Two-dimensional Raman Spectroscopy Research Articles

Rapid and accurate bacteria identification through deep-learning-based two-dimensional Raman spectroscopy

Surface-enhanced Raman spectroscopy (SERS) offers a distinctive vibrational fingerprint of the molecules and has led to widespread applications in medical diagnosis, biochemistry, and virology. With the rapid development of artificial intelligence (AI) technology, AI-enabled Raman spectroscopic techniques, as a promising avenue for biosensing applications, have significantly boosted bacteria identification. By converting spectra into images, the dataset is enriched with more detailed information, allowing AI to identify bacterial isolates with enhanced precision. However, previous studies usually suffer from a trade-off between high-resolution spectrograms for high-accuracy identification and short training time for data processing. Here, we present an efficient bacteria identification strategy that combines deep learning models with a spectrogram encoding algorithm based on wavelet packet transform and Gramian angular field techniques. In contrast to the direct analysis of raw Raman spectra, our approach utilizes wavelet packet transform techniques to compress the spectra by a factor of 1/15, while concurrently maintaining state-of-the-art accuracy by amplifying the subtle differences via Gramian angular field techniques. The results demonstrate that our approach can achieve a 99.64 % and a 90.55 % identification accuracy for two types of bacterial isolates and thirty types of bacterial isolates, respectively, while a 90 % reduction in training time compared to the conventional methods. To verify the model's stability, Gaussian noises were superimposed on the testing dataset, showing a specific generalization ability and superior performance. This algorithm has the potential for integration into on-site testing protocols and is readily updatable with new bacterial isolates. This study provides profound insights and contributes to the current understanding of spectroscopy, paving the way for accurate and rapid bacteria identification in diverse applications of environment monitoring, food safety, microbiology, and public health.

Macroscopic perspective on phase transition behavior of natural single-crystal graphite under different pressure environments

Comprehensive understanding of the direct transformation pathway from graphite to diamond under high temperature and high pressure has long been one of the fundamental goals in materials science. Despite considerable experimental and theoretical progress, current experimental studies have mainly focused on the local microstructural characterizations of recovered samples, which has certain limitations for high-temperature and high-pressure products, which often exhibit diversity. Here, we report on the pressure-induced phase transition behavior of natural single-crystal graphite under three distinct pressure-transmitting media from a macroscopic perspective using in situ two-dimensional Raman spectroscopy, scanning electron microscopy, and atomic force microscopy. The surface evolution process of graphite before and after the phase transition is captured, revealing that pressure-induced surface textures can impede the continuity of the phase transition process across the entire single crystal. Our results provide a fresh perspective for studying the phase transition behavior of graphite and greatly deepen our understanding of this behavior, which will be helpful in guiding further high-temperature and high-pressure syntheses of carbon allotropes.

Exploring the change of hydrogen bond evolution in NMP-H2O solution through 2D Raman-COS spectra analysis

The transitions of Hydrogen Bond (HB) structure with in the cluster structures of NMP-H2O solutions was conducted by combining Density Functional Theory (DFT) calculations and Two-dimensional Correlation Raman Spectroscopy (2D Raman-COS). When VNMP < 20 %, NMP molecule is incorporated into the tetrahedral structure of water through an "insertion" mechanism, by displacing some H2O molecules and establishing HB. This interaction strengthens the tetrahedral arrangement in water, causing the free OH bond length to be compressed. When VNMP > 20 %, large amounts of NMP molecules were self-assembled through dipole-dipole alignment, and the NMP·2H2O, NMP·H2O, and 2NMP·H2O clusters gradually substitute the tetrahedral structure of water, leading to the disruption of the HB network in water. Furthermore, it was observed that the pulsed laser beam accelerated the transition point of the HB structure in the NMP-H2O solution. This research provides references for the application of NMP in the fields of aqueous batteries from the view of HB with electrolyte.

High-precision bladder cancer diagnosis method: 2D Raman spectrum figures based on maintenance technology combined with automatic weighted feature fusion network

BackgroundRaman spectroscopy has been extensively utilized as a marker-free detection method in the complementary diagnosis of cancer. Multivariate statistical classification analysis is frequently employed for Raman spectral data classification. Nevertheless, traditional multivariate statistical classification analysis performs poorly when analyzing large samples and multicategory spectral data. In addition, with the advancement of computer vision, convolutional neural networks (CNNs) have demonstrated extraordinarily precise analysis of two-dimensional image processing. ResultCombining 2D Raman spectrograms with automatic weighted feature fusion network (AWFFN) for bladder cancer detection is presented in this paper. Initially, the s-transform (ST) is implemented for the first time to convert 1D Raman data into 2D spectrograms, achieving 99.2% detection accuracy. Second, four upscaling techniques, including short time fourier transform (STFT), recurrence map (RP), markov transform field (MTF), and grammy angle field (GAF), were used to transform the 1D Raman spectral data into a variety of 2D Raman spectrograms. In addition, a particle swarm optimization (PSO) algorithm is combined with VGG19, ResNet50, and ResNet101 to construct a weighted feature fusion network, and this parallel network is employed for evaluating multiple spectrograms. Class activation mapping (CAM) is additionally employed to illustrate and evaluate the process of feature extraction via the three parallel network branches. The results demonstrate that the combination of a 2D Raman spectrogram along with a CNN for the diagnosis of bladder cancer obtains a 99.2% accuracy rate，which indicates that it is an extremely promising auxiliary technology for cancer diagnosis. SignificanceThe proposed two-dimensional Raman spectroscopy method has an improved precision than one-dimensional spectroscopic data, which presents a potential methodology for assisted cancer detection and providing crucial technical support for assisted diagnosis.

Study on removal of oxytetracycline by KOH-modified chestnut shell biochar: Based on two-dimensional spectroscopy and molecular density functional theory

The adsorption type and mode of biochar have been extensive research. However, as an indispensable link to reveal the adsorption mechanism, the study of the adsorption sequence is greatly lacking, especially for different pollutants, the way of adsorption is different. In this study, the observation of the adsorption sequence was amplified by KOH modification and optimization of experimental conditions. Persistent radicals (PFRs) combined with liquid mass spectrometry (LC-MS) eliminated interference from oxidation-reduction. Notability, two-dimensional correlation spectroscopy (2D-COS), Raman and Fourier-transform infrared (FTIR) spectroscopy reveals that the vibration amplitude and velocity of the hydroxyl group are better than those of the carboxyl group, methyl group, and methylene group under time interference. Electrostatic adsorption (EA), H-bood (HB), and π-π* contribute 63.5 %, 35.3 %, and 1.2 %, respectively, to the adsorption of oxytetracycline (OTC). The density functional calculation shows that the nucleophilic and electrophilic reactions of OTC are easy to occur near oxygen atoms and nitrogen atoms. The Fukui function proves that the free radical weight of the N atom is 0.096, which is further confirmed the theoretical predictions by liquid chromatography and four-stage electrostatic field orbital trap mass spectrometry. Finally, this study provides a deeper insight into the biochar adsorption OTC.

Rapid-Scan Resonant Two-Dimensional Impulsive Stimulated Raman Spectroscopy of Excited States.

Photochemical reactions occur in the electronically excited state, which is effectively represented by a multidimensional potential energy surface (PES) with a vast degree of freedom of nuclear coordinates. The elucidation of the intricate shape of the PES constitutes an important topic in the field of photochemistry and has long been studied both experimentally and theoretically. Recently, fully time-domain resonant two-dimensional Raman spectroscopy has emerged as a potentially powerful tool to provide unique information about the coupling between vibrational manifolds in the excited state. However, the wide application of this technique has been significantly hampered by the technical difficulties associated with experimental implementation and remains challenging. Herein, we demonstrate time-domain resonant two-dimensional impulsive stimulated Raman spectroscopy (2D-ISRS) of excited states using sub-10 fs pulses based on the rapid scan of the time delay, which facilitates the efficient collection of time-domain vibrational signals with high sensitivity. As a proof-of-principle experiment, we performed 2D-ISRS of 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene) in solution. Through 2D Fourier transformation of the high-quality time-time oscillatory signal, we obtained a 2D frequency-frequency correlation map of excited-state TIPS-pentacene in the broad frequency window of 0-2000 cm-1. The data clearly resolve a number of cross peaks that signify the correlations among excited-state vibrational manifolds. The high capability of the rapid-scan-based 2D-ISRS spectrometer presented in this study enables the systematic investigation of various photochemical reaction systems, thereby further promoting the understanding and applications of this new multidimensional spectroscopy.

Tuning the Fermi resonance of pyridine using ethanol molecules

The Fermi resonance (FR) phenomenon is prevalent in infrared and Raman spectroscopy, and it can be observed in a variety of molecules. In particular, pyridine is a compound that has two Fermi doublets: ν1 ∼ ν12 and ν1 + ν6 ∼ ν8. To analyze the effect of environmental changes on the FR, this study first investigated the Raman spectra of pyridine mixed with ethanol at different concentrations. Results indicated that the FR parameters exhibited a nonlinear dependence on the pyridine concentration fractions, and changing the concentration fraction of pyridine led to different hydrogen bond strengths. Second, the interaction mechanism of pyridine-ethanol binary solutions was analyzed by two-dimensional correlation Raman spectroscopy (2DCRS). In addition, high-pressure Raman spectra of a 50% pyridine-ethanol binary solution were measured up to a pressure of 19.65 GPa by a diamond anvil cell technique, and the phase transition of the binary solution occurred at 6.35 GPa. Finally, the impact of ethanol on the FR of pyridine was determined by deducing the FR parameters at different pressures. The turning point at 6.35 GPa was consistent with the Raman frequency–pressure relationships. The results demonstrated that changes in the intensity of ν1 did not affect the FR of ν1 + ν6 ∼ ν8, whereas the undisturbed frequency ν1 still played a role in the FR. When the pressure was compressed to 13.36 GPa, the disappearance of the Raman peaks (ν1 and ν1′) was attributed to the tuning of the molecular symmetry by pressure during the phase transition.

Determination of temperature-dependent Fermi resonance in acetonitrile-water binary solution by two-dimensional correlation Raman spectroscopy.

Acetonitrile (AN), as an organic solvent, has a wide range of applications. The C≡N stretching vibration mode (ν2) and the combination mode (ν3 + ν4) are coupled by Fermi resonance (FR). In this work, the phase transition and the interaction mechanism of the 60% AN-water binary solution (AN-Water) were analyzed by calculating FR parameters and two-dimensional correlation Raman spectroscopy (2DCRS). The change in the ν2 band and the base bands ν3 and ν4 caused energy transfer by anharmonic interaction, which led to a change in FR parameters. With a reduced temperature, the energy transfer was caused by microheterogeneity and the energy transfer effect (293-273K), the phase separation (263-233K), and the phase transition of AN (223-173K). The 2DCRS and Gaussian deconvolution provided more information on FR, which revealed the interaction mechanism of the Fermi doublet. The polarity and binding modes of molecules provided a new perspective for analyzing the transmission of electrons and ions in the electrolyte at different temperatures.

Investigation of intermolecular interactions in organic solutions by combining two-dimensional correlation Raman spectroscopy and DFT simulation: Example of methanol and Chloralkane

Methanol (MeOH)-Dichloromethane (CH2Cl2) and methanol-Chloroform (CHCl3) binary solution systems under the different circumstances were studied using Raman spectroscopy combined with density functional theory (DFT) and two-dimensional correlation spectroscopy (2DCRS). Weak HBs interactions exist in the binary solutions, which can be reflected by the vibration of CH bond (in CH2Cl2 or CHCl3) and CO bond (in MeOH). We explore the influence of mole fractions and temperature of these two vibration modes and perform 2DCRS analysis to reveal the changes intermolecular interactions. The results showed that the Raman spectra of CH vibration of Chloralkane has a frequency shift as the molar fraction of methanol changes both in MeOHCH2Cl2 and MeOHCHCl3 binary solution. In MeOHCH2Cl2, both the bending and stretching vibration of CH move towards higher wavenumber as the MeOH mole fraction increases, but the bending vibration moved towards higher wavenumber and the stretching vibration moved towards lower wavenumber in MeOHCHCl3. This phenomenon is mainly due to the variation of intermolecular HBs and is affected by the vibrational coupling between different chemical bonds. The 2DCRS has a higher resolution, can be used to distinguish the weak peaks masked in one-dimensional spectra, showed that there is a correlation between the chemical bonds of MeOH and CH2Cl2, which proves the existence of HBs, and MeOH is more sensitive to the change of circumstance. The Raman intensity of CH2Cl2 increased more obvious than that of MeOH during the heating process in MeOHCH2Cl2 binary solution, and the full width at half maximum (FWHM) of the Raman peak in the solid phase changed more unregular than that in the liquid phase. Finally, the DFT simulation was used to optimize the geometrical structure under three modes, and vibration analysis and interaction energy calculation were performed. The HBs energies obtained in the three coordination modes are 9.68 kcal/mol, 5.04 kcal/mol and 11.31 kcal/mol, respectively, and the simulated vibration modes and Raman spectra are matched well with the experimental results.

The effect of drug loading on the properties of abiraterone–hydroxypropyl beta cyclodextrin solid dispersions processed by solvent free KinetiSol® technology

Abiraterone is a poorly water-soluble drug used in the treatment of prostate cancer. In our previous study, we reported that KinetiSol® processed solid dispersions (KSDs) based on hydroxypropyl β-cyclodextrin (HPBCD) showed improved dissolution and pharmacokinetics of abiraterone. However, the nature of abiraterone-HPBCD interaction within the KSDs or the effect of drug loading on the physicochemical properties and in vivo performance of HPBCD-based KSDs remain largely unknown. We hypothesize that KinetiSol technology can prepare abiraterone-HPBCD complexes within KSDs and that increasing the drug loading beyond an optimal point reduces the in vitro and in vivo performance of these KSDs. To confirm our hypothesis, we developed KSDs with 10–50% w/w drug loading and analyzed them using X-ray diffractometry and modulated differential scanning calorimetry. We found that KSDs containing 10–30% drug were amorphous. Interestingly, two-dimensional solid-state nuclear magnetic resonance and Raman spectroscopy indicated that the abiraterone-HPBCD complexes were formed. At elevated temperatures, the 10% and 20% drug-loaded KSDs were physically stable, while the 30% drug-loaded KSD showed recrystallization of abiraterone. In vitro dissolution and in vivo pharmacokinetic performances improved as the drug loading decreased; we attribute this to increased noncovalent interactions between abiraterone and HPBCD at lower drug loadings. Overall, the 10% drug loaded KSD showed a dissolution enhancement of 15.7-fold compared to crystalline abiraterone, and bioavailability enhancement of 3.9-fold compared to the commercial abiraterone acetate tablet Zytiga®. This study is first to confirm that KinetiSol, a high-energy, solvent-free technology, is capable of forming abiraterone-HPBCD complexes. Furthermore, in terms of in vitro and in vivo performance, a 10% drug load is optimal.

Full molecular dynamics simulations of molecular liquids for single-beam spectrally controlled two-dimensional Raman spectroscopy.

Single-beam spectrally controlled (SBSC) two-dimensional (2D) Raman spectroscopy is a unique 2D vibrational measurement technique utilizing trains of short pulses that are generated from a single broadband pulse by pulse shaping. This approach overcomes the difficulty of 2D Raman spectroscopy in dealing with small-signal extraction and avoids complicated low-order cascading effects, thus providing a new possibility for measuring the intramolecular and intermolecular modes of molecular liquids using fifth-order 2D Raman spectroscopy. Recently, for quantitatively investigating the mode-mode coupling mechanism, Hurwitz et al. [Opt. Express 28, 3803 (2020)] have developed a new pulse design for this measurement to separate the contributions of the fifth- and third-order polarizations, which are often overlapped in the original single-beam measurements. Here, we describe a method for simulating these original measurements and the new 2D Raman measurements on the basis of a second-order response function approach. We carry out full molecular dynamics simulations for carbon tetrachloride and liquid water using an equilibrium-nonequilibrium hybrid algorithm, with the aim of explaining the key features of the SBSC 2D Raman spectroscopic method from a theoretical point of view. The predicted signal profiles and intensities provide valuable information that can be applied to 2D spectroscopy experiments, allowing them to be carried out more efficiently.

Characterization of Fresh Milk Products Based on Multidimensional Raman Spectroscopy

The effect of integration time on Raman spectral data collected from fresh milk products was investigated and analyzed. The collected spectral data were denoised by wavelet transform to remove signal interference. Two-dimensional correlation Raman spectra of the fresh milk products were then constructed using two-dimensional correlation analysis and laser integrating time as an external perturbation. Finally, feature extraction was carried out, and the Euclidean distance was calculated. Thus, the similarities between fresh milk products of the same brand and different brands were quantitatively analyzed and calculated from Raman spectroscopy, two-dimensional correlation Raman spectroscopy, and feature extraction. The results showed that the quality of fresh milk products of the same brand fluctuated but maintained a high consistency. The differences between different brands of fresh milk products under the same detection conditions were much greater than within the same brand samples.

Two-dimensional Raman spectroscopy of Lennard-Jones liquids via ring-polymer molecular dynamics.

The simulation of multidimensional vibrational spectroscopy of condensed-phase systems including nuclear quantum effects is challenging since full quantum-mechanical calculations are still intractable for large systems comprising many degrees of freedom. Here, we apply the recently developed double Kubo transform (DKT) methodology in combination with ring-polymer molecular dynamics (RPMD) for evaluating multi-time correlation functions [K. A. Jung et al., J. Chem. Phys. 148, 244105 (2018)], providing a practical method for incorporating nuclear quantum effects in nonlinear spectroscopy of condensed-phase systems. We showcase the DKT approach in the simulation of the fifth-order two-dimensional (2D) Raman spectroscopy of Lennard-Jones liquids as a prototypical example, which involves nontrivial nonlinear spectroscopic observables of systems described by anharmonic potentials. Our results show that the DKT can faithfully reproduce the 2D Raman response of liquid xenon at high temperatures, where the system behaves classically. In contrast, liquid neon at low temperatures exhibits moderate but discernible nuclear quantum effects in the 2D Raman response compared to the responses obtained with classical molecular dynamics approaches. Thus, the DKT formalism in combination with RPMD simulations enables simulations of multidimensional optical spectroscopy of condensed-phase systems that partially account for nuclear quantum effects.

Dynamic Raman Fusion Spectroscopy for Rapid Quality Discriminant Analysis of Red Wine

The dynamic Raman spectra of a brand of red wine (aa) as the main research object were collected over a range of laser integration times (1–5 s) to observe the changing trends of molecules in the wine under experimental conditions. The three-dimensional Raman characteristic spectrum of this wine was then constructed further by two-dimensional correlation fusion analysis. The fluctuations of the three-dimensional Raman spectra were also evaluated using a similarity algorithm. The correlation coefficients were 0.977 ± 0.011 and 0.990 ± 0.006 based on synchronous and asynchronous two-dimensional correlation Raman spectroscopy, respectively. These results suggested that the samples of wine aa were highly self-similar and could be effectively distinguished from two different brands of red wine (bb and cc) based on their different spectral responses. Therefore, this method has the potential to supplement existing methods for the classification analysis of red wine.

Illuminating the dark metabolome to advance the molecular characterisation of biological systems.

The latest version of the Human Metabolome Database (v4.0) lists 114,100 individual entries. Typically, however, metabolomics studies identify only around 100 compounds and many features identified in mass spectra are listed only as 'unknown compounds'. The lack of ability to detect all metabolitespresent,andfully identify all metabolites detected (the dark metabolome) means that, despite the great contribution of metabolomics to a range of areas in the last decade, a significant amount of useful information from publically funded studies is being lost or unused each year. This loss of data limits our potential gain in knowledge and understanding of important research areas such as cell biology, environmental pollution, plant science, food chemistry and health and biomedical research. Metabolomics therefore needs to develop new tools and methods for metabolite identification to advance as a field. In this critical review, some potential issues with metabolite identification are identified and discussed. New and novel emerging technologies and tools which may contribute to expanding the number of compounds identified in metabolomics studies (thus illuminating the dark metabolome) are reviewed. The aim is to stimulate debate and research in the molecular characterisation of biological systems to drive forward metabolomic research. The work specifically discusses dynamic nuclear polarisation nuclear magnetic resonance spectroscopy (DNP-NMR), non-proton NMR active nuclei, two-dimensional liquid chromatography (2DLC) and Raman spectroscopy (RS). It is suggested that developing new methods for metabolomics with these techniques could lead to advances in the field and better characterisation of biological systems.

Two-Dimensional Resonance Raman Signatures of Vibronic Coherence Transfer in Chemical Reactions.

Two-dimensional resonance Raman (2DRR) spectroscopy has been developed for studies of photochemical reaction mechanisms and structural heterogeneity in condensed phase systems. 2DRR spectroscopy is motivated by knowledge of non-equilibrium effects that cannot be detected with traditional resonance Raman spectroscopy. For example, 2DRR spectra may reveal correlated distributions of reactant and product geometries in systems that undergo chemical reactions on the femtosecond time scale. Structural heterogeneity in an ensemble may also be reflected in the 2D spectroscopic line shapes of both reactive and non-reactive systems. In this chapter, these capabilities of 2DRR spectroscopy are discussed in the context of recent applications to the photodissociation reactions of triiodide. We show that signatures of "vibronic coherence transfer" in the photodissociation process can be targeted with particular 2DRR pulse sequences. Key differences between the signal generation mechanisms for 2DRR and off-resonant 2D Raman spectroscopy techniques are also addressed. Overall, recent experimental developments and applications of the 2DRR method suggest that it will be a valuable tool for elucidating ultrafast chemical reaction mechanisms.

Structural mechanism of iodine incorporation in As-Se-I glasses and its effects on physical properties

The structural evolution of ternary AsxSe100−x−yIy glasses (x=20, 30 and y=10, 20) upon progressive substitution of Se with I is studied using a combination of high-resolution, two-dimensional 77Se nuclear magnetic resonance (NMR) and Raman spectroscopy. The results suggest that the As-Se bonds in the As-Se-Se linkages in these glasses are severed and terminated by As-I bonds with a concomitant increase in the relative fraction of Se-Se-Se linkages and, in the case of As30Se70−yIy glasses, also in the relative fraction of As-Se-As linkages. This structural modification decreases the average connectivity of the network and its packing efficiency, which are manifested in an increase in molar volume and fragility and a decrease in glass transition temperature Tg and isothermal viscosity. Additionally, Tg and fragility are found to be only a function of average coordination number regardless of chemical composition. When taken together, these results indicate a relatively homogeneous distribution of the I atoms in the glass structure in “mixed-anion” AsSe(3−x)/2Ix pyramidal units.

Perspective: Two-dimensional resonance Raman spectroscopy.

Two-dimensional resonance Raman (2DRR) spectroscopy has been developed for studies of photochemical reaction mechanisms and structural heterogeneity in complex systems. The 2DRR method can leverage electronic resonance enhancement to selectively probe chromophores embedded in complex environments (e.g., a cofactor in a protein). In addition, correlations between the two dimensions of the 2DRR spectrum reveal information that is not available in traditional Raman techniques. For example, distributions of reactant and product geometries can be correlated in systems that undergo chemical reactions on the femtosecond time scale. Structural heterogeneity in an ensemble may also be reflected in the 2D spectroscopic line shapes of both reactive and non-reactive systems. In this perspective article, these capabilities of 2DRR spectroscopy are discussed in the context of recent applications to the photodissociation reactions of triiodide and myoglobin. We also address key differences between the signal generation mechanisms for 2DRR and off-resonant 2D Raman spectroscopies. Most notably, it has been shown that these two techniques are subject to a tradeoff between sensitivity to anharmonicity and susceptibility to artifacts. Overall, recent experimental developments and applications of the 2DRR method suggest great potential for the future of the technique.

Two-dimensional resonance Raman spectroscopy of oxygen- and water-ligated myoglobins.

Two-dimensional resonance Raman (2DRR) spectroscopy has recently been developed as a tool for studies of structural heterogeneity and photochemical dynamics in condensed phases. In this paper, 2DRR spectroscopy is used to investigate line broadening mechanisms of both oxygen- and water-ligated myoglobins. General signatures of anharmonicity and inhomogeneous line broadening are first established with model calculations to facilitate signal interpretation. It is shown that the present quasi-degenerate version of 2DRR spectroscopy is insensitive to anharmonicity, because signal generation is allowed for harmonic modes. Rather, the key information to be gained from 2DRR spectroscopy pertains to the line broadening mechanisms, which are fairly obvious by inspection of the data. 2DRR signals acquired for both heme protein systems reveal significant heterogeneity in the vibrational modes local to the heme's propionic acid side chains. These side chains are known to interact with solvent, because they protrude from the hydrophobic pocket that encloses the heme. Molecular dynamics simulations suggest that the heterogeneity detected in our 2DRR experiments reflects fluctuations in the geometries of the side chains. Knowledge of such thermal motions will be useful for understanding protein function (e.g., ligand binding) because the side chains are an effective "gateway" for the exchange of thermal energy between the heme and solvent.

Full molecular dynamics simulations of liquid water and carbon tetrachloride for two-dimensional Raman spectroscopy in the frequency domain

Frequency-domain two-dimensional (2D) Raman signals, which are equivalent to coherent two-dimensional Raman scattering (COTRAS) signals, for liquid water and carbon tetrachloride were calculated using an equilibrium–nonequilibrium hybrid molecular dynamics (MD) simulation algorithm. An appropriate representation of the 2D Raman spectrum obtained from MD simulations provides an easy-to-understand depiction of structural and dynamical properties. We elucidate mechanisms governing the 2D signal profiles involving anharmonic mode–mode coupling and the nonlinearities of the polarizability for the intermolecular and intramolecular vibrational modes. The predicted signal profiles and intensities can be utilized to analyze recently developed single-beam 2D spectra, whose signals are generated from a coherently controlled pulse, allowing the single-beam measurement to be carried out more efficiently. Moreover, the MD simulation results allow us to visualize the molecular structure and dynamics by comparing the accurately calculated spectrum with experimental result.