On 21st March 2018 I sucessfully defended my PhD Thesis entitled: “New Applications of Covariance NMR and Experimental Development for Measurements of Homonuclear Coupling Constants in Overlapping Signals” (ISBN: 9788449079252), supervised by Dr. Teodor Parella and Dr. Pau Nolis, and obtained the degree of Ph.D. in Chemistry at the Department of Chemistry, Universitat Autònoma de Barcelona.
The experimental results obtained in this thesis are presented in the form of three papers published in NMR specialised scientific peer-reviewed journals.
Exploring the use of Generalized Indirect Covariance to Reconstruct Pure shift NMR Spectra: Current Pros and Cons. André Fredi, Pau Nolis, Carlos Cobas, Gary E. Martin and Teodor Parella. Journal of Magnetic Resonance, Volume 266, May 2016, Pages 16-22. DOI: 10.1016/j.jmr.2016.03.003
Access to experimentally infeasible spectra by pure-shift NMR covariance. André Fredi, Pau Nolis, Carlos Cobas and Teodor Parella. Journal of Magnetic Resonance, Volume 270, September 2016, Pages 161-168. DOI: 10.1016/j.jmr.2016.07.010
Accurate measurement of JHH in overlapped signals by a TOCSY‐edited SERF Experiment. André Fredi, Pau Nolis and Teodor Parella. Magnetic Resonance in Chemistry, Volume 55, Issue 6, June 2017, Pages 525-529. DOI: 10.1002/mrc.4572
The first two articles deal with the use of covariance NMR as a general method to generate novel psNMR spectra. The last work describes a new selTOCSY G-SERF experiment, for accurately measuring JHH in overlapped regions.
The first publication describes a novel general protocol to generate psNMR spectra by Covariance NMR. This new approach is unique in NMR spectroscopy; giving a cheap, fast an easy way to reconstruct psNMR spectra without spending time in the spectrometer. This new strategy has been referenced to as psNMR Covariance.
The concept of psNMR Covariance has been extended in the second publication by inserting Multiplicity-Edited (ME) information into 2D experiments that are difficult or even impossible to achieve experimentally. It is shown how the ME information can be efficiently transferred to a set of homonuclear and heteronuclear 2D NMR spectra by Covariance processing, reconstructing new psME spectra in a fast way. Finally, G-SERF and related methods only work for isolated 1H signals on which selective excitation can be successfully applied.
Unfortunately, as it happens in other frequency-selective experiments, this approach fails for overlapped signals. A doubly-selective TOCSY G-SERF scheme is presented in the third publication to circumvent this limitation, by measuring JHH efficiently even for protons resonating in crowded regions.
A fast RDC-assisted strategy involving the simultaneous determination of scalar and total coupling constants from a single 1JCH/2JHH-resolved NMR spectrum is reported. It is shown that the concerted use of the directly measured 1DCH (for all CHn multiplicities) and 2DHH residual dipolar couplings allows an on-the-fly assignment of diastereotopic CH2 protons, as well as of an efficient discrimination between all eight possible diastereoisomeric structures of strychnine, which contains six stereocenters.
A versatile 1JCH-resolved HSQC pulse scheme for the speedy, accurate and automated determination of one-bond proton-carbon coupling constants is reported. The implementation of a perfectBIRD element allows a straightforward measurement from the clean doublets obtained along the highly resolved F1 dimension, even for each individual 1JCHa and 1JCHb in diastereotopic HaCHb methylene groups. Real-time homodecoupling during acquisition and other alternatives to minimize accidental signal overlapping in overcrowded spectra are also discussed.
“ 1JCH NMR Profile: Identification of key structural features and functionalities by visual observation and direct measurement of one-bond proton-carbon coupling constants” by Núria Marcó, A.A. Souza, Pau Nolis, Carlos Cobas, R. R. Gil and Teodor Parella. Journal of Organic Chemistry 2017, 276 : 37.42. DOI: 10.1021/acs.joc.6b02873
A user-friendly NMR interface for the visual and accurate determination of experimental one-bond proton-carbon coupling constants (1JCH) in small molecules is presented. This intuitive 1JCH profile correlates directly delta(1H) and 1JCH facilitates the rapid identification and assignment of 1H signals belonging to key structural elements and functional groups. Illustrative examples are provided for some target molecules including terminal alkynes, strained rings, electronegative substituents or lone-pair bearing heteronuclei.
Selective Refocusing (GSERF or the recent PSYCHEDELIC) experiments were originally designed to determine all proton-proton coupling constants (JHH) for a selected proton resonance. They work for isolated signals on which selective excitation can be successfully applied but, as happens in other selective experiments, fail for overlapped signals. To circumvent this limitation, a doubly-selective TOCSY-GSERF scheme is presented for the measurement of JHH in protons resonating in crowded regions. This new experiment takes advantage of the editing features of an initial TOCSY transfer to uncover hidden resonances that become accessible to perform the subsequent frequency-selective refocusing.
“Simultaneous measurement of J(HH) and two different nJ(CH) coupling constants from a single multiply-edited 2D cross-peak”, by Josep Saurí and Teodor Parella; Magn. Reson. Chem. 2013, 51, 397-402. DOI: 10.1002/mrc.3960