Shift Reagents

Why are the shift reagents used in NMR spectroscopy? Presence of paramagnetic impurities in

the sample: shortens the relaxation times, which causes

line broadening () useful in integration in 13C NMR: suppresses

the NOE () causes a shift of the signals, but not equally

for all resonances useful in spectral analysis ()

Lanthanide shift reagents (LSRs) Paramagnetic ions of Ni and Co were the

first used shift reagents a big drawback: severe line broadening On 1969 Hinckley discovered that

paramagnetic lanthanide ions gave shifts without significant line broadening

Example: 90 MHz 1HNMR spectrum of 1-hexanol in the presence of chelate complex Eu(III)-tris(dipivaloylmethanate)

remarks: all the protons become

less shielded; all the CH2 groups become separated

the shifts increase with the proximity of the protons to the OH group of alcohol

Eu(III)-tris(dipivaloylmethanate)

How does this shift effect occur?

interactions between nuclear spins and the spin of the unpaired electrons of paramagnetic ions

two types of interactions: the contact interactions the pseudocontact interactions

Both types of interaction depend on: the formation of a complex between the

substrate S and the paramagnetic metal ion L In solution there exists a dynamic equilibrium

between the free components and the complex:

L + S LS Example of a complex:

RO

HEu(DPM)3

The contact term is based on the contact interaction: the spin

density of the unpaired electron is transferred to the substrate molecule

the electron spin density is not the same at all positions of the observed nuclei throughout the molecule

in saturated compounds the most affected 13C nuclei are those in - and -positions relative to the complexing center (e.g. O, N or S)

In conjugated systems more distant positions could be affected as well

The contact term is very important in 13C NMR

The pseudocontact term this type of interaction is of greater importance

in 1H NMR then the contact term the name pseudocontact is used to describe a

dipolar interaction between the magnetic dipole field of the unpaired electron and that of the observed nucleus

the interaction is transmitted through space

Geometry of the complex the shift in the resonance

frequency of the observed nuclei depends on the geometry of the complex:

DDip= K(3cos2 -1)/r3K- constant which depends on

the magnetic dipol moment of the paramagnetic metal ion

the equation is valid if the complex is symmetrical about the L-O axis

L

O CR

H

r

Conclusion about 1H shifts in the presence of lanthanide reagents

Dip= K(3cos2 -1)/r3

the shift effect decreases in inverse proportion to r3

it is independent on the observed nuclides

can be positive or negative (depending on the sign of (3cos2 -1) term)

Applications simplifying complicated spectra

separation of overlapping signals easier assignment integration of signals which are otherwise

overlapped decoupling experiments

determining accurate geometrical data for the LS complex and hence for the molecule of interest

Applications (cont.) troubles with olefinic and aromatic protons - they do not

show lanthanide-induced shifts (do not form complexes with lanthanide ions)

however, a solution is found: silver(I) ions they make complexes with pi-electrons if they are added in the form of AgFOD to the solution

containing the substrate and the LSR, shifts are observed for olefines and arenes

obviously, the silver ions are able to transmit the shift effect

O O

CF2CF2CF3(CH3)3C

1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octandione(FOD)

Chiral LSR Enantiomers are indistinguishable by NMR not possible to determine if the sample is a

pure enantiomer or a racemate by using a chiral reagent and making

diastereoisomers or diastereomeric complexes, it becomes possible

example: mixture of 1-phenylethylamine's enantiomers

LSR: the chiral complex Eu(TFC)3

Chiral solvents Interactions between solutes and solvents can

induce shifts as well our focus: interactions between chiral

compounds and chiral solvents (CSAs, chiral solvating agents)

a racemate (S(+) and S(-)) dissolved in a chiral solvent (e.g. L(-)) gives the two solvation diastereomers (S(+)L(-) and S(-)L(-))

this can lead to separate resonances in the NMR spectrum

The most common CSAs chiral

acids amines alcohols

fluorinated sulfoxides cyclic compounds

C CF3H

OH

2,2,2-trifluoro-1-phenylethanol

C CH3H

NH2

1-phenylethylamine

Mixture of achiral solvent + chiral reagent + chiral substrate

A shift effects are observed very often in such mixtures

example: 1H NMR spectrum of mixture of the racemate of 1-phenylethylamine solvent: CDCl3/DMSO (+)-2-methoxy-2-(trifluoromethyl)phenylacetic

acid

C CF3CH3O

COOH

(+)-2-methoxy-2-(trifluoromethyl)phenylacetic acid

Influencing factors The induced shifts depend on:

the chosen solvent the substrate (analytes) the complexing strength temperature concentration ratio

The effect is not observed for solvent signals reason: fast exchange of solvent molecules

between complexes with both substrate enantiomers

Shift ReagentsWhy are the shift reagents used in NMR spectroscopy?Lanthanide shift reagents (LSRs)PowerPoint PresentationHow does this shift effect occur?Both types of interaction depend on:The contact termThe pseudocontact termGeometry of the complexConclusion about 1H shifts in the presence of lanthanide reagentsApplicationsApplications (cont.)Chiral LSRLysbilde 14Chiral solventsThe most common CSAsMixture of achiral solvent + chiral reagent + chiral substrateLysbilde 18Influencing factors