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A Theoretical Study on Derivatives of 1,2,4-trioxane as Potential Anti-malarials and an Analysis of the Mechanism of Drug Release in the Presence of Fe(III) Ions
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- 02 Mar 2024
- 12 Aug 2024
- 01 Oct 2024
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Abstract
A mechanism has been proposed for the targeted transfer of an antimalarial drug, which involves 1, 2, and 4 trioxane (TRX) reagents. The trioxane ring is sensitive to ferrous iron, Fe)II(, and when exposed to it, it breaks down into smaller pieces, releasing the antimalarial drug mML (a mock form of DPA1 inhibitor ML4118S).
The oxane ring is attached to a nanoparticle called adamantane, which helps facilitate the reaction. The mechanism has been investigated using two reactants: TRX-R-mML and TRX-H-mML complexes (R is a side chain). The researcher used the transition state theory, the Hartree-Fock level (HF), and the ground state series 6-31G** to investigate the mechanism. The physicochemical and geometric properties of the components involved in the reaction were measured to explain the mechanism better.
The results indicate that the R as a side chain significantly affects the mentioned mechanism and properties. Additionally, the results of the calculations show the stability of the complexes required as reactants in the reaction.
The TRX-mML-R complex has more strength, and polarity than TRX-mML-H, and the energy level of the transition state of TRX-mML-R is lower than that of TRX-mML-H, indicating faster passage of raw materials.