Year: 2005
Type: article
Abstract: The reactive intermediate produced upon photolysis of 8-azidoadenosine was studied by chemical trapping studies, laser flash photolysis with UV-Vis and IR detection, and modern computational chemistry.It is concluded that photolysis of 8-azidoadenosine in aqueous solution releases the corresponding singlet nitrene which rapidly tautomerizes to form a closed adenosine diazaquinodimethane in less than 400 fs.A perbenzoylated derivative of 8-azidoadenosine can not undergo this tautomerization, and it fragments upon photolysis to form an open adenosine diazaquinodimethane.The singlet nitrene is too short lived to be observed, and thus, to relax to the lowest triplet state or to become covalently attach to targeted biological macromolecules.The pivotal closed adenosine diazaquinodimethane, the product of nitrene tautomerization, has a lifetime of several minutes, ca. a minute or longer in water and in HEPES buffer at ambient temperature.However, this intermediate reacts rapidly with good nucleophiles such as amines, thiols, and phenolates, and significantly more slowly with weak nucleophile such as alcohols and water.On the basis of these studies, it is clear that the closed adenosine diazaquinondimethane, and not the singlet or triplet nitrene, is the pivotal reactive intermediate involved in photolabeling and cross-linking studies using the 8-azidoadenosine family of photoaffinity labeling reagents.Pyrene dihydrodioxins have been synthesized and shown to be effective photochemical blocking groups for pyrene-4,5-dione.The mechanism of quinone release proceeds through the formation of a remarkably stable radical cation.Direct evidence is provided that this radical cation is not only thermally labile, but also is photochemically labile, and that both pathways lead to quinone extrusion.Once initiated with UV light, the pyrene quinone product serves as an electron transfer photosensitizer for the further release of quinone with visible light.The water soluble pyrene dihydrodioxin has been shown to bind to duplex DNA by intercalation (K a = 7 × Section I 5 Section II.40 Section III.49 Conclusions 67 Experimental Section I. 69 Section II.203 Section III.251 anti trans-12c anti cis-12c E = 3.9 kcal/mol E = 4.9 kcal/mol (in water) λ = 551nm, 474 nm ν =1244 cm -1 , 1313 cm -1 , 1353 cm -1 , 1406 cm -1 , 1433 cm -1 , 1501 cm -1 1567 cm -1 1605 cm -1 1609 cm -1 E = 19.1 kcal/mol E = 19.1 kcal/mol (in water) λ = 453 nm, 404 nm ν =1258 cm -1 , 1463 cm -1 , 1524 cm -1 , 1550 cm -1 , 1639 cm -1 , 1678 cm -1 syn trans-12c E = 8.9 kcal/mol E = 11.8 kcal/mol (in water) λ = 576 nm, 488nm ν =1237 cm -1 , 1334 cm -1 , 1361 cm -1 , 1418 cm -1 , 1445 cm -1 , 1530 cm -1 1585 cm -1 1601 cm -1 1614 cm -1 13c E = 0.0 kcal/mol E = 0.0 kcal/mol (in water) λ = 563 nm, 430nm ν =1247 cm -1 , 1319 cm
Author: Eric T. Mack
Institution: University of Cincinnati
Language: English
Subfield: Physical and Theoretical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2258425965