BMe Research Grant
Figure 1: The route of drug development1
Figure 2: Examples of the biologic systems used in the metabolism studies
Figure 3: Comparing the general structure of Protoporphyrin IX and synthetic metalloporphyrins
Authorities require the determination of the exact structure and biological effect of the metabolites formed in the human body. Metabolites are formed only in low concentrations in the currently used biological systems and the present complex biological matrix makes the analysis more difficult. Preparation of metabolites in higher amounts is usually only possible through the development of new synthetic routes, which can increase the duration and expenses of the drug development. With the use of synthetic metalloporphyrins both the qualitative analysis (no complex biological matrix, and metabolites are formed in higher concentration) and the preparation of metabolites in higher amounts can be achieved. The metabolite composition of the reaction mixture can be enhanced by the systematic change of the reaction conditions (temperature, properties of oxidizing agent and metalloporphyrin, pH), thus the composition can be shifted towards the higher amount of the desired metabolite. The favorable conditions can be determined by optimizing the biomimetic reaction. A disadvantage of using synthetic metalloporphyrins is their easy degradation (for example metalloporphyrins can form the so-called µ-oxo-dimers in alkaline conditions which can inactivate the catalyst ), therefore, the stability of the porphyrins should be improved. The volume achieved by a homogeneous reaction may limit the formation of metabolites in large volumes, which can be overcome by using more catalyst; however, this significantly increases the expenses of the synthesis. These problems can be solved by the immobilization of porphyrin on solid supporters. The immobilized porphyrin based catalyst systems can offer a unique opportunity for high-efficiency, continuous-flow reaction pathway. During my research I try to find a novel solution for these problems by developing immobilized catalytic systems.
Figure 4: Demonstration of the homogeneous reaction
Figure 5: The properties of the mesoporous silica and the modified surface
Figure 6: Immobilization of the porphyrin catalyst and the value of the immobilization yield (IY, %)
Figure 7: The space time yield (STY) and comparing the presented systems
Figure 8: The general scheme of the microfluidic reaction
Figure 9: Microfluidic chip device in use
[S1] Decsi, B.; Krammer, R.; Hegedűs, K.; Ender, F.; Gyarmati, B.; Szilágyi, A.; Tőtős, R.; Katona, G.; Paizs, Cs.; Balogh, Gy., T.; Poppe, L.; Balogh-Weiser, D. Liver-on-a-Chip‒Magnetic Nanoparticle Bound Synthetic Metalloporphyrin-Catalyzed Biomimetic Oxidation of a Drug in a Magnechip Reactor. Micromachines 2019, 10, 668.
[S2] Fődi, T.; Ignácz, G.; Decsi, B.; Béni, Z.; Túrós, G.I.; Kupai, J.; Weiser, D.B.; Greiner, I.; Huszthy, P.; Balogh, Gy.T. Biomimetic Synthesis of Drug Metabolites in Batch and Continuous-Flow Reactors. Chem. - A Eur. J. 2018, 24, 9385–9392.
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