Effect of Basic Amino Acids on Photoreaction of Ketoprofen in Phosphate Buffer Solution

Abstract

Photoreaction of ketoprofen (KP), one of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs), was studied with transient absorption spectroscopy in phosphate buffer solution (pH 7.4) in the presence of basic amino acids of histidine (His), lysine (Lys) and arginine (Arg). Deprotonated form of KP (KP(-)) excited with UV-light irradiation gave rise to carbanion through a decarboxylation reaction. It was found that carbanion abstracted a proton from the side chain of the protonated amino acids to yield 3-ethylbenzophenone ketyl biradical (EBPH); however, no reaction was observed with alanine. The relative yield of EBPH by the proton transfer reaction with His was ca. 40 times larger than that of the other two basic amino acids, suggesting that the proton-donating ability of His (protonated His) should be quite high. The information on the photoreaction mechanism of NSAIDs with basic amino acids was essential to understand primary reaction of excited NSAIDs in vivo causing photosensitization on human skin.

Photoreaction of Ketoprofen with Tryptophan and Tyrosine in Phosphate Buffer Solution

“…In the phosphate buffer solution of pH 7.4, almost all KP exists in the deprotonated form of KP (KP − ) because of its acidity (p K a = 4.7). According to the previous report , an intense band around 600 nm appearing immediately after the laser irradiation was due to KP carbanion, and the band around 525 nm at 1.7 μs after the laser was assigned to EBPH. The same spectra were obtained with Tyr.…”

“… *Reference ; †For amino acids and dipeptides, correction of the concentration should be required because actual quencher for carbanion was the protonated form to the side chain of basic amino acids and dipeptides ; ‡Reference ; §Reference ; ∥Reference ; ¶This work. …”

“…Several proton‐donating sites for these compounds are considered. As for basic amino acids and dipeptides including a histidine moiety in the phosphate buffer solution at pH 7.4, the protonated side chain is the donating site not the protonated N ‐terminal because alanine and glycine have no effect on the lifetime of the carbanion . Therefore, on phenol compounds such as Tyr, DOPA, 4‐MP, the phenolic OH group is concluded to be the proton‐donating site.…”

“…An experimental setup of the transient absorption spectrum measurement has been reported elsewhere . Briefly, a XeCl excimer laser (Lamda Physik COMPex 102; 308 nm, 200 mJ, 20 ns pulse duration) was used as an excitation light and a Xe flash lamp (Ushio UXL‒300DO; 300 W) was used as a monitoring light source.…”

Aquatic photodegradation of sunscreen agent p-aminobenzoic acid in the presence of dissolved organic matter

“…According to the website of IHSS, amino acids are important compositions of DOM (IHSS website). Suzuki et al have demonstrated that the basic amino acids, including histidine, lysine and arginine, can accelerate the photoreaction of ketoprofen (Suzuki et al, 2012). Here, we used glycine and histidine to test the effect of amino acid on PABA photolysis (Fig.…”