Ninth Coordination Research Articles

Intrinsic anisotropy parameters of a series of lanthanoid complexes deliver new insights into the structure-magnetism relationship

Intrinsic anisotropy parameters of a series of lanthanoid complexes deliver new insights into the structure-magnetism relationship

Luminescent lanthanide(III) complexes of DTPA-bis(amido-phenyl-terpyridine) for bioimaging and phototherapeutic applications

We report here a series of coordinatively-saturated and thermodynamically stable luminescent [Ln(dtntp)(H2O)] [Ln(III) = Eu (1), Tb (2), Gd (3), Sm (4) and Dy (5)] complexes using an aminophenyl-terpyridine appended-DTPA (dtntp) chelating ligand as cell imaging and photocytotoxic agents. The N,N″-bisamide derivative of H5DTPA named as dtntp is based on 4′-(4-aminophenyl)-2,2′:6′,2″-terpyridine conjugated to diethylenetriamine-N,N′,N″-pentaacetic acid. The structure, physicochemical properties, detailed photophysical aspects, interaction with DNA and serum proteins, and photocytotoxicity were studied. The intrinsic luminescence of Eu(III) and Tb(III) complexes due to f → f transitions used to evaluate their cellular uptake and distribution in cancer cells. The solid-state structure of [Eu(dtntp)(DMF)] (1·DMF) shows a discrete mononuclear molecule with nine-coordinated {EuN3O6} distorted tricapped-trigonal prism (TTP) coordination geometry around the Eu(III). The {EuN3O6} core results from three nitrogen atoms and three carboxylate oxygen atoms, and two carbonyl oxygen atoms of the amide groups of dtntp ligand. The ninth coordination site is occupied by an oxygen atom of DMF as a solvent from crystallization. The designed probes have two aromatic pendant phenyl-terpyridine (Ph-tpy) moieties as photo-sensitizing antennae to impart the desirable optical properties for cellular imaging and photocytotoxicity. The photostability, coordinative saturation, and energetically rightly poised triplet states of dtntp ligand allow the efficient energy transfer (ET) from Ph-tpy to the emissive excited states of the Eu(III)/Tb(III), makes them luminescent cellular imaging probes. The Ln(III) complexes show significant binding tendency to DNA (K ~ 104 M−1), and serum proteins (BSA and HSA) (K ~ 105 M−1). The luminescent Eu(III) (1) and Tb(III) (2) complexes were utilized for cellular internalization and cytotoxicity studies due to their optimal photophysical properties. The cellular uptake studies using fluorescence imaging displayed intracellular (cytosolic and nuclear) localization in cancer cells. The complexes 1 and 2 displayed significant photocytotoxicity in HeLa cells. These results offer a modular design strategy with further scope to utilize appended N,N,N-donor tpy moiety for developing light-responsive luminescent Ln(III) bioprobes for theranostic applications.

Dinuclear lanthanoid(III) dithiocarbamato complexes bridged by (E)-N-benzylidenepicolinohydrazonate: Syntheses, crystal structures and spectroscopic properties

(E)-N-Benzylidenepicolinohydrazide (Hbphz) was used to synthesize a series of hydrazonato-bridged homodinuclear LnIII2 dithiocarbamato (RR′dtc−) complexes of the form [{Ln(RR′ dtc)2}2(µ-bphz)2] {Ln = La, Pr, Nd, Sm or Eu; RR′ = dimethyl-(Me2) or pyrrolidine-(pyr)}. X-ray crystallographic studies revealed that these complexes possessed a common head-to-tail type dinuclear structural motif in which two hydrazonato ligands bridged two LnIII centers in the μ − 1 κ2N(py),O:2 κ2O,N(imine) mode and two RR′dtc ligands coordinated to each LnIII center. Interestingly, while the SmIII and EuIII complexes crystallized as simple 8:8-coordinate dinuclear molecules, the lighter LnIII (i.e. LaIII, PrIII and NdIII) complexes afforded in some cases 9:9-coordinate molecules, where the ninth coordination site was occupied by a solvent ethanol or methanol molecule. Even for the lighter LnIII complexes, the complexes were solved in dichloromethane or chloroform as the 8:8-coordinate dimer, as revealed by 1H NMR spectroscopy. In the UV–visible absorption and magnetic circular dichroism (MCD) spectra of the complexes, similar spectral patterns for ligand-centered and Laporte forbidden f–f transitions were observed. The MCD spectral studies demonstrated the characteristic magneto-optical behavior of the complexes.

Water soluble Eu(III) complexes of macrocyclic triamide ligands: Structure, stability, luminescence and redox properties

Two macrocyclic triamide octadentate chelator scaffolds L1 and L2 were synthesized, characterized by several spectroscopic techniques, and their pKa values were determined by potentiometric titration. Using these ligands, two water soluble paramagnetic Eu(III) complexes, [EuL1(OH2)](NO3)3·H2O (EuL1) and [EuL2(OH2)](NO3)3·H2O (EuL2) were synthesized and characterized in the solid state and in solution. Single crystal X ray diffraction measurement of [EuL1(OH2)](NO3)3.H2O (EuL1) reveals octadentate binding of the ligand to Eu(III) and ninth coordination being completed by an oxygen atom of a solvent molecule (H2O). X-ray diffraction data of [EuL2(OH2)](NO3)3·H2O (EuL2) were severely disordered and hence its chloride analogue [EuL2(DMF)]Cl3·H2OMeOH (EuL2-Cl) was synthesized and characterized using single-crystal X-ray diffraction measurements. The crystal data of [EuL2(DMF)](Cl)3·H2OMeOH (EuL2-Cl) reveal octadentate binding of the ligand to Eu(III), with the ninth coordination being completed by an oxygen atom of a solvent molecule (DMF). Luminescence measurements confirm the presence of a water molecule coordinated to Eu(III) in aqueous solution. The stability of the Eu(III) complexes was investigated using spectrophotometric molar ratio method. Cyclic voltammetry studies obtained from aqueous solutions of the Eu(III) complexes show reversible one electron reduction processes at the glassy carbon electrode with E1/2 = −0.799 V and −0.777 V (versus Ag/AgCl) for the complexes of L1 and L2.

Lanthanide appended rotaxanes respond to changing chloride concentration

Lanthanide appended rotaxanes have been prepared by the CuAAC ‘click’ reaction between an azide appended rotaxane and lanthanide complexes of propargyl DO3A. The resulting complexes are luminescent, and exhibit chloride responsive luminescence behavior consistent with the existence of two independent halide binding pockets, one in the rotaxane cavity and one on the ninth (axial) coordination site of the lanthanide. Strong halide binding to europium gives rise to changes in the relative intensity of the hypersensitive ΔJ = 2 transition compared to the rest of the europium emission spectrum, combined with quenching of the overall intensity of emission as a consequence of non-radiative quenching by the bound halide. The weaker interaction with the rotaxane pocket mediates a subsequent recovery of intensity of the europium centered luminescence despite the considerable separation between the lanthanide and the rotaxane binding pocket.

A pH-Sensitive, Colorful, Lanthanide-Chelating Paramagnetic NMR Probe

Paramagnetic lanthanides ions are broadly used in NMR spectroscopy. The effects of unpaired electrons on NMR spectral parameters provide a powerful tool for the characterization of macromolecular structures and dynamics. Here, a new lanthanide-chelating NMR probe, Caged Lanthanide NMR Probe-7 (CLaNP-7), is presented. It can be attached to protein surfaces via two disulfide bridges, yielding a probe that is rigid relative to the protein backbone. CLaNP-7 extends the application range of available probes. It has a yellow color, which is helpful for sample preparation. Its effects are comparable to those of CLaNP-5, but its charge is two units lower (+1) than that of CLaNP-5 (+3), reducing the change in surface potential after probe attachment. It also has a different magnetic susceptibility tensor, so by using both tags, two sets of structural restraints can be obtained per engineered cysteine pair. Moreover, it was found that the orientation of the magnetic susceptibility tensor is pH dependent (pK(a) ≈ 7) when a histidine residue is located in the neighborhood of the probe attachment site. The results show that the His imidazole group interacts with the CLaNP-7 tag. It is proposed that the histidine residue forms a hydrogen bond to a water/hydroxyl molecule that occupies the ninth coordination position on the lanthanide, thus breaking the two-fold symmetry of the CLaNP tag in a pH-dependent way.

Positively Charged Lanthanide Complexes with Cyclen-Based Ligands: Synthesis, Solid-State and Solution Structure, and Fluoride Interaction

The syntheses of a new cyclen-based ligand L(2) containing four N-[2-(2-hydroxyethoxy)ethyl]acetamide pendant arms and of its lanthanide(III) complexes [LnL(2)(H(2)O)]Cl(3) (Ln = La, Eu, Tb, Yb, or Lu) are reported, together with a comparison with some Ln(III) complexes of a previously reported analogue L(1) in which two opposite amide arms have been replaced by coordinating pyridyl units. The structure and dynamics of the La(III), Lu(III), and Yb(III) complexes in solution were studied by using multinuclear NMR investigations and density functional theory calculations. Luminescence lifetime measurements in H(2)O and D(2)O solutions of the [Ln(L(2))(H(2)O)](3+) complexes (Ln = Eu or Tb) were used to investigate the number of H(2)O molecules coordinated to the metal ion, pointing to the presence of an inner-sphere H(2)O molecule in a buffered aqueous solution. Fluoride binding to the latter complexes was investigated using a combination of absorption spectroscopy and steady-state and time-resolved luminescence spectroscopy, pointing to a surprisingly weak interaction in the case of L(2) (log K = 1.4 ± 0.1). In contrast to the results in solution, the X-ray crystal structure of the lanthanide complex showed the ninth coordination position occupied by a chloride anion. In the case of L(1), the X-ray structure of the [(EuL(1))(2)F] complex features a bridging fluoride donor with an uncommon linear Eu-F-Eu entity connecting two almost identical [Eu(L(1))](3+) units. Encapsulation of the F(-) anion within the two complexes is assisted by π-π stacking between the pyridyl rings of two complexes and C-H···F hydrogen-bonding interactions involving the anion and the pyridyl units.

Lanthanide complexes of DOTA monoamide derivatives bearing an isophthalate pendent arm

An isophthalate-bearing DOTA monoamide derivative has been synthesised and used to prepare a family of lanthanide complexes. Luminescence and NMR studies in solution show that the predominant form of the complexes in solution is a mono-capped square antiprism about the lanthanide centre, in which a solvent molecule occupies the ninth coordination site. The crystal structure of the terbium complex is presented and is in close agreement with the solution state data.

Correlation of sulfur atoms in nonmetal planes of lead sulfide films with the D03 structure

The distribution of sulfur atoms S and vacancies □ in planar square and hexagonal nonmetal sublattices formed by the 4(b) and 8(c) sites in PbS nanocrystalline films with the cubic D03 structure and latent stoichiometry has been investigated. It has been demonstrated using the computer simulation that, in Sy□1 − y solid solutions with square and hexagonal lattices, the appearance of a correlation between the S atoms and □ vacancies in the first coordination shell leads to the appearance of correlations in the second and subsequent coordination shells. An increase in the radius of the coordination shell leads to a decrease in the magnitude of induced correlations, and the correlations completely decay in the ninth coordination shell. The functional dependence between the correlation in the first coordination shell and the induced correlations in the subsequent coordination shells has been established for different compositions of the Sy□1 − y solid solution. The results of the simulation can be used to refine the crystal structure of nanocrystalline films and particles of lead sulfide.

Conformational behaviour determines the low-relaxivity state of a conditional MRI contrast agent

The conformational behaviour in aqueous solution of the EgadMe complex, a conditional gadolinium-based contrast agent sensitive to beta-galactosidase enzymatic activity, is investigated by means of ab initio calculations and classical molecular dynamics simulations. Furthermore, force field parameterization of gadolinium-ligand interactions is performed, and its reliability is tested on the bench mark [Gd(DOTA)](-) system by MD simulations. Both computational methods highlight the presence in EgadMe of two main conformational isomers. The lowest energy conformation is a "close" form, corresponding to a state of low-relaxivity (MRI "inactive"), in which the ninth coordination site of the gadolinium ion is occupied by one oxygen atom of the galactopyranose residue. The second isomer, which is 2.9 (at ab initio level) and 4.2 (at MD level) kcal mol(-1) above the global minimum, presents an "open" form, corresponding to a state of high-relaxivity (MRI "active") in which one water molecule coordinates the ion. These results are consistent with experimental findings reported for EgadMe, and show that competition at the ninth coordination site of gadolinium ion, between the intra (the galactopyranose residue) and inter (water molecules) molecular interactions, affects the relaxivity of this system.

Lanthanide Complexes Based on a 1,7-Diaza-12-crown-4 Platform Containing Picolinate Pendants: A New Structural Entry for the Design of Magnetic Resonance Imaging Contrast Agents

We have synthesized a new macrocyclic ligand, N,N'-Bis[(6-carboxy-2-pyridyl)methyl]-1,7-diaza-12-crown-4 (H 2bp12c4), designed for complexation of lanthanide ions in aqueous solution. The X-ray crystal structure of the Gd (III) complex shows that the metal ion is directly bound to the eight donor atoms of the bp12c4 ligand, the ninth coordination site being occupied by an oxygen atom of a carboxylate group of a neighboring [Gd(bp12c4)] (+) unit, while the structure of the Lu (III) analogue shows the metal ion being only eight-coordinate. The hydration numbers obtained from luminescence lifetime measurements in aqueous solution of the Eu (III) and Tb (III) complexes suggest an equilibrium in aqueous solution between a dihydrated ( q = 2), ten-coordinate and a monohydrated ( q = 1), nine-coordinate species. This has been confirmed by a variable temperature UV-vis spectrophotometric study on the Eu (III) complex. The structure of the complexes in solution has been investigated by (1)H and (13)C NMR spectroscopy, as well as by theoretical calculations performed at the DFT (B3LYP) level. The results indicate that the change in hydration number occurring around the middle of the lanthanide series is accompanied by a change in the conformation adopted by the complexes in solution [Delta(lambdalambdalambdalambda) for q = 2 and Lambda(deltalambdadeltalambda) for q = 1]. The structure calculated for the Yb (III) complex (Lambda(deltalambdadeltalambda)) is in good agreement with the experimental structure in solution, as demonstrated by the analysis of the Yb (III)-induced paramagnetic (1)H shifts.

Short-range order and pair correlations in a binary solid solution with a square lattice

Using the example of a disordered AyB1 − y solid solution whose atoms are distributed over squarelattice sites, it is shown that correlations in the first coordination shell inevitably cause correlations in the second and more distant coordination shells. These induced correlations decay with distance extending to the ninth coordination shell in a square lattice. The induced correlations are calculated as a function of the correlation in the first coordination shell for binary solid solutions with various compositions. This dependence is described by a third-degree polynomial in the first-shell correlation to within the computational accuracy. The coefficients of the polynomial calculated in this paper using computer simulation can be useful in developing short-range order theory and in calculating the phase diagrams of binary solid solutions.

Modeling of short-range order in a defect square lattice

The short-range order and pair correlations in a square lattice in which some part of sites are occupied by A atoms and the other are vacant have been investigated by computer simulation. It is shown that, in the presence of interactions in the first coordination sphere of an A y □1 − y solid solution with a square lattice, induced pair correlations damp only in the ninth coordination sphere. A functional dependence between the correlation in the first coordination sphere and the induced correlations in the next coordination spheres has been established for different compositions of the solid solution.

Density-functional theory structures of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complexes for ions across the lanthanide series

The use of organically chelated lanthanides in diagnosis and treatment is a rapidly growing field in medicine. In order to gain a deeper understanding into the properties of these chelates, particularly spectroscopic, density-functional calculations have been performed on a series of lanthanide ions chelated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Based on the results of these calculations, it has been concluded that the local symmetry experienced by the chelated lanthanide ion may be treated as being axial, which will make the interpretation of their spectroscopic properties greatly simplified. It has also been suggested that the so-called "capping" water molecule at the ninth coordination position of the lanthanide is hydrogen bonded to the acetate oxygens of the sidearms, rather than coordinated as the ninth ligand of the lanthanide.

Complexation Properties of N,N′,N″,N′′′‐[1,4,7,10‐Tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(1‐oxoethane‐2,1‐diyl)]tetrakis[glycine] (H4dotagl). Equilibrium, Kinetic, and Relaxation Behavior of the Lanthanide(III) Complexes

AbstractEu3+, Dy3+, and Yb3+ complexes of the dota‐derived tetramide N,N′,N″,N′′′‐[1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(1‐oxoethane‐2,1‐diyl)]tetrakis[glycine] (H4dotagl) are potential CEST contrast agents in MRI. In the [Ln(dotagl)] complexes, the Ln3+ ion is in the cage formed by the four ring N‐atoms and the amide O‐atom donor atoms, and a H2O molecule occupies the ninth coordination site. The stability constants of the [Ln(dotagl)] complexes are ca. 10 orders of magnitude lower than those of the [Ln(dota)] analogues (H4dota=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid). The free carboxylate groups in [Ln(dotagl)] are protonated in the pH range 1–5, resulting in mono‐, di‐, tri‐, and tetraprotonated species. Complexes with divalent metals (Mg2+, Ca2+, and Cu2+) are also of relatively low stability. At pH>8, Cu2+ forms a hydroxo complex; however, the amide H‐atom(s) does not dissociate due to the absence of anchor N‐atom(s), which is the result of the rigid structure of the ring. The relaxivities of [Gd(dotagl)] decrease from 10 to 25°, then increase between 30–50°. This unusual trend is interpreted with the low H2O‐exchange rate. The [Ln(dotagl)] complexes form slowly, via the equilibrium formation of a monoprotonated intermediate, which deprotonates and rearranges to the product in a slow, OH−‐catalyzed reaction. The formation rates are lower than those for the corresponding Ln(dota) complexes. The dissociation rate of [Eu(dotagl)] is directly proportional to [H+] (0.1–1.0M HClO4); the proton‐assisted dissociation rate is lower for [Eu(H4dotagl)] (k1=8.1⋅10−6 M−1 s−1) than for [Eu(dota)] (k1=1.4⋅10−5 M−1 s−1).

Structural and photophysical behaviour of lanthanide complexes with a tetraazacyclododecane featuring carbamoyl pendant arms †

The crystal and molecular structure of 1,4,7,10-tetrakis(N-benzylcarbamoylmethyl)-1,4,7,10-tetraazacyclododecane, L1, revealed an S2-symmetric molecule. One pair of pendant arms is involved in intramolecular hydrogen bonding while the other interacts with two other ligand molecules through strong intermolecular hydrogen bonds. In solution, the ligand adopts a similar geometrical arrangement at low temperature but complexes with EuIII and LuIII display an averaged C4-symmetry on the NMR timescale. One isomer only was detected, as reported for similar complexes, and the arrangement around EuIII and LuIII appears to be rigid while it is more fluxional around LaIII. Rotation of the benzyl group around the amide function was observed for EuIII and a dynamic NMR study in the range 253–333 K yielded ΔH ‡ = 43.0 ± 0.1 kJ mol–1, ΔS ‡ = –49.3 ± 0.4 J K–1 mol–1 and k298 = 47.7 ± 1.1 s–1. In the solid state, anhydrous eight-co-ordinate complexes were isolated and high resolution luminescence spectroscopy of EuIII in the europium and Eu-doped compounds of La, Gd and Lu confirmed a site symmetry close to C4 along the lanthanide-series. Energy transfer from the L13ππ* state to the Tb(5D4) excited state is sizable leading to an absolute quantum yield of 6.4% in MeCN, while the EuIII luminescence is only poorly sensitized, possibly because of photoinduced electron transfer processes. The Tb(5D4) and Eu(5D0) lifetimes for both solid state samples and solutions in MeCN are consistent with no water molecule in the inner co-ordination sphere but addition of water results in the ninth co-ordination site being bound to H2O: number of bound waters, q = 0.96 (Eu) and 0.71 (Tb) in MeCN + 2 M H2O and 1.19 (Eu) and 1.30 (Tb) in water. The relaxivity r1 of the gadolinium(III) complex is pH dependent and varies between 4.08 (pH 0.8), 1.88 (6.7) and 6.14 (11.1) mM–1 s–1.

Synthesis and Structure of a New Macrocyclic Polyhydroxylated Gadolinium Chelate Used as a Contrast Agent for Magnetic Resonance Imaging.

Three approaches to the synthesis of a new ligand 1,4,7-tris(carboxymethyl)-10-(1-(hydroxymethyl)-2,3-dihydroxypropyl)-1,4,7,10-tetraazacyclododecane (6) are described. This ligand forms the both thermodynamically and kinetically very stable gadolinium chelate Gadobutrol (1), which is a neutral and highly hydrophilic compound that is used for magnetic resonance imaging in the clinic. According to the crystal structure the Gd(III) ion in 1 is nine coordinated. The ligand provides eight coordination sites whereas the ninth coordination partner surprisingly is a carboxylate oxygen of a neighboring centrosymmetrically-related complex molecule. Ligand 6 was also utilized to prepare the calcium complex 12 which is used as an additive in the pharmaceutical formulation of 1. For the calcium complex 12, two complex molecules adopting almost identical conformations are present in the crystal.

Highly polydentate ligands. Part 4. Crystal structures of neodymium(III) and erbium(III) complexes of 3,12-bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecanedioate(4–)

The structures of calcium salts of the erbium(III) and neodymium(III) chelates of the calcium-selective octadentate ligand egta4–[H4egta = 3,12-bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecanedioic acid] have been determined, in order to identify the structural changes that occur in a calcium-selective binding site when lanthanides are substituted for calcium. Ca[Er(egta)(OH2)]2·12H2O·(CH3)2CO (1) crystallizes in the monoclinic space group P21(Z= 2), with a= 12.710(2), b= 12.157(2), c= 17.765(3)A, and β= 105.79(1)°R= 0.027, R′= 0.035. Ca[Nd(egta)(OH2)]2·9H2O (2) crystallizes in the monoclinic space group P21/c(Z= 2), with a= 10.776(2), b= 18.218(4), c= 12.560(2)A, and β= 112.14(1)°; R= 0.028, R′= 0.040. The full octadentate chelating capability of egta4– is utilized in both chelates. In contrast to the eight-co-ordinate calcium ions in [Ca(egta)]2–, the ErIII ions in (1) are nine-co-ordinate; the ninth co-ordination site is occupied by a water molecule. Of the three ligand atom types, the carboxylate oxygen atoms are bound at the shortest distance [Er–O(carboxylate)av= 2.31(3)A], followed by the ether oxygen atoms [Er–O(ether)av= 2.42(5)A], and the amine nitrogen atoms [Er–Nav= 2.57(4)A]. The NdIII ions in (2) are ten-co-ordinate; ten-co-ordination is achieved in the solid state by binding a water molecule, as well as a carboxylate oxygen atom from an adjacent complex ion The order of metal–Iigand bond distances observed for NdIII is the same as that observed for ErIII Nd–O(carboxylate)av= 2.46(1), Nd–O(ether)av= 2.67(3), Nd–Nav= 2.81(7)A.

Selected properties of beryllium clusters in ab initio model approximations

Results of ab initio self-consistent field calculations are reported for electronic states of beryllium clusters comprised of 13, 19, 21, 33, 39, 51, 57, and 63 atoms. The clusters correspond to the second through ninth coordination shells of a central Be atom with internuclear separations taken from the lattice constants of the bulk hcp metal. Effective core potentials have been employed to replace the 1s core electrons, thereby reducing the complexity of the calculations. In addition, the use of the full D/sub 3h/ point group symmetry of each cluster results in substantial reductions of the number of two-electron integrals that must be computed and processed. Properties are calculated for selected electronic states and include binding energy, orbital energies, electric field gradient, nuclear-electron potential, diamagnetic shielding constant, second moments, and Mulliken populations. Overall net charges, second moments, and nuclear potentials become approximately constant in the larger clusters, indicating bulk behavior.

Kinetics of ligand exchange between a uranium(IV) β-diketonate and free β-diketone

The intermolecular ligand exchange kinetics between a uranium(IV) β-diketonate and free β-diketone were studied by 1H nmr as a function of temperature and concentration. The reaction was found to be of first order in both chelate and free ligand. The results suggest that the exchange mechanism involves a ninth coordination site in the uranium(IV) chelate.