Synthesis of Ln(III) chloride tetraphenylporphyrin complexes

The isolation and identification of the first examples of anhydrous lanthanide chloride tetraphenylporphyrin complexes have been described. The purple complexes were generated by the reaction of dilithiotetraphenylporphyrin bis(dimethoxyethane) with lanthanide trichloride tris(tetrahydrofuran) salts to yield the products in up to 85% yield. The crystal structures for the holmium and ytterbium complexes are also presented.     

Protein binding to lanthanide(III) complexes can reduce the water exchange rate at the lanthanide

The GdIII-based magnetic resonance imaging contrast agent MS-325 targets the blood protein serum albumin, resulting in an increased efficacy (relaxivity) as a relaxation agent. MS-325 showed different relaxivities when bound to serum albumin from different species, e.g., r1=30.5 mM-1 s-1 (rabbit) vs 46.3 mM-1 s-1 (human) at 35 degrees C and 0.47 T. To investigate the mechanism for this difference, surrogate complexes were prepared where the GdIII ion was replaced by other LnIII ions. Fluorescence lifetime measurements of the EuIII analogue indicated that the hydration number was q=1 and did not change when bound to either human, rat, rabbit, pig, or dog serum albumin. The YbIII analogue, YbL1, was prepared and characterized by 1H NMR. Line-shape analysis of the paramagnetic-shifted 1H NMR resonances in the presence of increasing amounts of human (HSA) or rabbit (RSA) serum albumin allowed estimation of the transverse relaxation rate, R2, of these resonances for the protein-bound YbL1. The rotational correlation time of YbL1 was calculated from R2, and the Yb-H distance and was tauR=8+/-1 ns when bound to HSA and 13+/-2 ns when bound to RSA. The water exchange rate at the DyIII analogue, DyL1, was determined from variable-temperature R2 measurements at 9.4 T when DyL1 was bound to either HSA or RSA. At 37 degrees C, water exchange at DyL1 was (31+/-5)x10(6) s-1 when bound to HSA but (3.8+/-0.2)x10(6) s-1 when bound to RSA. Slower water exchange upon RSA binding explains the differences in relaxivity observed. The approach of using surrogate lanthanides to identify specific molecular parameters influencing relaxivity is applicable to other protein-targeted GdIII contrast agents.     

trans-chloro(N,N-dimethyl-d-phenylglycine)-(3-methyl-1-phenylpent-1-ene)platinum(II) complexes. HPLC separation and identification of all the diastereomers

The diastereomeric trans-chloro(N,N-dimethyl-d-phenylglycine)(3-methyl-1-phenylpent-1-ene)platinum(II) complexes, derived by coordination of the enantiomeric and geometric isomers of 3-methyl-1-phenylpent-1-ene (2), were separated by HPLC. Four trans- and two cis-olefin complexes were recognized in the chromatogram. The configuration of all chiral centers of the olefin in the six complexes were assigned. Under the conditions of preparation, the pairs of diastereomers 1R,2R,3S/1S,2S,3S and 1S,2S,3R/1R,2R,3R were formed in a ratio > 1 for the trans-isomer, whereas the cis-isomer gave the 1R,2S,3S and 1S,2R,3R epimers only. The complexes do not epimerize on standing at room temperature in solution; similar behaviour of the corresponding complexes of trans-stilbene (4C) indicates that the conjugated aromatic double bond is coordinated more strongly than those aliphatic and cycloaliphatic olefins.The efficient HPLC separation of the diasteromeric complexes 2C, permits the enantiomeric analysis of 2, as well as the preparative resolution of the olefin.     

Pyridine- and phosphonate-containing ligands for stable Ln complexation. Extremely fast water exchange on the Gd(III) chelates

Two novel ligands containing pyridine units and phosphonate pendant arms, with ethane-1,2-diamine (L2) or cyclohexane-1,2-diamine (L3) backbones, have been synthesized for Ln complexation. The hydration numbers obtained from luminescence lifetime measurements in aqueous solutions of the Eu(III) and Tb(III) complexes are q = 0.6 (EuL2), 0.7 (TbL2), 0.8 (EuL3), and 0.4 (TbL3). To further assess the hydration equilibrium, we have performed a variable-temperature and -pressure UV-vis spectrophotometric study on the Eu(III) complexes. The reaction enthalpy, entropy, and volume for the hydration equilibrium EuL <--> EuL(H2O) were calculated to be DeltaH degrees = -(11.6 +/- 2) kJ mol(-1), DeltaS degrees = -(34.2 +/- 5) J mol(-1) K(-1), and = 1.8 +/- 0.3 for EuL2 and DeltaH degrees = -(13.5 +/- 1) kJ mol(-1), DeltaS degrees = -(41 +/- 4) J mol(-1) K(-1), and = 1.7 +/- 0.3 for EuL3, respectively. We have carried out variable-temperature 17O NMR and nuclear magnetic relaxation dispersion (NMRD) measurements on the GdL2(H2O)q and GdL3(H2O)q systems. Given the presence of phosphonate groups in the ligand backbone, a second-sphere relaxation mechanism has been included for the analysis of the longitudinal (17)O and (1)H NMR relaxation rates. The water exchange rate on GdL2(H2O)q, = (7.0 +/- 0.8) x 10(8) s(-1), is extremely high and comparable to that on the Gd(III) aqua ion, while it is slightly reduced for GdL3(H2O)q, = (1.5 +/- 0.1) x 10(8) s(-1). This fast exchange can be rationalized in terms of a very flexible inner coordination sphere, which is slightly rigidified for L3 by the introduction of the cyclohexyl group on the amine backbone. The water exchange proceeds via a dissociative interchange mechanism, evidenced by the positive activation volumes obtained from variable-pressure 17O NMR for both GdL2(H2O)q and GdL3(H2O)q (DeltaV = +8.3 +/- 1.0 and 8.7 +/- 1.0 cm(3) mol(-1), respectively).     

Sensitized near-IR luminescence of Ln(III) complexes with benzothiazole derivatives

Lanthanide complexes with benzothiazole derivatives (Btz-R, R = OCH(3) and OH) and terpyridine (tpy) ligands were synthesized, and their photophysical properties were precisely investigated. The free Btz-OCH(3) ligand in toluene, excited with UV light, produced the normal emission bands around 410 nm, whereas Btz-OH produced a strong excited-state intramolecular proton transfer (ESIPT) band at 510 nm. The Ln(III) complexes (Ln = Nd, Er, and Yb) exhibited sensitized near-IR luminescence when the Btz-R ligands were excited. The sensitized luminescence quantum yields (Phi(Ln)) of the lanthanide complexes were markedly enhanced by ESIPT: for [Nd(Btz-R)(tpy)] in toluene solution, Phi(Ln) = 0.04% for Btz-OCH(3) and 0.39% for Btz-OH. The sensitized luminescence of the Er(III) complexes (Phi(Ln) = 0.002% for Btz-OCH(3) and 0.009% for Btz-OH) was less efficient than that of the Nd(III) complexes. This difference is due to the smaller energy gap between the emitting and ground levels of the Er(III) ion. The rate constants for the energy transfer from Btz-R to Ln(III) were about approximately 10(9) s(-1), as evaluated by the F?rster resonance energy transfer mechanism.     

系列双核Ln(III)配合物的晶体结构和磁性

合成了分子式为[Ln~2(phen)~2L],phen=C~1~2H~8N~2[ALn=Nd,L=(CH~3COO)~4(ONO~2)~2,BLn=Sm,L=(C~6H~5COO)~6,CLn=Eu,L=(C~6H~5COO)~6]3种同双核配合物。用X射线四圆衍射仪测定了3种化合物的结构。在化合物A分子中,2个Nd(III)原子由4个CH~3COO^-基团桥联,以phen和ONO~2^-为端基,构成了一个具有C~2对称性的双核分子。配合物B和C具有完全相同的结构,它们是以4个苯甲酸根为桥,2个phen和2个C~6H~5COO^-为端基的中心对称双核分子,其中6个苯甲酸根的成键状态可分为3种状况。在3种化合物中,每个Ln均为9配位,呈不规则多面体。Ln-Ln距离,A为0.397nm,B和C均为0.405nm。测定了各配合物的变温磁化率,通过对磁性质研究,发现化合物A在低温下具有反铁磁物质行为,并由理论拟合,求得了磁参数g,J值。     

系列双核Ln(III)配合物的晶体结构和磁性

合成了分子式为[Ln~2(phen)~2L],phen=C~1~2H~8N~2[ALn=Nd,L=(CH~3COO)~4(ONO~2)~2,BLn=Sm,L=(C~6H~5COO)~6,CLn=Eu,L=(C~6H~5COO)~6]3种同双核配合物。用X射线四圆衍射仪测定了3种化合物的结构。在化合物A分子中,2个Nd(III)原子由4个CH~3COO^-基团桥联,以phen和ONO~2^-为端基,构成了一个具有C~2对称性的双核分子。配合物B和C具有完全相同的结构,它们是以4个苯甲酸根为桥,2个phen和2个C~6H~5COO^-为端基的中心对称双核分子,其中6个苯甲酸根的成键状态可分为3种状况。在3种化合物中,每个Ln均为9配位,呈不规则多面体。Ln-Ln距离,A为0.397nm,B和C均为0.405nm。测定了各配合物的变温磁化率,通过对磁性质研究,发现化合物A在低温下具有反铁磁物质行为,并由理论拟合,求得了磁参数g,J值。     

Synthesis and photophysical properties of new Ln(III) (Ln = Eu(III), Gd(III), or Tb(III)) complexes of 1-amidino-O-methylurea

Three new solid lanthanide(III) complexes, [Ln(1-AMUH)₃] · (NO₃)₃ (1-AMUH = 1-amidino-O-methylurea; Ln = Eu(III), Gd(III), or Tb(III)) were synthesised and characterised by elemental analysis, infrared spectra, magnetic moment measurement, and electron paramagnetic resonance (EPR) spectra for Gd(III) complex. The formation of lanthanide(III) complexes is confirmed by the spectroscopic studies. The photophysical properties of Gd(III), Eu(III), and Tb(III) complexes in solid state were investigated. The Tb(III) complex exhibits the strongest green emission at 543 nm and the Eu(III) complex shows a red emission at 615 nm while the Gd(III) complex shows a weak emission band at 303 nm. Under excitation with UV light, these complexes exhibited an emission characteristic of central metal ions. The powder EPR spectrum of the Gd(III) complex at 300 K exhibits a single broad band with g = 2.025. The bi-exponential nature of the decay lifetime curve is observed in the Eu(III) and Tb(III) complexes. The results reveal them to have potential as luminescent materials.     

The highest water exchange rate ever measured for a Gd(III) chelate

The complex [Gd(L)(H2O)]3- (H(6)L =N,N'-bis(6-carboxy-2-pyridylmethyl)ethylenediamine-N,N'-methylenephosphonic acid) displays the highest water exchange rate ever measured for a Gd(III) chelate (k(298)(ex)= 8.8 x 10(8) s(-1)), which is attributed to the flexibility of the metal coordination environment.     

Controlling the variation of axial water exchange rates in macrocyclic lanthanide(III) complexes

The rate of axial water exchange in well-defined series of lanthanide complexes depends on the extent of second sphere hydration which is determined by complex hydrophobicity and the nature of the lanthanide ion and its counter-ion.     

Modulation of water exchange in europium(III) DOTA-tetraamide complexes via electronic substituent effects

The chemical exchange saturation transfer (CEST) efficiency for a series Eu3+-based tetraamide complexes bearing p-substituents on a single coordinating pendant arm is highly sensitive to water exchange rates. The CEST effect increases in the order Me < MeO < F approximately CO2tBu < CN < H. These results show that CEST contrast can be modulated by changes in electron density at a single ligating atom, and this forms the basis of creating imaging agents that respond to chemical oxidation and reduction.     

Surface-based molecular self-assembly: Langmuir-Blodgett films of amphiphilic Ln(III) complexes

The unique photophysical properties of the Ln(III) series has led to significant research efforts being directed towards their application in sensors. However, for “real-life” applications, these sensors should ideally be immobilised onto surfaces without loss of function. The Langmuir-Blodgett (LB) technique offers a promising method in which to achieve such immobilisation. This mini-review focuses on synthetic strategies for film formation, the effect that film formation has on the physical properties of the Ln(III) amphiphile, and concludes with examples of Ln(III) LB films being used as sensors.     

Unequivocal synthetic pathway to heterodinuclear (4f,4f') complexes: magnetic study of relevant (Ln(III), Gd(III)) and (Gd(III), Ln(III)) complexes

The tripodal ligand tris[4-(2-hydroxy-3-methoxyphenyl)-3-aza-3-buten]amine (LH(3)) is capable of coordinating to two different lanthanide ions to give complexes formulated as [LLnLn'(NO(3))(3)].x H(2)O. The stepwise synthetic procedure consists of introducing first a Ln(III) ion in the inner N(4)O(3) coordination site. The isolated neutral complex LLn is then allowed to react with a second and different Ln' ion that occupies the outer O(6) site, thus yielding a [LLnLn'(NO(3))(3)].x H(2)O complex. A FAB(+) study has confirmed the existence of (Ln, Ln') entities as genuine, when the Ln' ion in the outer site has a larger ionic radius than the Ln ion in the inner site. The qualitative magnetic study of the (Gd, Ln) and (Ln, Gd) complexes, based on the comparison of the magnetic properties of (Gd, Ln) (or (Ln, Gd)) pairs and (Y, Ln) (or (Ln, La)) pairs, is very informative. Indeed, these former complexes are governed by the thermal population of the Ln(III) Stark levels and the Ln-Gd interaction, while the latter are influenced by the thermal population of the Ln(III) Stark levels. We have been able to show that a ferromagnetic interaction exists at low temperature in the (Gd, Nd), (Gd, Ce), and (Yb, Gd) complexes. In contrast, an antiferromagnetic interaction occurs in the (Dy, Gd) and (Er, Gd) complexes. Although we cannot give a quantitative value to these interactions, we can affirm that their magnitudes are weak since they are only perceptible at very low temperature.     

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.     

Structure and properties of new mixed-valent [Mn(III)2Mn(IV)3Ln(III)5O5] complexes (Ln(III) = Tm(III), Lu(III), and Yb(III))

By using 2'-hydroxyacetophenoxime, a new family of complexes with an [Mn(III)(2)Mn(IV)(3)Ln(5)O(5)] core was obtained with Ln = Tm (1), Lu (2), and Yb (3). Heterometallic Mn/Tm and Mn/Lu combinations have had no precedence so far. Studies of the magnetic properties indicate the presence of intracomplex antiferromagnetic interactions in 1 and 3, as well as a dominating ferromagnetic interaction between Mn(III) and Mn(IV) spins in 2, leading to an S(T) = 5/2 ground state.     

Carboxylate-free Mn(III)2Ln(III)2 (Ln = lanthanide) and Mn(III)2Y(III)2 complexes from the use of (2-hydroxymethyl)pyridine: analysis of spin frustration effects

The initial employment of 2-(hydroxymethyl)pyridine for the synthesis of Mn/Ln (Ln = lanthanide) and Mn/Y clusters, in the absence of an ancillary organic ligand, has afforded a family of tetranuclear [Mn(III)(2)M(III)(2)(OH)(2)(NO(3))(4)(hmp)(4)(H(2)O)(4)](NO(3))(2) (M = Dy, 1; Tb, 2; Gd, 3; Y; 4) anionic compounds. 1-4 possess a planar butterfly (or rhombus) core and are rare examples of carboxylate-free Mn/Ln and Mn/Y clusters. Variable-temperature dc and ac studies established that 1 and 2, which contain highly anisotropic Ln(III) atoms, exhibit slow relaxation of their magnetization vector. Fitting of the obtained magnetization (M) versus field (H) and temperature (T) data for 3 by matrix diagonalization and including only axial anisotropy (zero-field splitting, ZFS) showed the ground state to be S = 3. Complex 4 has an S = 0 ground state. Fitting of the magnetic susceptibility data collected in the 5-300 K range for 3 and 4 to the appropriate van Vleck equations revealed, as expected, extremely weak antiferromagnetic interactions between the paramagnetic ions; for 3, J(1) = -0.16(2) cm(-1) and J(2) = -0.12(1) cm(-1) for the Mn(III)···Mn(III) and Mn(III)···Gd(III) interactions, respectively. The S = 3 ground state of 3 has been rationalized on the basis of the spin frustration pattern in the molecule. For 4, J = -0.75(3) cm(-1) for the Mn(III)···Mn(III) interaction. Spin frustration effects in 3 have been quantitatively analyzed for all possible combinations of sign of J(1) and J(2).     

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.     

Equilibrium and formation/dissociation kinetics of some Ln(III)PCTA complexes

The protonation constants () of 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) and stability constants of complexes formed between this pyridine-containing macrocycle and several different metal ions have been determined in 1.0 M KCl at 25 degrees C and compared to previous literature values. The first protonation constant was found to be 0.5-0.6 log units higher than the value reported previously, and a total of five protonation steps were detected (log = 11.36, 7.35, 3.83, 2.12, and 1.29). The stability constants of complexes formed between PCTA and Mg2+, Ca2+, Cu2+, and Zn2+ were also somewhat higher than those previously reported, but this difference could be largely attributed to the higher first protonation constant of the ligand. Stability constants of complexes formed between PCTA and the Ln3+ series of ions and Y3+ were determined by using an "out-of-cell" potentiometric method. These values ranged from log K = 18.15 for Ce(PCTA) to log K = 20.63 for Yb(PCTA), increasing along the Ln series in proportion to decreasing Ln3+ cation size. The rates of complex formation for Ce(PCTA), Eu(PCTA), Y(PCTA), and Yb(PCTA) were followed by conventional UV-vis spectroscopy in the pH range 3.5-4.4. First-order rate constants (saturation kinetics) obtained for different ligand-to-metal ion ratios were consistent with the rapid formation of a diprotonated intermediate, Ln(H(2)PCTA)(2+). The stabilities of the intermediates as determined from the kinetic data were 2.81, 3.12, 2.97, and 2.69 log K units for Ce(H(2)PCTA), Eu(H(2)PCTA), Y(H(2)PCTA), and Yb(H(2)PCTA), respectively. Rearrangement of these intermediates to the fully chelated complexes was the rate-determining step, and the rate constant (k(r)) for this process was found to be inversely proportional to the proton concentration. The formation rates (k(OH)) increased with a decrease in the lanthanide ion size [9.68 x 10(7), 1.74 x 10(8), 1.13 x 10(8), and 1.11 x 10(9) M(-1) s(-1) for Ce(PCTA), Eu(PCTA), Y(PCTA), and Yb(PCTA), respectively]. These data indicate that the Ln(PCTA) complexes exhibit the fastest formation rates among all lanthanide macrocyclic ligand complexes studied to date. The acid-catalyzed dissociation rates (k1) varied with the cation from 9.61 x 10(-4), 5.08 x 10(-4), 1.07 x 10(-3), and 2.80 x 10(-4) M(-1) s(-1) for Ce(PCTA), Eu(PCTA), Y(PCTA), and Yb(PCTA), respectively.     

SCMEH-MO calculations on lanthanide systems. III. Ln(CO)6, Ln(OC)6 (Ln = Nd,Sm)

The SCMEH-MO method with average relativistic and spin-orbit effects has recently been applied to study the electronic structure and bonding in samarium pentamethylcyclopentadienyls. In this report the same approach has been utilized in studying the electronic structures of Nd and Sm hexacarbonyls. In contrast to the stable transition metal d-block carbonyls, these lanthanide carbonyls are found to be quite unstable. These findings are based on calculated electronic structures and bond energies. © 1996 John Wiley & Sons, Inc.