Pyrroles As Antioxidants: Solvent Effects and the Nature of the Attacking Radical on Antioxidant Activities and Mechanisms of Pyrroles, Dipyrrinones, and Bile Pigments

Abstract

The absolute rate constants, k(inh), and stoichiometric factors, n, of pyrroles, 2-methyl-3-ethylcarboxy-4,5-di-p-methoxyphenylpyrrole, 6, 2,3,4,5-tetraphenylpyrrole, 7, and 2,3,4,5-tetra-p-methoxyphenylpyrrole, 8, compared to the phenolic antioxidant, di-tert-butylhydroxyanisole, DBHA, during inhibited oxidation of cumene initiated by AIBN at 30 degrees C gave the relative antioxidant activities (k(inh)) DBHA > 8 > 7 > 6 and n = 2, whereas in styrene, 8 > DBHA. These results are explained by hydrogen atom transfer, HAT, from the N-H of pyrroles to ROO(*) radicals. The k(inh) values in styrene of dimethyl esters of the bile pigments of bilirubin ester (BRDE), of biliverdin ester (BVDE), and of a model compound (dipyrrinone, 1) gave k(inh) in the order pentamethylhydroxychroman (PMHC) >> BRDE > 1 > BVDE. These antioxidant activities for BVDE and the model compound, 1, and PMHC dropped dramatically in the presence of methanol due to hydrogen bonding at the pyrrolic N-H group. In contrast the k(inh) of BRDE increased in methanol. We now show that pyrrolic compounds may react by HAT, proton-coupled electron transfer, PCET, or single electron transfer, SET, depending on their structure, the nature of the solvent, and the attacking radical. Compounds BVDE and 1 react by the HAT or PCET pathway (HAT/PCET) in styrene/chlorobenzene with ROO(*) and with the DPPH(*) radical in chlorobenzene according to N-H/N-D kH/kD of 1.6, whereas the DKIE with BRDE was only 1.2 with ROO(*). The antioxidant properties of polypyrroles of the BVDE class and model compounds (e.g., 1) are controlled by intramolecular H bonding which stabilizes an intermediate pyrrolic radical in HAT/PCET. According to kinetic polar solvent effects on the monopyrrole, 8, and BRDE, which gave increased rates in methanol, some pyrrolic structures are also susceptible to SET reactions. This conclusion is supported by some calculated ionization potentials. The antioxidant mechanism for BRDE with peroxyl radicals is described by the PCET reaction. Experiments using the 2,6-di-tert-butyl-4-(4'-methoxyphenyl)phenoxyl radical (DBMP(*)) showed this to be a better radical to monitor HAT activities in stopped-flow kinetics compared to the use of the more popular DPPH(*) radical.

A Mussel‐Inspired Persistent ROS‐Scavenging, Electroactive, and Osteoinductive Scaffold Based on Electrochemical‐Driven In Situ Nanoassembly

“…The PPy‐PDA‐HA film exhibited persistent effective antioxidative activity due to the redox behavior of PPy‐PDA NPs. The mechanism by which a PPy‐PDA‐HA film eliminates ROS in physiological conditions is shown in Figure a . When ROS reacted with the PPy‐PDA‐HA film, electrons in the PPy‐PDA NPs will be captured by ROS, thus converting the catechol groups in PPy‐PDA NPs into quinones, and the dedoped state of PPy into the doped state.…”

Biliverdin’s regulation of reactive oxygen species signalling leads to potent inhibition of proliferative and angiogenic pathways in head and neck cancer

“…Previously, BV has been shown to possess highly potent antioxidant properties; significantly more so that BR or other tetrapyrroles found in the body (Asad et al , 2001; Stocker, 2004; MacLean et al , 2008; Molzer et al , 2012). Furthermore, reactive oxygen species (ROS)-mediated cellular signalling has shown to be critical for cellular growth, angiogenic, and other oncogenic pathways.…”

Extracellular and intracellular anti-mutagenic effects of bile pigments in the Salmonella typhimurium reverse mutation assay

“…Vastly unclear to date however, are the underlying mechanisms of anti-genoxic action. In this context mainly electron scavenging or hydrogen donating capacities (MacLean et al, 2008) and structural interactions between BPs and mutagens (Hayatsu, 1995) are discussed. However, data on cellular compound absorption are lacking and so far only one recent report on enzymatic BRDT reduction in bacteria (Konickova et al, 2012) exists.…”