Abstract:Lactose powder consisting of α-D-lactose monohydrate and anhydrous β-D-lactose was nondestructively and quantitatively evaluated by transmission-type Terahertz time-domain spectroscopy (THz-TDS). An absorption with peak at 39.7 cm −1 (1.19 THz) was assigned to be derived from anhydrous β-D-lactose, in addition to the absorptions due to α-Dlactose monohydrate with peak at 17.1 cm −1 (0.53 THz) and 45.6 cm −1 (1.37 THz). After deconvolution of the spectra using Lorentzian, integrated intensities of the absorptio… Show more
“…These are in accordance with previously reported characteristic resonances of lactose anomers, i . e ., the resonance at 0.531 THz due to an external hindered rotational mode along the B-axis of α-lactose crystal with intermolecular hydrogen-bond networks 31,32 , that at 1.371 THz due to inter- and intra-molecular vibrations in α-lactose 32 , and that at 1.188 THz due to β-lactose 33 . These results demonstrate the capability of THz s-SNOM not only to accurately measure local biomolecular resonances but also to detect them with high sensitivity considering that β-lactose anomer impurity consists of only ≤4% of the lactose sample.Figure 3Computed local permittivity of lactose anomer mixtures: THz s-SNOM vs THz-TDS.…”
Terahertz near-field microscopy (THz-NFM) could locally probe low-energy molecular vibration dynamics below diffraction limits, showing promise to decipher intermolecular interactions of biomolecules and quantum matters with unique THz vibrational fingerprints. However, its realization has been impeded by low spatial and spectral resolutions and lack of theoretical models to quantitatively analyze near-field imaging. Here, we show that THz scattering-type scanning near-field optical microscopy (THz s-SNOM) with a theoretical model can quantitatively measure and image such low-energy molecular interactions, permitting computed spectroscopic near-field mapping of THz molecular resonance spectra. Using crystalline-lactose stereo-isomer (anomer) mixtures (i.e., α-lactose (≥95%, w/w) and β-lactose (≤4%, w/w)), THz s-SNOM resolved local intermolecular vibrations of both anomers with enhanced spatial and spectral resolutions, yielding strong resonances to decipher conformational fingerprint of the trace β-anomer impurity. Its estimated sensitivity was ~0.147 attomoles in ~8 × 10−4 μm3 interaction volume. Our THz s-SNOM platform offers a new path for ultrasensitive molecular fingerprinting of complex mixtures of biomolecules or organic crystals with markedly enhanced spatio-spectral resolutions. This could open up significant possibilities of THz technology in many fields, including biology, chemistry and condensed matter physics as well as semiconductor industries where accurate quantitative mappings of trace isomer impurities are critical but still challenging.
“…These are in accordance with previously reported characteristic resonances of lactose anomers, i . e ., the resonance at 0.531 THz due to an external hindered rotational mode along the B-axis of α-lactose crystal with intermolecular hydrogen-bond networks 31,32 , that at 1.371 THz due to inter- and intra-molecular vibrations in α-lactose 32 , and that at 1.188 THz due to β-lactose 33 . These results demonstrate the capability of THz s-SNOM not only to accurately measure local biomolecular resonances but also to detect them with high sensitivity considering that β-lactose anomer impurity consists of only ≤4% of the lactose sample.Figure 3Computed local permittivity of lactose anomer mixtures: THz s-SNOM vs THz-TDS.…”
Terahertz near-field microscopy (THz-NFM) could locally probe low-energy molecular vibration dynamics below diffraction limits, showing promise to decipher intermolecular interactions of biomolecules and quantum matters with unique THz vibrational fingerprints. However, its realization has been impeded by low spatial and spectral resolutions and lack of theoretical models to quantitatively analyze near-field imaging. Here, we show that THz scattering-type scanning near-field optical microscopy (THz s-SNOM) with a theoretical model can quantitatively measure and image such low-energy molecular interactions, permitting computed spectroscopic near-field mapping of THz molecular resonance spectra. Using crystalline-lactose stereo-isomer (anomer) mixtures (i.e., α-lactose (≥95%, w/w) and β-lactose (≤4%, w/w)), THz s-SNOM resolved local intermolecular vibrations of both anomers with enhanced spatial and spectral resolutions, yielding strong resonances to decipher conformational fingerprint of the trace β-anomer impurity. Its estimated sensitivity was ~0.147 attomoles in ~8 × 10−4 μm3 interaction volume. Our THz s-SNOM platform offers a new path for ultrasensitive molecular fingerprinting of complex mixtures of biomolecules or organic crystals with markedly enhanced spatio-spectral resolutions. This could open up significant possibilities of THz technology in many fields, including biology, chemistry and condensed matter physics as well as semiconductor industries where accurate quantitative mappings of trace isomer impurities are critical but still challenging.
“…The periodic simulations for both α-lactose monohydrate and β -lactose are in good agreement with reported terahertz spectra. 110,111 To retain the anomeric differences and consequent long-range forces of the two solids in the gas phase simulations, clusters of lactose in both forms (Figure 6a) were constructed from a supercell constructed from single crystal X-ray experiments, from a single subunit to an octamer. 112,113 Following the trend of oxalic acid, the spectra produced from the gas-phase simulations of both lactose solids (Figure 6b,c) offer little agreement to the experimental spectra, with an excess of vibrational frequencies, absent in the experimental spectrum.…”
Section: Large Flexible Molecules and Polymorphismmentioning
Terahertz vibrational spectroscopy has emerged as a powerful spectroscopic technique, providing valuable information regarding long-range interactions -- and associated collective dynamics -- occurring in solids. However, the terahertz sciences are relatively nascent, and there have been significant advances over the last several decades that have profoundly influenced the interpretation and assignment of experimental terahertz spectra. Specifically, because there do not exist any functional group or material-specific terahertz transitions, it is not possible to interpret experimental spectra without additional analysis, specifically, computational simulations. Over the years simulations utilizing periodic boundary conditions have proven to be most successful for reproducing experimental terahertz dynamics, due to the ability of the calculations to accurately take long-range forces into account. On the other hand, there are numerous reports in the literature that utilize gas phase cluster geometries, to varying levels of apparent success. This perspective will provide a concise introduction into the terahertz sciences, specifically terahertz spectroscopy, followed by an evaluation of gas phase and periodic simulations for the assignment of crystalline terahertz spectra, highlighting potential pitfalls and good practice for future endeavors.
“…The periodic simulations for both α-lactose monohydrate and β -lactose are in good agreement with reported terahertz spectra. 110,111 To retain the anomeric differences and consequent long-range forces of the two solids in the gas phase simulations, clusters of lactose in both forms (Figure 6a) were constructed from a supercell constructed from single crystal X-ray experiments, from a single subunit to an octamer. 112,113 Following the trend of oxalic acid, the spectra produced from the gas-phase simulations of both lactose solids (Figure 6b,c) offer little agreement to the experimental spectra, with an excess of vibrational frequencies, absent in the experimental spectrum.…”
Section: Large Flexible Molecules and Polymorphismmentioning
Terahertz vibrational spectroscopy has emerged as a powerful spectroscopic technique, providing valuable information regarding long-range interactions -- and associated collective dynamics -- occurring in solids. However, the terahertz sciences are relatively nascent, and there have been significant advances over the last several decades that have profoundly influenced the interpretation and assignment of experimental terahertz spectra. Specifically, because there do not exist any functional group or material-specific terahertz transitions, it is not possible to interpret experimental spectra without additional analysis, specifically, computational simulations. Over the years simulations utilizing periodic boundary conditions have proven to be most successful for reproducing experimental terahertz dynamics, due to the ability of the calculations to accurately take long-range forces into account. On the other hand, there are numerous reports in the literature that utilize gas phase cluster geometries, to varying levels of apparent success. This perspective will provide a concise introduction into the terahertz sciences, specifically terahertz spectroscopy, followed by an evaluation of gas phase and periodic simulations for the assignment of crystalline terahertz spectra, highlighting potential pitfalls and good practice for future endeavors.
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