Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 12.7 Common 2D NMR experiments and their applications.2D NMR experiment

Application

Advantages

Limitations

Comments

COSY (correlated

spectroscopy)

Provides 2 and 3 bond

1 H



1 H

connectivity

Simple to run, resolves

overlapped protonresonances. Minimumamount required 1–2

m

g

Greater than three bond

correlations cannot beobserved

Any ambiguity in the

1D

1 H

assignment

should be followed bya COSY

TOCSY (total

correlatedspectroscopy)

Provides 2, 3, 4 and 5

bond

1 H



1 H

correlations

Simple to run, provides

long through-bondconnectivites.Minimum amountrequired 2–5

m

g

Sometimes, some long

bond correlation maynot be observed. Highpower may berequired for thespin lock pulse

Confirms the COSY as

signments or can beperformed instead ofa COSY. Used foridentifying contiguousproton spin systems

NOESY (NOE

spectroscopy)

Reveals through space

interactions

Stereochemical

questions can beanswered forappropriate molecules

Not a simple experiment to

perform. Data can becomplicated due toexchange peaks Insensitive

Only used where

appropriate

ROESY (rotating frame

noe spectroscopy)

Same as NOESY,

through-spaceinteractions

Same as NOESY plus can

distinguish betweenexchange and ROE peaks

Same as NOESY and

also insensitive

Same as NOESY

HMQC (heteronuclear

multiple quantumcorrelation) or HSQC(heternuclear singlequantum correlation)

Provides 1 bond

1 H



13

C

or

1 H



15

N

correlation

Can identify all the

protonated carbonsand nitrogens in amolecule

Less sensitive experiment

due to low sensitivity of 13

C

and

15

N

Compound

requirement is highMinimum 20

m

g or more

Can assist in identifying

complete unknowns,unexpected productsor metabolites

HMBC (heteronuclear

multiple bondcorrelation)

Provides 2 to 3 bonds

1 H



13

C

and

1 H



15

N

correlation.

Crucial for identifying

nonprotonatedcarbons and nitrogens

Most insensitive

experiment. 100

m

g

and higher amount ofmaterial required

Useful for complete

unknowns,unexpected productsand metabolites

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