SummaryThe mitochondrial membrane potential (Δψm) is a major determinant and indicator of cell fate, but it is not possible to assess small changes in Δψm within cells or in vivo. To overcome this, we developed an approach that utilizes two mitochondria-targeted probes each containing a triphenylphosphonium (TPP) lipophilic cation that drives their accumulation in response to Δψm and the plasma membrane potential (Δψp). One probe contains an azido moiety and the other a cyclooctyne, which react together in a concentration-dependent manner by “click” chemistry to form MitoClick. As the mitochondrial accumulation of both probes depends exponentially on Δψm and Δψp, the rate of MitoClick formation is exquisitely sensitive to small changes in these potentials. MitoClick accumulation can then be quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This approach enables assessment of subtle changes in membrane potentials within cells and in the mouse heart in vivo.
A 2,2'-bipyridine-appended ferrocene rotor, 1,1'-di(5-yl-ethynyl-2,2'-bipyridine)ferrocene, can be switched from a folded/stacked (syn) conformation to an extended/unstacked (anti) conformation by the addition of [Cu(CH3CN)4](PF6) and 6,6'-dimesityl-2,2'-bipyridine. This extension and contraction process was completely reversible and could be triggered either chemically or electrochemically.
Two 5-ferrocenyl-2,2′-bipyridine ligands were synthesised using the palladium(0) catalysed Suzuki–Miyaura cross-coupling reaction. Palladium(ii) and copper(i) complexes of these ligands were synthesised and the optical and electrochemical properties of the complexes were compared to those of the “free” ligands.
A new route to unsymmetrical derivatives of quino[7,8‐h]quinoline was developed. Substitutions at the 2,11‐, 4,9‐ and 6,7‐positions of quino[7,8‐h]quinoline were also successfully performed. X‐ray crystal structure determinations of the resulting products revealed the propensity for derivatives of this molecule to exist in either stabilised keto or imino forms as a result of the formation of a strong intramolecular N–H···N hydrogen bond.
The structures of a series of tetracoordinate beryllium(II) complexes with ligands derived from tertiary-substituted amines have been computationally modeled and their (9)Be magnetic shielding values determined using the gauge-including atomic orbital (GIAO) method at the 6-311++g(2d,p) level. A good correlation was observed between calculated (9)Be NMR chemical shifts when compared to experimental values in polar protic solvents, less so for the values recorded in polar aprotic solvents. A number of alternative complex structures were modeled, resulting in an improvement in experimental versus computational (9)Be NMR chemical shifts, suggesting that in some cases full encapsulation on the beryllium atom was not occurring. Several of the synthesized complexes gave rise to unexpected fluorescence, and inspection of the calculated molecular orbital diagrams associated with the electronic transitions suggested that the rigidity imparted by the locking of certain conformations upon Be(II) coordination allowed delocalization across adjacent aligned aromatic rings bridged by Be(II).
The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P. falciparum remains unclear. Current evidence suggests that the main role of chorismate is folate biosynthesis despite ubiquinone biosynthesis being active and essential in the malaria parasite. Our goal in the present work was to expand our knowledge of the ubiquinone head group biosynthesis and its potential metabolic dependency on chorismate in P. falciparum. We systematically assessed the development of both asexual and sexual stages of P. falciparum in a defined medium in the absence of an exogenous supply of chorismate end-products and present biochemical evidence suggesting that the benzoquinone ring of ubiquinones in this parasite may be synthesized through a yet unidentified route.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.