A pulse radiolysis study of free radicals formed by one-electron oxidation of the antimalarial drug pyronaridine

Abstract

Free radicals from one-electron oxidation of the antimalarial drug pyronaridine have been studied by pulse radiolysis. The results show that pyronaridine is readily oxidised to an intermediate semiiminoquine radical by inorganic and organic free radicals, including those derived from tryptophan and acetaminophen. The pyronaridine radical is rapidly reduced by both ascorbate and caffeic acid. The results indicate that the one-electron reduction potential of the pyronaridine radical at neutral pH lies between those of acetaminophen (707 mV) and caffeic acid (534 mV). The pyronaridine radical decays by a second order process which DFT calculations (UB3LYP/6-31+G* ) suggest is a disproportionation reaction. Important calculated dimensions of pyronaridine, its phenoxyl and aminyl radical as well as the iminoquinone are presented.

High-energy ionizing radiation-induced degradation of amodiaquine in dilute aqueous solution: radical reactions and kinetics

“…In OH reaction the 450 nm absorbance was also attributed to the aminophenoxy radical forming in dehydration of the hydroxycyclohexadienyl intermediate. The dehydration is fast process taking place on the few ms timescale [10,14,19]. Bisby [2] suggested a similar mechanism for the OH þ AQ reaction:…”

One-pot synthesis and negative ion mass spectrometric investigation of a densely functionalized cinnoline

“…1 Our strategy has been to identify compounds that initiate antiparasitic drug action from distonic anion radical cascades, 17 using an automated, non-biological screen that could be converted into a high-throughput mode using robotic auto-samplers. 18 We have previously reported that pulsed radiolysis 19 and subsequent negative ion electrospray mass spectrometry 20 were ideally suited to this task and have now identified selected cinnolines as potential antiparasitic agents. 21 In general, densely substituted cinnolines are difficult to construct in a reproducible manner, and to the best of our knowledge, one-pot methods from commercially available raw materials are rare.…”