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SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS‐XIV. THE SPIN TRAPPING OF FREE RADICALS FORMED DURING THE PHOTOLYSIS OF HALOGENATED SALICYLANILIDE ANTIBACTERIAL AGENTS
Author(s) -
Chignell Colin F.,
Sik Robert H.
Publication year - 1989
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1989.tb04162.x
Subject(s) - chemistry , radical , photochemistry , spin trapping , irradiation , photodissociation , aryl , solvent , ethanol , steric effects , medicinal chemistry , stereochemistry , organic chemistry , alkyl , physics , nuclear physics
— Several antibacterial halogenated salicylanilides, including 3,3′,4′,5‐tetrachlorosalicylanilide (TCSA) and 3,4′,5‐tribromosalicylanilide (TBSA) are known to cause photoallergy. We have carried out photochemical and spin trapping studies to determine whether free radicals may be involved in the photoallergic response. Irradiation (λ > 300 nm) of TCSA in buffered (pH 7.4) 50% ethanol resulted in the rapid loss of the 3‐chloro atom, followed by the much slower release of 5‐ and then the 4′‐chloro atoms to give 3′‐chlorosalicylanilide as a stable photoproduct. Under the same conditions TBSA successively lost the 3‐, 5‐ and 4′‐bromine atoms to give salicylanilide. When TCSA or TBSA were irradiated (λ= 356 nm) in buffered (pH 7.4) 50% ethanol containing 2‐methyl‐2‐nitrosopropane (MNP) only solvent‐derived free radicals were detected. However, irradiation (λ= 356 nm) of TCSA and MNP in 0.1 N NaOH generated an ESR spectrum consisting of a broad triplet (a N = 15.6 G).This spectrum was attributed to the adduct formed by the reaction of MNP with the aryl radical generated by the loss of a chlorine atom from the sterically hindered 3‐(or 4′‐)‐position. Under the same conditions TBSA initially generated a broad triplet (a N = 15.5 G) similar to that observed for TCSA. However, upon further irradiation a 21‐line spectrum (a N = 14.4 G, a 2H = 2.0 G and a 2H = 0.9 G) appeared. Since the same ESR spectrum was obtained by irradiating 4′‐bromosalicylanilide, the spectrum must be generated by an adduct formed by reaction of MNP with an aryl radical derived from loss of the 4′‐bromine atom of TBSA. Irradiation (λ= 356 nm) of TBSA, glutathione and the spin trap 5,5‐dirrrethyl‐l‐pyrroline‐N‐oxide (DMPO) yielded the glutathione thiyl adduct of DMPO. Irradiation of (λ= 356 nm) TCSA, MNP and glycylglycine resulted in the trapping of a carbon‐centered radical derived from hydrogen abstraction from the backbone methylene of the C‐terminal glycine residue. These studies demonstrate that photo‐irradiation of TCSA or TBSA generates highly reactive aryl radicals, which can react with peptides to form secondary radicals. The in vivo reaction of secondary protein radicals with the primary aryl radicals from TCSA or TBSA would result in the covalent binding of the salicylanilides to skin proteins to give molecules with antigenic potential.