Singlet Oxygen's Potential Role as a Nonoxidative Facilitator of Disulfide S-S Bond Rotation†.

The role of singlet oxygen potentially mediating increased conformational flexibility of a disulfide was investigated. Density functional theory (DFT) calculations indicate that the singlet oxygenation of 1,2-dimethyldisulfane produces a peroxy intermediate. This intermediate adopts a structure with a longer S-S bond distance and a more planar torsional angle θ (C-S-S-C) compared with the nonoxygenated 1,2-dimethyldisulfane. The lengthened S-S bond enables a facile rotation about the torsional angle in the semicircle region 0° < θ < 210°, that is ~5 kcal mol-1 lower in energy than the disulfane. The peroxy intermediate bears nO → σS-S and nO → σ*S-S interactions that stabilize the S-O bond but destabilize the S-S bond, which contrasts with stabilizing nS → σ*S-S hyperconjugative effects in the disulfane S-S bond. Subsequent departure of O2 from the disulfane peroxy intermediate is reminiscent of peroxy intermediates which also expel O2 , yet facilitate cis-trans isomerizations of stilbenes, hexadienes, cyanines, and carotenes. "Non-oxidative" 1 O2 interactions with a variety of bond types are currently underappreciated. We hope to raise awareness of how these interactions can help elucidate the origins of molecular twisting.

Synthetic feasibility of oxygen-driven photoisomerizations of alkenes and polyenes.

This review describes O2-dependent photoreactions for possible routes to double-bond isomerizations. E,Z-isomerizations triggered by O2 and visible light are a new area of potential synthetic interest. The reaction involves the reversible addition of O2 to form a peroxy intermediate with oxygen evolution and partial regeneration of the compound as its isomer. Targeting of O2-dependent photoisomerizations also relates to a practical use of visible light, for example the improved light penetration depth for visible as opposed to UV photons in batch sensitized reactions. This review is intended to draw a link between visible-light formation of a peroxy intermediate and its dark degradation with O2 release for unsaturated compound isomerization. This review should be of interest both to photochemists and synthetic organic chemists, as it ties together mechanistic and synthetic work, drawing attention to an overlooked subject.

Translational Repression in Malaria Sporozoites.

Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1), is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host.

Structural studies of molybdopterin synthase provide insights into its catalytic mechanism.

Molybdenum cofactor biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea, and eukaryotes, including humans. Genetic deficiencies of enzymes involved in cofactor biosynthesis in humans lead to a severe and usually fatal disease. The molybdenum cofactor contains a tricyclic pyranopterin, termed molybdopterin, that bears the cis-dithiolene group responsible for molybdenum ligation. The dithiolene group of molybdopterin is generated by molybdopterin synthase, which consists of a large (MoaE) and small (MoaD) subunit. The crystal structure of molybdopterin synthase revealed a heterotetrameric enzyme in which the C terminus of each MoaD subunit is deeply inserted into a MoaE subunit to form the active site. In the activated form of the enzyme, the MoaD C terminus is present as a thiocarboxylate. The present study identified the position of the thiocarboxylate sulfur by exploiting the anomalous signal originating from the sulfur atom. The structure of molybdopterin synthase in a novel crystal form revealed a binding pocket for the terminal phosphate of molybdopterin, the product of the enzyme, and suggested a binding site for the pterin moiety present in precursor Z and molybdopterin. Finally, the crystal structure of the MoaE homodimer provides insights into the conformational changes accompanying binding of the MoaD subunit.