[PPT] - Controlling and exploiting spin-spin interactions in NMR PowerPoint Presentation

SLIDE 1

Gareth Morris University of Manchester

New Fellows Seminar 9 vii 2014

Controlling and exploiting spin-spin interactions in NMR spectroscopy

SLIDE 2

Equation of motion of the nuclear spin angular momentum

nuclear spins precess about an applied magnetic field (as predicted by Sir Joseph Larmor MP FRS) at a rate determined by the chemical shift δ nuclear spins precess about each other at a rate determined by the scalar coupling J

SLIDE 3

1H NMR spectroscopy: chemical shift

CH3 OH CH2

CH3CH2OH

δ The electron clouds around the hydrogen nuclei shield them slightly from the applied magnetic field – the chemical shift δ The electrons in the bonds between nuclei communicate the magnetic fields the nuclei create, giving the scalar coupling J

and scalar coupling

J

SLIDE 4

1H NMR: ethanol, clarithromycin

CH3CH2OH

O O O O OH HO OMe O O O OMe NMe2 HO OH

SLIDE 5

SLIDE 6

10 ppm 5

Pulse Fourier Transform NMR Fourier transformation Spectrum FID We record NMR spectra by exciting the nuclear spins with short (ca. 10 µs) radiofrequency pulses, then recording the resultant “free induction decay” (ca. 1 s)

SLIDE 7

Pure shift spectrum

Switching off scalar coupling: “pure shift NMR”

Conventional spectrum

O O O O OH HO OMe O O O OMe NMe2 HO OH

SLIDE 8

The TOCSY 2D NMR experiment traces out scalar coupling relationships between hydrogen atoms.

J. Am. Chem. Soc. 132, 12770 (2010)

Conventional TOCSY Double pure shift TOCSY

Pure shift multidimensional NMR

SLIDE 9

Normal 3QF-COSY (a), CT-3QF pure shift COSY (b), and covariance double pure shift CT-3QF-COSY (c) cross-peaks for a mixture of four flavonoids in dmso-d6

Angew. Chem. Int. Ed. 51, 6460 (2012)

Pure shift 2D NMR of a mixture of flavonoids

SLIDE 10

An 800 MHz pure shift spectrum allows the enantiomeric excess induced at the end of the peptide analogue chain to be determined reliably

Angew. Chem. Int. Ed. 53, 151 (2014)

Solving a chemical problem: long-range stereocontrol

SLIDE 11

Using two swept-frequency (chirp) pulses, with opposite sweep directions, under a field gradient refocuses a small subset of coherences (diagonal responses) that are refocused by small flip angle excitations without changing frequency.

Recent results: Pure Shift Yielded by Chirp Excitation

t2

1H

Gz Φ1 Φ2 Φrec. 2 t1 Φ3 Φ4 2SW1 1 SW1 1 2 t1 G1 G1 G2 G3 G2

SLIDE 12

Comparing PSYCHE and ZS methods for a complex and strongly coupled region

f the 500 MHz 1H spectrum of estradiol, PSYCHE offers ca. 10 x more S/N for

similar spectral purity.

ppm 2.2 2.0 1.8 1.6 1.4 1.2 167 17 17

ZS, 12 ms rsnob PSYCHE ZS, 100 ms rsnob Conventional

PSYCHE: comparison with earlier methods

Angew. Chem. Int. Ed., in press

SLIDE 13

Covariance processing of a PSYCHE-TOCSY dataset for estradiol gives a very simple result, ideal for automated analysis

2D TOCSY-PSYCHE

TOCSY

F2 [ppm] 2.2 2.0 1.8 1.6 1.4 1.2 F1 [ppm] 2.2 2.0 1.8 1.6 1.4 1.2 e

TOCSY-PSYCHE

F2 [ppm] 2.2 2.0 1.8 1.6 1.4 1.2 F1 [ppm] 2.2 2.0 1.8 1.6 1.4 1.2 f

SLIDE 14

Acknowledgments

Ralph Adams, Juan Aguilar, Jill Barber, Liam Byrne, Jonathan Clayden, Adam Colbourne, Rob Evans, Mohammadali Foroozandeh, Péter Király, Liladhar Paudel, Nicola Meharry, Mathias Nilsson Manchester Damien Jeannerat Geneva Julia Cassani Mexico City

Funding

Ray Freeman FRS Cambridge il miglior fabbro