions that may have contributed to this. We then examine their implications for trust in long-term care, and consider how quality and safety can be further fostered in long-term care by working in partnership with family caregivers to rebuild trust through enquiry and collaboration. We advocate incorporating trust as an essential measure of quality health service.

Investigation of the Failure of Marcus Theory for Hydrated Electron Reactions.

Reactions of the hydrated electron with a wide variety of substrates have been found to exhibit unusually similar activation energies in a manner incompatible with Marcus electron transfer theory. Given the fundamental linear response assumption of Marcus theory, one possible explanation for this apparent failure is that the underlying free energy surfaces governing the reactions are not harmonic; i.e., hydrated electron structural fluctuations exhibit non-Gaussian behavior. In this work, we test this hypothesis by using simulations to calculate the hydrated electron vertical detachment energy distribution. We consider both cavity and noncavity models for the hydrated electron, between which the actual hydrated electron behavior is expected to lie. Our results identify a possible origin for non-Gaussian behavior of the hydrated electron but show that it is not of sufficient magnitude to explain the failure of Marcus theory to describe its reactions. Thus, other explanations must be sought.

Clinical agreement of a novel algorithm to estimate radial artery blood pressure from the non-invasive finger blood pressure.

STUDY OBJECTIVE: A new algorithm was developed that transforms the non-invasive finger blood pressure (BP) into a radial artery BP (B̂PRad), whereas the original algorithm estimated brachial BP (B̂PBra). In this study we determined whether this new algorithm shows better agreement with invasive radial BP than the original one and whether in the operating room this algorithm can be used safely. DESIGN, SETTING AND PATIENTS: This observational study was conducted on thirty-three non-cardiac surgery patients. INTERVENTION AND MEASUREMENTS: Invasive radial and non-invasive finger BP were measured, of the latter B̂PRad and B̂PBra were transformed. Agreement of systolic, mean, and diastolic arterial BP (SAP, MAP, and DAP, respectively) was assessed traditionally with Bland-Altman and trend analysis and clinically safety was quantified with error grid analyses. A bias (precision) of 5 (8) mmHg or less was considered adequate. MAIN RESULTS: Thirty-three patients were included with an average of 676 (314) 20 s segments. For both comparisons, bias (precision) of MAP was within specified criteria, whereas for SAP, precision was higher than 8 mmHg. B̂PRad showed a better agreement than B̂PBra with BPRad for DAP values (bias (precision): 0.7 (6.0) and - 6.4 (4.3) mmHg, respectively). B̂PRad and B̂PBra both showed good concordance in following changes in BPRad (for all parameters overall degree was <7°). There were slightly more measurement pairs of MAP within the no-risk zone for B̂PRad than for B̂PBra (96 vs 77%, respectively). CONCLUSIONS: In this cohort of non-cardiac surgery patients, we found good agreement between BPRad and B̂PRad. Compared to B̂PBra, B̂PRad shows better agreement although clinical implications are small. This trial was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03795831).

Shining (Infrared) Light on the Hofmeister Series: Driving Forces for Changes in the Water Vibrational Spectra in Alkali-Halide Salt Solutions.

The Hofmeister series is frequently used to rank ions based on their behavior from chaotropes ("structure breakers"), which weaken the surrounding hydrogen-bond network, to kosmotropes ("structure makers"), which enhance it. Here, we use fluctuation theory to investigate the energetic and entropic driving forces underlying the Hofmeister series for aqueous alkali-halide solutions. Specifically, we exploit the OH stretch infrared (IR) spectrum in isotopically dilute HOD/D2O solutions as a probe of the effect of the salt on the water properties for different concentrations and choice of halide anion. Fluctuation theory is used to calculate the temperature derivative of these IR spectra, including decomposition of the derivative into different energetic contributions. These contributions are used to determine the thermodynamic driving forces in terms of effective internal energy and entropic contributions. This analysis implicates entropic contributions as the key factor in the Hofmeister series behavior of the OH stretch IR spectra, while the effective internal energy is nearly ion-independent.

Probing electrolyte-silica interactions through simulations of the infrared spectroscopy of nanoscale pores.

The structural and dynamical properties of nanoconfined solutions can differ dramatically from those of the corresponding bulk systems. Understanding the changes induced by confinement is central to controlling the behavior of synthetic nanostructured materials and predicting the characteristics of biological and geochemical systems. A key outstanding issue is how the molecular-level behavior of nanoconfined electrolyte solutions is reflected in different experimental, particularly spectroscopic, measurements. This is addressed here through molecular dynamics simulations of the OH stretching infrared (IR) spectroscopy of NaCl, NaBr, and NaI solutions in isotopically dilute HOD/D2O confined in hydroxylated amorphous silica slit pores of width 1-6 nm and pH ∼2. In addition, the water reorientation dynamics and spectral diffusion, accessible by pump-probe anisotropy and two-dimensional IR measurements, are investigated. The aim is to elucidate the effect of salt identity, confinement, and salt concentration on the vibrational spectra. It is found that the IR spectra of the electrolyte solutions are only modestly blue-shifted upon confinement in amorphous silica slit pores, with both the size of the shift and linewidth increasing with the halide size, but these effects are suppressed as the salt concentration is increased. This indicates the limitations of linear IR spectroscopy as a probe of confined water. However, the OH reorientational and spectral diffusion dynamics are significantly slowed by confinement even at the lowest concentrations. The retardation of the dynamics eases with increasing salt concentration and pore width, but it exhibits a more complex behavior as a function of halide.

Water Diffusion Proceeds via a Hydrogen-Bond Jump Exchange Mechanism.

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.