Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators

Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting K_Ca1.1 and Ca_V1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Dalbergia tonkinensis Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba²⁺ currents through Ca_V1.2 channels (I_Ba1.2) were blocked in a concentration-dependent manner by sativanone, 3′-O-methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside], ambocin, butin, and biochanin A increased I_KCa1.1. In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, Dalbergia tonkinensis is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs.     

Terahertz Spectroscopic Analysis of Lactose in Infant Formula: Implications for Detection and Quantification

Lactose plays a significant role in daily lives as a constituent of various food and pharmaceutical products. Yet, lactose intolerance conditions demand low-lactose and lactose-free products in the market. These increasing nutritional claims and labels on food products entail simple and reliable methods of analysis that can be used for meeting quality standards, nutritional claims and legal requirements. In this study, terahertz time–domain spectroscopy (THz-TDS) was employed to analyse α-lactose monohydrate qualitatively and quantitatively in food products. Both absorption spectra and absorption coefficient spectra were investigated for their prediction performance. Regression models for lactose quantification using peak area and height of the absorption peaks 0.53 and 1.37 THz were developed and assessed in infant formula samples. Satisfactory prediction results were achieved in ideal conditions with pure standards, but not in all predictions of infant formula samples. Reasons and further implications are discussed.     

20种α-氨基酸的太赫兹光谱及其分子结构的相关性

应用太赫兹时域光谱(THz-TDS)技术, 在室温下对构成蛋白质的20种基本氨基酸的多晶粉末压片样品进行了光谱测试分析. 结果表明, 所有氨基酸对THz波反应非常灵敏, 在0.2-3.0 THz的有效频谱范围内, 表现出各自特征吸收峰, 故而利用THz光谱可以有效地区别不同种类的氨基酸. 我们以新数据验证和补充了前人的研究结果, 建立了以氨基酸分子结构及其THz光谱特征为基础的分类方案, 讨论并揭示了氨基酸分子的结构差异与其THz吸收光谱之间的相关性. 认知这些相关性将有助于鉴定氨基酸分子, 促进THz光谱学的理论研究以及在生物医学领域的推广应用.     

Identification of the Large-Conductance Ca2+-Regulated Potassium Channel in Mitochondria of Human Bronchial Epithelial Cells

Mitochondria play a key role in energy metabolism within the cell. Potassium channels such as ATP-sensitive, voltage-gated or large-conductance Ca²⁺-regulated channels have been described in the inner mitochondrial membrane. Several hypotheses have been proposed to describe the important roles of mitochondrial potassium channels in cell survival and death pathways. In the current study, we identified two populations of mitochondrial large-conductance Ca²⁺-regulated potassium (mitoBK_Ca) channels in human bronchial epithelial (HBE) cells. The biophysical properties of the channels were characterized using the patch-clamp technique. We observed the activity of the channel with a mean conductance close to 285 pS in symmetric 150/150 mM KCl solution. Channel activity was increased upon application of the potassium channel opener NS11021 in the micromolar concentration range. The channel activity was completely inhibited by 1 µM paxilline and 300 nM iberiotoxin, selective inhibitors of the BK_Ca channels. Based on calcium and iberiotoxin modulation, we suggest that the C-terminus of the protein is localized to the mitochondrial matrix. Additionally, using RT-PCR, we confirmed the presence of α pore-forming (Slo1) and auxiliary β3-β4 subunits of BK_Ca channel in HBE cells. Western blot analysis of cellular fractions confirmed the mitochondrial localization of α pore-forming and predominately β3 subunits. Additionally, the regulation of oxygen consumption and membrane potential of human bronchial epithelial mitochondria in the presence of the potassium channel opener NS11021 and inhibitor paxilline were also studied. In summary, for the first time, the electrophysiological and functional properties of the mitoBK_Ca channel in a bronchial epithelial cell line were described.     

In Silico and Ex Vivo Studies on the Spasmolytic Activities of Fenchone Using Isolated Guinea Pig Trachea

Fenchone is a bicyclic monoterpene found in a variety of aromatic plants, including Foeniculum vulgare and Peumus boldus, and is used in the management of airways disorders. This study aimed to explore the bronchodilator effect of fenchone using guinea pig tracheal muscles as an ex vivo model and in silico studies. A concentration-mediated tracheal relaxant effect of fenchone was evaluated using isolated guinea pig trachea mounted in an organ bath provided with physiological conditions. Sustained contractions were achieved using low K⁺ (25 mM), high K⁺ (80 mM), and carbamylcholine (CCh; 1 µM), and fenchone inhibitory concentration–response curves (CRCs) were obtained against these contractions. Fenchone selectively inhibited with higher potency contractions evoked by low K⁺ compared to high K⁺ with resultant EC₅₀ values of 0.62 mg/mL (0.58–0.72; n = 5) and 6.44 mg/mL (5.86–7.32; n = 5), respectively. Verapamil (VRP) inhibited both low and high K⁺ contractions at similar concentrations. Pre-incubation of the tracheal tissues with K⁺ channel blockers such as glibenclamide (Gb), 4-aminopyridine (4-AP), and tetraethylammonium (TEA) significantly shifted the inhibitory CRCs of fenchone to the right towards higher doses. Fenchone also inhibited CCh-mediated contractions at comparable potency to its effect against high K⁺ [6.28 mg/mL (5.88–6.42, n = 4); CCh] and [6.44 mg/mL (5.86–7.32; n = 5); high K⁺]. A similar pattern was obtained with papaverine (PPV), a phosphodiesterase (PDE), and Ca²⁺ inhibitor which inhibited both CCh and high K⁺ at similar concentrations [10.46 µM (9.82–11.22, n = 4); CCh] and [10.28 µM (9.18–11.36; n = 5); high K⁺]. However, verapamil, a standard Ca²⁺ channel blocker, showed selectively higher potency against high K⁺ compared to CCh-mediated contractions with respective EC₅₀ values of 0.84 mg/mL (0.82–0.96; n = 5) 14.46 mg/mL (12.24–16.38, n = 4). The PDE-inhibitory action of fenchone was further confirmed when its pre-incubation at 3 and 5 mg/mL potentiated and shifted the isoprenaline inhibitory CRCs towards the left, similar to papaverine, whereas the Ca²⁺ inhibitory-like action of fenchone pretreated tracheal tissues were authenticated by the rightward shift of Ca²⁺ CRCs with suppression of maximum response, similar to verapamil, a standard Ca²⁺ channel blocker. Fenchone showed a spasmolytic effect in isolated trachea mediated predominantly by K⁺ channel activation followed by dual inhibition of PDE and Ca²⁺ channels. Further in silico molecular docking studies provided the insight for binding of fenchone with Ca²⁺ channel (−5.3 kcal/mol) and K⁺ channel (−5.7), which also endorsed the idea of dual inhibition.     

5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis

TASK channels belong to the two-pore-domain potassium (K_2P) channels subfamily. These channels modulate cellular excitability, input resistance, and response to synaptic stimulation. TASK-channel inhibition led to membrane depolarization. TASK-3 is expressed in different cancer cell types and neurons. Thus, the discovery of novel TASK-3 inhibitors makes these bioactive compounds very appealing to explore new cancer and neurological therapies. TASK-3 channel blockers are very limited to date, and only a few heterofused compounds have been reported in the literature. In this article, we combined a pharmacophore hypothesis with molecular docking to address for the first time the rational design, synthesis, and evaluation of 5-(indol-2-yl)pyrazolo[3,4-b]pyridines as a novel family of human TASK-3 channel blockers. Representative compounds of the synthesized library were assessed against TASK-3 using Fluorometric imaging plate reader—Membrane Potential assay (FMP). Inhibitory properties were validated using two-electrode voltage-clamp (TEVC) methods. We identified one active hit compound (MM-3b) with our systematic pipeline, exhibiting an IC₅₀ ≈ 30 μM. Molecular docking models suggest that compound MM-3b binds to TASK-3 at the bottom of the selectivity filter in the central cavity, similar to other described TASK-3 blockers such as A1899 and PK-THPP. Our in silico and experimental studies provide a new tool to predict and design novel TASK-3 channel blockers.     

Angle-dependent terahertz time-domain spectroscopy of amino acid single crystals

The measurement of absorption spectra using angle-dependent terahertz (THz) time-domain spectroscopy for amino acid single crystals of l-cysteine and l-histidine is reported for the first time. Linearly polarized THz radiation enables us to observe angle-dependent far-infrared absorption spectra of amino acid single crystals and determine the direction of the oscillating dipole of the molecules in the 20-100 cm(-1) range. By comparing the THz spectra of a single crystal and powder, we found that there was a clear hydrogen-bond peak in the crystal spectrum as a result of the larger hydrogen-bond network. The low-temperature THz spectra of amino acid microcrystals showed more intermolecular vibrational modes than those measured at room temperature. An ab initio frequency calculation of a single amino acid molecule was used to predict the intramolecular vibrational modes. The validity of the calculation models was confirmed by comparing the results with experimentally obtained data in the Raman spectral region.     

Charge carrier mobility in poly[methyl(phenyl)silylene] studied by time-resolved terahertz spectroscopy and molecular modelling

Time-resolved terahertz spectroscopy and combination of quantum chemistry modeling and molecular dynamics simulations were used for the determination of charge carrier mobility in poly[methyl(phenyl)silylene]. Using time-resolved THz spectroscopy we established the on-chain charge carrier drift mobility in PMPSi as 0.02 cm(2) V(-1) s(-1). This value is low due to the formation of polarons: the hole is self-trapped in a potential formed by local chain distortion and the transient THz conductivity spectra show signatures of its oscillations within this potential well. This view is supported by the agreement between experimental and calculated values of the on-chain charge carrier mobility.     

Terahertz absorption spectra of some saccharides and their metal complexes

In this work, THz absorption spectra of some saccharides and their metal complexes were measured. The main purpose of this work is to investigate the M-O vibrations, intermolecular and intramolecular hydrogen bonds and other vibrations in the FIR region using powerful spectroscopic techniques adopting the metal-sugar complexes prepared in our laboratory. The M-O vibrations in the FIR spectra of metal-sugar complexes indicate the formation of metal complexes. The THz spectrum of glucose below 100cm(-1) was measured at first to confirm the THz experimental method. Characteristic absorption bands in the spectra of various samples are observed. THz spectra of saccharides below 100cm(-1) often have several absorption bands, and different saccharides have various absorption peaks in the THz region, which may be used to distinguish different saccharides. The differences in the number of bands observed are related to different structures of the samples, and these absorption bands are related to the collective motion of molecules. But the THz spectra of their metal complexes are different from the ligands, and no band appears in the region below 50cm(-1) at the present experimental condition, which indicates that THz spectroscopy may also be helpful to identify the formation of metal-sugar complexes, and the changes after complexation in the THz spectra below 100cm(-1) may be related to different metal ions. The metal-sugar complexes with similar crystal structures resemble mid-IR spectra, but their THz spectra may have some differences.     

Coffee varietal differentiation based on near infrared spectroscopy

Near infrared spectroscopy (NIRS) was used to discriminate between arabica and robusta pure coffee varieties and blends of varied varietal composition. Direct orthogonal signal correction (DOSC) pre-processing method was applied on a set of 191 roasted coffee NIR spectra from both pure varieties and blends varying the final robusta content from 0 to 60% (w/w) in order to remove information unrelated to the actual varietal composition of samples. The corrected NIR spectra, as well as raw NIR spectra, were used to develop separate classification models using the potential functions method as class-modelling technique, exploring several options more or less restrictive according to the final number of considered categories. All constructed classification models were compared to evaluate their respective qualities and to show the suitability of applying DOSC method as pre-processing step for developing improved classification models for coffee varietal identification purposes.     

Ion Hydration and Ion Pairing as Probed by THz Spectroscopy

Ion hydration is of pivotal importance for many fundamental processes. Various spectroscopic methods are used to study the retardation of the hydration bond dynamics in the vicinity of anions and cations. Here we introduce THz‐FTIR spectroscopy as a powerful method to answer the open questions. We show through dissection of THz spectra that we can pinpoint characteristic absorption features that can be attributed to the rattling modes of strongly hydrating ions within their hydration cages as well as vibrationally induced charge fluctuations in the case of weakly hydrating ions. Further analysis yields information on anion–cation cooperativity, the size of the dynamic hydration shell, as well as the lifetimes of these collective ion‐hydration water modes and their connecting thermal bath states. Our study provides evidence for a non‐additive behavior, thus questioning the simplified Hofmeister model. THz spectroscopy enables ion pairing to be observed and quantified at a high salt concentration.     

Spatial confinement alters the ultrafast photoisomerization dynamics of azobenzenes

Ultrafast transient absorption spectroscopy reveals new excited-state dynamics following excitation of trans-azobenzene (t-Az) and several alkyl-substituted t-Az derivatives encapsulated in a water-soluble supramolecular host–guest complex. Encapsulation increases the excited-state lifetimes and alters the yields of the trans → cis photoisomerization reaction compared with solution. Kinetic modeling of the transient spectra for unsubstituted t-Az following nπ* and ππ* excitation reveals steric trapping of excited-state species, as well as an adiabatic excited-state trans → cis isomerization pathway for confined molecules that is not observed in solution. Analysis of the transient spectra following ππ* excitation for a series of 4-alkyl and 4,4′-dialkyl substituted t-Az molecules suggests that additional crowding due to lengthening of the alkyl tails results in deeper trapping of the excited-state species, including distorted trans and cis structures. The variation of the dynamics due to crowding in the confined environment provides new evidence to explain the violation of Kasha''s rule for nπ* and ππ* excitation of azobenzenes based on competition between in-plane inversion and out-of-plane rotation channels.

Ultrafast transient absorption spectroscopy reveals new excited-state dynamics following excitation of trans-azobenzene (t-Az) and several alkyl-substituted t-Az derivatives encapsulated in a water-soluble supramolecular host–guest complex.     

Low-frequency vibrational modes of dl-homocysteic acid and related compounds

In this paper several polycrystalline molecules with sulfonate groups and some of their metal complexes, including dl-homocysteic acid (DLH) and its Sr- and Cu-complexes, pyridine-3-sulphonic acid and its Co- and Ni-complexes, sulfanilic acid and l-cysteic acid were investigated using THz time-domain methods at room temperature. The results of THz absorption spectra show that the molecules have characteristic bands in the region of 0.2–2.7 THz (6–90 cm⁻¹). THz technique can be used to distinguish different molecules with sulfonate groups and to determine the bonding of metal ions and the changes of hydrogen bond networks. In the THz region DLH has three bands: 1.61, 1.93 and 2.02 THz; and 0.85, 1.23 and 1.73 THz for Sr-DLH complex, 1.94 THz for Cu-DLH complex, respectively. The absorption bands of pyridine-3-sulphonic acid are located at 0.81, 1.66 and 2.34 THz; the bands at 0.96, 1.70 and 2.38 THz for its Co-complex, 0.76, 1.26 and 1.87 THz for its Ni-complex. Sulphanilic acid has three bands: 0.97, 1.46 and 2.05 THz; and the absorption bands of l-cysteic acid are at 0.82, 1.62, 1.87 and 2.07 THz, respectively. The THz absorption spectra after complexation are different from the ligands, which indicate the bonding of metal ions and the changes of hydrogen bond networks. M–O and other vibrations appear in the FIR region for those metal–ligand complexes. The bands in the THz region were assigned to the rocking, torsion, rotation, wagging and other modes of different groups in the molecules. Preliminary assignments of the bands were carried out using Gaussian program calculation.     

Solid-state density functional theory investigation of the terahertz spectra of the structural isomers 1,2-dicyanobenzene and 1,3-dicyanobenzene

The high-resolution waveguide terahertz (THz) time-domain spectra (20-100 cm(-1)) of the two structural isomers 1,2-dicyanobenzene (1,2-DCB) and 1,3-dicyanobenzene (1,3-DCB) have been modeled and assigned using solid-state density functional theory. The THz spectra of these similar molecules are distinctly different in the low-frequency region with the differences being driven by modifications of the crystal packing arrangement between the isomers. Simulations utilizing the hybrid density functionals B3LYP and PBE0 were performed to determine the origins of the observed vibrational features. External lattice vibrations (hindered translations and rotations) are found to dominate these spectra, reinforcing the need for proper solid-state models in the analysis of the THz spectra of organic molecular solids. These calculations were able to account for all of the observed spectral features exhibited by both isomers, even in the case of 1,2-DCB, where the spectrum was found to be the result of two coexisting crystalline polymorphs.     

β-丙氨酸的THz时域光谱研究

运用THz时域光谱测试技术(THz-TDS)与理论模拟相结合的方法, 研究了β-丙氨酸在THz波段的光谱特性. 在室温氮气环境中, 得到了样品在0.2～2.4 THz波段的吸收谱和折射率谱, 表明其特征吸收峰位于2.11 THz处, 平均折射率为1.96. 同时利用Gaussian 03软件的半经验理论计算了该分子在0.1～10.0 THz的振动吸收谱, 其在0.2～2.4 THz波段的吸收峰与实验相互对应, 且峰位符合较好. 研究了分子低频的振动模式, 并给出了分子的构象参数.     

Substituent Effects on the Low-Frequency Vibrational Modes of Benzoic Acid and Related Compounds

Well-resolved absorption spectra of benzoic acid and its derivatives with one hydrogen atom replaced by a substituent group CH3, OH, NH2 or NO2 were reported in the frequency region between 6 and 67 cm^-1 at room temperature with terahertz time-domain spectroscopy （THz-TDS）. These substances can be distinguished easily based on the terahertz absorption spectra. The measurements suggested that even minor changes in the molecular configuration and chemical composition lead to distinct differences in THz spectrum. Density functional theory （DFT） method was used to assist the analysis and assignment of the individual THz absorption spectra of benzoic acid and its methyl derivatives. Observed THz responses of samples can be assigned to the collective vibrations associated with intermolecular hydrogen bonds.     

Terahertz time-domain spectroscopy of imidazolium ionic liquids

We have measured the terahertz (THz) complex dielectric spectra of imidazolium ionic liquids by THz time-domain spectroscopy (THz-TDS) in the frequency range from 5 (0.15 THz) to 140 cm(-1) (4.2 THz). The ionic liquids investigated are 1-ethyl-3-methylimidazolium (EMIm+)/trifluoromethanesulfonate (TfO-), EMIm+/tetrafluoroborate (BF(4)-), 1-butyl-3-methylimidazolium (BMIm+)/TfO-, and BMIm+/BF(4)-. The dielectric values of the ionic liquids in the THz region are similar to those of short-chain alcohols. The THz dielectric values are related to subpicosecond-to-picosecond dynamics. The same trend has been observed in the empirical polarity ET(30) although it is related to the static characteristics of polarity and hydrogen bonding ability. A difference between the two types of liquids is observed in the THz dielectric spectral shapes: the ionic liquids show structured lineshapes but short-chain alcohols show much less structured ones. The structured lineshapes of the ionic liquids reflect the low-frequency motions of interion and/or intramolecular vibrations. When the ionic liquids composed of the different imidazolium cations contain the same anions as counterions, their density-normalized THz dielectric spectra above 20 cm(-1) bear strong resemblance to each other in shape and magnitude. It shows clearly that the THz spectra do not originate from the intramolecular vibrations of the imodazolium cations. All of the intramolecular vibrations of the anions are located above 140 cm(-1) except the CF3-SO3 torsion of TfO-, the band of which alone cannot explain the broad THz dielectric spectra of the ionic liquids. Therefore, we conclude that the interion vibrations rather than the intramolecular vibrations dominantly contribute to the THz dielectric spectra. The results strongly indicate that even in the liquid phase the ionic liquids have local structures similar to their solid-phase structures.     

Terahertz Time-Domain Spectroscopy of Naphthalene and Naphthols

Low-energy vibrational modes have been investigated in polycrystalline naphthalene and its derivatives naphthols using terahertz time-domain spectroscopy (THz-TDS) over the frequency range from 17 to 73 cm^–1 (0.5–2.2 THz) at room temperature. We propose that naphthalene and naphthols show spectral features originating from intermolecular vibrational modes. Because of the collective origin of the observed modes, the absorption spectra are highly sensitive to the overall structure and configuration of the molecules, as well as their environments. For light-sensitive materials, the THz-TDS procedure can avoid effects like photobleaching.     

Tracking Structural Evolution during Symmetry-Breaking Charge Separation in Quadrupolar Perylene Bisimide with Time-Resolved Impulsive Stimulated Raman Spectroscopy

Elucidating structural roles in photoinduced charge transfer is indispensable, as nuclear rearrangements are simultaneously usually involved in the dynamics. However, it is hard to evaluate whether the structural changes occur or not by using conventional time-resolved electronic spectroscopy. Here, time-resolved impulsive stimulated Raman spectroscopy is applied to record the evolution of vibrational snapshots during charge-separation dynamics of donor–acceptor–donor-type quadrupolar perylene bisimide in real time. Drastic frequency shifts were observed for several Raman bands with their population kinetics, thus symmetry-breaking charge separation accompanies significant structural changes, as supported by (TD)-DFT calculations. A comparison between time-resolved Raman spectra of the neutral S₁ state and the radical anion species shows that the spectral signatures, especially in high-frequency regions, provide important clues to bond length alternation patterns in the PBI core.     

Coherent vibrational dynamics of Au144(SR)60 nanoclusters

The coherent vibrational dynamics of gold nanoclusters (NCs) provides important information on the coupling between vibrations and electrons as well as their mechanical properties, which is critical for understanding the evolution from a metallic state to a molecular state with diminishing size. Coherent vibrations have been widely explored in small-sized atomically precise gold NCs, while it remains a challenge to observe them in large-sized gold NCs. In this work, we report the coherent vibrational dynamics of atomically precise Au₁₄₄(SR)₆₀ NCs via temperature-dependent femtosecond transient absorption (TA) spectroscopy. The population dynamics of Au₁₄₄(SR)₆₀ consists of three relaxation processes: internal conversion, core–shell charge transfer and relaxation to the ground state. After removing the population dynamics from the TA kinetics, fast Fourier transform analysis on the residual oscillation reveals distinct vibrational modes at 1.5 THz (50 cm⁻¹) and 2 THz (67 cm⁻¹), which arise from the wavepacket motions along the ground-state and excited-state potential energy surfaces (PES), respectively. These results are helpful for understanding the physical properties of gold nanostructures with a threshold size that lies in between those of molecular-like NCs and metallic-state nanoparticles.

The coherent vibrational dynamics of Au₁₄₄(SR)₆₀ nanoclusters was revealed by temperature-dependent ultrafast transient absorption spectroscopy. Both excited-state and ground-state wavepacket motions contribute to the vibrational coherence.