Controlling and exploiting spin-spin interactions in NMR spectroscopy Gareth Morris University of Manchester New Fellows Seminar 9 vii 2014
Equation of motion of the nuclear spin angular momentum nuclear spins precess about nuclear spins precess about an applied magnetic field each other at a rate (as predicted by determined by the scalar coupling J Sir Joseph Larmor MP FRS) at a rate determined by the chemical shift δ
1 H NMR spectroscopy: chemical shift and scalar coupling 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 CH 3 OH CH 2 CH 3 CH 2 OH J δ
1 H NMR: ethanol, clarithromycin O HO OMe OH NMe 2 O O HO O O O OMe OH O CH 3 CH 2 OH
Pulse Fourier Transform NMR 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) FID Fourier transformation Spectrum 10 ppm 5 0
Switching off scalar coupling: “pure shift NMR” O HO OMe OH NMe 2 O O HO O O O OMe OH O Pure shift spectrum Conventional spectrum
Pure shift multidimensional NMR Conventional TOCSY Double pure shift TOCSY The TOCSY 2D NMR experiment traces out scalar coupling relationships between hydrogen atoms. J. Am. Chem. Soc. 132 , 12770 (2010)
Pure shift 2D NMR of a mixture of flavonoids 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-d 6 Angew. Chem. Int. Ed. 51 , 6460 (2012)
Solving a chemical problem: long-range stereocontrol 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)
Recent results: Pure Shift Yielded by Chirp Excitation Φ 1 Φ 2 Φ rec. Φ 3 Φ 4 t 2 t 1 t 1 1 H 2 2 G z G 1 G 1 G 2 G 3 G 2 1 1 2SW1 SW1 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.
PSYCHE: comparison with earlier methods Conventional 17 PSYCHE 17 ZS, 12 ms rsnob 167 ZS, 100 ms rsnob 2.2 2.0 1.8 1.6 1.4 1.2 ppm Comparing PSYCHE and ZS methods for a complex and strongly coupled region of the 500 MHz 1 H spectrum of estradiol, PSYCHE offers ca. 10 x more S/N for similar spectral purity. Angew. Chem. Int. Ed. , in press
2D TOCSY-PSYCHE F1 [ppm] F1 [ppm] f e 1.2 1.2 1.4 1.4 1.6 1.6 1.8 1.8 2.0 2.0 2.2 2.2 2.2 2.0 1.8 1.6 1.4 1.2 F2 [ppm] 2.2 2.0 1.8 1.6 1.4 1.2 F2 [ppm] TOCSY TOCSY-PSYCHE Covariance processing of a PSYCHE-TOCSY dataset for estradiol gives a very simple result, ideal for automated analysis
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 Ray Freeman FRS Cambridge il miglior fabbro Funding
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