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

Abstract

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.

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

“…In this state a delocalization of the n electrons of the oxygen atoms (carbonylic and carboxylic) over the two rings takes place, while a minor participation of the sulfur atom is involved. This fact represents a difference with respect to the analogous state in SP, which was also suggested to participate in the photodecarboxylation reaction (25) and is consistent with the lack of effective intervention of the sulfur atom in the photochemistry of these molecules. In this mechanism we have to admit that the internal conversion between T2 and TI is faster than the reaction, the latter likely proceeding from a different nuclear geometry on the T2 potential energy surface.…”

“…Starting optimized ground-state geometries were obtained through the MM + Molecular Mechanics routine. The configuration interaction was limited to a space of 81 singly excited configurations, a space previously tested for similar compounds (25,26) and found reliable to describe, at least qualitatively, the main features of the excited states of diarylketones. The minimum energy configuration of TPA deviates from planarity with angles of 11" and 39" of the phenylic and thiophenic rings, respectively, with respect to the plane of the carbonyl.…”

The Photochemistry of Flutamide and its Inclusion Complex with β-Cyclodextrin. Dramatic Effect of the Microenvironment on the Nature and on the Efficiency of the Photodegradation Pathways¶

“…Due to their molecular structure, many drugs are suitable guests for CD receptors. In this regard, photophysics and photochemistry of drug-CD inclusion complexes have received considerable attention, especially in the last few years (22)(23)(24)(25)(26). The use of CD as a drug complexing agent can represent in fact not only a suitable biological mimicking environment but also a valid tool to minimize the drug-photoinduced biological damage as well as to increase the drug photostability (24,(27)(28)(29).…”

Use of Styrene Radical Cations as Probes for the Complexation Dynamics of Charged Guests with α- and β-Cyclodextrins

“…This reduction in phototoxicity could be related to a decrease in the photodecomposition quantum yield as well as to a change in the decomposition mechanism. Indeed, complexation of drug molecules and analogs to CD has shown a marked effect on the photochemistry of these molecules (7)(8)(9).…”

“…In this respect, incorporation of drugs into CD may lead to a decrease in the quantum yield of their photodecomposition or to a change in the degradation mechanism and production of less toxic by-products. The photodegradation of some drugs, such as ketoprofen and suprofen (7,23,24), leads to the formation of ionic intermediates. Because the reactive intermediates of these drugs may be responsible for some of the undesirable side effects, it is necessary to understand how efficiently CD bind to these transient species.…”