Interaction of α-Synuclein with Phospholipids and the Associated Restructuring of Interfacial Lipid Water: An Interface-Selective Vibrational Spectroscopic Study

Interaction of α-Synuclein (αS) with biological lipids is crucial for the onset of its fibrillation at the cell membrane/water interface. Probed herein is the interaction of αS with membrane-mimicking lipid monolayer/water interfaces. The results depict that αS interacts negligibly with zwitterionic lipids, but strongly affects the pristine air/water and charged lipid/water interfaces by perturbing the structure and orientation of the interfacial water. The net negative αS (−9 in bulk water; pH 7.4) reorients the water as hydrogen-up (H-up) at the air/water interface, and electrostatically interacts with positively charged lipids, making the interface nearly net neutral. αS also interacts with negatively charged lipids: the net H-up orientation of the interfacial water decreases at the anionic lipid/water interface, revealing a domain-specific interaction of net negative αS with the negatively charged lipids at the membrane surface.     

Hidden Isolated OH at the Charged Hydrophobic Interface Revealed by Two‐Dimensional Heterodyne‐Detected VSFG Spectroscopy

Water around hydrophobic groups mediates hydrophobic interactions that play key roles in many chemical and biological processes. Thus, the molecular‐level elucidation of the properties of water in the vicinity of hydrophobic groups is important. We report on the structure and dynamics of water at two oppositely charged hydrophobic ion/water interfaces, that is, the tetraphenylborate‐ion (TPB^?)/water and tetraphenylarsonium‐ion (TPA⁺)/water interfaces, which are clarified by two‐dimensional heterodyne‐detected vibrational sum‐frequency generation (2D HD‐VSFG) spectroscopy. The obtained 2D HD‐VSFG spectra of the anionic TPB^? interface reveal the existence of distinct π‐hydrogen bonded OH groups in addition to the usual hydrogen‐bonded OH groups, which are hidden in the steady‐state spectrum. In contrast, 2D HD‐VSFG spectra of the cationic TPA⁺ interface only show the presence of usual hydrogen‐bonded OH groups. The present study demonstrates that the sign of the interfacial charge governs the structure and dynamics of water molecules that face the hydrophobic region.     

Three distinct water structures at a zwitterionic lipid/water interface revealed by heterodyne-detected vibrational sum frequency generation

Lipid/water interfaces and associated interfacial water are vital for various biochemical reactions, but the molecular-level understanding of their property is very limited. We investigated the water structure at a zwitterionic lipid, phosphatidylcholine, monolayer/water interface using heterodyne-detected vibrational sum frequency generation spectroscopy. Isotopically diluted water was utilized in the experiments to minimize the effect of intra/intermolecular couplings. It was found that the OH stretch band in the Imχ((2)) spectrum of the phosphatidylcholine/water interface exhibits a characteristic double-peaked feature. To interpret this peculiar spectrum of the zwitterionic lipid/water interface, Imχ((2)) spectra of a zwitterionic surfactant/water interface and mixed lipid/water interfaces were measured. The Imχ((2)) spectrum of the zwitterionic surfactant/water interface clearly shows both positive and negative bands in the OH stretch region, revealing that multiple water structures exist at the interface. At the mixed lipid/water interfaces, while gradually varying the fraction of the anionic and cationic lipids, we observed a drastic change in the Imχ((2)) spectra in which spectral features similar to those of the anionic, zwitterionic, and cationic lipid/water interfaces appeared successively. These observations demonstrate that, when the positive and negative charges coexist at the interface, the H-down-oriented water structure and H-up-oriented water structure appear in the vicinity of the respective charged sites. In addition, it was found that a positive Imχ((2)) appears around 3600 cm(-1) for all the monolayer interfaces examined, indicating weakly interacting water species existing in the hydrophobic region of the monolayer at the interface. On the basis of these results, we concluded that the characteristic Imχ((2)) spectrum of the zwitterionic lipid/water interface arises from three different types of water existing at the interface: (1) the water associated with the negatively charged phosphate, which is strongly H-bonded and has a net H-up orientation, (2) the water around the positively charged choline, which forms weaker H-bonds and has a net H-down orientation, and (3) the water weakly interacting with the hydrophobic region of the lipid, which has a net H-up orientation.     

Ultrafast vibrational dynamics of water at a charged interface revealed by two-dimensional heterodyne-detected vibrational sum frequency generation

Two-dimensional heterodyne-detected vibrational sum frequency generation (2D HD-VSFG) spectroscopy is performed for an aqueous interface for the first time. The 2D HD-VSFG spectra in the OH stretch region are obtained from a positively charged surfactant∕water interface with isotopically diluted water (HOD∕D(2)O) to reveal the femtosecond vibrational dynamics of water at the charged interface. The 2D HD-VSFG spectrum is diagonally elongated immediately after photoexcitation, clearly demonstrating inhomogeneity in the interfacial water. This elongation almost disappears at 300 fs owing to the spectral diffusion. Interestingly, the 2D HD-VSFG spectrum at the 0 fs shows an oppositely asymmetric shape to the corresponding 2D IR spectrum in bulk water: The bandwidth of the bleach signal gets narrower when the pump wavenumber becomes higher. This suggests that the dynamics and mechanism of the hydrogen bond rearrangement at the charged interface are significantly different from those in bulk water.     

Aqueous Heterogeneity at the Air/Water Interface Revealed by 2D‐HD‐SFG Spectroscopy

Water molecules interact strongly with each other through hydrogen bonds. This efficient intermolecular coupling causes strong delocalization of molecular vibrations in bulk water. We study intermolecular coupling at the air/water interface and find intermolecular coupling 1) to be significantly reduced and 2) to vary strongly for different water molecules at the interface—whereas in bulk water the coupling is homogeneous. For strongly hydrogen‐bonded OH groups, coupling is roughly half of that of bulk water, due to the lower density in the near‐surface region. For weakly hydrogen‐bonded OH groups that absorb around 3500 cm^?1, which are assigned to the outermost, yet hydrogen‐bonded OH groups pointing towards the liquid, coupling is further reduced by an additional factor of 2. Remarkably, despite the reduced structural constraints imposed by the interfacial hydrogen‐bond environment, the structural relaxation is slow and the intermolecular coupling of these water molecules is weak.     

Sum-frequency spectroscopic study of Langmuir monolayers of lipids having oppositely charged headgroups

Sum-frequency vibrational spectroscopy, with the help of surface pressure-area (π-A) isotherm, was used to study lipid Langmuir monolayers composed of molecules with positively and negatively charged headgroups as well as a 1:1 neutral mixture of the two. The spectral profiles of the CH(x) stretch vibrations are similar for all monolayers in the liquid-condensed (LC) phase. They suggest a monolayer structure of closely packed alkyl chains that are nearly all-trans and well oriented along the surface normal. In the liquid-expanded (LE) phase, the spectra of all monolayers appear characteristic of loosely packed chains with significant gauche defects. The OH stretch spectra of interfacial water for both positively and negatively charged monolayers are significantly enhanced in comparison with a neutral water interface, but the phase measurement of SFVS indicates that OH in the two cases points toward the bulk and the interface, respectively. The enhancement results mainly from surface-field-induced polar ordering of interfacial water molecules. For a charge-neutral monolayer composed of an equal number of positively and negatively charged lipid molecules, no such enhancement is observed. This mixed monolayer exhibits a wide range of LC/LE coexistence region extended to very low surface pressure and its CH(x) spectral profile in the coexistence region resembles that of the LC phase. This result suggests that in the LC/LE coexistence region, the mixed monolayer consists of coexisting LC and LE patches in which oppositely charged lipid molecules are homogeneously mixed and dispersed.     

Molecular Structure and Dynamics of Water at the Water–Air Interface Studied with Surface‐Specific Vibrational Spectroscopy

Water interfaces provide the platform for many important biological, chemical, and physical processes. The water–air interface is the most common and simple aqueous interface and serves as a model system for water at a hydrophobic surface. Unveiling the microscopic (<1 nm) structure and dynamics of interfacial water at the water–vapor interface is essential for understanding the processes occurring on the water surface. At the water interface the network of very strong intermolecular interactions, hydrogen‐bonds, is interrupted and the density of water is reduced. A central question regarding water at interfaces is the extent to which the structure and dynamics of water molecules are influenced by the interruption of the hydrogen‐bonded network and thus differ from those of bulk water. Herein, we discuss recent advances in the study of interfacial water at the water–air interface using laser‐based surface‐specific vibrational spectroscopy.     

Sum-frequency observation of solvent structure at model chromatographic interfaces: acetonitrile-water and methanol-water systems

The adsorption of methanol-D2O and acetonitrile-D2O solutions at model chromatographic interfaces (octadecylsiloxane and quartz) was studied using sum-frequency spectroscopy. Methanol did not adsorb at either interface in detectable quantities, while acetonitrile adsorbs at the octadecylsiloxane- and quartz-solution interfaces in a concentration-dependent manner and is well ordered at the interface. Adsorption of acetonitrile was decreased by the addition of KCl at 10 and 100 mM. Acetonitrile adsorption was also observed during simulated gradient elution, demonstrating that adsorption of acetonitrile occurs on a time scale relevant to actual chromatographic separations. Examination of the OH stretch spectra of acetonitrile-H2O and methanol-H2O solutions at the interface revealed concentration-dependent changes in the acetonitrile-H2O spectra that are consistent with hydrogen bonding between interfacial water and acetonitrile, indicating that interfacial water is involved in mediating acetonitrile adsorption. The OH stretch spectra of methanol-H2O solutions showed no such changes.     

Surface Charges at the CaF2/Water Interface Allow Very Fast Intermolecular Vibrational‐Energy Transfer

We investigate the dynamics of water in contact with solid calcium fluoride, where at low pH, localized charges can develop upon fluorite dissolution. We use 2D surface‐specific vibrational spectroscopy to quantify the heterogeneity of the interfacial water (D₂O) molecules and provide information about the sub‐picosecond vibrational‐energy‐relaxation dynamics at the buried solid/liquid interface. We find that strongly H‐bonded OD groups, with a vibrational frequency below 2500 cm^?1, display very rapid spectral diffusion and vibrational relaxation; for weakly H‐bonded OD groups, above 2500 cm^?1, the dynamics slows down substantially. Atomistic simulations based on electronic‐structure theory reveal the molecular origin of energy transport through the local H‐bond network. We conclude that strongly oriented H‐bonded water molecules in the adsorbed layer, whose orientation is pinned by the localized charge defects, can exchange vibrational energy very rapidly due to the strong collective dipole, compensating for a partially missing solvation shell.     

Water dynamics--the effects of ions and nanoconfinement

Hydrogen bond dynamics of water in highly concentrated NaBr salt solutions and reverse micelles are studied using ultrafast 2D-IR vibrational echo spectroscopy and polarization-selective IR pump-probe experiments performed on the OD hydroxyl stretch of dilute HOD in H(2)O. The vibrational echo experiments measure spectral diffusion, and the pump-probe experiments measure orientational relaxation. Both experimental observables are directly related to the structural dynamics of water's hydrogen bond network. The measurements performed on NaBr solutions as a function of concentration show that the hydrogen bond dynamics slow as the NaBr concentration increases. The most pronounced change is in the longest time scale dynamics which are related to the global rearrangement of the hydrogen bond structure. Complete hydrogen bond network randomization slows by a factor of approximately 3 in approximately 6 M NaBr solution compared to that in bulk water. The hydrogen bond dynamics of water in nanoscopically confined environments are studied by encapsulating water molecules in ionic head group (AOT) and nonionic head group (Igepal CO 520) reverse micelles. Water dynamics in the nanopools of AOT reverse micelles are studied as a function of size by observing orientational relaxation. Orientational relaxation dynamics deviate significantly from bulk water when the size of the reverse micelles is smaller than several nm and become nonexponential and slower as the size of the reverse micelles decreases. In the smallest reverse micelles, orientational relaxation (hydrogen bond structural randomization) is almost 20 times slower than that in bulk water. To determine if the changes in dynamics from bulk water are caused by the influence of the ionic head groups of AOT or the nanoconfinement, the water dynamics in 4 nm nanopools in AOT reverse micelles (ionic) and Igepal reverse micelles (nonionic) are compared. It is found that the water orientational relaxation in the 4 nm diameter nanopools of the two types of reverse micelles is almost identical, which indicates that confinement by an interface to form a nanoscopic water pool is a primary factor governing the dynamics of nanoscopic water rather than the presence of charged groups at the interface.     

Distribution, structure, and dynamics of cesium and iodide ions at the H2O-CCl4 and H2O-vapor interfaces

Molecular dynamics simulations utilizing many-body potentials of H2O-CCl4 and H2O-vapor interfaces were carried out at different cesium and iodide ion concentrations to compare ion distribution, interfacial orientational and structural properties, and dynamics. It was found that cesium was repelled by both interfaces, and iodide was active at both interfaces, but to a much greater degree at the H2O-vapor interface. At the interface, the iodide dipole was strongly induced, orienting perpendicular to the interface for both systems, leading to stronger hydrogen bonds with water. For the H2O-CCl4 interface, though, there was a compensation between these strong hydrogen bonds and short to moderate ranged repulsion between iodide and CCl4. Hydrogen bond distance and angular distributions showed weaker water-water hydrogen bonds at both interfaces, but generally stronger water-iodide hydrogen bonds. Both translational and rotational dynamics of water were faster at the interface, while for CCl4, its translational dynamics was slower, but rotational dynamics faster at the interface. For many of the studied systems and species, translational diffusion was found to be anisotropic at both interfacial and bulk regions.     

Structures and charging of alpha-alumina (0001)/water interfaces studied by sum-frequency vibrational spectroscopy

Sum-frequency vibrational spectroscopy in the OH stretch region was employed to study structures of water/alpha-Al2O3 (0001) interfaces at different pH values. Observed spectra indicate that protonation and deprotonation of the alumina surface dominate at low and high pH, respectively, with the interface positively and negatively charged accordingly. The point of zero charge (pzc) appears at pH approximately = 6.3, which is close to the values obtained from streaming potential and second-harmonic generation studies. It is significantly lower than the pzc of alumina powder. The result can be understood from the pK values of protonation and deprotonation at the water/alpha-Al2O3 (0001) interface. The pzc of amorphous alumina was found to be similar to that of powder alumina.     

Confinement or the nature of the interface? Dynamics of nanoscopic water

The dynamics of water confined in two different types of reverse micelles are studied using ultrafast infrared pump-probe spectroscopy of the hydroxyl OD stretch of HOD in H2O. Reverse micelles of the surfactant Aerosol-OT (ionic head group) in isooctane and the surfactant Igepal CO 520 (nonionic head group) in 50/50 wt % cyclohexane/hexane are prepared to have the same diameter water nanopools. Measurements of the IR spectra and vibrational lifetimes show that the identity of the surfactant head groups affects the local environment experienced by the water molecules inside the reverse micelles. The orientational dynamics (time-dependent anisotropy), which is a measure of the hydrogen bond network rearrangement, are very similar for the confined water in the two types of reverse micelles. The results demonstrate that confinement by an interface to form a nanoscopic water pool is a primary factor governing the dynamics of nanoscopic water rather than the presence of charged groups at the interface.     

Development of non‐bonded interaction parameters between graphene and water using particle swarm optimization

New Lennard‐Jones parameters have been developed to describe the interactions between atomistic model of graphene, represented by REBO potential, and five commonly used all‐atom water models, namely SPC, SPC/E, SPC/Fw, SPC/Fd, and TIP3P/Fs by employing particle swarm optimization (PSO) method. These new parameters were optimized to reproduce the macroscopic contact angle of water on a graphene sheet. The calculated line tension was in the order of 10⁻¹¹ J/m for the droplets of all water models. Our molecular dynamics simulations indicate the preferential orientation of water molecules near graphene–water interface with one O H bond pointing toward the graphene surface. Detailed analysis of simulation trajectories reveals the presence of water molecules with ≤∼1, ∼2, and ∼4 hydrogen bonds at the surface of air–water interface, graphene–water interface, and bulk region of the water droplet, respectively. Presence of water molecules with ≤∼1 and ∼2 hydrogen bonds suggest the existence of water clusters of different sizes at these interfaces. The trends observed in the libration, bending, and stretching bands of the vibrational spectra are closely associated with these structural features of water. The inhomogeneity in hydrogen bond network of water at the air–water and graphene–water interface is manifested by broadening of the peaks in the libration band for water present at these interfaces. The stretching band for the molecules in water droplet shows a blue shift as compared to the pure bulk water, which conjecture the presence of weaker hydrogen bond network in a droplet. © 2017 Wiley Periodicals, Inc.     

Nature of hydration shells of a polyoxy‐anion with a large cationic centre: The case of iodate ion in water

The structural nature of the solvation shells of an iodate ion, which is known to be a polyoxy‐anion with a large cationic centre, is investigated by means of Born–Oppenheimer molecular dynamics (BOMD) simulations using BLYP and the dispersion corrected BLYP‐D3 functionals. The iodate ion is found to have two distinct solvation regions around the positively charged iodine (iodine solvation shell or ISS) and the negatively charged oxygens (oxygen solvation shell or OSS). We have looked at the spatial, orientational, and hydrogen bond distributions of water in the two solvation regions. It is found that the water orientational profile in the ISS is typical of a cation hydration shell. The hydrogen bonded structure of water in the OSS is found to be very similar to that of the bulk water structure. Thus, the iodate ion essentially behaves like a positively charged iodine ion in water as if there is no anionic part. This explains why the cationic character of the iodate ion was prominently seen in earlier studies. The arrangement of water molecules in the two solvation shells and in the intervening regions around the iodate ion is further resolved by looking at structural cross‐correlations. The electronic properties of the solvation shells are also looked at by calculating the solute–solvent orbital overlap and dipole moments of the solute and solvation shell water. We have also performed BOMD simulations of iodate ion‐water clusters at experimentally relevant conditions. The simulation results are found to be in agreement with experimental results. © 2018 Wiley Periodicals, Inc.     

Structure and dynamics of water confined in silica nanopores

We report the results of molecular simulation of water in silica nanopores at full hydration and room temperature. The model systems are approximately cylindrical pores in amorphous silica, with diameters ranging from 20 to 40 ?. The filled pores are prepared using grand canonical Monte Carlo simulation and molecular dynamics simulation is used to calculate the water structure and dynamics. We found that water forms two distinct molecular layers at the interface and exhibits uniform, but somewhat lower than bulk liquid, density in the core region. The hydrogen bond density profile follows similar trends, with lower than bulk density in the core and enhancements at the interface, due to hydrogen bonds between water and surface non-bridging oxygens and OH groups. Our studies of water dynamics included translational mean squared displacements, orientational time correlations, survival probabilities in interfacial shells, and hydrogen bond population relaxation. We found that the radial-axial anisotropy in translational motion largely follows the predictions of a model of free diffusion in a cylinder. However, both translational and rotational water mobilities are strongly dependent on the proximity to the interface, with pronounced slowdown in layers near the interface. Within these layers, the effects of interface curvature are relatively modest, with only a small increase in mobility in going from the 20 to 40 ? diameter pore. Hydrogen bond population relaxation is nearly bulk-like in the core, but considerably slower in the interfacial region.     

空气/水界面水分子的取向和运动

Here we report a quantitative study of the orientational structure and motion of water molecule at the air/water interface. Analysis of Sum Frequency Generation (SFG) vibrational peak of the free O-H stretching band at 3700 cm-1 in four experimental configurations showed that orientational motion of water molecule at air/water interface is libratory within a limited angular range. The free OH bond of the interfacial water molecule is tilted around 33° from the interface normal and the orientational distribution or motion width is less than 15°. This picture is significantly different from the previous conclusion that the interfacial water molecule orientation varies over a broad range within the ultrafast vibrational relaxation time, the only direct experimental study concluded for ultrafast and broad orientational motion of a liquid interface by Wei et al.(Phys. Rev. Lett. 86, 4799, (2001)) using single SFG experimental configuration.     

Excited‐State Charge Separation in the Photochemical Mechanism of the Light‐Driven Enzyme Protochlorophyllide Oxidoreductase

The unique light‐driven enzyme protochlorophyllide oxidoreductase (POR) is an important model system for understanding how light energy can be harnessed to power enzyme reactions. The ultrafast photochemical processes, essential for capturing the excitation energy to drive the subsequent hydride‐ and proton‐transfer chemistry, have so far proven difficult to detect. We have used a combination of time‐resolved visible and IR spectroscopy, providing complete temporal resolution over the picosecond–microsecond time range, to propose a new mechanism for the photochemistry. Excited‐state interactions between active site residues and a carboxyl group on the Pchlide molecule result in a polarized and highly reactive double bond. This so‐called “reactive” intramolecular charge‐transfer state creates an electron‐deficient site across the double bond to trigger the subsequent nucleophilic attack of NADPH, by the negatively charged hydride from nicotinamide adenine dinucleotide phosphate. This work provides the crucial, missing link between excited‐state processes and chemistry in POR. Moreover, it provides important insight into how light energy can be harnessed to drive enzyme catalysis with implications for the design of light‐activated chemical and biological catalysts.     

Fabrication of Mesoporous‐Silica‐Coated Upconverting Nanoparticles with Ultrafast Photosensitizer Loading and 808 nm NIR‐Light‐Triggering Capability for Photodynamic Therapy

A novel photodynamic therapy nanoplatform based on mesoporous‐silica‐coated upconverting nanoparticles (UCNP) with electrostatic‐driven ultrafast photosensitizer (PS) loading and 808 nm near infrared (NIR)‐light‐triggering capabilities has been fabricated. By positively charging inner channels of the mesoporous silica shell with amino groups, a quantitative dosage of negatively charged PS, exemplified with Rose Bengal (RB) molecules, can be loaded in 2 min. In addition, the electrostatic‐driven technique simultaneously provides the platform with both excellent PS dispersity and leak‐proof properties due to the repulsion between the same‐charged molecules and the electrostatic attraction between different‐charged PS and silica channel walls, respectively. The as‐coated silica shell with an ultrathin thickness of 12±2 nm is delicately fabricated to facilitate ultrafast PS loading and efficient energy transfer from UCNP to PS. The outside surface of the silica shell is capped with hydrophilic β‐cyclodextrin, which not only enhances the dispersion of resulting nanoparticles in water but also plays a role of “gatekeeper”, blocking the pore opening and preventing PS leaking. The in vitro cellular lethality experiment demonstrates that RB molecules can be activated to effectively generate singlet oxygen and kill cancer cells upon 808 nm NIR light irradiation.