Revisiting Ultrafast Dynamics in Carbonate-Based Electrolytes for Li-Ion Batteries: Clarifying 2D-IR Cross-Peak Interpretation.

Understanding chemical exchange in carbonate-based electrolytes employed in Li-ion batteries (LIBs) is crucial for elucidating ion transport mechanisms. Ultrafast two-dimensional (2D) IR spectroscopy has been widely used to investigate the solvation structure and dynamics of Li-ions in organic carbonate-based electrolytes. However, the interpretation of cross-peaks observed in picosecond carbonyl stretch 2D-IR spectra has remained contentious. These cross-peaks could arise from various phenomena, including vibrational couplings between neighboring carbonyl groups in the first solvation shell around Li-ions, vibrational excitation transfers between carbonyl groups in distinct solvation environments, and local heating effects. Therefore, it is imperative to resolve the interpretation of 2D-IR cross-peaks to avoid misinterpretations regarding ultrafast dynamics found in LIB carbonate-based electrolytes. In this study, we have taken a comprehensive investigation of carbonate-based electrolytes utilizing 2D-IR spectroscopy and molecular dynamics (MD) simulations. Through meticulous analyses and interpretations, we have identified that the cross-peaks observed in the picosecond 2D-IR spectra of LIB electrolytes predominantly arise from intermolecular vibrational excitation transfer processes between the carbonyl groups of Li-bound and free carbonate molecules. We further discuss the limitations of employing a picosecond 2D-IR spectroscopic technique to study chemical exchange and intermolecular vibrational excitation transfer processes, particularly when the effects of the molecular photothermal process cannot be ignored. Our findings shed light on the dynamics of LIB electrolytes and resolve the controversy related to 2D-IR cross-peaks. By discerning the origin of these features, we could provide valuable insights for the design and optimization of next-generation Li-ion batteries.

Free Volume Element Sizes and Dynamics in Polystyrene and Poly(methyl methacrylate) Measured with Ultrafast Infrared Spectroscopy.

The size, size distribution, dynamics, and electrostatic properties of free volume elements (FVEs) in polystyrene (PS) and poly(methyl methacrylate) (PMMA) were investigated using the Restricted Orientation Anisotropy Method (ROAM), an ultrafast infrared spectroscopic technique. The restricted orientational dynamics of a vibrational probe embedded in the polymer matrix provides detailed information on FVE sizes and their probability distribution. The probe's orientational dynamics vary as a function of its frequency within the inhomogeneously broadened vibrational absorption spectrum. By characterizing the degree of orientational restriction at different probe frequencies, FVE radii and their probability distribution were determined. PS has larger FVEs and a broader FVE size distribution than PMMA. The average FVE radii in PS and PMMA are 3.4 and 3.0 Å, respectively. The FVE radius probability distribution shows that the PS distribution is non-Gaussian, with a tail to larger radii, whereas in PMMA, the distribution is closer to Gaussian. FVE structural dynamics, previously unavailable through other techniques, occur on a ∼150 ps time scale in both polymers. The dynamics involve FVE shape fluctuations which, on average, conserve the FVE size. FVE radii were associated with corresponding electric field strengths through the first-order vibrational Stark effect of the CN stretch of the vibrational probe, phenyl selenocyanate (PhSeCN). PMMA displayed unique measured FVE radii for each electric field strength. By contrast, PS showed that, while larger radii correspond to unique and relatively weak electric fields, the smallest measured radii map onto a broad distribution of strong electric fields.

Quantifying tensile forces at cell-cell junctions with a DNA-based fluorescent probe.

Cells are physically contacting with each other. Direct and precise quantification of forces at cell-cell junctions is still challenging. Herein, we have developed a DNA-based ratiometric fluorescent probe, termed DNAMeter, to quantify intercellular tensile forces. These lipid-modified DNAMeters can spontaneously anchor onto live cell membranes. The DNAMeter consists of two self-assembled DNA hairpins of different force tolerance. Once the intercellular tension exceeds the force tolerance to unfold a DNA hairpin, a specific fluorescence signal will be activated, which enables the real-time imaging and quantification of tensile forces. Using E-cadherin-modified DNAMeter as an example, we have demonstrated an approach to quantify, at the molecular level, the magnitude and distribution of E-cadherin tension among epithelial cells. Compatible with readily accessible fluorescence microscopes, these easy-to-use DNA tension probes can be broadly used to quantify mechanotransduction in collective cell behaviors.

Structural Heterogeneity in the Preamyloid Oligomers of ß-2-Microglobulin.

In dialysis patients, the protein ß2-microglobulin (ß2m) forms amyloid fibrils in a condition known as dialysis-related amyloidosis. To understand the early stages of the amyloid assembly process, we have used native electrospray ionization (ESI) together with ion mobility mass spectrometry (IM-MS) to study soluble preamyloid oligomers. ESI-IM-MS reveals the presence of multiple conformers for the dimer, tetramer, and hexamer that precede the Cu(II)-induced amyloid assembly process, results which are distinct from ß2m oligomers formed at low pH. Experimental and computational results indicate that the predominant dimer is a Cu(II)-bound structure with an antiparallel side-by-side configuration. In contrast, tetramers exist in solution in both Cu(II)-bound and Cu(II)-free forms. Selective depletion of Cu(II)-bound species results in two primary conformers-one that is compact and another that is more expanded. Molecular modeling and molecular dynamics simulations identify models for these two tetrameric conformers with unique interactions and interfaces that enthalpically compensate for the loss of Cu(II). Unlike with other amyloid systems in which conformational heterogeneity is often associated with different amyloid morphologies or off-pathway events, conformational heterogeneity in the tetramer seems to be a necessary aspect of Cu(II)-induced amyloid formation by ß2m. Moreover, the Cu(II)-free models represent a new advance in our understanding of Cu(II) release in Cu(II)-induced amyloid formation, laying a foundation for further mechanistic studies as well as development of new inhibition strategies.

Modulation of Amyloid-ß42 Conformation by Small Molecules Through Nonspecific Binding.

Aggregation of amyloid-ß (Aß) peptides is a crucial step in the progression of Alzheimer's disease (AD). Identifying aggregation inhibitors against AD has been a great challenge. We report an atomistic simulation study of the inhibition mechanism of two small molecules, homotaurine and scyllo-inositol, which are AD drug candidates currently under investigation. We show that both small molecules promote a conformational change of the Aß42 monomer toward a more collapsed phase through a nonspecific binding mechanism. This finding provides atomistic-level insights into designing potential drug candidates for future AD treatments.

Two-Dimensional Infrared Spectroscopy and Molecular Dynamics Simulation Studies of Nonaqueous Lithium Ion Battery Electrolytes.

Lithium ion battery (LIB) technology is undoubtedly indispensable to modern life. However, despite enormous and extended effort to improve LIB performance, our understanding of the underlying principles and mechanisms of lithium ion transport in nonaqueous LIB electrolytes remained limited until recently. There is a particular lack of knowledge of the microscopic solvation structures and fluctuation dynamics around charge carriers in real electrolytes. Typical electrolytes found in commercially available LIBs consist of lithium salts and mixed carbonate solvents, with the latter playing an essential role in promoting lithium ion transport and forming an electrically stable solid electrolyte interphase. Although a number of linear spectroscopic studies of LIB electrolytes aiming at understanding the complex nature of lithium ion solvation processes have been reported, the notion that each lithium ion is strongly solvated by carbonate molecules to form a long-lasting solvation sheath structure has remained the subject of intense debate. Here, we present the results of FTIR, fs IR pump-probe, two-dimensional IR spectroscopy, and molecular dynamics simulations reported by us and others and discuss the possible interplay of picosecond solvation dynamics and macroscopic ion transport processes within the framework of the fluctuation-dissipation relationship. Further, by measuring the time-dependent fluctuations and spectral diffusions of carbonate carbonyl stretch modes that act as excellent infrared probes for the local electrostatic environment, we show that lithium cations are not only solvated by carbonate molecules but also interact with counteranions at equilibrium depending on solvent composition. Molecular dynamics simulations support the notion that rapid chemical exchanges between carbonate solvent molecules in the first and outer solvation shells are critical for describing mobile lithium ion transport phenomena. We thus anticipate that time-resolved coherent multidimensional vibrational spectroscopy is capable of providing decisive evidence on the ultrafast solvent dynamics of various electrolytes, which is potentially helpful for designing improved and more efficient LIB electrolytes in the future.

Ab initio Modeling of the Vibrational Sum-Frequency Generation Spectrum of Interfacial Water.

Understanding the structural and dynamical features of interfacial water is of greatest interest in physics, chemistry, biology, and materials science. Vibrational sum-frequency generation (SFG) spectroscopy, which is sensitive to the molecular orientation and dynamics on the surfaces or at the interfaces, allows one to study a wide variety of interfacial systems. The structural and dynamical features of interfacial water at the air/water interface have been extensively investigated by SFG spectroscopy. However, the interpretations of the spectroscopic features have been under intense debate. Here, we report a simulated SFG spectrum of the air/water interface based on ab initio molecular dynamics simulations, which covers the OH stretching, bending, and libration modes of interfacial water. Quantitative agreement between our present simulations and the most recent experimental studies ensures that ab initio simulations predict unbiased structural features and electrical properties of interfacial systems. By utilizing the kinetic energy spectral density (KESD) analysis to decompose the simulated spectra, the spectroscopic features can then be assigned to specific hydrogen-bonding configurations of interfacial water molecules.

Revealing the Solvation Structure and Dynamics of Carbonate Electrolytes in Lithium-Ion Batteries by Two-Dimensional Infrared Spectrum Modeling.

Carbonate electrolytes in lithium-ion batteries play a crucial role in conducting lithium ions between two electrodes. Mixed solvent electrolytes consisting of linear and cyclic carbonates are commonly used in commercial lithium-ion batteries. To understand how the linear and cyclic carbonates introduce different solvation structures and dynamics, we performed molecular dynamics simulations of two representative electrolyte systems containing either linear or cyclic carbonate solvents. We then modeled their two-dimensional infrared (2DIR) spectra of the carbonyl stretching mode of these carbonate molecules. We found that the chemical exchange process involving formation and dissociation of lithium-ion/carbonate complexes is responsible for the growth of 2DIR cross peaks with increasing waiting time. In addition, we also found that cyclic carbonates introduce faster dynamics of dissociation and formation of lithium-ion/carbonate complexes than linear carbonates. These findings provide new insights into understanding the lithium-ion mobility and its interplay with solvation structure and ultrafast dynamics in carbonate electrolytes used in lithium-ion batteries.

Orientational ordering of water in extended hydration shells of cations is ion-specific and is correlated directly with viscosity and hydration free energy.

Specific ion effects in aqueous solutions are investigated at the molecular, nanoscopic and macroscopic levels. Femtosecond elastic second harmonic scattering (fs-ESHS) is used here to assess the chemical effects of ions on molecular and nanoscopic length scales of water, probing changes in the charge distribution around ions as well as structural orientational order of water molecules in extended hydration shells. We measured >0.05 M electrolyte solutions with a series of chloride salts (LiCl, NaCl, KCl, CsCl, RbCl, NH4Cl, MgCl2, CaCl2, and SrCl2). Ion specificity is observed in both the local electronic anisotropy and the nanoscopic orientational ordering of water. Both observables are influenced more by cations with larger valencies and smaller sizes and follow a direct Hofmeister trend. These ion-induced structural changes in the hydrogen-bond network of water are strongly correlated with the viscosity B-coefficient and the Gibbs free energy of hydration of ions. Such a connection between the nanoscopic and macroscopic changes provides a possibility to construct a molecular model for specific ion effects in aqueous solutions.

Second-Harmonic Scattering as a Probe of Structural Correlations in Liquids.

Second-harmonic scattering experiments of water and other bulk molecular liquids have long been assumed to be insensitive to interactions between the molecules. The measured intensity is generally thought to arise from incoherent scattering due to individual molecules. We introduce a method to compute the second-harmonic scattering pattern of molecular liquids directly from atomistic computer simulations, which takes into account the coherent terms. We apply this approach to large-scale molecular dynamics simulations of liquid water, where we show that nanosecond second-harmonic scattering experiments contain a coherent contribution arising from radial and angular correlations on a length scale of ≲1 nm, much shorter than had been recently hypothesized ( Shelton , D. P. J. Chem. Phys. 2014 , 141 ). By combining structural correlations from simulations with experimental data ( Shelton , D. P. J. Chem. Phys. 2014 , 141 ), we can also extract an effective molecular hyperpolarizability in the liquid phase. This work demonstrates that second-harmonic scattering experiments and atomistic simulations can be used in synergy to investigate the structure of complex liquids, solutions, and biomembranes, including the intrinsic intermolecular correlations.

Electrolytes induce long-range orientational order and free energy changes in the H-bond network of bulk water.

Electrolytes interact with water in many ways: changing dipole orientation, inducing charge transfer, and distorting the hydrogen-bond network in the bulk and at interfaces. Numerous experiments and computations have detected short-range perturbations that extend up to three hydration shells around individual ions. We report a multiscale investigation of the bulk and surface of aqueous electrolyte solutions that extends from the atomic scale (using atomistic modeling) to nanoscopic length scales (using bulk and interfacial femtosecond second harmonic measurements) to the macroscopic scale (using surface tension experiments). Electrolytes induce orientational order at concentrations starting at 10 µM that causes nonspecific changes in the surface tension of dilute electrolyte solutions. Aside from ion-dipole interactions, collective hydrogen-bond interactions are crucial and explain the observed difference of a factor of 6 between light water and heavy water.

Molecular determinants of desensitization in an ENaC/degenerin channel.

Epithelial Na(+) channel (ENaC)/degenerin family members are involved in mechanosensation, blood pressure control, pain sensation, and the expression of fear. Several of these channel types display a form of desensitization that allows the channel to limit Na(+) influx during prolonged stimulation. We used site-directed mutagenesis and chemical modification, functional analysis, and molecular dynamics simulations to investigate the role of the lower palm domain of the acid-sensing ion channel 1, a member of the ENaC/degenerin family. The lower palm domains of this trimeric channel are arranged around a central vestibule, at ∼20 Šabove the plasma membrane and are covalently linked to the transmembrane channel parts. We show that the lower palm domains approach one another during desensitization. Residues in the palm co-determine the pH dependence of desensitization, its kinetics, and the stability of the desensitized state. Mutations of palm residues impair desensitization by preventing the closing movement of the palm. Overexpression of desensitization-impaired channel mutants in central neurons allowed--in contrast to overexpression of wild type--a sustained signaling response to rapid pH fluctuations. We identify and describe here the function of an important regulatory domain that most likely has a conserved role in ENaC/degenerin channels.

Simulation of two-dimensional sum-frequency generation response functions: application to amide I in proteins.

We present the implementation of an approach to simulate the two-dimensional sum frequency generation response functions of systems with numerous coupled chromophores using a quantum-classical simulation scheme that was previously applied successfully to simulate two-dimensional infrared spectra. We apply the simulation to the amide I band of a mechanosensitive channel protein. By examining the signal generated from different segments of the protein, we find that the overall signal is impossible to interpret without the aid of simulations due to the interference of the response generated on different segments of the protein. We do not find significant cross-peaks in the spectra, even when the waiting time is increased. The spectra are thus not sensitive to coupling between different structural elements. Despite this, we conclude that two-dimensional sum frequency generation spectroscopy will be a powerful tool to investigate membrane bound proteins.

Vibrational Spectra of a Mechanosensitive Channel.

We report the simulated vibrational spectra of a mechanosensitive membrane channel in different gating states. Our results show that while linear absorption is insensitive to structural differences, linear dichroism and sum-frequency generation spectroscopies are sensitive to the orientation of the transmembrane helices, which is changing during the opening process. Linear dichroism cannot distinguish an intermediate structure from the closed structure, but sum-frequency generation can. In addition, we find that two-dimensional infrared spectroscopy can be used to distinguish all three investigated gating states of the mechanosensitive membrane channel.

Proton transport in a membrane protein channel: two-dimensional infrared spectrum modeling.

We model the two-dimensional infrared (2DIR) spectrum of a proton channel to investigate its applicability as a spectroscopy tool to study the proton transport process in biological systems. Proton transport processes in proton channels are involved in numerous fundamental biochemical reactions. However, probing the proton transport process at the molecular level is challenging, because of the limitation in both spatial and time resolution of the traditional experimental approaches. In this paper, we perform proton transport molecular dynamics simulations and model the amide I region of the 2DIR spectrum of a proton channel to examine its sensitivity to the proton transport process. We first report the position dependent proton transfer rates along the channel. The rates in the middle of the channel are larger than those in the entrance. In the presence of protons, we find that the antidiagonal line width of the 2DIR spectrum is larger, and the time evolution of the 2DIR spectrum is slower than that without proton. The time evolution of the 2DIR spectrum with different isotope-labeled residues is similar, even if the local proton transfer rates are different. This results from the proton hopping and the channel water rotation being collective mechanisms, and these effects are convoluted in the spectra.

An Efficient N(3)-Scaling Propagation Scheme for Simulating Two-Dimensional Infrared and Visible Spectra.

In this paper, we develop and test a new approximate propagation scheme for calculating two-dimensional infrared and visible spectra. The new scheme scales one order more efficiently with the system size than the existing schemes. A Trotter type of approximation is used for the matrix exponent that describes the time evolution of the quantum system. This is needed for calculating the third-order response functions governing the two-dimensional infrared and visible spectra. The method is tested on a model dimer system, the amide I spectrum of the Gramicidin A antimicrobial peptide, the spectrum of the OH stretching vibration of bulk water, and a homogeneous J-aggregate. Errors due to the approximation are hardly observable in the calculated spectra. Scaling simulations with different system sizes are used to demonstrate that the new scheme is indeed scaling with the system size to the third power, one order faster than the existing methods.

Proton transport in a binary biomimetic solution revealed by molecular dynamics simulation.

We report the simulation results of the proton transport in a binary mixture of amphiphilic tetramethylurea (TMU) molecules and water. We identify different mechanisms that either facilitate or retard the proton transport. The efficiency of these mechanisms depends on the TMU concentration. The overall picture is more complicated than a recent suggestion that the presence of amphiphilic molecules suppresses the proton mobility by slowing down the reorientation of the surrounding water molecules. It has also been suggested that the hydronium ion induces local water orientational order, which results in an ordered region that has to move along with the proton potentially slowing down the proton transport as suggested by experiment. We find that water-wire like structures formed at low amphiphile concentrations facilitate proton transfer, and reduction of the hydrogen bond connectivity induced at high concentrations retards it.

Proton transport in biological systems can be probed by two-dimensional infrared spectroscopy.

We propose a new method to determine the proton transfer (PT) rate in channel proteins by two-dimensional infrared (2DIR) spectroscopy. Proton transport processes in biological systems, such as proton channels, trigger numerous fundamental biochemical reactions. Due to the limitation in both spatial and time resolution of the traditional experimental approaches, describing the whole proton transport process and identifying the rate limiting steps at the molecular level is challenging. In the present paper, we focus on proton transport through the Gramicidin A channel. Using a kinetic PT model derived from all-atom molecular dynamics simulations, we model the amide I region of the 2DIR spectrum of the channel protein to examine its sensitivity to the proton transport process. We demonstrate that the 2DIR spectrum of the isotope-labeled channel contain information on the PT rate, which may be extracted by analyzing the antidiagonal linewidth of the spectral feature related to the labeled site. Such experiments in combination with detailed numerical simulations should allow the extraction of site dependent PT rates, providing a method for identifying possible rate limiting steps for proton channel transfer.