NMR and Electron Paramagnetic Resonance Studies of [Gd(CH₃CN)₉]³⁺ and [Eu(CH₃CN)₉]²⁺: Solvation and Solvent Exchange Dynamics in Anhydrous Acetonitrile

Homoleptic acetonitrile complexes [Gd­(CH3CN)9]­[Al­(OC­(CF3)3)4]3 and [Eu­(CH3CN)9]­[Al­(OC­(CF3)3)4]2 have been studied in anhydrous acetonitrile by 14N- and 1H NMR relaxation as well as by X- and Q-band EPR. For each compound a combined analysis of all experimental data allowed to get microscopic information on the dynamics in solution. The second order rotational correlation times for [Gd­(CH3CN)9]3+ and [Eu­(CH3CN)9]2+ are 14.5 ± 1.8 ps and 11.8 ± 1.1 ps, respectively. Solvent exchange rate constants determined are (55 ± 15) × 106 s–1 for the trivalent Gd3+ and (1530 ± 200) × 106 s–1 for the divalent Eu2+. Surprisingly, for both solvate complexes CH3CN exchange is much slower for the less strongly N-binding acetonitrile than for the more strongly coordinated O-binding H2O. It is concluded that this exceptional behavior is due to the extremely fast water exchange, whereas the exchange behavior of CH3CN is more regular. Electron spin relaxation on the isoelectronic ions is much slower than on the O-binding water analogues. This allowed a precise determination of the hyperfine coupling constants for each of the two stable isotopes of Gd3+ and Eu2+ having a nuclear spin

Water Exchange on [Ln(DO3A)(H₂O)₂] and [Ln(DTTA–Me)(H₂O)₂]⁻ Studied by Variable Temperature, Pressure, and Magnetic Field NMR

Water exchange kinetics of [Ln­(L)­(H₂O)₂]^<i>x</i> complexes (Ln = Pr, Nd, Dy, Tm, and Yb; L = DO3A and DTTA–Me) were studied by ¹⁷O NMR spectroscopy as a function of temperature, pressure, and frequency and by ¹H nuclear magnetic relaxation dispersion. Water exchange rate constants of both complexes show a maximum at dysprosium. Water exchange on negatively charged complexes of the acyclic DTTA–Me ligand is much faster than on the neutral complexes of the macrocyclic DO3A. Small activation volumes |Δ<i>V</i>^⧧| < 1 cm³ mol^–1 measured for water exchange on [Ln­(DO3A)­(H₂O)₂] indicate an interchange type of mechanism (I) for the lanthanide complexes studied. In the case of [Ln­(DTTA–Me)­(H₂O)₂]⁻, a change in mechanism is detected from a dissociative mechanism (D, Δ<i>V</i>^⧧ = 7 cm³ mol^–1) for complexes with larger ions (Pr to Gd) to an interchange mechanism (I_d, I; Δ<i>V</i>^⧧ = +1.8 and +0.4 cm³ mol^–1) for complexes with smaller ions (Dy and Tm)

Solvent Exchange and Electron-Spin Relaxation on Homoleptic Acetonitrile Complexes of Trivalent Lanthanides

Homoleptic acetonitrile complexes [Nd­(CH₃CN)₉]­[Al­(OC­(CF₃)₃)₄]₃, [Dy­(CH₃CN)₉]­[Al­(OC­(CF₃)₃)₄]₃, and [Tm­(CH₃CN)₈]­[Al­(OC­(CF₃)₃)₄]₃ have been studied in anhydrous acetonitrile by ¹⁴N and ¹H NMR relaxation. Solvent-exchange rate constants increase from (22 ± 6) × 10⁶ s^–1 (Nd³⁺) and (160 ± 40) × 10⁶ s^–1 (Dy³⁺) for the nonasolvated ions to (360 ± 40) × 10⁶ s^–1 (Tm³⁺) for the octasolvated ions. Electron-spin relaxation of the lanthanide ions studied is similar to that found in aqua ions. This dependence on the binding properties of the coordinating molecules is consistent with the model proposed by Fries et al. for fast electron-spin relaxation of lanthanide ions other than Gd³⁺

Dinuclear, Bishydrated Gd^III Polyaminocarboxylates with a Rigid Xylene Core Display Remarkable Proton Relaxivities

Two novel dinuclear GdIII complexes have been synthesized, based on a xylene core substituted with diethylenetriamine-N,N,N‘ ‘,N‘ ‘-tetraacetate (DTTA) chelators in para or meta position. The complexes [Gd2(pX(DTTA)2)(H2O)4]2- and [Gd2(mX(DTTA)2)(H2O)4]2- both exhibit high complex stability (log KGdL = 19.1 and 17.0, respectively), and a good selectivity for GdIII against ZnII, the most abundant endogenous metal ion (log KZnL = 17.94 and 16.19). The water exchange rate is identical within experimental error for the two isomers:  kex298 = (9.0 ± 0.4) × 106 s-1 for [Gd2(pX(DTTA)2)(H2O)4]2- and (8.9 ± 0.5) × 106 s-1 for [Gd2(mX(DTTA)2)(H2O)4]2-. It is very similar to the kex298 of the structural analogue, bishydrated [Gd(TTAHA)(H2O)2]3-, and about twice as high as that of the monohydrated [Gd(DTPA)(H2O)]2- (TTAHA6- = N-tris(2-aminoethyl)amine-N‘,N‘,N‘ ‘,N‘ ‘,N‘ ‘‘,N‘ ‘‘-hexaacetate; DTPA5- = diethylenetriamine-N,N,N‘,N‘ ‘,N‘ ‘-pentaacetate). This relatively fast water exchange can be related to the presence of two inner sphere water molecules which decrease the stereorigidity of the inner sphere thus facilitating the water exchange process. At all frequencies, the water proton relaxivities (r1 = 16.79 and 15.84 mM-1 s-1 for the para and meta isomers, respectively; 25 °C and 20 MHz) are remarkably higher for the two dinuclear chelates than those of mononuclear commercial contrast agents or previously reported dinuclear GdIII complexes. This is mainly the consequence of the two inner-sphere water molecules. In addition, the increased molecular size as compared to monomeric compounds associated with the rigid xylene linker between the two GdIII chelating subunits also contributes to an increased relaxivity. However, proton relaxivity is still limited by fast molecular motions which also hinder any beneficial effect of the increased water exchange rate

Multiexponential Electronic Spin Relaxation and Redfield's Limit in Gd(III) Complexes in Solution: Consequences for ¹⁷O/¹H NMR and EPR Simultaneous Analysis

Multiple experiments (17O NMR, 1H NMR, and EPR) have been performed in the past to understand the microscopic parameters that control the magnetic relaxation rate enhancement induced by paramagnetic molecules on neighboring water protons, the so-called relaxivity. The generally accepted theories of the electron spin relaxation of S = 7/2 ions such as Gd3+ (Solomon−Bloembergen−Morgan or simplified Hudson−Lewis) are unsatisfactory for a simultaneous analysis. Recently, an improved theory, where the electron spin relaxation is due to the combination of a static (thus explicitly linked to the molecular structure) and a dynamic zero field splitting, has been developed and tested on experimental EPR data. The model has also been extended beyond the electronic Redfield limit using Monte Carlo simulations. Using the aqua ion [Gd(H2O)8]3+ as a test case, we present here the first simultaneous analysis of 17O NMR, 1H NMR, and EPR relaxation data using this rigorous approach of the electron spin relaxation. We discuss the physical meaning of the calculated parameters. The consequences on future experiments are also considered, especially regarding the analysis of nuclear magnetic relaxation dispersion (NMRD) profiles in the study of Gd3+ complexes

Evaluation of Water Exchange Kinetics on [Ln(AAZTAPh–NO₂)(H₂O)_<i>q</i>]^<i>x</i> Complexes Using Proton Nuclear Magnetic Resonance

Water exchange kinetics on [Ln­(AAZTAPh–NO₂)­(H₂O)_<i>q</i>]⁻ (Ln = Gd³⁺, Dy³⁺, or Tm³⁺) were determined by ¹H nuclear magnetic resonance (NMR) measurements. The number of inner-sphere water molecules was found to change from two to one when going from Dy³⁺ to Tm³⁺. The calculated water exchange rate constants obtained by variable-temperature proton transverse relaxation rates are 3.9 × 10⁶, 0.46 × 10⁶, and 0.014 × 10⁶ s^–1 at 298 K for Gd³⁺, Dy³⁺, and Tm³⁺, respectively. Variable-pressure measurements were used to assess the water exchange mechanism. The results indicate an associative and dissociative interchange mechanism for Gd³⁺ and Dy³⁺ complexes with Δ<i>V</i>^⧧ values of −1.4 and 1.9 cm³ mol^–1, respectively. An associative activation mode (I_a or A mechanism) was obtained for the Tm³⁺ complex (Δ<i>V</i>^⧧ = −5.6 cm³ mol^–1). Moreover, [Dy­(AAZTAPh–NO₂)­(H₂O)₂]⁻ with a very high transverse relaxivity value was found as a potential candidate for negative contrast agents for high-field imaging applications

Structural Investigation of the Aqueous Eu²⁺ Ion: Comparison with Sr²⁺ Using the XAFS Technique

Structural parameters of the Sr2+ and, for the first time, of the Eu2+ ions in aqueous solution were determined by the XAFS method. For the Sr2+, the use of an improved theoretical approach led to a first shell coordination number of 8.0 (3), a Sr−O distance of 2.600 (3) Å and a Debye−Waller factor of σ2 = 0.0126 (5) Å2. These results were confirmed by an analysis performed with experimental phase and amplitude, extracted from the solid reference compound [Sr(H2O)8](OH)2. The same theoretical approach was used for the analysis of the Eu2+ XAFS spectra in aqueous solution. This gives a first coordination shell of Eu2+ formed by 7.2 (3) water molecules, an Eu−O distance of 2.584 (5) Å, and a high Debye−Waller factor of σ2 = 0.0138 (5) Å2. Whereas Eu3+ occurs as an equilibrium between the [Eu(H2O)8]3+ and the [Eu(H2O)9]3+ ions, Eu2+ occurs in aqueous solution as an equilibrium between a predominant [Eu(H2O)7]2+ ion and a minor [Eu(H2O)8]2+ species

Mechanistic Diversity Covering 15 Orders of Magnitude in Rates: Cyanide Exchange on [M(CN)₄]^2- (M = Ni, Pd, and Pt)¹

Kinetic studies of cyanide exchange on [M(CN)4]2- square-planar complexes (M = Pt, Pd, and Ni) were performed as a function of pH by 13C NMR. The [Pt(CN)4]2- complex has a purely second-order rate law, with CN- as acting as the nucleophile, with the following kinetic parameters:  (k2Pt,CN)298 = 11 ± 1 s-1 mol-1 kg, ΔH2⧧ Pt,CN = 25.1 ± 1 kJ mol-1, ΔS2⧧ Pt,CN = −142 ± 4 J mol-1 K-1, and ΔV2⧧ Pt,CN = −27 ± 2 cm3 mol-1. The Pd(II) metal center has the same behavior down to pH 6. The kinetic parameters are as follows:  (k2Pd,CN)298 = 82 ± 2 s-1 mol-1 kg, ΔH2⧧ Pd,CN = 23.5 ± 1 kJ mol-1, ΔS2⧧ Pd,CN = −129 ± 5 J mol-1 K-1, and ΔV2⧧ Pd,CN = −22 ± 2 cm3 mol-1. At low pH, the tetracyanopalladate is protonated (pKaPd(4,H) = 3.0 ± 0.3) to form [Pd(CN)3HCN]-. The rate law of the cyanide exchange on the protonated complex is also purely second order, with (k2PdH,CN)298 = (4.5 ± 1.3) × 103 s-1 mol-1 kg. [Ni(CN)4]2- is involved in various equilibrium reactions, such as the formation of [Ni(CN)5]3-, [Ni(CN)3HCN]-, and [Ni(CN)2(HCN)2] complexes. Our 13C NMR measurements have allowed us to determine that the rate constant leading to the formation of [Ni(CN)5]3- is k2Ni(4),CN = (2.3 ± 0.1) × 106 s-1 mol-1 kg when the following activation parameters are used:  ΔH2⧧ Ni,CN = 21.6 ± 1 kJ mol-1, ΔS2⧧ Ni,CN = −51 ± 7 J mol-1 K-1, and ΔV2⧧ Ni,CN = −19 ± 2 cm3 mol-1. The rate constant of the back reaction is k-2Ni(4),CN = 14 × 106 s-1. The rate law pertaining to [Ni(CN)2(HCN)2] was found to be second order at pH 3.8, and the value of the rate constant is (k2Ni(4,2H),CN)298 = (63 ± 15) ×106 s-1 mol-1 kg when ΔH2⧧ Ni(4,2H),CN = 47.3 ± 1 kJ mol-1, ΔS2⧧ Ni(4,2H),CN = 63 ± 3 J mol-1 K-1, and ΔV2⧧ Ni(4,2H),CN = − 6 ± 1 cm3 mol-1. The cyanide-exchange rate constant on [M(CN)4]2- for Pt, Pd, and Ni increases in a 1:7:200 000 ratio. This trend is modified at low pH, and the palladium becomes 400 times more reactive than the platinum because of the formation of [Pd(CN)3HCN]-. For all cyanide exchanges on tetracyano complexes (A mechanism) and on their protonated forms (I/Ia mechanisms), we have always observed a pure second-order rate law:  first order for the complex and first order for CN-. The nucleophilic attack by HCN or solvation by H2O is at least nine or six orders of magnitude slower, respectively than is nucleophilic attack by CN- for Pt(II), Pd(II), and Ni(II), respectively

Quantum Chemical Investigation of Hyperfine Coupling Constants on First Coordination Sphere Water Molecule of Gadolinium(III) Aqua Complexes

Hyperfine interactions (HFI) on the nuclei of the first coordination sphere water molecules in a model [Gd(H2O)8]3+ aqua complex and in the magnetic resonance imaging contrast agent [Gd(DOTA)(H2O)]- were studied theoretically. Density functional theory (DFT) calculations combined with classical molecular dynamics (MD) simulations have been used in order to take into account dynamic effects in aqueous solution. DFT relativistic calculations show a strong spin-polarization of the first coordination sphere water molecules. This spin-polarization leads to a positive 17O isotropic hyperfine coupling constant (Aiso(17O) = 0.58 ± 0.11 MHz) and to a significant increase of the effective distance (〈reff(Gd−O)〉 = 2.72 ± 0.06 Å) of dipolar interaction compared to the mean internuclear distance (〈r(Gd−O)〉 = 2.56 ± 0.06 Å) obtained from the MD trajectory of [Gd(DOTA)(H2O)]- in aqueous solution. The point-dipole model for anisotropic hyperfine interaction overestimates therefore the longitudinal relaxation rate of the 17O nucleus by ∼45%. The 1H isotropic hyperfine coupling constant of the bound water molecule is predicted to be very small (Aiso(1H) = 0.03 ± 0.02 MHz), and the point-dipole approximation for first coordination sphere water protons holds. The calculated hyperfine parameters are in good agreement with available experimental data

Relevance of the Ligand Exchange Rate and Mechanism of <i>f</i><i>ac</i>-[(CO)₃M(H₂O)₃]⁺ (M = Mn, Tc, Re) Complexes for New Radiopharmaceuticals

The water exchange process on fac-[(CO)3Mn(H2O)3]+ and fac-[(CO)3Tc(H2O)3]+ was kinetically investigated by 17O NMR as a function of the acidity, temperature, and pressure. Up to pH 6.3 and 4.4, respectively, the exchange rate is not affected by the acidity, thus demonstrating that the contribution of the monohydroxo species fac-[(CO)3M(OH)(H2O)2] is not significant, which correlates well with a higher pKa for these complexes compared to the homologue fac-[(CO)3Re(H2O)3]+ complex. The water exchange rate /s-1 (ΔHex⧧/kJ mol-1; ΔSex⧧/J mol-1 K-1; ΔV⧧/cm3 mol-1) decreases down group 7 from Mn to Tc and Re:  23 (72.5; +24.4; +7.1) > 0.49 (78.3; +11.7; +3.8) > 5.4 × 10-3 (90.3; +14.5; −). For the Mn complex only, an O exchange on the carbonyl ligand could be measured ( = 4.3 × 10-6 s-1), which is several orders of magnitude slower than the water exchange. In the case of the Tc complex, the coupling between 17O (I = 5/2) and 99Tc (I = 9/2) nuclear spins has been observed (1J99Tc,O = 80 ± 5 Hz). The substitution of water in fac-[(CO)3M(H2O)3]+ by dimethyl sulfide (DMS) is slightly faster than that by CH3CN:  3 times faster for Mn, 1.5 times faster for Tc, and 1.2 times faster for Re. The pressure dependence behavior is different for Mn and Re. For Mn, the change in volume to reach the transition state is always clearly positive (water exchange, CH3CN, DMS), indicating an Id mechanism. In the case of Re, an Id/Ia changeover is assigned on the basis of reaction profiles with a strong volume maximum for pyrazine and a minimum for DMS as the entering ligand