چكيده لاتين
The aim of this thesis is to investigate the interaction between a drug delivery system, consisting of pemetrexed immobilized on a gold electrode, and heavy metal ions of Zr, Hf, Fe, Pb, As, and Cd. Accordingly, in the first chapter, the behavior of heavy metal ions in relation to environmental and pharmaceutical concerns, as well as their interaction with drug systems, is reviewed from the perspective of chemical literature. The importance of studying their interaction with the self-assembled monolayer system of pemetrexed is also discussed.
In the second chapter, the practical method for modifying the electrode surface and the fabrication of the monolayer system, gold-mercaptopropionic acid-pemetrexed (Au-MPA-PMTXD) is described. The procedure for collecting selected heavy metal ions on this drug system is then presented, along with the use of cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques and the instruments employed.
In the third chapter, the interaction of the prepared systems with the metal ions of Zr, Hf, Fe, As, Cd, and Pb is individually examined. The data showed that these ions are adsorbed onto the Au-MPA-PMTXD system and reduce the electrochemical activity of the drug (i.e., decrease the redox peak current and move the peak potential to unfavorable direction). This behavior is attributed to the blocking of the drug active sites by the metal ions. The most significant surface blocking effect was observed with Zr and Hf, followed by Cd, Pb, and As, respectively. The Fe ion exhibited a different behavior: the oxidation peak potential of the system shifted from 0.208 V to a more favorable 0.021 V, most probably, due t different formation of Fe(II) and Fe(III) with drug (similar to the behavior if well-know Fe-phenantheroline systems).
Later in this chapter, the interaction of systems containing adsorbed Zr, Hf, and Fe ions with MCF-7 cancer cells was investigated. According to these studies, Zr and Fe ions-unlike Hf-enhanced the electrochemical activity of the drug in the presence of cancer cells. This suggests that in the presence of Zr and Fe ions, the redox-active part of the drug remains uncomplexed and electrochemically active.
So, according to the obtained data, it can be concluded that the efficacy of pemetrexed in patients may be affected when exposed to environments contaminated with the mentioned heavy metals. Specifically, in the presence of Zr and Hf ions, the drug appears to have little to no effect on cancer cells. Nevertheless, more comprehensive studies on this drug and similar compounds in the presence of metal ions in living organisms and cancer patients are required to further explore this issue.
Finally, based on the conducted studies, the potential for sensor development using this system was evaluated. Since the magnitude of the drug redox signals is influenced by the adsorbed ions, it seems feasible to design, fabricate, and study suitable sensors for some of these ions. However, this activity requires further investigation and is beyond the defined scope of this thesis.
