Water concentration dependent photochemistry of ketoprofen in aqueous solutions

Abstract

Ketoprofen is an important photosensitive drug molecule that has received much attention for the study of its photochemistry in different solvents. In this paper, nanosecond time-resolved resonance Raman spectroscopy was utilized to investigate the photochemistry of ketoprofen in aqueous solutions with varying water concentrations. The rate constants and reaction mechanism of ketoprofen are strongly dependent on the concentration of the solvent. In neat acetonitrile and solvents with low concentrations of water (like water-acetonitrile <or= 1 : 1, v/v), ketoprofen exhibits mostly benzophenone-like photochemistry to generate a triplet state which in turn produces a ketyl radical-like species by a hydrogen abstraction reaction. However, in solvents with very high concentrations of water (such as water-acetonitrile >or= 9 : 1, v/v), the triplet state ketoprofen is observed first and then undergoes a prompt decarboxylation process to form a triplet protonated biradical carbanion species. For solvents with moderate higher water concentrations (such as between 50% and 90% water by volume), the hydrogen abstraction and decarboxylation processes are two competitive pathways with different rate constants. The triplet state of ketoprofen will simultaneously produce a ketyl radical species and a triplet protonated biradical carbanion species with the amount of each species dependent on the water concentration.

Water‐ and Acid‐Mediated Excited‐State Intramolecular Proton Transfer and Decarboxylation Reactions of Ketoprofen in Water‐Rich and Acidic Aqueous Solutions

“…[22] Although water is a poor hydrogen donor, the ketyl radical intermediate may be produced and is readily observed in aqueous solutions. [29] However, two competitive pathways (ketyl radical formation and decarboxylation) exist in water-rich solutions when the water concentrations are !…”

“…A majority of the 3 [KP] produced will experience the decarboxylation process to evolve into the 3 BCH intermediate in the 90 % water solution. [22] Figure 1 presents the ns-TA spectra recorded in the different water and acetonitrile mixtures when using 266 nm laser excitation. In solvents like neat acetonitrile and lowerwater-concentration aqueous solutions, KP exhibits a ns-TA spectra with maxima at 323 and 525 nm, which is consistent with the observation obtained in neat acetonitrile by Scaiano and co-workers.…”

“…[17,21] Our previous study proposed that the rate of an apparent hydrogen abstraction or other process that forms ketyl radicals from the triplet state KP ( 3 [KP]) exhibits an intriguing dependence on the ratio of water in less than 50 % water concentration solutions. [22] However, further increasing the ratio of water may lead KP to exhibit a significant decarboxylation process, especially in solutions with a very high ratio of water (such as water/acetonitrile ! 9:1 v/ v), [22] although most early studies suggested that only the dissociated…”

“…[22] However, further increasing the ratio of water may lead KP to exhibit a significant decarboxylation process, especially in solutions with a very high ratio of water (such as water/acetonitrile ! 9:1 v/ v), [22] although most early studies suggested that only the dissociated…”

“…In water-rich solutions, the dissociated KP is the predominant form and appears tied to the experimental observation of triplet-protonated carbanion biradical ( 3 BCH) intermediate, and this suggests, to some extent, that the decarboxylation may take place with the assistance of water molecules in water-rich solutions. [22] To further study and characterize the reaction mechanism, we performed nanosecond transient absorption (ns-TA) and nanosecond time-resolved resonance Raman (ns-TR 3 ) experiments in a variety of water/ acetonitrile and acidic aqueous mixtures. The ns-TR 3 spectra provide useful vibrational spectroscopic information that can be used to help elucidate the photochemical mechanism(s) and solvent effects on the intermediates involved in the reactions.…”