Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Metabolism of Chloroquine by Human, Rat, and Mouse Microsomal Reaction
2.2.2. HPLC-DAD-MS Measurement
2.2.3. Biomimetic Oxidation of Chloroquine Catalyzed by Dissolved FeTPPS Metalloporphyrin
2.2.4. Surface Functionalization of Silica Particles
2.2.5. Immobilization of FeTPPS Metalloporphyrin on Functionalized Silica Particles in Batch Mode
2.2.6. Determination of Immobilization Yield (YI)
2.2.7. SEM/EDAX Analysis
2.2.8. Biomimetic Oxidation of Chloroquine Catalyzed by Dissolved FeTPPS in Batch Reaction Mode
2.2.9. Biomimetic Oxidation of Chloroquine Catalyzed by Immobilized FeTPPS in Batch Mode
2.2.10. Immobilization of FeTPPS Metalloporphyrin on Functionalized Silica Particles in Continuous-Flow Mode
2.2.11. Biomimetic Oxidation of Chloroquine Catalyzed by Immobilized FeTPPS in Continuous-Flow Mode
2.2.12. Calculation of Biomimetic Reaction Parameters
3. Results
3.1. Metabolic Stability Study for Chloroquine by Liver Microsome from Different Origins
3.2. Immobilization of Metalloporphyirin onto Amino-Functionalized Silica Particles
3.3. Biomimetic Oxidation of Chloroquine by Dissolved and Immobilized Metalloporphyrin in Batch Mode
3.4. Biomimetic Oxidation of Chloroquine by Dissolved and Immobilized Metalloporphyirin in Continuos-Flow Mode
3.5. Comparison of the Effectivity of Liver Microsomal and Biomimetic Systems for the Investigation on Chloroquine Metabolism
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Metabolite Profile | |||
---|---|---|---|
HLM | RLM | MLM | |
Chloroquine (CQ) | 97.4 | 97.5 | 94.8 |
M1 (CQ − 28u, −Et) | 2.6 | 2.1 | 3.4 |
M2 (CQ + 16, +O) | – | 0.5 | 1.8 |
c1 (%) | 2.6 | 2.5 | 5.2 |
Metabolite Profile (%) | ||||
---|---|---|---|---|
FeTPPS | Silica-Am-1-FeTPPS | Silica-Am-2-FeTPPS | Silica-Am-3-FeTPPS | |
CQ | 60.5 | 47.4 | 73.6 | 81.4 |
M1 (CQ − 28u) | 28.4 | 39.6 | 19.8 | 13.8 |
M2 (CQ + 16) | – | – | – | – |
M3 (M1 − 28u) | – | 12.5 | 6.6 | – |
M4 (M3 + 16u) | 0.2 | 0.2 | 0.1 | <0.1 |
M5 (M1 + 30u) | 0.1 | – | – | <0.1 |
M6 (M5 − 2u) | 0.2 | 0.1 | – | – |
Other | 0.4 | 0.4 | – | – |
c1 (%) | 39.5 | 52.6 | 26.4 | 18.6 |
Silica-Am-1-FeTPPS | Silica-Am-2-FeTPPS | Silica-Am-3-FeTPPS | |
---|---|---|---|
CQ | 98.0 | 23.6 | 49.6 |
M1 (DCQ) | 2.0 | 29.3 | 29.9 |
M3 (DDCQ) | – | 36.6 | 19.3 |
Other | – | 10.4 | 2.1 |
c1 (%) | 2.0 | 76.4 | 50.4 |
Catalyst | Reaction Mode | TON (–) | STY (mg L−1 h−1) |
---|---|---|---|
HLM | batch | – | 0.32 |
RLM | – | 0.31 | |
MLM | – | 0.64 | |
FeTPPS | 6.56 | 184 | |
Silica-Am-1-FeTPPS | batch | 8.73 | 296 |
Silica-Am-2-FeTPPS | 4.38 | 119 | |
Silica-Am-3-FeTPPS | 3.09 | 84 | |
Silica-Am-1-FeTPPS | continuous-flow | 0.04 | 2309 |
Silica-Am-2-FeTPPS | 1.62 | 88,213 | |
Silica-Am-3-FeTPPS | 1.07 | 58,193 |
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Balogh, G.T.; Decsi, B.; Krammer, R.; Kenéz, B.; Ender, F.; Hergert, T.; Balogh-Weiser, D. Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin. Metabolites 2022, 12, 1269. https://doi.org/10.3390/metabo12121269
Balogh GT, Decsi B, Krammer R, Kenéz B, Ender F, Hergert T, Balogh-Weiser D. Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin. Metabolites. 2022; 12(12):1269. https://doi.org/10.3390/metabo12121269
Chicago/Turabian StyleBalogh, György T., Balázs Decsi, Réka Krammer, Balázs Kenéz, Ferenc Ender, Tamás Hergert, and Diána Balogh-Weiser. 2022. "Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin" Metabolites 12, no. 12: 1269. https://doi.org/10.3390/metabo12121269
APA StyleBalogh, G. T., Decsi, B., Krammer, R., Kenéz, B., Ender, F., Hergert, T., & Balogh-Weiser, D. (2022). Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin. Metabolites, 12(12), 1269. https://doi.org/10.3390/metabo12121269