2D NMR Spectroscopy Research Articles

Sustainable synthesis of cyclic carbonates from CO2 using zinc adeninium bromide as a biorenewable catalyst

The design of green catalysts for CO2 utilization purposes is considered a great challenge and a motivation for a sustainable future. In this work, a first-time zinc adeninium bromide (Zn-AHBr) was synthesized and fully characterized using far and mid ATR-FTIR, 1D and 2D NMR spectroscopy, including 1H, 13C and [1H,15N] correlation spectroscopy (HMBC/HSQC), cyclic voltammetry and further supported with theoretical calculations involving energetics using Density functional theory (DFT). The Zn-AHBr was exploited as an unprecedented biorenewable, sustainable catalyst for CO2/epoxide coupling at ambient reaction conditions (1 atm, 80 °C over 8 to 16 h) with quantitative conversion of epichlorohydrin, epibromohydrin, glycidol, glycidyl ether, and 1,2-epoxy-3-phenoxypropane. Moreover, other Zn-AHX (X: Cl and I) showed excellent up to quantitative conversions toward epichlorohydrin cycloaddition. Furthermore, a plausible mechanism for the cycloaddition reaction was investigated using DFT calculations which indicated a relatively low activation energy (1.1 kcal.mol−1) for the epoxide ring opening, and a much higher value (9.4 kcal.mol−1) for the cyclic carbonate ring closure as a rate determining step for the reaction.

Six sesquiterpenoids from the stems and leaves of Chrysanthemum morifolium Ramat and their anti-asthma activities

Six previously undescribed sesquiterpenoids, chrysanthterpenoids H-M (1–6), were isolated from the stem and leaves of Chrysanthemum morifolium Ramat. Structure elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. Furthermore, computational prediction of ECD was used to propose the absolute configurations of the compounds. All compounds were evaluated for their anti-asthma effects on RBL-2H3 cells in vitro. The results showed that Compounds 2 and 3 significantly inhibited the release of β-aminohexosidase and improved RBL-2H3 degranulation by chromogenic substrate and high-content imaging. These results suggest that Compounds 2 and 3 may exhibit anti-asthma activities.

Application of 2D NMR Spectroscopy in Combination with Chemometric Tools for Classification of Natural Lignins.

Lignin is considered a promising renewable source of valuable chemical compounds and a feedstock for the production of various materials. Its suitability for certain directions of processing is determined by the chemical structure of its macromolecules. Its formation depends on botanical origin, isolation procedure and other factors. Due to the complexity of the chemical composition, revealing the structural differences between lignins of various origins is a challenging task and requires the use of the most informative methods for obtaining and processing data. In the present study, a combination of two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy and multivariate analysis of heteronuclear single quantum coherence (HSQC) spectra is proposed. Principal component analysis and hierarchical cluster analysis techniques demonstrated the possibility to effectively classify lignins at the level of belonging to classes and families of plants, and in some cases individual species, with an error rate for data classification of 2.3%. The reverse transformation of loading plots into the corresponding HSQC loading spectra allowed for structural information to be obtained about the latent components of lignins and their structural fragments (biomarkers) responsible for certain differences. As a result of the analysis of 34 coniferous, deciduous, and herbaceous lignins, 10 groups of key substructures were established. In addition to syringyl, guaiacyl, and p-hydroxyphenyl monomeric units, they include various terminal substructures: dihydroconiferyl alcohol, balanopholin, cinnamic acids, and tricin. It was shown that, in some cases, the substructures formed during the partial destruction of biopolymer macromolecules also have a significant effect on the classification of lignins of various origins.

Efficient determination of scalar coupling networks by band selective decoupled 2D NMR spectroscopy

Scalar (J) couplings constitute one of vital features observed in NMR spectroscopy and show valuable information for molecular structure elucidation and conformation analysis. However, existing J coupling measurement techniques are generally confined by the concerns of resolution, SNR, and experimental efficiency. Herein, we exploit an efficient 2D NMR protocol to deal with the above concerns by enabling rapid, sensitive, and high-resolution J coupling extraction. This protocol delivers full-resolved pure shift 2D absorption-mode spectroscopy to gain great convenience for efficient coupling measurements on overcrowded NMR signals. Resulting from band selective signal evolution, this protocol ensures high signal intensity with full magnetization preservation to meet the demand on probing low-concentration samples. This protocol focuses on accessing coupling information between specific two coupled spin families, and it is not applicable to all possible spin systems. Besides, it adopts echo-train selective refocusing acquisition to accelerate pure shift 2D J-edited implementations into pseudo-2D acquisition, and thus holding the experimental efficiency similar to conventional SERF experiments. Therefore, this study presents a promising tool for efficient extraction of J coupling networks, and takes an important step for coupling measurement techniques with wide applications on molecular conformation elucidation and stereochemical configuration analysis.

N-acetyldopamine oligomers from Periplaneta americana with anti-inflammatory and vasorelaxant effects and their spatial distribution visualized by mass spectrometry imaging

Ethnopharmacological relevancePeriplaneta americana is a medicinal insect that has been applied to promote blood circulation and remove blood stasis based on traditional Chinese medicine (TCM) for a long time. Its modern preparation, Xinmailong injection, was adopted for the treatment of congestive heart failure (CHF). The bioactive constituents of P. americana and their correlation with its traditional uses need further investigation. Aim of the studyThis study aimed to elucidate the N-acetyldopamine (NADA) oligomers from P. american, determine their spatial distribution, and investigate their anti-inflammatory and vasorelaxant effects to provide scientific evidence supporting the clinical use of this medicinal insect. Material and methodsNADA oligomers were isolated from the CH2Cl2: CH3OH (2:1) extract of P. americana, through sequential chromatographic methods including silica gel, Sephadex LH-20, preparative HPLC, and chiral-phase separation. Their structures were determined by HRESIMS, 1D and 2D NMR spectroscopic analysis, chiral resolution, and calculated electronic circular dichroism analysis. With the aid of atmospheric pressure scanning matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI), the isolated compounds in a spatial profile within P. americana were identified. NO production was measured to assess anti-inflammatory activity. Vasorelaxant activity assessments were performed on the norepinephrine-precontracted 3rd-order mesenteric arteries. ResultsSeven new NADA trimers, peridopamines A−G (1−7), two new NADA dimers, peridopamines H and I (8 and 9), and six known NADA derivatives (10−15), were obtained from P. americana. The trimers and dimers were detected and showed similar pattern of distribution with accumulation in peripheral and rigid parts of P. americana, based on quasimolecular ion AP-SMALDI MS images of sections from the whole body and dissected areas of the insect. Furthermore, the anti-inflammatory and vasorelaxant effects of isolated compounds were investigated. Compounds 8 and 9 presented significant and moderate anti-inflammatory potentials, respectively. Compounds 8, 10, 12 and 15 possess significant vasorelaxant potentials at concentrations correlated with EC50 values of 6.7–23.7 μM. ConclusionFifteen NADA oligomers were isolated from P. americana. The distribution of these compounds was visualized by AP-SMALDI imaging experiments and NADA oligomers were mainly observed in peripheral parts. Bioassays showed that the tested compounds had anti-inflammatory and vasorelaxant activities, which indicated that NADA oligomers are active ingredients of this insect-based TCM and have potential for the treatment of cardiovascular disease.

Catalytic Alkyne Semihydrogenation with Polyhydride Ni/Ga Clusters.

The bimetallic, decanuclear Ni3 Ga7 -cluster of the formula [Ni3 (GaTMP)3 (μ2 -GaTMP)3 (μ3 -GaTMP)] (1, TMP=2,2,6,6-tetramethylpiperidinyl) reacts reversibly with dihydrogen under the formation of a series of (poly-)hydride clusters 2. Low-temperature 2D NMR experiments at -80 °C show that 2 consist of a mixture of a di- (2Di ), tetra- (2Tetra ) and hexahydride species (2Hexa ). The structures of 2Di and 2Tetra are assessed by a combination of 2D NMR spectroscopy and DFT calculations. The cooperation of both metals is essential for the high hydrogen uptake of the cluster. Polyhydrides 2 are catalytically active in the semihydrogenation of 4-octyne to 4-octene with good selectivity. The example is the first of its kind and conceptually relates properties of molecular, atom-precise transition metal/main group metal clusters to the respective solid-state phase in catalysis.

New Janus Tricyclic Laddersiloxanes: Synthesis, Characterization, and Reactivity.

The synthesis of four novel syn-type tricyclic laddersiloxanes bearing eight or six alkenyl groups is presented. These compounds possess reactive alkenyl groups on both the bridged and side silicon atoms, and their structures were determined through characterization using multinuclear 1D and 2D NMR spectroscopy, mass spectrometry, and elemental analysis techniques. To investigate their reactivity, the compounds were subjected to hydrosilylation using two different silanes, and the resulting fully hydrosilylated compounds were thoroughly analyzed. Remarkably, all the synthesized laddersiloxanes displayed high thermal stability, suggesting their potential as promising precursors for the development of new hybrid materials. Additionally, preliminary findings indicate the possibility of exploiting the reactivity difference between the alkenyl groups attached to the D- and T-unit silicon atoms for the synthesis of Janus molecules. These findings highlight the potential of the reported compounds as valuable building blocks in the construction of innovative materials.

Chemical constituents from the aerial parts of Launaea sarmentosa (Asteraceae)

The phytochemical investigation of the aerial parts of Launaea sarmentosa (LS) led to the isolation of two new compounds (2 and 11) along with 14 known compounds (1, 3–10, and 12–16). The structures of these compounds were determined through 1D and 2D-NMR spectroscopic analysis, MS, electron circular dichroism spectra calculations, and comparison with published spectroscopic data. The isolated compounds include methyl pyroglutamate (1), sarmentosin A (2), caffeic acid (3), ferulic acid (4), umbelliferon (5), esculetin (6), α-conidendrin (7), apigenin (8), luteolin (9), quercetin (10), sarmentosin B (11), cynaroside (12), luteolin 7-O-rutinoside (13), rutin (14), lupeol (15), and β-sitosterol (16). Compounds 1 and 7 were isolated from the Launaea genus for the first time, while compounds 3–6, 8, 10, and 12–16 were reported for the first time in this species.

Solution structure of the N-terminal extension domain of a Schistosoma japonicum asparaginyl-tRNA synthetase

Several secreted proteins from helminths (parasitic worms) have been shown to have immunomodulatory activities. Asparaginyl-tRNA synthetases are abundantly secreted in the filarial nematode Brugia malayi (BmAsnRS) and the parasitic flatworm Schistosoma japonicum (SjAsnRS), indicating a possible immune function. The suggestion is supported by BmAsnRS alleviating disease symptoms in a T-cell transfer mouse model of colitis. This immunomodulatory function is potentially related to an N-terminal extension domain present in eukaryotic AsnRS proteins but few structure/function studies have been done on this domain. Here we have determined the three-dimensional solution structure of the N-terminal extension domain of SjAsnRS. A protein containing the 114 N-terminal amino acids of SjAsnRS was recombinantly expressed with isotopic labelling to allow structure determination using 3D NMR spectroscopy, and analysis of dynamics using NMR relaxation experiments. Structural comparisons of the N-terminal extension domain of SjAsnRS with filarial and human homologues highlight a high degree of variability in the β-hairpin region of these eukaryotic N-AsnRS proteins, but similarities in the disorder of the C-terminal regions. Limitations in PrDOS-based intrinsically disordered region (IDR) model predictions were also evident in this comparison. Empirical structural data such as that presented in our study for N-SjAsnRS will enhance the prediction of sequence-homology based structure modelling and prediction of IDRs in the future. Communicated by Ramaswamy H. Sarma

Sn(IV)-corroles reversibly bind carboxylates in the axial position

We present the synthesis of Sn(IV)-corrole complexes that bind to carboxylate moieties reversibly, via axial ligation. The systems have been predominantly characterized using 1H NMR spectroscopy, X-ray crystallography, and MALDI mass spectrometry. The dynamic nature of the Sn(IV)−O2CR bond has been studied in solution using 2D-NMR spectroscopy.

Paraflexinols A−G, rare flexibilane-based diterpenoids from the soft coral Paralemnalia thyrsoides

Seven undescribed diterpenoids paraflexinols A–G (1–7), possessing a fifteen-membered macrocyclic ring, have been isolated from the ethyl acetate extract of the soft coral Paralemnalia thyrosides. The structures of 1–7 have been established by the detailed spectroscopic analysis, including 2D NMR spectroscopy, while their absolute configurations were determined using a modified Mosher's method for 1–3, 6, and 7. For over four decades after the first discovery of the ancestor of these compounds flexibilene (8) from the soft coral Sinularia flexibilis until the current report, no flexibilane-based diterpenoids had been isolated or identified. This study provides detailed NMR data for metabolites of this type for the first time.

Quinoxaline-derived “turn-off” fluorescent sensor for the selective detection of Fe3+: Synthesis, spectroscopic analysis, BSA binding and computational studies

A simple quinoxaline-based “turn-off” fluorescent sensor 12-{[1-(4-isopropylphenyl)-1H-1,2,3-triazol-5-yl]methyl}c-12H-benzo[5,6][1,4]thiazino[2,3-b]quinoxaline (BTQT) was synthesised and characterised by various spectroscopic technique including FT-IR, 1D, 2D NMR and mass spectrometry. DFT-based studies have been employed to calculate reactivity descriptor-associated with the molecular structure. UV–visible absorption and fluorescence spectral studies revealed a selective “turn-off” fluorescent response towards Fe3+ with a detection limit of 3.5 µM and a response time of 5 s. Job's plot and mass spectrum establish 1:1 binidng stoichiometry between Fe3+ and BTQT. Spectral studies revealed a static mode of BTQT binding with bovine serum albumin accompanied by hydrogen bonding and weak van der Waals force of interactions. The experimental results of BSA binding were further supported by in silico studies and are in good corroboration with the experimental findings. Such a convenient and simple methodology could impart an auspicious tool for rapid, selective and sensitive analysis of Fe3+ and BSA.

A novel skeleton alkaloid from Portulaca oleracea L. and its bioactivities

A novel skeleton alkaloid was obtained from Portulaca oleracea L., which was identified as 10,11-dihydroxybenzo[5′,6′] pentaleno[1′,2′:3,4]pyrrolo[2,1-b]oxazol-7(11bH)-one, named oleracone M, and its structure was determined using UHPLC-ESI-QTOF/MS, 1D NMR and 2D NMR spectroscopy, and circular dichroism. Then the bioactivities of the compound were investigated including the anti-inflammatory, anti-acetylcholinesterase and antioxidant activities. The results showed that the novel skeleton alkaloid exhibited the potent effect on inhibiting the secretion of IL-1β at 10 μM, anticholinesterase activity with IC50 value of 49.58 μM, and antioxidant activity with IC50 value of 66.43 μM.

Hericioic Acids A-G and Hericiofuranoic Acid; Neurotrophic Agents from Cultures of the European Mushroom Hericium flagellum.

Neurodegenerative diseases are currently posing huge social, economic, and healthcare burdens among the aged populations worldwide with few and only palliative treatment alternatives available. Natural products continue to be a source of a vast array of potent neurotrophic molecules that could be considered as drug design starting points. The present study reports eight new isoindolinone and benzofuranone derivatives, for which we propose the trivial names, hericioic acids A-G (1-7) and hericiofuranoic acid (8), which were isolated from a solid culture (using rice as substrate) of the rare European edible mushroom Hericium flagellum. The chemical structures of these compounds were determined based on extensive 1D and 2D NMR spectroscopy along with HRESIMS analyses. The isolated compounds were assessed for their neurotrophic activity in rat pheochromocytoma cells (PC-12) to promote neurite outgrowth on 5 ng NGF supplementation; all the compounds increased neurite outgrowths, with compounds 3, 4, and 8 exhibiting the strongest effects.

Structural characterisation and pH-dependent preference of pyrrole cross-link isoforms from reactions of oxoenal with cysteine and lysine side chains as model systems.

In this study, we subjected 5,5-diethoxy-4-oxopent-2-enal (DOPE), a model amino acids cross-linking reagent, to reactions with N-acetylcysteine (Ac-Cys) and Nα-acetyllysine (Ac-Lys), and identified three pyrrole cross-links. The compounds were isolated and their structures were rigorously determined by spectrometric and spectroscopic methods, including 2D NMR experiments. The use of 2D NMR spectroscopy was crucial to determine the position of the substituents in the pyrrole rings. The products were identified as 2,4-, 2,3-, and 2,5-substituted pyrroles. The data obtained from their structural characterisation can help similar studies on amino acids modifications induced by analogous bifunctional carbonyl compounds. Our results show that the study of pathways in which model electrophiles modify amino acids may be helpful for similar studies dealing with identification of structural changes in cysteine- and lysine-containing proteins associated with oxidative stress.

Novel compounds of Djulis (Chenopodium formosanum Koidz) increases collagen, antioxidants, inhibits adipogenesis

Djulis (Chenopodium formosanum Koidz), is rich in nutrients and contains various bioactive components such as polyphenols and alkaloids. The new compound has a broad application prospect, including food additives, health products, drugs, etc. The purpose of this study was to find out new compounds from Djulis. It was found that 24 compounds including 7 phenols, 11 flavonoids, 4 plant alkaloids, 2 sterols. Among those, TCI-CF-22-S (Methyl 3,6-dihydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate), TCI-CF-23-S (Methyl 6-hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate), TCI-CF-24-S (Kaempferol-3-O-b-D-apifuranosyl-(1→2)-a-L-arabinopyranoside) were isolated from djulis sources for the first time, and the structures of compounds were assigned by 1D, 2D NMR spectroscopy. TCI-CF-01(Caffeic acid), TCI-CF-02 (20-Hydroxyecdysone), TCI-CF-03 (Japonicone), TCI-CF-04 (3,4-Dihydroxyphenylacetiate), TCI-CF-05 (Quercetin-3-O-rutinoside-7-O-rhamnopyranoside), TCI-CF-06 (Guanosine), TCI-CF-07(Adenine), TCI-CF-08 (Coumaric acid) increased collagen production, and TCI-CF-03 (Japonicone), TCI-CF-04 (3,4-Dihydroxyphenylacetiate), TCI-CF-06 (Guanosine), TCI-CF-17 (Rutin), TCI-CF-20 (Protocatechuic acid) decreased advanced glycation end products (AGEs). In addition, TCI-CF-22-S (Methyl 6-hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate), TCI-CF-23-S (Methyl 3,6-dihydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate) inhibited the formation of fatty oil droplets. Djulis has 24 compounds that may have various applications, including increasing collagen production and reducing advanced glycation end products and fatty oil droplets.

Bioactive fatty acids from non-conventional lipid sources and their potential application in functional food development.

There is growing evidence that bioactive fatty acids (BFAs), including eicosapentaenoic acid (EPA; 20:5-3), docosahexaenoic acid (DHA; 22:6-3), and conjugated fatty acids offer multiple biological benefits and constitute ingredients in functional food development. Despite their potential, novel and alternative/nonconventional sources with unique bioactive properties to meet growing demand remain largely unexplored, poorly characterized, and their effects are not well understood. We systematically reviewed the literature to identify studies on alternative sources of BFAs, their functions, extraction, and application in the food and nutraceutical industry. Twenty studies delved into alternate sources such as plants, bacteria, and algae. Six studies found EPA and DHA as the dominant FA in algal sources, while ten studies reported several BFAs from plant sources. Five studies assessed the health benefits of docosapentaenoic acid (DPA), arachidonic acid (ARA), EPA, γ-linolenic acid (GLA), and linoleic acid (LA). Eleven studies compared the quality of oil recovered by green solvents, pressurized liquid, supercritical fluid, and assisted extraction methods.Three studies assessed the effects of assisted extraction methods and reported that these approaches improved oil yield and quality, but the findings may have limited applicability to other lipid sources. The quality of nonconventional lipids largely depends on extraction techniques. Four studies suggested methods like 1D and 2D NMR spectroscopy, LC-MS/MS; however, their analytical differencesmake accurate comparison inadequate. Five studies found that the incorporation of algal and seafood biolipids during product development increased EHA and DHA contents.

Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate.

Malaria is one of the major life-threatening health problems worldwide. Artesunate is the most potent antimalarial drug to combat severe malaria. However, development of drug resistance, short plasma half-life, and poor bioavailability limit the efficacy of this drug. Here, we applied the dimerization concept to synthesize dimeric artesunate glycerol monocaprylate conjugate (D-AS-GC) by conjugating artesunate (AS) with glycerol monocaprylate (GC) via esterification reaction. D-AS-GC conjugate, AS, and GC were well characterized by 1H NMR, attached proton test (APT) 13C NMR and 2D NMR spectroscopy. D-AS-GC conjugate was further analyzed by ESI-TOF MS. Finally, a series of nanoemulsion preconcentrate (F1-F6) of D-AS-GC was prepared by mixing different ratios of oil and surfactant/cosurfactant and evaluated after dilution with an aqueous phase. The optimized formulation (F6) exhibits a clear nanoemulsion and the hydrodynamic diameter of the dispersed phase was determined by DLS and DOSY NMR spectroscopy. The morphology of the nanoemulsion droplets of F6 was investigated by AFM, which revealed the formation of tiny nanoemulsion droplets on a hydrophilic mica substrate. Moreover, using a less polar silicon wafer led to the formation of larger droplets with a spherical core shell-like structure. Overall, the rational design of the dimeric artesunate-based nanoemulsion preconcentrate could potentially be used in more efficient drug delivery systems.

Structural characterization of exopolysaccharide from Leuconostoc mesenteroides P35 and its binding interaction with bovine serum albumin using surface plasmon resonance biosensor

This paper describes the structural elucidation of Leuconostoc mesenteroides P35 exopolysaccharide (EPS-LM). Ln. mesenteroides P35 strain was isolated from a French goat cheese for its capacity to produce EPS increasing the viscosity of a whey-based fermentation medium. The chemical structure of EPS-LM analysis was elucidated by determination of optical rotation degree, macromolecular characterization, sugar units and methylation analyses, FT-IR, 1D NMR spectroscopy (1H and 13C NMR), 2D NMR spectroscopy (1H1H COSY, HSQC and HMBC). EPS-LM was a high molecular weight (ranging from 6.7 × 106 Da to 9.9 × 106 Da) dextran that is composed of only d-glucose units containing α (1 → 6) linkages and paltry α (1 → 3) branches. Since polysaccharide-protein interactions can be exploited to control and design food matrices, EPS-LM interactions with bovine serum albumin (the main constituent of bovine plasma) were investigated by surface plasmon resonance (SPR). Kinetic properties of EPS-LM binding with immobilized BSA via showed an increase of EPS-LM affinity (equilibrium constant (Kd)) for BSA from (2.50 ± 0.01) × 10−5 M−1 at 298 K to (9.21 ± 0.05) × 10−6 M−1 at to 310 K. The thermodynamic parameters revealed that van der Waals and hydrogen binding forces play a major role in the interaction of EPS-LM with BSA. However, EPS-LM-BSA interaction was non-spontaneous, entropy driven and an EPS-LM - BSA binding process was endothermic (ΔG > 0). The structural findings suggested that Ln. mesenteroides P35 α-D-glucan might find widespread technological applications in the biopolymer, medical and food industries.

The sesquiterpenes with the COVID-19 Mpro inhibitory activity from the Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded four new sesquiterpenes including a novel skeleton (claroguaiane A, 1), two guaianolides (claroguaianes B–C, 2–3), and one eudesmanolide (claroeudesmane A, 4), together with three known sesquiterpenoids (5–7). The structures of the new compounds were elucidated by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitive activity of COVID-19 Mpro. As a result, compound 5 showed moderate activity with an IC50 value of 36.81 μM and compound 6 exhibited a potent inhibitory effect with an IC50 value of 16.58 µM, while other compounds were devoid of noticeable activity (IC50 > 50 μM).