(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 metallothioneine due to their strong affinity for metal ions. ‖ ‖ 2 ⋮ **Synthetic strategies**: To enhance the biological stability of platinum compounds, several strategies can be employed: ‖ ‖ 2.1 ⋮ **Use of bulky ligands**: Introducing bulky ligands around the platinum center can sterically hinder the approach of deactivating peptides. ‖ ‖ 2.2 ⋮ **Increasing kinetic inertness**: Modifying the leaving groups to those that are less labile can slow down substitution reactions with peptides. ‖ ‖ 2.3 ⋮ **Optimizing electronic properties**: Adjusting the electronic properties of the ligands can decrease the reactivity of the platinum center towards nucleophilic attack. ‖ ∻Answer∻ ⚹ Strategies to enhance the biological stability of platinum compounds include using bulky ligands, increasing kinetic inertness, and optimizing electronic properties. ⚹ ∻Key Concept∻ ⚹ Enhancing biological stability of metallodrugs ⚹ ∻Explanation∻ ⚹ To prevent deactivation by peptides, metallodrugs can be modified to be sterically hindered, less labile, and less reactive towards nucleophiles. ⚹ ∻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), $K_2[PtCl_4]$, by reaction with ammonia. ‖ ‖ 2 ⋮ **Comparison with trans isomer**: The 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 ligands in the cis and trans configurations. ‖ ∻Answer∻ ⚹ Cisplatin is synthesized from $K_2[PtCl_4]$ and ammonia. The trans isomer requires controlled synthesis. IR and NMR spectroscopy can distinguish between the isomers. ⚹ ∻Key Concept∻ ⚹ Synthesis and differentiation of cisplatin and its isomer ⚹ ∻Explanation∻ ⚹ Cisplatin is synthesized from potassium tetrachloroplatinate(II) and ammonia. Controlled conditions favor the trans isomer. IR and NMR spectroscopy are used to distinguish between the isomers. ⚹◊What is the mechanism by which peptides such as glutathione and metallothionein deactivate metallodrugs like platinum compounds?⍭ Generate me a similar question◊

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