Design of inhibitors for amyloid-β (Aβ) peptide aggregation has been widely investigated over the years towards developing viable therapeutic agents for Alzheimer’s disease (AD). The biggest challenge seems to be inhibiting Aβ aggregation at the early stages of aggregation possibly at the monomeric level, as oligomers are known to be neurotoxic. In this regard, exploiting the metal chelating property of Aβ to generate molecules that can overcome this impediment presents some promise. Recently, one such metal complex containing PtII ([Pt(BPS)Cl2]) was reported to effectively inhibit Aβ42 aggregation and toxicity (1). This complex was able bind to Aβ42 at the N-terminal part of the peptide and triggered a conformational change resulting in effective inhibition. In the current report, we have generated a mixed-binuclear metal complex containing PtII and RuII that inhibited Aβ42 aggregation at an early stage of aggregation and seemed to have different modes of interaction than the previously reported PtII complex, suggesting an important role of the second metal center. This ‘proof-of-concept’ compound will help in developing more effective molecules against Aβ aggregation by modifying the two metal centers as well as their ligands, which will open doors to new rationale for Aβ inhibition.
The title compound, [Co3Na2(C7H2ClNO4)4(H2O)12][Co(C7H2ClNO4)(H2O)3]2·6H2O, consists of a centrosymmetric dimer of [CoII(dipicCl)2]2− complex dianions [dipicCl is 4-chloropyridine-2,6-dicarboxylate] bridged by an [Na2CoII(H2O)12]4+ tetracationic cluster, two independent [Co(dipicCl)(H2O)3] complexes, and six water molecules of crystallization. The metals are all six-coordinate with distorted octahedral geometries. The [CoII(dipicCl)(H2O)3] complexes are neutral, with one tridentate ligand and three water molecules. The [CoII(dipicCl)2]2− complexes each have two tridentate ligands. The [Na2CoII(H2O)12]4+ cluster has a central CoII ion which is coordinated to six water molecules and lies on a crystallographic inversion center. Four of the water molecules bridge to two sodium ions, each of which have three other water molecules coordinated along with an O atom from the [CoII(dipicCl)2]2− complex. In the crystal structure, the various units are linked by O—H⋯O hydrogen bonds, forming a three-dimensional network. Two water molecules are disordered equally over two positions.
This chapter reviews the literature reported during 2007 on some important advances in the area of inorganic pharmaceuticals. Research highlights for the respective metals during the year are also given.
HighlightsThe main highlights include (i) dodecaborate-conjugated cholesterol liposome having toxicity of 25 ppm of boron concentration towards colon 26 cells, 43 (ii) the bactericidal action of Al 2 O 3 , Ag/Al 2 O 3 and AgCl/Al 2 O 3 on Escherichia coli K 12, 45 (iii) bis(a-furancarboxylato)oxovanadium(IV) as a new orally active anti-diabetic organic vanadium complex, 48 (iv) two mono-substituted manganese polyoxometallates, K 6 MnSiW 11 O 39 and K 8 MnP 2 W 17 O 61 as candidates of potential tissue-specific contrast agents for MRI, where the T 1 -relaxivities were higher than or similar to that of the Magnevist s , 57 and (v) the in vitro photobiology of the supramolecular complexes [((bpy) 2 Ru(dpp)) 2 RhCl 2 ]Cl 5 and [((bpy) 2 Os(dpp)) 2 RhCl 2 ]Cl 5 with African green monkey kidney epithelial (Vero) cells.
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