Lanthanide complexes of DOTA-nitroxide conjugates for redox imaging: spectroelectrochemistry, CEST, relaxivity, and cytotoxicity.

The lanthanide(iii) complexes (Gd, Eu, Dy, and Yb) of DOTA tris(amide) and bis(amide) derivatives (L1 and L2) featuring one redox active TEMPO arm were prepared. Ligand L2 harbours an alkyne fragment for further functionalization. The X-ray crystal structure of ligand L2 in complexation with Na+ was solved. The complexes showed in their CV one oxidation wave (0.26-0. 34 V vs. Fc+/Fc) due to an oxoammonium/nitroxide redox couple and a broad reduction corresponding to the nitroxide/hydroxylamine system. The Eu complexes demonstrated the presence of one water molecule in their coordination sphere. The nitroxide complexes were characterized by EPR spectroscopy, showing the typical 3-line pattern in the high temperature regime, which is quenched upon the addition of ascorbate (reduction into hydroxylamine). In their nitroxide form, the complexes show essentially no CEST peak. Conversely, the reduced complexes demonstrate a 12% CEST peak at 51 ppm, corresponding to the metal bound water molecule. Fast exchange precluded the CEST activity for the amide protons. All the complexes proved to be essentially non-toxic for M21 cells at concentrations up to 50 µM.

Distorted copper(ii) radicals with sterically hindered salens: electronic structure and aerobic oxidation of alcohols.

The sterically hindered salen ligands featuring biphenyl and tetramethyl putrescine linkers were synthesized and chelated to copper. The resulting complexes CuLbp,tBu, CuLbp,OMe, CuLpu,tBu and CuLpu,OMe were structurally characterized, showing a significanty tetrahedrally distorted metal center. The complexes show two reversible oxidation waves in the range 0.2 to 0.8 V vs. Fc+/Fc. A further reduction wave is detected in the range -1.4 to -1.7 V vs. Fc+/Fc. It is reversible for CuLbp,tBu and CuLbp,OMe and assigned to the CuII/CuI redox couple. One-electron oxidation of CuLbp,OMe, CuLpu,tBu and CuLpu,OMe was performed chemically and electrochemically. It is accompanied by a quenching of the EPR resonances. Phenoxyl radical formation was established by X-Ray diffraction on the cations [CuLbp,OMe]+ and [CuLpu,OMe]+, whereby the coordination sphere is elongated upon oxidation with quinoidal distributions of bond distances. The cations exhibit a NIR band of moderate intensity in their optical spectrum, supporting their classification as class II mixed-valent radical species according to the Robin Day classification. The proposed electronic structures are supported by DFT calculations. The cations [CuLbp,OMe]+, [CuLpu,tBu]+ and [CuLpu,OMe]+ were active towards aerobic oxidation of the unactivated alcohol 2-phenylethanol, with TON numbers up to 58 within 3 h.

Structural and spectroscopic investigations of nine-coordinate redox active lanthanide complexes with a pincer O,N,O ligand.

The lanthanide complexes EuL3, GdL3, YbL3 and LuL3 of the N,N'-bis(2-hydroxy-di-3,5-tert-butylphenyl)amine were prepared. The X-Ray crystal structures of GdL3 and LuL3 demonstrated a nine-coordinate sphere with three ligand molecules under their anionic diamagnetic form (Cat-N-BQ)-. The complexes showed three oxidation events (Eox11/2 = 0.15-0.16 V, E1/22 = 0.51-55 V, and E1/23 = 0.75-0.78 V vs. Fc+/Fc) via cyclic voltammetry, corresponding to the successive oxidation of the aminophenolate moeities to iminosemiquinone species. The complexes GdL3 and YbL3 were characterized by EPR spectroscopy, allowing for the determination of the zero field splitting (ZFS) parameters in the first case. The monocations (LnL3)+ and monoanions (LnL3)- were electrochemically generated (Ln = Eu, Gd, Yb, Lu), as well as the dications YbL32+ and LuL32+. The spins are antiferromagnetically exchange coupled in the diradical species LuL32+ (|D| = 260 MHz, E = 0). All the complexes (incl. neutral) possess a strong absorption band in the NIR region (730-840 nm, ε > 19 mM-1 cm-1) corresponding to ligand-based transitions.

Structural snapshots of the rearrangement of the bis(di-tert-butyl-aminophenyl)amine pincer ligand in the presence of transition metal ions.

The bis(di-tert-butyl-aminophenyl)amine ligand H3LN,N,N was reacted with Mn(ii), Co(ii), Fe(iii) and Cu(ii) salts in air. The ligand undergoes oxidative transformations, which involve intra and intermolecular C-N and N-N bond formations. A rare aromatic C-N bond cleavage leading to a C-O bond has also been observed.

Tetranuclear and dinuclear phenoxido bridged copper complexes based on unsymmetrical thiosemicarbazone ligands.

We report on the synthesis of new dinucleating phenol-based "end-off" compartmental ligands HLMeH and HLMe2 bearing two different binding sites, one bis(2-methylpyridyl)aminomethyl (BPA) and one thiosemicarbazone (TSC) site, and their corresponding copper(ii) complexes 1t and 2d. With the ligand HLMeH, a tetranuclear entity (1t) has been isolated in the solid state, whereas with HLMe2, which differs from HLMeH by a methyl substituent on the N-terminal amino group of the TSC arm, a dinuclear form (2d) is obtained. X-ray crystallography analysis shows that the nuclearity di vs. tetra is modulated by interactions between copper atoms and hydroxido bridges along with the sulphur atoms of TSC arms. From a magnetic point of view, 1t can be considered as an association of two dinuclear forms leading for both complexes to overall antiferromagnetic coupling. Analysis in acetonitrile solution of structure-property relationships has been carried out by comparing their UV/Vis, electrochemistry, ESI-MS, and NMR (variable temperature and DOSY = diffusion ordered spectroscopy) properties with trends from computational calculations (DFT). HRMAS-DOSY (High Resolution Magic Angle Spinning) NMR spectroscopy has been performed to evaluate the presence of different species in solution at room temperature.

A redox active switch for lanthanide luminescence in phenolate complexes.

The reversible oxidation of coordinated phenolates into phenoxyl radicals results in a dramatic quenching (>95%) of the luminescence of the f metal ion.

Unprecedented redox-driven ligand ejection in nickel(II)-diiminosemiquinonate radical complexes.

Nickel(II) complexes of (M : L) stoichiometries 1 : 1 (1) and 1 : 2 (2) were prepared from a polydentate ligand involving diiminosemiquinonate radicals. Both were characterized by X-ray diffraction, Vis-NIR and EPR spectroscopy as well as electrochemistry. Ligand-centered oxidation of 1 promotes ligand ejection to give 2.

Spin interaction in octahedral zinc complexes of mono- and diradical Schiff and mannich bases.

The four Schiff bases 2-tert-butyl-4-methoxy-6-[(pyridin-2-ylmethylimino)methyl]phenol, 2,4-di-tert-butyl-6-[(pyridin-2-ylmethylimino)methyl]phenol, 2-tert-butyl-4-methoxy-6-(quinolin-8-yliminomethyl)phenol, and 2,4-di-tert-butyl-6-(quinolin-8-yliminomethyl)phenol) as well as one Mannich base, N,N',N,N'-bis[(2-hydroxy-3,5-di-tert-butylbenzyl)(2-pyridylmethyl)]ethylenediamine, and their zinc bis-phenolate complexes 1-5, respectively, have been prepared. The complexes 4 and 5 have been characterized by X-ray diffraction crystallography, showing a zinc ion within an octahedral environment, with a cis orientation of the phenolate moieties. 1-5 exhibit in their cyclic voltammetry curves two anodic reversible waves attributable to the successive oxidation of the phenolates into phenoxyl radicals. Bulk electrolysis at ca. +0.1 V affords the zinc-coordinated monophenoxyl radical species (1(*))(+)-(5(*))(+) characterized by UV-vis absorption bands at 400-440 nm. The more stable radicals are (3(*))(+) and (4(*))(+) (half-life higher than 90 min at 298 K), likely due to the increased charge delocalization within the quinoline moieties. These species exhibit a significant additional near-IR band (epsilon > 1650 M(-1) cm(-1)) attributed to a CT transition. In the two-electron-oxidized species (1(**))(2+)-(5(**))(2+) the radical spins present a weak magnetic coupling. EPR reveals an antiferromagnetic exchange interaction for (1(**))(2+)-(4(**))(2+), whereas an unusual ferromagnetic exchange coupling is operative in (5(**))(2+). The weak magnitude of experimental |J| values (within the 1-5 cm(-1) range) as well as their sign could be well reproduced by DFT calculations at the B3LYP level. The small energy gap between the ground and the first excited spin states allows us to investigate the zero-field splitting (ZFS) of the triplet by EPR spectroscopy. This parameter is found to be axial for all systems, with |D| values of 0.0163 cm(-1) for (1(**))(2+), 0.0182 cm(-1) for (2(**))(2+), 0.0144 cm(-1) for (3(**))(2+), 0.0160 cm(-1) for (4(**))(2+), and 0.0115 cm(-1) for (5(**))(2+). The trend between experimental ZFS is confirmed by DFT calculations, which give further insight regarding its sign (negative for all the compounds). Lower ZFS values are obtained for (2(**))(2+) compared to (1(**))(2+) (and also for (4(**))(2+) compared to (3(**))(2+)), which can be interpreted by an increased delocalization of the spin density over the methoxy para substituent. Significant spin population on the quinoline also contributes to a lowering of the |D| value, as observed when (3(**))(2+) is compared to (1(**))(2+) (and also when (4(**))(2+) is compared to (2(**))(2+)).

Dicopper(II) complexes of H-BPMP-type ligands: pH-induced changes of redox, spectroscopic ((19)F NMR studies of fluorinated complexes), structural properties, and catecholase activities.

Substitution of the methyl group from the H-BPMP (HL(CH)3) ligand (2,6-bis[(bis(2-pyridylmethyl)amino)methyl]-4-methylphenol) by electron withdrawing (F or CF(3)) or electron donating (OCH(3)) groups afforded a series of dinucleating ligand (HL(OCH)3, HL(F), HL(CF)3), allowing one to understand the changes in the properties of the corresponding dicopper complexes. Dinuclear Cu(II) complexes have been synthesized and characterized by spectroscopic (UV-vis, EPR, (1)H NMR) as well as electrochemical techniques and, in some cases, by single-crystal X-ray diffraction: [Cu(2)(L(OCH)3)(muOH)][(ClO(4))(2)].C(4)H(8)O, [Cu(2)(L(F))(muOH)][(ClO(4))(2)], [Cu(2)(L(F))(H(2)O)(2)][(ClO(4))(3)].C(3)D(6)O, and [Cu(2)(L(CF)3)(H(2)O)(2)][(ClO(4))(3)].4H(2)O. Significant differences are observed for the Cu-Cu distance in the two mu-hydroxo complexes (2.980 A (R = OCH(3)) and 2.967 A (R = F)) compared to the two bis aqua complexes (4.084 A (R = F) and 4.222 A (R = CF(3))). The mu-hydroxo and bis aqua complexes are reversibly interconverted upon acid/base titration. In basic medium, new species are reversibly formed and identified as the bis hydroxo complexes except for the complex from HL(CF)3 which is irreversibly transformed near pH = 10. pH-driven interconversions have been studied by UV-vis, EPR, and (1)H NMR, and the corresponding pK are determinated. In addition, with the fluorinated complexes, the changes in the coordination sphere around the copper centers and in their redox states are evidenced by the fluorine chemical shift changes ((19)F NMR). For all the complexes described here, investigations of the catechol oxidase activities (oxidation of 3,5-di-tert-butylcatechol to the corresponding quinone) are of interest in modeling the catecholase enzyme active site and in understanding aspects of structure/reactivity. These studies show the pH-dependence for the catalytic abilities of the complexes, related with changes in the coordination sphere of the metal centers: only the mu-hydroxo complexes from HL(CH)3, HL(F), and HL(OCH)3 exhibit a catecholase activity. Modification on R-substituent induces a drastic effect on the catecholase activity: the presence of an electron donating group on the ligand increases this activity; the reverse effect is observed with an electron withdrawing group.

(1S)-(Z)-2-benzyloxy-N-(3-methyl-1-butylidene)-1-phenylethylamine N-oxide.

The preparation and crystal structure of the title compound, C(20)H(25)NO(2), are described. The N atom substituent of the nitrone function adopts a conformation which minimizes the 1,3-allylic strain.

N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D-galactopyranosyloxy)succinimide.

The crystal structure of the title compound, C18H24N2O11, a GalNAc mimic containing an alpha-glycosyloxysuccinimide linkage, has been determined. The pyranose ring geometry is an almost perfect (4)C(1) chair. The torsion angle of the exocyclic hydroxymethyl group is shown to be gauche-trans with respect to O1 and C4, respectively.

Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxyamino-alpha-D-glucopyranoside.

The crystalline-state conformation of the title compound, C(29)H(29)NO(9), has been established unequivocally. The R absolute configuration is observed at the 4-methoxyamino moiety and the pyranose ring adopts essentially a perfect (4)C(1) chair. The torsion angle of the exocyclic hydroxymethyl group is shown to be gauche--gauche with respect to O1 and C4, respectively. The conformation along the methoxyamino bond is consistent with that observed for calicheamicin gamma(1)(I).

First chiral selenium ylides used for asymmetric conversion of aldehydes into epoxides.

Enantioenriched selenonium ylides have been generated by addition of benzyl bromide to C2 symmetric (2R,5R)-2,5-dimethylselenolane in the presence of NaOH, and subsequently reacted with a variety of aldehydes to give oxiranes with excellent enantiomeric excesses (a catalytic version has been achieved); also, an aliphatic cyclic hypervalent dibromoselenurane structure has been demonstrated by X-ray analysis.

(1R,2s,3S,6R,9S)-5,5,10,10-tetrachloro-2-methyltricyclo

The title compound, C(12)H(10)Cl(4)O(2), has a pseudoasymmetric centre at the methyl-substituted carbon and, in the solid state, a boat-like conformation.

Self-recognition based on atropoisomerism with new chiral bidentate ligands and copper(I)

A new family of atropoisomeric bidentate ligands that have a dissymmetric benzimidazole-pyridine binding site has been synthesized. Aromatic rings, that is, naphthyl, tolyl and cumyl, were introduced in order to fine tune the complexation properties of the ligands. The tetrahedral copper(I) complexes L2Cu were prepared and the structure of the complex with the naphthyl-substituted ligand was established by X-ray diffraction. The behavior of the L2Cu complexes in solution was studied by 1H NMR spectroscopy. With the most crowded cumyl-derived ligand, ligand self-recognition based on chirality occured: 95% of the complex was present in solution as a racemate RRdelta/SSlambda, the heterochiral RSdelta/SRlambda isomers represented only 5 % of the mixture, and the RRlambda/SSdelta isomers were not detected. Owing to lower steric repulsions within the other L2Cu complexes (i.e., with the naphthyl- and tolyl-based ligands) the homorecognition is less pronounced, as diastereomeric excesses of 6 and 26% were measured, respectively.