Category Archives: Our Publications

These are the scientific articles published by SeRMN personnel. Posts may contain a short description of the research work objective and relevance, in addition to the abstract of the article, the bibliographic reference, and the article DOI if available.

Simultaneous Enantiospecific Detection of Multiple Compounds in Mixtures using NMR Spectroscopy

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Simultaneous Enantiospecific Detection of Multiple Compounds in Mixtures using NMR Spectroscopy, by Lars T. Kuhn, Kumar Motiram-Corral, Toby J. Athersuch, Teodor Parella, Míriam Pérez-Trujillo*

Angew. Chem. Int. Ed., 2020 / doi:10.1002/anie.202011727

Chirality plays a fundamental role in nature, but its detection and quantification still face many limitations. To date, the enantiospecific analysis of mixtures necessarily requires prior separation of the individual components. The simultaneous enantiospecific detection of multiple chiral molecules in a mixture represents a major challenge, which would lead to a significantly better understanding of the underlying biological processes; e.g. via enantiospecifically analysing metabolites in their native environment. Here, we report on the first in situ enantiospecific detection of a thirty‐nine‐component mixture. As a proof of concept, eighteen essential amino acids at physiological concentrations were simultaneously enantiospecifically detected using NMR spectroscopy and a chiral solvating agent. This work represents a first step towards the simultaneous multicomponent enantiospecific analysis of complex mixtures, a capability that will have substantial impact on metabolism studies, metabolic phenotyping, chemical reaction monitoring, and many other fields where complex mixtures containing chiral molecules require efficient characterisation.

Simultaneous enantiospecific detection of a mixture of amino acids by NMR spectroscopy

This work has been selected to be presented as a talk at 2021 scientific conferences:

· 42nd FGMR (German Chemical Society, Magnetic Resonance Section) Annual Discussion Meeting – Virtual, Sep 27 to Oct 1.

· SMASH- Small Molecule NMR Conference 2021 – Virtual, Aug 30 to Sep 2.

· Euromar 2021 Conference – Virtual, 5 to 8 July.

· 10th GERMN (Spanish NMR group of the Real Sociedad Española de Química) biennial & 9th IberoAmerican NMR Meeting – Virtual, 26 to 19 April.

Electrochemical dehalogenation of dibromomethane and 1,2‐dibromoethane to non‐toxic products using a carbon fiber brush electrode

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Wiley Chemistry - उत्पादन/सेवा - १,०९१ वटा फोटोहरू | Facebook

by David Fernández‐Verdejo, Mira LK Sulonen, Míriam Pérez‐Trujillo, Ernest Marco‐Urrea, Albert Guisasola, Paqui Blánquez,  J. Chem. Technol. Biotechnol. 2020. https://doi.org/10.1002/jctb.6542

Dibromomethane (DBM) and 1,2‐dibromoethane (DBA) are two brominated volatile contaminants used in several industrial applications which are often detected in groundwater. The electrochemical degradation of DBM and DBA was studied at different cathode potentials (−0.8, −1 and −1.2 V versus Standard Hydrogen Electrode) in aqueous solution using an inexpensive graphite fiber brush electrode.

The degradation followed first‐order kinetics with respect to the nominal concentration of the brominated compounds, and the kinetic constant increased concomitantly with the decrease of the cathode potential. During the electrochemical dehalogenation 96.8% and 99.8% of the bromide in DBM and DBA was released as bromine ions, respectively. The main non‐brominated compounds detected during the degradation of DBM and DBA were methane and ethene, respectively. In addition, traces of formic acid for DBM and acetic acid for DBA degradation were detected by NMR spectroscopy. The non‐toxicity of the effluent was confirmed by a Microtox test. The efficient electrochemical degradation of DBM and DBA and the lack of toxic products open the door for a simple and non‐toxic electrochemical approach for removing aliphatic brominated compounds from aquifers and other water sources.

31P-NMR Metabolomics Revealed Species-Specific Use of Phosphorous in Trees

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31P-NMR Metabolomics Revealed Species-Specific Use of Phosphorous in Trees of a French Guiana Rainforest, by Gargallo-Garriga, A.; Sardans, J.; Llusià, J.; Peguero, G.; Asensio, D.; Ogaya, R.; Urbina, I.; Langenhove, L.V.; Verryckt, L.T.; Courtois, E.A.; Stahl, C.; Grau, O.; Urban, O.; Janssens, I.A.; Nolis, P.; Pérez-Trujillo, M.; Parella, T.; Peñuelas, J.  Molecules 2020, 25, 3960. https://doi.org/10.3390/molecules25173960

Productivity of tropical lowland moist forests is often limited by availability and functional allocation of phosphorus (P) that drives competition among tree species and becomes a key factor in determining forestall community diversity. We used non-target 31P-NMR metabolic profiling to study the foliar P-metabolism of trees of a French Guiana rainforest. The objective was to test the hypotheses that P-use is species-specific, and that species diversity relates to species P-use and concentrations of P-containing compounds, including inorganic phosphates, orthophosphate monoesters and diesters, phosphonates and organic polyphosphates. We found that tree species explained the 59% of variance in 31P-NMR metabolite profiling of leaves. A principal component analysis showed that tree species were separated along PC 1 and PC 2 of detected P-containing compounds, which represented a continuum going from high concentrations of metabolites related to non-active P and P-storage, low total P concentrations and high N:P ratios, to high concentrations of P-containing metabolites related to energy and anabolic metabolism, high total P concentrations and low N:P ratios. These results highlight the species-specific use of P and the existence of species-specific P-use niches that are driven by the distinct species-specific position in a continuum in the P-allocation from P-storage compounds to P-containing molecules related to energy and anabolic metabolism.

This article belongs to the Special Issue:

https://www.mdpi.com/journal/molecules/special_issues/nmr_metabolomics

In vivo MRI/MRS longitudinal study of immunotherapy in Alzheimer’s

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Progression of Alzheimer’s disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy by Güell-Bosch J, Lope-Piedrafita S, Esquerda-Canals G, Montoliu-Gaya L, and Villegas S. NMR in Biomedicine 33(5):e4263; DOI: 10.1002/nbm.4263.

Alzheimer’s disease (AD) is an incurable disease that affects most of the 47 million people estimated as living with dementia worldwide. The main histopathological hallmarks of AD are extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein.  In recent years, Aβ-immunotherapy has been revealed as a potential tool in AD treatment. One strategy consists of using single-chain variable fragments (scFvs), which avoids the fragment crystallizable (Fc) effects that are supposed to trigger a microglial response, leading to microhemorrhages and vasogenic edemas, as evidenced in clinical trials with bapineuzumab. The scFv-h3D6 generated by our research group derives from this monoclonal antibody, which targets the N-terminal of the Aβ peptide and recognizes monomers, oligomers and fibrils.

In this study, 3xTg-AD mice were intraperitoneally and monthly treated with 100 μg of scFv-h3D6 (a dose of ~3.3 mg/kg) or PBS, from 5 to 12 months of age (-mo), the age at which the mice were sacrificed and samples collected for histological and biochemical analyses. During treatments, four monitoring sessions using magnetic resonance imaging and spectroscopy (MRI/MRS) were performed at 5, 7, 9, and 12 months of age. MRI/MRS techniques allow, in a non-invasive manner, to draw an in vivo picture of concrete aspects of the pathology and to monitor its development across time. Compared with the genetic background, 3xTg-AD mice presented a smaller volume in almost all cerebral regions and ages examined, an increase in both the intra and extracellular Aβ1-42 at 12-mo, and an inflammation process at this age, in both the hippocampus (IL-6 and mIns) and cortex (IL-6). In addition, treatment with scFv-h3D6 partially recovered the values in brain volume, and Aβ, IL-6, and mIns concentrations, among others, encouraging further studies with this antibody fragment.

Measuring Long-Range Heteronuclear NMR Correlations in Natural Products

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LR-HSQMBC versus LR-selHSQMBC: Enhancing the Observation ofTiny Long-Range Heteronuclear NMR Correlations

Kumar Motiram-Corral, Pau Nolis, Josep Saurí, and Teodor Parella

https://doi.org/10.1021/acs.jnatprod.0c00058

selHSQMBC

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.

Microwave-Assisted Synthesis of SPION-Reduced Graphene Oxide Hybrids for Magnetic Resonance Imaging (MRI)

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by Llenas M, Sandoval S, Costa PM, Oró-Solé J, Lope-Piedrafita S, Ballesteros B, Al-Jamal KT, Tobias G. Nanomaterials 24;9(10), 1364; DOI: 10.3390/nano9101364.

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.

Removal of the synthetic hormone methyltestosterone from aqueous solution using a β-cyclodextrin/silica composite

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Lucas Bragança Carvalho, Pricila Maria BatistaChagas, Tamara Rezende Marques, Angelina Razafitianamaharavo, Manuel Pelletier, Pau Nolis, Carlos Jaime, Sérgio Scherrer Thomasi, Lucianade Matos Alves Pinto.

Journal of Environmental Chemical Engineering – Available online 20 October 2019

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. 

Recyclable Mesoporous Organosilica Nanoparticles (MSN) for Asymmetric Organocatalysis

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Li, Hao, Míriam Pérez-Trujillo, Xavier Cattoën & Roser Pleixats. 2019. Recyclable Mesoporous Organosilica Nanoparticles Derived from Proline-Valinol Amides for Asymmetric Organocatalysis. ACS Sustainable Chemistry & Engineering 7(17). 14815-14828. DOI: 10.1021/acssuschemeng.9b02838

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.

Measuring Long-Range Heteronuclear Coupling Constants with Sel-HSQMBC Experiments: A Tutorial

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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.

Strychnine dataset examples available here.