ABSTRACT:The detection of ultra-long-range (4JCHand higher) heteronuclear connectivities can complement the conventionaluse of HMBC/HSQMBC data in structure elucidation NMR studies of proton-deficient natural products, where two-bond andthree-bond correlations are usually observed. The performance of the selHSQMBC experiment with respect to its broadbandHSQMBC counterpart is evaluated. Despite its frequency-selectivity nature, selHSQMBC efficiently prevents any unwanted signalphase and intensity modulations due to passive proton−proton coupling constants typically involved in HSQMBC. As a result,selHSQMBC offers a significant sensitivity enhancement and provides pure in-phase multiplets, improving the detection levels forshort- and long-range cross-peaks corresponding to small heteronuclear coupling values. This is particularly relevant for experimentsoptimized to smallnJCHvalues (2−3 Hz), referred to as LR-selHSQMBC, where key cross-peaks that are not visible in the equivalentbroadband LR-HSQMBC spectrum can become observable in optimum conditions.
The optimum detection and accurate measurement of longer-range ( 4 J and higher) heteronuclear NMR correlations is described. The magnitude and/or the sign of a wide range of large and small long-range couplings can be simultaneously determined for protonated and non-protonated 13 C and 15 N nuclei using the LR-selHSQMBC experiment.
Magnetic resonance imaging (MRI) is a useful tool for disease diagnosis
and treatment monitoring. Superparamagnetic iron oxide nanoparticles (SPION)
show good performance as transverse relaxation (T2) contrast agents, thus
facilitating the interpretation of the acquired images. Attachment of SPION
onto nanocarriers prevents their agglomeration, improving the circulation time
and efficiency. Graphene derivatives, such as graphene oxide (GO) and reduced
graphene oxide (RGO), are appealing nanocarriers since they have both high
surface area and functional moieties that make them ideal substrates for the
attachment of nanoparticles. A fast, simple, and environmentally friendly
microwave-assisted approach for the synthesis of SPION-RGO hybrids has been demonstrated
in this study. Different iron precursor/GO ratios were used leading to SPION,
with a median diameter of 7.1 nm, homogeneously distributed along the RGO
surface. Good relaxivity (r2*) values were obtained in MRI studies and no
significant toxicity was detected within in vitro tests following GL261 glioma
and J774 macrophage-like cells for 24 h with SPION-RGO, demonstrating the
applicability of the hybrids as T2-weighted MRI contrast agents.
“Supramolecular Fullerene Sponges as Catalytic Masks for Regioselective Functionalization of C60“, by Carles Fuertes-Espinosa, Cristina García-Simón, Míriam Pujals, Marc Garcia-Borràs, Laura Gómez, Teodor Parella, Judit Juanhuix, Inhar Imaz, Daniel Maspoch, Miquel Costas and Xavi Ribas.
The supramolecular mask protocol is a significant step forward for the regioselective functionalization of fullerenes. The exquisite ability to form pure-isomer poly-functionalized C60 adducts, overcoming tedious and non-practical chromatographic separations, allows for their direct testing in solar cell prototypes. Furthermore, the supramolecular mask strategy can be applied to C70 or higher fullerenes, opening a plethora of poly-functionalized fullerene derivatives to be synthesized and tested. Moreover, apart from the nucleophilic cyclopropanations reported herein, the protocol is currently being expanded to Diels-Alder (DA), 1,3-dipolar cycloadditions and PC60BM-type cyclopropanations, thus enabling a variety of regioselective functionalization reactions. This supramolecular mask strategy can help the discovery of the next generation of improved solar cells (organic or perovskite based) or new drug candidates.
This research has been carried out in close collaboration with Dr. Xavi Ribas (from the QBIS-CAT research group of the University of Girona (UdG)), the Catalan Institute of Nanotechnology (ICN2), the ALBA-BCN synchrotron and the NMR Service of the Autonomous University of Barcelona ( UAB). The results have just been published in the online version of the prestigious CHEM scientific journal .
ABSTRACT Contamination of water with steroid residues can cause a number of environmental damages, affecting exposed organisms including man. The development of technologies for treatment or removal of this type of micropollutant from water is of paramount importance. In this study, citric acid was used to functionalize β-cyclodextrin (bCD) on the silica surface generating an organic-inorganic hybrid composite for application in molecular sequestration. The functionalization percentage was high, with about 62.6% of the composite mass corresponding to the organic part of the material. 13C NMR and infrared spectroscopic analysis indicate that the functionalization mechanism occurs by an esterification reaction between the citric acid with the silanol groups from silica and the primary hydroxyls of the bCDs. Fast adsorption of the methyltestosterone steroid was observed at acid pH, with a high adsorption capacity of 11 mg g-1. The best kinetic and isotherm models fit indicated that the adsorption occurred by a physical mechanism at independent sites with the steroid molecule possibly captured by two bCDs. The removal process was spontaneous and exothermic, with the existence of weak interactions between the hormone and the composite, and its regeneration is quite fast efficient with the displacement of the complexation equilibrium. The results obtained in this study demonstrate the considerable potential of the composite for use in the treatment of wastewater containing the steroid studied, and its efficacy should be evaluated for other steroid molecules.
This is the first report on the obtention of functionalized MSN by a co-condensation procedure with a structurally complex chiral precursor. The functionalized MSN have been characterized by elemental analysis, 29Si and 13C CP MAS NMR, transmission electron microscopy, scanning electron microscopy, N2-sorption measurements, dynamic light scattering, ζ-potential, and powder X-ray diffraction. We have evaluated the activity of these materials as recyclable catalysts in the asymmetric aldol reaction. The use of organosilica nanoparticles reduces the problems of diffusion and low reaction rates encountered with bulk organosilicas.
We are recruiting an Early Stage Researcher to work on a decision-support system based on MRSI data at 3T, for glioblastoma therapy response follow- up, as part of the INSPiRE-MED European project.
We seek a highly motivated and qualified individual as Early Stage Researcher for a three-year applied research project. The successful candidate will contribute to the development of advanced biomedical research tools in the field of Magnetic Resonance Spectroscopy and Imaging, and its application to the clinical day-to-day practice.
Project description: This position is one of the 15 ESR positions of the INSPiRE-MED European Training Network, which focuses on the development of Magnetic Resonance Spectroscopy (MRS) and MR Spectroscopic Imaging (MRSI) combined with Positron Emission Tomography (PET), enhanced by machine learning techniques.
The main aim of the PhD project (ESR12) will be development of a Machine Learning medical decision-support system based on MRSI data at 3T, for glioblastoma therapy response follow-up.
The
ESR will develop a novel medical decision support system (MDSS)
focused on glioblastoma therapy response follow-up, based on magnetic
resonance spectroscopic imaging (MRSI) data, able to take and process
data from multiple MRSI formats and centres. For each patient’s
MRSI, the MDSS should deliver a nosological or classification image,
ready to be fused with images of other MR modalities from the same
patient. The DSS will be integrated into the interface of the
academic version of jMRUI, in a way that allows clinicians evaluate
the system with their data. An important part of of the project will
be the incorporation of automated MRSI artifact detection and removal
tools.
Kumar Motiram-Corral presented a poster titled “Implementing one-shot multiple-FID acquisition into homonuclear and heteronuclear NMR experiments” at SMASH 19 in Porto (Portugal).
To date, time-efficient approaches are a challenged task for spectroscopists. The goal is to obtain chemical information reducing experimental time without considerably losing of sensitivity.
Different time-efficient approaches have been described over the years. Time sharing (Parella et. al.) tactic acquires the 15N and 13C nuclei in the same spectrum in spectrometers which have a triple channel hardware configuration[1]. Non-Uniform Sampling (NUS) [2] algorithm has achieved a substantial reduction of experimental time reducing the number of t1 increments needed by multidimensional experiments. Recently, NOAH [3] (NMR by ordered Acquisition using 1H detection) has been developed by Kupče (Bruker Co.) and Claridge (University of Oxford) provides the way to get proper experiments in different spectra with the same spectral quality.
[4]MFA (Multiple FID Acquisition) consists in obtaining up to four different experiments decreasing close to 60% of time. MFA provides a new novel proof concept of COSY, TOCSY and HMBC experiments in small molecules. Actually, MFA strategy was proposed many years ago with the COCONOSY experiment [5-7], which could be collected 2D COSY and NOESY data with a single pulse scheme. [4]MFA has also been implemented in magic-angle-spinning solid-state NMR experiments devoted for biomacromolecules using standard spectrometer configuration. Despite its limitations related to the use of long acquisition of free-induction decays (FIDs) to accurately digitalize the data and the mandatory use of long phase cycles for convenient pathway selection, nowadays, the use of pulsed field gradients (PFGs) is the solution for this drawback. [4]MFA is based on the relaxation of the remaining transverse magnetization, which usually relaxes to its original magnetization, can be manipulated by an appropriate additional mixing process and recorded again to obtain a second or third NMR data provided that T2 (transverse relaxation times) are long enough. [4]Its main advantage is that each experiment is acquired in a different display. [4]MFA is a powerful experiment for the sequential structural assignment of a whole spin system without ambiguities. This method is also useful for selective experiments as SE-TOCSY.
References:
Nolis, P., Pérez, M., & Parella, T. (2006). Time-sharing evolution and sensitivity enhancements in 2D HSQC-TOCSY and HSQMBC experiments. Magnetic Resonance in Chemistry, 44, 11, 1031-1036, 2006
K. Kazimierczuk and V. Y. Orekhov , Angew. Chem., Int. Ed., 2011, 50 , 5556 -5559
Kupče, E., & Claridge, T. D. W. (2018). Molecular structure from a single NMR supersequence. Chemical Communications, 54, 7139-7142, 2018.
Motiram-Corral, K., Pérez-Trujillo, M., Nolis, P., & Parella, T. (2018). Implementing one-shot multiple-FID acquisition into homonuclear and heteronuclear NMR experiments. Chemical Communications, 54(96), 13507–13510, 2018.
A. Z. Gurevich , I. L. Barsukov , A. S. Arseniev and V. F. Bystrov , J. Magn. Reson.,56, 471 -478, 1984.
C. A. G. Haasnoot , F. J. M. van de Ven and C. W. Hilbers , J. Magn. Reson., 56 , 343 -349, 1984.
J. Cavanagh and M. Rance , J. Magn. Reson., 14 , 408 -414, 1990.
How to measure long‐range proton‐carbon coupling constants from 1H‐selective HSQMBC experiments, by Josep Saurí, Pau Nolis and Teodor Parella. Magn. Reson. Chem. 2019. Early View, DOI: https://onlinelibrary.wiley.com/doi/10.1002/mrc.4928
Heteronuclear long‐range scalar coupling constants (nJCH) are a valuable tool for solving problems in organic chemistry and are especially suited for stereochemical and configurational analyses of small molecules and natural products. This tutorial will focus on the step‐by‐step implementation of several 2D 1H frequency selective HSQMBC experiments for the easy and accurate measurement of either the magnitude or both the magnitude and the sign of long‐range nJCH couplings. The performance of these experiments will be showcased with several scenarios in a range of different experimental conditions.
Bruker pulse program code for selHSQMBC experiments available here.
Bruker pulse program code for selHSQMBC-TOCSY experiment available here.
Some of the SeRMN staff will present our last research works at the annual meeting of the European magnetic resonance community ISMAR EUROMAR 2019 Conference that will take place from 25th to 30th August in Berlin. Find below a summary of our contributions.
Speeding-up NMR molecular analysis is an
important research field which has been continuously advancing since NMR early
days. The relevant benefits are clear and evident: reduce the time per analysis
directly reduce its cost and gaining spectrometer time to analyze new samples. Many
interesting tools and concepts have been appearing in last decades. Concretely,
our experience focuses on the development of new NMR experiments using TS
(Time-Shared), SA (Spectral Aliasing) and MFA (Multiple Fid Acquisition). MFA
strategy is an interesting strategy that allows the acquisition of different structural
information in a single experiment. Basically, MFA experiments consist in the
design of pulse sequence experiments which accommodate several acquisition
windows per experi-ment, each registering different relevant information for
the structural molecular character-ization. The methodology brings a
corresponding important time benefit. Last year, we have reported several new
NMR experiments designed with MFA stratey and herein we would present the most
relevant achievements. The overall discussion will be mainly focused on the
sensitivity gains per time unit of the presented experiments.
The
3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane
commonly named pentaspiroglycol
(PSG) or spiroglycol (SPG) is a high molecular weight rigid alicy-clic diol widely used in the chemical
industry. SPG has no hazardous classification, it is not mutagenic and is a safe alternative to
Bisphenol A, a well-known chemical which is rising concern due to his proved endocrine
disruptor activity. Moreover, some of the SPG main applications are focused on epoxy resins,
liquid polyester resins, radiation curing resins and
in polymer film material field. However, the spiroglycol structure,
configuration and conformation
have never been deeply studied. Herein,
we perform for the first time a preliminary NMR and computational study of the spiroglycol structure. SPG is a highly
symmetrical molecule but it should be chiral due to
the presence of a chiral axis. The presence of two enantiomers was demonstrated
per-forming NMR
enantiodifferentiation experiments using α,α’-bis(trifluoromethyl)-9,10-an-thracenedimethanol (ABTE) as chiral
solvating agent (CSA). The addition of 0.6 equivalents of ABTE allows the differentiation of
several spiroglycol proton signals. The lack of resolu-tion observed in the proton spectrum can be
tackled through the corresponding 13C NMR spectrum
where a significant enantiodifferentiation at the spirocarbon atom was observed.In order to physically separate both
enantiomers, a SPG derivatization with camphor-sulphonic
acid was performed affording the corresponding diastereoisomeric ester mixture.
by Llenas M, Sandoval S, Costa PM, Oró-Solé J, 
Chem, in press (2020). DOI: 
