Photochemical Activities of N‐Nitroso Carboxamides and Sulfoximides and Their Application to DNA Cleavage

Abstract

N-Nitroso compounds containing benzene, fluorene or fluorenone rings were synthesized. Photolysis of these compounds with 312-nm UV light provided the NO(*) species, the presence of which was corroborated by use of an EPR method and of 2-phenyl-4,4,5,5-tetramethylimidazolin-1-oxyl 3-oxide (PTIO) as a trapping agent. During irradiation of N-methyl-N-nitroso-9-fluorenone carboxamide (14 c) in the absence of PTIO, it underwent decomposition followed by recombination to give the heterocyclic nitric oxide radical 15. Incorporation of intercalating moieties endowed the N-nitroso compounds with DNA-cleaving ability through single-strand scission upon UV irradiation in a phosphate buffer (pH 5.0-8.0) under aerobic conditions.

Comment on “Photochemical Activities of N‐Nitroso Carboxamides and Sulfoximides and Their Application to DNA Cleavage”

“…The percentage of strand scission increased to ≥ 99 % at pH 5, but dropped to 78 % at pH 8 (see Table 1 of ref. [1]). Notably, such a pH dependence is just what would be expected for N 2 O 3 as the DNA‐cleaving agent, because the rate of the competitive hydrolytic destruction of N 2 O 3 not only depends on [OH − ] but is also catalyzed by HPO 4 2− [12]…”

“…In 2009, Hwu and colleagues reported in this journal on the photochemical activities of the N ‐nitroso compounds 1 – 5 and their application in DNA cleavage (Figure 1). [1] …”

“…This spectrum, characterized by hyperfine splittings of a ( 14 N)=13.34 (1N) and a ( 1 H)=5.57 (2 H) G and a g value of 2.0062 (see Figure 3 of ref. [1]), was attributed to the cyclic alkoxy nitroxide radical 10 (Scheme 1). The formation of the latter was proposed to proceed via disproportionation of the initially produced amidyl radical 6 to yield amide 7 and the carboximide 8 .…”

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

“…Several organic compounds were found to be "DNA photocleavers", exhibiting their action at 312 nm, like [1,2,4]triazolo [4,3-a]quinoxaline [28] and quinoxalin-4(5H)one [29] derivatives, various enediyne [30][31][32], proflavine [33], N-nitroso carboxamide [34], naphazoline [35] and triazole [36] derivatives, azido carbonyl compounds [37] and N,O-diacyl-4benzoyl-N-phenylhydroxylamines [38].…”

Oxime Esters of 2,6-Diazaanthracene-9,10-dione and 4,5-Diazafluoren-9-one as Photo-induced DNA-Cleaving Agents

“…If such OPEN ACCESS "photocleavage agents" absorb light at wavelengths longer than 300 nm, nucleic acids will not be affected while selective excitation of the photocleavage agents can be achieved [4]. Since single-strand DNA damage is easily repaired by enzymatic processes [5], photocleavage of double-strand DNA molecules would be a more efficient tool for cancer therapy [6][7][8][9][10][11][12].…”