Thermodynamic parameters governing the self-assembly of head-head-head lanthanide bimetallic helicates

The heterobitopic ligands L ABX (X=1, 2, 3, 4 or 5), differing only by a Cl or NEt(2) substituent, have been designed to complex with a pair of lanthanide ions to form triple-stranded bimetallic helicates of overall composition [Ln2(L ABX)3]6+. The percentage of HHH (head-head-head) isomer, in which each of the three ligand strands coordinates to the same lanthanide ion with the same coordination unit, is deciding the ability of the ligands to selectively form heterobimetallic complexes containing one luminescent and one magnetic or two different luminescent ions. It deviates significantly from the statistical value of 25 % and ranges from 6-20 % for L AB2 complexes to 93-96 % for L AB4 complexes. The equilibrium between HHT (head-head-tail) and HHH isomers has been investigated in detail for homobimetallic helicates (Ln=Y, La, Ce, Pr, Nd, Sm, Eu, Lu) by means of variable temperature NMR and thermodynamic parameters have been determined. The equilibrium is characterized by small values of DeltaH and DeltaS, which vary in opposite direction along the lanthanide series for complexes with the same ligand in a way that keeps the value of DeltaG almost constant. The results are interpreted in terms of differences in interstrand stacking, ion-dipole interactions and metal-metal repulsion.     

A novel extended covalent tripod for assembling nine-coordinate lanthanide(III) podates: a delicate balance between flexibility and rigidity

The introduction of long semirigid spacers between the capping carbon atom of the tripod and the unsymmetrical tridentate binding units provides the novel, extended covalent podand tris-[2-[2-(6-diethylcarbamoylpyridin-2-yl)-1-ethyl-1H-benzoimidazol-5-yl-methoxy]ethyl]methane (L(15)). Reaction of L(15) with lanthanide(III) in acetonitrile produces stable podates [Ln(L(15))](3+) (Ln=La-Lu) in which three tridentate binding units are facially organized. These wrap around the nine-coordinate pseudo-tricapped trigonal-prismatic metal ions. The crystal structure of [La(L(15))](ClO(4))(3) (18, LaC(67)H(82)N(12)O(18)Cl(3), trigonal, R3c, Z=6) reveals the formation of a C(3)-symmetrical triple-helical podate. Two slightly different arrangements of the flexible ethylenoxy parts of the spacer are observed in the solid state in agreement with the formation of two conformational isomers (M:m) in a 4:1 ratio. A qualitative analysis of the aromatic diamagnetic anisotropies affecting the NMR signals of [Ln(L(15))](3+) (Ln=La, Y, Lu) in solution, combined with the quantitative determination of electron-induced relaxation in the paramagnetic complex [Nd(L(15))](3+), demonstrate that the solid state structure is maintained in solution. This leads to a mixture of two triple-helical conformers of similar stabilities and that do not interconvert on the NMR timescale between 243 and 343 K. Particular attention has been given to the structural programming of extended covalent tripods for facially organizing unsymmetrical tridentate binding units around Ln(III). Photophysical measurements show that L(15) efficiently protects the metallic coordination spheres and sensitizes Eu(III) and Tb(III) upon UV irradiation.     

Thermodynamics, structure and properties of polynuclear lanthanide complexes with a tripodal ligand: insight into their self-assembly

Self-assembly processes between a tripodal ligand and Ln(III) cations have been investigated by means of supramolecular analytical methods. At an equimolar ratio of components, tetranuclear tetrahedral complexes are readily formed in acetonitrile. The structural analysis of the crystallographic data shows a helical wrapping of binding strands around metallic cations. The properties of this series of highly charged 3D compounds were examined by using NMR spectroscopy and optical methods in solution and in the solid state. In the presence of excess metal, a new trinuclear complex was identified. The X-ray crystal structure elucidated the coordination of metallic cations with two ligands of different conformations. By varying the metal/ligand ratio, a global speciation of this supramolecular system has been evidenced with different spectroscopic methods. In addition, these rather complicated equilibria were successfully characterised with the thermodynamic stability constants. A rational analysis of the self-assembly processes was attempted by using the thermodynamic free energy model and the impact of the ligand structure on the effective concentration is discussed.     

Adjustment of twist angles in pseudo-helical lanthanide complexes by the size of metal ions

Control of self-assembled nanostructures is a promising technique for nanotechnology. We have examined as to whether nanostructures could be controlled by the size of the central metal ion. Lanthanides are a natural choice for such a study as the size of their trivalent ions changes with atomic number gradually. For this investigation, a series of rare earth complexes ([LaL(1)], [CeL(1)], [SmL(1)], [TbL(1)], [YL(1)], and [LuL(1)]) with a tripodal heptadentate ligand L(1) were synthesized, and their X-ray crystallographic analysis was performed. Although the structures of the ligand (H(3)L(1)) and of the metal complex ([ML(1)]) were quite different, all complexes were almost isostructural pseudohelices. The result of the crystallographic studies demonstrated that the twist angles of helices in the complexes depend on the ionic size of the central metal. A detailed analysis helped determine which portion of the helical strand contributed to the total helicity, and the major cause for the difference in helicity among the lanthanides is discussed. Moreover, this result is the first example showing that La(I) (II) and Lu(I) (II) complexes with the same tripodal heptadentate ligand are isostractural.     

A simple thermodynamic model for quantitatively addressing cooperativity in multicomponent self-assembly processes--Part 2: Extension to multimetallic helicates possessing different binding sites

The extended site-binding model, which explicitly separates intramolecular interactions (i.e., intermetallic and interligand) from the successive binding of metal ions to polytopic receptors, is used for unravelling the self-assembly of trimetallic double-stranded Cu(I) and triple-stranded Eu(III) helicates. A thorough analysis of the available stability constants systematically shows that negatively cooperative processes operate, in strong contrast with previous reports invoking either statistical behaviours or positive cooperativity. Our results also highlight the need for combining successive generations of complexes with common binding units, but with increasing metallic nuclearities, for rationalizing and programming multicomponent supramolecular assemblies.     

Silver baits for the "miraculous draught" of amphiphilic lanthanide helicates

The axial connection of flexible thioalkyls chains of variable length (n=1–12) within the segmental bis‐tridentate 2‐benzimidazole‐8‐hydroxyquinoline ligands [ L12 ^Cn?2 H]^2? provides amphiphilic receptors designed for the synthesis of neutral dinuclear lanthanides helicates. However, the stoichiometric mixing of metals and ligands in basic media only yields intricate mixtures of poorly soluble aggregates. The addition of Ag^I in solution restores classical helicate architectures for n=3, with the quantitative formation of the discrete D₃‐symmetrical [Ln₂Ag2( L12 ^C3?2 H)₃]²⁺ complexes at millimolar concentration (Ln=La, Eu, Lu). The X‐ray crystal structure supports the formation of [La₂Ag₂( L12 ^C3?2 H)₃][OTf]₂, which exists in the solid state as infinite linear polymers bridged by S‐Ag‐S bonds. In contrast, molecular dynamics (MD) simulations in the gas phase and in solution confirm the experimental diffusion measurements, which imply the formation of discrete molecular entities in these media, in which the sulfur atoms of each lipophilic ligand are rapidly exchanged within the Ag^I coordination sphere. Turned as a predictive tool, MD suggests that this Ag^I templating effect is efficient only for n=1–3, while for n>3 very loose interactions occur between Ag^I and the thioalkyl residues. The subsequent experimental demonstration that only 25 % of the total ligand speciation contributes to the formation of [Ln₂Ag₂( L12 ^C12?2 H)₃]²⁺ in solution puts the bases for a rational approach for the design of amphiphilic helical complexes with predetermined molecular interfaces.     

The first self-assembled trimetallic lanthanide helicates driven by positive cooperativity

The segmental tris-tridentate ligand L7 reacts with stoichiometric quantities of Ln(III) (Ln=La-Lu) in acetonitrile to give the complexes [Ln(2)(L7)(3)](6+) and [Ln(3)(L7)(3)](9+). Formation constants point to negligible size-discriminating effects along the lanthanide series, but Scatchard plots suggest that the self-assembly of the trimetallic triple-stranded helicates [Ln(3)(L7)(3)](9+) is driven to completion by positive cooperativity, despite strong intermetallic electrostatic repulsions. Crystallization provides quantitatively [Ln(3)(L7)(3)](CF(3)SO(3))(9) (Ln=La, Eu, Gd, Tb, Lu) and the X-ray crystal structure of [Eu(3)(L7)(3)](CF(3)SO(3))(9).(CH(3)CN)(9).(H(2)O)(2) (Eu(3)C(216)H(226)N(48)O(35)F(27)S(9), triclinic, P1, Z=2) shows the three ligand strands wrapped around a pseudo-threefold axis defined by the three metal ions rigidly held at about 9 A. Each metal ion is coordinated by nine donor atoms in a pseudo-trigonal prismatic arrangement, but the existence of terminal carboxamide units in the ligand strands differentiates the electronic properties of the terminal and the central metallic sites. Photophysical data confirm that the three coordination sites possess comparable pseudo-trigonal symmetries in the solid state and in solution. High-resolution luminescence analyses evidence a low-lying LMCT state affecting the central EuN(9) site, so that multi-metal-centered luminescence is essentially dominated by the emission from the two terminal EuN(6)O(3) sites in [Eu(3)(L7)(3)](9+). New multicenter equations have been developed for investigating the solution structure of [Ln(3)(L7)(3)](9+) by paramagnetic NMR spectroscopy and linear correlations for Ln=Ce-Tb imply isostructurality for these larger lanthanides. NMR spectra point to the triple helical structure being maintained in solution, but an inversion of the magnitude of the second-rank crystal-field parameters, obtained by LIS analysis, for the LnN(6)O(3) and LnN(9) sites with respect to the parameters extracted for Eu(III) from luminescence data, suggests that the geometry of the central LnN(9) site is somewhat relaxed in solution.     

Ruthenium(II) as a novel "labile" partner in thermodynamic self-assembly of heterobimetallic d-f triple-stranded helicates

Unsymmetrical substituted bidentate benzimidazol-2-ylpyridine ligands L2 and L3 react with [Ru(dmso)(4)Cl(2)] in ethanol to give statistical 1:3 mixtures of fac-[Ru(Li)(3)](2+) and mer-[Ru(Li)(3)](2+) (i=2, 3; DeltaGtheta(isomerisation)=-2.7 kJ mol(-1)). In more polar solvents (acetonitrile, methanol), the free energy of the facial<=>meridional isomerisation process favours mer-[Ru(Li)(3)](2+), which is the only isomer observed in solution at the equilibrium (DeltaGtheta(isomerisation)< or = -11.4 kJ mol(-1)). Since the latter process takes several days for [Ru(L2)(3)](2+), fac-[Ru(L2)(3)](2+) and mer-[Ru(L2)(3)](2+) have been separated by chromatography, but the 28-fold increase in velocity observed for [Ru(L3)(3)](2+) provides only mer-[Ru(L3)3](ClO(4))2 after chromatography (RuC(60)H(51)N(9)O(8)Cl(2), monoclinic, P2(1)/n, Z=4). The facial isomer can be stabilised when an appended tridentate binding unit, connected at the 5-position of the benzimidazol-2-ylpyridine unit in ligand L1, interacts with nine-coordinate lanthanides(III). The free energy of the facial<=>meridional isomerisation is reversed (DeltaGtheta(isomerisation)> or =11.4 kJ mol(-1)), and the Ru--N bonds are labile enough to allow the quantitative thermodynamic self-assembly of HHH-[RuLu(L1)(3)]5+ within hours ([RuLu(L1)3](CF(3)SO(3))(4.5)Cl(0.5)(CH(3)OH)(2.5): RuLuC(106)H(109)Cl(0.5)N(21)O(19)S(4.5)F(13.5), triclinic, P(-)1, Z=2). Electrochemical and photophysical studies show that the benzimidazol-2-ylpyridine units in L1-L3 display similar pi-acceptor properties to, but stronger pi-donor properties than, those found in 2,2'-bipyridine. This shifts the intraligand pi-->pi* and the MLCT transitions toward lower energies in the pseudo-octahedral [Ru(Li)(3)](2+) (i=2, 3) chromophores. The concomitant short lifetime of the (3)MLCT excited state points to efficient, thermally activated quenching via low-energy Ru-centred d-d states, a limitation which is partially overcome by mechanical coupling in HHH-[RuLu(L1)(3)]5+.     

Readily prepared metallo-supramolecular triple helicates designed to exhibit spin-crossover behaviour

New dinuclear supramolecular cylinders have been designed to exhibit spin-crossover behaviour, a form of molecular bistability. This has been achieved within the framework of our imine-based approach to supramolecular architecture by switching from pyridylimine systems to imidazolimines. Spin-crossover behaviour is achieved while retaining the simplicity and ease-of-synthesis of our molecular design. The imidazole groups used also introduce additional NH groups that engage in hydrogen-bonding to anions and solvents. In the case of the iron(II) tetrafluoroborate complex this hydrogen bonding links supramolecular cylinders into an extended two-dimensional array. Consistent with this, a sharper spin-crossover transition is observed for this compound than for the corresponding hexafluorophosphate salt. More subtle anion effects are indicated in the perchlorate salt which gives a two-step spin conversion, thereby displaying tristability.     

Tuning the polarization along linear polyaromatic strands for rationally inducing mesomorphism in lanthanide nitrate complexes

The opposite orientation of the ester spacers in the rodlike ligands L 4C12 (benzimidazole-OOC-phenyl) and L 5C12 (benzimidazole-COO-phenyl) drastically changes the electronic structure of the aromatic systems, without affecting their meridional tricoordination to trivalent lanthanides, Ln(III), and their thermotropic liquid crystalline (i.e., mesomorphic) behaviors. However, the rich mesomorphism exhibited by the complexes [Ln(L 4C12)(NO3)3] (Ln=La-Lu) vanishes in [Ln(L 5C12)(NO3)3], despite superimposable molecular structures and comparable photophysical properties. Density functional theory (DFT) and time-dependant DFT calculations performed in the gas phase show that the inversion of the ester spacers has considerable effects on the electronic structure and polarization of the aromatic groups along the strands, which control residual intermolecular interactions responsible for the formation of thermotropic liquid-crystalline phases. As a rule of thumb, an alternation of electron-poor and electron-rich aromatic rings favors intermolecular interactions between the rigid cores and consequently mesomorphism, a situation encountered for L 4C12, L 5C12, [Ln(L 4C12)(NO3)3], but not for [Ln(L 5C12)(NO3)3]. The intercalation of an additional electron-rich diphenol ring on going from [Ln(L 5C12)(NO3)3] to [Ln(L 6C12)(NO3)3] restores mesomorphism despite an unfavorable orientation of the ester spacers, in agreement with our simple predictive model.     

A versatile ditopic ligand system for sensitizing the luminescence of bimetallic lanthanide bio-imaging probes

The homoditopic ligand 6,6'-[methylenebis(1-methyl-1H-benzimidazole-5,2-diyl)]bis(4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}pyridine-2-carboxylic acid) (H(2)L(C2)) has been tailored to self-assemble with lanthanide ions (Ln(III)), which results in the formation of neutral bimetallic helicates with the overall composition [Ln(2)(L(C2))(3)] and also provides a versatile platform for further derivatization. The grafting of poly(oxyethylene) groups onto the pyridine units ensures water solubility, while maintaining sizeable thermodynamic stability and adequate antenna effects for the excitation of both visible- and NIR-emitting Ln(III) ions. The conditional stability constants (log beta(23)) are close to 25 at physiological pH and under stoichiometric conditions. The ligand triplet state features adequate energy (0-phonon transition at approximately 21 900 cm(-1)) to sensitize the luminescence of Eu(III) (Q=21 %) and Tb(III) (11 %) in aerated water at pH 7.4. The emission of several other VIS- and NIR-emitting ions, such as Sm(III) (Q=0.38 %) or Yb(III) (0.15 %), for which in cellulo luminescence is evidenced for the first time, is also sensitized. The Eu(III) emission spectrum arises from a main species with pseudo-D(3) symmetry and without coordinated water. The cell viability of several cancerous cell lines (MCF-7, HeLa, Jurkat and 5D10) is unaffected if incubated with up to 500 microM [Eu(2)(L(C2))(3)] during 24 h. Bright Eu(III) emission is seen for incubation concentrations above 10 microM and after a 15-minute loading time; similar images are obtained with Tb(III) and Sm(III). The helicates probably permeate into the cytoplasm of HeLa cells by endocytosis. The described luminescent helical stains are robust chemical species which remain undissociated in the cell medium and in presence of other complexing agents, such as edta, dtpa, citrate or L-ascorbate. Their derivatization, which would open the way to the sensing of targeted in cellulo phenomena, is currently under investigation.     

Equilibrium and Kinetic Properties of the Lanthanoids(III) and Various Divalent Metal Complexes of the Heptadentate Ligand AAZTA

Towards improved kinetic stability : A detailed account of the complexation properties of the ligand 1,4‐bis(hydroxycarbonylmethyl)‐6‐[bis(hydroxycarbonylmethyl)]amino‐6‐methylperhydro‐1,4‐diazepine (AAZTA; see figure) is reported. Its Gd³⁺ complex shows a kinetic stability superior to that of complexes formed by higher denticity ligands and opens the way for a new reference structure for MRI contrast agents.