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:

© 2018, Núria. All rights reserved by the author(s) and Universitat Autonoma de Barcelona except for texts and images already copyrighted by third parties (e.g. journal publishers) and used here under the fair use provision.