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Heavier chalcogenones (S, Se and Te) of imidazole act as versatile ligands to yield a series of mononuclear and dinuclear bismuth(III)complexes of heavier chalcogenones in excellent yield. These new bismuth heavier chalcogen derivatives are the first structurally characterized molecules, where the bismuth and heavier chalcogen ratio is 1 : 1. There is only one previous report of a crystal structure of a bismuth(III)imidazol selone compound and none with bismuth(III)-imidazol tellone. The bismuth center in monomeric bismuth chalcogen trihalides depicts pseudo trigonal bipyramidal geometry, while the dimeric bismuth chalcogen trihalides demonstrate distorted square pyramidal geometry. The solid state structures of bismuth chalcogenone derivatives feature rare Bi/p(aryl) interactions. Thus, the centroid of the C6-ring suggests a half sandwich type of bismuth environment in mononuclear and dinuclear bismuth(III) chalcogenone complexes. Notably, the Bi/p(aryl) interaction is not often noticed for mononuclear bismuth chalcogen compounds. Some of the bismuth(III) chalcogenone complexes also exhibit C-H/p(aryl), C-H/S and C-H/Cl types of hydrogen bonding. The bismuth-chalcogen bond distance in mononuclear bismuth(III)tribromide chalcogenone complexes is slightly longer than in mononuclear bismuth(III)trichloride chalcogenone complexes. A gradual increase in carbon-chalcogen bond distance was observed from the free imidazole-chalcogenone to mononuclear bismuth(III)trichloride chalcogenones, dinuclear bismuth(III)trichloride chalcogenones and mononuclear bismuth(III)tribromide chalcogenones and dinuclear bismuth(III)tribromide chalcogenones. The UV-vis absorption properties and thermal decomposition properties of imidazol chalcogenones and their bismuth derivatives were investigated. Furthermore, the O-acylative cleavage of cyclic ethers was demonstrated using mononuclear and dinuclear bismuth(III)complexes of heavier chalcogenones as catalysts. In contrast to bismuth(III)trichloride and bismuth(III)tribromide catalysts, mononuclear and dinuclear bismuth(III)complexes of heavier chalcogenones are very active towards an acylative cleavage of cyclic ethers through a mild and regioselective strategy. In particular, mononuclear imidazolthione-bismuth(III)trichloride is very active towards O-acylative cleavage of 2-methyl tetrahydrofuran.

TLR4 in complex with MD2 senses the presence of lipid A (LA) and initiates a signaling cascade that curb the infection. This complex is evolutionarily conserved and can initiate the immune system in response to a variety of LAs. In this study, molecular dynamics simulation (25 ns) was performed to elucidate the differential behavior of TLR4/MD2 complex in response to Rhodobacter sphaeroides lipid A (RsLA). Penta-acyl chain-containing RsLA is at the verge of agonist (6 acyl-chains) and antagonist (4 acyl-chains) structure, and activates the TLR4 pathway in horses and hamsters, while inhibiting in humans and murine. In the time-evolved coordinates, the promising factors that dictated the differential response included the local and global mobility pattern of complexes, solvent-accessible surface area of ligand, and surface charge distributions of TLR4 and MD2. We showed that the GlcN1-GlcN2 backbone acquires agonist (3FXI)-like configurations in horses and hamsters, while acquiring antagonist (2E59)-like configurations in humans and murine systems. Moreover, analysis of F126 behavior in the MD2 F126 loop (amino acids 123–129) and loop EF (81–89) suggested that certain sequence variations also contribute to species-specific response. This study underlines the TLR4 signaling mechanism and provides new therapeutic opportunities.

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The p53 protein is an important transcription factor that modulates signaling pathways for both cell death and survival. Its antiapoptotic mechanisms that correlate with necrotic and apoptotic cell death are not well understood. Here, we report that etoposide promotes progression of the DNA damage response as well as necrotic morphological changes including plasma membrane rupture using carbon nanotube-tipped/atomic force microscopy (CNT/AFM) probes in human kidney proximal tubule (HK-2) cells. Inhibition of p53 abrogated cell cycle arrest and led to a decrease in the expression levels of repair proteins that were induced by DNA damage. Mitochondrial biogenesis and cytosolic production of reactive oxygen species were also reduced after p53 inhibition; the latter change induced mitochondrial superoxide accumulation and mitochondrial damage, which triggered the activation of caspase 3. Inhibition of p53 also led to a loss of cell adhesion and converted necrotic cell death to apoptotic cell death, with appreciable cell shrinkage and appearance of apoptotic bodies that were observed using CNT/AFM probes. Thus, our study demonstrated that p53 protects against apoptosis, and leads to etoposide-induced necrosis. These results are expected to aid in the understanding of mechanism of antiapoptosis and its relationship to cell death.