Chemical Exchange
Dynamic processes can be observed by NMR if the spectral
parameters are changed by the process on the NMR time scale.
-
Hindered rotation about a partial double bond.
-
Ring inversion.
-
Reorientation in solids
-
Carbonyl scrambling in metal complexes
Example - Dimethylacetamide
Equally populated 2-site mutual exchange
A
A
CH3 2
O
k
N
N
H3C
CH3 1
O
CH3 1
B
H3C
CH3
B
2
Slow Exchange
 k is much smaller than (A - B).
 Two separate lines at A and B.
k
=
0
.
1

k
=
0

A

B
 Spectrum not sensitive to rate.

Rate are measured using T1 based techniques.
Intermediate Exchange
 k of the same order of magnitude as (A - B)
 The two lines broaden, move towards each other and eventually
coalesce

9
9
9
9
.
0
=
k

5
.
0
=
k

A

B
 Spectrum very sensitive to rate
 Rate measurements are made by spectral simulation
Fast Exchange
 k is larger than (A - B)
k
=
3

k
=
1
.
3

k
=
1
.
0
2


A
 Spectrum becomes insensitive to rate.
 Rate measurements based on T2 methods


Selective Inversion Experiment
x

RD
C
B
A
z
VD
Acq
E
D
F
z
A
z
C
B
y
x
y
x
z
y
x
z
D
z
E
y
x
x
x
F
y
x
y
x
Signal of both magnetisation as a
function of delay time
1
0
NormalizedSignalItensiy
N
o
n
s
e
l
e
c
t
i
v
e
i
n
v
e
r
s
i
o
n
r
e
c
o
v
e
r
y
I
n
v
e
r
t
e
d
L
i
n
e
U
n
p
e
r
t
u
r
b
e
d
L
i
n
e
1
0 51
01
52
02
53
03
5
T
i
m
e
(
s
)
Rate =0.5 s-1 T1= 4 s
Accurate rates are possible for 1/T1 < k.
Offset-Saturation Experiment
 Makes it possible to measure accurate T2 values independent of
coherent dephasing mechanisms.
Decoupler

5xT1
90o
Transmitter
Acq.
6
0
4
0


1
/
2


=

B
(
T
/
T
)
1
/
2
2
1
2
1
/
2
SignalItensiy
2
0
0
6
0
0
0
6
5
0
0
7
0
0
0
7
5
0
0
F
r
e
q
u
e
n
c
y
(
H
z
)


Accurate Activation Parameters
 Eyring equation
æ- D G † ö
kbT
÷
k =
exp çç
÷
÷
çè R T ø
h
I.e.
k
ln
T
( )
ækb ÷
ö DS †
- DH †
=
+ ln çç ÷
+
èh ÷
ø
RT
R
k
1
†
as a function of
one obtains D H from
T
T
†
the slope and D S from the y-intercept.
 Plotting
ln
( )
 Small temperature range:
Large error in slope and hence in y-intercept.
 Accurate rate measurements are possible in all three exchange
regimes:
rate data is available over a large temperature range
(c.a. 150 oC)
D H † to within 1 kJ/mol.
D S † to within 5 J/mol K.
Eyring Plot of Furfural in Acetone-d6
1
0
b/h)
0
O
f
f
s
e
t
s
a
t
u
r
a
t
i
o
n
Ln(k/T)-Ln(k
1
0
L
i
n
e
s
h
a
p
e
2
0
3
0
0
S
e
l
e
c
t
i
v
e
i
n
v
e
r
s
i
o
n
1
2
3
4
5
1
1
0
0
0
/
T
(
K
)
6
7
Large Systems
Complications:
 Spectral overlap
 Second Order effects
 Complicated exchange mechanism
Both full spectral assignment and the exchange mechanism are
required for complete lineshape analysis
Solution:
Obtain assignment via two-dimensional NMR methods such as:
 COSY - Correlation spectroscopy
 NOESY - Nuclear Overhauser Effect Spectroscopy
 HMBC - Heteronuclear Multiple Bond Correlation
Spectroscopy
Measure spectral parameters
 simulation of the complete spectrum
 simulation of a series of subspectra obtained by selective
TOCSY (Total Correlation Spectroscopy)
Exchange mechanism determined by Exchange Spectroscopy
DADS
N,N’-[Dimethyl-(2,2’-dithiobisacetyl)]ethylenediamine
CH3
N
S
S
OO
N
CH3
A challenge
Ten-membered ring with 5 observable conformations.
 2 Symmetric conformations each with
2 equivalent AB’s and CH3’s and an AA’BB’
 3 Non-symmetric conformations each with
2 non-equivalent AB’s and CH3’s and an ABCD
Exchange mechanism of DADS
O
O
MS
E (3.1)
N
74.1
S
N
M
O
M
S
N
O
S
S
N
S
N
O
B (0.9)
81.2
M
M
O
N
A (3.6)
M
71.6 O
O
M
S
N
S
S
O
D (5.4)
S
N
M
80.1
O
N
M
N
M
C (0.0)
Selective Inversion of the Methyl resonance of
Conformer C
3
2
signal(rb.units)
1
0
1
A
N
m
e
t
h
y
l
C
N
m
e
t
h
y
l
E
N
m
e
t
h
y
l
2
01234567891
0
t
i
m
e
(
s
)
 Data indicates no direct exchange between C and A.
 Rates were measured between 273 to 283 K
Eyring Plot for all Observed Processes of DADS
b/h)
2
0
log(k/T)-log(k
2
5
3
0
2
A
t
o
C
A
t
o
E
A
t
o
B
C
t
o
D
3
1
1
0
0
0
/
T
(
K
)
4
The activation parameters of all four exchange
processes of DADS.
H†
S†
(kJ mol-1)
(J K-1)
G†300
(kJ mol-1)
71.6 +/- 1
3 +/- 3
71.6
C to D
85.7 +/- 1.5 19 +/- 4
80.0
A to B
84.4 +/- 1.2 22 +/- 4
77.8
Process
C to A
A to E
73.8 +/- 1
11 +/- 3
70.5
Conclusions
 Barriers were determined for all four processes with errors in
the activation parameters compatible to those in studies on small
molecules.
 9 points on the potential energy surface were determined
 2-D methods were invaluable in the application of complete
lineshape methods.