Coupled local mode method for simulating vibrational spectroscopy.

Experimental and theoretical studies have highlighted protonated water clusters (PWCs) as important models of the excess proton in aqueous systems. A significant focus has been characterizing the spectral signatures associated with different excess proton solvation motifs. Accurate vibrational frequency calculations are crucial for connecting the measured spectra to the structure of PWCs. In this paper, we extend and characterize a coupled local mode (CLM) approach for calculating the infrared spectra of PWCs using the H+(H2O)4 cluster as a benchmark system. The CLM method is relatively low cost and incorporates the anharmonicity and coupling of OH vibrations. Here, we demonstrate the accuracy of the technique compared to experiments. We also illustrate the dependence of calculated spectral features on the underlying electronic structure theory and basis sets used in the local mode frequency and coupling calculations.

Coupled Local-Mode Approach for the Calculation of Vibrational Spectra: Application to Protonated Water Clusters.

Spectroscopic studies of protonated water clusters (PWCs) have yielded enormous insights into the fundamental nature of the hydrated proton. Here, we introduce a new coupled local-mode (CLM) approach to calculate PWC OH stretch vibrational spectra. The CLM method combines a sampling of representative configurations from density functional theory (DFT)-based ab initio molecular dynamics (AIMD) simulations with DFT calculations of local-mode vibrational frequencies and couplings. Calculations of inhomogeneous OH stretch vibrational spectra for H+(H2O)4 and H+(H2O)21 agree well with experiment and higher-level calculations, and decompositions of the calculated spectra in terms of the coupled modes aids in the interpretation of the spectra. This observation is consistent with the idea that capturing anharmonicity and coupling is as important to accuracy as the underlying level of electronic structure theory. The CLM calculations can easily discern the configuration that dominates the experimental measurement for H+(H2O)5, which can adopt several low-energy conformations.

Nonlinear measurements of kinetics and generalized dynamical modes. II. Application to a simulation of solvation dynamics in an ionic liquid.

Solvation dynamics in ionic liquids show features that are often associated with supercooled liquids, including "stretched" nonexponential relaxation. To better understand the mechanism behind the stretching, the nonlinear mode-correlation methods proposed in Paper I [S. R. Hodge and M. A. Berg, J. Chem. Phys. 155, 024122 (2021)] are applied to a simulation of a prototypical ionic liquid. A full Green's function is recovered. In addition, specific tests for non-Gaussian dynamics are made. No deviations from Gaussian dynamics are found. This finding is incompatible with rate heterogeneity as a cause of the nonexponential relaxation and appears to be in conflict with an earlier multidimensional analysis of the same data. Although this conflict is not resolved here, this work does demonstrate the practicality of mode-correlation analysis in the face of finite datasets and calculations.

Local Electric Fields in Aqueous Electrolytes.

Vibrational Stark shifts were explored in aqueous solutions of organic molecules with carbonyl- and nitrile-containing constituents. In many cases, the vibrational resonances from these moieties shifted toward lower frequency as salt was introduced into solution. This is in contrast to the blue-shift that would be expected based upon Onsager's reaction field theory. Salts containing well-hydrated cations like Mg2+ or Li+ led to the most pronounced Stark shift for the carbonyl group, while poorly hydrated cations like Cs+ had the greatest impact on nitriles. Moreover, salts containing I- gave rise to larger Stark shifts than those containing Cl-. Molecular dynamics simulations indicated that cations and anions both accumulate around the probe in an ion- and probe-dependent manner. An electric field was generated by the ion pair, which pointed from the cation to the anion through the vibrational chromophore. This resulted from solvent-shared binding of the ions to the probes, consistent with their positions in the Hofmeister series. The "anti-Onsager" Stark shifts occur in both vibrational spectroscopy and fluorescence measurements.

Spectroscopic and Structural Characterization of Water-Shared Ion-Pairs in Aqueous Sodium and Lithium Hydroxide.

The structures of the ion-pairs formed in aqueous NaOH and LiOH solutions are elucidated by combining Raman multivariate curve resolution (Raman-MCR) experiments and ab initio molecular dynamics (AIMD) simulations. The results extend prior findings to reveal that the initially formed ion-pairs are predominantly water-shared, with the hydroxide ion retaining its full first hydration-shell, while direct contact ion-pairing only becomes significant at higher concentrations. Our results confirm previous experiments and simulations indicating greater ion-pairing in aqueous LiOH than NaOH as well as at high temperatures. Our results further imply that NaOH and LiOH ion-pairing free energies have an approximately linear (rather than square-root) dependence on ion concentration (in the molar range), with positive enthalpies and entropies that increase with concentration, thus implying that water-mediated interactions enthalpically disfavor and entropically favor ion-pair formation.

DNA minor-groove binder Hoechst 33258 destabilizes base-pairing adjacent to its binding site.

Understanding the dynamic interactions of ligands to DNA is important in DNA-based nanotechnologies. By structurally tracking the dissociation of Hoechst 33258-bound DNA (d(CGCAAATTTGCG)2) complex (H-DNA) with T-jump 2D-IR spectroscopy, the ligand is found to strongly disturb the stability of the three C:G base pairs adjacent to A:T the binding site, with the broken base pairs being more than triple at 100 ns. The strong stabilization effect of the ligand on DNA duplex makes this observation quite striking, which dramatically increases the melting temperature and dissociation time. MD simulations demonstrate an important role of hydration water and counter cations in maintaining the separation of terminal base pairs. The hydrogen bonds between the ligand and thymine carbonyls are crucial in stabilizing H-DNA, whose breaking signal appearing prior to the complete dissociation. Thermodynamic analysis informs us that H-DNA association is a concerted process, where H cooperates with DNA single strands in forming H-DNA.

Hydrogen Bond Exchange and Ca2+ Binding of Aqueous N-Methylacetamide Revealed by 2DIR Spectroscopy.

Cation effects on proteins have been a challenge to understand. Herein, we present two-dimensional infrared (2DIR) spectroscopic measurements, coupled with molecular dynamics and spectroscopic calculations, of N-methylacetamide (NMA), a common model of the peptide backbone, in aqueous CaCl2. The 2DIR spectra reveal that the dynamics of the amide carbonyl of NMA is dominated by exchange between two states of varying hydration, one possessing a structure similar to aqueous NMA and one that is dehydrated by one hydrogen bond. In addition, we demonstrate that at high (>5 M) CaCl2 concentrations, direct binding of Ca2+ to the carbonyl of NMA occurs, stabilizing an iminium-type resonance structure of NMA, with a characteristic C═N+ stretch frequency at 1680 cm-1. This species is only marginally populated and is only detectable in 2DIR spectra due to its larger transition strength.

Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction.

Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structural dynamics and functions, characteristic processes of functional materials, and so on. In order to gain incisive and quantitative information on the local electrostatic environment, molecular conformation, protein structure and interprotein contacts, ligand binding kinetics, and electric and optical properties of functional materials, a variety of vibrational probes have been developed and site-specifically incorporated into molecular, biological, and material systems for time-resolved vibrational spectroscopic investigation. However, still, an all-encompassing theory that describes the vibrational solvatochromism, electrochromism, and dynamic fluctuation of vibrational frequencies has not been completely established mainly due to the intrinsic complexity of intermolecular interactions in condensed phases. In particular, the amount of data obtained from the linear and nonlinear vibrational spectroscopic experiments has been rapidly increasing, but the lack of a quantitative method to interpret these measurements has been one major obstacle in broadening the applications of these methods. Among various theoretical models, one of the most successful approaches is a semiempirical model generally referred to as the vibrational spectroscopic map that is based on a rigorous theory of intermolecular interactions. Recently, genetic algorithm, neural network, and machine learning approaches have been applied to the development of vibrational solvatochromism theory. In this review, we provide comprehensive descriptions of the theoretical foundation and various examples showing its extraordinary successes in the interpretations of experimental observations. In addition, a brief introduction to a newly created repository Web site (http://frequencymap.org) for vibrational spectroscopic maps is presented. We anticipate that a combination of the vibrational frequency map approach and state-of-the-art multidimensional vibrational spectroscopy will be one of the most fruitful ways to study the structure and dynamics of chemical, biological, and functional molecular systems in the future.

Machine Learning for Vibrational Spectroscopic Maps.

Maps that relate spectroscopic properties of a vibrational mode and collective solvent coordinates have proven useful in theoretical vibrational spectroscopy of condensed-phase systems. It has been realized that the predictive power of such an approach is limited and there is no clear systematic way to improve its accuracy. Here, we propose an adaptation of Δ-machine-learning methodology that goes beyond the spectroscopic maps. The machine-learning part of our approach combines Gaussian process regression used to generate the data set with an artificial neural network used to predict spectroscopic properties of interest. A specific application to the OH-stretch frequencies and transition dipoles of water is presented. Our method approximates these properties about two times more accurately than the spectroscopic-maps-only-based approach. Our results suggest that the new approach may become useful in the study of vibrational spectroscopy of condensed-phase systems.

Dynamics and Vibrational Spectroscopy of Alcohols in Ionic Liquids: Methanol and Ethanol.

The structure, dynamics, and vibrational spectroscopy of dilute HOD, methanol, and ethanol in the 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [emim][NTf2], ionic liquid (IL) are investigated with molecular dynamics (MD) simulations. The structure of the ILs around the solutes is qualitatively similar, where the OD bond of the deuterated alcohols donates an interaction to an [NTf2] anion and the [emim] cations interact with the oxygen atom of the OD group. The slowest time scale for the reorientational dynamics of the OD bond varied considerably for HOD, methanol, and ethanol (27, 71, and 87 ps, respectively). In contrast, the slowest time scales for spectral diffusion of the OD vibrational frequency were 11 ps for each of the three solutes, which indicates that the dynamics of the IL is relatively unchanged by the presence of the alcohols at dilute concentration. The theoretical results for the reorientational and spectral diffusion dynamics compare favorably with prior two-dimensional infrared (2D IR) spectroscopic measurements.

Dynamically Driven Allostery in MHC Proteins: Peptide-Dependent Tuning of Class I MHC Global Flexibility.

T cell receptor (TCR) recognition of antigenic peptides bound and presented by class I major histocompatibility complex (MHC) proteins underlies the cytotoxic immune response to diseased cells. Crystallographic structures of TCR-peptide/MHC complexes have demonstrated how TCRs simultaneously interact with both the peptide and the MHC protein. However, it is increasingly recognized that, beyond serving as a static platform for peptide presentation, the physical properties of class I MHC proteins are tuned by different peptides in ways that are not always structurally visible. These include MHC protein motions, or dynamics, which are believed to influence interactions with a variety of MHC-binding proteins, including not only TCRs, but other activating and inhibitory receptors as well as components of the peptide loading machinery. Here, we investigated the mechanisms by which peptides tune the dynamics of the common class I MHC protein HLA-A2. By examining more than 50 lengthy molecular dynamics simulations of HLA-A2 presenting different peptides, we identified regions susceptible to dynamic tuning, including regions in the peptide binding domain as well as the distal α3 domain. Further analyses of the simulations illuminated mechanisms by which the influences of different peptides are communicated throughout the protein, and involve regions of the peptide binding groove, the ß2-microglobulin subunit, and the α3 domain. Overall, our results demonstrate that the class I MHC protein is a highly tunable peptide sensor whose physical properties vary considerably with bound peptide. Our data provides insight into the underlying principles and suggest a role for dynamically driven allostery in the immunological function of MHC proteins.

Modeling Carbon Dioxide Vibrational Frequencies in Ionic Liquids: IV. Temperature Dependence.

In previous papers in the series, the vibrational spectroscopy of CO2 in ionic liquids (ILs) was investigated at ambient conditions. Here, we extend these studies to understand the temperature dependence of the structure, dynamics, and thermodynamics of CO2 in the 1-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF6], IL. Using spectroscopic mapping techniques, the infrared absorption spectrum of the CO2 asymmetric stretch mode is simulated at a number of temperatures, and the results are found to be consistent with similar experimental studies. Structural correlation functions are used to reveal the thermodynamics of complete CO2 solvent cage breakdown. The enthalpy and entropy of activation for solvent cage reorganization are found to be 6.9 and 7.6 (kcal/mol)/K, respectively, and these values are similar to the those for spectral, orientational, and translational diffusion. Caging times for CO2 are calculated, and it is shown that the short time dynamics of CO2 are unaffected by temperature, even though the long-time dynamics are highly sensitive to temperature.

Counter Cations Affect Transport in Aqueous Hydroxide Solutions with Ion Specificity.

The anomalously high mobility of hydroxide and hydronium ions in aqueous solutions is related to proton transfer and structural diffusion. The role of counterions in these solutions, however, is often considered to be negligible. Herein, we explore the impact of alkali metal counter cations on hydroxide solvation and mobility. Impedance measurements demonstrate that hydroxide mobility is attenuated by lithium relative to sodium and potassium. These results are explained by ab initio molecular dynamics simulations and experimental vibrational hydration shell spectroscopy, which reveal substantially stronger ion pairing between OH- and Li+ than with other cations. Hydration shell spectra and theoretical vibrational frequency calculations together imply that lithium and sodium cations have different effects on the delocalization of water protons donating a hydrogen bond to hydroxide. Specifically, lithium leads to enhanced proton delocalization compared with sodium. However, proton delocalization and the overall diffusion process are not necessarily correlated.

Modeling Carbon Dioxide Vibrational Frequencies in Ionic Liquids: III. Dynamics and Spectroscopy.

In recent years, interest in carbon capture and sequestration has led to numerous investigations of the ability of ionic liquids to act as recyclable CO2-sorbent materials. Herein, we investigate the structure and dynamics of a model physisorbing ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([C4C1Im][PF6]), from the perspective of CO2 using two-dimensional (2D) IR spectroscopy and molecular dynamics simulations. A direct comparison of experimentally measured and calculated 2D IR line shapes confirms the validity of the simulations and spectroscopic calculations. Taken together, the simulations and experiments reveal new insights into the interactions of a CO2 solute with the surrounding ionic liquid and how these interactions manifest in the 2D IR spectra. In particular, higher CO2 asymmetric stretch vibrational frequencies are associated with softer, less populated solvent cages and lower frequencies are associated with tighter, more highly populated solvent cages. The CO2 interacts most strongly with the anions, and these interactions persist for more than 1 ns. The second strongest interactions are with the imidazolium cation ring that last 100 ps, and the weakest interactions are with the cation butyl tail that persist for 10 ps. The principal contributors to spectral diffusion of the CO2 asymmetric stretch vibrational frequency due to the dynamical evolution of the solvent are through Lennard-Jones interactions at short times and electrostatics at long times.

Reaction Ensemble Monte Carlo Simulations of CO2 Absorption in the Reactive Ionic Liquid Triethyl(octyl)phosphonium 2-Cyanopyrrolide.

The absorption of CO2 into an aprotic heterocyclic anion ionic liquid (IL) is modeled using reaction ensemble Monte Carlo (RxMC) with the semigrand reaction move. RxMC has previously been unable to sample chemical equilibrium involving molecular ions in nanostructured liquids due to the high free-energy requirements to open and close cavities and restructure the surrounding environment. Our results are validated by experiments in the modeled IL, triethyl(octyl)phosphonium 2-cyanopyrrolide ([P2228][cnp]), and in a close analog with longer alkyl chains on the cation. Heats of absorption and reaction from both experiment and simulation are exothermic and of comparable magnitude. Replacing experimental Henry's constants with their simulated counterparts improves the accuracy of a Langmuir-type model at moderate pressures. Nonidealities that affect chemical equilibrium are identified and calculated with high precision.

Enthalpic Driving Force for the Selective Absorption of CO2 by an Ionic Liquid.

Molecular dynamics (MD) simulations validated against two-dimensional infrared (2D-IR) measurements of CO2 in an imidazolium-based ionic liquid have revealed new insights into the mechanism of CO2 solvation. The first solvation shell around CO2 has a distinctly quadrupolar structure, with strong negative charge density around the CO2 carbon atom and positive charge density near the CO2 oxygen atoms. When CO2 is modeled without atomic charges (thus removing its strong quadrupole moment), its solvation shell weakens and changes significantly into a structure that is similar to that of N2 in the same liquid. The solvation shell of CO2 evolves more quickly when its quadrupole is removed, and we find evidence that solvent cage dynamics is measured by 2D-IR spectroscopy. We also find that the solvent cage evolution of N2 is similar to that of CO2 with no atomic charges, implying that the weaker quadrupole of N2 is responsible for its higher diffusion and lower absorption in ionic liquids.

Structural Polymorphism as the Result of Kinetically Controlled Self-Assembly.

Traditionally, the goal of self-assembly and supramolecular chemistry is to engineer an equilibrium structure with a desired geometry and functionality; this is achieved through careful choice of molecular monomers, growth conditions, and substrate. Supramolecular assemblies produced under nonequilibrium conditions, in contrast, can form metastable structures with conformations quite different from those accessible in equilibrium self-assembly. The study of nonequilibrium growth of clusters potentially impacts the study of nucleation in atmospheric aerosols, nucleation in organic crystallization, and mesoscale organization for systems ranging from biological molecules to molecular electronics. In our experiments, we prepare surface monolayers of small organic and organometallic molecules through direct injection of a solution onto a substrate in high vacuum. During this process, the rapid evaporation of small solution droplets in high vacuum can lead to nonequilibrium growth conditions. The resulting structures are then characterized by scanning tunneling microscopy. Among the features observed in these experiments are cyclic, hydrogen-bonded pentamers. For carboxylic acids, the two-molecule ring dimer is the common binding motif. Large, cyclic hydrogen-bonded systems are uncommon, especially so for rings with five members. Despite this, pentagonal clusters appear to be a general phenomenon for systems containing adjacent strong and weak hydrogen-bonding elements on five-member aromatic rings. Regular pentamers have been observed as metastable structures for ferrocenecarboxylic acid, indole-2-carboxylic acid, and isatin (1-H-indole-2,3-dione). Electronic structure calculations confirm the relative stability of these structures with respect to the dimer or catemer conformations which are observed in the solid-state crystal structures. For ferrocenecarboxylic acid, cyclic pentamers undergo further self-assembly, resulting in long-range order in conjunction with local 5-fold rotational symmetry. This system is the first reported self-assembled molecular quasicrystal, and it remains the only example of a hydrogen-bonded quasicrystal. This supramolecular structure forms as a result of the cocrystallization of hydrogen-bonded cyclic pentamers with intercalated molecular dimers. The shared bonding to a single dimer is responsible for locking the adjacent pentamers in specific distances and orientations, which produces the quasicrystal. Careful analysis of experimental data provides evidence that, in some cases, metastable clusters are formed in solution and then subsequently adsorb on the surface. This is a unusual mechanism for supramolecular assembly, and it has important implications for understanding questions in crystal growth, namely: what the initial stages of crystal growth are as molecules are first precipitating from solution; what role the solvent plays in determining crystal structure; and whether solvent-mediated clustering is important in the broader phenomenon of solid-state polymorphism.

Effect of pH and Salt on Surface pKa of Phosphatidic Acid Monolayers.

The pH-induced surface speciation of organic surfactants such as fatty acids and phospholipids in monolayers and coatings is considered to be an important factor controlling their interfacial organization and properties. Yet, correctly predicting the surface speciation requires the determination of the surface dissociation constants (surface pKa) of the protic functional group(s) present. Here, we use three independent methods-compression isotherms, surface tension pH titration, and infrared reflection-absorption spectroscopy (IRRAS)-to study the protonation state of dipalmitoylphosphatidic acid (DPPA) monolayers on water and NaCl solutions. By examining the molecular area expansion at basic pH, the pKa to remove the second proton of DPPA (surface pKa2) at the aqueous interface is estimated. In addition, utilizing IRRAS combined with density functional theory calculations, the vibrational modes of the phosphate headgroup were directly probed and assigned to understand DPPA charge speciation with increasing pH. We find that all three experimental techniques give consistent surface pKa2 values in good agreement with each other. Results show that a condensed DPPA monolayer has a surface pKa2 of 11.5, a value higher than previously reported (∼7.9-8.5). This surface pKa2 was further altered by the presence of Na+ cations in the aqueous subphase, which reduced the surface pKa2 from 11.5 to 10.5. It was also found that the surface pKa2 value of DPPA is modulated by the packing density (i.e., the surface charge density) of the monolayer, with a surface pKa2 as low as 9.2 for DPPA monolayers in the two-dimensional gaseous phase over NaCl solutions. The experimentally determined surface pKa2 values are also found to be in agreement with those predicted by Gouy-Chapman theory, validating these methods and proving that surface charge density is the driving factor behind changes to the surface pKa2.

Decomposition of the Experimental Raman and Infrared Spectra of Acidic Water into Proton, Special Pair, and Counterion Contributions.

Textbooks describe excess protons in liquid water as hydronium (H3O+) ions, although their true structure remains lively debated. To address this question, we have combined Raman and infrared (IR) multivariate curve resolution spectroscopy with ab initio molecular dynamics and anharmonic vibrational spectroscopic calculations. Our results are used to resolve, for the first time, the vibrational spectra of hydrated protons and counterions and reveal that there is little ion-pairing below 2 M. Moreover, we find that isolated excess protons are strongly IR active and nearly Raman inactive (with vibrational frequencies of ∼1500 ± 500 cm-1), while flanking water OH vibrations are both IR and Raman active (with higher frequencies of ∼2500 ± 500 cm-1). The emerging picture is consistent with Georg Zundel's seminal work, as well as recent ultrafast dynamics studies, leading to the conclusion that protons in liquid water are primarily hydrated by two flanking water molecules, with a broad range of proton hydrogen bond lengths and asymmetries.