Comparative study of the photophysical properties of indoprofen photoproducts in relation with their DNA photosensitizing properties

Abstract

The photophysical properties of indoprofen photoproducts have been examined in various solvents by absorbance and emission spectroscopies in relation with their photosensitizing properties. The photophysical properties of 2-[4-(1-hydroxy)ethylphenyl]isoindolin-1-one (HOINP) and 2-(4-ethylphenyl)isoindolin-1-one (ETINP) are typical of a singlet excited state when the ones of 2-(4-acetylphenyl)isoindolin-1-one (KINP) are based on its triplet excited state according to previous work. The effect of solvent polarity on the absorption and fluorescence properties of HOINP and ETINP has been investigated as a function of Delta f, the Lippert solvent polarity parameter. A solvatochromic effect, function of the polarity region, has been observed for both photoproducts due to a change in the dipole moment of the compound upon excitation. In low-polarity regions, the excited state dipole moment of HOINP undergoes only a moderate increase (11.5 D) as compared to the dipole moment of the ground state (4.5 D) suggesting that the fluorescence arises from the locally excited state while in high-polarity regions it is strongly increased (42.9 D), which can imply that the emission takes place from a charge transfer state. In the case of ETINP, it would seem that the emitting state is rather a charge transfer state whatever the region is (16.9 and 31.8 D for the calculated excited-state dipole moments in the low and high-polarity regions, respectively). HOINP and ETINP do not produce thymine dimers by photosensitization but induce photooxidative damage via an electron transfer mechanism.

Contribution of Cytosine‐Containing Cyclobutane Dimers to DNA Damage Produced by Photosensitized Triplet–Triplet Energy Transfer

“…In the case of TTET in DNA, major differences in photosensitization mediated by either a parent compound or its photoproducts have been reported. [45,46] Once the conditions for linearity had been established, we could compare the efficiency of the different photosensitizers at inducing CPDs in DNA. Drastic differences were observed, even for the same class of photosensitizers.…”

Correlations between electrochemical behaviors and DNA photooxidative properties of non-steroïdal anti-inflammatory drugs and their photoproducts

“…Indeed, it has been previously demonstrated that the photosensitizing properties of KP and other benzophenone derivatives in DNA depend mainly on the benzophenone chromophore [8]. The involvement of photoproducts in DNA photosensitization processes was already reported for some NSAIDs [17][18][19]. From a chemical point of view, the alkali-labile lesion to DNA photosensitized, via an electron transfer mechanism, appears to be a redox reaction between DNA and the excited state of the photosensitizer.…”

Development of an RPLC‐based Method for Measurement of Indoprofen Stability and Validation of the Method

“…16 Recently, they reported that the photophysical properties of INP photoproducts correlated with their DNA photosensitizing properties. 17 A rapid and sensitive RPLC-based analytical procedure was previously described by Lakings et al, 18 which was proved effective for the simultaneous measurement of INP and its acidic and basic degradants in human milk. However, the applicability of existing RPLC methods for measurements of INP in samples containing photodegradants of this agent was uncertain.…”