Multifunctional Heterometallic IrIII -AuI Probes as Promising Anticancer and Antiangiogenic Agents.

A new class of emissive cyclometallated IrIII -AuI complexes with a bis(diphenylphosphino) methanide bridging ligand was successfully synthesised from the diphosphino complex [Ir(N^C)2 (dppm)]+ (1). The different gold ancillary ligand, a triphenylphosphine (2), a chloride (3) or a thiocytosine (4) did not reveal any significant effect on the photophysical properties, which are mainly due to metal-to-ligand charge-transfer (3 MLCT) transitions based on IrIII . However, the AuI fragment, along with the ancillary ligand, seemed crucial for the bioactivity in A549 lung carcinoma cells versus endothelial cells. Both cell types display variable sensitivities to the complexes (IC50 =0.6-3.5 µM). The apoptotic pathway is activated in all cases, and paraptotic cell death seems to take place at initial stages in A549 cells. Species 2-4 showed at least dual lysosomal and mitochondrial biodistribution in A549 cells, with an initial lysosomal localisation and a possible trafficking process between both organelles with time. The bimetallic IrIII -AuI complexes disrupted the mitochondrial transmembrane potential in A549 cells and increased reactive oxygen species (ROS) generation and thioredoxin reductase (TrxR) inhibition in comparison with that displayed by the monometallic complex 1. Angiogenic activity assays performed in endothelial cells revealed the promising antimetastatic potential of 1, 2 and 4.

Heterotrimetallic Mixed-Valent Molecular Precursors Containing Periodic Table Neighbors: Assignment of Metal Positions and Oxidation States.

A known trinuclear structure was used to design the heterobimetallic mixed-valent, mixed-ligand molecule [CoII (hfac)3 -Na-CoIII (acac)3 ] (1). This was used as a template structure to develop heterotrimetallic molecules [CoII (hfac)3 -Na-FeIII (acac)3 ] (2) and [NiII (hfac)3 -Na-CoIII (acac)3 ] (3) via isovalent site-specific substitution at either of the cobalt positions. Diffraction methods, synchrotron resonant diffraction, and multiple-wavelength anomalous diffraction were applied beyond simple structural investigation to provide an unambiguous assignment of the positions and oxidation states for the periodic table neighbors in the heterometallic assemblies. Molecules of 2 and 3 are true heterotrimetallic rather than a statistical mixture of two heterobimetallic counterparts. Trinuclear platform 1 exhibits flexibility in accommodating a variety of di- and trivalent metals, which can be further utilized in the design of molecular precursors for the NaMM'O4 functional oxide materials.

Aluminates with Fluorinated Schiff Bases: Influence of the Alkali Metal⁻Fluorine Interactions in Structure Stabilization.

New heterometallic aluminium-alkali metal compounds have been prepared using Schiff bases with electron withdrawing substituents as ligands. The synthesis of these new species was achieved via the reaction of AlMe3 with the freshly prepared alkali-metallated ligand. The derivatives formed were characterized by NMR in solution and by single crystal X-ray diffraction in the solid state. Aluminate derivatives with lithium and sodium were prepared and a clear influence of the alkali metal in the final outcome is observed. The presence of a Na···F interaction in the solid state has a stabilization effect and the species [NaAlMe3L]2 can de isolated for the first time, which was not possible when using Schiff bases without electron withdrawing substituents as ligands.

A Nona-nuclear Heterometallic Pd3 Pt6 "Donut"-Shaped Cage: Molecular Recognition and Photocatalysis.

We report a simple, low-symmetry 2-(1-(pyridine-4-methyl)-1H-1,2,3-triazol-4-yl)pyridine ligand that has both monodentate and bidentate binding sites. With platinum(II) and/or palladium(II) ions, two examples of a new nona-nuclear metallo-assembly have been accessed. These complexes were characterized by NMR spectroscopy, electrospray mass spectrometry (ESI-MS), and in key cases, X-ray crystallography. The cages possess three clefts comprised of planar cationic panels. This structural feature enables the binding of planar aromatic guests such as anthracene. More interestingly, the heterometallic assembly was able to catalyze the light-induced [4+2] cycloaddition of anthracene with singlet oxygen.

Effects of Metal Blending in Random Bimetallic Single-Chain Magnets: Synergetic, Antagonistic, or Innocent.

A family of isomorphous three-dimensional metal-organic frameworks based on bimetallic (FeCo, FeNi, and CoNi) chains with random metal sites have been prepared and magnetically characterized. The solid-solution-type bimetallic materials inherit intrachain ferromagnetic interactions and single-chain-magnet (SCM) behaviors from the homometallic parent materials. Interestingly, different composition dependence of magnetic behaviors has been found. The FeII1-x NiIIx series (0≤x≤1) show an innocent composition dependence, where the blocking temperature of slow relaxation decreases monotonically as FeII is replaced by less anisotropic NiII . The FeII1-x CoIIx series show an unexpected antagonistic blending effect on slow relaxation: blending FeII and CoII tends to depress the spin dynamics, and the bimetallic materials with intermediate composition show significantly lower blocking temperature than both FeII and CoII materials. This is quite the opposite of what happens in the Co1-x Nix series, where CoII and NiII seem to have a synergetic effect so that slow relaxation in bimetallic systems can be promoted to higher temperature than both CoII and NiII materials.

Use of Supramolecular Assemblies as Lithographic Resists.

A new resist material for electron beam lithography has been created that is based on a supramolecular assembly. Initial studies revealed that with this supramolecular approach, high-resolution structures can be written that show unprecedented selectivity when exposed to etching conditions involving plasmas.

Synthetically important alkali-metal utility amides: lithium, sodium, and potassium hexamethyldisilazides, diisopropylamides, and tetramethylpiperidides.

Most synthetic chemists will have at some point utilized a sterically demanding secondary amide (R2 N(-) ). The three most important examples, lithium 1,1,1,3,3,3-hexamethyldisilazide (LiHMDS), lithium diisopropylamide (LiDA), and lithium 2,2,6,6-tetramethylpiperidide (LiTMP)-the "utility amides"-have long been indispensible particularly for lithiation (Li-H exchange) reactions. Like organolithium compounds, they exhibit aggregation phenomena and strong Lewis acidity, and thus appear in distinct forms depending on the solvents employed. The structural chemistry of these compounds as well as their sodium and potassium congeners are described in the absence or in the presence of the most synthetically significant donor solvents tetrahydrofuran (THF) and N,N,N',N'-tetramethylethylenediamine (TMEDA) or closely related solvents. Examples of hetero-alkali-metal amides, an increasingly important composition because of the recent escalation of interest in mixed-metal synergic effects, are also included.

Preparation of Titanocene-Gold Compounds Based on Highly Active Gold(I)-N-Heterocyclic Carbene Anticancer Agents: Preliminary in†vitro Studies in Renal and Prostate Cancer Cell Lines.

Heterometallic titanocene-based compounds containing gold(I)-phosphane fragments have been extremely successful against renal cancer in vitro and in vivo. The exchange of phosphane by N-heterocyclic carbene ligands to improve or modulate their pharmacological profile afforded bimetallic complexes effective against prostate cancer, but less effective against renal cancer in vitro. Herein we report the synthesis of new bimetallic Ti-Au compounds by the incorporation of two previously reported highly active gold(I)-N-heterocyclic carbene fragments derived from 4,5-diarylimidazoles. The two new compounds [(η5 -C5 H5 )2 TiMe(µ-mba)Au(NHC)] (where NHC=1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene, NHC-Bn 2 a; or 1,3-diethyl-4,5-diphenylimidazol-2-ylidene, NHC-Et 2 b) with the dual linker (-OC(O)-p-C6 H4 -S-) containing both a carboxylate and a thiolate group were evaluated in vitro against renal and prostate cancer cell lines. The compounds were found to be more cytotoxic than previously described Ti-Au compounds containing non-optimized gold(I)-N-heterocyclic fragments. We present studies to evaluate their effects on cell death pathways, migration, inhibition of thioredoxin reductase (TrxR) and vascular endothelial growth factor (VEGF) in the PC3 prostate cancer cell line. The results show that the incorporation of a second metallic fragment such as titanocene into biologically active gold(I) compounds improves their pharmacological profile.