Ghenadie Novitchi

Heterometallic CuII/DyIII 1D chiral polymers: chirogenesis and exchange coupling of toroidal moments in trinuclear Dy3 single molecule magnets

The first example of exchange coupling between the toroidal moments in chiral heterometallic CuII/DyIII 1D polymers built from alternating trinuclear Dy3 SMM-building blocks and chiral copper(II) complexes is reported. A very strong toroidal magnetization can be induced by applying a magnetic field at low temperature in single-crystals of these compounds.

A Top‐Down Synthesis Route to Ultrasmall Multifunctional Gd‐Based Silica Nanoparticles for Theranostic Applications

New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid)-Gd(3+) chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd(3+) by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID) and electron paramagnetic resonance (EPR) to demonstrate the dissolution of the oxide core and by inductively coupled plasma mass spectrometry (ICP-MS), mass spectrometry, fluorescence spectroscopy, (29)Si solid-state NMR, (1)H NMR and diffusion ordered spectroscopy (DOSY) to determine the nanoparticle composition. Relaxivity measurements gave a longitudinal relaxivity r1 of 11.9 s(-1)  mM(-1) per Gd at 60 MHz. Finally, potentiometric titrations showed that Gd(3+) is strongly chelated to DOTAGA (complexation constant logβ110 =24.78) and cellular tests confirmed the that nanoconstructs had a very low toxicity. Moreover, SRPs are excreted from the body by renal clearance. Their efficiency as contrast agents for MRI has been proved and they are promising candidates as sensitising agents for image-guided radiotherapy.

Probing Lanthanide Anisotropy in Fe–Ln Aggregates by Using Magnetic Susceptibility Measurements and 57Fe Mössbauer Spectroscopy

The use of lanthanides to modulate the magnetic properties of transition-metal single-molecule magnets has become more common in recent years, mainly as a result of the magnetic anisotropy of some lanthanides that can increase the blocking temperature for reversal of magnetization. The main technique used to probe the reorientation of the magnetisation is ac magnetic susceptibility, but this technique yields only averaged magnetic moment information. Another more sensitive technique is Fe Mçssbauer spectroscopy, which can give information about oxidation levels and spin states, local moments at the iron nuclei, and spin-relaxation dynamics, and, more importantly, about the anisotropy not only of the studied isotope, but also of elements interacting with this isotope. Herein, the magnetic properties of complexes containing iron and lanthanide (or rareearth) cations have been probed by a combination of both Mçssbauer spectroscopy and magnetic susceptibility measurements. Reaction between FeCl2·4 H2O, Ln ACHTUNGTRENNUNG(NO3)3·6H2O, pivalic acid, H4edte (N,N,N’,N’-tetrakis-(2-hydroxyethyl)ethylenediamine) and phenol in a 1:0.5:5:1:1 molar ratio in MeCN/ CH2Cl2 gave a red solution from which light red crystals of isomorphous compounds [FeIII4Ln2ACHTUNGTRENNUNG(m4-O)2ACHTUNGTRENNUNG(NO3)2ACHTUNGTRENNUNG(piv)6ACHTUNGTRENNUNG(Hedte)2]·x CH3CN·y CH2Cl2·z C6H5OH, (Ln =Y (1, x= 2.3, y=1.7, z=0), Gd (2, x=1.8, y= 2.2, z=0), Dy (3, x= 4, y=0, z=1)) deposited after 24 h. The structure of the Dy compound 3 is described here. The central core of the aggregate possesses a [FeIII4Dy2ACHTUNGTRENNUNG(m4-O)2]14+ architecture with the four Fe ions arranged in what is often termed a “butterfly” shape, although here the Fe centers are strictly coplanar. Each Fe3 triangle is connected to the capping Dy through m4-O bridges, which are thus displaced out of such a triangle comprising one wingand two body-iron atoms, for example, Fe(2), Fe(1), and Fe(1’) bridged to Dy(1) through O(1) (Figure 1). Peripheral ligation is provided by one nitrato and one pivalato ligand chelating Dy(1), four m-pivalato ligands in their common syn,syn bridging mode between body-iron atoms and Dy centers, and two triply deprotonated (Hedte) ions. Each Hedte ligand chelates Fe(2) through its two nitrogens and provides three m-alkoxo oxygen bridges from Fe(2) to Fe(1), Fe(1’), and Dy(1), respectively. The fourth protonated arm of each Hedte ligand does not coordinate, but forms an intermolecular hydrogen bond to a chelating pivalato oxygen atom of a neighboring molecule, forming 1D supramolecular chains. Taking the structural information of Fe4Y2 (1) into account, the general spin-Hamiltonian describing the isotropic [a] M. N. Akhtar, Dr. V. Mereacre, Dr. G. Novitchi, Dr. C. E. Anson, Prof. Dr. A. K. Powell Institut f r Anorganische Chemie, Universit t Karlsruhe Engesserstrasse 15, 76128 Karlsruhe (Germany) Fax: (+49) 721-608-8142 E-mail : powell@aoc.uni-karlsruhe.de [b] Prof. Dr. J.-P. Tuchagues Laboratoire de Chimie de Coordination du CNRS, UPR 8241 205 Route de Narbonne, 31077 Toulouse Cedex 04 (France) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200900758. Figure 1. Molecular structure of 3 (molecule 1). Solvent molecules, disordered atoms, and organic H atoms have been omitted for clarity.

Benzoxazole-Based Heterometallic Dodecanuclear Complex [DyIII4CuII8] with Single-Molecule-Magnet Behavior

Three Cu-Ln (Ln = Dy, Gd, Y) dodecanuclear clusters assembled by a novel ligand of the benzoxazole type are reported. The dysprosium cluster exhibits a frequency dependence of the alternating-current susceptibility and hysteresis loop at low temperature, indicating single-molecule-magnet behavior.

A single molecule magnet (SMM) with a helicate structure

The X-ray structure determination of [L2Cu2Gd2(NO3)6(H2O)2](0.5H2O) (L = bis-[(2-hydroxy-3-ethoxyphenyl)methylene]-4,4′-methylenedianiline) confirms the existence of a tetranuclear double-stranded homotopic and unsaturated helicate. In each Cu–Gd pair, the reduced Cu⋯Gd distance allows ferromagnetic Cu–Gd superexchange interactions through two phenoxo oxygen atoms. Replacement of gadolinium ions by terbium ions yields the first example of a helicate behaving as a single molecule magnet (SMM).

Ferromagnetic heteronuclear {Fe4(Er,Lu)2} cyclic coordination clusters based on ferric wheels

A new family of hexanuclear ferric-lanthanide [Fe(III)(4)Ln(III)(2)(Htea)(4)(Piv)(6)(N(3))(4)] clusters, where Ln(III) = Er(1) and Lu(2) is reported. Variable temperature solid-state magnetic susceptibility studies of 1 and 2 reveal the presence of ferromagnetic (1) or competing anti- and ferromagnetic exchange interactions (2) between the constituent Fe(III) ions.

L- and D-proline thiosemicarbazone conjugates: coordination behavior in solution and the effect of copper(II) coordination on their antiproliferative activity.

Two enantiomerically pure thiosemicarbazone-proline conjugates with enhanced aqueous solubility, namely, 2-hydroxy-3-methyl-(S)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [L-Pro-STSC or (S)-H(2)L] and 2-hydroxy-3-methyl-(R)-pyrrolidine-2-carboxylate-5-methylbenzaldehyde thiosemicarbazone [D-Pro-STSC or (R)-H(2)L] have been synthesized and characterized by elemental analysis, spectroscopic methods (UV-vis and (1)H and (13)C NMR), and electrospray ionization mass spectrometry. The metal complexation behavior of L-Pro-STSC, stoichiometry, and thermodynamic stability of iron(II), iron(III), copper(II), and zinc(II) complexes in 30% (w/w) dimethyl sulfoxide/H(2)O solvent mixture have been studied by pH-potentiometric, UV-vis-spectrophotometric, circular dichroism, electron paramagnetic resonance, (1)H NMR spectroscopic, and spectrofluorimetric measurements. By the reaction of CuCl(2)·2H(2)O with (S)-H(2)L and (R)-H(2)L, respectively, the complexes [Cu[(S)-H(2)L]Cl]Cl and [Cu[(R)-H(2)L]Cl]Cl have been prepared and comprehensively characterized. An X-ray diffraction study of [Cu[(R)-H(2)L]Cl]Cl showed the formation of a square-planar copper(II) complex, which builds up stacks with interplanar separation of 3.3 Å. The antiproliferative activity of two chiral ligands and their corresponding copper(II) complexes has been tested in two human cancer cell lines, namely, SW480 (colon carcinoma) and CH1 (ovarian carcinoma). The thiosemicarbazone-proline conjugates L- and D-Pro-STSC show only moderate cytotoxic potency with IC(50) values of 62 and 75 μM, respectively, in CH1 cells and >100 μM in SW480 cells. However, the corresponding copper(II) complexes are 13 and 5 times more potent in CH1 cells, based on a comparison of IC(50) values, and in SW480 cells the increase in the antiproliferative activity is even higher. In both tested cell lines, L-Pro-STSC as well as its copper(II) complex show slightly stronger antiproliferative activity than the compounds with a D-Pro moiety, yielding IC(50) values of 4.6 and 5.5 μM for [Cu(L-Pro-STSC)Cl]Cl in CH1 and SW480 cells, respectively.

Lanthanide Triangles Sandwiched by Tetranuclear Copper Complexes Afford a Family of Hendecanuclear Heterometallic Complexes [LnIII3CuII8] (Ln = La–Lu): Synthesis and Magnetostructural Studies

Reaction in ethanol of 3-hydroxymethylen-5-methylsalicylaldoxime (H3L) with CuCl2·2H2O and LnCl3·xH2O [Ln = La (1), Ce (2), Pr (3), Nd (4), Eu (5), Gd (6), Tb (7), Dy (8), Er (9), Yb (10), Lu (11), Ho (12)] allowed the synthesis of a family of hendecanuclear heterometallic copper(II)-lanthanide(III) clusters with general formula [Ln(III)3Cu(II)8(HL)6(μ4-O)2Cl6(H2O)8]Cl3 (1-12). According to the single-crystal X-ray diffraction investigation, the complexes are isomorphous and crystallize in the trigonal R32 group. The hendecanuclear cluster is formed by two tetrahedral μ4-oxo {Cu4} clusters assembled by three lanthanide ions sandwiched in between. Along the family, the separation between the {Cu4} moieties increases linearly from Lu to La in good correlation with ionic radius of the lanthanide ions. A comparative analysis of the magnetic data for the lanthanum (1) and lutetium (11) compounds shows the presence of ferromagnetic and antiferromagnetic interactions within the μ4-oxo {Cu4} moieties. For the gadolinium (6) and terbium (7) compounds, the magnetic interactions between the lanthanide and the copper ions are found to be ferromagnetic. The dysprosium (8) compound exhibits single-molecule magnet behavior.

Striking difference in antiproliferative activity of ruthenium- and osmium-nitrosyl complexes with azole heterocycles.

Ruthenium nitrosyl complexes of the general formulas (cation)+[cis-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (Hind) (1c), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (Hpz) (2c), (cation)+ = (H2bzim)+, Hazole = 1H-benzimidazole (Hbzim) (3c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (Him) (4c) and (cation)+[trans-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (1t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (2t), as well as osmium analogues of the general formulas (cation)+[cis-OsCl4(NO)(Hazole)]−, where (cation)+ = (n-Bu4N)+, Hazole =1H-indazole (5c), 1H-pyrazole (6c), 1H-benzimidazole (7c), 1H-imidazole (8c), (cation)+ = Na+; Hazole =1H-indazole (9c), 1H-benzimidazole (10c), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11c), (cation)+ = H2pz+, Hazole = 1H-pyrazole (12c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (13c), and (cation)+[trans-OsCl4(NO)(Hazole)]−, where (cation)+ = n-Bu4N+, Hazole = 1H-indazole (5t), 1H-pyrazole (6t), (cation)+ = Na+, Hazole = 1H-indazole (9t), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (12t), have been synthesized. The compounds have been comprehensively characterized by elemental analysis, ESI mass spectrometry, spectroscopic techniques (IR, UV–vis, 1D and 2D NMR) and X-ray crystallography (1c·CHCl3, 1t·CHCl3, 2t, 3c, 6c, 6t, 8c). The antiproliferative activity of water-soluble compounds (1c, 1t, 3c, 4c and 9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c) in the human cancer cell lines A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma) has been assayed. The effects of metal (Ru vs Os), cis/trans isomerism, and azole heterocycle identity on cytotoxic potency and cell line selectivity have been elucidated. Ruthenium complexes (1c, 1t, 3c, and 4c) yielded IC50 values in the low micromolar concentration range. In contrast to most pairs of analogous ruthenium and osmium complexes known, they turned out to be considerably more cytotoxic than chemically related osmium complexes (9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c). The IC50 values of Os/Ru homologs differ by factors (Os/Ru) of up to ∼110 and ∼410 in CH1 and SW480 cells, respectively. ESI-MS studies revealed that ascorbic acid may activate the ruthenium complexes leading to hydrolysis of one M–Cl bond, whereas the osmium analogues tend to be inert. The interaction with myoglobin suggests nonselective adduct formation; i.e., proteins may act as carriers for these compounds.

Synthesis and characterization of multinuclear manganese-containing tungstosilicates

The five manganese-containing, Keggin-based tungstosilicates [Mn(II)3(OH)3(H2O)3(A-α-SiW9O34)](7-) (1), [Mn(III)3(OH)3(H2O)3(A-α-SiW9O34)](4-) (2), [Mn(III)3(OH)3(H2O)3(A-β-SiW9O34)](4-) (3), [Mn(III)3Mn(IV)O3(CH3COO)3(A-α-SiW9O34)](6-) (4), and [Mn(III)3Mn(IV)O3(CH3COO)3(A-β-SiW9O34)](6-) (5) were synthesized in aqueous medium by interaction of [A-α-SiW9O34](10-) or [A-β-SiW9O34H](9-) with either MnCl2 (1) or [Mn(III)8Mn(IV)4O12(CH3COO)16(H2O)4] (2-5) under carefully adjusted reaction conditions. The obtained salts of these polyanions were analyzed in the solid state by single-crystal X-ray diffraction, IR spectroscopy, and thermogravimetric analysis. The salts of polyanions 1, 2, and 4 were further characterized in the solid state by magnetic studies, as well as in solution by electrochemistry.