Multiplicity-edited 1H-1H TOCSY experiment

Pau Nolis and Teodor Parella

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

Abstract

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

Abstract
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.

SeRMN contribution to Symmetry 2017 Conference

 

Some of the SeRMN staff  presented our last research work about chirality at The first International Conference on Symmetry, Symmetry 2017, that took place from16th to 18th October in Barcelona. Find below a summary of our contribution.

Míriam Pérez-Trujillo presented a lecture entitled: “Chiral Recognition by Dissolution Dynamic Nuclear Polarization NMR Spectroscopy

Abstract: The recognition of enantiomeric molecules by chemical analytical techniques is still a challenge. A method based on d-DNP (dissolution dynamic nuclear polarization) NMR spectroscopy to study chiral recognition was described for the first time [1]. DNP allows boosting NMR sensitivity by several orders of magnitude, overcoming one of the main limitations of NMR spectroscopy [2]. A method integrating d-DNP and 13C NMR-aided enantiodifferentiation using chiral solvating agents (CSA) was developed, in which only the chiral analyte was hyperpolarized and selectively observed by NMR. The described method enhances the sensitivity of the conventional NMR-based procedure [3] and lightens the common problem of signal overlapping between analyte and CSA. As proof on concept, racemic metabolite 13C-labeled DL-methionine was enantiodifferentiated by a single-scan 13C NMR experiment. This method entails a step forward in the chiral recognition of small molecules by NMR spectroscopy; it opens new possibilities in situations where the sensitivity is limited, for example, when low analyte concentration available or when measurement of an insensitive nucleus required. The advantages and current limitations of the method, as well as future perspectives, are discussed.

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: http://dx.doi.org/10.1021/acs.analchem.7b01567

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:   spectroscopynow.com  phys.org  / sciencedaily.com  /  canadafreepress.com / forensicmag.com  / cbinsights.com

NMR identification of monstrous mycobacterial lipids in cell wall of Mycobacterium abcessus

” Trehalose polyphleates, external cell wall lipids in Mycobacterium abcessus, are associated with the formation of clumps with cording morphology, which have been associated with virulence” by M. Llorens-Fons, M. Pérez-Trujillo, E. Julián, C. Brambilla, F. Alcaide, T. F. Byrd and M. Luquin. Frontiers in Microbiology, 2017, 8:1402. DOI: http://dx.doi.org/10.3389/fmicb.2017.01402

Mycobacterium abscessus is a reemerging pathogen that causes pulmonary diseases similar to tuberculosis, which is caused by Mycobacterium tuberculosis. When grown in agar medium, M. abscessus strains generate rough (R) or smooth colonies (S). R morphotypes are more virulent than S morphotypes. In searching for the virulence factors responsible for this difference, R morphotypes have been found to form large aggregates (clumps) that, after being phagocytozed, result in macrophage death. Furthermore, the aggregates released to the extracellular space by damaged macrophages grow, forming unphagocytosable structures that resemble cords. In contrast, bacilli of the S morphotype, which do not form aggregates, do not damage macrophages after phagocytosis and do not form cords. Cording has also been related to the virulence of M. tuberculosis. A comparative study of the pattern and structure of mycolic acids was performed on R (cording) and S (non-cording) morphotypes derived from the same parent strains, and no differences were observed between morphotypes. Furthermore, cords formed by R morphotypes were disrupted with petroleum ether (PE), and the extracted lipids were analyzed by thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry. Substantial amounts of trehalose polyphleates (TPP) were recovered as major lipids from PE extracts, and images obtained by transmission electron microscopy suggested that these lipids are localized to the external surfaces of cords and R bacilli. The structure of M. abscessus TPP was revealed to be similar to those previously described in Mycobacterium smegmatis. Although the exact role of TPP is unknown, our results demonstrated that TPP are not toxic by themselves and have a function in the formation of clumps and cords in M. abscessus, thus playing an important role in the pathogenesis of this species.


Folding peptides studied by NMR

The relevance of the relative configuration in the folding of hybrid peptides containing β-cyclobutane amino acids and γ-amino-L-proline residues

O. Illa, J.A. Olivares, P. Nolis, R.M. Ortuño

DOI: 10.1016/j.tet.2017.09.011

Four new series of diastereomeric β,γ-di- and β,γ-tetrapeptides derived from conveniently protected (1R,2S)- and (1S,2S)-2-aminocyclobutane-1-carboxylic acid and cis- and trans-γ-amino-l-proline joined in alternation have been synthesized. High resolution NMR experiments show that peptides containing trans-cyclobutane amino acid residues adopt a more folded structure in solution than those containing a cis-cyclobutane residue, which adopt a strand-like structure. The cis/trans relative configuration of the cyclobutane residue is the origin of the folding pattern of each peptide due to either intra- or inter-residue hydrogen-bonded ring formation, whereas the cis/trans isomerism of the γ-amino-l-proline residue does not have a significantly relevant role on the folding ability of these peptides.

Solid-state NMR supports a study on Rh nanoparticles

NHC-stabilised Rh nanoparticles: Surface study and application in the catalytic hydrogenation of aromatic substrates

F. Martinez-Espinar, P. Blondeau, P. Nolis, B. Chaudret, C. Claver, S. Castillón and C. Godard

DOI: 10.1016/j.jcat.2017.08.010

Highlights

  • Synthesis and characterisation of small RhNPs stabilised by N-heterocyclic carbenes.
  • Evidence of the location of the ligands on the faces, edges and apexes of the NPs.
  • Hydrogenation of aromatic ketones, phenols and N-heteroaromatic substrates.
  • Tuning of the selectivity as a function of the reaction conditions.
  • Full reduction of quinoline under mild conditions with total selectivity.

13C{1H} CP-MAS spectra of (a) L, (b) Rh0.4, (c) Rh0.4 + CO and (d) 13C-Rh0.4.

Removal of pharmaceuticals from hospital wastewater by Pleurotus ostreatus. Identification of pharmaceuticals metabolites by NMR

“Preliminary evaluation of Pleurotus ostreatus for the removal of selected pharmaceuticals from hospital wastewater” by L. Palli,* F. Castellet‐Rovira, M. Pérez‐Trujillo, D. Caniani, M. Sarrà‐Adroguer, R. Gori Biotechnology Progress, 2017. DOI: http://dx.doi.org/10.1002/btpr.2520

The fungus Pleurotus ostreatus was investigated to assess its ability to remove diclofenac, ketoprofen, and atenolol in hospital wastewater. The degradation test was carried out in a fluidized bed bioreactor testing both the batch and the continuous mode. In batch mode, diclofenac disappeared in less than 24 h, ketoprofen was degraded up to almost 50% in 5 days while atenolol was not removed. In continuous mode, diclofenac and ketoprofen removals were about 100% and 70% respectively; atenolol degradation was negligible during the first 20 days but it increased up to 60% after a peak of laccase production and notable biomass growth. In order to identify the enzymatic system involved, further experiments were carried out in flasks. Two intermediates of diclofenac and ketoprofen were detected by nuclear magnetic resonance (NMR) spectroscopy. Moreover P. ostreatus was able to reduce chemical oxygen demand of the hospital wastewater which is an important advantage comparing to other fungi in order to develop a wastewater treatment process.

 

Pd-complex characterization by NMR

Dissimilar catalytic behavior of molecular or colloidal palladium systems with a new NHC ligand

Fernando Gómez-Villarraga,  Jonathan De Tovar,  Miguel Guerrero,  Pau Nolis,  Teodor Parella,  Pierre Lecante,  Nuria Romero,  Lluís Escriche,  Roger Bofill,  Josep Ros,  Xavier Sala,  Karine Philippot  and  Jordi García-Antón 

DOI: 10.1039/C7DT02729J

Abstract

In this work, we describe the synthesis of a new N-heterocyclic carbene (NHC) ligand, derived from a hybrid pyrazole-imidazolium scaffold, namely 1-[2-(3,5-dimethylpyrazol-1-yl)ethyl]-3-((S)-1-phenylethyl)-3H-imidazol-2-ylidene (L). This ligand has been used as a stabilizer for the organometallic synthesis of palladium(0) nanoparticles (Pd NPs). L presents a better stabilizing effect than its pre-carbenic HLCl counterpart, allowing the formation of isolated Pd NPs while HLCl yields aggregated ones. Additionally, molecular Pd(II) coordination compounds of L and HLCl were synthesized and characterized to better understand the coordination modes of these ligands. Both molecular and colloidal Pd systems have been further tested in catalytic C–C coupling processes. Three different types of reactions have been observed depending on the catalytic system: (i) the Suzuki–Miyaura reaction takes place with Pd molecular complexes; (ii) a secondary reaction, the dehalogenation of the substrate, is always detected and (iii) the C–C homocoupling between two molecules of bromoarenes is observed with colloidal catalysts.