(b) Answer All Parts
[50 marks]
(i) Metallodrugs can be deactivated by peptides such as glutathione and metallothionine. Describe in detail synthetic strategies that can be used to enhance the biological stability of platinum compounds. Include relevant structures and schemes in your answer. [25 marks]
(ii) Describe in detail the synthetic method used to prepare the anticancer drug cisplatin, cis- $\left[\mathrm{Pt}\left(\mathrm{NH}_{3}\right)_{2} \mathrm{Cl}_{2}\right]$. Compare this method to that used to develop the less active isomer, trans- $\left[\mathrm{Pt}\left(\mathrm{NH}_{3}\right)_{2} \mathrm{Cl}_{2}\right]$. Describe one suitable spectroscopic and one suitable molecular (or biophysical) assay you could use to distinguish both cis- and trans- isomers. Include relevant structures and schemes in your answer. [25 marks]

Question

(b) Answer All Parts
[50 marks]
(i) Metallodrugs can be deactivated by peptides such as glutathione and metallothionine. Describe in detail synthetic strategies that can be used to enhance the biological stability of platinum compounds. Include relevant structures and schemes in your answer. [25 marks]
(ii) Describe in detail the synthetic method used to prepare the anticancer drug cisplatin, cis- $\left[\mathrm{Pt}\left(\mathrm{NH}_{3}\right)_{2} \mathrm{Cl}_{2}\right]$. Compare this method to that used to develop the less active isomer, trans- $\left[\mathrm{Pt}\left(\mathrm{NH}_{3}\right)_{2} \mathrm{Cl}_{2}\right]$. Describe one suitable spectroscopic and one suitable molecular (or biophysical) assay you could use to distinguish both cis- and trans- isomers. Include relevant structures and schemes in your answer. [25 marks]

Accepted Answer

∻Solution∻ ‖ 1 ⋮ **Identify the challenge**: Metallodrugs, such as platinum compounds, can be deactivated by peptides like glutathione and metallothionine due to their strong affinity for metal ions. ‖ ‖ 2 ⋮ **Synthetic strategies**: To enhance the biological stability of platinum compounds, several strategies can be employed: ‖ ‖ ⋮ - **Use of bulky ligands**: Introducing bulky ligands around the platinum center can sterically hinder the approach of deactivating peptides. ‖ ‖ ⋮ - **Optimizing leaving groups**: Modifying the leaving groups to be less labile can reduce the rate of deactivation by peptides. ‖ ‖ ⋮ - **Increasing hydrophobicity**: Making the complex more hydrophobic can decrease its interaction with the aqueous environment inside the body, thus reducing the rate of deactivation. ‖ ‖ 3 ⋮ **Relevant structures**: The structures of modified platinum compounds would include bulky ligands such as phosphines or amines, and optimized leaving groups like amides or sulfonates. ‖ ∻Answer∻ ⚹ Enhance biological stability of platinum compounds by using bulky ligands, optimizing leaving groups, and increasing hydrophobicity. ⚹ ∻Key Concept∻ ⚹ Enhancing biological stability of metallodrugs ⚹ ∻Explanation∻ ⚹ Strategies include steric protection, leaving group optimization, and hydrophobicity increase to prevent deactivation by peptides. ⚹ ∻Solution∻ ‖ 1 ⋮ **Synthesis of cisplatin**: The anticancer drug cisplatin, cis-$\left[\mathrm{Pt}\left(\mathrm{NH}_{3}\right)_{2} \mathrm{Cl}_{2}\right]$, is typically synthesized from potassium tetrachloroplatinate(II), $\mathrm{K}_{2}\left[\mathrm{PtCl}_{4}\right]$, by reaction with ammonia. ‖ ‖ 2 ⋮ **Comparison with trans isomer**: The less active trans isomer, trans-$\left[\mathrm{Pt}\left(\mathrm{NH}_{3}\right)_{2} \mathrm{Cl}_{2}\right]$, can be synthesized under similar conditions but requires more controlled synthesis to favor the trans configuration over the more thermodynamically stable cis isomer. ‖ ‖ 3 ⋮ **Spectroscopic assay**: Infrared (IR) spectroscopy can be used to distinguish between cis and trans isomers due to differences in their vibrational modes. ‖ ‖ 4 ⋮ **Molecular assay**: Nuclear Magnetic Resonance (NMR) spectroscopy can differentiate the isomers based on the distinct chemical environments of the hydrogen atoms in the ammonia ligands. ‖ ∻Answer∻ ⚹ Synthesize cisplatin from $\mathrm{K}_{2}\left[\mathrm{PtCl}_{4}\right]$ with ammonia. Trans isomer synthesis requires controlled conditions. Use IR and NMR spectroscopy to distinguish isomers. ⚹ ∻Key Concept∻ ⚹ Synthesis and differentiation of cisplatin and its isomers ⚹ ∻Explanation∻ ⚹ Cisplatin is synthesized from potassium tetrachloroplatinate(II) and ammonia. IR and NMR spectroscopy can distinguish between cis and trans isomers. ⚹◊What is the mechanism by which peptides such as glutathione and metallothionine deactivate metallodrugs like platinum compounds?⍭ Generate me a similar question◊

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