Improving NMR and Computational Methods for 3D Molecular Structure Determination

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

The experimental measurement of 3D structure parameters such as scalar couplings, NOE-distances, residual dipolar couplings and residual chemical shift anisotropies has focussed on the precision, rather than accuracy of measurement. By improving accuracy (compared to ideal experimental or computed results) we aim to increase the quality of 3D structure prediction. This will be applied to two situations: (i) Population elucidation in multi-conformer systems (ii) ab initio structure determination of unknown compounds.

Publications

10 25 50
publication icon
Shchukina A (2019) Accelerated acquisition in pure-shift spectra based on prior knowledge from H NMR. in Chemical communications (Cambridge, England)

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R51245X/1 01/10/2017 30/09/2021
1954826 Studentship EP/R51245X/1 18/09/2017 17/09/2021 Matthew Davy
 
Description My work has been on development of existing NMR methods. One line of work has been on pureshift NMR spectra - these can simplify the spectra of complicated molecules and thus allow a chemist to properly characterise a molecule and ultimately determine its 3D structure. However such methods have poor sensitivity. The paper I am included as an author on focusses on computational methods to reconstruct pureshift NMR spectra with collecting a fraction of the data, and thus taking a fraction of the time.

I am also doing research for purely experimental methods that enhance the actual sensitivity of Pureshift NMR, by allowing longer data acqusition periods than traditionally used - however this has not yet been publsihed.

My other line of work has focussed on enhancing the SHARPER NMR experiment, which is used when conditions during a chemical reaction normally make that reaction difficult to study via NMR. The SHARPER experiment is limited to examining a single signal in an NMR spectrum - my modifications are capable of examining two or three peaks at a time. This is very desirable for monitoring a chemical reaction where there will always be multiple signals of interest - at the very least a product and a reactant.

My other line of work has focussed on enhancing the SHARPER NMR experiment, which is used when conditions during a chemical reaction normally make that reaction difficult to study via NMR. The SHARPER experiment is limited to examining a single signal in an NMR spectrum - my modifications are capable of examining two or three peaks at a time. This is very desirable for monitoring a chemical reaction where there will always be multiple signals of interest - at the very least a product and a reactant.
Exploitation Route The aim would be to roll the NMR experiments created in this project out for wider use by chemists. Whilst the experiments do not provide any information that could not normally be gleaned from existing NMR experiments they are more sensitive, faster or can interrogate more signals than the existing experiments. This means that a chemist may be able to make use of them on samples where existing experiments would be too time consuming or that the experiments could be run on smaller amounts of material.

The ideal outcome is that this allows chemists to answer questions not normally possible via existing methods.
Sectors Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description SMASH Scholarship
Amount $500 (USD)
Organisation Royal Society of Chemistry 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 09/2019
 
Description Accelerated acquisition in pure-shift spectra based on prior knowledge from 1H NMR 
Organisation Lancaster University
Country United Kingdom 
Sector Academic/University 
PI Contribution Testing of the actual pulse sequences and associated scripts for the accelerated acquisition, optimision of experimental conditions (PSYCHE flip angle) and running some of the samples in the paper. I also contributed towards the documentation for running the scripts.
Collaborator Contribution Writing and optimising the scripts to produce an ideal sampling schedule for the EXACT PSYCHE and interfacing those scripts with existing automation software (topspin peak picking)
Impact This has led to a paper - DOI: 10.1039/C9CC05222D
Start Year 2018
 
Description Accelerated acquisition in pure-shift spectra based on prior knowledge from 1H NMR 
Organisation University of Warsaw
Department Search Results Centre of New Technologies
Country Poland 
Sector Academic/University 
PI Contribution Testing of the actual pulse sequences and associated scripts for the accelerated acquisition, optimision of experimental conditions (PSYCHE flip angle) and running some of the samples in the paper. I also contributed towards the documentation for running the scripts.
Collaborator Contribution Writing and optimising the scripts to produce an ideal sampling schedule for the EXACT PSYCHE and interfacing those scripts with existing automation software (topspin peak picking)
Impact This has led to a paper - DOI: 10.1039/C9CC05222D
Start Year 2018
 
Description Multiple Peak SHARPER 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution A set of scripts which allow calculation of nanosecond specific timings in order to run Edinburgh's SHARPER experiment on multiple NMR signals at a time.
Collaborator Contribution Practical testing of the scripts on difficult chemical reactions which warrant the use of the multiple peak SHARPER experiment
Impact This collaboration should lead to publication of a paper. We are in the process of identifying a suitable set of reaction conditions with which to best demonstrate the experiment.
Start Year 2019