2D NMR Studies Research Articles

Triterpenoid Saponins from the Pericarps of Sapindus mukorossi

A novel acetylated triterpene bisdesmoside saponin is elucidated as named Hederagenin 3‐O‐α‐L‐rhamnopyranosyl (3 → 1)‐[2,4‐O‐diacetyl‐α‐L‐arabinopyranosyl]‐28‐O‐β‐D‐glucopyranosyl‐(2 → 1) [3‐O‐acetyl‐β‐D‐glucopyranosyl] ester (1) along with two known saponins, hederagenin 3‐O‐(α‐L‐arabinopyranoside‐(1 → 3)‐α‐L‐rhamnopyranosyl‐(1→2)‐α‐L‐arabinopyranoside (2) and hederagenin 3‐O‐[β‐D‐xylopyranosyl‐(1 → 3)‐α‐L‐rhamnopyranosyl‐(1 → 2)‐α‐L‐arabinopyranoside] (3), from the pericarps of Sapindus mukorossi. The structures of these saponins were characterized by means of chemical and spectral methods including advanced 2D NMR studies.

Identification and biochemical characterization of a 5-dimethylallyl tryptophan synthase in Streptomyces coelicolor A3(2)

The genome sequencing of Streptomyces coelicolor A3(2) has lead to the identification of numerous cryptic gene clusters involved in the biosynthesis of secondary metabolites; throwing open the challenge of identifying the enzymatic functions that the gene clusters are associated with. In this work, we report the biochemical characterization of one such cryptic gene, SCO7467 from S. coelicolor A3(2), which is annotated as a prenyltransferase. Based on LC–MS and 2D-NMR studies, we show that SCO7467 acts as a 5-dimethylallyl tryptophan synthase (5-DMATS), and catalyzes the transfer of a dimethylallyl group to the C-5 position of the indole ring of l-tryptophan. The studies indicate that SCO7467 could be involved in the synthesis of C-5 prenylated indole alkaloids, which may exhibit unique pharmacological and biological properties.

New ursane-type triterpenes from the root bark of Calotropis procera

As a part of our continuing interest in identifying anticancer drug leads from natural sources, we have investigated the in vitro growth inhibitory effects of the hexane fraction of the root bark of Calotropis procera (Ait) R. Br. (Asclepiadaceae). This study reports the isolation and structure elucidation of four new ursane-type triterpenes named calotroprocerol A (1), calotroproceryl acetate A (2), calotroprocerone A (3) and calotroproceryl acetate B (4) in addition to five known compounds including pseudo-taraxasterol acetate (5), taraxasterol (6), calotropursenyl acetate B (7), stigmasterol (8) and (E)-octadec-7-enoic acid (9). Their structures were established on the basis of 1D and 2D NMR studies (1H–1H COSY, HSQC, and HMBC) and HRMS spectral data. The in vitro growth inhibitory activity of the isolated compounds was evaluated against three human cancer cell lines including the A549 non-small cell lung cancer (NSCLC), the U373 glioblastoma (GBM) and the PC-3 prostate cancer cell lines.

Synthesis of Alkyl and Aryl Substituted Benzo[h]Naphtho[1,2-b][1,6]naphthyridines

The reaction of 4-chloro-2-methylquinolines and 1-naphthylamine under neat conditions yielded 2-methyl-N-(1-naphthyl)quinolin-4-amines. These potential intermediates on reaction with aliphatic and aromatic carboxylic acids yielded the respective 7-alkyl and -aryl substituted benzo[h]naphtho[1,2-b][1,6]naphthyridines. The highly deshielded protons in the final compounds were assigned on the basis of 2D NMR studies.

Evaluation of microlithographic performance of ‘deep UV’ resists: Synthesis, and 2D NMR studies on alternating ‘high ortho’ novolak resins

Lithographic evaluation of a ‘deep UV’ negative photoresist is discussed along with the synthesis of an alternating ‘high-ortho’ novolak resin. 2-D NMR studies (COSY, NOESY, HSQC, HMBC) on this resin are also discussed.

Synthesis, 2D-NMR and molecular modelling studies of pentacycloundecane lactam-peptides and peptoids as potential HIV-1 wild type C-SA protease inhibitors

In this study, eight non-natural peptides and peptoids incorporating the pentacycloundecane (PCU) lactam were designed and synthesized as potential inhibitors of the wild type C-SA HIV-protease. Five of these inhibitors gave IC50 values ranging from 0.5 up to 0.75 µM against the resistance-prone wild type C-South African HIV-protease. NMR EASY-ROESY studies enabled us to describe the secondary structure of three of these compounds in solution. The 3D structures of the selected cage peptides were also modelled in solution using QM/MM/MD simulations. Satisfactory agreement between the NMR observations and the low energy calculated structures exists. Only one of these inhibitors (11 peptoid), which showed the best IC50(0.5 µM), exhibited a definable 3-D structure in solution. Autodock4 and AutodockVina were used to model the potential interaction between these inhibitors and the HIV-PR. It appears that the docking results are too crude to be correlated with the relative narrow range of experimental IC50 values (0.5–10 µM). The PCU-peptides and peptoides were several orders less toxic (145 μM for 11 and 102 μM for 11 peptoid) to human MT-4 cells than lopinavir (0.025 μM). This is the first example of a polycyclic cage framework to be employed as an HIV-PR transition state analogue inhibitor and can potentially be utilized for other diseases related proteases.Graphical abstract: PCU-diastereomers peptide and peptoid inhibitors with arrows showing the observed EASY-ROESY correlations.

Phosphorescent molecular tweezers based on alkynylplatinum(ii) terpyridine system: turning on of NIR emission via heterologous Pt⋯M interactions (M = PtII, PdII, AuIII and AuI)

A novel molecular tweezers-type complex 1, based on a phosphorescent cationic alkynylplatinum(II) terpyridine building block, has been synthesized and characterized by NMR, mass spectroscopy, elemental analysis and X-ray diffraction study. Host–guest chemistry of the host complex 1 and various guest metal complexes with different ligands, charges and/or metal centres has been investigated. Various metal complexes including the negatively charged platinum complexes can interact with 1 in a 1 : 1 manner, which is in contrast to the commonly observed formation of insoluble platinum(II) double salts in a one-dimensional infinite chain such as the Magnus's green salt. Upon addition of guest molecules to 1 in CH2Cl2 solution, spectroscopic changes with new absorptions and emissions in the lower-energy region were observed as a result of significant metal–metal, π–π, and electrostatic interactions. 1H NMR titration and 2D NMR studies suggest that the host–guest interaction is predominantly in the sandwiched association mode of the molecular tweezers.

Aluminium(iii) porphyrin based axial-bonding type dyads containing thiaporphyrins and expanded thiaporphyrins as axial ligands

Four axial-bonding type Al(III) porphyrin based dyads, containing thiaporphyrins with N3S 1 and N2S22 cores and expanded thaiporphyrins with N2S33 and N2S44 cores, were synthesised by treating [(TPP)AlIIIOH] with the corresponding mono-functionalised meso-4-hydroxyphenyl thiaporphyrin or expanded thiaporphyrin building blocks in benzene at refluxing temperature. The stable dyads 1–4 are freely soluble in common organic solvents and characterized by mass, 1D and 2D NMR, absorption, electrochemical and fluorescence techniques. 1D and 2D NMR studies unambiguously confirmed the dyads. The absorption and electrochemical studies show weak interaction between the two macrocycles in dyads and the constituted macrocycles in dyads mostly retain their characteristic individual features. The steady state fluorescence studies indicate a decrease in the quantum yield of Al(III) porphyrin unit in dyads 1–4 and invoked the possibility of singlet–singlet energy transfer from the Al(III) porphyrin unit to the N3S porphyrin unit in dyad 1 and N2S2 porphyrin unit in dyad 2. Structural information of these dyads in their ground (S0) state are generated by applying density functional theory (DFT) based quantum chemical calculations. Excited state calculations are carried out following time dependent density functional theory (TD-DFT) and UV-Vis spectra of these dyads are simulated in the Soret band region.

Insight Into the Conformational Arrangement of a Bis-THF Diol Compound Through 2D-NMR Studies and X-Ray Structural Analysis

The conformational arrangement of an all-threo bis-THF diol compound, synthesized through the RuO4-catalysed oxidative bis-cyclization of farnesyl acetate, was determined via crystallographic analysis and detailed 2D-NMR solution studies. The bis-THF compound crystallizes in the orthorhombic Pbca space group, with unit cell parameters a = 10.496(1), b = 17.974(1), c = 19.777(2) A, Z = 8. The final refinement converged to R 1 = 0.0484 for 4714 independent observed reflections having I > 2σ(I). There is a good agreement between the solution molecular conformation determined by 2D-NMR and the X-ray molecular conformation. The molecule adopts a folded, horse shoe-type conformation both in solution and in the crystal, that suggests aptitude to coordinate cations. Additionally, in the crystals, the molecular conformation is stabilized by intramolecular and intermolecular H-bonding. 2D-NMR and X-ray studies indicate that the bis-THF shown adopts a folded, horse shoe-type, conformation both in solution and in the crystal, that suggests aptitude to coordinate cations.

Competitive displacement of drugs from cyclodextrin inclusion complex by polypseudorotaxane formation with poloxamer: Implications in drug solubilization and delivery

The competitive interactions between the poly-[propylene oxide] (POO)–poly-[ethylene oxide] (PEO) block copolymer poloxamer 407 (Pluronic F127) and two drugs, triamcinolone acetonide and ciclopirox olamine, by the formation of inclusion complexes with two cyclodextrin hydrophilic derivatives, hydroxypropyl-β-cyclodextrin (HPβCD; molar substitution (MS) 0.65) and partially methylated-β-cyclodextrin (MβCD; MS 0.57), were studied by means of one-dimensional 1H NMR, 2D ROESY experiments, solubility studies and drug release studies. 1D and 2D NMR and solubility studies indicate that both triamcinolone acetonide and ciclopirox olamine form stable inclusion complexes with the cyclodextrin derivatives. In the case of ciclopirox olamine the complex was more stable at pH 1. Effective complexation of poloxamer with the two cyclodextrins (CDs) was also evidenced by NMR analysis, and competitive displacement of the drugs from the CD cavity by the polymer was observed. Drug solubility in CD solutions was not modified by the addition of polymers, indicating that a decrease in solubility due to the competitive displacement is probably compensated by the solubilizing effect of polymer micellization. Finally, polypseudorotaxanes formation has a significant influence on the release of the drugs studied. Changes in the release rate depend on the stability of drug–CD inclusion complex and on cyclodextrin concentration in the bulk solution; so polypseudorotaxane formation can be employed to modulate drug controlled release from thermosensitive hydrogels.

Secondary Metabolites from Two Species of Pulicaria and Their Cytotoxic Activity

Two new compounds, the sesquiterpene (1E,5E)-8β-acetoxy-4α-hydroxy-7βH-germacra-1(10),5-dien-14-oic acid (2), and a nor-sesquiterpene, (5E)-8β-acetoxy-4α-hydroxy-7βH-germacr-5-en-10-one (3), were isolated from Pulicaria canariensis ssp. lanata, along with ten known compounds, including the flavonoid 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (4). From Pulicaria burchardii, we isolated seven known compounds; the physical and spectroscopic data of the triterpenoid 3β-hydroxytaraxaster-20-en-30-al (1) are reported. The structures of compounds 1-3 were determined on the basis of HR-MS, and 1D- and 2D-NMR studies. The structure of 2 was corroborated by X-ray crystal diffraction. Cell viability experiments revealed that the semisynthetic flavonoid 4b was the most cytotoxic compound against human leukemia cells, and the cytotoxicity was caused by induction of apoptosis, as determined by microscopy of nuclear changes.

External-Stimuli Responsive Photophysics and Liquid Crystal Properties of Self-Assembled “Phosphole-Lipids”

A series of new amphiphilic phosphonium materials that combine the electronic features of phospholes with self-assembly features of lipids were synthesized. Variable concentration/temperature and 2D NMR studies suggested that the systems undergo intramolecular conformation changes between a "closed" and "open" form that are triggered by intermolecular interactions. The amphiphilic features of the phospholium species also induce liquid crystalline and soft crystal phase behavior in the solid state, which was studied by differential scanning calorimetry (DSC), polarized optical microscopy (POM), and variable temperature powder X-ray diffraction (VT-PXRD). The studies revealed that both conjugated backbones and counteranions work together to organize the systems into different morphologies (liquid crystal/soft crystal). Dithieno[3,2-b:2',3'-d]phosphole-based compounds exhibit enhanced emission in the solid state and at low temperature in solution due to aggregation-induced enhanced emission (AIEE). Photoinduced electron transfer (PET) induced via the alkoxybenzyl group at the phosphonium center in the fused-ring systems can be effectively suppressed through intermolecular charge transfer (ICT) processes within the main scaffold of a nonfused system, which was confirmed by static and dynamic fluorescence spectroscopy. The dynamic features of these new materials also endow the systems with external-stimuli responsive photophysical properties that can be triggered by temperature and/or mechanical forces.

1D and 2D NMR studies of isobornyl acrylate – Methyl methacrylate copolymers

Isobornyl acrylate – methyl methacrylate (B/M) copolymers of different compositions were synthesized by atom transfer radical polymerization (ATRP) using methyl-2-bromopropionate as an initiator and PMDETA copper complex as catalyst under nitrogen atmosphere at 70 °C. 1H NMR spectrum was used to determine the compositions of copolymer. The copolymer compositions were then used to determine the reactivity ratios of monomers. Reactivity ratios of co-monomers in B/M copolymer, determined from linear Kelen–Tudos method (KT) and non linear Error-in-Variable Method (EVM), are r B = 0.41 ± 0.11, r M = 1.11 ± 0.33 and r B = 0.52, r M = 1.31 respectively. The complete resonance assignments of 1H and 13C{ 1H} NMR spectra were carried out with the help of Distortion less Enhancement by Polarization Transfer (DEPT), two-dimensional Heteronuclear Single Quantum Coherence (HSQC). 2D HSQC assignments were further confirmed by 2D Total Correlation Spectroscopy (TOCSY). The carbonyl carbon of B and M units and methyl carbon of M unit were assigned up to triad compositional and configurational sequences whereas β-methylene carbons were assigned up to tetrad compositional and configurational sequences. Similarly the methine carbon of B unit was assigned up to pentad level. 1,3 and 1,4 bond order couplings of carbonyl carbon and quaternary carbon resonances with methine, methylene and methyl protons were studied in detail using 2D Hetero Nuclear Multiple Bond Correlation (HMBC) spectra.

A complete 1D and 2D NMR studies of variously substituted 3-azabicyclo[3.3.1]nonan-9-ones

Variously substituted 3-azabicyclo[3.3.1]nonan-9-ones viz, 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones, 2,4-diaryl-1-methyl-3-azabicyclo[3.3.1]nonan-9-ones and 2,4-diaryl-7-methyl-3-azabicyclo[3.3.1]nonan-9-ones were conveniently synthesized by a modified and an optimized one-pot Mannich condensation of cyclohexanones, benzaldehydes and ammonium acetate in 1:2:1.5 M ratio. All the synthesized bicycles were examined by their physical and spectral (IR, HR-MS, 1H NMR and 13C NMR) techniques. In order to establish their unambiguous stereochemical assignments, H,H-COSY, HET-COSY, HMBC, NOESY and dynamic NMR investigations have been carried out for some of the representative compounds. The detailed NMR analysis proved that all the synthesized 3-azabicycles exist in a twin-chair conformation with an equatorial orientation of the substituents, regardless the incorporation of either linear or bulkier groups on the phenyl and/or methyl on the heterocycle or carbocycle. The electronic effects of methylation on the azabicycle as well as the ortho substitution on the phenyl provided some useful insights.

Synthesis, 2D NMR and X-ray diffraction studies on Cu(II) and Ni(II) complexes with ligands derived from azobenzene-cored Schiff base: Mesomorphic behaviors of Cu(II)–phenolates and crystal structure of bis[4-(4-alkoxy-2-hydroxybenzylideneamino)azobenzene]copper(II)

Two new homologous series of copper(II) and nickel(II) complexes derived from bidentate Schiff bases 4-(4-alkoxy-2-hydroxybenzylideneamino)azobenzene have successfully been synthesized. Their molecular structures were elucidated by FT-IR, 1H and 13C NMR along with 1H– 1H COSY, 1H– 13C HMQC, 1H and 13C HMBC. Mesomorphic behaviors of ligands and metal complexes have been investigated by differential scanning calorimetry and polarizing optical microscope. All ligands and their copper complexes exhibit exclusively the mesomorphic properties. The X-ray diffraction studies have confirmed the presence of smectic A (SmA) phase in copper(II)–phenolate complexes. The molecular structure of bis[4-(4-alkoxy-2-hydroxybenzylideneamino)azobenzene]copper(II) have been determined by using X-ray crystallographic techniques. It was found that the ligands have square planar configuration around the Cu center ion as evident by the N Cu N and O Cu O angles of 180°.

An Efficient One Pot Synthesis of New Indanopyrazoline and Indanopyrazole Derivatives

Synthesis of a series of novel fused pyrazolines and pyrazoles has been accomplished in good yields by regio- and diastereoselective 1,3-dipolar cycloaddition of enamines of indan-1-one 1a-c towards C-aryl-N-phenylnitrilimines 2d- f. The structure of the cycloadducts was elucidated by 1D and 2D NMR studies.

CCoAOMT suppression modifies lignin composition in Pinus radiata

A cDNA clone encoding the lignin-related enzyme caffeoyl CoA 3-O-methyltransferase (CCoAOMT) was isolated from a Pinus radiata cDNA library derived from differentiating xylem. Suppression of PrCCoAOMT expression in P.radiata tracheary element cultures affected lignin content and composition, resulting in a lignin polymer containing p-hydroxyphenyl (H), catechyl (C) and guaiacyl (G) units. Acetyl bromide-soluble lignin assays revealed reductions in lignin content of up to 20% in PrCCoAOMT-deficient transgenic lines. Pyrolysis-GC/MS and 2D-NMR studies demonstrated that these reductions were due to depletion of G-type lignin. Correspondingly, the proportion of H-type lignin in PrCCoAOMT-deficient transgenic lines increased, resulting in up to a 10-fold increase in the H/G ratio relative to untransformed controls. 2D-NMR spectra revealed that PrCCoAOMT suppression resulted in formation of benzodioxanes in the lignin polymer. This suggested that phenylpropanoids with an ortho-diphenyl structure such as caffeyl alcohol are involved in lignin polymerization. To test this hypothesis, synthetic lignins containing methyl caffeate or caffeyl alcohol were generated and analyzed by 2D-NMR. Comparison of the 2D-NMR spectra from PrCCoAOMT-RNAi lines and synthetic lignins identified caffeyl alcohol as the new lignin constituent in PrCCoAOMT-deficient lines. The incorporation of caffeyl alcohol into lignin created a polymer containing catechyl units, a lignin type that has not been previously identified in recombinant lignin studies. This finding is consistent with the theory that lignin polymerization is based on a radical coupling process that is determined solely by chemical processes.

Toward carboxylate group functionalized A 4, A 2B 2, A 3B oxaporphyrins and zinc complex of oxaporphyrins

Series of new oxaporphyrins were isolated from the reaction of furan-1,4-diol, pyrrole, and an aldehyde under Lindsey’s conditions, which gives easy access to ester group functionalized oxaporphyrins. The ester substituents can be readily hydrolyzed to terminal carboxylic acid in the presence of KOH. The Zn(II) oxaporphyrins have been synthesized from the reaction of free base with ZnCl 2 and fully characterized by variable temperature NMR, 2D NMR, and single crystal X-ray diffraction studies.

RETRACTED ARTICLE: Total spectral assignments and 2D NMR study of PVAc-b-PMA and PVAc-b-PMMA block copolymers

This article has been retracted. Due to a dispute over authorship of the paper and ownership of the data, the Editor-in-Chief of the Journal of Polymer Research decided to retract the article “Total spectral assignments and 2D NMR study of PVAc-b-PMA and PVAc-bPMMA block copolymers” by corresponding author Mohammad Reza Rostami Daronkola. M. M. Ajjalallah :M. R. R. Daronkola (*) Polymer Engineering Group, Chemical Engineering Department, Tarbiat Modares University, Jalal Al Ahmad Highway, P.O. Box 14115-143, Tehran, I.R, Iran e-mail: mr_rostami@modares.ac.ir

Dendrophen, a Novel Glycyrrhetyl Amino Acid from Dendronephthya hemprichi

Chemical investigation of the extract of Dendronephthya hemprichi, collected from the Red Sea, Egypt, delivered dendrophen (1), the first 3β -acetoxy-glycyrrhetyl amino acid conjugate obtained from nature. Additionally, a new polyhydroxy sterol, dendrotriol (2), together with cholesterol and hexitol were isolated. Chromatographic separation of the low-polarity components of the D. hemprichi extract afforded 4-oxo-pentanoic acid, 2-methyl-acrylic acid 2-diethylaminoethyl ester (3), juniper camphor (4), and 2-octadecanone. The structures of 1 and 2 were confirmed by 1D and 2D NMR studies and mass spectrometry.