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Article: Time-Resolved Spectroscopic Characterization of a Novel Photodecarboxylation Reaction Mediated by Homolysis of a Carbon α-Bond in Flurbiprofen

TitleTime-Resolved Spectroscopic Characterization of a Novel Photodecarboxylation Reaction Mediated by Homolysis of a Carbon α-Bond in Flurbiprofen
Authors
Issue Date2013
Citation
The Journal of Physical Chemistry B, 2013, v. 117, p. 8347-8359 How to Cite?
AbstractFlurbiprofen (Fp), a nonsteroidal anti-inflammatory drug (NSAID) currently in use for arthritis pain relief and in clinical trials for metastatic prostate cancer, can induce photosensitization and phototoxicity upon exposure to sunlight. The mechanisms responsible for Fp phototoxicity are poorly understood and deserve investigation. In this study, the photodecarboxylation reaction of Fp, which has been assumed to underpin its photoinduced side effects, was explored by femtosecond transient absorption (fs-TA), nanosecond transient absorption (ns-TA), and nanosecond time-resolved resonance Raman (ns-TR3) spectroscopic techniques in pure acetonitrile (MeCN) solvent. Density functional theory (DFT) calculations were also performed to facilitate the assignments of transient species. The resonance Raman and DFT calculation results reveal that the neutral form of Fp was the predominant species present in MeCN. Analysis of the ultraviolet/visible absorption spectrum and results from TD-DFT calculations indicate that the second excited singlet (S2) can be excited by 266 nm light. Due to its intrinsic instability, S2 rapidly underwent internal conversion (IC) to decay to the lowest lying excited singlet (S1), which was observed in the fs-TA spectra at very early delay times. Intriguingly, three distinct pathways for S1 decay seem to coexist. Specifically, other than fluorescence emission back to the ground state and transformation to the lowest triplet state T1 through intersystem crossing (ISC), the homolysis of the carbon α-bond decarboxylation reaction proceeded simultaneously to give rise to two radical species, one being carboxyl and another being the residual, denoted as FpR. The coexistence of the triplet Fp (T1) and FpR species was verified by means of TR3 spectra along with ns-TA spectra. As a consequence of its apparent high reactivity, the FpR intermediate was observed to undergo oxidation under oxygen-saturated conditions to yield another radical species, denoted as FOR, which subsequently underwent intramolecular hydrogen transfer (IHT) and dehydroxylation (DHO) to form a final product, which could react with the carboxyl from the decarboxylation reaction to generate a minor final product. TD-DFT and transient state (TS) calculations for predicting the absorption bands and activation energies of the transient species produced in the photodecarboxylation reaction have provided valuable mechanistic insights for the assignment of the intermediate species observed in the time-resolved spectroscopy experiments reported here. The results of the time-resolved spectroscopy experiments and DFT calculations were used to elucidate the reaction mechanisms and intermediates involved in the photochemistry of Fp.
Persistent Identifierhttp://hdl.handle.net/10722/202565
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSu, Ten_US
dc.contributor.authorMa, Jen_US
dc.contributor.authorWong, Nen_US
dc.contributor.authorPhillips, DLen_US
dc.date.accessioned2014-09-19T08:41:14Z-
dc.date.available2014-09-19T08:41:14Z-
dc.date.issued2013en_US
dc.identifier.citationThe Journal of Physical Chemistry B, 2013, v. 117, p. 8347-8359en_US
dc.identifier.urihttp://hdl.handle.net/10722/202565-
dc.description.abstractFlurbiprofen (Fp), a nonsteroidal anti-inflammatory drug (NSAID) currently in use for arthritis pain relief and in clinical trials for metastatic prostate cancer, can induce photosensitization and phototoxicity upon exposure to sunlight. The mechanisms responsible for Fp phototoxicity are poorly understood and deserve investigation. In this study, the photodecarboxylation reaction of Fp, which has been assumed to underpin its photoinduced side effects, was explored by femtosecond transient absorption (fs-TA), nanosecond transient absorption (ns-TA), and nanosecond time-resolved resonance Raman (ns-TR3) spectroscopic techniques in pure acetonitrile (MeCN) solvent. Density functional theory (DFT) calculations were also performed to facilitate the assignments of transient species. The resonance Raman and DFT calculation results reveal that the neutral form of Fp was the predominant species present in MeCN. Analysis of the ultraviolet/visible absorption spectrum and results from TD-DFT calculations indicate that the second excited singlet (S2) can be excited by 266 nm light. Due to its intrinsic instability, S2 rapidly underwent internal conversion (IC) to decay to the lowest lying excited singlet (S1), which was observed in the fs-TA spectra at very early delay times. Intriguingly, three distinct pathways for S1 decay seem to coexist. Specifically, other than fluorescence emission back to the ground state and transformation to the lowest triplet state T1 through intersystem crossing (ISC), the homolysis of the carbon α-bond decarboxylation reaction proceeded simultaneously to give rise to two radical species, one being carboxyl and another being the residual, denoted as FpR. The coexistence of the triplet Fp (T1) and FpR species was verified by means of TR3 spectra along with ns-TA spectra. As a consequence of its apparent high reactivity, the FpR intermediate was observed to undergo oxidation under oxygen-saturated conditions to yield another radical species, denoted as FOR, which subsequently underwent intramolecular hydrogen transfer (IHT) and dehydroxylation (DHO) to form a final product, which could react with the carboxyl from the decarboxylation reaction to generate a minor final product. TD-DFT and transient state (TS) calculations for predicting the absorption bands and activation energies of the transient species produced in the photodecarboxylation reaction have provided valuable mechanistic insights for the assignment of the intermediate species observed in the time-resolved spectroscopy experiments reported here. The results of the time-resolved spectroscopy experiments and DFT calculations were used to elucidate the reaction mechanisms and intermediates involved in the photochemistry of Fp.en_US
dc.languageengen_US
dc.relation.ispartofThe Journal of Physical Chemistry Ben_US
dc.titleTime-Resolved Spectroscopic Characterization of a Novel Photodecarboxylation Reaction Mediated by Homolysis of a Carbon α-Bond in Flurbiprofenen_US
dc.typeArticleen_US
dc.identifier.emailPhillips, DL: phillips@hku.hken_US
dc.identifier.authorityPhillips, DL=rp00770en_US
dc.identifier.doi10.1021/jp403053fen_US
dc.identifier.pmid23750456-
dc.identifier.hkuros237009en_US
dc.identifier.volume117en_US
dc.identifier.spage8347en_US
dc.identifier.epage8359en_US
dc.identifier.isiWOS:000322149900006-

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