NMR Nuclear Magnetic Resonance

1 H, 13 C, 15 N, 19 F, 31 P

One Level is more populated than the other Therefore a Resulting Net Magnetization will be Macroscopically Observable

CW Continous Wave

The Exact Resonance Frequency Varies with the Chemical and Electronical Environment of the Nucleus – This is Called the Chemical Shift  (measured in ppm)

The Chemical Shift is Measured Relative to a Reference or ‘Standard’ ppm ‘parts per million’  =(  -  ref )/  ref * 10 6 The most common standard for 1 H and 13 C NMR is TMS Tetramethylsilan CH 3 CH 3 – Si - CH 3 CH 3

NMR is ‘quantitative’ The intensity is measured as the integral below the resonance signal. The intensities are proportional to the number of protons, that contribute to the signal.

A – B B – A – B C – B – A Each Particular Arrangement of Nuclei has a Characteristic Coupling Pattern n Neighbors – (n+1) Lines

CH 3 CH 2 No spin-spin coupling is observed if: 1.protons are separated by four or more single bonds, i.e., 2.H-C-C-C-H 3.protons are equivalent, i.e.,within a CH 3 or CH 2 group example

Pick the molecule that gives rise to the following 1 H NMR spectrum!

Assign the Signals to the Correct Hydrogens

(almost) pure  D Glucose ~50% - 50%  D Glucose

FT NMR ‘Pulse Echo’ NMR ‘Broadband Excitation’ Record ‘Transient Response’ FID Free Induction Decay Extract Frequencies by Fourier Transform to get NMR Spectrum

More Complex Experiments Measurement of Relaxation Times (‘Lifetimes’) Inversion Recovery

?

?

13 C NMR Spectroscopy Sensitivity low: only 1.1% natural abundance Complicated 1 H coupling pattern, no couplings between 13 Cs (due to low abundance) S/N can be improved by 1 H ‘broadband decoupling’ and FT averaging

3 J HH coupling constants contain Geometrical Information on Torsion Angles ‘Karplus Relation’

COSY Correlated SpectroscopY Two Dimensional NMR Spectroscopy A Signal as a function of two times becomes after 2D FT Spectrum as a function of two frequencies Usually presented as ‘contour plot’

Cyclosporin A

HNHN HH HH CH 3  /  etc

‘complex’ spectra can be resolved using 2dimensional NMR methods