👤 Nesterov SV

One of the deepest branches in the tree of life separates the Archaea from the Bacteria. These prokaryotic groups have distinct cellular systems including fundamentally different phospholipid membrane bilayers. This dichotomy has been termed the lipid divide and possibly bestows different biophysical and biochemical characteristics on each cell type. Classic experiments suggest that bacterial membranes (formed from lipids extracted from Escherichia coli, for example) show permeability to key metabolites comparable to archaeal membranes (formed from lipids extracted from Halobacterium salinarum), yet systematic analyses based on direct measurements of membrane permeability are absent. Here, we develop a new approach for assessing the membrane permeability of approximately 10 μm unilamellar vesicles, consisting of an aqueous medium enclosed by a single lipid bilayer. Comparing the permeability of 18 metabolites demonstrates that diether glycerol-1-phosphate lipids with methyl branches, often the most abundant membrane lipids of sampled archaea, are permeable to a wide range of compounds useful for core metabolic networks, including amino acids, sugars, and nucleobases. Permeability is significantly lower in diester glycerol-3-phosphate lipids without methyl branches, the common building block of bacterial membranes. To identify the membrane characteristics that determine permeability, we use this experimental platform to test a variety of lipid forms bearing a diversity of intermediate characteristics. We found that increased membrane permeability is dependent on both the methyl branches on the lipid tails and the ether bond between the tails and the head group, both of which are present on the archaeal phospholipids. These permeability differences must have had profound effects on the cell physiology and proteome evolution of early prokaryotic forms. To explore this further, we compare the abundance and distribution of transmembrane transporter-encoding protein families present on genomes sampled from across the prokaryotic tree of life. These data demonstrate that archaea tend to have a reduced repertoire of transporter gene families, consistent with increased membrane permeation. These results demonstrate that the lipid divide demarcates a clear difference in permeability function with implications for understanding some of the earliest transitions in cell origins and evolution. Show less

A series of novel mono- and binuclear arene-ruthenium(II) complexes [(p-cym)Ru(L)Cl] containing 11H-indeno[1,2-b]quinoxalin-11-one derivatives or tryptanthrin-6-oxime were synthesized and characterized by X-ray crystallography, IR, NMR spectroscopy, cyclic voltammetry, and elemental analysis. Theoretical calculations invoking singlet state geometry optimization, solvation effects, and noncovalent interactions were done using density functional theory (DFT). DFT calculations were also applied to evaluate the electronic properties, and time-dependent DFT was applied to clarify experimental UV-vis results. Cytotoxicity for cancerous and noncancerous human cell lines was evaluated with cell viability MTT assay. Complexes demonstrated a moderate cytotoxic effect toward cancerous human cell line PANC-1. The catalytic activity of the complexes was evaluated in transfer hydrogenation of aryl ketones. All complexes exhibited good catalytic activity and functional group tolerance. Show less

Neutral half-sandwich organometallic ruthenium(II) complexes of the type [(η(6)-cymene)RuCl(2)(L)] (H1-H10), where L represents a heterocyclic ligand, have been synthesized and characterized spectroscopically. The structures of five complexes were also established by single-crystal X-ray diffraction confirming a piano-stool geometry with η(6) coordination of the arene ligand. Hydrogen bonding between the N-H group of the heterocycle and a chlorine atom attached to Ru stabilizes the metal-ligand interaction. Complexes coordinated to a mercaptobenzothiazole framework (H1) or mercaptobenzoxazole (H6) showed high cytotoxicity against several cancer cells but not against normal cells. In vitro studies have shown that the inhibition of cancer cell growth involves primarily G1-phase arrest as well as the generation of reactive oxygen species (ROS). The complexes are found to bind DNA in a non-intercalative fashion and cause unwinding of plasmid DNA in a cell-free medium. Surprisingly, the cytotoxic complexes H1 and H6 differ in their interaction with DNA, as observed by biophysical studies, they either cause a biphasic melting of the DNA or the inhibition of topoisomerase IIα activity, respectively. Substitution of the aromatic ring of the heterocycle or adding a second hydrogen-bond donor on the heterocycle reduces the cytotoxicity. Show less