“A New Chirally Organized Trifluoromethylanthrylmethanol Derivative and Its Application as Chiral Solvating Agent” By Eva Monteagudo, Pere de March, Ángel Álvarez‐Larena and Albert Virgili. ChemistrySelect, 2017, 2, pp. 7362-7367 DOI:10.1002/slct.201701429
The synthesis and structure of 1,1′‐(((10,10’‐(1,1′‐binaphthalene)‐2,2′‐diylbis(oxy))bis(methylene))bis(anthracene‐10,9‐diyl))bis(2,2,2‐trifluoroethanol), 4, is reported. This compound owns both axial and central chirality allowing its use as a chiral solvating agent (CSA) for the enantiomeric composition determination of several mixtures of chiral aromatic alcohols and amines using NMR. The study of the resulting diastereoisomeric complexes was carried out by determining its stoichiometry and association binding constants.
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 . DNP allows boosting NMR sensitivity by several orders of magnitude, overcoming one of the main limitations of NMR spectroscopy . 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  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.
“Chiral Recognition by Dissolution DNP NMR Spectroscopy of 13C-Labeled DL-Methionine” By Eva Monteagudo, Albert Virgili, Teodor Parella and Míriam Pérez-Trujillo.. Anal. Chem., 2017, 89 (9), pp 4939–4944 DOI: 10.1021/acs.analchem.7b00156
A method based on d-DNP NMR spectroscopy to study chiral recognition is described for the first time. The enantiodifferentiation of a racemic metabolite in a millimolar aqueous solution using a chiral solvating agent was performed. Hyperpolarized 13C-labeled DL-methionine enantiomers were differently observed with a single-scan 13C NMR experiment, while the chiral auxiliary at thermal equilibrium remained unobserved. The method developed entails a step forward in the chiral recognition of small molecules by NMR spectroscopy, opening new possibilities in situations where the sensitivity is limited, for example, when a low concentration of analyte is available or when the measurement of an insensitive nucleus, like 13C, is required. The advantages and current limitations of the method, as well as future perspectives, are discussed.
Studies on cycloalkane‐based bisamide organogelators: A new example of stochastic chiral symmetry breaking induced by sonication
Ortuno, R. M., Pi-Boleda, B., Sans, M., Campos, M., Nolis, P., Illa, O., Estévez, J. C. and Branchadell, V. (2016), Chem. Eur. J.. Accepted Author Manuscript. doi:10.1002/chem.201604818
Enantiomerically pure C16-alkyl amides derived from cis and trans cycloalkane-1,2-dicarboxylic acids, respectively, have been synthesized and their behaviour as organogelators has been investigated. These compounds include cis/trans diastereomeric cyclobutane and cyclohexane derivatives with the aim to explore the influence of the ring size as well as the relative configuration in their hierarchical self-assembly to form gels. High resolution 1H NMR spectroscopy studies allowed the determination of the dynamics of the gelation process in [D8]-toluene and the sol-gel transition temperature. The morphology and size of the aggregates have been investigated and results have shown that, in the case of cyclobutane derivatives, the cis/trans stereochemistry is not relevant for the gelation behaviour and the properties of the soft-materials obtained, but it is remarkable for cyclohexane diamides, which are better organogelators. The four compounds produce chiral aggregates despite that two of them are meso achiral molecules. We show in this work that this fact is an example of stochastic symmetry breaking induced by sonication. The self-assembly of these molecules has been modelled providing information and support about the structure and the chirality of the aggregates.
Today we are saying goodbye to our dear Yaoyao, though we hope to see her very soon again.
Yaoyao is currently finishing her PhD on metabonomics applied to clinical biomarkers in the Legido-Quigley Lab at King’s College London (KCL).
She has been visiting us for the last two months, during which we have been working together in two metabonomics projects related to drug misuse biomarkers and chiral metabonomics. It has been a great pleasure for us to spend this time with her and continue with this collaboration from now on.
“NMR-Aided Differentiation of Enantiomers: Signal Enantioresolution” by Míriam Pérez-Trujillo, Teodor Parella and Lars T. Kuhn. Analytica Chimica Acta, 2015. DOI: 10.1016/j.aca.2015.02.069
NMR-aided enantiodiscrimination using chiral auxiliaries (CAs) is a recognized method for differentiating enantiomers and for measuring enantiomeric ratios (er). Up to the present, the study, optimization, and comparison of such methods have been performed based on the enantiodifferentiation of NMR signals via analysing non-equivalent chemical-shift values (ΔΔδ) of the diastereoisomeric species formed. However, a poor and non-reliable comparison of results is often obtained via the analysis of ΔΔδ exclusively. In here, the concept of enantioresolution of an individual NMR signal and its importance for NMR-aided enantiodifferentiation studies is introduced and discussed. Continue reading NMR-Aided Differentiation of Enantiomers: Signal Enantioresolution
Some of our last research work will be presented next week at the VI Ibero-American NMR – VII GERMN Bienal – IV Iberian NMR joint meeting that will take place in Alcalá de Henares, Madrid (Spain) from 22nd to 25th September. Find below a summary of our contributions.
Laura Castañar presents an oral communication and a poster entitled “Enantiodifferentiation throgh frequency-selective pure shift 1H NMR”. NMR-aided discrimination of enantiomers using chiral solvating agents (CSAs) is a well established method to carry out enantiodifferentiation studies. Continue reading SeRMN presentations at the 2014 Ibero-American NMR & GERMN Bienal & Iberian NMR meeting
“Simultaneous 1H and 13C NMR enantiodifferentiation from highly-resolved pure shift HSQC spectra” by Miriam Pérez-Trujillo, Laura Castañar, Eva Monteagudo, Lars T. Kuhn, Pau Nolis, Albert Virgili, R. Thomas Williamson and Teodor Parella. Chemical Communications 50:10214-10217 (2014). DOI: 10.1039/C4CC04077E
NMR-aided discrimination of enantiomers using chiral solvating agents (CSAs) is a well established method of enantiodifferentiation and measurement of enantiomeric ratios (er). The analysis is traditionally performed by observing chemical shift differences (ΔΔδ) in 1H signals by conventional 1D 1H NMR spectra. However, low ΔΔδ values and signal overlap caused by complex multiplets lead to the lack of spectral signal dispersion that preclude a straightforward analysis. Continue reading Simultaneous 1H and 13C NMR enantiodifferentiation from highly-resolved pure shift HSQC spectra
“13C NMR spectroscopy for the differentiation of enantiomers using chiral solvating agents” Míriam Pérez-Trujillo, Eva Monteagudo and Teodor Parella. Analytical Chemistry, 2013, 85 (22), pp 10887–10894. DOI: 10.1021/ac402580j
The utility of 13C NMR spectroscopy for the differentiation of enantiomers using chiral solvating agents (CSA) is stated. Three examples involving the enantiodifferentiation of a drug, a metabolite and a reactant in aqueous and organic solutions have been chosen to show it. Continue reading Enantiodifferentiation through 13C NMR Spectroscopy and CSAs
Find below an abstract of SeRMN contribution at 4th International DNP Symposium that will be held August 28-31, 2013, in Copenhagen (Denmak).
Enantiodiscrimination Studies by 13C DNP-NMR Spectroscopy
The determination of enantiomeric purity of drugs and/or endogenous molecules is crucial since its chirality could determine its pharmacological or biological behavior . Many analytical techniques are available to determine the enantiomeric excess (ee) such as, circular dichroism, capillary electrophoresis, chromatographic techniques with chiral stationary phases, etc.; having each of them drawbacks and advantages . Nuclear magnetic resonance (NMR) using a chiral solvating agent (CSA) as chiral auxiliary is an easy, fast and very powerful analytical tool that allows the measurement of ee by simple signal integration . Continue reading Poster presentation at 4th International DNP Symposium