On the photooxidation of the multifunctional drug niclosamide. A kinetic study in the presence of vitamin B2 and visible light

Abstract

Objectives: The multifunctional drug niclosamide (NSD), extensively employed therapeutically, is a frequent pollutant of surface waters. Considering the environmental importance of photodegradative processes for this type of contaminant, the kinetic and mechanistic aspects of the possible visible-light-mediated photooxidation of NSD were studied under naturalistic conditions.

Methods: The visible-light absorber riboflavin (vitamin B2) was employed as a photosensitizer. The vitamin can usually be found in natural waters and is the most common endogenous photosensitizer in mammals. The interaction of NSD with electronically excited states of Rf and with photogenerated reactive oxygen species (ROS) was evaluated through conventional UV spectroscopy, laser flash photolysis, time-resolved phosphorescence detection of singlet molecular oxygen (O2((1)Δg)), and polarographic dosage of dissolved oxygen.

Results: Ground state NSD quenched the long-lived triplet excited state of Rf ((3)Rf*) and the photogenerated ROS (O2((1)Δg)) and superoxide radical anion (O2•−). As a result, NSD was photooxidized. The rate constants for the interaction NSD-O2((1)Δg) are particularly low, in the order of 10(6)/M/s, although the whole interaction is attributable to a pure reactive process. The O2((1)Δg) quenching was faster in alkaline medium, favored by the ionization of the NSD phenolic group. Under Rf-photosensitization, NSD was degraded very much more rapidly than phenol, the latter being considered a paradigmatic water-contaminant model compound. NSD may behave as an antioxidant in bio-environments, as demonstrated employing the photooxidizable amino acid tryptophan as a relevant biological target.

Discussion: The results indicate that a O2•−-mediated process is the main route for the Rf-sensitized photooxidation of NSD. Photodegradation of the biocide in the presence and absence of phenol and tryptophan was quantitatively evaluated, discussed, and interpreted in terms of competitive quenching processes of (3)Rf*, O2((1)Δg), and O2•− by the substrates.

Keywords: Niclosamide; Photodegradation; Photooxidation; Reactive oxygen species; Riboflavin.

Figure 1

Acid-base equilibrium of NSD species: (a) NSD in MeOH, (b) NSD in MeOH plus 50 mM NaOH. The spectra were normalized at 330 nm.

Figure 2

Changes in the UV-vis absorption spectrum of a methanolic solution of 0.05 mM Rf plus 0.03 mM NSD upon photoirradiation, taken vs. 0.05 mM Rf in the same solvent. Inset (A): absorption spectrum of 0.05 mM Rf in MeOH shown for comparative purposes. Inset (B): monitoring of the absorption changes at 378 nm upon photoirradiation of: Rf 0.05 mM in MeOH (a); the main figure (b).

Figure 3

Bar diagram for the relative rates of oxygen uptake for 0.5 mM NSD + Riboflavin (A₄₄₅ = 0.4) as a function of photoirradiation time in MeOH, in the absence (1) and in the presence of 1 μg/ml SOD (2); and 1 mM NaN₃ (3). Bar (4) corresponds to the relative rate for riboflavin (A₄₄₅ = 0.4) in MeOH.

Figure 4

Stern–Volmer plot for the quenching of ³Rf* by NSD in MeOH. The ordinate axis represents the inverse of ³Rf* lifetime in the presence of different NSD concentrations.

Figure 5

Stern–Volmer plot for the quenching of O₂(¹Δ_g) by NSD in MeOD plus 50 mM NaOH. Inset (A): first-order plot for oxygen uptake upon visible-light irradiation by solutions containing RB (A₅₄₉ = 0.32) plus: 0.5 mM FFAc (a) and 0.5 mM NSD (b), in MeOH plus 50 mM NaOH. Inset (B): spectral evolution of 0.04 mM NSD plus RB A₅₅₇ = 0.54 vs. RB A₅₅₇ = 0.54 upon photoirradiation (cutoff 400 nm) in MeOH plus 50 mM NaOH.

Figure 6

Bar diagram for the relative rates of oxygen uptake as a function of photoirradiation time (cut-off 400 nm) for 0.035 mM Riboflavin + 0.45 mM NSD + 0.45 mM Trp (1); 0.035 mM Riboflavin + 0.45 mM Trp (2); 0.035 mM Riboflavin + 0.45 mM NSD (3); 0.035 mM Riboflavin + 0.45 mM PHE (4). Bar (5) corresponds to the relative rate for 0.035 mM Riboflavin in MeOH.

Figure 7

Evolution of the absorption spectrum of 0.08 mM NSD in MeOH plus 50 mM NaOH upon photolysis at 254 nm. Numbers on the spectra represent irradiation time, in minutes. Inset (a): molar consumption as a function of irradiation time for 0.08 mM NSD in MeOH plus 50 mM NaOH monitored at 380 nm. Inset (b): molar consumption as a function of irradiation time for 0.16 mM BXN in H₂O (the actinometer) monitored at 285 nm.