👤 Xie FL

Corrinoids are cobalt-containing tetrapyrroles. They include adenosylcobalamin (vitamin B12) and cobamides that function as cofactors and coenzymes for methyl transfer, radical-dependent and redox reactions. Though cobamides are the most complex cofactors in nature, they are essential in the acetyl-CoA pathway, thought to be the most ancient CO2-fixation pathway, where they perform a pterin-to-cobalt-to-nickel methyl transfer reaction catalyzed by the corrinoid iron-sulphur protein (CoFeS). CoFeS occurs in H2-dependent archaeal methanogens, the oldest microbial lineage by measure of physiology and carbon isotope data, dating corrinoids to ca. 3.5 billion years. However, CoFeS and cobamides are also essential in the acetyl-CoA pathway of H2-dependent bacterial acetogens. To determine whether corrin biosynthesis was established before archaea and bacteria diverged, whether the pathways arose independently or whether cobamide biosynthesis was transferred from the archaeal to the bacterial lineage (or vice versa) during evolution, we investigated phylogenies and structural data for 26 enzymes of corrin ring and lower ligand biosynthesis. The data trace cobamide synthesis to the common ancestor of bacteria and archaea, placing it in the last universal common ancestor of all lifeforms (LUCA), while pterin-dependent methyl synthesis pathways likely arose independently post-LUCA in the lineages leading to bacteria and archaea. Enzymes of corrin biosynthesis were recruited from preexisting ancient pathways. Evolutionary forerunners of CoFeS function were likely Fe-, Ni- and Co-containing solid-state surfaces, which, in the laboratory, catalyze the reactions of the acetyl-CoA pathway from CO2 to pyruvate under serpentinizing hydrothermal conditions. The data suggest that enzymatic corrin biosynthesis replaced insoluble solid-state catalysts that tethered primordial CO2 assimilation to the Earth's crust, suggesting a role for corrin synthesis in the origin of free-living cells. Show less

Three iridium (III) polypyridine complexes [Ir(bzq)₂(maip)](PF₆) (Ir1，bzq = benzo[h]quinoline, maip = 3-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(bzq)₂(apip)](PF₆) (Ir2, apip = 2-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(bzq)₂(paip)](PF₆) (Ir3, paip = 4-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The cytotoxic activities of the three complexes against human osteosarcoma HOS, U2OS, MG63 and normal LO2 cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The results showed that Ir1-3 exhibited moderate antitumor activity against HOS with IC₅₀ of 21.8 ± 0. 4 μM,10.5 ± 1.8 μM and 7.4 ± 0.4 μM, respectively. We found that Ir1-3 can effectively inhibit HOS cells growth and blocked the cell cycle at the G0/G1 phase. Further studies revealed that complexes can increase intracellular reactive oxygen species (ROS) and Ca²⁺, which accompanied by mitochondria-mediated intrinsic apoptosis pathway. In addition, autophagy was also investigated. Taken together, the complexes induce HOS apoptosis through a ROS-mediated mitochondrial dysfunction pathway and inhibition of the PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway. This study provides useful help for understanding the anticancer mechanism of iridium (III) complexes toward osteosarcoma treatment. Show less

Two iridium (III) polypyridine complexes [Ir(ppy)₂(BIP)]PF₆ (ppy = 2-phenylpyridine, BIP = 2-biphenyl-1H-imidazo[4,5-f][1,10]phenanthroline, Ir1), [Ir(piq)₂(BIP)]PF₆ (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxic activity against several cancer cells (A549, HepG2, SGC-7901, Bel-7402, HeLa) and non-cancer cell (mouse embryonic fibroblast, NIH3T3). The results showed that Ir1lipo displays the high cytotoxicity toward SGC-7901 with IC₅₀ value of 5.8 ± 0.2 μM, while the complexes have no cytotoxicity toward A549, HepG2, Bel-7402 and HeLa cells. The cell colony demonstrated that the iridium (III) complexes-loaded liposomes can inhibit cell proliferation, induce cell cycle arrest at G0/G1 phase. Moreover, they also cause autophagy, induce a decrease of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) content. These results suggest that the complexes encapsulated liposomes Ir1lipo and Ir2lipo inhibit the growth of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction and activating the PI3K (phosphoinositide-3 kinase)/ AKT (protein kinase B) signaling pathways. Show less

Life is the harnessing of chemical energy in such a way that the energy-harnessing device makes a copy of itself. This paper outlines an energetically feasible path from a particular inorganic setting for the origin of life to the first free-living cells. The sources of energy available to early organic synthesis, early evolving systems and early cells stand in the foreground, as do the possible mechanisms of their conversion into harnessable chemical energy for synthetic reactions. With regard to the possible temporal sequence of events, we focus on: (i) alkaline hydrothermal vents as the far-from-equilibrium setting, (ii) the Wood-Ljungdahl (acetyl-CoA) pathway as the route that could have underpinned carbon assimilation for these processes, (iii) biochemical divergence, within the naturally formed inorganic compartments at a hydrothermal mound, of geochemically confined replicating entities with a complexity below that of free-living prokaryotes, and (iv) acetogenesis and methanogenesis as the ancestral forms of carbon and energy metabolism in the first free-living ancestors of the eubacteria and archaebacteria, respectively. In terms of the main evolutionary transitions in early bioenergetic evolution, we focus on: (i) thioester-dependent substrate-level phosphorylations, (ii) harnessing of naturally existing proton gradients at the vent-ocean interface via the ATP synthase, (iii) harnessing of Na(+) gradients generated by H(+)/Na(+) antiporters, (iv) flavin-based bifurcation-dependent gradient generation, and finally (v) quinone-based (and Q-cycle-dependent) proton gradient generation. Of those five transitions, the first four are posited to have taken place at the vent. Ultimately, all of these bioenergetic processes depend, even today, upon CO2 reduction with low-potential ferredoxin (Fd), generated either chemosynthetically or photosynthetically, suggesting a reaction of the type 'reduced iron → reduced carbon' at the beginning of bioenergetic evolution. Show less