The surprising lability of bis(2,2’:6’,2’’-terpyridine)- chromium(III) complexes

The complex [Cr(tpy)(O3SCF3)3] (tpy = 2,2′:6′,2′′-terpyridine) is readily made from [Cr(tpy)Cl3] and is a convenient precursor to [Cr(tpy)2][PF6]3 and to [Cr(tpy)(4′-(4-tolyl)tpy)][PF6]3 and [Cr(tpy)(5,5′′-Me2tpy)][PF6]3 (4′-(4-tolyl)tpy = 4′-(4-tolyl)-2,2′:6′,2′′-terpyridine; 5,5′′-Me2tpy = 5,5′′-dimethyl-2,2′:6′,2′′-terpyridine); these are the first examples of heteroleptic bis(tpy) chromium(III) complexes. The single crystal structures of 2{[Cr(tpy)2][PF6]3}·5MeCN, [Cr(tpy)(4′-(4-tolyl)tpy)][PF6]3·3MeCN and [Cr(tpy)(5,5′′-Me2tpy)][PF6]3·3MeCN have been determined. Each cation contains the expected octahedral {Cr(tpy)2}3+ unit; in all three structures, the need to accommodate three anions per cation and the solvent molecules prevents the formation of a grid-like array of cations that is typical of many lattices containing {M(tpy)2}2+ motifs. Three reversible electrochemical processes are observed for [Cr(tpy)(4′-(4-tolyl)tpy)][PF6]3 and [Cr(tpy)(5,5′′-Me2tpy)][PF6]3, consistent with those documented for [Cr(tpy)2]3+. At pH 6.36, aqueous solutions of [Cr(tpy)2][PF6]3 are stable for at least two months. However, contrary to the expectations of the d3 Cr3+ ion being a kinetically inert metal centre, the tpy ligands in [Cr(tpy)2]3+are labile in the presence of base; absorption and 1H NMR spectroscopies have been used to monitor the effects of adding NaOH to aqueous and CD3OD solutions, respectively, of the homo- and heteroleptic complexes. Ligand dissociation is also observed when [Bu4N]F is added to CD3OD solutions of the complexes, but in aqueous solution, [Cr(tpy)2][PF6]3 is stable in the presence of fluoride ion

Homoleptic and heteroleptic complexes of chromium(III) containing 4'-diphenylamino-2,2':6',2''-terpyridine ligands

Two heteroleptic bis(2,2′:6′,2″-terpyridine)chromium(III) complexes [Cr(1)(4′-(4-tolyl)tpy)][CF3SO3]3 and [Cr(2)(4′-(4-tolyl)tpy)][CF3SO3]3 (1 = 4-([2,2′:6′,2″-terpyridin]-4′-yl)-N,N-diphenylaniline, 2 = 4-([2,2′:6′,2″-terpyridin]-4′-yl)-N,N-bis(4-methoxyphenyl)aniline, 4′-(4-tolyl)tpy = 4′-(4-tolyl)-2,2′:6′,2″-terpyridine) have been prepared and their spectroscopic and electrochemical properties compared with those of [Cr(4′-(4-tolyl)tpy)2][CF3SO3]3 and [Cr(1)2][CF3SO3]3. The single crystal structure of [Cr(4′-(4-tolyl)tpy)2][CF3SO3]3·2MeCN is presented, and the effects of accommodating three triflate anions and two MeCN molecules per cation are discussed in terms of related structures. The coordination of 1 or 2 to chromium(III) red-shifts the intra-ligand charge transfer (ILCT) band and this band exhibits a negative solvatochromic effect in some solvents. However, in H2O, MeOH, DMSO and DMF, the tpy ligands are labile; changes in the absorption spectra of solutions of [Cr(2)(4′-(4-tolyl)tpy)][CF3SO3]3 are consistent with the formation of [Cr(4′-Xtpy)(Solv)3]3+ (Solv = solvent) rather than complete ligand displacement or a ligand redistribution

Heteroleptic chromium(III) tris(diimine) [Cr(N^N)2(N'^N')]3+ complexes

A series of heteroleptic tris(diimine) complexes of chromium(III) is reported and the crystal structures of {4[Cr(bpy)2(phen)][PF6]3}·11MeCN and 4[Cr(4,4′-Me2bpy)2(bpy)][PF6]3}·12MeCN·H2O are described. The combined effects of a 1:3 cation: anion ratio and lattice solvent molecules are discussed, in particular in the context of the influence on intercation embraces. The presence of the methyl substituents in {4[Cr(4,4′-Me2bpy)2(bpy)][PF6]3}·12MeCN·H2O results in Me–πbpy contacts becoming the dominant packing interactions and in the assembly of motifs distinct from those in {4[Cr(bpy)2(phen)][PF6]3}·11MeCN

Copper(I) dye-sensitized solar cells with [Co(bpy)3]2+/3+ electrolyte

The hierarchical assembly of DSCs containing a new heteroleptic copper(I) complex with a phosphonic acid anchoring ligand is described; it is shown that conventional I−/I3− electrolytes may be replaced by [Co(bpy)3]2+/3+ with no loss in performance

The endogenous caspase-8 inhibitor c-FLIPL regulates ER morphology and crosstalk with mitochondria

Components of the death receptors-mediated pathways like caspase-8 have been identified in complexes at intracellular membranes to spatially restrict the processing of local targets. In this study, we report that the long isoform of the cellular FLICE-inhibitory protein (c-FLIPL), a well- known inhibitor of the extrinsic cell death initiator caspase-8, localizes at the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). ER morphology was disrupted and ER Ca2+-release as well as ER-mitochondria tethering were decreased in c-FLIP-/- mouse embryonic fibroblasts (MEFs). Mechanistically, c-FLIP ablation resulted in enhanced basal caspase-8 activation and in caspase-mediated processing of the ER-shaping protein reticulon-4 (RTN4) that was corrected by re-introduction of c-FLIPL and caspase inhibition, resulting in the recovery of a normal ER morphology and ER-mitochondria juxtaposition. Thus, the caspase-8 inhibitor c-FLIPL emerges as a component of the MAMs signaling platforms, where caspases appear to regulate ER morphology and ER-mitochondria crosstalk by impinging on ER-shaping proteins like the RTN4

Identification of tetrahydrocarbazoles as novel multifactorial drug candidates for treatment of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder and the most frequent cause of dementia. To date, there are only a few approved drugs for AD, which show little or no effect on disease progression. Impaired intracellular calcium homeostasis is believed to occur early in the cascade of events leading to AD. Here, we examined the possibility of normalizing the disrupted calcium homeostasis in the endoplasmic reticulum (ER) store as an innovative approach for AD drug discovery. High-throughput screening of a small-molecule compound library led to the identification of tetrahydrocarbazoles, a novel multifactorial class of compounds that can normalize the impaired ER calcium homeostasis. We found that the tetrahydrocarbazole lead structure, first, dampens the enhanced calcium release from ER in HEK293 cells expressing familial Alzheimer's disease (FAD)-linked presenilin 1 mutations. Second, the lead structure also improves mitochondrial function, measured by increased mitochondrial membrane potential. Third, the same lead structure also attenuates the production of amyloid-beta (A beta) peptides by decreasing the cleavage of amyloid precursor protein (APP) by beta-secretase, without notably affecting alpha- and gamma-secretase cleavage activities. Considering the beneficial effects of tetrahydrocarbazoles addressing three key pathological aspects of AD, these compounds hold promise for the development of potentially effective AD drug candidates

New therapeutic targets in Alzheimer's disease: brain deregulation of calcium and zinc

The molecular determinants of Alzheimer's (AD) disease are still not completely known; however, in the past two decades, a large body of evidence has indicated that an important contributing factor for the disease is the development of an unbalanced homeostasis of two signaling cations: calcium (Ca2+) and zinc (Zn2+). Both ions serve a critical role in the physiological functioning of the central nervous system, but their brain deregulation promotes amyloid-β dysmetabolism as well as tau phosphorylation. AD is also characterized by an altered glutamatergic activation, and glutamate can promote both Ca2+ and Zn2+ dyshomeostasis. The two cations can operate synergistically to promote the generation of free radicals that further intracellular Ca2+ and Zn2+ rises and set the stage for a self-perpetuating harmful loop. These phenomena can be the initial steps in the pathogenic cascade leading to AD, therefore, therapeutic interventions aiming at preventing Ca2+ and Zn2+ dyshomeostasis may offer a great opportunity for disease-modifying strategies

Phosphonate-functionalized heteroleptic ruthenium(II) bis(2,2':6',2''-terpyridine) complexes

The heteroleptic complexes [Ru(1)(4)][PF6]2, [Ru(2)(4)][PF6]2, [Ru(Phtpy)(4)][PF6]2, and [Ru(pytpy)(4)][PF6]2 (Phtpy = 4′-phenyl-2,2′:6′,2″-terpyridine, pytpy = 4′-(4-pyridyl)-2,2′:6′,2″-terpyridine, 1 and 2 = 4-methyl ester substituted derivatives of Phtpy and pytpy, 4 = ethyl 2,2′:6′,2″-terpyridine-4′-phosphonate) have been prepared. The single crystal structure of ligand 1 (1 = methyl 4-carboxy-4′-phenyl-2,2′:6′,2″-terpyridine) is reported. The introduction of the 4-methyl ester group causes a small red shift in the MLCT band of the ruthenium(II) complexes and a small shift to a more positive potential for the Ru2+/Ru3+ couple. The new complexes should serve as a useful starting point for development of ruthenium(II) dyes suited for sensitization of p-type semiconductors