Molecular Mechanisms of Photosensitization Induced by Drugs XII. Photochemistry and Photosensitization of Rufloxacin: An Unusual Photodegradation Path for the Antibacterials Containing a Fluoroquinolone‐like Chromophore

Abstract

The UVA irradiation of 9-fluoro-2,3-dihydro-10-4'-methyl-1' -piperazinyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzo-thiazine-6-carboxylic acid, rufloxacin, a fluoroquinolone antibacterial that shows photosensitizing properties toward biological substrates, leads to formation of two main steady photoproducts characterized by a decarboxylation process and an opening of the piperazinyl ring, respectively. The deprotonation of the 10-piperazinyl group and the dissociation of the 6-carboxyl group of rufloxacin are strictly pH dependent. The photosensitizing activity was tested toward membranes as biological targets. Red blood cell hemolysis and lipid peroxidation were considered as markers of photosensitization. Ultraviolet A-induced damage is strongly influenced by the presence of oxygen, it is triggered by transient species, such as singlet oxygen and free radicals, photogenerated via rufloxacin irradiation, whereas no drug photoproduct is involved in the photosensitization process.

Photochemistry of 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (piperazin-1-yl)quinoline-3-carboxylic Acid (=Ciprofloxacin) in Aqueous Solutions

“…Mass-spectrometry evidence has suggested that a photodimer of unknown structure is formed [12], while further studies have led to the isolation of products resulting from the degradation of the piperazinyl side chain [13]. On the basis of our studies on the photochemistry of related molecules [4] [8], the fact that defluorination had not been detected was difficult to account for. This fact as well as our continuing interest in the field and the importance of compound 1 as a drug encouraged us to carry out a detailed study of its photochemistry.…”

“…The latter process is quite efficient with some derivatives of the series. Processes observed only in some cases are decarboxylation [5d] [8] as well as loss of the 1-alkyl chain, when this is a cyclopropyl group [6a] [7b]. Product studies have been supplemented by photophysical investigations, mainly by laser flash photolysis [4d,e] [8 ± 10], aimed to establishing the complex mechanism involved in the above photoreactions.…”

“…s, NH); 8.55 (s, HÀC(2)); 9.5 (br., OH); 10.7 (s, OH). 13 C-NMR ((CD 3 ) 2 SO): 7.8 (CH 2 ); 36.0 (CH); 43.0 (CH 2 ); 46.2 (CH 2 ); 105.9 (CH(5)); 106.5 (C(3)); 109.0 (CH(8)); 120.4 (C); 136.1 (C); 145.7 (C(7)); 146.2 (CH(2)); 149.3 (C(6)); 166 8. (COOH), 176.4 (C(4)O).…”

Enhanced Photostability of Fluoroquinolone Antibacterials Capped on Silver Nanoparticles

“…The excited triplet state is effectively quenched by oxygen leading to the effective formation of singlet oxygen, [33] which has been labeled as one of the main species induced in the phototoxic effects induced by RF on biosubstrates. [40][41][42] In the case of Ag@RF nanoparticles, no significant transient absorption is observed [ Figure 6(D)]. At this point, it is unclear if this may reflect a complete suppression of the isc quantum yield, a dramatic shortening of the triplet lifetime whose decay fall in the subnanosecond time regime, or both.…”

Isolation of Two Isolates from Abrus precatorius Methanolic Extract Using Spectrometry

“…Sources of impurities are organic, which include decarboxylation and hydrolysis photolytic cleavage, which include enantiomeric inorganic, reagents, ligands, catalysis and heavy metals. Others are in-process production related impurities, which include stereochemistry, solvent, synthetic intermediate, byproducts, storage, leachable and extractable related impurities [2,[4][5][6][7][8][9][10][11].…”