Effect of Magnesium and Calcium Complexation on the Photochemical Properties of Norfloxacin

Abstract

The fluoroquinolone antibiotics can induce skin photosensitivity in some patients and this has been ascribed to the generation of reactive oxygen species, such as singlet oxygen (OZ[lAg]). We have studied the photochemical properties of the different ionized forms of the fluoroquinolone norfloxacin upon complexation with MgZ+ and Caz+ ions, as it is proposed that the antibiotic exists mainly as a complex in the blood plasma. We found that the norfloxacin cation (pH < 6) shows no photodegradation after UVA irradiation and has a low quantum yield of 02(lAg) generation. The norfloxacin cation does not complex.Ca2+ or Mgz+ ions; when these ions are added to the solution, we observed no changes in the fluorescence quantum yields and singlet oxygen yields (aA). In contrast, the neutral (6 5 pH 4 8.5) and anionic (pH > 9) forms of norfloxacin are able to complex calcium and magnesium, and their generation of Oz ('Ag) is decreased by complexation. The neutral zwitterionic form and the anionic form also quench singlet oxygen by both chemical and physical pathways regardless of complex formation, while physical quenching is observed for the cation. At pH 2 7.4, norfloxacin photobleaches and complexation to Ca2+ and Mgz+ increases the rate at which photobleaching occurs. Thus, both the pH of the medium and complexation with metal cations may affect the phototoxic potential of this antibiotic.

Structure and Medium-Dependent Photodecomposition of Fluoroquinolone Antibiotics

“…The photoprocess causing this effect has not yet been unambiguously recognized, however. Several reports have shown that the photoreactivity of FQ is strongly dependent on the pH (5942), as one may expect with such zwitterionic species and also on the presence of some cations (63). Evidence has been reported for a role of reactive oxygen species such as singlet oxygen, the superoxide anion or the hydroxyl radical (3933,6449) to the FQ-induced phototoxicity, and it has been proposed that oxygen activation is the mechanism involved.…”

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

“…The neutral and anionic forms of NOR complex calcium and magnesium (the antibacterial exists mainly as a complex in the blood plasma); 1 O 2 generation is decreased by complexation. At pH ≥ 7.4, complexation to Ca 2+ and Mg 2+ increases the rate of NOR photodegradation (77). Cu 2+ in the micromolar range modulates RUF photodegradation rate.…”

Elucidating Direct Photolysis Mechanisms of Different Dissociation Species of Norfloxacin in Water and Mg2+ Effects by Quantum Chemical Calculations

“…The order of the computed wavelength at maximum electronic absorbance of the three dissociation species in water is NOR 2+ (280 nm) < NOR 0 (282 nm) < NOR + (308 nm) at TDDFT/B3LYP/6-311++G (d,p) level. The corresponding experimental data is around 275 nm in water (pH = 7.0) [ 21 ] and 274 nm in water (pH = 7.4) [ 23 ].…”

“…Recently, issues related to the study of pollution resulting from the combination of antibiotics and metals have been drawing a lot of attention [ 20 , 22 , 23 ]. Previous studies have suggested that metal ions such as Mg 2+ can have an effect on the photochemical behavior of organic pollutants [ 20 , 24 ].…”

“…For example, Werner et al [ 22 ] found that the direct photolysis rate constant of tetracycline was greatly influenced by the presence of Ca 2+ or Mg 2+ . Martínez et al [ 23 ] found that metal cations may affect the photochemical properties of NOR. Metal ion Mg 2+ occurs at a high concentration in natural water environment [ 25 ].…”