Low-frequency Raman Spectroscopy Research Articles

Toward On-Demand Polymorphic Transitions of Organic Crystals via Side Chain and Lattice Dynamics Engineering.

Controlling polymorphism, namely, the occurrence of multiple crystal forms for a given compound, is still an open technological challenge that needs to be addressed for the reliable manufacturing of crystalline functional materials. Here, we devised a series of 13 organic crystals engineered to embody molecular fragments undergoing specific nanoscale motion anticipated to drive cooperative order-disorder phase transitions. By combining polarized optical microscopy coupled with a heating/cooling stage, differential scanning calorimetry, X-ray diffraction, low-frequency Raman spectroscopy, and calculations (density functional theory and molecular dynamics), we proved the occurrence of cooperative transitions in all the crystalline systems, and we demonstrated how both the molecular structure and lattice dynamics play crucial roles in these peculiar solid-to-solid transformations. These results introduce an efficient strategy to design polymorphic molecular crystalline materials endowed with specific molecular-scale lattice and macroscopic dynamics.

Surface-Enhanced, Low-Frequency Raman Spectroscopy: A Sensitive Screening Tool for Structural Characterization of Pharmaceuticals.

Surface-enhanced, low-frequency Raman spectroscopy (SELFRS) was explored for its potential as a structural screening tool within pharmaceutical applications, including facile small-scale multicomponent analysis. Paracetamol was used as the model drug, and its crystallization behavior with or without the presence of a templating agent (benzoic acid) was investigated using commercial silver-based SERS substrates. The Raman imaging was carried out using two different LFR-enabled instruments employing 532 and 785 nm incident lasers, where each of the setups showed certain affinity for differentiating lattice vibrations of the polymorphic forms of interest: form I and form II. A comparison of SELFRS, SERS, and their combination using chemometrics showed the potential for the LFR spectral range to improve surface-enhanced measurements either individually or in combination with the typically-used fingerprint region without the need to alter the experimental configuration. Additionally, the use of crystallization additives that helped to drive the formation of metastable form II was shown using SELFRS to provide additional mechanistic understanding of the template-assisted crystallization processes.

Influence of Rheological Modifications on Primary Network Chemical and Structural Cure Kinetics for an Interpenetrating Polymer Network Resin.

The development of non-contact in situ techniques for monitoring cure kinetics has the potential to greatly improve both resin formulation and processing. We have recently shown that low-frequency Raman spectroscopy is a viable method for assessing resin structural cure kinetics and complements the traditional chemical conversion determined from the fingerprint region of the spectrum. In this work, we further evaluate the relationship between structural and chemical conversion by investigating two chemically identical yet rheologically different interpenetrating polymer network resin formulations. Rheological analysis demonstrates a relationship between structural conversion and storage modulus, which is not observed in the chemical conversion data. We show that one can produce master cure kinetics curves with comparable kinetic constants using both the chemical and structural conversion methodologies. Parametric analysis of the structural conversion, chemical conversion, and photorheological conversion was combined with a semi-empirical model for the storage shear modulus as a function of the extent of cure.

Inelastic light scattering study of fast relaxation in dibutyl phthalate glass

The organic glass-forming dibutyl phthalate (DBP) has been studied applying low-frequency Raman and Brillouin spectroscopy in the temperature range from 90 K to 200 K, covering glassy and liquid states. Spectra of fast relaxation in the GHz-THz frequency range were determined from the inelastic light scattering spectra. The line width and position of the Brillouin peak were used to determine the Q-1-factor, which is inversely proportional to susceptibility at the Brillouin peak frequency. It was discovered that the temperature evolution of the fast relaxation susceptibility and the Q-1-factor agree well with a mobility parameter from pulse EPR experiment. The findings show that peculiarities in the temperature dependence the EPR data found early for DBP have are accompanied by a redistribution of the relaxation times.

Low-frequency Raman spectrum of methamphetamine hydrochloride and its alterations induced by impurities

Methamphetamine is one of the most abused drugs worldwide. Forensic laboratories have developed various methods to analyze methamphetamine for identifying and comparing seizures. These methods basically focus on the physicochemical properties of the methamphetamine molecule. Because methamphetamine is commonly distributed in its hydrochloride salt form, information on the crystalline state of methamphetamine could give new insight for forensic drug analysis. To grasp this information, we applied low-frequency Raman spectroscopy to methamphetamine hydrochloride. A laboratory-built low-frequency Raman microspectrometer was used for measuring low-frequency Raman spectra of optically pure and racemic methamphetamine hydrochloride. A mixture of methamphetamine hydrochloride with dimethyl sulfone, which is frequently added as a diluent to illicit methamphetamines, was also measured. An ab initio calculation was performed to assign peaks in the low-frequency spectra. The phonon modes of methamphetamine hydrochloride, and their changes induced by impurities are discussed. To the best of our knowledge, this is the first reported application of low-frequency Raman spectroscopy technique to methamphetamine hydrochloride.

Is Ortho-Terphenyl a Rigid Glass Former?

Ortho-terphenyl (OTP) has long been used as a model system to study the glass transition due to its apparent simplicity and a widespread assumption that it is a rigid molecule. Here, we employ terahertz time-domain spectroscopy and low-frequency Raman spectroscopy to investigate the rigidity of OTP by direct observation of the low-frequency vibrational dynamics. These terahertz phonons involve complex large-amplitude atomic motions where intramolecular and intermolecular displacements are often mixed. Comparison of experimental results with density functional theory and ab initio molecular dynamics simulations shows that the assumption of rigidity neglects important implications for the glass transition and must be revisited. These results highlight the significance of terahertz modes on elasticity, which will be even more critical in more complex systems such as biomolecules.

Enhanced Interlayer Interaction in Top‐Layer Twisted Trilayer MoS2 with Moiré Superlattice

AbstractMoiré superlattices, induced by an angular mismatch in layered materials provide a new index of freedom to manipulate the correlated electron states and many‐body properties of excitons. Here, trilayer MoS2 homostructures with the 3R configuration between the middle (M) and the bottom (B) layer and the top‐to‐middle (T‐M) interlayer twists ranging from 10° to 40° are fabricated via NaCl‐assisted chemical vapor deposition. The twist‐dependent interlayer interactions are systematically investigated by polarized low frequency (PLF) and high frequency (HF) Raman spectroscopy. PLF Raman results show that the energy shift in the shear mode, the breathing modes of LB31 and LB32 is respectively the much in 14°‐ and 28°‐T‐M twisted trilayer, among as‐prepared trilayer MoS2 homostructures. Moreover, the T‐M twist further affects the optical properties of the twisted MoS2 trilayer, evidenced by the photoluminescence (PL) spectroscopy. Moiré excitons are enhanced in the top‐layer twisted MoS2 trilayer with a T‐M twists of 28°, which may originate from the interlayer exciton trapped by the periodical moiré potential. The present work demonstrates that the trilayer homostructures tuned by interlayer twists can be an ideal system to tune the energy band structures and exciton properties for their potential applications in the nano‐optical electronics.

Evolution of structural dynamics in cesium lead halide perovskite colloidal nanocrystals from temperature-controlled synthesis.

Halide perovskite nanocrystals are at the forefront of materials research due to their remarkable optoelectronic properties and versatile applications. While their lattice structure and optical properties have been extensively investigated for the structure-property correlation, their lattice dynamics, the physical link between the lattice structure and optoelectronic properties, has been much less visited. We report the evolution of structural dynamics of a series of cesium lead halide perovskite nanocrystals whose size and morphology are systematically varied by synthesis temperature. Low-frequency Raman spectroscopy uncovers the nanocrystals' structural dynamics, including a relaxational spectral continuum from ligand librations and a phonon spectrum evolving with nanocrystal size. As the size of nanocrystals increases, their phonon spectrum becomes more intense, and their spectral weights redistribute with new first- and second-order modes being activated. The linewidth of the observed phonon modes generally broadens as the nanocrystal grows larger, an interesting deviation from the established phonon confinement model. We suggest that strong confinement and truncation of the lattice and ligands anchoring on the surface might lead to pinning of the lattice dynamics at nanoscale. These findings offer new insights into the bulk-nano-transition in halide perovskite soft semiconductors.

Assessment of dynamic disorder in DNA oligonucleotides using low-frequency Raman spectroscopy

The degree of DNA compaction in various regions of the cell nucleus determines whether the corresponding genes should be expressed, and whether other important cellular processes, such as DNA replication and repair, should take place. However, approaches to the experimental assessment of the compactness of DNA in cell nuclei, as well as its indicator, dynamic disorder — thermal fluctuations in the position and mutual orientation of molecular fragments — are practically not developed. In this paper, using single-stranded oligonucleotides guanine and cytosine, as well as their double-stranded combination as an example, we show that dynamic disorder in DNA can be estimated using low-frequency Raman spectroscopy. For the first time, the Raman spectra of oligonucleotides were measured in a wide range including the low-frequency and high-frequency regions. It was found that the low-frequency Raman intensity is maximal for single-stranded oligocytosine and minimal in double-stranded oligonucleotide, in full agreement with the magnitude of dynamic disorder estimated from the molecular dynamics simulations. The results obtained indicate the prospects of using low-frequency Raman spectroscopy to assess the dynamic disorder and compactness of DNA. It is expected that the use of such a technique should contribute to the understanding of key cellular processes and their underlying physical mechanisms, which is necessary for the development of advanced methods of molecular biophysics and cell biology.

In Situ Imaging of Subcutaneous Drug Delivery Systems Using Microspatially Offset Low-Frequency Raman Spectroscopy.

The noninvasive in situ monitoring of the status of drug retention and implant integrity of subcutaneous implants would allow optimization of therapy and avoid periods of subtherapeutic delivery kinetics. A proof-of principle study was conducted to determine the use of microspatially offset low-frequency Raman spectroscopy (micro-SOLFRS) for nonintrusive in situ analysis of subcutaneous drug delivery systems. Caffeine was used as the model drug, and it was embedded in a circular-shape Soluplus matrix via vacuum compression molding. For the exploratory analysis, prototype implants were positioned underneath skin tissue samples, and various caffeine concentrations (1-50% w/w) and micro-SOLFRS displacement settings (Δz = 0-8 mm) were tested from the pseudo three-dimensional (3D)-imaging perspective. This format allowed the optimization of real-time micro-SOLFRS analysis of implants through skin tissue that was embedded in an agarose hydrogel. Notably, this analytical approach allowed the temporal and spatial erosion of the implant and solid-state transformations of caffeine to be distinguished. The spectrometric results correlated with complementary high-performance liquid chromatography (HPLC) determination of changes in drug concentration, illustrating drug dissipation/diffusion characteristics. The discovered capability of micro-SOLFRS for in situ measurements of drugs and implants makes it attractive for biomedical diagnostics that, ultimately, could result in development of a new point-of-care technology.

Assessment of Dynamic Disorder in DNA Oligonucleotides Using Low-Frequency Raman Spectroscopy

Assessment of Dynamic Disorder in DNA Oligonucleotides Using Low-Frequency Raman Spectroscopy

Medium-range structure modifications induced by Fe3+/Fetot. in volcanic glasses: a low-frequency Raman spectroscopy study

Here is carried out a Raman scattering study on the boson peak evolution of an iron-rich peralkaline rhyolite in function of both the iron oxidation state and the glass transition temperature. It is reported here that the distribution of low-frequency modes in the boson peak range is only slightly affected for an iron ratio (Fe3+/Fetot.) from 0.83 down to 0.24. Their distribution does not change in the boson peak range as a function of Fe3+/Fetot., until the reduction process starts to modify the glass network from a dominantly fourfold coordinated Fe3+ structures into a structure mostly governed by fivefold coordinated Fe2+. This trend is also related to a decreasing glass transition temperature peak, mirroring an increasing proportion of weakest bonds with respect to the stronger ones.

In Operando Analysis of Milk-Based Oral Formulations during Digestion Using Synchrotron Small-Angle X-ray Scattering Coupled to Low-Frequency Raman Spectroscopy.

A low-frequency Raman (LFR) probe was coupled to an in-line small-angle X-ray scattering (SAXS) beamline to test the capabilities of a combinatory approach for the determination of lipid and drug behavior during the enzymatic lipolysis of milk-based oral formulations. Cinnarizine was used as the model drug, and its solubilization dynamics as well as its potential impact on the supramolecular structures formed by the digestion products of bovine milk were evaluated from the perspective of both techniques. The SAXS data were superior in distinguishing various liquid crystalline assemblies formed during the digestion process, with LFR providing complementary information regarding the formation of calcium soaps. On the other hand, studying changes in the LFR domain allowed the differentiation of drug solubilization and precipitation; processes that were less clear from the X-ray scattering data. Given the relative simplicity of the combined experimental setup, these results highlight the advantages that the combination of the two techniques can provide for understanding and developing new lipid-based formulations and will help to translate the results obtained at synchrotron facilities to routine analysis procedures in laboratory/industry-based environments.

Probing of nucleic acid compaction using low-frequency Raman spectroscopy.

Compaction of nucleic acids, namely DNA and RNA, determines their functions and involvement in vital cell processes including transcription, replication, DNA repair and translation. However, experimental probing of the compaction of nucleic acids is not straightforward. In this study, we suggest an approach for this probing using low-frequency Raman spectroscopy. Specifically, we show theoretically, computationally and experimentally the quantifiable correlation between the low-frequency Raman intensity from nucleic acids, magnitude of thermal fluctuations of atomic positions, and the compaction state of biomolecules. Noteworthily, we highlight that the LF Raman intensity differs by an order of magnitude for different samples of DNA, and even for the same sample in the course of long-term storage. The feasibility of the approach is further shown by assessment of the DNA compaction in the nuclei of plant cells. We anticipate that the suggested approach will enlighten compaction of nucleic acids and their dynamics during the key processes of the cell life cycle and under various factors, facilitating advancement of molecular biology and medicine.

Fundamentally intertwined: anharmonic intermolecular interactions dictate both thermal expansion and terahertz lattice dynamics in molecular crystals.

We investigate the anisotropic thermal expansion behavior of a co-crystalline system composed of 4,4'-azopyridine and trimesic acid (TMA-azo). Using variable-temperature single-crystal X-ray diffraction (SC-XRD), low-frequency Raman spectroscopy, and terahertz time-domain spectroscopy (THz-TDS), we observe significant temperature-induced shifting and broadening of the vibrational absorption features, indicating changes in the intermolecular potential. Our findings reveal that thermal expansion is driven by anharmonic interactions and the potential energy topography, rather than increased molecular dynamics. Density functional theory (DFT) simulations support these results, highlighting significant softening of the potential energy surface (PES) with temperature. This comprehensive approach offers valuable insights into the relationship between structural dynamics and thermal properties, providing a robust framework for designing materials with tailored thermal expansion characteristics.

Terahertz and Low-Frequency Raman Spectroscopy of Polymers

Terahertz and Low-Frequency Raman Spectroscopy of Polymers

Description of an original molecular ordering process into a disordered crystalline form: the atypical low-temperature transformation of the disordered form III of linezolid.

Form III of linezolid was prepared by heating the commercial form above 150 °C and subsequently analyzed upon cooling down to -160 °C, by low- and high-frequency Raman spectroscopy, differential scanning calorimetry and powder X-ray diffraction (PXRD). It was observed that form III was preserved down to 0 °C. At lower temperatures a soft mode was clearly detected by low-frequency Raman spectroscopy associated with the detection of additional Raman bands distinctive of additional intermolecular H-bond interactions. Raman spectroscopy investigations performed in a wide frequency range revealed a continuous transformation characterized by both displacive and order-disorder signatures. By contrast, PXRD highlighted the absence of symmetry breaking, Bragg peaks being still indexed in the same unit cell from room temperature down to -160 °C. Additionally, a significant broadening of Bragg peaks was observed with decreasing temperature interpreted as being a consequence of a distribution of frozen molecular conformations.

Cross-domain growth and angle-dependent interlayer coupling of twisted bilayer MoS2

Twisted 2D transition metal dichalcogenides (TMDCs) play a significant role in the development of twistronics. However, it is still challenging to prepare high-quality twisted TMDCs by current stacking or folding techniques. Herein, we propose a cross-domain chemical vapor deposition method to synthesize twisted bilayer MoS2 through precisely controlling the supply of molybdenum precursor. It is found that the top layer of a bilayer MoS2 grain maintains its original orientation even when it crosses over to neighboring monolayer MoS2 grain. This suggests that the van der Waals epitaxy can be prevented with the assistance of covalent bonds. Furthermore, the interlayer coupling strength reaches a maximum value at the twisted angle (θ) of 0° or 60° and a minimum at θ = 30°. Moreover, the evolution of in-plane shear mode and out-of-plane breathing mode obtained from low-frequency Raman spectroscopy reveals atomic reconstructions of the moiré pattern. Meanwhile, the shift of the indirect bandgap exhibits an angle dependence consistent with the interlayer coupling strength, which likely comes from the mixing of pz orbitals. The change in A−/A intensity ratio is not mainly originated from the trion binding energy, but the excess electron concentration. Our results offer a feasible approach to prepare high-quality twisted TMDCs and provide a good platform for studying twistronics and related phenomena.

Probing Dielectric Relaxation of Water at Electrochemical Interfaces with Low-Frequency SERS Spectroscopy

Dynamic and structural properties of hydrogen-bonded water molecules in liquid phase have a significant impact on many chemical and biological processes in aqueous systems. Therefore, the bulk behavior of water is quite actively studied from both experimental and theoretical point of view. In the frequency domain, collective motions of water molecules appear in the terahertz (THz) range. For example, the central frequency of Debye-type dielectric relaxation of water exists at around 1 cm-1, and that of the so-called fast Debye relaxation is found at around 10 cm-1. There are several spectroscopic means to obtain such low-frequency information in the bulk liquid of water. However, for interfacial water molecules interacting with a solid surface, their dynamic behavior of hydrogen-bond networks remains unexplored in the experimental research field, despite of the importance of such behavior to molecular-level understanding of heterogeneous electrochemical processes. The reason for lack of such information is due to lack of adequate surface-selective spectroscopic means. In this talk, in-situ observation of the relaxational and vibrational dynamics of water at electrochemical interfaces is demonstrated using low-frequency surface-enhanced Raman spectroscopy (SERS). In this spectroscopic method, not only intermolecular dynamics but also intramolecular vibrational behaviors of water can be simultaneously monitored due to the intrinsic nature of the inelastic scattering technique accessible in the wide frequency range covering both THz and mid-IR regions, which helps us to understand the relation between microscopic and macroscopic behaviors of water molecules.To obtain low-frequency SERS spectrum, volume Bragg grating filters were used for both monochromatization of He-Ne laser radiation of 632.8 nm and removal of Rayleigh scattered light [1]. SERS-active Au electrodes were prepared by electrochemical surface roughening of Au surface in 0.1M KCl solution. For SERS-active Pt electrodes, monoatomic Pt overlayers were formed on the roughened Au surfaces. SERS spectra for interfacial water were measured on these electrode surfaces under application of electrochemical potentials. The measured spectra were converted to density states of formats by reducing the Purcell factor, Bose-Einstein thermal factor, and frequency factor, which can unveil vibrational features in low-frequency range [2-5].The measured spectra clearly showed potential-dependent features in the THz region. According to the previously reported spectra for bulk water, these features were assigned to the fast Debye relaxation component and two intermolecular vibration modes of interfacial water layer. By analyzing the observed spectral features by the assistance of classical molecular dynamics (MD) simulations, we found that the potential-induced change of water orientation causes formation of local defects in hydrogen-bonded networks of interfacial water layer and the lateral mobility of such defects on negatively charged surface is larger than that on positively charged surface [6]. Figure shows the dynamical behavior of potential-induced defects in hydrogen-bonded networks of interfacial water molecules on negatively and positively charge surfaces. The details will be discussed in the presentation.[1] M. Inagaki, K. Motobayashi, K. Ikeda, J. Phys. Chem. Lett., 8, 4236-4240 (2017).[2] M. Inagaki, T. Isogai, K. Motobayashi, K. -Q. Lin, B. Ren, K. Ikeda, Chem. Sci., 11, 9807-9717 (2020).[3] M. Inagaki, K. Motobayashi, K. Ikeda, Nanoscale, 12, 22988-22994 (2020).[4] R. Kamimura, T. Kondo, K. Motobayashi, K. Ikeda, Phys. Status Solidi B, 259, 2100589 (2022).[5] T. Kondo, M. Inagaki, K. Motobayashi, K. Ikeda, Catal. Sci. Technol., 12, 2670-2676 (2022).[6] T. Isogai, M. Inagaki, M. Uranagase, K. Motobayashi, S. Ogata, K. Ikeda, submitted. Figure 1

Low-frequency Raman Spectroscopy as a diagnostic tool for COVID-19 and other coronaviruses

Low-frequency Raman Spectroscopy as a diagnostic tool for COVID-19 and other coronaviruses