Towards Binuclear Polyaminocarboxylate MRI Contrast Agents? Spectroscopic and MD Study of the Peculiar Aqueous Behavior of the LnIII Chelates of OHEC (Ln=Eu,Gd, and Tb): Implications for Relaxivity

We report the study of binuclear Ln(III) chelates of OHEC (OHEC=octaazacyclohexacosane-1,4,7,10,14,17,20,23-octaacetate). The interconversion between two isomeric forms, which occurs in aqueous solution, has been studied by NMR, UV/Vis, EPR, and luminescence spectroscopy, as well as by classical molecular dynamics (MD) simulations. For the first time we have characterized an isomerization equilibrium for a Ln(III) polyaminocarboxylate complex (Ln(III)=Y, Eu, Gd and Tb) in which the metal centre changes its coordination number from nine to eight, such that: [Ln(2)(ohec)(H(2)O)(2)](2-) r<==>[Ln(2)(ohec)](2-)+2 H(2)O. The variable temperature and pressure NMR measurements conducted on this isomerization reaction give the following thermodynamic parameters for Eu(III): K(298)=0.42+/-0.01, DeltaH(0)=+4.0+/-0.2 kJ mol(-1), DeltaS(0)=+6.1+/-0.5 J K(-1) mol(-1) and DeltaV(0)=+3.2+/-0.2 cm(3) mol(-1). The isomerization is slow and the corresponding kinetic parameters obtained by NMR spectroscopy are: k(298)(is)=73.0+/-0.5 s(-1), DeltaH++(is)=75.3+/-1.9 kJ mol(-1), DeltaS++(is)= +43.1+/-5.8 J K(-1) mol(-1) and DeltaV++(is)=+7.9+/-0.7 cm(3) mol(-1). Variable temperature and pressure (17)O NMR studies have shown that water exchange in [Gd(2)(ohec)(H(2)O)(2)](2-) is slow, k(298)(ex)=(0.40+/-0.02)x10(6) s(-1), and that it proceeds through a dissociative interchange I(d) mechanism, DeltaV( not equal )=+7.3+/-0.3 cm(3) mol(-1). The anisotropy of this oblong binuclear complex has been highlighted by MD simulation calculations of different rotational correlation times. The rotational correlation time directed on the Gd-Gd axis is 24 % longer than those based on the axes orthogonal to the Gd-Gd axis. The relaxivity of this binuclear complex has been found to be low, since 1) only [Gd(2)(ohec)(H(2)O)(2)](2-), which constitutes 70 % of the binuclear complex, contributes to the inner-sphere relaxivity and 2) the anisotropy of the complex prevents water molecules from having complete access to both Gd(III) cages; this decreases the outer-sphere relaxivity. Moreover, EPR measurements for the Gd(III) and for the mixed Gd(III)/Y(III) binuclear complexes have clearly shown that the two Gd(III) centres interact intramolecularly; this enhances the electronic relaxation of the Gd(III) electron spins.     

Lanthanide chelates containing pyridine units with potential application as contrast agents in magnetic resonance imaging

A new pyridine-containing ligand, N,N'-bis(6-carboxy-2-pyridylmethyl)ethylenediamine-N,N'-diacetic acid (H(4)L), has been designed for the complexation of lanthanide ions. (1)H and (13)C NMR studies in D(2)O solutions show octadentate binding of the ligand to the Ln(III) ions through the nitrogen atoms of two amine groups, the oxygen atoms of four carboxylates, and the two nitrogen atoms of the pyridine rings. Luminescence measurements demonstrate that both Eu(III) and Tb(III) complexes are nine-coordinate, whereby a water molecule completes the Ln(III) coordination sphere. Ligand L can sensitize both the Eu(III) and Tb(III) luminescence; however, the quantum yields of the Eu(III)- and Tb(III)-centered luminescence remain modest. This is explained in terms of energy differences between the singlet and triplet states on the one hand, and between the 0-phonon transition of the triplet state and the excited metal ion states on the other. The anionic [Ln(L)(H2O)]- complexes (Ln=La, Pr, and Gd) were also characterized by theoretical calculations both in vacuo and in aqueous solution (PCM model) at the HF level by means of the 3-21G* basis set for the ligand atoms and a 46+4 f(n) effective core potential for the lanthanides. The structures obtained from these theoretical calculations are in very good agreement with the experimental solution structures, as demonstrated by paramagnetic NMR measurements (lanthanide-induced shifts and relaxation-rate enhancements). Data sets obtained from variable-temperature (17)O NMR at 7.05 T and variable-temperature (1)H nuclear magnetic relaxation dispersion (NMRD) on the Gd(III) complex were fitted simultaneously to give insight into the parameters that govern the water (1)H relaxivity. The water exchange rate (k(298)(ex)=5.0 x 10(6) s(-1)) is slightly faster than in [Gd(dota)(H2O)]- (DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane). Fast rotation limits the relaxivity under the usual MRI conditions.     

A heterobimetallic ruthenium-gadolinium complex as a potential agent for bimodal imaging

Trinuclear heterobimetallic Ln(III)-Ru(II) complexes (Ln = Eu, Gd) based on a 1,10-phenanthroline ligand bearing a diethylenetriaminepentaacetic acid (DTPA) core have been synthesized and fully characterized by a range of experimental techniques. The (17)O NMR and proton nuclear magnetic relaxation dispersion (NMRD) measurements of Gd(III)-Ru(II) show that, in comparison to the parent Gd-DTPA, this complex exhibits improved relaxivity, which is the result of an increase of the rotational correlation time. Relaxometry and ultrafiltration experiments indicate that the 1,10-phenanthroline ligand has a high affinity for noncovalent binding to human serum albumin, which results in a high relaxivity r(1) of 14.3 s(-1) mM(-1) at 20 MHz and 37 °C. Furthermore, the Ln(III)-Ru(II) complexes (Ln = Eu, Gd) show an intense light absorption in the visible spectral region due to metal-to-ligand charge transfer (MLCT) transitions. Upon excitation into the MLCT band at 440 nm, the complexes exhibit a bright-red luminescence centered at 610 nm, with a quantum yield of 4.7%. The luminescence lifetime equals 540 ns and is therefore long enough to exceed the fluorescent background. Monometallic lanthanide complexes have also been synthesized, and the Eu(III) analogue shows a characteristic red luminescence with a quantum yield of 0.8%. Taking into account the relaxometric and luminescent properties, the developed Gd(III)-Ru(II) complex can be considered as a potential in vitro bimodal imaging agent.     

Tetranuclear d-f Metallostars: Synthesis, Relaxometric, and Luminescent Properties

A novel ditopic ligand DTPA-ph-phen, based on 1,10-phenanthroline and diethylenetriaminepentaacetic acid (DTPA) units, has been designed and fully characterized by (1)H, (13)C, and 2D-COSY NMR spectroscopy, IR and electrospray ionization mass spectrometry (ESI-MS) techniques. The DTPA core of the ligand specifically binds Ln(III) ions (Ln = Eu, Gd) resulting in formation of the [Ln{DTPA-ph-phen}(H(2)O)](-) complex. The photophysical properties of the Eu(III) compound have been investigated, and the complex shows characteristic red luminescence with an overall quantum yield of 2.2%. Reaction of [Gd{DTPA-ph-phen}(H(2)O)](-) with Ru(II) leads to further self-assembly into a heterobimetallic metallostar complex containing Gd(III) and Ru(II) in a 3:1 ratio. This tetranuclear [(Gd{DTPA-ph-phen})(3)(H(2)O)(3)Ru](-) complex (Gd(3)Ru), formed by the coordination of Ru(II) to the 1,10-phenanthroline unit, has been characterized by a range of experimental techniques and evaluated toward its feasibility as a potential bimodal optical/MRI agent. The Gd(3)Ru metallostar shows intense metal-to-ligand charge transfer (MLCT) transition resulting in intense light absorption in the visible spectral region. Upon irradiation into this MLCT band at 450 nm, the Gd(3)Ru complex exhibits red broad-band luminescence in the range of 550-800 nm centered at 610 nm with a quantum yield of 4.8%. Proton nuclear magnetic relaxation dispersion (NMRD) measurements indicate that the Gd(3)Ru complex exhibits an enhanced relaxivity value r(1) of 36.0 s(-1) mM(-1) per metallostar molecule at 20 MHz and 310 K. The ability of the complex to noncovalently bind to human serum albumin (HSA) was investigated, but no significant interaction was detected.     

A self-assembled complex with a titanium(IV) catecholate core as a potential bimodal contrast agent

A ditopic chelating ligand (H(6)4) that bears catechol and diethylenetriamine-N,N,N',N',N'-pentaacetate (DTPA) has been designed and shown to specifically bind lanthanide(III) ions at the DTPA core ([Ln(H(2)4)(H(2)O)](-)) and further self-assemble with titanium(IV), thereby giving rise to the formation of a supramolecular metallostar complex with a lanthanide(III)-to-titanium(IV) ratio of 3:1, [(Ln4)(3)Ti(H(2)O)(3)](5-) (Ln=La, Eu, Gd). The efficacy of the metallostar complex as a potential bimodal optical/magnetic resonance imaging (MRI) agent has been evaluated. Nuclear magnetic relaxation dispersion (NMRD) measurements for the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex have demonstrated an enhanced r(1) relaxivity that corresponds to 36.9 s(-1) mM(-1) per metallostar molecule at 20 MHz and 310 K, which is a result of a decreased tumbling rate. The ability of the complex to bind to human serum albumin (HSA) was also examined by relaxometric measurements. In addition, upon UV irradiation the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex exhibits broad-band green emission in the range 400-750 nm with a maximum at 490 nm. Taking into account the high relaxivity and luminescence properties, the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex is a good lead compound for the development of efficient bimodal contrast agents.     

Lanthanide(III) complexes with ligands derived from a cyclen framework containing pyridinecarboxylate pendants. The effect of steric hindrance on the hydration number

Two new macrocyclic ligands, 6,6′-((1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolinic acid (H2DODPA) and 6,6′-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolinic acid (H2Me-DODPA), designed for complexation of lanthanide ions in aqueous solution, have been synthesized and studied. The X-ray crystal structure of [Yb(DODPA)](PF6)·H2O shows that the metal ion is directly bound to the eight donor atoms of the ligand, which results in a square-antiprismatic coordination around the metal ion. The hydration numbers (q) obtained from luminescence lifetime measurements in aqueous solution of the Eu(III) and Tb(III) complexes indicate that the DODPA complexes contain one inner-sphere water molecule, while those of the methylated analogue H2Me-DODPA are q = 0. The structure of the complexes in solution has been investigated by 1H and 13C NMR spectroscopy, as well as by theoretical calculations performed at the density functional theory (DFT; mPWB95) level. The minimum energy conformation calculated for the Yb(III) complex [Λ(λλλλ)] is in good agreement with the experimental structure in solution, as demonstrated by the analysis of the Yb(III)-induced paramagnetic 1H shifts. The nuclear magnetic relaxation dispersion (NMRD) profiles recorded for [Gd(Me-DODPA)]+ are typical of a complex with q = 0, where the observed relaxivity can be accounted for by the outer-sphere mechanism. However, [Gd(DODPA)]+ shows NMRD profiles consistent with the presence of both inner- and outer-sphere contributions to relaxivity. A simultaneous fitting of the NMRD profiles and variable temperature 17O NMR chemical shifts and transversal relaxation rates provided the parameters governing the relaxivity in [Gd(DODPA)]+. The results show that this system is endowed with a relatively fast water exchange rate k(ex)(298) = 58 × 10(6) s(–1).     

Structure, stability and relaxivity of trinuclear triangular complexes

The self-assembly of a carbonylpyridine-based heptadentate ligand with Ln(III) results in the formation of triangular trinuclear europium complexes, which exhibit interesting luminescent properties in the solid state and in solution. With a view to developing multimodal responsive systems, we report here the preparation and characterisation of analogous complexes with Gd(III). The X-ray crystal structure of Gd(3)L2(3) indeed reveals the isostructurality with the Eu(III) complexes. A combination of (1)H NMRD and variable temperature studies yields the parameters elucidating the exchange of coordinated water and relaxivity properties. Conveniently, the competitive spectrophotometric titrations with EDTA and NTA are used to determine the thermodynamic stability constants of the europium complexes in aqueous media. In addition, the exchange reaction with EDTA is monitored with NMR and fluorimetry. The interactions of the Eu(III) trinuclear complex with some potentially interfering ligands are qualitatively investigated by means of luminescence titrations.     

Trinuclear lanthanide complexes of a compartmental ligand N,N'-bis(2-pyridinyl)-2,6-pyridinedicarboxamide: a spectroscopic investigation

Trinuclear lanthanide complexes of the formula [Ln(3)(PPDA)(NO(3))(6)(H(2)O)(2)].NO(3).2H(2)O where Ln=La(III), Pr(III), Sm(III), Nd(III), Eu(III) Gd(III) Tb(III), Dy(III) and Y(III); H(2)PPDA=N,N'-bis(2-pyridinyl)-2,6-pyridinedicarboxamide, have been isolated. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility measurements and spectral (IR, NMR, UV-vis, fluorescence, FAB and EPR) and thermal studies.     

Synthesis of a bifunctional monophosphinic acid DOTA analogue ligand and its lanthanide(III) complexes. A gadolinium(III) complex endowed with an optimal water exchange rate for MRI applications

A new bifunctional octa-coordinating ligand containing an aminobenzyl moiety, DO3APABn (H4DO3APABn = 1,4,7,10-tetraazacyclododecane-4,7,10-triacetic-1-{methyl[(4-aminophenyl)methyl]phosphinic acid}), has been synthesized. Its lanthanide(III) complexes contain one water molecule in the first coordination sphere. The high-resolution 1H and 31P spectra of [Eu(H2O) (DO3APABn)]- show that the twisted square-antiprismatic form of the complexes is more abundant in respect to the corresponding Eu(III)-DOTA complex. The 1H NMRD and variable-temperature 17O relaxation measurements of [Gd(H2O)(DO3APABn)]- show that the water residence time is short (298tauM = 16 ns) and falls into the optimal range predicted by theory for the attainment of high relaxivities once this complex would be endowed by a slow tumbling rate. The relaxivity (298r1 = 6.7 mM(-1) s(-1) at 10 MHz) is higher than expected as a consequence of a significant contribution from the second hydration sphere. These results prompt the use of [Gd(H2O)(DO3APABn)]- as a building block for the set-up of highly efficient macromolecular MRI contrast agents.     

Fixation of carbon dioxide by macrocyclic lanthanide(III) complexes under neutral conditions producing self-assembled trimeric carbonato-bridged compounds with μ3-η2:η2:η2 bonding

A series of mononuclear lanthanide(III) complexes [Ln(LH(2))(H(2)O)(3)Cl](ClO(4))(2) (Ln = La, Nd, Sm, Eu, Gd, Tb, Lu) of the tetraiminodiphenolate macrocyclic ligand (LH(2)) in 95 : 5 (v/v) methanol-water solution fix atmospheric carbon dioxide to produce the carbonato-bridged trinuclear complexes [{Ln(LH(2))(H(2)O)Cl}(3)(μ(3)-CO(3))](ClO(4))(4)·nH(2)O. Under similar conditions, the mononuclear Y(III) complex forms the dimeric compound [{Y(LH(2))(H(2)O)Cl}(μ(2)-CO(3)){Y(LH(2))(H(2)O)(2)}](ClO(4))(3)·4H(2)O. These complexes have been characterized by their IR and NMR ((1)H, (13)C) spectra. The X-ray crystal structures have been determined for the trinuclear carbonato-bridged compounds of Nd(III), Gd(III) and Tb(III) and the dinuclear compound of Y(III). In all cases, each of the metal centers are 8-coordinate involving two imine nitrogens and two phenolate oxygens of the macrocyclic ligand (LH(2)) whose two other imines are protonated and intramolecularly hydrogen-bonded with the phenolate oxygens. The oxygen atoms of the carbonate anion in the trinuclear complexes are bonded to the metal ions in tris-bidentate μ(3)-η(2):η(2):η(2) fashion, while they are in bis-bidentate μ(2)-η(2):η(2) mode in the Y(III) complex. The magnetic properties of the Gd(III) complex have been studied over the temperature range 2 to 300 K and the magnetic susceptibility data indicate a very weak antiferromagnetic exchange interaction (J = -0.042 cm(-1)) between the Gd(III) centers (S = 7/2) in the metal triangle through the carbonate bridge. The luminescence spectral behaviors of the complexes of Sm(III), Eu(III), and Tb(III) have been studied. The ligand LH(2) acts as a sensitizer for the metal ions in an acetonitrile-toluene glassy matrix (at 77 K) and luminescence intensities of the complexes decrease in the order Eu(3+) > Sm(3+) > Tb(3+).     

Synthetic and spectral studies of some 4ƒ-metal complexes

Salicylaldehyde(N-benzoyl)glycyl hydrazone (SalBzGH) has been synthesized and characterized. Metal complexes of the empirical formula [Ln(SalBzGH-2H)OH(H₂O)₂] where Ln = Y, Pr, Nd, Sm, Eu, Gd and Dy, have been synthesized and their structures studied by infrared, far-infrared, absorption, emission and NMR spectra. ¹H and ¹³C NMR spectra indicate the presence of dynamic equilibrium between two isomers of SalBzGH over the 298–368 K temperature range and stabilization of a single isomer upon complexation with Ln(III). The hypersensitive band profile of the Nd(III) complex indicates a change in metal coordination number due to solvation, while an increase of temperature results in a decrease of ε_max of the hypersensitive band. The emission spectrum of [Eu(SalBzGH-2H)OH(H₂O)₂] at 77 K indicates a low site symmetry. SalBzGH coordinates through imidolic oxygen, azomethine nitrogen and phenolate oxygen.     

Unexpected aggregation of neutral, xylene-cored dinuclear GdIII chelates in aqueous solution

We have synthesized ditopic ligands L(1), L(2), and L(3) that contain two DO3A(3-) metal-chelating units with a xylene core as a noncoordinating linker (DO3A(3-) = 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate; L(1) = 1,4-bis{[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl]methyl}benzene; L(2) = 1,3-bis{[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl]methyl}benzene; L(3) = 3,5-bis{[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl]methyl}benzoic acid). Aqueous solutions of the dinuclear Gd(III) complexes formed with the three ligands have been investigated in a variable-temperature, multiple-field (17)O NMR and (1)H relaxivity study. The (17)O longitudinal relaxation rates measured for the [Gd(2)L(1-3)(H2O)(2)] complexes show strong field dependence (2.35-9.4 T), which unambiguously proves the presence of slowly tumbling entities in solution. The proton relaxivities of the complexes, which are unexpectedly high for their molecular weight, and in particular the relaxivity peaks observed at 40-50 MHz also constitute experimental evidences of slow rotational motion. This was explained in terms of self-aggregation related to hydrophobic interactions, pi stacking between the aromatic linkers, or possible hydrogen bonding between the chelates. The longitudinal (17)O relaxation rates of the [Gd(2)L(1-3)(H2O)(2)] complexes have been analysed with the Lipari-Szabo approach, leading to local rotational correlation times tau(1)(298) of 150-250 ps and global rotational correlation times tau(g)(298) of 1.6-3.4 ns (c(Gd): 20-50 mM), where tau(1)(298) is attributed to local motions of the Gd segments, while tau(g)(298) describes the overall motion of the aggregates. The aggregates can be partially disrupted by phosphate addition; however, at high concentrations phosphate interferes in the first coordination sphere by replacing the coordinated water. In contrast to the parent [Gd(DO3A)(H2O)(1.9)], which presents a hydration equilibrium between mono- and dihydrated species, a hydration number of q = 1 was established for the [Ln(2)L(1-3)(H2O)(2)] chelates by (17)O chemical shift measurements on Ln = Gd and UV/Vis spectrophotometry for Ln = Eu. The exchange rate of the coordinated water is higher for [Gd(2)L(1-3)(H2O)(2)] complexes k(ex)(298) = 7.5-12.0 x 10(6) s(-1)) than for [Gd(DOTA)(H2O)](-). The proton relaxivity of the [Gd(2)L(1-3)(H2O)(2)] complexes strongly decreases with increasing pH. This is related to the deprotonation of the inner-sphere water, which has also been characterized by pH potentiometry. The protonation constants determined for this process are logK(OH) = 9.50 and 10.37 for [Gd(2)L(1)(H2O)(2)] and [Gd(2)L(3)(H2O)(2)], respectively.     

Studies on 1H NMR, infrared and fluorescence spectra of rare earth complexes with a new binaphthylamide

Solid complexes of lanthanide picrates with N,N-dibenzyl-2-[2'-[(dibenzylcarbamoyl)-methoxy]-[1,1']binaphthalenyl-2-yloxy]-acetamide (L), [Ln(pic)(3)L] (Ln = La, Nd, Eu, Gd, Tb, Dy, Y), have been prepared and characterized by elemental analysis, IR, 1H NMR, UV-Vis spectra and conductivity measurements. The fluorescence property of the europium complex in solid state and in CHCl(3), acetone, AcOEt and DMF was studied.     

Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2':6',2'-terpyridine ligand: implications for actinide(III)/lanthanide(III) partitioning

The quadridentate N-heterocyclic ligand 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2'?:?6',2'-terpyridine (CyMe(4)-hemi-BTBP) has been synthesized and its interactions with Am(III), U(VI), Ln(III) and some transition metal cations have been evaluated by X-ray crystallographic analysis, Am(III)/Eu(III) solvent extraction experiments, UV absorption spectrophotometry, NMR studies and ESI-MS. Structures of 1:1 complexes with Eu(III), Ce(III) and the linear uranyl (UO(2)(2+)) ion were obtained by X-ray crystallographic analysis, and they showed similar coordination behavior to related BTBP complexes. In methanol, the stability constants of the Ln(III) complexes are slightly lower than those of the analogous quadridentate bis-triazine BTBP ligands, while the stability constant for the Yb(III) complex is higher. (1)H NMR titrations and ESI-MS with lanthanide nitrates showed that the ligand forms only 1:1 complexes with Eu(III), Ce(III) and Yb(III), while both 1:1 and 1:2 complexes were formed with La(III) and Y(III) in acetonitrile. A mixture of isomeric chiral 2:2 helical complexes was formed with Cu(I), with a slight preference (1.4:1) for a single directional isomer. In contrast, a 1:1 complex was observed with the larger Ag(I) ion. The ligand was unable to extract Am(III) or Eu(III) from nitric acid solutions into 1-octanol, except in the presence of a synergist at low acidity. The results show that the presence of two outer 1,2,4-triazine rings is required for the efficient extraction and separation of An(III) from Ln(III) by quadridentate N-donor ligands.     

How does internal motion influence the relaxation of the water protons in Ln(III)DOTA-like complexes?

Taking advantage of the Curie contribution to the relaxation of the protons in the Tb(III) complex, and the quadrupolar relaxation of the 17O and 2H nuclei on the Eu(III) complex, the effect of the internal motion of the water molecule bound to [Ln(DOTAM)(H2O)]3+ complexes was quantified. The determination of the quadrupolar coupling constant of the bound water oxygen chi(Omicron)(1 + eta(Omicron)2/3)1/2 = 5.2 +/- 0.5 MHz allows a new analysis of the 17O and 1H NMR data of the [Gd(DOTA)(H2O)]- complex with different rotational correlation times for the Gd(III)-O(water) and Gd(III)-H(water) vectors. The ratio of the rotational correlation times for the Ln(III)-H(water) vector and the overall rotational correlation time is calculated tau(RH)/tau(RO) = 0.65 +/- 0.2. This could have negative consequences on the water proton relaxivity, which we discuss in particular for macromolecular systems. It appears that the final effect is actually attenuated and should be around 10% for such large systems undergoing local motion of the chelating groups.     

Synthesis, characterization and luminescence property of N,N'-di(pyridine N-oxide-2-yl)pyridine-2,6-dicarboxamide and corresponding lanthanide (III) complexes

A new ligand, N,N'-di(pyridine N-oxide-2-yl)pyridine-2,6-dicarboxamide (LH2) and its several lanthanide (III) complexes (La, Eu, Gd, Tb, Y) were synthesized and characterized in detail based on elemental analysis, conductivity measurements, IR, 1H NMR, MS (FAB) and UV spectra and TG-DTA studies. The results indicated that the composition of these binary complexes is [Ln(LH2)(NO3)2.H2O]NO3.nH2O (n=0-1); while the ligand has a good planar structure with strong hydrogen bonds. The fluorescence spectra exhibits that the Tb (III) complex and the Eu (III) complex display characteristic metal-centered fluorescence in solid state while ligand fluorescence is completely quenched. However, the Tb (III) complex displays more effective luminescence than the Eu (III) complex, which is attributed to especial effectivity in transferring energy from the lowest triplet energy level of the ligands (T) onto the excited state (5D4) of Tb (III) than that (5D1) of Eu (III).     

Rare earth complexes with a novel ligand N-(naphthalen-2-yl)-N-phenyl-2-(quinolin-8-yloxy)acetamide: preparation and spectroscopic studies

Six complexes of rare earth nitrates (Ln=La, Sm, Eu, Gd, Tb, Dy) with a new amide type ligand, N-(naphthalen-2-yl)-N-phenyl-2-(quinolin-8-yloxy)acetamide (L) have been prepared and characterized by elemental analysis, conductivity measurements, IR and and 1H NMR spectra. Under excitation, Eu(III) and Sm(III) complexes exhibited strong red emissions. And the luminescence intensity of Sm(III) complex is higher than that of Eu(III) complex. Thus the Eu(III) and Sm(III) complexes are the potential light conversion agent. However, the Tb(III) and Dy(III) complexes cannot exhibit characteristic emissions of terbium and dysprosium ions, respectively. The results of phosphorescence spectrum show that the triplet-state energy level of the ligand matches better to the resonance level of Eu(III) than Tb(III) ion. In addition, the luminescence of the Eu(III) complex is also relatively strong in highly diluted tetrahydrofuran solution (2 x 10(-4)mol/L) compared with the powder. This is not only due to the solvate effects but also to the changes of the structure of the Eu(III) complex after being dissolved into the solvents. Furthermore, owing to the co-luminescence effect, the proper La(III) or Gd(III) doped Eu(III) complexes show stronger luminescence than the pure Eu(III) complex.     

Lanthanide(III) complexes of DOTA-glycoconjugates: a potential new class of lectin-mediated medical imaging agents

The synthesis and characterization of a new class of DOTA (1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane) monoamide-linked glycoconjugates (glucose, lactose and galactose) of different valencies (mono, di and tetra) and their Sm(III), Eu(III) and Gd(III) complexes are reported. The 1H NMR spectrum of Eu(III)-DOTALac2 shows the predominance of a single structural isomer of square antiprismatic geometry of the DOTA chelating moiety and fast rotation about the amide bond connected to the targeting glycodendrimer. The in vitro relaxivity of the Gd(III)-glycoconjugates was studied by 1H nuclear magnetic relaxation dispersion (NMRD), yielding parameters close to those reported for other DOTA monoamides. The known recognition of sugars by lectins makes these glycoconjugates good candidates for medical imaging agents (MRI and gamma scintigraphy).     

Lanthanide(III) Complexes of Cyclen Triacetates and Triamides Bearing Tertiary Amide-Linked Antennae

The coordination compounds of the trivalent lanthanide ions (Ln(III)) have unique photophysical properties. Ln(III) excitation is usually performed through a light-harvesting antenna. To enable Ln(III)-based emitters to reach their full potential, an understanding of how complex structure affects sensitization and quenching processes is necessary. Here, the role of the linker between the antenna and the metal binding fragment was studied. Four macrocyclic ligands carrying coumarin 2 or 4-methoxymethylcarbostyril sensitizing antennae linked to an octadentate macrocyclic ligand binding site were synthesized. Complexation with Ln(III) (Ln = La, Sm, Eu, Gd, Tb, Yb and Lu) yielded species with overall −1, 0, or +2 and +3-charge. Paramagnetic ¹H NMR spectroscopy indicated subtle differences between the coumarin- and carbostyril-carrying Eu(III) and Yb(III) complexes. Cyclic voltammetry showed that the effect of the linker on the Eu(III)/Eu(II) apparent reduction potential was dependent on the electronic properties of the N-substituent. The Eu(III), Tb(III) and Sm(III) complexes were all luminescent. Coumarin-sensitized complexes were poorly emissive; photoinduced electron transfer was not a major quenching pathway in these species. These results show that seemingly similar emitters can undergo very different photophysical processes, and highlight the crucial role the linker can play.     

Gadolinium(III) complexes of mono- and diethyl esters of monophosphonic acid analogue of DOTA as potential MRI contrast agents: solution structures and relaxometric studies

Two new macrocyclic DOTA-like chelates containing one phosphonate pendant arm were synthesised as potential contrast agents for MRI (magnetic resonance imaging). The chelates bind to the lanthanide(III) in an octadentate manner, via four nitrogen atoms, three carboxylate and one phosphonate oxygen atoms. Solution structures of [Ln(do3ap(OEt2))(H(2)O)] and [Ln(do3ap(OEt))(H(2)O)](-) were studied using (31)P and (1)H NMR spectroscopy and SAP (square-antiprismatic)/TSAP (twisted square-antiprismatic) isomerism was observed. Depending on the nature of the lanthanide(III) ion, the lanthanide(III) complexes of H(4)do3ap(OEt) are present in solution as up to four different diastereoisomers observable with NMR. The TSAP isomer is the most abundant at the beginning of the lanthanide series and, with a decrease of the ionic radius of lanthanide(III) ions, both TSAP and SAP forms were observed. A second interconversion (SAP<-->TSAP') becomes important at the end of the series (TSAP' means the TSAP species without a coordinated water molecule). The remaining axial coordination site is occupied by one water molecule for the Gd(3+)-complex. The calculated fraction of the TSAP isomer in the gadolinium(III) complexes increases in the order [Gd(DOTA)(H(2)O)](-) < [Gd(do3ap(OEt2))(H(2)O)] < [Gd(do3ap(OEt))(H(2)O)](-) < [Gd(do3ap)(H(2)O)](2-). Gadolinium(III) complexes of phosphorus-containing chelates, generally, have the advantage of a relatively fast water exchange rate due to a greater sterical demand of the phosphorus acid moiety and of the presence of the second-sphere water shell, which also contributes to the overall relaxivity. The [Gd(do3ap(OEt2))(H(2)O)] and [Gd(do3ap(OEt))(H(2)O)](-) complexes were studied by variable-temperature (17)O NMR and (1)H NMRD. The experimental data were evaluated simultaneously with commonly used equations based on Solomon-Bloembergen-Morgan approximation, extended by a contribution of the second coordination sphere. The water exchange rates were found to be strongly dependent on the TSAP/SAP isomeric ratio and the overall charge of the complex: the monoanionic [Gd(do3ap(OEt))(H(2)O)](-) complex with TSAP molar fraction equal to 0.36 has the water exchange rate of 20 x 10(6) s(-1) (tau(M) = 50 ns) while neutral [Gd(do3ap(OEt2))(H(2)O)] complex with TSAP molar fraction 0.28 has an exchange rate equal to 4.4 x 10(6) s(-1) (tau(M) = 227 ns).