For medium 2-4k Da molecules NOE depends on shape, how rigid the molecule is weighted average of the shape of the combination of all conformers. Also viscosity (dipole) of the solvent. The NOESY crosspeak sign will tell you if the NOE effect is adding or subtracting relative to the diagonal crosspeak: -I(a)
zcos(Ωt
1)
-I(a)
zcos(Ω(a)t
1) [diagonal] + R
abτ
mI(b)
zcos(Ω(a)t
1) [crosspeak]. If H
a experiences negative NOE then it adds to H
b's signal. R
ab is the cross-relaxation rate. For small molecules R
ab is linear i.e. w(larmor frequency)*τ(tumbling rate)<<1 where double quantum relaxation dominates(ββ<->αα). For very large molecules ωτ>>1 where zero quantum relaxation dominates (αβ<->βα), and R
ab gains a negative coefficient making the crosspeaks and the diagonal peaks the same sign. For the medium sized molecules ωτ≈1 DQR and ZQR are about the same which depends on field strength and the stuff mentioned above, and the signal goes down into the noise. The ROESY pulse sequence puts the spins on the X' axis and the signal becomes double quantum only.