Notes on relaxation and dynamics

EMBO Practical Course on NMR, Basel, July 20 - 27, 2013

Stephan Grzesiek
Biozentrum der Universitt Basel
Klingelbergstr 70
CH-4056 Basel, Switzerland
e-mail: [email protected]

1. RELAXATION AND DYNAMICS ................................................................................................................ 2

1.1 GENERAL REMARK ........................................................................................................................................... 2

1.2 THE DIPOLAR INTERACTION .............................................................................................................................. 4
1.3 T2 MEASURED BY THE CARR-PURCELL-MEIBOOM-GILL EXPERIMENT.............................................................. 5
1.4 THE LINEWIDTH INCREASES WITH INCREASING MOLECULAR WEIGHT............................................................... 6
1.5 A SIMPLE EXAMPLE OF FLUCTUATION-DISSIPATION: WHY IS T2 FOR LARGER MOLECULES INVERSELY
PROPORTIONAL TO THE MOLECULAR TUMBLING TIME? .............................................................................................. 7
1.6 T1 RELAXATION ............................................................................................................................................... 13
1.7 SPIN-FLIPS INDUCED BY BROWNIAN MOTION, THE NUCLEAR OVERHAUSER EFFECT ...................................... 15
1.8 THE SOLOMON EQUATION............................................................................................................................... 17
1.9 HOMONUCLEAR NOE ..................................................................................................................................... 19
1.10 HETERONUCLEAR NOE ................................................................................................................................ 21
1.11 DYNAMICAL INFORMATION FROM RELAXATION EXPERIMENTS .................................................................... 23

2. A QUICK DERIVATION OF THE MASTER EQUATION .................................................................... 26

2.1 THE TOTAL HAMILTONIAN.............................................................................................................................. 26

2.2 LIOUVILLE-VON NEUMANN EQUATION ........................................................................................................... 26
2.3 TRANSFORM OPERATORS TO INTERACTION PICTURE ....................................................................................... 26
2.4 INTEGRATE ONCE ............................................................................................................................................ 27
2.5 TAKE ENSEMBLE AVERAGE () OF ALL TERMS.............................................................................................. 27
2.6 INTRODUCE RETURN TO EQUILIBRIUM AD HOC ............................................................................................... 27
2.7 EXPAND H1 IN SPIN AND TIME DEPENDENT PART ............................................................................................ 28
2.8 USE ASSUMPTIONS ON RANDOM MOTIONS ...................................................................................................... 28
2.9 USE ONE MORE ASSUMPTIONS ON RANDOM MOTIONS ..................................................................................... 28
2.10 SECULAR APPROXIMATION ........................................................................................................................... 30

3. REFERENCES ............................................................................................................................................... 31

4. APPENDIX ..................................................................................................................................................... 32

4.1 EFFICIENCY OF SCALAR MAGNETIZATION TRANSFER IN THE PRESENCE OF RELAXATION ............................... 32

4.2 THE SIZE OF THE SCALAR COUPLINGS ............................................................................................................. 33
4.3 SOME PRODUCT OPERATOR GYMNASTICS ....................................................................................................... 33
4.4 IRREDUCIBLE REPRESENTATION OF THE DIPOLAR INTERACTION ..................................................................... 34
4.5 EXAMPLE: HETERONUCLEAR T2 FROM REDFIELD THEORY.............................................................................. 35

14/07/2013 16:31

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 1. Relaxation and dynamics

1.1 General Remark

Application of RF-frequency pulses changes the density matrix and moves the spins away
from their thermal equilibrium distribution. E.g. for protons in a 14T magnetic field the
density matrix at thermal equilibrium (T = 293K) is given by

exp(#H /kT) 1 1 1
"eq = $ (1 # H /kT) = (1 # (#%!Iz B) /kT) $ (1 + 10#4 Iz )
trace (exp(#H /kT)) 2 2 2
(1.1)

where H = "#!Iz B , exp("H /kT) # 1 " H /kT (since H << kT ), 1 is the unity matrix,
! trace 1 = 2 , trace H = 0 .

A 180 pulse around the x-axis (NOE-experiment) transfers this density matrix to
! ! !
! ! 1 1
180I x
(1 + 10 !4 Iz ) "" "# (1 ! 10 !4 Iz )
" (1.2)
2 2

Relaxation is the phenomenon that the spins have the tendency to come back to their thermal
equilibrium distribution eq. The time constants for the return to thermal equilibrium are T1
for the longitudinal magnetization (z-magnetization) and T2 for the transverse magnetization
(x,y-magnetization). For somewhat historical reasons T1 is also called spin-lattice and T2 is
called spin-spin relaxation time.

For the relaxation phenomenon to happen, internal forces must act on the individual spins. In
solution, the main source for these forces are random fields caused by the random (Brownian)
motion of the molecule. Individual spins experience different random field fluctuations. The
average of these fluctuations leads to the return to thermal equilibrium of the entire
macroscopic ensemble of all spins.

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The macroscopic relaxation rates can be calculated from a statistical description of the
individual microscopic fluctuations. Thus the macroscopic relaxation rates contain
information on the average dynamical behavior of individual spins and their surroundings

The approach of thermal equilibrium is mainly induced by the following internal forces
(interactions):

1. dipolar interactions between the magnetic moments of the spins (typical energies in
biomacromolecules < 104-105 Hz * h)
2. the anisotropy of the chemical shift (CSA). Different orientations of the molecule in the
solution lead to different shieldings, i.e. different Larmor frequencies. This results in
internal forces on the spins (Energies/h < 104-105 Hz).
3. electric quadrupolar interactions of the nucleus with the inhomogeneous electric field
produced by the electrons. This interaction is very large, but it is only observed for spins
with I > 1/2. (quadrupolar energy/h ~ 200 kHz for 2H and ~ 3 MHz for 14N).

Remark 1: In NMR, the forces resulting from these random fields are rather weak compared
to the force that the external magnetic field exerts on the spins. These weak forces lead to
rather long relaxation times, e.g. for biological macromolecules in solution T2 values are in
the range of tens of milliseconds and T1 values are on the order of seconds. Therefore we can
observe the oscillations of the magnetic moments on the order of 600 MHz * 10 ms =
6 000 000 times. This is the reason why despite of the small magnitude of the equilibrium
polarisation (10-4), NMR can still be observed with reasonable sensitivity.

Remark 2: The correlation between macroscopic relaxation phenomena and microscopic

fluctuations is described in a very general way by the fluctuation-dissipation theorem: the
macroscopic relaxation rates are proportional to (the Fourier transform of) the autocorrelation
function of the fluctuating forces (see e.g. F. Reif). This is for example the case for the
viscosity of a medium (proportional to the autocorrelation of Brownian force fluctuations
on individual particles) or the electrical resistance R (proportional to the autocorrelation of
thermal voltage fluctuations in a conductor). The NMR theory of relaxation (Redfield theory)
is the equivalent of the fluctuation-dissipation theorem applied to an ensemble of spins
described by quantum statistics: the NMR relaxation rates are proportional to the
autocorrelation function of the fluctuating microscopic fields. We shall see this in detail
below.

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1.2 The dipolar interaction
The dipolar interaction is the most important contribution to relaxation for biological
macromolecules. A magnetic nucleus with gyromagnetic ratio and spin I is surrounded by a
magnetic dipolar field Bd which is given by the following equation:

"! 0 % r(I $ r) (
Bd = ! 3 &I - 3 ) (1.3)
4#r ' r2 *

where r is the distance vector to the nucleus.

!hI/2" Bd

Fig.: dipolar field around nucleus with magnetic moment = !!I

The dipolar energy Hd of a second nucleus with gyromagnetic ratio 2 and spin I2 in the field
of the first nucleus with gyromagnetic ratio 1 and spin I2 is then given as

!1! 0 # r(I1 " r) & !1! 2 ! 2 0 # (I " r)(I " r) &

H d = ! 2 " B d1 = (! 2 !I 2 )" 3
$ I1 -3 2
'= 3
$ I1 " I 2 -3 1 2 2 ' (1.4)
4" r % r ( 4" r % r (

We notice that depending on the position of the second nucleus (distance vector r), the
dipolar field and therefore the dipolar energy can have different values. If the two nuclei are
part of the same molecule, then during the thermal movement of the molecule (Brownian
rotation) the direction of r changes, whereas the length of r stays usually more or less
constant. If the molecule has isotropic orientation in solution then the average of the dipolar
interaction energy over all angles vanishes.

The Brownian rotation, however, leads to fluctuations in the dipolar field and dipolar
interaction energy. These fluctuating fields can induce rotations of the spins. As the
fluctuations are driven by the Brownian motion, this provides a mechanism to exchange
energy between the spins and also between the spins and the mechanical motion of the
molecule.

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1.3 T2 measured by the Carr-Purcell-Meiboom-Gill experiment
A classical experiment to visualize T2 is the spin-echo experiment with the Carr-Purcell-
Meiboom-Gill (CPMG) sequence:

90x- [ 180y echo]n

Fig.: Harris p 83.

An initial 90 pulse turns the equilibrium magnetization into the xy-plane. The magnetization
vectors from different nuclei then begin to fan out (b) and the signal decays. A 180y pulse is
applied after time (c) which has the effect of rotating all the magnetization vectors about the
y-axis, or in other words reflecting them in the zy-plane, they continue to move in the same
direction (d), and after a further time (e) they are again in phase in the y-direction, and the
signal in the receiver coil is maximal. The process of refocusing by the 180 pulse can be
repeated many times. The amplitudes of successive echoes decay exponentially and the true
value of T2 can be found from the envelope of the echoes:

Fig.: Harris p. 83.

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1.4 The linewidth increases with increasing molecular weight

A puzzle for many students of NMR is the fact that the line widths of the nuclear resonance
lines are becoming larger when the molecular weight of the molecules in solution is
increased. Remember that the linewidth is given by

! " = !# / 2$ = 1/ ($T2 ) (1.5)

An example for this increase can be seen for the three molecules magainin (3 kDa), BPTI (7
kDa), and staphyloccocal nuclease (18 kDa):

Fig.: one-dimensional proton spectra of magainin, BPTI, and staphyloccocal nuclease.

This increase in linewidth has very important consequences for high resolution NMR in
solution:

1. It leads to unsolvable overlap problems

2. As the lines are becoming wider, their amplitudes decrease. Remember that the integral of
the line stays constant. The smaller amplitude corresponds to a loss in the signal to noise
ratio.
3. The speed of magnetization transfer in COSY experiments is given by the size of the
scalar coupling constant J. The time required for this transfer is given by ~1/J. Only when
the magnetization lives long enough, i.e. T2 > ~1/J, the transfer can be carried out in an
effective way. This means that for very large molecules, COSY experiments become
completely inefficient.

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1.5 A simple example of fluctuation-dissipation: why is T2 for larger
molecules inversely proportional to the molecular tumbling time?

A simple explanation for this behavior will be attempted in the following section. Consider a
system of two spins A and B, which are close to each other in a molecule. The magnetic
moment of spin B produces a dipolar magnetic field at the location of spin A. The Brownian
motion of the molecule in solution has the effect that this dipolar magnetic field fluctuates. In
principle there can be x,y, and z-components of the dipolar field at the location of A
depending on the relative orientation of the two nuclei.

Fig.: Derome p.102

If the dipolar field at the location of A is parallel to the external field, the magnetic moment
of A will rotate a little faster, if the dipolar filed is antiparallel, A will rotate a little slower
than its normal Larmor frequency which is given by Bo. Now, lets make the
simplification that the dipolar field has a constant size Bd and that the field can only have two
orientations, i.e. parallel or antiparallel to z. At the same time we assume that the field stays
constant in one direction for a characteristic time c and that after this time it can either invert
its direction or continue in the same orientation. This change is completely random and
occurs with equal probability. Now lets also assume that the magnetic moment of A is in the
xy-plane. In the absence of the dipolar field, after a time c, the magnetic moment would have
rotated by an angle

! = "# c = $ Bo # c (1.6)

Because of the presence of the random dipolar field this angle is modified by an addition
which is given by

! " = #Bd $ c = % d $ c (1.7)

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where the plus and minus sign depends on whether the dipolar field had been parallel or
antiparallel to Bo and where we have use the abbreviation d = Bd. Now, lets wait for a
longer period t:

t = n !c (1.8)

In this case, the dipolar field had had n times the possibility to change its direction. The
problem is identical to the random walk (or drunken mans walk) in one dimension. How far
does the drunken man get if he only steps left and right by a length L of 1 m with equal
probability and he repeats this process n times?

Fig.: Reif pg.5

If this experiment is repeated many times (by many drunkards) the answer is the binomial
probability distribution:

n
n! !1$
Pn (m) = # &
!n+m$ !n'm$ "2% (1.9)
# &!# &!
" 2 %" 2 %
This is the probability of finding the man at position m*L after n steps with equal probability
to left or right. After their walk, some men will end up a little bit to the left, some men a little
to the right, but the average position of all men after their walk is the spot where they started
(x=0).

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 binomial distribution n = 20
0.18

0.16

0.14

0.12

0.1
P(m)

0.08

0.06

0.04

0.02

0
-20 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20
m

Fig.: Binomial probability distribution for n = 20 steps with equal probability (p = q = 0.5) in
left and right direction. The graph shows the probability Pn(m) of a net displacement of m
units to the right (adapted from Reif p. 11).

However, the width of the probability distribution or the root mean square displacement
increases with the number of steps. For a large number of steps n, the binomial distribution
becomes the Gaussian distribution:

2 2
Pn (m) ! e"m 2n (1.9a)
2! n
1/2
Its full width at e-1/2 = 0.61 is 2*n .

Now consider the situation for the dipolar coupling of the two spins A and B in a molecule in
solution: of course we are not just dealing with a single molecule but with many molecules
and we detect the nuclear moments of the spins A of all the molecules as a sum. After the
time t, i.e. after doing n times the random addition of dc to the phase angle of the single
spins A, the phase angles of all the spins A of all the molecules will have a random
distribution. The width of this random distribution of phases is given by

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 1
1 " t %2 1
! ! " d # c 2n = 2" d # c $ ' = 2" d (# c t ) 2
2
(1.10)
##c &
Now, when reaches the value 2 the spins A of all the molecules are more or less
completely spread out in the xy plane. The result is that the sum of all the magnetic moments
becomes 0 and the signal becomes zero.

Fig.: the distribution of phase angles over the whole circle (pizza distribution) gives a net
magnetic moment of zero for the whole ensemble of spins A.

To a first approximation, the relaxation time T2 is the time when has reached the value 2.

2 2
1 1 #! & #H &
2! ! 2" d (# c T2 ) 2
" ! 4% d ( # c = 4% d ( # c (1.11)
T2 $ 2" ' $ h '

Thereby one can see that T2 is inversely proportional to c and it is directly proportional to the
square of the (dipolar) interaction energy Hd. This is a very general principle resulting from
the fluctuation-dissipation theorem, which would also hold if the system had been disturbed
by a different interaction.

In reality, the dipolar field does not only jump between the +z and -z direction. The dipolar
field moves continuously as the molecules rotate. The characteristic time for this molecular
Brownian rotation is called the molecular tumbling time or rotational correlation time c. For
a spherical molecule of radius a rotating in a liquid of viscosity , c is given by

4" a 3# V#
!c = = (1.12)
3kT kT
where V is the volume of the molecule. As the volume is proportional to the molecular
weight, the rotational correlation time is proportional to the molecular weight. Therefore, T2
is inversely and the line width is directly proportional to the molecular weight. As a rule of
thumb, the rotational correlation time [given in ns] of a molecule in aqueous solution at room
temperature is about half its molecular weight in kDa.

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 1.5.1 Example:
15
Estimate the dipolar T2 for a proton which is 1.01 away from a N nucleus with a
rotational correlation time of 8 ns.

Answer: the dipolar frequency is derived from the dipolar coupling:

"1" 2 !0
"1Bd 2 = # d = H d /! =
4 $r 3
"15N = %2.71&10 7 (Ts)%1; "1H = 2.68&10 8 (Ts)%1
o = 4 $ 10%7 VsA-1m-1; T = Vsm-2
! = 1.054&10%34 Js
r = 1.01& 10%10 m; ' c = 8 &10%9 s
# d /2$ = %1.18 &10 4 Hz
2
1 2 1 ! 0 $ # I2# S2 ! 2
= 4 (! d / 2" ) ! c = 4 # & !c
T2 (2" )2 " 4" % r 6
! (1.13)
1
= 4.5 Hz
T2

The above simplifications have neglected a number of things:

1. the movement of the molecules is continuous and not a two-site random jump
2. there are also contributions of the dipolar field along the x- and y-axis which remove
magnetization from the xy-plane
3. the assumption that T2 corresponds to the time when the Gaussian width of the phase
distribution has reached a full circle is crude.

An exact calculation for two (dipolarly) interacting spins I and S at a distance r shows that

2
1 1 ! 0 $ " I2" S2 ! 2 ( 4J(0, ! c ) + J(" I ' " S, ! c ) + +
= # & ) ,
T2I 20 " 4! % r 6 *3J(" I , ! c ) + 6J(" S, ! c ) + 6J(" I + " S, ! c )- (1.14)

and by symmetry:

1 1
(! I , ! S ) = (! S, ! I ) (1.15)
T2I T2S

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 The function J(,c) is called spectral density. It gives the probability of finding the
frequency (energy) within the thermal motions of the molecule. For spherical molecules,
J(,c) has the following form:

"c
J(!," c ) =
1+ ! 2 " c2 (1.16)

where c is the rotational correlation time of the molecule.

Remark 1: in the slow motion limit (c >> 1), the terms J(,c) in Eq. 1.14 are very small
compared to J(0,c) = c. Thus 1/T2 is simply proportional to c. This holds also for other
relaxation mechanism such as quadrupolar relaxation and CSA relaxation. Therefore T2s for
different nuclei and from different relaxation mechanisms within a single molecule should be
proportional to each other (provided there is no variation in local mobility and there is no
additional line broadening from chemical exchange).

Remark 2: In the slow motion limit, the crude estimate for the heteronuclear1/T2 that we
derived above is off from the exact value by a factor of 4*5/(2)2 0.5.

Remark 3: Redfield theory (see below, Eq. 2.16) shows that the spectral density is given by
the Fourier transform of the autocorrelation function of the field fluctuations F(t) resulting
from the thermal motions:

$
*
J(" ) = % F(0)F ( t #)exp(i"t #)dt # (1.17)
0

where the overbar presents the ensemble average over all spins. Thus the relaxation rates, e.g.
Eq. 1.14 are proportional to the square (autocorrelation) of the field fluctuations. This is
(again) the central point of the fluctuation-dissipation theorem.
! In an equilibrium situation, the autocorrelation of the field fluctuations K(s) = F(t)F * (t + s)
does not depend on the absolute value of the time t, but only on the difference s. K(s) is a
decaying function with a maximum at s = 0. In the case of rotational Brownian motion, the
decay is monoexponential and the decay time is the rotational correlation time c. The Fourier
transform of the monoexponential decay gives Eq. 1.16. !

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Fig.: Illustration of the correlation function K(s) = F(t)F * (t + s) of a random function F(t).
(From Reif, pg. 571)

1.6 T1 relaxation !

The return to equilibrium along the z-axis of the spins involves transitions of the spins from
the down to the up state and vice versa. Therefore in the random magnetic fields at the
location of the nucleus I, there must be components that correspond to this transition, which
happens at the frequency o. It can be shown that for dipolar relaxation the T1 relaxation rate
is proportional to the square of the dipolar field strength times the spectral density of the field
"c
fluctuations at frequency o. The spectral density J(!," c ) = has the following
1+ ! 2 " c2
appearance:
x 10 -8
1
"c = 10 ns
MWT ~ 20 KDa

0.8
fast motion
spectral density [s]

!"c << 1
J ~ "c
slow motion
0.6 !"c >> 1
"c = 5 ns
J ~ 1/"c
MWT ~ 10 KDa

0.4

0.2 "c = 1 ns
MWT ~ 2 KDa

0
6 7 8 9 10
10 10 10 10 10
Larmor freq. ! [Hz]

Fig.: the spectral density or the efficiency of relaxation for different Larmor frequencies and
rotational correlation times c.

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What the graphic shows is that the spectral density is more or less constant from zero
frequency up to a limiting frequency, which is given by 1/c. For larger frequencies the
spectral density goes to zero. The area under the spectral density function stays the same
independent of c. For small molecules (short correlation time, c << 1) the function is
spread out such that there is not much density at the position of the Larmor frequency. For
large molecules (long correlation time, c >> 1) the spectral density is very small at the
position of . Therefore both for small and large molecules T1 relaxation is inefficient.
Between the two limits, there is the most efficient T1 relaxation, the T1 minimum. The
exact calculation of T1 (non-selective T1) for two identical spins I (two protons) by dipolar
coupling yields:

2
1 3 ! 0 $ " I4 ! 2
= # & {J(! I, " c ) + 4J(2! I, " c )} (1.18)
T1 10 " 4! % r 6

The behavior of the T1 and T2 as a function of the correlation time is shown in the following
figure:

10 3

10 2
T1
10 1
[s]

400, 600, 800 MHz

10 0

10 -1
400, 600, 800 MHz
T2
10 -2

10 -3
10 -12 10 -11 10 -10 10 -9 10 -8 10 -7
tau_c [s]
Fig.: T1 and T2 for two-spin system consisting of two protons with identical Larmor
frequencies (400, 600 or 800 MHz) at a distance of 2 as a function of the correlation time.

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1.7 Spin-flips induced by Brownian motion, the nuclear Overhauser effect

Consider now a system of two spins I and S, which are in dipolar interaction. Spin I is moved
away from thermal equilibrium by a 180 Ix-pulse as described above. The dipolar field of the
second nucleus S at the position of nucleus I fluctuates because of the Brownian motion of
the molecule. These fluctuations generate transitions between the states of the IS spin
system. The dominant transition is the so-called spin flip process where spin I changes from
the up-state to the down-state and spin S from the down-state to the up-state and vice versa
( ). We look at the spin system for the following sequence of events: (1) 180 Ix
(2) I-S spin-flip (3):

IS IS IS IS
spin states at
equilibrium (1)
probability 1 !P(I) !P(S) 1 !P(I) !P(S) 1 "P(I) "P(S) 1 "P(I) "P(S)
+ + + " ! + ! !
4 2 2 4 2 2 4 2 2 4 2 2
spin states after
180-Ix pulse (2)
spin states after
spin
flip (3)

Consider the table above and the distribution of states at equilibrium. We calculate for the
ensemble average values of the observables (time point 1):

1 !P(I) !P(S) 1 !P(I) !P(S) 1

<<I >> (1) = + + + + " = + !P(I)
! 4 2 2 4 2 2 2
1 !P(I) !P(S) 1 !P(I) !P(S) 1
<<I >> (1) = " + + " " = " !P(I) (1.19)
" 4 2 2 4 2 2 2
1 !P(I) !P(S) 1 !P(I) !P(S) 1
<<S >> (1) = + + + " + = + !P(S)
! 4 2 2 4 2 2 2
1 !P(I) !P(S) 1 !P(I) !P(S) 1
<<S >> (1) = + " + " " = " !P(S)
" 4 2 2 4 2 2 2

where the Ps are given from the Boltzmann distribution. We also notice that

1$
<< I >> " << I >>& = << I >>
2% ! # ' z (1.20)
1$
<< S! >> " << S >>& =<< Sz >>
2% # '

and therefore

<<I >> (1) = !P(I)

z (1.21)
<<S >> (1) = !P(S)
z

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After the 180 Ix-pulse (time point 2), the following ensemble averages are calculated:

1 "P(I) "P(S) 1 "P(I) "P(S) 1

<<I >> (2) = ! + + ! ! = ! "P(I)
! 4 2 2 4 2 2 2
1 "P(I) "P(S) 1 "P(I) "P(S) 1
<<I >> (2) = + + + + ! = + "P(I) (1.22)
" 4 2 2 4 2 2 2
1 "P(I) "P(S) 1 "P(I) "P(S) 1
<<S >> (2) = + + + ! + = + "P(S)
! 4 2 2 4 2 2 2
1 "P(I) "P(S) 1 "P(I) "P(S) 1
<<S >> (2) = + ! + ! ! = ! "P(S)
" 4 2 2 4 2 2 2

and therefore

<<I >> (2) = !"P(I)

z (1.23)
<<S >> (2) = "P(S)
z

If the spin flips between point (2) and (3) happened with a 100% probability the
distribution of states would be the following:

1 !P(I) !P(S) 1 !P(I) !P(S) 1

<<I >> (3) = + + + " + = + !P(S)
! 4 2 2 4 2 2 2
1 !P(I) !P(S) 1 !P(I) !P(S) 1
<<I >> (3) = + " + " " = " !P(S) (1.24)
" 4 2 2 4 2 2 2
1 !P(I) !P(S) 1 !P(I) !P(S) 1
<<S >> (3) = " + + " " = " !P(I)
! 4 2 2 4 2 2 2
1 !P(I) !P(S) 1 !P(I) !P(S) 1
<<S >> (3) = + + + + " = + !P(I)
" 4 2 2 4 2 2 2

and therefore

<<I >> (3) = !P(S) = <<S >> (1)

z z (1.25)
<<S >> (3) = "!P(I) = "<<I >> (1)
z z

Clearly the spin flips exchange the z-magnetizations between the two spins (trivial). If the
probablities P(I) and P(S) were equal, then the net effect from time point (1) to (3) would
be that spin I is back to equilibrium whereas spin S has its equilibrium distribution inverted.
The effect that z-magnetization can be exchanged between spins on the way to thermal
equilibrium by means of the dipolar interaction is called the nuclear Overhauser effect.

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1.8 The Solomon equation

The probability for the spin-flips is not 100%, but is given as a rate constant (per unit time).
This constant is the NOE build-up rate kNOE. kNOE is proportional to the square of the dipolar
interaction times a function that depends on the rotational correlation time c (spectral
density). The total return to equilibrium for the z-magnetizations of a two-spin system is
described by the Solomon equation [Solomon, I. (1955). Phys. Rev. 99, 559]:

! $ ! 'k (I) 'k $! << I >> ' << I >> $

d # << Iz >> &=# 1 NOE
&# z z eq
& (1.26)
dt #" << Sz >> & # 'kNOE 'k1 (S) &# << Sz >> ' << Sz >>eq
% " %"
&
%

In the case of an isolated, heteronuclear two-spin system, the rate constants k1(I), k1(S), kNOE
are given by

2
1 ! $ " 2" 2 ! 2
k1 (I) = # 0 & I S6 {3J(! I , " c ) + J(! I ' ! S, " c ) + 6J(! I + ! S, " c )}
10 " 4! % r
2
1 ! $ " 2" 2 ! 2
k1 (S) = # 0 & I S6 {3J(! S, " c ) + J(! S ' ! I , " c ) + 6J(! s + ! I , " c )} (1.27)
10 " 4! % r
2
1 ! 0 $ " I2" S2 ! 2
kNOE = # & {6J(! I + !S, " c ) ' J(! I ' !S, " c )}
10 " 4! % r 6

Remark: the approach to thermal equilibrium described by the Solomon equation, i.e by the
NOE, i.e. by the spin-flips resembles very much the propagation of a heat wave. At time zero
spin I is heated, then the heat dissipates to the next neighbor to the next neighbor to the next
neighbor ...

-17-
 inversion of spin I:
deviation from
thermal equilibrium
t=0

some spin flips with

next neigbors
t = !t

some spin flips with

next neigbors
t = 2!t

some spin flips with

next neigbors
t = 3!t

equal distribution at
t="

Fig.: approach to thermal equilibrium by NOESY spin-flips

1.8.1 Initial rate approximation

For NOE mixing times tm, which are short compared to the NOE buildup rate kNOE, the
increase in z-magnetization on spin S due to NOE transfer from spin I can be approximated
from the Solomon equation (dt t = tm):

-18-
 " << I >> % " )k (I) )k %" << I >> ) << I >> %
z z eq
!$
z
'($ 1 NOE
'$ ' !t (1.28)
$ << Sz >> ' $ )kNOE )k1 (S) '$ << Sz >> ) << Sz >>eq '
# & # &# &

The amount of magnetization, which has started on Iz and was transferred to Sz during the
mixing time, is given by:

! << Sz >>NOE " #kNOE (<< Iz >>(t=0) # << Iz >>eq ) tm (1.29)

In the NOESY experiment, the amount of Iz-magnetization at the beginning of the mixing
period ( << I z >> (t =0) ) equals ! << I z >> eq cos(" I t) . Therefore

! << Sz >>NOE = kNOE ( cos(! It1 ) +1) tm << Iz >>eq (1.30)

This means that the NOESY (I->S) cross-peak intensity (value in the original equation of
the NOESY experiment) is given by

! " #k NOE t m << I z >> eq (1.31)

Therefore the NOESY crosspeak intensity is proportional to the NOESY build-up rate kNOE in
the initial rate approximation. From the Solomon equation we realize that kNOE is proportional
2 2 6
to ! I ! S r . It follows that the NOE is strongest for short distances and between protons
(because protons have the largest gyromagnetic ratios).

1.9 Homonuclear NOE

For the homonuclear case (e.g. NOE between protons) we can set ! I " ! S " ! . kNOE is then
given as

2
1 ! $ " 4!2
kNOE = # 0 & 6 {6J(2!, " c ) ' J(0, ! c )} (1.32)
10 " 4! % r

For spherical Brownian motion, this function has a zero crossing at

!" c = 5 / 4 ! 1.12 (1.33)

This means that for B = 14T, no NOE can be observed between protons if
! c " 1.12 /(2# 600MHz) = 0.3 ns . At correlation times larger than 0.3 ns, kNOE becomes
negative (but the cross peak in the NOESY spectrum will have the same sign as the diagonal
peak). For !" c >> 1 (slow tumbling limit), the contribution of J(2!, " c ) can be neglected
and kNOE is simply given by

2
1 # 0 & " 4!2
kNOE ! " % ( 6 !c (1.34)
10 $ 4! ' r

-19-
 0.4
400 MHz
600 MHz
0.2
800 MHz
0

-0.2
k_noe [Hz]

-0.4

-0.6

-0.8

-12 -11 -10 -9

10 10 tau_c [s] 10 10

Fig.: NOE buildup rate kNOE for two protons at a distance of 2 for Larmor frequencies of
400, 600, 800 MHz.

-5

-10
k_noe [Hz]

-15

-20

-25

-30
0 0.5 1 1.5 2 2.5 3
-8
tau_c [s] x 10
Fig.: NOE buildup rate kNOE for two protons at a distance of 2 for Larmor frequencies of
400, 600, 800 MHz.

-20-
1.10 Heteronuclear NOE

From the homonuclear case, we have seen that kNOE depends on the rotational correlation time
of the internuclear vector of the two nuclei, which undergo dipolar relaxation. In principle,
the rotational correlation time could be extracted from the intensities of the homonuclear
proton-proton NOESY experiment. In practice, this is very difficult, because often the exact
distances are not known and secondly many protons interact at equal strength since their
distances are similar. The heteronuclear NOE between a proton and a directly bonded
heteronucleus is much easier to interpret, because the one-bond distance is rather well
determined and because this NOE is the dominant relaxation effect on the heteronucleus.
{1H}-15N NOEs and to a lesser extent {1H}-13C NOEs are used to obtain information on the
correlation times of the respective internuclear vectors in biological macromolecules. Usually
the steady-state NOE effect is measured. The proton spin is often called I and the
heteronuclear spin S. The steady state NOE enhancement compares the z-magnetization of
the S-spin in thermal equilibrium to the z-magnetization of the S-spin at equilibrium when
the I-spin is saturated:

<< Sz >>(I-sat)
NOE({I}-S}) = (1.35)
<< Sz >>eq
Saturation of the I-spin means that its magnetization vanishes. This can be obtained by
applying a large number or random RF-pulses on I. The z-magnetization of the S-spin for this
case can be calculated as a steady state solution of the Solomon equation. For the steady
state, the time-derivatives are simply set to 0. Because of the saturation of spin I, we use
<<Iz>> = 0:

" !k (I) !k %" ! << Iz >>eq %

0 =$
1 NOE
'$ ' (1.36)
$ !kNOE !k1 (S) '$ << Sz >>I-sat ! << Sz >>eq '
# &# &

Solving for <<Sz>>I-sat yields:

0 = kNOE << Iz >>eq !k1 (S) (<< Sz >>I-sat ! << Sz >>eq )

kNOE (1.37)
<< Sz >>I-sat = << Iz >>eq + << Sz >>eq
k1

And therefore:

kNOE << Iz >>eq k !

NOE({I}-S}) = +1 = NOE I +1 (1.38)
k1 << Sz >>eq k1 ! S

k1 is the longitudinal relaxation rate (1/T1). It can also contain contributions from other
relaxation mechanisms besides the dipolar 1-bond relaxation. A significant contribution to k1
for 15N amide nuclei is the relaxation stemming from chemical shift anisotropy. The figure
shows the behavior of the amide {1H}-15N-NOE as a function of the correlation time when

-21-
this mechanism is taken into account. The effect clearly distinguishes between motions faster
or slower than ~ 0.5 ns.

0
{1H}-15 N NOE

-1

-2

-3 800
600
400

-4
-11 -10 -9 -8 -7
10 10 10 10 10
!c [s]

Fig: values of the steady state heteronuclear {1H}-15N NOE as a function of correlation time
for magnetic field strengths corresponding to 400, 600, and 800 MHz proton Larmor
frequency. The effect of 160 ppm chemical shift anisotropy ( - ) on k1 has been taken

into account.

-22-
1.11 Dynamical information from relaxation experiments

The relaxing way to study motion (adapted from G. Wagner, 1995, nature structural
biology, 2, 255-257)
15
N NMR relaxation studies have emerged as a powerful approach for the determination of
the motional properties of molecules in solution. In an 15N relaxation experiment, one creates
non-equilibrium spin order and records how this relaxes back to equilibrium. At equilibrium,
the magnetization of the 15N spins is aligned along the external field, and this alignment can
be inverted by radio frequency pulses. The spins will relax back to equilibrium along the
direction of the magnetic field with a longitudinal relaxation time, T1, or the longitudinal
relaxation rate RN(Nz). The magnetization can also be oriented perpendicular to the external
magnetic field. The relaxation time of this spin order back to equilibrium is called the
transverse relaxation time, T2, and the rate can be denoted as RN(Nx). A third relaxation
parameter is the so-called heteronuclear nuclear Overhauser effect (NOE). This is measured
by saturating the proton (1H) signal and observing changes in the 15N signal. The rate at
which this occurs is the heteronuclear cross relaxation rate, RHN(HZ<->NZ); for long proton
saturation, it reaches the steady state NOE(HZ<->NZ) value. These are essentially the three
experiments Nicholson et al1 perform to learn about mobility in HIV protease. Other spin
orders could be created and the relaxation analyzed. The relaxation of the spin orders is due
to rotational diffusive motions of the nitrogen atom and the orientation of its chemical bonds
(N-H bond) relative to the external field. The molecular motions cause the 15N nucleus to
experience energy fluctuations inducing transitions between the Zeeman energy levels - and
result in relaxation. Thus, the relaxation of spin orders is related to rotational motions of the
amide group; this includes the overall, and internal motions of the HIV protease. The effect
of the motions on relaxation rates is described with a spectral density function J(). This
function describes the relative distribution of the frequencies of the rotational diffusive
motions. For the three parameters measured by Nicholson and colleagues, these relations are:

RN (N z ) = d 2 [ J(! N ! ! H ) + 3J(! N ) + 6J(! N + ! H )] + c 2 J(! N )

RN (N x ) = 0.5d 2 [ 4J(0) + J(! N ! ! H ) + 3J(! N ) + 6J(! H ) + 6J(! N + ! H )] +
c2
[ 4J(0) + 3J(! N )] + Rex (1.39)
6
!Hd2
NOE(H z " N z ) = 1+ [6J(! N + ! H ) ! J(! N ! ! H )]
! N RN (N z )

In these relations, d and c represent the strengths of the dipolar interaction between the proton
and nitrogen, and the chemical shift anisotropy: they also represent the main relaxation
mechanisms for 15N in proteins. N and H are the resonance frequencies of 15N and 1H. In a
typical spectrometer, these are 50 and 500 MHz, respectively. The equations indicate that 15N

1
L. Nicholson, T. Yamazaki, D.A. Torchia, S. Grzesiek, A. Bax, S.J. Stahl, J.D. Kaufman, P.T. Wingfield,
P.Y.S. Lam, P.K. Jadhav, C.N. Hodge, P.J. Domaille, and C.-H. Chang: Flexibility and function in HIV-1
protease. Nature Structural Biology 2, 274-279, 1995.

-23-
relaxation is primarily sensitive to very fast motions in the order of the frequencies of protons
and nitrogens as well as the sum and difference thereof. However, the transverse relaxation
rates can also be influenced by slow conformational exchange, represented by Rex. Typically,
motions on the order of ms to s would have an effect on the transverse relaxation rates.
To measure dynamics from such relaxation experiments one has to perform further ex-
periments, or alternatively one can make assumptions about an analytical form of the spectral
density function that contains a sufficiently small number of parameters can be fitted to the
experiments. The most commonly used analytical form for a spectral density function has
been proposed by Lipari and Szabo which is a sum of two Lorentzian shapes:

"m !
J(! ) = S 2 2
+ (1! S 2 )
1+ (!" m ) 1+ ("! )2 (1.40)
!1 !1 !1
with ! = ! +!
m e

Accepting that this is a reasonable assumption, the relaxation rates depend on only one global
and two local parameters, the overall correlation time m which is the same for all residues, a
correlation time for internal motions, e and an order parameter S2 which is a measure of the
amplitude of the internal motions, With the measurement of three relaxation parameters, the
longitudinal relaxation rate, RN(Nz), the transverse relaxation rate, RN(Nx), and the
heteronuclear NOE(HZ<->NZ), the three parameters, m, e, and S2, can readily be fitted.

The following figure shows the measured T1, T2, and NOE values for the HIV-1 protease in
complex with two different inhibitors:

-24-
A fit of the parameters S2 and Rex is shown in the next figure (Fig. 2). Clearly visible is the
enhanced mobility around residues 38-42. These residues are at the hinges of the two enzyme
flaps that have to open in order to allow the binding of an inhibitor or substrate to the
protease active site.

Fig.: The mobility of HIV-1 protease as determined by NMR relaxation experiments. The
mobility of the two enzyme flaps makes it possible for the substrate to enter into the active
site of the protease. All three figures from Nicholson et al. (1995) Flexibility and function in
HIV-1 protease. Nature Structural Biology 2, 274-279.

-25-
2. A quick derivation of the master equation
according to M. Goldman (1993) with special thanks to Bloembergen, Purcell, Pound (1948),
Wangsness and Bloch (1953), Bloch (1956), Solomon (1955), Redfield (1957), Abragam
(1961), Ernst, Bodenhausen, Wokaun (1987).

2.1 The total Hamiltonian

H = H 0 + H1 (t) (2.1)

H0: main Hamiltonian, discrete levels, time-independent

H1: random, spin-lattice coupling

2.2 Liouville-von Neumann equation

d!
= !i [ H, ! ] (2.2)
dt

2.3 Transform operators to interaction picture

i.e. into the rotating frame

! = exp(iH t)Q exp(!iH t)

Q(t) 0 0

d!!
= !i "#( H! ! H 0 ), !! $%
dt
& (2.3)
d!!
= !i "# H! 1 (t), !! $%
dt
H0 disappears!

-26-
2.4 Integrate once

!! (t) = !! (0) ! i ' 0 #$ H! 1 (t"), !! (t")%&dt"

t
(2.4)

put into original Liouville-von Neumann equation:

d!! (t)
= !i "# H! 1 (t), !! (0)$% ! " H! (t), " H! (t&), !! (t&)$$dt&
t

dt
' 0# 1 # 1 %% (2.5)

2.5 Take ensemble average () of all terms

d!! (t)
= ! ' #$ H! 1 (t), #$ H! 1 (t"), !! (t")%&%&dt"
t
(2.6)
dt 0

( H 1 (t) from random inner forces ! H 1 (t) = 0 ). This equation is exact. It shows nicely the
second order nature of relaxation theory, i.e. time derivatives are proportional to the square of
the disturbing Hamiltonian.
Remark: Taking the ensemble average seems strange, since the very concept of density
matrix is intimately linked to the ensemble average. That a further averaging is necessary
stems from the fact that the operator H 1 (t) is a random function of time; in different parts of
the system otherwise identical, simulated by different members of a Gibbs ensemble, it may
have a different history, resulting in a different density matrix ! . (M. Goldman, 1993).

2.6 Introduce return to equilibrium ad hoc

!! (t) ! !! (t) " !! eq (2.7)

This forces ! (t) to end up at ! eq . This hat trick is necessary because the lattice is not treated
quantum-mechanically.

d!! (t)
= ! ' #$ H! 1 (t), #$ H! 1 (t"), !! (t") ! !! eq %&%&dt"
t
(2.8)
dt 0

-27-
2.7 Expand H1 in spin and time dependent part

H1 (t) = !V! F! (t) = !V!+ F!* (t) (2.9)

! !

V! spin part
F! (t) random function of time

V!! (t) = exp(iH 0 t)V! exp(!iH 0 t) = exp(i"! t)V! (2.10)

such a decomposition is always possible =>

d!! (t)
= !( ' #$V!" (t), #$V!#+ (t"), !! (t") ! !! eq %&%& F" (t)F#* (t")dt" (2.11)
t

dt ",#
0

2.8 Use assumptions on random motions

1. F! (t)F"* (t # ) $ 0, when t - t # >> % c

2. ! (t ") varies slowly on time scale of c

This has the following consequences:

1. ! (t ") can be replaced by ! (t) in the integral

2. all members of the ensemble experience many random events , when |t-t'| >> c
=> all ! (t) are nearly the same and they are nearly equal to ! (t)
=> can be omitted on ! (t)
=>

d!! (t)
= !) ( #$V!" (t), #$V!#+ (t"), !! (t) ! !! eq %&%& ' F" (t)F#* (t")dt" (2.12)
t

dt ",#
0

2.9 Use one more assumptions on random motions

F! (t)F"* (t!) = G!" ( t " t! ) (2.13)

-28-
d!! (t) " $ t
" ! ! $
= !(#V" , #V# , ! (t) ! ! eq %% ' exp(i"# t ! i" $ t&)G#$ (t-t&)dt&
+

dt #,$
0

t t
' dt& = exp(i(!" ! ! # )t) ' exp(i! # (t ! t&))G"# (t-t&)dt&
0 0
(2.14)

The integral can be extended to infinity since G!" (t) # 0, for t >> $ c

t t
# 0
exp(i! " (t ! t"))G#" (t-t")dt" = # 0
exp(i! " $ )G#" ($ )d$ $
%
$ # 0
exp(i! " $ )G#" ($ )d$ = J#" (! " )
(2.15)

where the definition

"
J!" (# ) ! #G !" ($ )exp(i#$ )d$
0
(2.16)

has been used.

=>

d!! (t)
= !&"#V" , "#V#+, !! (t) ! !! eq $%$% exp(i($" ! $ # )t)J"# ($ # )
dt ",#
(2.17)

This is the principal result of Redfield's theory!

-29-
2.10 Secular approximation

The secular approximation retains only terms with = in the Redfield equation, since

other terms are assumed to oscillate rapidly on the time scale of the changes of the density
matrix. This approximation leads to a system of coupled linear differential equations, which

is easily solved by standard methods of linear algebra. The relaxation supermatrix R adopts
the Redfield kite structure.

d!! (t) !
dt
!" ' #$V , #$V
" #
+
, !! (t) " !! eq %&%& J"# ($ # ) ( " R( ! (t) " !! eq )
",#
$" =$ #
(2.18)

From Ernst, Bodenhausen, Wokaun 1987, pg. 54

-30-
3. References
Abragam, A. (1961) The Principles of Nuclear Magnetism (Clarendon Press, Oxford)
Bloch, F. (1956) Phys. Rev. 102, 1956.
Bloembergen, N.; Purcell, E.M.; Pound, R.V. (1948) Phys. Rev. 73, 679.
Cavanagh, W. J. Fairbrother, A.G. Palmer, N.J. Skelton, Protein NMR Spectroscopy,
Academic Press, San Diego, 1996.
Ernst, G. Bodenhausen, A. Wokaun, Principles of Nuclear Magnetic Resonance in One and
Two Dimensions, Clarendon Press, Oxford, 1987.
M. Goldman, Quantum Description of High-Resolution NMR in Liquids, Oxford University
Press, Oxford, 1988.
M. Goldman, Introduction to Some Basic Aspects of NMR, appeared in Rendiconti della
Scuola Internazionale di Fisica Enrico Fermi (S.I.F.) - corso CXXIII (Ravenna, 13.-21.
10. 1992), pg. 1-66. Title of course: Nuclear Magnetic Double Resonance. English series
title: Proc. Intl. School of Physics Enrico Fermi, course 123. Maraviglia, B. (Ed.),
Amsterdam, 1993. My all time favourite!!!
Redfield, A.G. (1957) IBM J. Res. Develop., 1, 19; Theory of relaxation processes in
Advances in Magnetic Resonance, edited by J.S. Waugh, Vol. 1 (Academic Press, New
York, N.Y., 1965), p. 1.
F. Reif, Fundamentals of Statistical and Thermal Physics, McGraw-Hill Kogakusha, Tokyo,
1965.
Solomon, I. (1955) Phys. Rev. 99, 559.
Wangsness, R.K.; Bloch, F. (1953) Phys. Rev. 89, 278.

-31-
4. Appendix

4.1 Efficiency of scalar magnetization transfer in the presence of

relaxation

In the presence of relaxation the efficiency of the scalar magnetization transfer depends
strongly on the ratio of the transfer speed J and the decay rate 1/T2. If the magnetization has
decayed too fast at the end of the transfer internal, no efficient transfer is possible.
90x 180y 90y
1H ! ! "INEPT"
180y 90x
15N

2"JHzNz*2!
Hz -Hy
-Hycos(2"J!)+ -Hycos(2"J!)+
2HxNzsin(2"J!) 2HzNysin(2"J!)
Relaxation: exp(-2!/T2(H)) transfer term
1
0.9 sin(2"J!)
0.8
0.7
0.6
transfer

0.5 exp(-2!/T2(H))
0.4
!opt < 0.25*J
0.3
0.2
0.1 sin(2"J!)*exp(-2!/T2(H))
0
0 0.25 0.5
!*J
1
! opt = atan "JT2 ; JT2 << 1# no efficient transfer
2" J
Fig.: efficiency of scalar magnetization transfer by INEPT

-32-
4.2 The size of the scalar couplings

The size of the coupling constants between protons that are connected via three bonds varies
in the range from ~ 3 to 10 Hz. This means that it takes between 0.1 to 0.3 s to transfer
magnetization completely via the proton-proton three-bond J-couplings. The size of the
heteronuclear one-bond coupling constants is usually much larger, e.g. ~ 140 Hz for 1H-13C
and ~ 93 Hz for 1H-15N. This means that the magnetization transfer takes ~ 7 ms for 1H ->
13
C and ~ 11 ms for 1H -> 15N

C!
6 8 6
slow tumbling limit:
H C H
#
1/T2 ~ J(0) ~ $c ~ MWT
42 14 52
N C" C

H 13 H 8 O

Typical T2-values (ms) for a ($c ~ 15 ns) protein

(MWT ~ 30 kDa)

J T2 << 0.5 => no efficient transfer

1J
140 NC" T2(C") = 0.15 !! for 30 kDa
H C H
# -7
35

N C" C N C"
11 55 15 11
92 140
H H O H H

3 - 10

J-values (Hz) of a protein

Fig.: T2-values for a 30 kDa protein and J-couplings of a protein.

4.3 Some product operator gymnastics

The following commutator rules hold for any spin I:

-33-
 !"I x , I y #$ =I x % I y & I y % I x = iIz
[and cylcic permutations thereof (x->y->z->x)] (4.3.1)

For a spin-1/2 particle the angular momentum operators can be represented by 2 x 2 matrices,
which are called Pauli matrices:

1! 0 1 $ 1 ! 0 'i $ 1! 1 0 $
Ix = # &, I y = # &,Iz = # & (4.3.2)
2" 1 0 % 2" i 0 % 2 " 0 '1 %

In addition to the canonical commutator rules, the following relations hold for spin-1/2:

1" 1 0 %
I x ! I x = I 2x = I 2y = Iz2 = $ ' (4.3.3)
4# 0 1 &

1
I x !I y = "Iy ! Ix =
iI
2 z
[and cylcic permutations thereof (x->y->z->x)] (4.3.4)

4.4 Irreducible representation of the dipolar interaction

The dipolar Hamiltonian (in angular momentum units)

!1! 2 ! 0 " (I ! r)(I ! r) %

Hd = 3
# I1 ! I 2 -3 1 2 2 & (4.4.1)
4! r $ r '

can be written as

4"
Hd = !d
5
"Y 2m (# , $ )"Vm,i
+
= !d " 2
D0m ($, # , % )"Vm,i
+

m=!2,2 i m=!2,2 i
(4.4.2)
& & !
with ! d = 1 2 3 0
4! r

and Y2 m (! ," ) is the second order spherical harmonic with angular arguments that correspond
2
to the polar angles of the internuclear distance vector r, and D0m (! , ", # ) is a Wigner rotation
matrix.

The spin part of the Hamiltonian and its characteristic frequencies are given by

-34-
 V0,1 = !2I z Sz ;! 0,1 = 0
1
V0,2 = I + S! ;! 0,2 = ! I ! ! S
2
1
V0,3 = I ! S+ ;! 0,3 = ! S ! ! I
2
6
V1,1 = I + Sz ;!1,1 = ! I (4.4.3)
2
6
V1,2 = I z S+ ;!1,2 = ! S
2
6
V2,1 = ! I + S+ ;! 2,1 = ! I + ! S
2
for m " 0 :V!m,i = (!1)m Vm,i +
;! m,i = !! !m,i

4.5 Example: heteronuclear T2 from Redfield theory

We want to use the Redfield equation and calculate an expression for the T2 for a
heteronuclear two spin-system IS due to dipolar interaction under the assumption of
spherical diffusion. We further assume the slow motion limit (c >> 1), such that all spectral
densities besides J(0) can be neglected.

An inspection of the operators for the dipolar interaction shows that only the term V0,1 = -2
IzSz will give rise to a zero frequency spectral density. Therefore, the summation in the
Redfield sum over the indices and reduces to the case where = = (0,1)

d!! (t) #V , #V +, !! (t) " !! %% J ($ ) =

dt
!" ' $ "$ # eq && "# #
",#
$" =$ # =0

= "#$V(0,1), #$V(0,1)
+
, !! (t) " !! eq %&%& J(0,1)(0,1) ($ (0,1) ) = (4.5.1)

= "#$"2I z Sz , #$"2I z Sz , !! (t) " !! eq %&%& J(0,1)(0,1) (0)

Note that the indices and are used to label different parts of the random Hamiltonian
corresponding to distinct rotational frequencies in the rotating frame. If we look at the
expansion of the dipolar Hamiltonian, we see that every pair of indices (m,i) corresponds to a
distinct frequency m,i and vice versa. Therefore we can just make the identification
= (m , i ) and = (m , i ).

We need to find an expression for J(0,1)( 0,1) (0) . From the expansion of the dipolar interaction,
we see that the rotational diffusion of the molecule leads to a time-dependent variation of the
spherical harmonical functions Y2 m (! ," ) . The random functions F (t) are therefore given by

4#
F! (t) = " d Y2m! ($ (t), % (t)) (4.5.2)
5

-35-
For spherical diffusion, the correlation function F! (t)F"* (t!) = G!" ( t " t! ) is given by

4$
F! (t)F"* (t!) = # d2 *
Y2m! (% (t), & (t))Y2m (% (t!), & (t!)) =
5 "

(4.5.3)
#2
= d 'm! m" exp(" t " t! / ( c )
5

Such that J!" (# ) is given by

!
% d2 !
J!" (# ) = " F! ($ )F"* (0)exp(i#$ )d$ = 5
&m! m" " exp(#$ / $ c )exp(i#$ )d$
0 0
(4.5.4)
% 2
1 % 2 $ $c #$ c '
= d &m! m" = d &m! m" & 2 2
+ i 2 2)
5 1 / $ c # i# 5 %1+ # $ c 1+ # $ c (

And we realize that

! d2
J(0,1)(0,1) (0) = "c (4.5.5)
5

Therefore

d!! (t) " d2

# # ! ! %%
! "4 $ I z Sz , $ I z Sz , ! (t) " ! eq && # c (4.5.6)
dt 5

The equilibrium magnetization ! eq contains only longitudinal or unity operators which

commute with IzSz and can be omitted in this equation.

d!! (t) !2
! "4 #$ I z Sz , [ I z Sz , !! (t)]%& d " c (4.5.7)
dt 5

From the commutator algebra (Eqs. 4.3.1, 4.3.3), it is easy to see that a density matrix which
proportional to Ix at time 0, will always be proportional to Ix (I and S are assumed to be spin
1/2).

!! (0) = a(0)I x ! !! (t) = a(t)I x (4.5.8)

Putting this Ansatz into Eq. 4.5.7 yields

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 da(t) !2
Ix ! "4 #$ I z Sz , [ I z Sz , a(t)I x ]%& d " c =
dt 5
2
!
= "4 #$ I z Sz , [ I z Sz , I x ]%& a(t) d " c = (4.5.9)
5
2
# % !d ! d2
= "4 $ I z Sz , iI y Sz & a(t) " c = "I x a(t) " c
5 5

or

da(t) !2 1
! " d " c a(t) = " a(t)
dt 5 T2
# a(t) ! a(0)exp("t / T2 )
(4.5.10)
2
1 ! d2 $ # # ! ' "
! "c = & 1 2 30 ) c
T2 5 % 4! r ( 5

This expression for T2 corresponds to textbook expressions (Eq. 1.14) in the slow tumbling
limit. The complete expression for spectral density terms at non-zero frequencies is derived
in an analogous manner.

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