Heteronuclear 2D Research Articles

ChemInform Abstract: The Structure of Isoflavones by 1D and 2D Homonuclear and Heteronuclear NMR Spectroscopy

AbstractReview: 24 refs.

Synthesis, Crystal Structure and Catalytic Behavior of Homo- and Heteronuclear Coordination Polymers [M(tdc)(bpy)] (M2+ = Fe2+, Co2+, Zn2+, Cd2+; tdc2– = 2,5-thiophenedicarboxylate)

A series of isostructural 3D coordination polymers (3)∞[M(tdc)(bpy)] (M(2+) = Zn(2+), Cd(2+), Co(2+), Fe(2+); tdc(2-) = 2,5-thiophenedicarboxylate; bpy = 4,4'-bipyridine) was synthesized and characterized by X-ray diffraction, thermal analysis, and gas adsorption measurements. The materials show high thermal stability up to approximately 400 °C and a solvent induced phase transition. Single crystal X-ray structure determination was successfully performed for all compounds after the phase transition. In the zinc-based coordination polymer, various amounts of a second type of metal ions such as Co(2+) or Fe(2+) could be incorporated. Furthermore, the catalytic behavior of the homo- and heteronuclear 3D coordination polymers in an oxidation model reaction was investigated.

Synthesis, characterization and biological evaluation of some novel P-heterocyclic androst-4-ene derivatives

The reactions of 21-hydroxyprogesterone with Lawesson's reagent in toluene or [Formula: see text] gave four P-heterocyclic androst-4-ene derivatives (two tautomeric pairs): 4-(3-thioxoandrost-4-en-17[Formula: see text]-yl)-1,3,2-oxathiaphosphole-2- sulfide (2), 4-(3-thioxoandrost-4-en-17[Formula: see text]-ylidene)-1,3,2-oxathiaphospholane-2-sulfide (3), 4-(3-oxoandrost-4-en-17[Formula: see text]-yl)-1,3,2-oxathiaphosphole-2-sulfide (4), and 4-(3-oxoandrost-4-en-17[Formula: see text]-ylidene)-1,3,2- oxathiaphospholane-2-sulfide (5). The structures of all novel 17-substituted steroids were elucidated from their analytic and spectral data (HRMS, IR, 1D NMR and 2D NMR-HSQC, HMBC, NOESY, COSY). The detailed NMR analysis for all compounds revealed the presence of two pairs of signals in approx. 8:2 ratio indicating the existence of two diastereoisomers (a and b) with different configurations at the phosphorus atom. A parallel analysis of heteronuclear 2D [Formula: see text]-[Formula: see text] spectra (HSQC and HMBC) and homonuclear 2D spectra (NOESY and COSY) enabled complete [Formula: see text] and [Formula: see text] assignments of each isomer and provided evidence for the preferred configuration on phosphorus atom. Cytotoxic activity in vitro was tested against four tumor cell lines (human cervix carcinoma HeLa cells, chronic myelogenous leukemia K-562 and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compounds 3a,b and 4a,b showed a poor activity against HeLa and MDA-MB-453 cell lines, while against MDA-MB-361 cell line, all tested compounds exerted very weak cytotoxic effect. All compounds exerted moderate activity against K562 cells. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp Artemia salina were evaluated. All tested compounds showed strong antifungal activity.

Aliasing functions and a dynamic approach to optimizing spectral widths in 2D experiments

We reduce the modulo function that describes the aliasing of an NMR signal to a floor function form. An analysis of this function is carried out and an expression that defines its points of discontinuity is derived. Based only on this definition we develop a new method to optimize the spectral widths in the $$^{13}\text{ C }$$ dimension of heteronuclear 2D experiments of small organic compounds using neither the modulo function nor the definition of the overlap points. We apply this method to the carbon chemical shifts of cholesterol, and find that it unambiguously assigns all of the signals acquired in the aliased Heteronuclear Single Quantum Coherence spectrum of cholesterol with the calculated spectral width. Previous reports do not show a fully resolved 2D spectrum of cholesterol.

Fast Quantitative 1H–13C Two-Dimensional NMR with Very High Precision

Quantitative analysis by nuclear magnetic resonance (NMR) requires highly precise measurements to achieve reliable quantification. It is particularly true in (13)C site-specific natural isotope fractionation studied by nuclear magnetic resonance, where the range of values of (13)C isotopic deviations at natural abundance is highly restricted. Consequently, an NMR method capable of measuring δ(13)C ‰ values with a very high precision (a few per mil) is indispensable. This high degree of precision has already been achieved by one-dimensional (13)C acquisitions; however, this approach is limited by peak overlaps which reduce the precision of the isotope content determination, even for certain small molecules. It is therefore necessary to extend this promising methodology to a higher dimensionality. In this context, this paper aims at determining conditions that allow the achievement of two-dimensional (2D) (1)H-(13)C heteronuclear experiments with a precision of a few per mil in a reasonable time. Our results demonstrate that a high precision (repeatability of 2 per mil) can be reached with the (1)H-(13)C HSQC (Heteronuclear Single Quantum Correlation) experiment, thus satisfying the conditions needed to perform (13)C isotope analysis by 2D NMR. We also consider the impact of several approaches which have been proposed to reduce the duration of heteronuclear 2D experiments. Two of these common time-saving strategies, spectral aliasing and linear prediction, are fully compatible with the high-precision requirements of isotopic NMR, while a third one, nonuniform sampling, leads to dramatic precision losses. In conclusion, this study demonstrates the feasibility of very precise 2D NMR measurements and opens a number of application perspectives.

Molecular structures of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate and methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate

The structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate is determined by X-ray crystallography and further used to elucidate the structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate, using the data of homo- and heteronuclear 2D NMR correlation spectroscopy.

Study of the thermal processes in molecular crystals of peptides by means of NMR crystallography

1D and 2D Very Fast Magic Angle Spinning (VF MAS) NMR experiments with sample rotation up to 55 kHz were applied to study both the dihydrate form of Tyr–(D)Ala–Phe–Gly (N-terminal sequence of opioid peptide dermorphin) and the anhydrous form, which was obtained by thermal treatment. Employing both homo-nuclear (1H–1H BABA, 13C–13C SHANGHAI) and hetero-nuclear 2D correlations (1H–13C and 1H–15N) with inverse detection, it was shown that removing water from the crystal lattice of this tetrapeptide does not destroy its subtle pseudo-cyclic structure, and its supramolecular array is preserved. The GIPAW method was employed to compute the geometry of the peptides and calculate the 13C σii principal elements of the NMR shielding tensor parameters and 1H isotropic NMR shifts. The theoretical values of 13C σii were compared with the experimental 13C δii chemical shift tensor values obtained by a 2D PASS experiment. The correlations 13C σii versus δii and 1H σiso versus δiso were used to evaluate the quality of the computational approach. With the new set of coordinates obtained by the GIPAW method, the crystal and molecular structure of the dehydrated Tyr–(D)Ala–Phe–Gly peptide that was obtained by thermal treatment was constructed. Methodology used in this project combining NMR measurements, analysis of X-ray powder diffraction data and advanced quantum mechanical calculations is known as NMR crystallography.

Iterative One‐Pot α‐Glycosylation Strategy: Application to Oligosaccharide Synthesis

AbstractBased on the combined use of dimethylformamide (DMF) modulation and neighboring group participation, three iterative one‐pot α‐glycosylation methods, i.e., one‐pot (α,α)‐, one‐pot (β,α)‐, and one‐pot (α,β)‐glycosylations, were developed. These methods are applicable to a range of thioglycosyl donors, confer stereocontrol in α‐/β‐glycosidic bond formation, and thus provide for rapid access to oligosaccharides with various permutations of anomeric configurations. The utility of these one‐pot glycosylation methods is demonstrated in the synthesis of eight non‐natural and natural oligosaccharide targets, including the core 1 serine conjugate, core 8 serine conjugate, the D‐Gal‐α(1→3)‐D‐Glc‐α(1→3)‐L‐Rha trisaccharide unit of the cell wall component in Streptococcus pneumoniae, and the D‐Glc‐α(1→2)‐D‐Glc‐α(1→3)‐D‐Glc trisaccharide terminus of the N‐linked glycan precursor. Confirmation of the anomeric configurations of these oligosaccharides is evidenced by 1H, 13C, 13C‐non‐proton decoupling, and heteronuclear correlation 2D NMR experiments. Global deprotection of selected oligosaccharide targets is illustrated.

Triterpene saponins of Maesa lanceolata stem wood

Phytochemical analysis of aqueous MeOH extract of Maesa lanceolata stem wood has led to the isolation of four new triterpene saponins characterized as 16α,21β-diacetoxy-22α-angeloyl-28-hydroxyolean-12-ene 3-O-[α-rhamnopyranosyl-(1″″ → 6‴)-β-glucopyranosyl-(1‴ → 3′)][β-glucopyranosyl-(1″ → 2′)]-β-glucuronopyranoside (1), 16α-acetoxy-21β-hydroxy-22α-angeloyl-13β,28-oxydoolean-28α-ol 3-O-[α-rhamnopyranosyl-(1″″ → 6‴)-β-glucopyranosyl-(1‴ → 4′)][β-glucopyranosyl-(1″ → 2′)]-α-arabinopyranoside (2), 16α-acetoxy-21β,22α-diangeloyl-13β,28-epoxyoleanane 3-O-[α-rhamnopyranosyl-(1″″ → 6‴)-β-glucopyranosyl-(1‴ → 4′)][β-glucopyranosyl-(1″ → 2′)]-β-xylopyranoside (3), and 16α,22α-diacetoxy-13β,28-oxydoolean-28α-ol 3-O-[β-glucopyranosyl-(1″ → 2′)][β-glucopyranosyl-(1‴ → 3′)]-β-glucuronopyranoside (4), together with the known compounds β-acetylamyrin, physcion, emodin, chrysophanol, ursolic acid, 16α-hydroxy-12-oleanene 3-O-glucoside, β-amyrin, sitosterol 3-O-β-glucoside, stigmasterol, and 3β,28-dihydroxyolean-12-ene. Their structural elucidation was accomplished by homo- and heteronuclear 2D NMR technique as well as comparison with data from known compounds. The in vitro antibacterial activity of the aqueous MeOH extract was also investigated and zones of inhibition ranging from 32 ± 1.1 to 14 ± 0.2 mm were observed. Among the isolates, compound 1 was the most active with an minimum inhibitory concentration value of 25 μg/ml against Staphylococcus aureus.

On the Morphology of a Discotic Liquid Crystalline Charge Transfer Complex

Discotic liquid crystalline (DLC) charge transfer (CT) complexes, which combine visible light absorption with rapid charge transfer characteristics within the CT complex, can have a great potential for photovoltaic applications when they can be made to self-assemble in a bulk heterojunction arrangement with separate channels for electron and hole conduction. However, the morphology of some liquid crystalline CT complexes has been under debate for many years. In particular, the liquid crystalline CT complex built from the electron acceptor 2,4,7-trinitro-9-fluorenone (TNF) and discotic molecules has been reported to have the TNF "sandwiched" either between the discotic molecules within the same column or between the columns within the aliphatic tails of the discotic molecules. We present a detailed structural study of the prototypic 1:1 mixture of the discotic 2,3,6,7,10,11-hexakis(hexyloxy)triphenylene (HAT6) and TNF. Nuclear magnetic resonance (NMR) line widths and cross-polarization rates are consistent with the picosecond time scale anisotropic thermal motions of the HAT6 and TNF molecules previously observed. By computational integration of Rietveld refinement analyses of neutron diffraction patterns with density experiments and short-range structural constraints from heteronuclear 2D NMR, we determine that the TNF molecules are vertically oriented between HAT6 columns. The data provide the insight that a morphology of separate hole conducting channels of HAT6 molecules can be realized in the liquid crystalline CT complex.

2D Solid-State NMR Analysis of Inclusion in Drug–Cyclodextrin Complexes

The solubility of drug molecules can often be improved through preparation and delivery of cyclodextrin (CD) inclusion complexes. These drug-oligosaccharide complexes can be prepared in solution and converted to the solid state via methods such as lyophilization and spray-drying, or they can be prepared directly from solids by a variety of methods. The development of drug-CD complexes as solids allows for potential advantages in dosage form design, such as the preparation of layered formulations, and it also can yield improvements in chemical and physical stability. 2D solid-state NMR (SSNMR) methods provide a direct way to probe drug-CD interactions in solid complexes through dipolar interactions between nuclei within the drug and CD molecules. In this study, 2D heteronuclear and homonuclear correlation SSNMR experiments involving (1)H, (13)C, (19)F, and (31)P nuclei are used to demonstrate the inclusion of drug within the CD cavity in a variety of powder samples. To illustrate the general applicability of the SSNMR approach presented, examples are shown for the drugs diflunisal, adefovir dipivoxil, voriconazole, dexamethasone, and prednisolone in complexes with α-CD, β-CD, and sulfobutylether-substituted β-CD. The quantitative analysis of included and free drug fractions in a solid drug-CD complex using SSNMR is also demonstrated. On the basis of these results, general approaches to the characterization of these materials using SSNMR are proposed.

Salen-type heteronuclear 3d–4f complexes engineering by anion PF6 with near-infrared (NIR) and luminescent properties

Abstract Two heteronuclear 3d–4f complexes obtained by salen-type ligand N,N′-bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminopropane (H2L1) and N,N′-bis(2-hydroxy-3-methoxy benzylidene)-1,2-diaminohexane (H2L2) have been isolated. They are co-crystallized complex [Yb(ZnL1)(OAc)2(H2O)]·[Yb(ZnL1)(OAc)3]·PF6·CH3OH (1), trinuclear complex [Sm(ZnL2)2Cl2(H2O)2]·PF6 (2). In complexes 1 and 2 the anion PF6 called counteranion is not only a role to neutralize overall charge in the solid but also to regulate frameworks. The complexes were structurally characterized by single crystal X-ray crystallographic studies and their photophysical properties were investigated.

Accurate Structural Description of the Two Nanoporous Fluorinated Aluminophosphates ULM-3(Al) and ULM-4(Al) by Solid-State NMR

This work reports an investigation of the localization of F atoms and OH groups in the two fluorinated aluminophosphates ULM-3(Al) and ULM-4(Al) by multinuclear and multidimensional high-resolution solid-state magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy. First, in ULM-3(Al), we show that the compound is fully fluorinated. A whole set of state-of-the-art homonuclear and heteronuclear 2D NMR experiments (19F–31P, 19F–19F, 31P–31P, 27Al–31P, and 1H–31P) have been recorded, yielding a unique line assignment of all the 31P and 19F resonances to the corresponding crystallographic sites. In a second part, ULM-4(Al) is shown to be a quite remarkable sample because it contains both fully and partially fluorinated building units. The structural differences between ULM-3(Al) and ULM-4(Al) are finally discussed in the light of the results in terms of potential templating role of water.

Quantitation of components in complex mixtures utilizing two dimensional NMR spectroscopy

Nuclear Magnetic Resonance (NMR) spectroscopy is well documented to provide qualitative data for structural determination of chemical compounds. More recently, numerous applications of NMR for quantitative analyses of chemical mixtures have been utilized. The majority of these applications use integration of discrete 1D NMR spectral resonances to quantitate individual components of the mixtures. 1D 1H NMR typically provides the highest sensitivity analyses with excellent linear response to component concentrations. Quantitative analyses of complex mixtures via 1D NMR however are often hindered by resonance overlap. Utilization of 1H-13C heteronuclear correlation (HSQC) and 2D J-resolved experiments provides dispersion in a second dimension, 13C chemical shift and 1H coupling constant respectively, for better identification and quantification of signals. The HSQC cross-peak volumes are influenced by uneven excitation, etc. and therefore the volumes for different resonances from the same molecule can vary based on these factors. Nevertheless, utilizing the same experimental parameters for any given cross-peak, the areas for the same peak should scale linearly with molar concentration. In this study, we have investigated the quantitative accuracy of these 2D spectra on a complex model system containing phenolics, alkaloids, sugars, terpenes, and polyketides and made comparisons to quantification using chemometric approaches. Applications to natural product extracts and formulations and ability to implement this into automated analysis methods will be presented.

Synthesis and NMR Spectral Studies of the 7-C60-Adduct of N,N-(Tetrachlorophthaloyl) Dehydroabietylamine

The 7-C60-adduct of N,N-(tetrachlorophthaloyl)dehydroabietylamine was synthesized for the first time and characterized by IR, UV-vis, mass and NMR spectral studies. The 1H-NMR and 13C-NMR resonance signals of the new compound are unambiguously assigned by using homo- and heteronuclear 2D NMR spectroscopic techniques such as COSY, ROESY, HSQC and HMBC. The C1 symmetric structure with 6,6-junction of compound was determined.

A new arabinomannan from the cell wall of the chlorococcal algae Chlorella vulgaris

A new arabinomannan has been isolated from the cell wall of the green algae Chlorella vulgaris by extraction with 0.1M NaOH, dialysis and SEC fractionation. Mw was about 8000u. Terminal, 2- and 5-O-linked arabinofuranosyl residues, and 2,6-O-linked mannopyranosyl residues were detected as the main constituents beside some minor mannose components by methylation analysis. Electrospray ionisation mass spectrometry (ESI–MS) with collision induced dissociation (CID) up to MS3 experiments of oligosaccharides obtained by partial methanolysis or partial acid hydrolysis indicated the presence of Man→Man- and Ara→Ara- as well as Ara→Man- and also Man→Ara-sequences. MS2 experiments gave evidence of a (1→6)-linked mannan, probably also including some (1→2)-linked mannosyl and 5-linked arabinofuranosyl residues. Mannooligosaccharides up to DP5 with mainly (1→6)-, but at higher DP also (1→2)-linkages were obtained by acid hydrolysis, and arabino oligomers up to DP4 could be detected after mild methanolysis. In accordance with results from methylation analysis and ESI–MS/CID t-β-Araf, 2-α-Araf, 5-α-Araf and 2,6-α-Manp were identified from homo- and heteronuclear 1D- and 2D NMR experiments in a molar ratio of ∼2:2:1:2. A highly branched structure is suggested with a 6- and 2-O-linked mannan main chain, comprising 5-Araf residues. Araf-β-[(1→2)-Araf-α-(1→]n side chains with an average chain length of 2 are linked to the mannan main chain. The configuration of Ara is d. The new polysaccharide shows structural similarities with the (lipo)arabinomannans of Mycobacterium tuberculosis.

New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities

The reactions of 17α-hydroxyprogesterone with Lawesson’s reagent (LR) in toluene, CH2Cl2 and/or CCl4 gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D 1H–13C spectra (HSQC and HMBC) and homonuclear 2D spectra (NOESY) enabled complete 1H and 13C assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-453 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia salina, were evaluated. All tested compounds showed strong antifungal activity.

Rational Design and Synthesis of a New Organometallic Ligand, 1-Ferrocenyl-3-(5-bromopyridyl)-prop-3-enol-1-one and Its Heteronuclear Coordination Polymer, {Cu[1-ferrocenyl-3-(5-bromopyridyl)prop-1,3-dionate]2}n

A new bifunctional organometallic ligand was synthesized, by reacting ferroceneacyl anion with ethyl-5-bromonicotinic acid, isolated, and characterized as 1-ferrocenyl-3-(5-bromopyridyl)-prop-3-enol-1-one (HL1). This new ligand reacts with Cu(II) salt to yield a new two-dimensional (2D) heteronuclear (Fe–Cu) coordination polymer of type [Cu(L1)2]n. Single crystal X-ray diffraction analysis of both the ligand and the coordination polymer is provided in this report.

Three-dimensional deuterium-carbon correlation experiments for high-resolution solid-state MAS NMR spectroscopy of large proteins

Well-resolved (2)H-(13)C correlation spectra, reminiscent of (1)H-(13)C correlations, are obtained for perdeuterated ubiquitin and for perdeuterated outer-membrane protein G (OmpG) from E. coli by exploiting the favorable lifetime of (2)H double-quantum (DQ) states. Sufficient signal-to-noise was achieved due to the short deuterium T (1), allowing for high repetition rates and enabling 3D experiments with a (2)H-(13)C transfer step in a reasonable time. Well-resolved 3D (2)H(DQ)-(13)C-(13)C correlations of ubiquitin and OmpG were recorded within 3.5days each. An essentially complete assignment of (2)H(DQα) shifts and of a substantial fraction of (2)H(DQβ) shifts were obtained for ubiquitin. In the case of OmpG, (2)H(DQα) and (2)H(DQβ) chemical shifts of a considerable number of threonine, serine and leucine residues were assigned. This approach provides the basis for a general heteronuclear 3D MAS NMR assignment concept utilizing pulse sequences with (2)H(DQ)-(13)C transfer steps and evolution of deuterium double-quantum chemical shifts.

Resolving overlaps in diffusion encoded spectra using band-selective pulses in a 3D BEST-DOSY experiment

A novel diffusion-edited 3D NMR experiment that incorporates a BEST-HMQC pulse sequence in its implementation is presented. Heteronuclear 3D DOSY NMR experiments are useful in elucidating the diffusion coefficients of individual constituents of a mixture, especially in cases where the proton NMR 2D DOSY spectra show considerable overlap. The present 3D BEST-DOSY pulse sequence provides a more sensitive and less time-consuming alternative to standard 3D HMQC-DOSY experiments. Cleanly separated subspectra of individual mixture components are obtained, leading to the determination of diffusion coefficients with better accuracy. The feasibility of the technique is demonstrated on a mixture of amino acids, on a mixture of small molecules with similar diffusion coefficients, and on a complex mixture with large dynamic range (commercial gasoline). The implications of using adiabatic decoupling schemes and band-selective shaped pulses for selective BEST-DOSY experiments on proteins are also discussed.