2D NMR Spectroscopy Research Articles

Intramolecular Pericyclic Re-hydroboration via Six-membered Transition State: Synthesis of Fused Borolo[3,2-b]siloles.

We experimentally demonstrate a new type of the intramolecular reaction between non-activated alkyne units and the dialkylboryl group (9-BBN), which was previously only hypothesized and studied on a calculational level. The reaction described here can formally be classified as a 1,2-hydroboration reaction, but, in contrast to the classical mechanism via a cyclic four-membered transition state, the reaction proceeds by a pericyclic mechanism involving a six-membered transition state. In practice, the reaction allows the synthesis of a new class of the borolenes fused with silole or dihydrosilole units. Thus, the heating (125°C) of 2,3-dihydrosiloles or 2,3-dihydrosilolo[2,3-b]silole bearing 9-BBN and propargyl or dimethylpropargyl groups in positions 4 and 5, respectively, affords, in high to moderate yields, di- and tricyclic compounds containing a borolo[3,2-b]silole unit. In all cases, the reactions are accompanied by an unprecedented dehydroboration of the 9-BBN fragment, leading, in the final products, to a cyclooct-4-enyl group on the boron atom. The effects of the substituents on the rate and the selectivity of the reaction are discussed. The structures of all the new compounds have been determined from HRMS together with multinuclear 1D and 2D NMR spectroscopy, the results of which are in excellent agreement with DFT calculated chemical shifts.

Structure-aided function assignment to the transcriptomic conopeptide Am931

Implementation of the next-generation technologies for gene sequencing of venom duct transcriptome has provided a large number of peptide sequences of marine cone snails. Emerging technologies on computational platforms are now rapidly evolving for the accurate predictions of the 3D structure of the polypeptide using the primary sequence. The current report aims to integrate the information derived from these two technologies to develop the concept of structure-aided function assignment of Conus peptides. The proof of the concept was demonstrated using the transcriptomic peptide Am931 of C. amadis. The 3D structure of Am931 was computed using Density Functional Theory (DFT) and the quality of the predicted structure was confirmed using 2D NMR spectroscopy of the corresponding synthetic peptide. The computed structure of Am931 aligns with the active site motif of thioredoxins, possess catalytic disulfide conformation of (+, −)AntiRHHook and selectively modulate the N-terminal Cys3 thiol. These structural features indicate that Am931 may act as a disulfide isomerase and modulate the oxidative folding of conotoxins. Synthetic peptide Am931 provides proof-of-function by exhibiting catalytic activity on the oxidative folding of α-conotoxin ImI and improving the yield of native globular fold. The approach of integration of new technologies in the Conus peptide research may help to accelerate the discovery pipeline of new/improved conotoxin functional.

Phenolic Constituents, Photoprotective Effect, and Antioxidant Capacities of Achillea ligustica All.

The present investigation was performed to figure out the chemical constituents and biological potential of polar extracts (AcOEt and BuOH) from Achillea ligustica, a medicinal species of the Asteraceae family. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) was utilized to conduct a preliminary analysis of the phytochemical profiles of the AcOEt and BuOH extracts. The analysis revealed the existence of twenty compounds in the AcOEt extract and twenty-two in the BuOH extract, classified into various types of secondary metabolites. Subsequently, the exudate from the plant yielded five flavonoids, including two 6-methoxyflavonols identified for the first time in this genus. The isolation of compounds from AcOEt and BuOH extracts was achieved through the combined use of column chromatography (silica gel and Sephadex LH-20) and preparative TLC chromatography. The structures have been elucidated using 1D and 2D NMR spectroscopy, alongside comparisons with research data. Our study measured the total phenolic and flavonoid contents and carried out a comprehensive range of antioxidant tests using DPPH, GOR, CUPRAC, reducing power, and O-phenanthroline assays. Both extracts exhibited considerable antioxidant potential and contained high levels of phenolic and flavonoid compounds. The photoprotective effect of the AcOEt and BuOH extracts was evaluated in vitro by measuring the sun protection factor. Both extracts exhibited a high capacity for UV radiation absorption. Consequently, this plant presents an intriguing prospect for future research focused on incorporating it into photoprotective cosmetic products and pharmaceutical formulations.

Urea-lactic acid as efficient lignin solvent and its practical utility in sustainable electrospinning

The development of lignin-based materials presents a promising avenue for advancing green chemistry and mitigating environmental impact. However, the key challenge lies in the processability of lignin, which significantly affects its practical applications. Addressing the issues related to lignin's complex structure, variability, and reactivity is crucial for optimizing its incorporation into high-performance materials. Therefore, in this study we explore the efficacy of a urea-lactic acid-based deep eutectic solvent (ULA) for the dissolution of kraft lignin, aiming to enhance its practical utility in sustainable electrospinning processes, for the first time. Results of elemental analysis, IR and 2D NMR spectroscopy, provide crucial insights into the structural properties of the regenerated material post-DES treatment. The findings confirm a high lignin recovery rate, reaching up to 96.6 % for samples dissolved at 100°C. Additionally, 2D NMR analysis indicates that the process leads to partial esterification of lignin with lactate ions. The ability of the studied DES to effectively solubilize lignin underscores its potential as an efficient lignin solvent and facilitates the fabrication of lignin-based nanofibers via electrospinning. The incorporation of this DES in electrospinning processes promises significant advancements in the development of sustainable, lignin-derived materials and offers a green alternative for production of high-performance nanofibers. Preliminary results of electrochemical impedance spectroscopy and galvanostatic charge/discharge measurements confirm that the EDLC with prepared hydrogel electrolyte demonstrates attractive electrochemical properties (specific capacitance, CSP = 95 F g–1; series resistance RS = 2.2 Ω; charge transfer resistance, RCT = 1.6 Ω), which are comparable with the reference cell based on a commercial glass fibre separator. Hence, the DES-assisted-electrospinned lignin membrane can be viewed as a potential gel electrolyte matrix for practical use in construction of sustainable energy storage devices.

Fruits from Rosa roxburghii: A Valuable Bioresource of Potent Radical Scavengers and Novel Ursane-Type Triterpenoids.

Four new ursane-type triterpenoids named rosaroxine A-D and 21 known compounds were identified from Rosa roxburghii fruits. The structures of all compounds were established by 1D and 2D NMR spectroscopy and mass spectrometry. The phenolics catechin (EC50 13.4 μM), quercetin (13.1 μM), gallic acid (10.0 μM), and protocatechuic acid (15.2 μM) were identified as powerful in vitro antioxidants with EC50 values lower than ascorbic acid (31.3 μM). The triterpenoids rosaroxine C (EC50 37.4; 40.3 μM) and 2-oxo-pomolic acid (16.6; 28.2) and the phenolics catechin (53.3; 29.0), quercetin (18.8; 33.1), and gallic acid (26.3; 40.0) exerted partly higher activities in the cyclo-oxygenase (COX 1/2) assay than the positive control acetaminophen (EC50 45.0; >100 μM). The triterpenoids rosaroxine C and 2-oxo-pomolic acid also performed well in the anti-aging assay using HaCaT cells. Quantification of the bioactive compounds by LC-MS revealed concentrations of 3.08 mg kg-1 rosaroxine C, 17.40 mg kg-1 2-oxo-pomolic acid, 76.29 mg kg-1 catechin, and 5.58 mg kg-1 protocatechuic acid in the dried fruits. Overall, this work provides detailed phytochemical information, and the results from the accomplished bioassay point toward health promoting properties of these fruits.

8-(2-Methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of the Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D and 2D NMR spectroscopy, IR spectroscopy, high-resolution mass spectrometry and X-ray analysis.

Ent-Kaurane diterpenoids from Isodon henryi and their anti-inflammatory activities

Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C–K (1–9). Compounds 1–6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2–6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 μM, respectively.

Nuciferol C, a new sesquineolignan dimer from Cocos nucifera L.: bioactivity and theoretical investigation.

Nuciferol C (NC), an undescribed dimer of nuciferol B (NB), was isolated from the endocarp of Cocos nucifera L. The planar structure of NC was determined using 1D- and 2D-NMR spectroscopy as well as high resolution MS spectrometry. The absolute configuration was concluded based on analysis of NOESY spectra. NC showed cytotoxic activity against colon cancer cells (CaCo-2) with an IC50 value of 76 μM, and significantly decreased the expression of human epidermal growth factor receptor (EGFR) and tumor necrosis factor alpha (TNF-α) in CaCo-2 as compared with untreated cells by 39% and 33%, respectively (p < 0.05). In addition, NC exhibited anti-herpes simplex virus (HSV-I) activity with an IC50 value of 23 μM. In silico study of NC was implemented at three levels: density functional theory (DFT) was used to study its electronic properties, molecular mechanics was used to estimate the docking results, and finally, molecular dynamic simulation was used to study the behavior and stability of NC inside the active site of the target protein of HSV-1.

Diels-Alder Cycloaddition of 2,5-Bis(hydroxymethyl)furan (BHMF) and N-Phenylmaleimide Derivatives.

Currently, amidst atmospheric menace where natural calamities such as wildfire and floods are becoming more frequent than ever, biobased derivatives offer a sustainable alternative to conventional ways, for instance, petrochemical commodities. Biobased products, obtained from agricultural waste, including 5-(hydroxymethyl)furfural (HMF), 2,5-bis(hydroxymethyl)furan (BHMF), and 2,5-furandicarboxylic acid (FDCA) are promising chemical platforms in the biorefinery, which is yet to be explored. The Diels-Alder cycloaddition of BHMF and N-phenylmaleimide derivatives under optimal reaction conditions is investigated in this report. First, HMF is reduced to BHMF in the presence of NaBH4, and then the Diels-Alder reaction of BHMF and N-phenylmaleimide derivatives is investigated to produce Diels-Alder adducts. All novel compounds are synthesized in acceptable yields and effectively characterized by employing important techniques such as one-dimensional (1D) NMR spectroscopy (1H, 13C, DEPT-90, and DEPT- 135), two-dimensional (2D) NMR spectroscopy (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC), IR spectroscopy, elemental analysis, mass spectrum (QTOF), and single-crystal X-ray diffraction (SC-XRD). Furthermore, this study underlines the necessity of sustainable synthetic methodologies and gives critical insights into the progress of ecologically friendly methodologies, providing a new avenue as a tunable precursor for the challenging functionalized polymer in the future.

Chemical Composition, Antioxidant and Anti-Inflammatory Activity of Shiitake Mushrooms (Lentinus edodes).

Shiitake mushrooms (Lentinus edodes) are renowned as the "King of mountain treasures" in China due to their abundant nutritional and health-enhancing properties. Intensive chemical investigations of the fruiting bodies and mycelium of Shiitake mushrooms (Lentinus edodes) afforded five new compounds (1-5), named lentinmacrocycles A-C and lentincoumarins A-B, along with fifteen known compounds (6-20). Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, including one-and two-dimensional (1D and 2D) NMR spectroscopy, circular dichroism (CD), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The anti-inflammatory activity test showed that lentincoumarins A (4), (3S)-7-hydroxymellein (9), (3R)-6-hydroxymellein (11) and succinic acid (18) exhibited strong NO inhibitory effects (IC50 < 35 μM), and that (3S)-5-hydroxymellein (10) and (3R)-6-hydroxymellein (11) exhibited potent TNF-α inhibitory effects (IC50 < 80 μM) and were more potent than the positive control, Indomethacin (IC50 = 88.5 ± 2.1 μM). The antioxidant activity test showed that (3R)-6-hydroxymellein (11) had better DPPH radical scavenging activity (IC50 = 25.2 ± 0.5 μM).

A coumarin containing hemicyanine-based probe for dual channel detection of cyanide ion

Cyanide(CN−) is known as one of the most toxic inorganic anions and is harmful to the environment and human health. Its wide use and severe toxicity have led to the development of highly selective cyanide detection, and quantification is desirable. A coumarin-containing hemicyanine-based probe has been developed for highly selective colorimetric and fluorometric detection of cyanide in acetonitrile and aqueous medium. The probe was characterized by 1D NMR (1H and 13C) and HRMS Spectroscopy, and the sensing properties have been studied in colorimetric and fluorometric methods. The high selectivity of the probe for CN− was established by UV–vis and fluorescence spectroscopy in the presence of other competing anions. The probe can detect cyanide as low as 0.7 μM within 90 s. A remarkable change in spectroscopic properties has been observed upon adding cyanide ion. The weakly luminescent probe emitted strongly upon the reaction with CN− which is due to the inhibition of internal charge transfer (ICT) from coumarin to indolinium moiety. Furthermore, the colour change from yellow to colourless and the appearance of a blue luminescence, which can be observed by the naked eye, provides a simple real-time method for cyanide detection, also supported by 1H NMR titration and theoretical study. Furthermore, a paper strip kit loaded with probe has been constructed for a real-time application of CN detection without any interference from other competitive analytes.

Synthesis of 1,2,3-triazole functionalized derivatives of metronidazole as potent inhibitors of urease: Synthesis via click chemistry, in vitro urease inhibition, kinetics and molecular docking studies

Current study is based on multistep synthesis of sixteen new 1,2,3-triazole functionalized derivatives of metronidazole drug 3–18 by using a Cu(I)-catalysed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) reaction via a click chemistry approach. All the compounds were purified by using conventional silica gel column chromatography with isocratic eluent. Their structures were confirmed by using various spectroscopic techniques including UV, IR, LR and HR MS, 1H-, 13CNMR , and 2D-NMR spectroscopy. The library of 1,2,3-triazole derivatives of metronidazole 3–18 was evaluated for urease inhibitory activity, and cytotoxicity against normal cells. Compound 8 (IC50= 6.8 ± 0.8 µM) was found to be the most potent urease inhibitor, while acetohydroxamic acid (IC50 = 20.3 ± 0.4 µM) was used as experimental standard. Compounds 5 (IC50 = 7.9 ± 0.9 µM), 6 (IC50 = 9.5 ± 0.2 µM), 7 (IC50 = 8.5 ± 1.0 µM), 10 (IC50 = 9.3 ± 1.1 µM), and 18 (IC50 = 7.2 ± 0.6 µM) were also found to be potent inhibitors of urease. Parent drug metronidazole also showed a potent urease enzyme inhibitory activity with IC50= 10.54 ± 0.8 µM. All compounds were found to be non-cytotoxic against the human fibroblast (B.J.) cell line. Molecular docking and kinetic studies were performed for compounds 5–8, 10, and 18 which showed that these compounds are competitive inhibitors of urease enzyme inhibition. Urease inhibition is a therapeutic approach to help in the treatment of peptic ulcers, caused by ureolytic bacteria. The initial findings presented herein therefore, deserve further studies.

Bioactive alkaloids from Nepalese Corydalis chaerophylla D.C. acting on the regulation of PCSK9 and LDL-R in vitro.

Four new alkaloids Chaeronepaline-A (1), Chaeronepaline-B (2), Chaeronepaline-C (3), and Chaeronepaline-D (4) were isolated from Corydalis chaerophylla D.C. collected from Nepal and their structures were elucidated by spectroscopic data, 1D, 2D NMR and mass spectrometry. The structures were established as 3,12- Dimethoxy-5,6-dihydroisoquinolino [2,1-b] isoquinolin- 7- ium- 2, 9- diol (1), 7-methyl-5, 6, 7, 8-tetrahydroisoquinoline- 2, 3- methylenedioxy- (8-> 9)- 10, 12- methylenedioxy- benzoic-16-acid (2), 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline (3) and 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline-N-oxide (4). The new alkaloids were tested in human hepatoma cell line to assess their ability to modulate the expression of low-density lipoprotein receptor (LDL-R), of proprotein convertase subtilisin/kexin 9 (PCSK9) and to affect cellular cholesterol biosynthesis with the aim to evaluate their potential hypocholesterolemic effect. Results indicated that compounds 2 and 3 upregulate the LDLR, and inhibited the cholesterol biosynthesis with compound 2, which also reduced the secretion of PCSK9 by Huh7 cells. These in vitro data indicated a potential hypocholesterolemic effect of compound 2 that requires further in vivo validation.

Eight new dammarane-type triterpenoid saponins from Gynostemma pentaphyllum

Phytochemical investigation of Gynostemma pentaphyllum led to the purification of five novel dammarane-type triterpene isolates, gypenosides B1 − B5 (1–5). Their structures were determined through comprehensive 1D and 2D NMR spectroscopic analyses and HRESIMS data. Of note, 1–3 are inseparable mixtures of epimers due to their unstable nature, and a total of eight dammarane-type triterpene saponins were identified. Additionally, the protective activities of these new compounds against PC12 cell injury induced by hypoxia were evaluated.

Modeling Ligand Exchange Kinetics in Iridium Complexes Catalyzing SABRE Nuclear Spin Hyperpolarization.

Large signal enhancements can be obtained for NMR analytes using the process of nuclear spin hyperpolarization. Organometallic complexes that bind parahydrogen can themselves become hyperpolarized. Moreover, if parahydrogen and a to-be-hyperpolarized analyte undergo chemical exchange with the organometallic complex it is possible to catalytically sensitize the detection of the analyte via hyperpolarization transfer through spin-spin coupling in this organometallic complex. This process is called Signal Amplification By Reversible Exchange (SABRE). Signal intensity gains of several orders of magnitude can thus be created for various compounds in seconds. The chemical exchange processes play a defining role in controlling the efficiency of SABRE because the lifetime of the complex must match the spin-spin couplings. Here, we show how analyte dissociation rates in the key model substrates pyridine (the simplest six-membered heterocycle), 4-aminopyridine (a drug), and nicotinamide (an essential vitamin biomolecule) can be examined. This is achieved for the most widely employed SABRE motif that is based on IrIMes-derived catalysts by 1H 1D and 2D exchange NMR spectroscopy techniques. Several kinetic models are evaluated for their accuracy and simplicity. By incorporating variable temperature analysis, the data yields key enthalpies and entropies of activation that are critical for understanding the underlying SABRE catalyst properties and subsequently optimizing behavior through rational chemical design. While several studies of chemical exchange in SABRE have been reported, this work also aims to establish a toolkit on how to quantify chemical exchange in SABRE and ensure that data can be compared reliably.

Isolation and biological activity of six new polyketide and terpenoid derivatives from Neopestalotiopsis Clavispora AL01

A fungus strain, Neopestalotiopsis clavispora AL01, was isolated from the leaf spot of the plant Phoenix dactylifera. Further chemical investigation of the fermentation extract of this strain afforded six new secondary metabolites (1–6), along with 11 known compounds (7–17) which included a new natural compound (7). Their structures were determined by extensive spectroscopic analysis including one-and two-dimensional (1D and 2D) NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and ECD and NMR calculations. All compounds were evaluated for their phytotoxic activities. Among them, compounds 10, 12 and 13 exhibited phytotoxic activities against Nicotiana tabacum. Compound 3 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus, Micrococcus luteus and Vibrio harveyi. Taken collectively, these findings establish a solid research foundation for future investigations on bioactive natural products derived from phytopathogenic fungi.

Dactylfungins and Tetralones: Bioactive Metabolites from a Nematode-Associated Laburnicola nematophila.

A chemical investigation of Laburnicola nematophila, isolated from cysts of the plant parasitic nematode Heterodera filipjevi, affored three dactylfungin derivatives (1-3) and three tetralone congeners (4-6). Dactylfungin C (1), laburnicolin (4), and laburnicolenone (5) are previously undescribed natural products. Chemical structures of the isolated compounds were determined based on 1D and 2D NMR spectroscopic analyses together with HR-ESI-MS spectrometry and comparison with data reported in the literature. The relative configurations of compounds 1, 2, and 4-6 were determined based on their ROESY data and analysis of their coupling constants (J values). The absolute configurations of 4-6 were determined through the comparison of their measured and calculated TDDFT-ECD spectra. Compounds 1-3 were active against azole-resistant Aspergillus fumigatus.

Myxaoside A, a new triterpenoid saponin from Cordia myxa L. (Boraginaceae)

The phytochemical study of Cordia myxa L. led to the isolation, through chromatographic techniques, of a new triterpenoid saponin, 3-O-[α-L-rhamnopyranosyl-(1→3)-(6-O-acetyl-β-D-glucopyranosyl)]-22β-hydroxyolean-12-ene (3) namely Myxaoside A, together with three known compounds, Soyasaponine I (1), oleanolic acid (2), and 3-O-acetyl-oleanolic acid (4). All structures were established, based on 1 & 2D-NMR spectroscopic analysis and comparison with previous published reports. Compound 1-4 were evaluated for their antibacterial activity on various strains of bacteria including Salmonella typhi, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Vibrio cholerae. It appears that compounds 1 and 3 were active on all the tested microbial species, while compounds 2 and 4, shown no significant effect on S. aureus and K. pneumoniae at low concentrations 6.5 mg/mL and 3.0 mg/mL.

Crystal structure of the cytotoxic macrocyclic trichothecene Isororidin A.

The highly cytotoxic macrocyclic trichothecene Isororidin A (C29H40O9) was isolated from the fungus Myrothesium verrucaria endophytic on the wild medicinal plant `Datura' (Datura stramonium L.) and was characterized by one- (1D) and two-dimensional (2D) NMR spectroscopy. The three-dimensional structure of Isororidin A has been confirmed by X-ray crystallography at 0.81 Å resolution from crystals grown in the orthorhombic space group P212121, with one molecule per asymmetric unit. Isororidin A is the epimer of previously described (by X-ray crystallography) Roridin A at position C-13' of the macrocyclic ring.

Two new diterpenoid alkaloids from the roots of Aconitum nagarum and their cytotoxic activity

A chemical investigation on the roots of Aconitum nagarum afforded two undescribed C19-diterpenoid alkaloids nagarumines D and E (1 and 2). The structures of the new compounds were elucidated by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, as well as HR-ESI-MS. The two isolated alkaloids were tested in vitro for cytotoxic activity against five gastric tumor cell lines. Consequently, compound 2 exhibited some cytotoxicities against several human cancer cell lines with IC50 value less than 20.0 μM.