ReviewPseudocontact shifts in lanthanide complexes with variable crystal field parameters
Highlights
► The standard and an alternative method for separating pseudocontact shifts (PCS) are reviewed. ► We show how to overcome any variation in crystal field parameters in the separation of PCS. ► Variable coordination number and ligand polarizability can be accounted for by our method. ► The scope embraces MRI contrast agents and (enantioselective) catalysts. ► The case of structural equilibria in DOTA derivatives is discussed.
Introduction
Paramagnetic NMR provides some of the most sensitive and accurate experimental parameters for structural determinations in solution [1], [2]. Paramagnetism enhances relaxation rates and induces remarkable shift of nuclear resonances. This is true for both d- and f-metals, where the former have been very widely used in the context of biomolecular NMR [1], while the latter have widespread interest for small or medium-size molecules [3], [4], although their use in proteins and nucleic acids is gaining increasing interest [5], [6].
Owing to the very similar ionic radius and identical structure of the frontier orbitals, lanthanide(III) ions are usually considered to provide isostructural complexes throughout the series, possibly with a higher degree of homogeneity within the elements at the beginning or at the end of the series [7]. This fact is the basis for extracting contributions containing structural information from experimental observables, because one is able to compare the values of observables, measured on complexes having the same geometrical and electronic structure but different magnetic properties. A very relevant case is provided by the extraction of pseudocontact shifts (PCS), which are valuable pieces of geometrical information [8]. This is because they display a marked dependence on the polar coordinates of the observed nucleus in a reference system based on the magnetic anisotropy tensor. Thus, they offer the basis for accurate geometry determination in solution, provided they are reliably extracted from the observed shifts. To this end, Reilley developed a procedure, which is based on the conservation of crystal field parameters from one complex to another of the same ligand [9].
The existence of an exchangeable coordination site is a key feature for functional systems: molecular recognition [10], enantiomer discrimination [11], substrate activation [12], luminescence quenching [13], water nuclear relaxation (T1-contrast in MRI) [14], and saturation transfer contrast enhancement [15] are all dependent on the dynamic binding of a ligand (most often water) to Ln3+. As a consequence, most complexes are designed with a good chelating agent (often macrocyclic), leaving at least one position (hereafter called axial) open to dynamic coordination. This feature is associated with a variable coordination number (CN) along the series, whereby early lanthanides tend to bind ancillary ligands, which may be absent in the complexes of the late ions [16]. This has a negative effect on the separation of PCS because one cannot treat simultaneously data of complexes with different CN (usually before or after the so-called “gadolinium break”) [17], [18].
We shall develop a simple set of equations, directly derived from the standard Reilley treatment, for achieving the isolation of PCS, in cases with variable CN. We shall then see that the same treatment can be extended to other cases, where the properties of the main chelating agent are modulated, because of polarizability effects, as in heterobimetallic systems or because of a peculiar conformational feature, typical of DOTA derivatives. In all these cases, we shall see how can one take advantage of a large set of data and extract reliable PCS.
This alternative procedure for achieving separation of Fermi contact (FC) shifts from PCS is independent of crystal field parameters and provides reliable results even in cases of variable (possibly fractional) occupancy of the axial coordination site. It may be regarded as an extension of the “two nuclei” method [19], and its power resides in two points: (1) it is very straightforward to use and may be easily implemented on spreadsheets set up for the standard Reilley procedure and (2) it does not depend on the choice of nuclei nearby in the transition, but uses all the available set of experimental data. In its present form, our theory is addressed to complexes endowed with axial symmetry, i.e. containing a Cn-axis with n ≥ 3. While we are currently working at systems with lower symmetry, where rhombic term cannot be neglected, we must observe that fast geometric rearrangements and ligand exchange often render effective axial symmetry much more common than expected [20], [21].
Section snippets
Total paramagnetic shifts and pseudocontact shifts
The paramagnetic shift, δpara, is defined as the difference between the observed shift, δobs, of a certain nucleus on a ligand in a paramagnetic complex and in a reference diamagnetic compound (δdia), which should have the same geometrical and electronic structures (from the ligand point of view) [2], [3]. This is the first aspect which makes lanthanides unique: La3+ and Lu3+ are ideal standards for obtaining δdia, because they provide isostructural complexes for the early and the late elements
Two-lanthanides method
If we could neglect Fermi contact shifts altogether, by plotting vs. for two different isostructural complexes with lanthanides Ln1 and Ln2, we would obtain a straight line passing through the origin (which is rigorously true for PCS). The slope of this line is equal to the ratioIn the case of no variation in axial coordination (i.e. with the identity xLn1 = xLn2) or in the crystal field parameters B, the above equation would reduce to the predictable constant
The “all lanthanides” method
As an alternative and an extension to the method outlined above, we can take advantage of a set of Ln3+complexes simultaneously.
- (1)
We select a reference compound, which must be chosen for being the best characterized one (with the largest set of unambiguously assigned resonances) and that is endowed with a large CJ and ratio (see Table 1): the best choices may be in this order, Yb, Pr, and Ce. From now on, this reference lanthanide will be called ref. We must plot all the vs.
Applications
We shall discuss below a few practical cases, mostly taken from the literature, which will hopefully clarify the above outlined procedures and show their scope, their merit and their limitations.
It should be stressed that our approach is only applicable to systems with a set of pseudocontact-shifted signals, because only this ensures a good linear fitting for deriving the slopes m which must substitute the CJ in the standard Reilley treatment Consequently, some small-size traditional ligands
Conclusions
We here briefly reviewed the standard protocol for separating pseudocontact and contact terms from total paramagnetic shifts in lanthanide compounds, with particular reference to axial symmetry. We proposed a simple but not previously described modification of this protocol for compensating for any variation in crystal field parameters. We discussed the standard and modified protocols on four sets of NMR data taken from the literature and on an unreported set for a chiral derivative of Ln DOTA.
References (46)
- et al.
Prog. NMR Spectrosc.
(1996) - et al.
Coord. Chem. Rev.
(2005) J. Magn. Reson.
(1982)- et al.
J. Magn. Reson.
(1972)- et al.
Polyhedron
(2010) - et al.
Tetrahedron Asymmetr.
(2006) - et al.
Dalton Trans.
(2008) - et al.
Coord. Chem. Rev.
(1996) - et al.
Acc. Chem. Res.
(2007)
J. Biomol. NMR
Lanthanide and Actinide Chemistry
Anal. Chem.
J. Am. Chem. Soc.
Dalton Trans.
Chem. Rev.
Chem. Soc. Rev.
Chem. Soc. Rev.
Chem. Soc. Rev.
Chem. Eur. J.
J. Am. Chem. Soc.
Inorg. Chem.
J. Chem. Soc. Perkin Trans.
Cited by (42)
The heterospin cobalt complexes: peculiarities of high-resolution NMR spectra
2022, HeliyonCitation Excerpt :Such a coupling dramatically transforms the NMR spectra, i.e. it induces paramagnetic chemical shifts of signals and their broadening. These features (with an appropriate analysis of such a transformation) permits to establish the peculiarities of spatial and electronic structure of multielectron (molecular) compounds (see, for example, reviews [1, 2, 3] and references cited therein). The real and wide possibilities of application of the HFC-modified NMR spectra were, for instance, summarized in the works [4, 5, 6].
Application of paramagnetic lanthanoid chelating tags in NMR spectroscopy and their use for the localization of ligands within biomacromolecules
2021, Comprehensive Coordination Chemistry IIIThe chemical consequences of the gradual decrease of the ionic radius along the Ln-series
2020, Coordination Chemistry Reviews