Structures and Functions of Nucleic Acids Modified with S, Se, and Te and Complexed with Small Molecules

Organoselenium Compounds: Chemistry and Applications in Organic Synthesis

“…Selenium has been integrated into various other positions of synthetic nucleosides not exclusively to replace an oxygen atom but also a carbon atom at the furanose ring [23] as it was the case of the selenium-containing analogue of the anti-HIV agent 2',3'-dideoxy-3-thiacytidine 479 (compound 480) exhibiting an ED 50 value of 0.9 μM. [372] In addition, the synthesis of other selenium-containing nucleosides and, even, telluriumcontaining derivatives where the chalcogen atom did not replace any of the oxygen atoms neither in the ribose ring nor in the rest of the corresponding nucleoside molecule has been described whose chemical structure is a seleno(telluro)anhydroglycofuranoside or the respective nucleosides such as 481 and 482 as shown in Figure 5.…”

“…[22] Moreover, in view of its atomic radius compared to oxygen and sulfur (oxygen, 0.73 Å; sulfur, 1.02 Å; selenium, 1.16 Å) and its electronic density, selenium can be used to design not only selenium-containing nucleic acids, but also any isostere of a molecule bearing an oxygen atom or a sulfur atom in its structure with unique chemical and physical properties. [23] All in all, the growing interest in selenium chemistry began with the finding of selenocysteine in the active site of glutathione peroxidase, a crucial enzyme that acts as an antioxidant in living systems. [24] In this respect, the pharmacological relevance of the synthetic analogue of glutathione ebselen, and other pharmacologically relevant selenium-based compounds, increased the attention in this area of research.…”

Organoselenium Compounds in Catalysis

“…18 Considering its atomic radius compared to oxygen and sulfur (oxygen, 0.73 Å; sulfur, 1.02 Å; selenium, 1.16 Å) and its electronic density, selenium can be used to design any isostere of a molecule bearing an oxygen atom or a sulfur atom in its structure with distinctive chemical and physical properties. 19 The discovery of selenocysteine in the active site of glutathione peroxidase, a key antioxidant enzyme, together with the pharmacological relevance of ebselen, the synthetic analogue of glutathione, has increased attention in organoselenium chemistry. 20 Certainly, this area of research has attracted a tirelessly escalating attention due to the ability of organoselenium compounds to catalyze a variety of distinctive chemical reactions.…”

Mononucleoside phosphorodithiolates as mononucleotide prodrugs

“…During the last decades, the replacement of oxygen by sulfur as modification of DNA's backbone has extensively been studied for mechanistic and structural investigations [8]. Thus, the variation, in which a sulfur atom replaces one of the non-bridging oxygen atoms in a phosphate group (phosphorothioation) that links DNA nucleotides together, is the first known modification of DNA's backbone [9] and confers increased resistance to nuclease degradation of the corresponding phosphorothioate oligonucleotides [10].…”

“…4.1.3. S,S 0 -bis(O-pivaloyl-2-oxyethyl) O-2 0 ,3 0 -didehydro-2 0 ,3 0dideoxythymidin-5 0 -yl thionophosphorodithiolate (8) The crude resulting from the reaction of d4T and 2mercaptoethyl pivalate was purified by silica gel column chromatography (gradient ethyl acetate 20e30% in dichloromethane). The fractions enriched in this side-product were purified several times in the same chromatographic conditions to obtain a pure sample of the title compound 8.…”