Triplet Photoreactivity of the Diaryl Ketone Tiaprofenic Acid and Its Decarboxylated Photoproduct. Photobiological Implications

Encinas, Susana; Miranda, Miguel A.; Marconi, Giancarlo; Monti, Sandra

doi:10.1562/0031-8655(1998)067<0420:tpotdk>2.3.co;2

Cited by 11 publications

(21 citation statements)

References 16 publications

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“…Semiempirical calculations of the electron density in both the triplet and the ground-state anions 2 and 3, based on the ZINDO 1 method (Hyperchem software package) indicate that the negative charge is rather delocalized and large fractions reside on the oxygen atom of the carbonyl (-0.48 and -0.51, respectively) and on the a-carbon atom of the substituent (-0.15 and -0.25, respectively). This charge distrihution, also found in the corresponding structures derived from suprofen (10) and from ketoprofen, confirms the key role of the carbonyl group in the mechanism of photodecarboxylation of these molecules (4,(9)(10)(11)(12). We finally note that the mechanism of decarboxylation in TPA is similar to that of suprofen, in which a decarboxylated triplet biradical with 4 p lifetime at 25°C was suggested to form from the lowest triplet state via a thermally activated process (10).…”

Section: Laser Flash Photolysis Of Tpa In Phosphate Buffersupporting

confidence: 79%

“…The photoreactivity of the two compounds has been recently investigated by means of emission studies and steadystate photolysis and has been shown to be mediated by the lowest T,T* triplet state (4). The TPA in aqueous medium undergoes a photodecarboxylation, characterized by relatively high quantum yields (0.25 at 25°C) and by an activation energy of 7-10 kcal/mol.…”

Section: Introductionmentioning

confidence: 99%

“…In both photoinduced decarboxylation and reduction, the involvement of the n,n* triplet state is proposed on the basis of temperature-dependence studies and quantum mechanical calculations. On the contrary, the lowest T,T* triplet was found to be active in electron transfer reactions with p-cresol and tyrosine methyl ester in alcoholic medium (4). This paper deals with the characterization of the intermediates involved in the photochemistry of DTPA and TPA by nanosecond laser flash photolysis.…”

Section: Introductionmentioning

confidence: 99%

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Transient Species in the Photochemistry of Tiaprofenic Acid and Its Decarboxylated Photoproduct*

Encinas

Miranda

Marconi

et al. 1998

Photochem & Photobiology

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Photoexcitation of tiaprofenic acid (TPA) in aqueous medium leads with almost unitary efficiency to the lowest m,n* triplet, which is detected by transient absorption. The deactivation of this state occurs in the microsecond time domain and is dominated by a thermally activated spin-allowed process with -10 kcaVmol energy barrier. The occurrence of decarboxylation from an upper state, likely the second triplet of n,m* character, is confirmed by the study of the transients toward the final keto photoproduct, i.e. the benzoylthiophene ethyl derivative (DTPA). At neutral pH, upon adiabatic release of the C 0 2 fragment, long-lived triplet biradicals and groundstate intermediates with a protonated carbonyl oxygen are formed. Laser flash photolysis of DTPA leads almost quantitatively to the lowest m,m* triplet, with similar T-T absorption features as those of TPA. However the DTPA triplet appears essentially unreactive in aqueous medium. In isopropanol H-abstraction from the solvent is demonstrated by the formation of the ketyl radical.

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Section: Laser Flash Photolysis Of Tpa In Phosphate Buffersupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transient Species in the Photochemistry of Tiaprofenic Acid and Its Decarboxylated Photoproduct*

Encinas

Miranda

Marconi

et al. 1998

Photochem & Photobiology

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“…The very high preexponential factor A, (>lo" S K I ) indicates that the photochemical channel is actually open from a triplet close in energy to T2 (n,r*). Similar features are observed in the photochemistry of the related molecule tiaprofenic acid also (24). The behavior of SPF can be compared to that of ketoprofen.…”

Section: Photoprocesses In Aqueous Mediumsupporting

confidence: 62%

Triplet Photochemistry of Suprofen in Aqueous Environment and in the β-Cyclodextrin Inclusion Complex

Sortino¹,

Guidi²,

Marconi³

et al. 1998

Photchem. Photbio.

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The photodecarboxylation of suprofen in the carboxylate form was studied in aqueous medium as a function of the temperature, the concentration and the presence of oxygen by steady-state and time-resolved photochemical techniques. The process is characterized by an activation energy of 9-10 kcal/mol, the precursor state being the lowest triplet which is of pi-pi* nature. The reactivity of the drug was also studied in the beta-cyclodextrin inclusion complex and an additional photoreaction involving the macrocycle as reactive species was observed. Representative NMR and circular dichroism measurements were performed. Singlet molecular oxygen formation was also investigated.

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“…The key drug-derived chemical entity appears to be the excited triplet state, with a transient absorption spectrum very similar to those of other benzophenone derivatives (33), which was quenched by 2Ј-deoxyguanosine and less efficiently by thymidine. In fact, the active chromophore of TPA is the 2benzoyltiophene moiety, a heterocyclic benzophenone also present in its photoproduct DTPA (34,35). This chromophore was able to photosensitize the oxidation of 2Ј-deoxyguanosine and thymidine, giving a variety of photoproducts ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Tiaprofenic Acid-photosensitized Damage to Nucleic Acids: A Mechanistic Study Using Complementary in vitro Approaches

Agapakis-Causse

Boscá

Castell

et al. 2000

Photochem Photobiol

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In order to determine whether or not tiaprofenic acid (TPA) could cause cellular DNA damage, human fibroblasts were irradiated in the presence of the drug and subsequently examined by means of the comet assay. This led to the observation that TPA actually sensitizes cellular DNA to the subsequent irradiation. When TPA was irradiated in the presence of supercoiled plasmid DNA, it produced large amounts of single-strand breaks (SSB); this is consistent with the effects observed on cellular genomic DNA by the comet assay. More importantly, low concentrations of TPA, unable to produce direct SSB, caused photo-oxidative damage to DNA as revealed by the use of excision-repair enzymes. The fact that TPA-irradiated DNA was a substrate of formamidopyrimidine glycosylase as well as endonuclease III revealed that both purine and pyrimidine bases were oxidized. This was further supported by the TPA-photosensitized oxidation of 2'-deoxyguanosine which led to a product mixture characteristic of mixed type-I/II mechanisms. Thymidine was less reactive under similar conditions, but it also decomposed to give a typical type-I product pattern. Accordingly, the TPA triplet was quenched by the two nucleosides with clearly different rate constants (10(8) vs 10(7) M-1 s-1, respectively). As cellular RNA also contains oxidizable bases, it could be the target of similar processes, thus interfering with the biosynthesis of proteins by the cells. Extraction of total RNA from TPA-irradiated human fibroblasts, followed by gel electrophoresis and PCR analysis, confirmed this hypothesis. Finally, photosensitization experiments with Saccharomyces cerevisiae showed that, in spite of an efficient drug-yeast interaction leading to cytotoxicity, neither intergenic recombination nor gene conversion took place. Thus, while TPA-photosensitized damage to nucleic acids can result in genotoxicity, the risk of mutagenicity does not appear to be significant.

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Triplet Photoreactivity of the Diaryl Ketone Tiaprofenic Acid and Its Decarboxylated Photoproduct. Photobiological Implications

Cited by 11 publications

References 16 publications

Transient Species in the Photochemistry of Tiaprofenic Acid and Its Decarboxylated Photoproduct*

Transient Species in the Photochemistry of Tiaprofenic Acid and Its Decarboxylated Photoproduct*

Triplet Photochemistry of Suprofen in Aqueous Environment and in the β-Cyclodextrin Inclusion Complex

Tiaprofenic Acid-photosensitized Damage to Nucleic Acids: A Mechanistic Study Using Complementary in vitro Approaches

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