Analysis Of NMR Spectra Research Articles

NMR Screen Reveals the Diverse Structural Landscape of a G-Quadruplex Library.

G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanosine tetrads. Despite their functional and structural diversity, a single consensus model is typically used to describe sequences with the potential to form G-quadruplex structures. We are interested in developing more specific sequence models for G-quadruplexes. In previous work, we functionally characterized each sequence in a 496-member library of variants of a monomeric reference G-quadruplex for the ability to bind GTP, promote a model peroxidase reaction, generate intrinsic fluorescence, and to form multimers. Here we used NMR to obtain a broad overview of the structural features of this library. After determining the 1H NMR spectrum of each of these 496 sequences, spectra were sorted into multiple classes, most of which could be rationalized based on mutational patterns in the primary sequence. A more detailed screen using representative sequences provided additional information about spectral classes, and confirmed that the classes determined based on analysis of 1H NMR spectra are correlated with functional categories identified in previous studies. These results provide new insights into the surprising structural diversity of this library. They also show how NMR can be used to identify classes of sequences with distinct mutational signatures and functions.

Combining the Strengths of MS and NMR in Biochemometrics: A Case Study on Buddleja officinalis.

Biochemometrics has emerged as promising strategy for the targeted identification of bioactive constituents from natural sources. It is based on the correlation of bioactivity data with chemical data to reveal constituents contributing to activity. Providing complementary data and structural information, MS- and NMR-based biochemometric approaches have both been separately applied in the past. The herein presented study is dedicated to the evaluation of a combined MS- and NMR-based biochemometric workflow for the unambiguous identification of bioactives. As an example, a flower extract of Buddleja officinalis Maxim. was selected to unravel bioactive constituents in the context of dry eye disease pathology. While NMR-based biochemometrics relies on heterocovariance analysis (HetCA) of 1H NMR spectra using the previously established ELINA approach, a biochemometric molecular network was generated for the MS-based approach. Both analyses were performed in parallel and were ultimately combined to increase their power to identify the bioactive constituents from the complex mixture. As a result, phenylethanoid glycosides and triterpene saponins were discovered as main contributors for the antioxidant and cytotoxic effects of the extract. This article illustrates the advantages, opportunities, and limitations of MS and NMR in the context of biochemometrics.

Twisted Amide-Mediated Peptide Synthesis.

A robust, practical, and sustainable isomerization-suppressed peptide bond formation via acyl sulfonamide, a twisted amide, is disclosed. Tosyl isocyanate and pentafluorobenzyl bromide were applied in combination to activate the peptide C-terminus, which then reacted with an amine to yield an elongated peptide with high stereochemical purity. Careful analysis of NMR spectra of the active intermediate revealed the presence of an intramolecular hydrogen bond, suggesting that the hydrogen bond suppressed Cα-epimerization during amidation. The isomerization suppression by the intramolecular hydrogen bond is expected to be effective even under high dilution conditions, making the present method a powerful tool for the synthesis of complex macrocyclic peptides. In addition to peptide synthesis, the developed synthetic entry to twisted amides can be applied to the investigation of transition metal-catalyzed N-C bond activation. Moreover, the application to the N-C bond activation returned insight into peptide synthesis, leading to the use of sulfonamide as a protecting group of carboxylic acid that can be orthogonally removed in the presence of other conventional protecting groups.

Synthesis, Docking, and Dynamic Studies of New Pyrano‐[3,2‐e]‐Pyrazole Fused 1,2,4‐Triazolo‐[4,3‐c]‐pyrimidine Analogues as Anticancer Agents

AbstractA novel series of dihydropyrazolo‐[4′,3′:5,6]‐pyrano[3,2‐e][1,2,4]triazolo[4,3‐c]‐pyrimidine analogues were designed, synthesized, and their cytotoxic potential against four tumor cell lines assessed. HRMS, 1H NMR, and 13C NMR spectra analysis were used to describe the novel compounds. Compound 9c had noteworthy anticancer activity in vitro against the Hela, MCF‐7, A549, and A2780 cell lines, with IC50 values of 0.98 ± 0.26, 3.11 ± 0.18, 1.24 ± 0.88, and 2.62 ± 0.56 µM, in that order. The molecular docking and dynamics simulation studies revealed the lead molecule's action mechanism with EGFR target protein.

Synthesis, spectroscopic, computational, topology, and molecular docking studies on N,N'-(4-methyl-1,3-phenylene)bis(1-(2,4-dichlorophenyl)methanimine)

The study extensively examined N,N'-(4-methyl-1,3-phenylene)bis(1-(2,4-dichlorophenyl)methanimine) (6D). Advanced spectroscopic techniques, including IR, Raman, NMR, and UV-VIS spectroscopies, were employed to analyse the molecule. The Schiff base was ultimately confirmed using NMR spectrum analysis. The UV-VIS study revealed a notable bathochromic change in the compound, indicating their electronic transitions. By using the HOMO–LUMO bond gap the titled compound reactivity sites were identified. The compound 6D HOMO–LUMO band gap is 3.70 eV. Various wave function investigations like MESP, HOMO–LUMO, RDG, ELF, LOL, and ALIE were conducted to elucidate the distribution of electronic charge, providing valuable insights into the behaviour of molecules. The biological probability of the synthesised compound was extensively assessed using a docking study. Using MEP and HOMO–LUMO investigations, we confirm nucleophilic and electrophilic attacking sites. In the docking study, the protein Bovine cytochrome bc1 complex stigma Tellin bound (PDB ID–1PP9) was downloaded. The docking study identified the most stable minimum binding energy is –6.26 kcal/mol.

Assessment of Conjugation Pathways in N-Methylporphyrins that Are Fused to Acenaphthylene, Phenanthrene, or Pyrene: Evidence for the Presence of Alternative Aromatic Circuits.

Acenaphtho-, phenanthro-, and pyrenopyrrole esters, readily available from Barton-Zard reactions of ethyl isocyanoacetate with nitroarenes, were reacted with methyl iodide and KOH in DMSO to give N-methylpyrroles and subsequent cleavage of the ester moieties was accomplished with KOH in ethylene glycol at 200 °C. Condensation with two equiv of an acetoxymethylpyrrole in refluxing acetic acid-2-propanol afforded a series of annulated tripyrranes. Cleavage of the terminal tert-butyl ester groups with trifluoroacetic acid, followed by condensation with a diformylpyrrole and oxidation with FeCl3, gave N-methyl acenaphtho-, phenanthro-, and pyrenoporphyrins. The N-methyl substituent effectively freezes the tautomeric equilibria to maximize interactions between the porphyrin nucleus and the fused aromatic substructures. Analysis of the proton NMR spectra provides evidence of the presence of extended aromatic circuits within these structures. Anisotropy of induced ring current (AICD) plots clearly shows the presence of 30π electron pathways in phenanthro- and pyrenoporphyrins that run around the exterior of the benzenoid fragments. These results demonstrate that N-alkylation can be used to relocate aromatic pathways in porphyrinoid systems.

Advance Screening of Bis- Azetidinone Derivatives: Synthesis, Spectroscopy, Antioxidant and Antimicrobial Analysis with Molecular Docking Assessment

Introduction: This study includes synthesis, characterizations, antimicrobial, antiox-idant, and docking molecular study of novel Bis-Azetidinone compounds that combined two units of β-lactam rings .In the present investigation, the aromatic aldehydes with primary amine were condensed to create Schiff's base, which was then reacted with chloroacetylchloride to pro-duce bis-Azetidinone compounds. Methods: Melting points, FTIR, and NMR spectrum analyses were used to examine the mor-phological and topological characteristics of the Bis-Azetidinone compounds. The results indi-cate that the prepared Compounds synthesis has excellent antimicrobial activity against both Gram-negative (Escherichia coli,), Gram-positive bacteria (Staphylococcus aureus) and fungal (Candida albicans) and also indicated that the Compounds synthesis (A2) gave a higher antimi-crobial effect than the B2, C2. The synergistic activity was examined against the pathogenic microbial strains. It was observed that employing compound synthesis combined with antibiot-ics enhanced the synergistic efficacy compared to using compound synthesis alone or antibiotic alone on Gram-positive bacteria and fungi. Results: The antioxidant efficiency was assessed by DPPH, the results show that the compound synthesis has antioxidant activity, and also indicated that the synthesized compound (A2) gave a higher antioxidant effect than the B2, C2. Docking study confirmed via redocking of crystal-ized substrate or inhibitor within target binding pocket. The docking results reveal that the syn-thesized compounds, with a total binding affinity of less than -48 kcal/mol, could be clinically used for future therapeutic purposes. Conclusion: The present research demonstrates the advantageous effectiveness of a simpler pro-duction procedure, novel Bis-Azetidinone compounds, for producing high-purity with low haz-ard that may be utilized as future possible medical therapies.

Neural net analysis of NMR spectra from strongly-coupled spin systems

Extracting parameters such as chemical shifts and coupling constants from proton NMR spectra is often a first step in using spectra for compound identification and structure determination. This can become challenging when scalar couplings between protons are comparable in size to chemical shift differences (strongly coupled), as is often the case with low-field (bench top) spectrometers. Here we explore the potential utility of AI methods, in particular neural networks, for extracting parameters from low-field spectra. Rather than seeking large experimental sets of spectra for training a network, we chose quantum mechanical simulation of sets, something that is possible with modern software packages and computer resources. We show that application of a network trained on 2-D J-resolved spectra and applied to a spectrum of iduronic acid, shows some promise, but also meets with some obstacles. We suggest that these may be overcome with improved pulse sequences and more extensive simulations.

DBN-based molecular solvents for highly efficient and reversible CO2 capture

Reducing greenhouse gas emissions is a crucial step in mitigating global warming. Carbon dioxide (CO2) represents one of the most pivotal greenhouse gases contributing to climate change. Many researchers are actively engaged in the development of effective and reversible CO2 absorbents to control and reduce CO2 gas emissions. In this paper, we synthesized a series of molecular solvents (MSs) based on the superbase 1,5-diazabicyclo [4.3.0]-5-nonene (DBN) and used them for CO2 capture. The CO2 capture capacity of MSs composed of DBN and different alcohols was systematically investigated, with DBN-Methanol (1:1.25) demonstrating superior absorption performance by achieving a maximum absorption capacity of 0.263 g CO2/g MS. The effects of temperature, pressure, the molar ratio of the hydrogen bond acceptor (HBA) to hydrogen bond donor (HBD), and moisture on the absorption process were studied. The experimental results were corroborated by NMR spectra analysis and FTIR spectra analysis, confirming that these MSs can effectively react with CO2 to produce carbonate and carbamate compounds through synergistic absorption involving hydroxyl group as primary component and amino group as secondary component. In addition, it is worth noting that the MSs studied in this work exhibit only glass transition at low temperatures and transform into ionic liquids (ILs) after capturing CO2, resulting in a significant increase in conductivity and demonstrating considerable electrochemical potential.

Reactivity of Strontium Hydride Supported by the Superbulky Hydrotris(pyrazolyl)borate Ligand.

Hydrogenolysis of [(TpAd,iPr)Sr{CH(SiMe3)2}] (1) (TpAd,iPr = hydrotris(3-adamantyl-5-isopropyl-pyrazolyl)borate) in hexane solution under 20 atm of H2 allowed for the isolation of strontium hydride [(TpAd,iPr)Sr(μ-H)]2 (2) in good yield. Complex 2 exhibits the dimeric nature in solid state, featuring two different bond modes between the Sr center and TpAd,iPr ligand. Treatment of complex 2 with PhC(H)═NtBu or PhCH2Bpin (Bpin = pinacolateborane) afforded the strontium amide complex [(TpAd,iPr)Sr{N(CH2Ph)(tBu)}] (4) and hydroborate complex [(TpAd,iPr)Sr{μ-HBpin(CH2Ph)}] (5), respectively. Reactions of complex 2 with 2-picoline, 2-phenylquinoline, or 2-phenylpyridine led to the formation of strontium 2-pyridylmethylene/2-picoline complex [(TpAd,iPr)Sr(2-CH2-Py)(2-picoline)] (6), reductively coupling diphenyl-biquinolide complex [{(TpAd,iPr)Sr}2(2,2'-Ph2-4,4'-dihydro-4,4'-biquinolide)] (7), and diphenyl-bipyridyl radical complex [(TpAd,iPr)Sr(6,6'-Ph2-2,2'-bipyridyl)] (8), separately. All of the complexes have been well characterized, including NMR spectrum and single-crystal X-ray analysis.

Albusamides A-G: Hydroxylated Fatty Amine Derivatives from the Deep-Sea-Derived Actinomycete Streptomyces albus 228DD-066 and Their Cytotoxic Activity.

A series of new hydroxylated fatty amine derivatives, albusamides A-G (1-7), along with four known compounds (8-11), which are reported for the first time from a natural source, were isolated from the culture broth of Streptomyces albus 228DD-066 derived from a deep-sea sediment sample gathered off the coast of Dokdo Island, Republic of Korea. Their structures were elucidated through the comprehensive analysis of 1D and 2D NMR spectra and HRESIMS, and absolute configurations were determined using the modified Mosher's method. Biological evaluations against solid and blood cancer cell lines revealed that these new metabolites have moderate to strong cytotoxic activity. Compound 3 exhibited high cytotoxic activity with GI50 values ranging from 0.4 to 0.6 μM against solid cancer cell lines and exhibited the strongest cytotoxicity (GI50 value = 0.2 μM) against the WSU-DLCL2 blood cancer cell line.

Pleiotropically activation of azaphilone biosynthesis by overexpressing a pathway-specific transcription factor in marine-derived Aspergillus terreus RA2905

The genome sequencing of Aspergillus terreus reveals that the vast number of predicted biosynthetic gene clusters have not reflected by the metabolic profile observed under conventional culture conditions. In this study, a silent azaphilone biosynthetic gene cluster was activated by overexpressing a pathway-specific transcription factor gene2642 in marine-derived fungus A. terreus RA2905. Consequently, twenty azaphilone compounds were identified from the OE2642 mutant, including 11 new azaphilones and their precursors, azasperones C−J (1−5, 7−9) and preazasperones A−C (15−17). The structures of those new compounds were unambiguously determined on the basis of NMR and HRESIMS spectra analysis, and the absolute configurations were established depending on ECD calculations. Compounds 1 and 2 were the rarely reported naturally occurring azaphilones with 2-N coupled phenyl-derivative. The bioactivity assay revealed that compounds 18−20 exhibited significant anti-inflammatory activity. Based on the occurrence of diverse intermediates and the putative gene functions, a plausible biosynthetic pathway of these compounds was proposed. The above results demonstrated that overexpression of the pathway-specific transcription factor presents a promising approach for enriching fungal secondary metabolites and accelerating the targeted discovery of novel biosynthetic products.

Heterologous Biosynthesis of New Lanthipeptides Nocardiopeptins with an Unprecedented Bridging Pattern of Lanthionine and Labionin.

The class III lanthipeptide synthetase (LanKC) installs unusual amino acids, such as lanthionine and labionin, in lanthipeptides. Through genome mining, we discovered a new class III lanthipeptide synthetase coding gene (nptKC) and precursor peptide coding genes (nptA1, nptA2, and nptA3) in the genome of the actinobacterium Nocardiopsis alba. Coexpression experiments of the biosynthetic genes in Escherichia coli resulted in the production of new lanthipeptides named nocardiopeptins A1-A3. Analysis of two-dimensional NMR spectra after enzymatic degradation and partial basic hydrolysis of nocardiopeptin A2 revealed that labionin was located in lanthionine with opposite orientations, forming a nesting structure in nocardiopeptin A2. To the best of our knowledge, this bridging pattern in the lanthipeptides was unprecedented, indicating a novel reaction characteristic of the class III lanthipeptide synthetase NptKC.

Design, Synthesis, and Evaluation of Quinoline‐1,2,3‐Triazole Hybrids as CYP51 Inhibitors: In Silico Study and In Vitro Antimicrobial Assessment

AbstractNovel Quinoline‐triazole hybrid derivatives (9 a–9 l) were designed and synthesized via click reaction methodology to develop lead compounds with good antibacterial and antifungal potency. Synthetic compounds have been characterized using 1H NMR, 13C NMR, and mass spectrum analysis. In‐vitro antibacterial activity against two gram‐positive and two gram‐negative strains and in‐vitro antifungal activity against three different strains were performed for the synthesized compounds. Compounds 9 a, 9 d, and 9 i exhibited potent inhibition activity against S. aureus ranging from MIC=12.5–50 μg/mL, and compounds 9 a, 9 c, 9 d, 9 e, 9 f, 9 j, and 9 l exhibited potent inhibition activity against C. albicans fungal strains ranging from MFC=250–500 μg/mL. Molecular docking study of C. albicans Sterol 14α‐demethylase (CYP51) protein (PDB ID:5TZ1) and S. aureus tyrosyl‐tRNA synthetase (PDB ID: 1JIJ) was performed to understand the mechanism of action through which these derivatives work. In silico studies of Hybrid 9 d demonstrated strong hydrogen bonding and π–π interactions with Tyr64, Phe233, and Phe228 in line with the co‐crystals SB‐239629 and VT1161 exhibiting favorable interactions that inhibits both bacterial and fungal strains.

Okeaniazole A: Thiazole-containing cyclopeptide from the marine cyanobacterium Okeania hirsuta with antileishmanial activity

A macrocyclic peptide, okeaniazole A (1), was isolated from the Okinawan marine cyanobacterium, Okeania hirsuta. The planar structure was elucidated by the analyses of MS and NMR spectra. The absolute configuration of the amino acid residues was determined by a combination of ozonolysis, hydrolysis, and Marfey’s analysis. Okeaniazole A (1) and a related cyclic heptapeptide dolastatin 3 (2) exhibited antileishmanial activity, with IC50 values of 12.1 and 12.5 µM, respectively. These two compounds did not show any cytotoxicity toward L1210 mouse leukemia cells at concentrations of 100 µM.

A Study of Micellar Catalyses on Oxidation of Glycine by QDC in the Presence of Sodium Dodecyl Sulphate (SDS) in Aqueous Perchloric Acid Medium

Aims: To study the micellar effect of SDS on the oxidation of glycine by Quinolinium Dichromate (QDC) in perchloric acid medium. Background: Among the amino acids, glycine plays a major role in multiple metabolic reactions, such as glutathione synthesis and one-carbon metabolism. The oxidation of glycine has received importance because it is the major neurotransmitter inhibitor in the spinal cord and brainstem. In the oxidation process of amino acids, highly toxic chromium (VI) compounds are converted into non-toxic chromium (III) by quinolinium dichromate (QDC) oxidant in an appropriate pH value medium. Objective: 1. To study the catalytic role of anionic surfactant (SDS) on the oxidation of glycine by QDC through micellization, evaluation of critical micelles concentration (CMC) in the presence and absence of glycine and other surface properties along with thermodynamic quantities. 2. Determination of rate constant and order of reaction with respect to QDC, glycine, acid and surfactant which will help to study the kinetics of the reaction 3. Analysis of oxidation product by FT-IR and calculation of activation parameters. 4. Synthesis of oxidant (QDC) and its characterization by UV-Visible spectrophotometer and NMR spectroscopy. Results: First-order kinetics was observed with respect to oxidant, glycine and hydrogen ions. The rate of reaction increased remarkably with an increase in the concentration of surfactant (SDS). The kinetic results show that the ionic strength variation does not have any significant effect on the rate whereas the increase in the dielectric constant of the medium shows a remarkable effect on the rate constant. From stoichiometry study, it was found that 2 moles of oxidant (QDC) consumed 3 moles of glycine to produce aldehyde (Formaldehyde). Conclusion: The observed negative value of (ΔS) entropy of activation and positive (ΔH) enthalpy of activation suggests a more ordered activated complex formation and highly solvated transition state. The kinetics of the reaction in a perchloric acid medium is found to be accelerated in the presence of surfactant (SDS). The kinetics of the reaction follow pseudo first-order decay of Cr(VI) species (QDC), a unity dependence of rate on glycine and perchloric acid. The oxidation product formaldehyde was identified by FTIR. NMR spectrum analysis of synthesized QDC shows a resemblance with pure QDC.

LAMAIS: A library-aided approach for efficient 1D 1H NMR qualitative analysis in plant metabolomics

BackgroundOne-dimensional proton nuclear magnetic resonance (1D 1H NMR) spectroscopy is a non-destructive, non-targeted analytical technique providing both qualitative and quantitative insights, particularly beneficial for mixture analysis. However, the qualitative analysis of 1D 1H NMR spectra for mixture samples is laborious and time-consuming, involving extensive database searches and verification experiments like spiking. This process heavily relies on the analyst's expertise, leading to efficiency discrepancies. There is a pressing need for a reliable method to streamline operations and enhance the efficiency of qualitative analysis in complex mixtures. ResultsWe introduce a library-aided method for spectral profiling, named LAMAIS. This method achieves compound identification through similarity assessment between samples and template data, allowing rapid, automatic compound identification and full-spectrum peak assignment without the need for fitting. LAMAIS correctly identifies over 90 % of components in synthetic mixtures and more than 75 % in experimental mixtures, surpassing other representative methods with a higher F2 score. Our reference library, which currently includes 71 compounds, is tailored to capture the commonality of primary metabolites across diverse plant species. The analysis of real-world samples yielded encouraging results, underscoring LAMAIS's versatility as an auxiliary tool suitable for a variety of botanical sources. For analyst convenience, interactive graphics are utilized as the output format. SignificanceLAMAIS excels, demonstrating competitiveness and reliability. The approach minimizes repetitive tasks and sample wastage, improving the efficiency of 1D 1H NMR qualitative analysis. Constructing a reference library effectively preserves knowledge, mitigates reliance on human experience, and addresses gaps in the analysis of plant source samples.

Polyketide Derivatives from the Mangrove-Derived Fungus Penicillium sp. HDN15-312.

Four new polyketides, namely furantides A-B (1-2), talamin E (3) and arugosinacid A (4), and two known polyketides were obtained from the mangrove-derived fungus Penicillium sp. HDN15-312 using the One Strain Many Compounds (OSMAC) strategy. Their chemical structures, including configurations, were elucidated by detailed analysis of extensive NMR spectra, HRESIMS and ECD. The DPPH radicals scavenging activity of 3, with an IC50 value of 6.79 µM, was better than vitamin C.

Novel glucomannan-like polysaccharide from Lycium barbarum L. ameliorates renal fibrosis via blocking macrophage-to-myofibroblasts transition

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-β. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.

Bis-piperidine alkaloids from the peels of Areca catechu

Four new alkaloids, arecatines A–D (1–4), were isolated from the peels of Areca catechu. Compound 1 is an unusual piperidine-pyridine hybrid alkaloid, whereas compounds 2–4 feature bis-piperidine alkaloids. Their structures were elucidated by UV, IR, HRESIMS, and NMR spectra analysis. The molecular docking analysis indicated that compound 3 exhibited the best binding affinity with the GABAA receptor, indicating its potential anti-epilepsy activity.