Lanthanides pseudocontact shift

Crudely approximated, the magnitude of the pseudocontact shift Afipolai, which predominates in lanthanide shift reagents, decreases with increasing distance between the observed nucleus i and the paramagnetic ion ... 

In accordance with the proportionality (3.8 a), the magnitude of the pseudocontact shift, which predominates for lanthanide shift reagents, decreases with the distance of nucleus i from the paramagnetic ion. Thus, C-9 of camphor is shifted more than C-10 on addition of the europium chelate. Often, the crude approximation (3.8 a) is a valuable assignment aid. 

By plotting 5 S0/5J° vs. gj(gj — 1 )J(J + 1 )/S J° for all the lanthanides, the intercept gives / , and hence the ratio between pairs of pseudocontact shifts (Fig. 2.22). Within this approximation, the requirement for axial symmetry was found to hold for many systems, even with low symmetry, possibly as a result of ligand rearrangement which might be fast on the NMR time scale. 

Separation of pseudocontact and contact shifts in axial systems can also be achieved, again by using a variety of lanthanides, without assuming that for a given signal the contact shift is zero, as long as the expected patterns of both pseudocontact and contact shifts (Fig. 2.21) hold. Here, the hyperfine shift can be expressed as the sum of contact and pseudocontact shifts (Eqs. (2.39) and (2.37)) ... 

Fig. 5.56. Some lanthanide-chelating ligands used as pseudocontact shift reagents.

Lanthanides have been used as substitutes for calcium in calcium binding proteins since the early days in NMR [155,156]. Remarkable information was obtained on systems such as Yb(III)-substituted parvalbumin (which contains a typical calcium binding site called EF-hand [157,158]) from ID spectroscopy alone [159-164], later complemented by 2D spectroscopy [165]. More recently, pseudocontact shifts and longitudinal proton relaxation times have been used to... 

Analogously, the pseudocontact shifts were used to refine the solution structure of the Ce(III), Dy(III) and Yb(III) derivatives of monolanthanide-substituted Calbindin D9k. Since the three lanthanides span a wide range of magnetic anisotropies, the refinement was effective in shells from the metal of 5—15 A for Ce(III), 9-25 A for Yb(III), 13-40 A for Dy(III), as useful pseudocontact shifts were observed in these shells (Fig. 5.59) [167]. Therefore, by using different lanthanides it was possible to enlighten shells at variable distances from the metal itself. 

The paramagnetic properties of the lanthanides have been exploited in NMR spectroscopy for many years [16,17], The paramagnetic lanthanide induced shift is generally considered as the sum of the contact and pseudocontact terms (Equation 1) [16-18]... 

As we pointed out in Section 4.11, lanthanide shift reagents owe their utility partly to the fact that the electron spin-lattice relaxation time for the lanthanides is very short, so that NMR lines are not exceptionally broad. On the other hand, there are shiftless paramagnetic reagents that shorten both Tx and T2 to a moderate degree without causing contact or pseudocontact shifts. 

The lanthanide induced shifts (LIS) arise from the interaction of the magnetic nucleus with the magnetic field of the paramagnetic lanthanide ion. This could arise via two mechanisms either a pseudocontact (dipolar) through-space fashion involving a dipole dipole interaction, or by a contact mechanism with delocahzation of unpaired spin density from the lanthanide f-orbitals via the lanthanide substrate bond on to the organic molecule the former is more important. 

Further developments of pseudocontact shift theory applicable to lanthanide ion systems are discussed later. 

Studies of Ln(in) nitrilotriacetate (539) and ethylenediamine (540) complexes have been reported. In the latter case a contact mechanism is responsible for the shifts in the lighter lanthanides (up to Ho) whereas a pseudocontact shift is dominant for the remainder of the series. Some novel lanthanide-cobalt sandwich complexes have also been reported. (587) Uranium(iv) complexes continue to be the most extensively studied of the actinide ion complexes. Appreciable dipolar interactions are expected to arise from the orbitally degenerate ground term arising from the 5f configuration of U(iv). However, in practice isotropic shifts of U(iv) complexes are not dominated by dipolar interactions. 

Quantitative separation of the n contact and pseudocontact contributions to the lanthanide induced shifts (LIS) in aniline and m-and p-toluidines has been reported. (395, 396) The contact shift patterns are estimated from the rr-spin density distribution of the appropriate cation radical or from the Ni(acac)2 induced shifts. The separation of the shifts was checked by comparing the relative contact shift contribution with the <5 ) value of Golding and Halton (389) and the remaining pseudocontact contribution with the calculated values of Bleaney s theory. (380)... 

After protons, C is the most widely detected nucleus in NMR. Proton cross-polarization and decoupling are usually applied to increase the S/N, and these types of experiment can result in substantial sample heating. Many forms of C-based NMR thermometers have been proposed. The first such system was based on the cis-trans conformational equilibrium of furfural, with the linewidths of carbon-3 and the aldehyde carbon being temperature-dependent. There are many disadvantages of linewidth-based measurements, and subsequent developments concentrated almost wholely on temperature-dependent C chemical shifts. The first such system utilized a temperature-dependent lanthanide-induced pseudocontact shift in a complex of acetone-de and ytterbium(III)1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octadionate (Yb (fod)3). The 6co of the acetone-dg, measured with respect to a CS2 standard, was almost linearly dependent on 1 / T with a small quadratic term over a range 200-315 K. If a small amount of protonated acetone was added, then the proton resonance, measured with respect to the protons of TMS, was also found to be temperature dependent ... 

Only the pseudocontact shifts give exact information on the location of the cation, and, therefore, on the structure of the complex. According to an equation developed by McConnell and Robertson,the lanthanide-induced shift, Av, is... 

With polyols, the procedure of separating contact from pseudocontact shifts sometimes proves unsatisfactory some of the higher lanthanides give discordant results. - It appears that complexes of these higher lanthanides, that have smaller ionic radii, have different interatomic distances and valency angles, and probably different coordination numbers, even if they have the same structures. Theoretical studies confirmed these differences. It is advisable, therefore, to disregard the higher lanthanides in this procedure. ... 

Lanthanide Shift Reagents.—The effects of random co-ordinate error in analysis of lanthanide-induced axial pseudocontact shifts have been discussed, " and the contributions of contact and pseudocontact shifts in the n.m.r. spectra of isoquinoline and of endo-norbornenol have been evaluated. An experimental and computational approach to the use of lanthanide-induced shifts as a rigorous method for structure determination has been described. The method was used to predict the lanthanide-induced shift behaviour of a substrate. The recording of experimental data in excellent agreement with the molecular structure was reported. Contact shift contributions to lanthanide isotropic shifts have been found to be important for organic compounds even where the carbon atom is five bonds away from the lanthanide. 

Lanthanide ions with anisotropic molecular magnetic susceptibility tensor Ay, for example, Er , Tm , or Yb , allow valuable structural information to be extracted from pseudocontact shifts (PCS, see also Section 3.6) and residual dipolar couplings (RDCs) arising from the partial alignment of the -labeled biomolecules in the induced magnetic field (Su et al., 2008b) ... 

The conformational space sampled by the two-domain protein calmodulin has been explored by an approach based on four sets of NMR observables obtained on Tb " and Tm -substituted proteins. The observables are the pseudocontact shifts and residual dipolar couplings of the C-terminal domain when lanthanide substitution is at the N-terminal domain. Each set of observables provides independent information on the conformations experienced by the molecule. It was found that not all sterically allowed conformations are equally populated. For example, taking the N-terminal domain as the reference, the C-terminal domain preferentially resides in a region of space inscribed in a wide elliptical cone. 

---