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.

Solid State NMR supports a new study on hydride composite for hydrogen storage

A hydride composite featuring mutual destabilisation and reversible boron exchange: Ca(BH4)2–Mg2NiH4

N. Bergemann, C. Pistidda, C. Milanese, M. Aramini, S. Huotari, P. Nolis, A. Santoru, M. R. Chierotti, A.-L. Chaudhary, M. D. Baro, T. Klassen and M. Dornheim.

ABSTRACT:The system Ca(BH4)2–Mg2NiH4 is used as a model to prove the unique possibility to fully reverse the borohydride decomposition process even in cases where the decomposition reaction leads to undesired stable boron containing species (boron sinks). The formation of MgNi2.5B2 directly from Ca(BH4)2 or from CaB12H12 and amorphous boron allows an unexpectedly easy transfer of the boron atoms to reversibly form Ca(BH4)2 during rehydrogenation. In addition, to the best of our knowledge, the mutual destabilisation of the starting reactants is observed for the first time in Ca(BH4)2 based Reactive Hydride Composite (RHC) systems. A detailed account of dehydrogenation and rehydrogenation reaction mechanisms as the function of applied experimental conditions is given.


PhD Thesis: Development of Resolution-Enhanced NMR Techniques for Improved Small Molecules Structural Analysis

Last July 14th 2018 Núria Marcó defended her PhD Thesis entitled: Development of Resolution-Enhanced NMR Techniques for Improved Small Molecules Structural Analysis


The present doctoral thesis is framed within the field of Nuclear Magnetic Resonance (NMR) spectroscopy.

NMR spectroscopy is an analytic technique and, therefore, one of its main objectives is to unravel the correct structure of the molecules analyzed.This present doctoral thesis  is focused on this main objective. This work consists in a compendium of 7 publications, written in several prestigious scientific journals, that develop in depth the efficient and accurate determination of the constitution, configuration and conformation of small molecules thanks to the application of resolution improvements techniques.

In order to do that it is studied the accurate and efficient measurement of isotropic (homo- and heteronuclear scalar coupling constants) for the 2D structre determination, as well as the anisotropic parameters (RDCs, RCSAs and RQCs) for the 3D structure analysis. These anisotropic parameters allows us the discrimination of the different conformers of a molecule and can be found in weakly alignment media. PMMA gel provides an easy, reusable, and practical way to obtain this weakly alignment media. In this work, It has been researched the best way to get these anisotropic parameters, developing and adapting new pulse sequences to this type of media.

To get the correct structure (2D and 3D) it is important to obtain a precise and accurate measurement. In this thesis the great accuracy of isotropic and anisotropic parameters has been achieved through the use of resolution improvement techniques such as Pure-Shift, Spectral Aliasing and Non Uniform Sampling.

In addition it has been applied protocols for the easy automatization and measurement of coupling constants in isotropic and anisotropic media.

Also it has been design improved pulse sequences to achieve the measurement of longer- range heteronuclear connectivities that will  increase the amount of information that we will have available to do the structural analysis

Each experiment has been discussed from a methodological point of view. An assessment on its application has been also performed.

Pulse Programs and Data Set Examples:

Publication 1:
Extending long-range heteronuclear NMR connectivities by HSQMBC-COSY and HSQMBC-TOCSY experiments Saurí, J.; Marcó, N.; Williamson, R. T.; Martin, G. E.; Parella, T. J. Magn. Reson. 2015, 258, 25–32.
DOI 10.1016/j.jmr.2015.06.004

Pulse Program Code for Bruker:

Data set Example:


Publication 2:
Ultra high-resolution HSQC: Application to the efficient and accurate measurement of heteronuclear coupling constants  Marcó, N.; Fredi, A.; Parella, T. Chem. Commun. 2015, 51 (15), 3262–3265.
DOI 10.1039/C4CC10279G

Pulse Program Code for Bruker:

Data set Example:


Publication 3:
Isotropic/Anisotropic NMR Editing by Resolution-Enhanced NMR Spectroscopy Marcó, N.; Gil, R. R.; Parella, T. ChemPhysChem 2018, 19, 9, 1024-1029.
DOI: 10.1002/cphc.201800094

Pulse Programs Code for Bruker:


Publication 4:
Structural discrimination from in situ measurement of 1DCH and 2DHH residual dipolar coupling constants Marcó, N.; Gil, R. R.; Parella, T. Magn. Reson. Chem. 2017, 55 (6), 540–545.
DOI 10.1002/mrc.4575

Pulse Programs Code for Bruker:

Data set Example:


Publication 5:
Perfect 1JCH-resolved HSQC: Efficient measurement of one-bond proton-carbon coupling constants along the indirect dimension Marcó, N.; Souza, A. A.; Nolis, P.; Gil, R. R.; Parella, T. J. Magn. Reson. 2017, 276, 37–42.
DOI: 10.1016/j.jmr.2017.01.002

Pulse Programs Code for Bruker:

Data set Example:


Publication 6:
1JCH NMR Profile: Identification of key structural features and functionalities by visual observation and direct measurement of one-bond proton-carbon coupling constants Marcó, N.; Souza, A. A.; Nolis, P.; Cobas, C.; Gil, R. R.; Parella, T. J. Org. Chem. 2017, 82 (4), 2040–2044.
DOI: 10.1021/acs.joc.6b02873

Pulse Programs Code for Bruker:


Publication 7:
2JHH-resolved HSQC: Exclusive determination of geminal proton-proton coupling constants Marcó, N.; Nolis, P.; Gil, R. R.; Parella, T. J. Magn. Reson. 2017, 282, 18–26.
DOI: 10.1016/j.jmr.2017.06.014

Pulse Programs Code for Bruker:


Solid-State-NMR a useful tool for the characterization of Hydrogen Storage Composite System

In Situ Formation of TiB2 Nanoparticles for Enhanced Dehydrogenation/Hydrogenation Reaction Kinetics of LiBH4–MgH2 as a Reversible Solid-State Hydrogen Storage Composite System

Fahim Karimi* , María V. C. Riglos, Antonio Santoru , Armin Hoell, Vikram S. Raghuwanshi, Chiara Milanese, Nils Bergemann, Claudio Pistidda, Pau Nolis , Maria D. Baro, Gökhan Gizer, Thi-Thu Le, P. Klaus Pranzas, Martin Dornheim, Thomas Klassen, Andreas Schreyer, and Julián Puszkiel

J. Phys. Chem. C, Article ASAP
DOI: 10.1021/acs.jpcc.8b02258
Publication Date (Web): May 9, 2018
ABSTRACT:To enhance the dehydrogenation/rehydrogenation kinetic behavior of the LiBH4–MgH2 composite system, TiF4 is used as an additive. The effect of this additive on the hydride composite system has been studied by means of laboratory and advanced synchrotron techniques. Investigations on the synthesis and mechanism upon hydrogen interaction show that the addition of TiF4 to the LiBH4–MgH2 composite system during the milling procedure leads to the in situ formation of well-distributed nanosized TiB2 particles. These TiB2 nanoparticles act as nucleation agents for the formation of MgB2 upon dehydrogenation process of the hydride composite system. The effect of TiB2 nanoparticles is maintained upon cycling.

NEW BOOK RELEASE: “Preclinical MRI methods and protocols”

“Preclinical MRI: Methods and Protocols” by Maria Luisa Garcia Martin and Pilar Lopez Larrubia (Editors). Part of the Methods in Molecular Biology book series (MIMB, volume 1718). DOI: 10.1007/978-1-4939-7531-0.

This book was conceived with the idea of providing an update on a wide variety of preclinical MRI methods and protocols to help technicians and researchers interested in this technology. The basics of MRI physics are introduced, followed by chapters describing updated methodology and protocols for some standard and more advanced MRI techniques covering diffusion, perfusion, functional imaging, in-vivo spectroscopy (proton and heteronuclear), susceptibility contrast MRI… The book also contains some chapters where some applications of those methods are illustrated in animal models of several diseases including cancer, stroke and neurodegeneration. Protocols are described in a step-by-step approach, with interesting notes and tips at the end of each chapter, which -a priori- should allow the new worker to obtain successful results with the first attempt ;o) .

Simultaneous RCSA and RDC measurement

Isotropic/Anisotropic NMR Editing by Resolution-Enhanced NMR Spectroscopy by Núria Marcó,  R. R. Gil and Teodor Parella. ChemPhysChem 2018, DOI: 10.1002/cphc.201800094

Modern resolution-enhanced NMR techniques can monitor the in-situ discrimination of co-existing isotropic and anisotropic contributions of small molecules dissolved in weakly aligning PMMA/CDCl3 media. The simultaneous sign-sensitive determination of accurate Δδ(1H) and Δδ(13C) between isotropic and anisotropic signals,  and/or  1TCH and 1JCH coupling constants (and consequently 1H-13C RDCs and 1H/13C RCSAs) can be performed from spectral-aliased HSQC spectra.

Pulse Programs Code for Bruker:

Precise characterization of mycobacterial cell wall lipid PTTM

Molecule confirmation and structure characterization of pentatriacontatrienyl mycolate in Mycobacterium smegmatisby M. Llorens-Fons, E. Julián, M. Luquin and M. Pérez-Trujillo. Chemistry and Physics of Lipids, 2018, Accepted Manuscript. DOI:

Mycobacterium smegmatis is often used to study the different components of mycobacterial cell wall. Mycolic acids are important components of mycobacterial cell wall that have been associated with virulence. Recently, a novel lipid containing mycolic acids has been described in M. smegmatis. However, some uncertainties regarding the structure of this molecule named mycolate ester wax have been reported. The objective of this work was to perform an in depth structural study of this molecule for its precise characterization. Using 1H and 13C NMR spectroscopy, the molecular structure of mycolate ester wax found in M. smegmatis has been elucidated. The characterization was complemented with MS analyses. This molecule is formed by a carbon chain with three methyl substituted olefinic units and a mycolate structure with trans double bonds and cis cyclopropane rings. The present molecular study will facilitate the detection and identification of pentatriacontatrienyl mycolate (PTTM) in future studies by the performance of a simple 1D 1H NMR experiment.

Assessment of biodistribution using mesenchymal stromal cells

“Assessment of biodistribution using mesenchymal stromal cells: Algorithm for study design and challenges in detection methodologies” by Reyes B, Coca MI, Codinach M, López-Lucas MD, Del Mazo-Barbara A, Caminal M, Oliver-Vila I, Cabañas V, S. Lope-Piedrafita, García-López J, Moraleda JM, Fontecha CG, Vives J. Cytotherapy. 2017 :1060-1069. doi: 10.1016/j.jcyt.2017.06.004.

Biodistribution of candidate cell-based therapeutics is a critical safety concern that must be addressed in the preclinical development program. We aimed to design a decision tree based on a series of studies included in actual dossiers approved by competent regulatory authorities, noting that the design, execution and interpretation of pharmacokinetics studies using this type of therapy is not straightforward and presents a challenge for both developers and regulators. This work contributes to the standardization in the design of biodistribution studies by improving methods for accurate assessment of safety.

Eight studies were evaluated for the definition of a decision tree, in which mesenchymal stromal cells (MSCs) were administered to mouse, rat and sheep models using diverse routes (local or systemic), cell labeling (chemical or genetic) and detection methodologies (polymerase chain reaction (PCR), immunohistochemistry (IHC), fluorescence bioimaging, and magnetic resonance imaging (MRI). Moreover, labeling and detection methodologies were compared in terms of cost, throughput, speed, sensitivity and specificity.

Multiplicity-edited 1H-1H TOCSY experiment

Pau Nolis and Teodor Parella

Magnetic Resonance in Chemistry 2017 (DOI: 10.1002/mrc.4695)


A 1H-1H TOCSY experiment incorporating 13C multiplicity information is proposed. In addition, broadband 1H homodecoupling in the indirect dimension can be implemented using a perfect BIRD module that affords exclusive 1H chemical shift evolution with full decoupling of all heteronuclear and homonuclear (including 2JHH) coupling constants. As a complement to the normal TOCSY and the recent PSYCHE-TOCSY experiments, this novel multiplicity-edited TOCSY experiment distinguishes between CH/CH3 (phased up) and CH2 (phased down) cross-peaks which facilitates resonance analysis and assignment.

Tripeptides studied by NMR

Stereoselectivity of Proline / Cyclobutane Amino Acid-Containing Peptide Organocatalysts for Asymmetric Aldol Additions: a Rationale

Ona Illa, Oriol Porcar-Tost, Carme Robledillo, Carlos Elvira, Pau Nolis, Oliver Reiser, Vicenç Branchadell, and Rosa M. Ortuño

J. Org. Chem., Just Accepted Manuscript
DOI: 10.1021/acs.joc.7b02745
Publication Date (Web): November 29, 2017

Several α,β,α- or α,γ,α-tripeptides, consisting of a central cyclobutane β- or γ-amino acid being flanked by two (D)- or (L)-proline residues, have been synthesized and tested as organocatalysts in asymmetric aldol additions. High yields and enantioselectivities have been achieved with α,γ,α-tripeptides, being superior to the peptides containing a cyclobutane β-amino acid residue. This can probably be due to their high rigidity, which hinders the peptide catalysts to adopt the proper active conformation. This reasoning correlates with the major conformation of the peptides in the ground state, as suggested by 1H NMR and computational calculations. The configuration of the aldol products is controlled by the proline chirality, and consequently, the R/S configuration of aldol products can be tuned by the use of either commercially available (D)- or (L)-proline enantiomers. The enantioselectivity in the aldol reactions is reversed if the reactions are carried out in the presence of water or other protic solvents such as methanol. Spectroscopic and theoretical investigations revealed that this effect is not the consequence of conformational changes in the catalyst but rather caused by the participation of a water molecule in the rate determining transition state, in such a way that the preferential nucleophilic attack is oriented to the opposite enantiotopic aldehyde face.

NMR could improve the detection of “date rape” drug GHB

Direct Monitoring of Exogenous γ-Hydroxybutyric Acid in Body Fluids by NMR Spectroscopy” by M. Palomino-Schätzlein, Y. Wang, A. Brailsford, T. Parella, D. Cowan, C. Legido-Quigley, M. Pérez-Trujillo. Anal. Chem., 2017, 89 (16), pp 8343–8350. DOI:

γ-Hydroxybutyric acid (GHB) is a popular drug increasingly associated with cases of drug-facilitated sexual assault (DFSA). Currently, expanding procedures of analysis and having forensic evidence of GHB intake in a long term are mandatory. Up to now, most studies have been performed using GC/MS and LC-MS as analytical platforms, which involve significant manipulation of the sample and, often, indirect measurements. In this work, procedures used in NMR-based metabolomics were applied to a GHB clinical trial on urine and serum. Detection, identification, and briefly quantification of the drug by NMR methods were surveyed, as well as the use of NMR-based metabolomics for the search of potential surrogate biomarkers of GHB consumption. Results demonstrated the suitability of NMR spectroscopy, as a robust nondestructive technique, to fast and directly monitor exogenous GHB in almost intact body fluids and its high potential in the search for metabolites associated with GHB intake. This initial work show some strengths of  NMR spectroscopy and standard methods routinely used in the NMR analysis of biological samples to approach the problem. These features could open up new interesting possibilities in future studies, complementing current procedures.

This work on media:  /  / /  /