1,720,977 research outputs found
Long-Range Residual Dipolar Couplings: A Tool for Determining the Configuration of Small Molecules
No full textTogether with NOE and J coupling, one-bond residual dipolar coupling (RDC), which reports on the three-dimensional orientation of an internuclear vector in the molecular frame, plays an important role in the conformation and configuration analysis of small molecules in solution by NMR spectroscopy. When the molecule has few C-H bonds, or too many bonds are in parallel, the available RDCs may not be sufficient to obtain the alignment tensor used for structure elucidation. Long-range RDCs that connect nuclei over multiple bonds are normally not parallel to the single bonds and therefore complement one-bond RDCs. Herein we present a method for extracting the long-range RDC of a chosen proton or group of protons to all remotely connected carbon atoms, including non-protonated carbon atoms. Alignment tensors fitted directly to the total long-range couplings (T=J+D) enabled straightforward analysis of both the long-range and one-bond RDCs for strychnine
Residual Chemical Shift Anisotropies in the Structure Determination of Small Molecules
No full textABSTRACT The determination of the relative and absolute configuration of natural compounds is a very challenging task. Among other anisotropic NMR parameters, residual chemical shift anisotropy (RCSA) induced by anisotropic media is an invaluable tool to determine relative configurations of natural and synthetic organic molecules in solution. This review introduces various RCSA‐based methodologies for the structural elucidation of natural products. The current availability of alignment media in organic solvents for RCSA measurements is also discussed as are applications of RCSAs for structural analysis of various natural products.Science and Engineering Research Board https://doi.org/10.13039/50110000184
Real time band selective F-<sub>1</sub>-decoupled proton NMR for the demixing of overlay spectra of chiral molecules.
Full text linkThe small chemical shift dispersion and complex multiplicity pattern in proton NMR limit quantifications, for instance the determination of enantiomeric excess (ee) for an enantiomeric mixture. Herein, we present a simple proton-proton correlation experiment with band selective homonuclear (BASH) decoupling in both F-1 and F-2 dimensions, for the removal of scalar and residual dipolar couplings to provide collapsed singlet for each chemical site. The method has been demonstrated to separate the severely overlapped spectra of enantiomers using both chiral isotropic and anisotropic phases as well as a small biomolecule, particularly for the diastereotopic protons and also for the determination of ee
Correction to “Probing the Accuracy of Explicit Solvent Constant pH Molecular Dynamics Simulations for Peptides”
No full textAuthor Correction: Relative configuration of micrograms of natural compounds using proton residual chemical shift anisotropy
No full textAn amendment to this paper has been published and can be accessed via a link at the top of the paper
Probing the accuracy of explicit solvent constant pH molecular dynamics simulations for peptides
Full text linkProtonation states of titratable amino acids play a key role in many biomolecular processes. Knowledge of protonatable residue charges at a given pH is essential for a correct understanding of protein catalysis, inter- and intramolecular interactions, substrate binding, and protein dynamics for instance. However, acquiring experimental values for individual amino acid protonation states of complex systems is not straightforward; therefore, several in silico approaches have been developed to tackle this issue. In this work, we assess the accuracy of our previously developed constant pH MD approach by comparing our theoretically obtained pKa values for titratable residues with experimental values from an equivalent NMR study. We selected a set of four pentapeptides, of adequately small size to ensure comprehensive sampling, but concurrently, due to their charge composition, posing a challenge for protonation state calculation. The comparison of the pKa values shows good agreement of the experimental and the theoretical approach with a largest difference of 0.25 pKa units. Further, the corresponding titration curves are in fair agreement, although the shift of the Hill coefficient from a value of 1 was not always reproduced in simulations. The phase space overlap in Cartesian space between trajectories generated in constant pH and standard MD simulations is fair and suggests that our constant pH MD approach reasonably well preserves the dynamics of the system, allowing dynamic protonation MD simulations without introducing structural artifacts
Quantification of geometric isomers of citral and minor oleochemicals in Cymbopogon flexuosus (lemongrass) and Cymbopogon nardus (citronella) essential oils by <sup>1</sup>H qNMR method
No full textThe 1H quantitative Nuclear Magnetic Resonance (qNMR) has emerged as a powerful analytical tool due to its high sensitivity, ability to provide absolute quantification, and most importantly, its univocal structural assignment. So far, 1H qNMR has been used to quantify only the major constituents of the essential oils (EOs). Since the minor constituents of the EOs play a role in its various properties, quantification of minor constituents is essential. In this study, a 1H qNMR method is developed to quantify major and minor oleochemicals in the multifaceted Cymbopogon flexuosus (lemongrass) and Cymbopogon nardus (citronella) EOs. The 1H qNMR method is validated in terms of selectivity, linearity, robustness, and accuracy/precision using the 1H NMR spectra of citral. The use of a high-field 800 MHz NMR provides high spectral resolution, allowing discrimination between closely spaced signals. This enables in-depth analysis of the complex mixtures of essential oils, facilitating the quantification of twelve distinct components, including some at concentrations in the double-digit μg range. These results align with prior reports demonstrating the suitability of high-field NMR spectrometers for accurate quantification of analytes at low μg/mL concentrations. This method demonstrates high sensitivity, with a limit of detection (LOD) of 30.09 μg/mL and a limit of quantification (LOQ) of 90.93 μg/mL. It also proves to be highly reliable, showing a coefficient of variation (CV) of less than 1% across different acquisition and processing conditions tested. The key distinction between lemongrass and citronella oils lies in their citral content, which ranges from 72 to 74% in lemongrass oil compared to only 12–18% in citronella oil. The quantification of both major as well as minor constituents highlights the applicability of the 1H qNMR method for comprehensive profiling of EOs
Methodological Developments in NMR for Chiral Analysis using Selective Excitation
No full textThe NMR spectroscopy as usually practiced in isotropic achiral solvents is unable to differentiate enantiomers, unless the intermolecular diastereomeric interactions are imposed with an enantiomerically pure reagent. Chiral auxiliaries such as chiral solvating agents (CSAs), chiral derivatizing agents (CDAs), chiral lanthanide shift reagents (CLSRs) in isotropic solvents and chiral liquid crystals are utilized to distinguish enantiomers. Chiral auxiliaries make use of chemical shift difference between the enantiomeric resonances to visualize enantiomers. On the other hand, chiral liquid crystals (CLCs) give access to different order sensitive NMR parameters for the enantiomers because of differential ordering effect on them. Among all the NMR active nuclei available for the investigation of chiral molecules, 1H and 13C at natural abundance are largely explored. However, the high sensitivity of proton and its ubiquitous presence in all organic molecules renders proton NMR as one of the foremost analytical tools for the study of enantiomers dissolved in chiral isotropic and anisotropic solvents. Despite its merits, proton detection has not been a preferred method for chiral discrimination in CLC, due to overcrowding of the spectra, resulting in non-resolution of coupling fine structures even for a molecule with few interacting protons. This is because of the presence of numerous couplings yielding large number of transitions in addition to doubling of signals from both the enantiomers. Nevertheless, the 1H NMR spectrum is rich in information content and the errors associated in the measurement of enantiomeric excess (ee) is reported to be relatively less (< 5%). Therefore, in this thesis, we have focused our attention to the use of proton NMR for chiral analysis. Selective excitation in 2D NMR techniques is a general strategy to simplify unresolved proton NMR spectra of enantiomers. Though other methodological developments for chiral liquid crystal NMR are progressing well, the work reported herein is the development of novel strategies using selective excitations for the resolution of overlapped-crowded 1H NMR spectra of enantiomers. The thesis is organized in six chapters and brief discussions of the contents of the individual chapters are given below.
Chapter 1 covers the theoretical preliminaries required for experimental works described in the rest of the thesis. After a brief discussion about NMR, its basic principle, and the interaction Hamiltonians responsible for yielding NMR spectra are discussed. Subsequently, it is followed by an introduction to product and polarization operator formalisms that gives an insight into the spin dynamics for designing two-dimensional NMR experiments. This introduction sets the foundation to understand the spectral patterns obtained from the experiments presented in this thesis. Since this thesis work involves the study of enantiomers embedded in CLC, a brief introduction is provided about chirality and liquid crystals. In the following sections, mechanism and spectral parameters used for the chiral discrimination process are discussed in detail.
Chapter 2 deals with a method based on transition selective one-dimension proton-proton COSY experiment for the selective detection of a single-enantiomer spectrum. The presence of numerous long-range couplings is considered as a hindrance for proton detection. On the other hand, in this method, the benefit is derived from the presence of numerous couplings among the various protons to single out the single-enantiomer or enantiopure spectrum from the severely overlapped spectrum of a racemic or scalemic mixture. The distinct advantage of the method is the determination of ee with an error of less than 3%. The method also finds significant advantage in the selective and systematic determination of proton-proton couplings of one of the enantiomers.
In chapter 3, two correlation experiments using 13C as a spy nucleus are described. It is divided in three parts. Part-I deals with the CESS-COSY experiment, where a single 13C spin edited selective proton-proton correlation is used to decipher overcrowded carbon coupled 1H NMR spectra of enantiomers embedded in CLC. The experiment unravels the masked 13C satellites in proton spectrum and permits the measurement of one bond carbon proton total (sum of indirect and direct) couplings in methyl group and for each diastereotopic proton in the methylene group. It also provides homonuclear proton-proton total couplings among the selectively excited protons for each enantiomer which are otherwise difficult to extract from the broad and featureless one dimensional 1H NMR spectrum. Employment of heteronuclear (13C) decoupling in the indirect dimension results
in complete resolution of overlapped signals. The anomalous intensity pattern, approximately in the ratio 1:2:3 for the dipolar coupled methyl protons observed in methyl selective CESS-COSY spectrum has been explained using polarization operator formalism.
In Part-II, another spin selective correlation experiment, designated as C-HetSERF is discussed not only for enantiodiscrimination, but also for the measurement of short and long range homonuclear and heteronuclear total couplings from the broad and featureless carbon-coupled 1H NMR spectra. The method employs a single natural abundant 13C spin as a spy nucleus to probe all the coupled protons and permits the determination of couplings of negligible strengths. This technique has been demonstrated for the study of organ soluble chiral molecules aligned in CLC where additional challenge is to unravel the overlapped spectrum of enantiomers. The significant advantage of the method in better chiral discrimination using homonuclear total couplings as additional parameters is described. The method also finds significant advantage in the measurement of relative signs of long-range heteronuclear total couplings. The merits and demerits of this method over the HetSERF experiment are highlighted.
In Part-III, C-HetSERF experiment is applied to the isotropic systems, especially for the measurement of long-range heteronuclear J-coupling. This extension of C-HetSERF experiment and its utilization signifies the importance. The measurement of these couplings is difficult because they are small in magnitudes and their measurement is associated with the low dilute nuclei such as 13C, 15N etc. A salient feature about C-
HetSERF experiment is that 13C α/β cross peaks appear in different cross-sections instead of a single cross-section in 2D. Therefore, the displacement between them pertains to the long-range couplings. This application has been demonstrated on an alkaloid and an undecapeptide.
Chapter 4 describes J/D-resolved techniques, cited as CH-SERF and CH-DQSERF for the visualization of enantiomers. These techniques utilize 13C-bound proton signals for the selective refocusing of the single and double quantum coherences of the methyl protons. Both methods yield distinct proton-proton couplings among the selectively excited protons and carbon-proton couplings to their directly attached carbon for each enantiomer thereby
simplifying the spectrum in indirect dimension. In the CH-DQSERF, each cross-section taken along the direct dimension represents the enantiopure spectrum of the methyl group and provides all proton-proton total couplings. CH-SERF also overcomes the problem of overlap of central transitions of the methyl selective refocusing (SERF) experiment resulting in better chiral discrimination.
In chapter 5, several protons detected 13C-filtered ω1-heterodecoupled resolved experiments and homonuclear multiple-quantum NMR experiments developed for the accurate measurement of ee are described. These methods retain the differential values of both 1H-1H and 13C-1H dipolar couplings for the enantiomers in the direct dimension and only 1H-1H dipolar couplings in the indirect dimension enabling complete unraveling of overlapped enantiomeric peaks. The creation of unequal 13C-edited proton signal because of average delay used in the INEPT block in resolved experiments and non-uniform excitation of coherences in homonuclear multiple quantum experiments for the enantiomers do not yield accurate measurement of ee. In order to combat these difficulties, a coupling dependent intensity correction factor has been invoked which substantially reduces the errors providing the accurate information. The error in the measurement of the ee is demonstrated to be within 2%. The phase sensitive DQ-SERF experiment using an adiabatic z-filter and its utility in the accurate measurement of ee is also demonstrated.
Chapter 6 discusses the study of chiral molecules in isotropic phase employing either a CLSR or a CSA as chiral auxiliaries. The higher substrate and chiral auxiliary concentration is a pre-requisite to obtain efficient separation of 1H NMR signals of enantiomers. The higher concentration of CLSRs causes spectral lines to broaden due to paramagnetic relaxation of lanthanide ions resulting in severe loss of resolution between the enantiomer resonances. To circumvent such difficulties, the application, and the usefulness of a selective F1 decoupled correlation (COSY) experiment which yields proton decoupled proton spectrum in the indirect dimension have been demonstrated. Use of this methodology overcomes the effect of paramagnetic relaxation online broadening at lower shift reagent concentration. The potential of the experiment is demonstrated on several chiral compounds possessing different functional groups
Residual‐Chemical‐Shift‐Anisotropy‐Based Enantiodifferentiation in Lyotropic Liquid Crystalline Phases Based on Helically Chiral Polyacetylenes
Full text linkAnisotropic NMR spectroscopy, revealing residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) has emerged as a powerful tool to determine the configurations of synthetic and complex natural compounds. The deduction of the absolute in addition to the relative configuration is one of the primary goals in the field. Therefore, the investigation of the enantiodiscriminating capabilities of chiral alignment media becomes essential. While RDCs and RCSAs are now used for the determination of the relative configuration routinely, RCSAs have not been measured in chiral alignment media such as chiral liquid crystals. Herein, we present this application by measuring RCSAs for chiral analytes such as indanol and isopinocampheol in the lyotropic liquid crystalline phase of an L-valine derived helically chiral polyacetylenes. We have also demonstrated that a single 1D 13C−{1H} NMR spectrum suffices to get the RCSAs circumventing the necessity to acquire two spectra at two alignment conditions
Hypalocrinins, Taurine-Conjugated Anthraquinone and Biaryl Pigments from the Deep Sea Crinoid <i>Hypalocrinus naresianus</i>
Full text linkFive new water-soluble amido- and
aminoanthraquinone pigments,
hypalocrinins A–E (1–5), the
new amidoanthraquinone biaryls hypalocrinin F (6) and
hypalocrinin G (7), and the known compounds 6-bromoemodic
acid (8), crinemodin (9), and crinemodin
sulfate (10) were isolated from the deep sea crinoid Hypalocrinus naresianus collected off Japan. The structures
of the compounds were elucidated by NMR spectroscopy and mass spectrometry.
Amido- and aminoquinones are quite unusual among natural products.
The hypalocrinins are the first naturally occurring anthraquinones
and anthraquinone biaryls conjugated with taurine
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