Identification of Enantiomeric Byproducts During Microalgae-Mediated Transformation of Metoprolol by MS/MS Spectrum Based Networking

Abstract

Metoprolol (MPL) is a chiral β-blocker ubiquitously detected in various environments due to its low to moderate removal in wastewater treatment plants. This study was conducted to test the potential of using microalgae to degrade emerging contaminant MPL and to characterize the enantiomeric enrichment during MPL degradation by microalgae. The results showed that PO43−- P, NO3−- N and MPL could be simultaneously removed in the synthetic effluent by the targeted microalgae species, indicating microalgae were promising in wastewater treatment. Stereoselectivity was observed during MPL degradation by microalgae, with R-form enrichment. A marginal linear relationship between MPL degradation and enantiomeric enrichment was observed, implying that the enantiomeric tool, used as a quantitative indicator of biodegradation, could possibly be applied in MPL degradation by microalgae. An efficient liquid chromatograph tandem high resolution mass spectrometry (LC-HRMS/MS) chiral analytical method was developed to identify transformation products (TPs). The results showed that MS/MS spectral similarity networking could be used as a powerful tool to quickly identify unknown TPs. A total of 6 pairs of chiral TPs were identified, among which two new TPs of MPL including hydroxy{4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl}acetic acid (α-HMPLA) and 4-[2-Hydroxy-3-(isopropylamino)propoxy]benzaldehyde (DMPLD) were firstly reported, and proposed transformation pathways of MPL by microalgae were given. Considering the paired TPs detected and that the degradation of the two enantiomers followed first order kinetics, the two enantiomers likely had the same degradation mechanism.

Enantiomeric Fractionation during Biotransformation of Chiral Pharmaceuticals in Recirculating Water-Sediment Test Flumes

“…A common (and major) TP of atenolol and metoprolol (and other structurally similar β-blockers) is atenolol (metoprolol) acid. It is formed from atenolol by (enzymatic) hydrolysis, e.g., in cyanobacteria or abiotically, and dealkylation of metoprolol (aerobic biotransformation in humans , microalgae, , and fungi). In the test flumes, atenolol/metoprolol acid emerged at medium and low bacterial diversity (S3 and S6) where it was further attenuated (details in ref ): the lower the bacterial diversity (the higher the sediment dilution), the slower was its further attenuation.…”

Effect of PHRs and PCPs on Microalgal Growth, Metabolism and Microalgae-Based Bioremediation Processes: A Review

“…Removal of PHRs and PCPs from wastewaters can be achieved via adsorption on the surface of microalgal cell biomass and absorption (accumulation) inside microalgal cells, as well as via intracellular and/or extracellular biotransformation/biodegradation [18]. Efficiency of pollutant removal is dependent on microalgal strain adaptability and specificity towards a target pollutant, as well as initial microalgal cell densities, initial pollutant loadings, enantiomeric form of the pollutant [261], contact time and cultivation parameters (pH, salinity, light intensity). Removal of amoxicillin and cefradine by Microcystis aeruginosa was also greatly improved in the presence of NaAc or glucose [285].…”

“…Besides proper cultivation systems, microalgae require microelements and macroelements (nitrates, ammonium, phosphates) [261,262,263], which can be found at different concentrations in wastewaters.…”

“…Such photodegradation products can be more toxic than a parent compound itself [131,188,260]. Large-volume microalgal cultures can require high amounts of nitrogen and phosphorous in wastewaters as sources of nutrients [261,262,263,264] for growth. The concentrations of N and P should be monitored during PHRs/PCPs’ biotreatment because different N and P concentrations can influence microalgal cell–PHRs/PCPs interactions [129,228,240,241].…”

Complementary Analytical Platforms of NMR Spectroscopy and LCMS Analysis in the Metabolite Profiling of Isochrysis galbana

“…This approach offers new ways of exploring the metabolome of biological samples by providing essential analog knowledge among the metabolites identified. Numerous MN applications in microalgae chemistry have been documented in recent years [ 40 , 41 , 42 ].…”