Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 12.3 Properties of common NMR spectral characteristics.Chemical shifts

Coupling constants

Integration

Relaxation times

Chemical shift of a nucleus

depends on its electronicenvironment and the magnitudeof the local magnetic field

Interaction of

nonequivalentatoms through bonds,generally 1-, 2- and3-bonds distances.

Integration of a

1 H

spectrum

provides quantitativeinformation

Nuclei return to the equilibrium

state after excitation by variousmechanisms. Two most commonones are described below

Coupling patterns or

multiplicity:

In

1 H

spectra, integral of each

peak determines the number ofhydrogens present in thestructure

T^1

relaxation

B

eff

=

B

 0

sB

0

B

= main field 0

M

=2

nI

+1

B

eff

= reduced field

M = Multiplicityn = number of

equivalent nuclei

Spin–Spin relaxation

I = ½ for most of

the nuclei

The equivalent Hydrogens on

a methyl, CH

3

residue integrate

to three times the areacompared to a methine CHresidue

Determines the interaction of spins

that are close to each other

nu

=

g/2

p

(1



s)

B

0

Common homo-nuclear

coupling

T^1

relaxation time depends onthe other spins in the molecule

Chemical shift scale is a parts per

million (ppm) scale. The

1 H

and

13

C

scale is referenced to

4-trimethyl silane (TMS) at0 ppm

1 H



1 H

and

19

F

19

F

External compound of known

amount is used to quantitatethe amount of compound inthe solution

T^1

is extremely critical foroptimizing all the NMRexperiments

(continued

)

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