Lanthanide Complexes (GdIII and EuIII ) Based on a DOTA-TEMPO Platform for Redox Monitoring via Relaxivity.

Three lanthanide complexes (Ln=Gd, Eu) based on a DO3 A ([Ln(L1 )]) or DO2 A ([Ln(L2-3 )]+ ) platform appended by a redox active TEMPO-based arm were prepared. Complex [Ln(L2 )]+ shows an alkyne arm, offering the possibility of postfunctionalization by click reaction to yield [Ln(L3 )]+ . The complexes demonstrate a redox response whereby the hydroxylamine, nitroxide and oxoammonium forms of the arm can be obtained in turn. Luminescence measurements on the europium complexes support an octadentate (L1 , L3 ) or heptadentate (L2 ) chelation by the ligand, with one water molecule in the inner coordination sphere. The relaxivity was determined from 20 kHz to 30 MHz by fast-field cycling NMR. The three GdIII complexes under their hydroxylamine form [Gd(L1 )] and [Gd(L2-3 )]+ show r1 values of 7.0, 5.1 and 5.0 mM-1 s-1 (30 KHz), which increase to 8.8, 5.5 and 6.1 mM-1 s-1 in the nitroxide form. The radical complexes are not toxic against M21 cell lines, at least up to 40 µM. By using EPR spectroscopy we establish that they do not penetrate the cells with the exception of [Eu(L2 )]+ .

Fast-field-cycling NMR at very low magnetic fields: water molecular dynamic biomarkers of glioma cell invasion and migration.

Our objective was to study NMR relaxometry of glioma invasion/migration at very low field (<2 mT) by fast-field-cycling NMR (FFC-NMR) and to decipher the pathophysiological processes of glioma that are responsible for relaxation changes in order to open a new diagnostic method that can be extended to imaging. The phenotypes of two new glioma mouse models, Glio6 and Glio96, were characterized by T2w -MRI, HE histology, Ki-67 immunohistochemistry (IHC) and CXCR4 RT-qPCR, and were compared with the U87 model. R1 dispersions of glioma tissues were acquired at low field (0.1 mT-0.8 T) ex vivo and were fitted with Lorentzian and power-law models to extract FFC biomarkers related to the molecular dynamics of water. In order to decipher relaxation changes, three main invasion/migration pathophysiological processes were studied: hypoxia, H2 O2 function and the water-channel aquaporin-4 (AQP4). Glio6 and Glio96 were characterized with invasion/migration phenotype and U87 with high cell proliferation as a solid glioma. At very low field, invasion/migration versus proliferation was characterized by a decrease in the relaxation-rate constant (ΔR1 ≈ -32% at 0.1 mT) and correlation time (≈-40%). These decreases corroborated the AQP4-IHC overexpression (Glio6/Glio96: +92%/+46%), suggesting rapid transcytolemmal water exchange, which was confirmed by the intracellular water-lifetime τIN decrease (ΔτIN ≈ -30%). In functional experiments, AQP4 expression, τIN and the relaxation-rate constant at very low field were all found to be sensitive to hypoxia and to H2 O2 stimuli. At very low field the role of water exchanges in relaxation modulation was confirmed, and for the first time it was linked to the glioma invasion/migration and to its main pathophysiological processes: hypoxia, H2 O2 redox signaling and AQP4 expression. The method appears appropriate to evaluate the effect of drugs that can target these pathophysiological mechanisms. Finally, FFC-NMR operating at low field is demonstrated to be sensitive to invasion glioma phenotype and can be straightforwardly extended to FFC-MRI as a new cancer invasion imaging method in the clinic.

Nuclear relaxation rate enhancement by a 14N quadrupole nucleus in a fluctuating electric-field gradient.

We consider the longitudinal quadrupole relaxation rate enhancement (QRE) of a 1H nucleus due to the time fluctuations of the local dipolar magnetic field created by a close quadrupole 14N nucleus, the electric-field gradient (EFG) Hamiltonian of which changes with time because of vibrations/distortions of its chemical environment. The QRE is analytically expressed as a linear combination of the cosine Fourier transforms of the three quantum time auto-correlation functions GAA(t) of the 14N spin components along the principal axes A = X, Y, and Z of the mean (time-averaged) EFG Hamiltonian. Denoting the three transition frequencies between the energy levels of this mean Hamiltonian by νA, the functions GAA(t) oscillate at frequencies νA + sA/(2π) with mono-exponential decays of relaxation times τA, where the frequency dynamic shifts sA and the relaxation times τA are closed expressions of the magnitude of the fluctuations of the instantaneous EFG Hamiltonian about its mean and of the characteristic fluctuation time. Thus, the theoretical QRE is the sum of three Lorentzian peaks centered at νA + sA/(2π) with full widths at half maxima 1/(πτA). The predicted peak widths are nearly equal. The predicted dynamic shifts of the peaks are much smaller than their widths and amazingly keep proportional to the transition frequencies νA for reasonably fast EFG fluctuations. The theory is further improved by correcting the transition frequencies by the 14N Zeeman effects of second order. It is successfully applied to reinterpret the QRE pattern measured by Broche, Ashcroft, and Lurie [Magn. Reson. Med. 68, 358 (2012)] in normal cartilage.

Field-dependent paramagnetic relaxation enhancement in solutions of Ni(II): What happens above the NMR proton frequency of 1 GHz?

An extended set of paramagnetic relaxation enhancement (PRE) data, up to the field of 32.9 Tesla, is reported for protons in an acidified aqueous solution of a Ni(II) salt in the presence and in the absence of added glycerol. For the 55% w/w glycerol sample, a distinct maximum in the PRE vs magnetic field curve is observed for the first time. The data are analysed using the Swedish slow-motion theory, including both the intramolecular (inner-sphere) and intermolecular (outer-sphere) contributions. The results indicate that estimating the outer-sphere part in the presence of the more efficient inner-sphere term is a difficult task.

Dynamics of Solid Proteins by Means of Nuclear Magnetic Resonance Relaxometry.

1H Nuclear magnetic resonance (NMR) relaxometry was exploited to investigate the dynamics of solid proteins. The relaxation experiments were performed at 37 °C over a broad frequency range, from approximately 10 kHz to 40 MHz. Two relaxation contributions to the overall 1H spin-lattice relaxation were revealed; they were associated with 1H-1H and 1H-14N magnetic dipole-dipole interactions, respectively. The 1H-1H relaxation contribution was interpreted in terms of three dynamical processes occurring on timescales of 10-6 s, 10-7 s, and 10-8 s, respectively. The 1H-14N relaxation contribution shows quadrupole relaxation enhancement effects. A thorough analysis of the data was performed revealing similarities in the protein dynamics, despite their different structures. Among several parameters characterizing the protein dynamics and structure (e.g., electric field gradient tensor at the position of 14N nuclei), the orientation of the 1H-14N dipole-dipole axis, with respect to the principal axis system of the electric field gradient, was determined, showing that, for lysozyme, it was considerably different than for the other proteins. Moreover, the validity range of a closed form expression describing the 1H-14N relaxation contribution was determined by a comparison with a general approach based on the stochastic Liouville equation.

Simple expressions of the nuclear relaxation rate enhancement due to quadrupole nuclei in slowly tumbling molecules.

For slowly tumbling entities or quasi-rigid lattices, we derive very simple analytical expressions of the quadrupole relaxation enhancement (QRE) of the longitudinal relaxation rate R1 of nuclear spins I due to their intramolecular magnetic dipolar coupling with quadrupole nuclei of arbitrary spins S ≥ 1. These expressions are obtained by using the adiabatic approximation for evaluating the time evolution operator of the quantum states of the quadrupole nuclei S. They are valid when the gyromagnetic ratio of the spin S is much smaller than that of the spin I. The theory predicts quadrupole resonant peaks in the dispersion curve of R1 vs magnetic field. The number, positions, relative intensities, Lorentzian shapes, and widths of these peaks are explained in terms of the following properties: the magnitude of the quadrupole Hamiltonian and the asymmetry parameter of the electric field gradient (EFG) acting on the spin S, the S-I inter-spin orientation with respect to the EFG principal axes, the rotational correlation time of the entity carrying the S-I pair, and/or the proper relaxation time of the spin S. The theory is first applied to protein amide protons undergoing dipolar coupling with fast-relaxing quadrupole (14)N nuclei and mediating the QRE to the observed bulk water protons. The theoretical QRE agrees well with its experimental counterpart for various systems such as bovine pancreatic trypsin inhibitor and cartilages. The anomalous behaviour of the relaxation rate of protons in synthetic aluminium silicate imogolite nano-tubes due to the QRE of (27)Al (S = 5/2) nuclei is also explained.

Confinement of a tris-aqua Gd(iii) complex in silica nanoparticles leads to high stability and high relaxivity and supresses anion binding.

The water soluble tris-aqua complex [Gd(dhqN-SO3)(H2O)3](3-) based on a hexadentate hydroxyquinoline ligand shows high thermodynamic stability and high relaxivity (12.54 mM(-1) s(-1) at 1.2 T). Its non-covalent confinement in 25 nm silica nanoparticles prevents transmetallation and endogenous anion binding and leads to higher relaxivity over a wide range of magnetic fields.

Experimental measurement and theoretical assessment of fast lanthanide electronic relaxation in solution with four series of isostructural complexes.

The rates of longitudinal relaxation for ligand nuclei in four isostructural series of lanthanide(III) complexes have been measured by solution state NMR at 295 K at five magnetic fields in the range 4.7-16.5 T. The electronic relaxation time T(le) is a function of both the lanthanide ion and the local ligand field. It needs to be considered when relaxation probes for magnetic resonance applications are devised because it affects the nuclear relaxation, especially over the field range 0.5 to 4.7 T. Analysis of the data, based on Bloch-Redfield-Wangsness theory describing the paramagnetic enhancement of the nuclear relaxation rate has allowed reliable estimates of electronic relaxation times, T(1e), to be obtained using global minimization methods. Values were found in the range 0.10-0.63 ps, consistent with fluctuations in the transient ligand field induced by solvent collision. A refined theoretical model for lanthanide electronic relaxation beyond the Redfield approximation is introduced, which accounts for the magnitude of the ligand field coefficients of order 2, 4, and 6 and their relative contributions to the rate 1/T(le). Despite the considerable variation of these contributions with the nature of the lanthanide ion and its fluctuating ligand field, the theory explains the modest change of measured T(le) values and their remarkable statistical ordering across the lanthanide series. Both experiment and theory indicate that complexes of terbium and dysprosium should most efficiently promote paramagnetic enhancement of the rate of nuclear relaxation.

Determination of the static zero-field splitting of Gd3+ complexes in solution from the shifts of the central magnetic fields of their EPR spectra.

In principle, the Redfield theory of EPR spectra applies only to fast-rotating complexes with rather small static zero-field splitting (ZFS) terms. However, at sufficiently high frequencies, typically of 35 GHz and above, it predicts values of the central magnetic fields which are surprisingly accurate well beyond its expected applicability range. This remarkable feature is demonstrated by showing that the Redfield EPR spectrum crosses its baseline at the same point as its "exact" simulated counterpart. It is shown that the shift of the central magnetic field with respect to its limiting value in the absence of ZFS terms is often simply proportional to the square of the magnitude of the static ZFS term divided by the spectrometer frequency. This property is used to determine the magnitude of the static ZFS term independently of its fluctuation dynamics and of the presence of the transient ZFS term.

Quantitative interpretation of the very fast electronic relaxation of most Ln3+ ions in dissolved complexes.

In a reference frame rigidly bound to the complex, we consider two Hamiltonians possibly at the origin of the very fast electronic relaxation of the paramagnetic lanthanide Ln(3+) ions (Ln = Ce to Nd, Tb to Yb), namely the mean (static) ligand-field Hamiltonian and the transient ligand-field Hamiltonian. In the laboratory frame, the bombardment of the complex by solvent molecules causes its Brownian rotation and its vibration-distorsion dynamics governing the fluctuations of the static and transient terms, respectively. These fluctuations are at the origin of electronic relaxation. The electronic relaxation of a Ln(3+) ion is defined by the decays of the time correlation functions (TCFs) of the longitudinal and transverse components of the total angular momentum J of its ground multiplet. The Brownian rotation of the complex and its vibration-distorsion dynamics are simulated by random walks, which enable us to compute the TCFs from first principles. It is shown that the electronic relaxation is governed mainly by the magnitude of the transient ligand-field, and not by its particular expression. The range of expected values of this ligand-field together with the lower limit of relaxation time enforced by the values of the vibration-distortion correlation time in liquids give rise to effective electronic relaxation times which are in satisfactory overall agreement with the experimental data. In particular, these considerations explain why the electronic relaxation times vary little with the coordinating ligand and are practically independent of the external field magnitude.

Model-free nuclear magnetic resonance study of intermolecular free energy landscapes in liquids with paramagnetic Ln3+ spotlights: theory and application to Arg-Gly-Asp.

We propose an easily applicable method for investigating the pair distribution function of a lanthanide Ln(3+) complex LnL (L = ligand) with respect to any solvent or solute molecule A carrying observable nuclear spins. Let r be the distance of Ln(3+) to the observed nuclear spin I. We derive a simple expression of the experimental value of the configurational average of 1/r(6) in terms of longitudinal paramagnetic relaxation (rate) enhancements (PREs) of the spin I measured on a standard high-resolution NMR spectrometer and due to well-chosen concentrations of LnL complexes in which Ln(3+) is a fast-relaxing paramagnetic lanthanide or the slowly-relaxing gadolinium Gd(3+). The derivation is justified in the general case of a molecule A which is by turns in a bound state where it follows the complex and a free state where it moves independently. It rests on the expression of the underlying PRE theory in terms of the angle-dependent pair distribution function of LnL and A. The simplifications of this theory in the high-field regime and under the condition of fast exchange between bound and free states are carefully discussed. We also show that original information on the angle dependence of the molecular pair distribution function can be gained from the measured paramagnetic dipolar shifts induced by complexed fast-relaxing Ln(3+) ions. The method is illustrated by the case study of the anionic Lnttha(3-) = [Ln(3+)(ttha)](3-) (ttha(6-) = triethylene tetraamine hexacetate) complex interacting with the biologically important tripeptide Arg-Gly-Asp (RGD) which carries peripheral ionic groups. The usefulness of an auxiliary reference outer sphere probe solute is emphasized.

High relaxivity and stability of a hydroxyquinolinate-based tripodal monoaquagadolinium complex for use as a bimodal MRI/optical imaging agent.

An octadentate ligand based on triazacyclononane and 8-hydroxyquinolinate/phenolate binding units leads to very soluble, highly stable lanthanide complexes. The monoaquagadolinium complex shows a high relaxivity as a result of the unusually long rotational correlation time, fast water exchange rate, and slow electronic relaxation. The ligand also acts as sensitizer of the near-IR luminescence emission of the Yb and Nd ions. It appears as an excellent candidate for use as a bimodal imaging agent.

Paramagnetic relaxation enhancements in acetate and its fluorine derivatives interacting with Gd3+: complex formation, structure, and transmetallation.

The relative spatial distribution and motion with respect to Gd(3+) of the (1)H and (19)F nuclei in the acetate ion and its fluorine derivatives are studied in D(2)O solutions through the paramagnetic relaxation rate enhancements (PREs) of these nuclei. We derive general theoretical expressions of the longitudinal PRE in terms of the analytical concentrations of metal and ligands, formation constants of the complexes, metal-nucleus distances, and coordination lifetimes of the ligands. The observed formation constants of the 1 metal: 1 ligand complexes markedly decrease with increasing number of fluorine atoms, the electronegativity of which reduces the negative partial charge of the coordinating COO(-) group. The coordination lifetimes are very short at the scale of the relaxation times of the protons of metal bound acetate, that is, shorter than about 10 µs. The average distance of the acetate protons from Gd(3+) is in fair agreement with independent crystallographic determination. The release of free Gd(3+) from the very stable Gddtpa (dtpa=diethylene-triaminepentaacetate) complex caused by the competition of Zn(2+) for dtpa, is evidenced by an increase of the PREs with Zn(2+) concentration. The observed PRE increase is consistent with the known equilibrium constants governing the speciation involving Gd(3+), Zn(2+), and dtpa. The present case study illustrates a method which easily yields experimental tunable properties suitable to test the ongoing theories of lanthanide Ln(3+) complexation in solution.

Highly stable and soluble bis-aqua Gd, Nd, Yb complexes as potential bimodal MRI/NIR imaging agents.

A tripodal ligand based on the 8-hydroxyquinolinate binding unit yields a soluble and highly stable bis-hydrated Gd(3+) complex in water (pGd = 19.2(3)) with relaxivity change in the pH range 4.5-7.4 and Nd(3+), Yb(3+) analogues with sizeable NIR emission upon excitation at 370 nm providing a new architecture for the development of bimodal agents.

Enhancement of the water proton relaxivity by trapping Gd3+ complexes in nanovesicles.

We present a theoretical model for calculating the relaxivity of the water protons due to Gd(3+) complexes trapped inside nanovesicles, which are permeable to water. The formalism is applied to the characterization of apoferritin systems [S. Aime et al., Angew. Chem., Int. Ed. 41, 1017 (2002); O. Vasalatiy et al., Contrast Media Mol. Imaging 1, 10 (2006)]. The very high relaxivity due to these systems is attributed to an increase of the local viscosity of the aqueous solution inside the vesicles and to an outer-sphere mechanism which largely dominates the inner-sphere contribution. We discuss how to tailor the dynamic parameters of the trapped complexes in order to optimize the relaxivity. More generally, the potential of relaxivity studies for investigating the local dynamics and residence time of exchangeable molecules in nanovesicles is pointed out.

Two-particle random walk simulation of outer-sphere nuclear relaxation.

We present a two-particle Monte Carlo method for computing the outer-sphere (OS) dipolar time correlation function (DTCF) of the relative position of a nuclear spin I on a diamagnetic molecule M(I) with respect to a nuclear or electronic spin S on a molecule M(S) when both molecules are anisotropic and undergo translational and rotational diffusion. As a first application, we question the validity of the appealing interspin procedure [L. P. Hwang, Mol. Phys. 51, 1235 (1984); A. Borel et al., Chem. Eur. J. 7, 600 (2001)] based on the solutions of a Smoluchowski diffusion equation, which conserve the interspin radial distribution function in the course of time. We show that the true random spatial motion of the interspin vector obtained by simulation can be very different from that given by the Smoluchowski solutions and lead to notable retardation of the time decay of the OS-DTCF. Then, we explore the influence of the solvation properties of M(S) on the decay rate of the DTCF. When M(S) is significantly larger than M(I), its rotation accelerates the decay only weakly, even if M(I) follows M(S) in its Brownian tumbling. By contrast, viscous solvation layers in OS pockets of M(S) can yield an important local slowdown of the relative translational diffusion of M(I), leading to a decay retardation of the DTCF, which adds to that due to the shape anisotropy of M(S). When M(S) is a Gd(3+)-based contrast agent, this retardation leads to a notable increase of the OS contribution to relaxivity even at rather high imaging field.

Outer-sphere investigation of MRI relaxation contrast agents. Example of a cyclodecapeptide gadolinium complex with second-sphere water.

We show how the purely outer-sphere (OS) relaxivity of a probe solute due to a Gd(3+) complex can help characterize the outer (O), inner (I), and second (2) sphere (S) contributions to the water proton relaxivity. Because of the difficulties of accurate theoretical predictions, we propose an experimental determination of the OS dipolar time correlation function (OS-DTCF) of the relative position of Gd(3+) with respect to any of the equivalent protons of the purely OS probe p-dioxane, which moves around the complex without binding to it. The method is illustrated by the GdPA complex with PA = c(AspArgGluProGlyGluTrpAspProGly). The experimental DTCF for dioxane is obtained by a model-free analysis of the high-field relaxivity of its protons. The time-modulation of the dioxane DTCF by the Gd(3+) electronic spin relaxation yields a measurable quenching of the longitudinal relaxivity at low-to-medium field, which serves us to deduce the fluctuating zero-field splitting (ZFS) Hamiltonian causing this electronic relaxation. The DTCF for water is derived from that for dioxane by appropriate scaling of the geometry of collision and relative diffusion coefficients of these molecules with respect to GdPA. The information obtained on the OS motion for water and the ZFS Hamiltonian together with an independent characterization of the IS contribution allows us to disentangle the OS, IS, and 2S mechanisms and interpret the relaxivity profile of the water protons from 2.35 mT to 18.8 T. The presence of a large 2S contribution is confirmed.

Almost ideal 1D water diffusion in imogolite nanotubes evidenced by NMR relaxometry.

The longitudinal proton relaxation rates R(1) of water diffusing inside synthetic aluminium silicate imogolite nanotubes are measured by fast field-cycling NMR for frequencies between 0.02 and 35 MHz at 25, 37 and 50 degrees C. We give analytical expressions of the dominant intermolecular dipolar spin-spin contribution to R(1) and to the transverse relaxation rate R(2). A remarkable variation of R(1) by more than two orders of magnitude is observed and shown to be close to the theoretical law, inversely proportional to the square root of the resonance frequency, which is characteristic of perfect molecular 1D diffusion. The physics of diffusion is discussed.

Determination of outer-sphere dipolar time correlation functions from high-field NMR measurements. Example of a Gd(3+) complex in a viscous solvent.

We consider a diamagnetic species carrying a nuclear spin and having a purely outer-sphere dynamics with respect to a Gd(3+) complex. The maximal structural and dynamic information attainable from the paramagnetic relaxation (rate) enhancement (PRE) of this nuclear spin due to the Gd(3+) electronic spin is the outer-sphere dipolar time correlation function (OS-DTCF) of the relative position of these spins. We show how to determine this OS-DTCF by a model-free analysis of high-field PRE measurements, which accounts for the relative diffusion coefficient of the spin carrying species derived from pulsed-gradient spin-echo experiments. The method rests on the spectral characterization of the OS-DTCF through a PRE property, the "star" relaxivity, which can be measured over an unexpectedly large frequency range by combining multiple field and temperature NMR experiments. It is illustrated in the case of the (1)H spins on the three diamagnetic probes tert-butanol CHD(2)(CD(3))(2)COD and glycerol (CD(2)OD)(2)CHOD and CHDOD-CDOD-CD(2)OD interacting with Gddtpa(2-) (dtpa(5-)=diethylen triamin pentaacetate) in a viscous glycerol-d8/D(2)O solvent. The general usefulness of the OS-DTCF for the description of the liquid state and electronic spin relaxation is discussed.

Gadolinium(III) complexes of 1,4,7-triazacyclononane based picolinate ligands: simultaneous optimization of water exchange kinetics and electronic relaxation.

The two new tripodal picolinate H(3)ebpatcn (1-carboxyethyl-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane) and H(4)pbpatcn (1-methylphosphonic-acid-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane) ligands based on the 1,4,7-triazacyclononane anchor were prepared and their lanthanide complexes were characterized by NMR, fluorescence and potentiometric studies. The [Gd(ebpatcn)(H(2)O)] complex displays a relaxivity of r(1) = 4.68 mM(-1) s(-1) at 45 MHz and 298 K, whereas r(1) = 4.55 mM(-1) s(-1) was measured for [Gd(Hpbpatcn)(H(2)O)] under the same conditions. The modified scaffold of the ligands with respect to the previously reported H(3)bpatcn (1-(carboxymethyl)-4,7-bis[(6-carboxypyridin-2-yl)methyl]-1,4,7-triazacyclononane) leads to an optimization of the properties of these gadolinium complexes. The replacement of an acetate binding group of the H(3)bpatcn ligand with a propionate group (H(3)ebpatcn) or a phosphonate group (H(4)pbpatcn) leads to a faster exchange rate of the coordinated water molecule in both mono-aquo gadolinium complexes. The resulting water exchange rate is optimized for the future design of high relaxivity macromolecular gadolinium based contrast agents with a value measured by O(17) NMRD of k(ex) = 34 x 10(6) s(-1) for [Gd(Hpbpatcn)(H(2)O)] falling in the range of optimum values of (30 to 50) x 10(6) s(-1) predicted by the SBM theory. The water exchange rate k(ex)(298) = 86 x 10(6) s(-1) of the complex [Gd(ebpatcn)(H(2)O)] is the fastest reported in the literature for a neutral complex with only one inner-sphere water molecule. The relatively high stability of these modified gadolinium complexes (pGd = 14.1 for Gd(pbpatcn) and 13.1 for Gd(ebpatcn)) is similar to that of the [Gd(bpatcn)(H(2)O)] complex (pGd = 13.6). The high luminescence efficiency is also retained for the terbium complex. However, whereas the longitudinal electronic spin relaxation time keeps a value for [Gd(ebpatcn)(H(2)O)], which is long enough not to affect the relaxivity in macromolecular complexes (transient ZFS amplitude Delta(2) [10(20) rad(2) s(-2)] = 0.39), the O(17) relaxation and the (1)H NMRD indicate a rather fast electron spin relaxation for the phosphonate containing complex (Delta(2) [10(20) rad(2) s(-2)] = 1.3).