Studies on the Mechanism of the Photo-Induced DNA Damage in the Presence of Acridizinium SaltsInvolvement of Singlet Oxygen and an Unusual Source for Hydroxyl Radicals

Abstract

Mechanistic investigations of the photoinduced DNA damage by acridizinium salts (4a-azonia-anthracene derivatives) are presented. Irradiation of 9-bromoacridizinium in the presence of defined double- and single-stranded DNA oligomers under aerobic conditions leads to both frank strand breaks and alkali-labile sites as determined by polyacrylamide gel electrophoresis (PAGE). The extent of the DNA damage increases significantly in D(2)O and occurs selectively at guanosine residues. These observations reveal the formation of singlet oxygen ((1)O(2)) as reactive species, which oxidizes the DNA bases, above all the guanine bases. Further evidence for (1)O(2) formation was obtained from laser-flash spectroscopic investigations, which show intersystem crossing (S(1) to T(1)) of the excited states of the parent acridizinium and of the 9-bromo- and 9-amino-substituted derivatives. The resulting triplet state is efficiently quenched by oxygen (k(q) > 10(9) s(-)(1)M(-)(1)) to yield (1)O(2). Under anaerobic conditions, no significant alkali-labile lesions are observed, but frank strand breaks are induced; however, to lesser extent than under aerobic conditions. The DNA damage is suppressed in the presence of a radical scavenger, namely t-BuOH, and hydroxyl radicals are shown to be the reactive intermediates by trapping experiments with terephthalic acid. Moreover, the intercalated acridizinium molecules are not involved in the DNA damage reactions. The intercalated acridizinium salt leads to a primary PET reaction with the DNA bases; however, a fast BET transfer is proposed that regains the dye and the DNA, so that the excited intercalated dye does not contribute significantly to the overall DNA damage.

Effects of Different Phases of Cigarette Smoke on Lipid Peroxidation and Membrane Structure in Liposomes

“…[35,36] The high reactivity of electronically excited species towards biological materials constitutes a subject matter of 'photobiology without light' and is of prime concern in terms of photooxidative damage of biomolecules (most prominently, DNA). [37][38][39][40] Lipid peroxidation (LPO) induces peroxidative destruction of cell membranes and thereby leads to a loss of their functional integrity and formation of early (such as dienic conjugates, DC) and terminal (such as malondialdehyde, MDA) LPO products. [18][19][20][21][41][42][43][44][45][46] In turn, diverse LPO products (peroxides, oxides, aldehydes, ketones, etc.)…”

Cucurbit[8]uril/Cucurbit[7]uril Controlled Off/On Fluorescence of the Acridizinium and 9‐Aminoacridizinium Cations in Aqueous Solution

“…This is the first example of using CB[n] host molecules of different sizes to control fluorescence intensity as a result of the binding stoichiometries between the cyclic hosts and the fluorophore guests. Both ADZ + and AADZ + are dyes, [16][17][18][19][20] which are intensely colored and have the propensity towards efficient emission properties, whose fluorescence may be used as a probe and as an intercalating DNAdamaging chromophore. [16][17][18] In addition, N-aryl-9-aminosubstituted acridizinium derivatives have been reported to act as fluorescent "light-up" probes for DNA and protein detection.…”

“…Both ADZ + and AADZ + are dyes, [16][17][18][19][20] which are intensely colored and have the propensity towards efficient emission properties, whose fluorescence may be used as a probe and as an intercalating DNAdamaging chromophore. [16][17][18] In addition, N-aryl-9-aminosubstituted acridizinium derivatives have been reported to act as fluorescent "light-up" probes for DNA and protein detection. [18] Another phenomenon observed for ADZ + and AADZ + cations was that increasing the concentrations A C H T U N G T R E N N U N G (>10 À2 m) of these fluorophores resulted in a decrease in their fluorescence intensity (quenching) and a redshift of the emission wavelength maxima.…”

Selective Stabilization of Abasic Site‐Containing DNA by Insertion of Sterically Demanding Biaryl Ligands

“…[12] It was demonstrated for benzo [b]quinolizinium derivatives that the quenching of the emission is mainly caused by a photoinduced electron-transfer reaction between the excited quinolizinium and the nucleic bases. [23] Although the photometric titrations clearly reveal multiple binding modes (see above), the plots of the relative emission intensity versus concentration of DNA appear as monophasic binding isotherms. This observation indicates essentially similar quenching efficiencies of the differently bound ligands, that is, the fractional emission quenching relates directly to the fraction of the bound ligand, independent of the binding mode.…”