Question

Draw dashed and solid wedge diagrams of transplatin, trans-Pt( \(\mathrm{NH}_{3}\) ) \(_{2} \mathrm{Cl}_{2}\), and cisplatin, \(\operatorname{cis}-\mathrm{Pt}\left(\mathrm{NH}_{3}\right)_{2} \mathrm{Cl}_{2}\) Then, explain how transplatin can be more reactive yet less effective at killing cancer cells than is cisplatin.

Short answer

Transplatin and Cisplatin are isomers, with chloride ions in opposite placements in Transplatin, making it more reactive, yet less effective against cancer cells because the cis configuration in Cisplatin allows for more effective DNA cross-linking which triggers cell death in cancer treatment.

Step-by-step solution

Draw the wedge diagrams for transplatin

Draw a square in the plane of the screen to represent the platinum atom and mark the two sides as top and bottom. Draw the two ammonia molecules attached to the top and the bottom of the square using filled lines. Then draw the two chlorine atoms attached to the two sides of the square, one using a dashed line (representing going into the plane of the screen) and the other using a wedge (representing coming out of the plane of the screen). This represents the trans isomer where the chlorine atoms are on opposite sides.

Draw the wedge diagrams for cisplatin

Draw a square in the plane of the screen to represent the platinum atom and mark the two sides as top and bottom. Draw the two ammonia molecules attached to the top and the bottom of the square using filled lines. Then draw the two chlorine atoms attached to the one side of the square, one using a dashed line (representing going into the plane of the screen) and the other using a wedge (representing coming out of the plane of the screen). This represents the cis isomer where the chlorine atoms are on the same side.

Explain reactivity and effectiveness

Transplatin is more reactive due to the position of chloride ions on opposite sides, which facilitates the leaving of chloride ions making the compound more ready for interaction. However, it is less effective at killing cancer cells than cisplatin, because the cis configuration allows cisplatin to form a more effective cross-link within the DNA molecule. The DNA cross-link distorts the DNA structure which triggers the repair mechanism of the cell and can lead to cell death, which is beneficial in cancer treatment.

Key concepts

Transplatin

Transplatin, chemically known as trans-Pt(\(\mathrm{NH}_{3}\) ) \(_{2} \mathrm{Cl}_{2}\), is a platinum-based compound similar to its better-known counterpart, cisplatin. Transplatin differentiates itself by having chlorine and ammonia groups arranged opposite to each other, referred to as the 'trans' configuration. This spatial arrangement significantly affects how the compound behaves chemically. Transplatin tends to have chloride ions located on opposite sides, a fact that influences its increased reactivity.

However, despite being more reactive, transplatin is surprisingly less effective as a chemotherapy drug. The reason lies in its inability to cross-link DNA in the same efficacious manner as cisplatin. Its linear geometry, where chlorides sit opposite one another, fails to achieve the critical distortion needed to trigger effective DNA repair mechanisms.

Understanding the structural differences between trans and cis configurations is key to appreciating why transplatin's heightened reactivity doesn’t translate into cancer-killing effectiveness.

Wedge Diagrams

Wedge diagrams are a simple yet powerful tool used to visualize molecular structures in three-dimensional space. They help us understand spatial relationships and interactions between different atoms in a molecule, especially in complex compounds such as organometallics.

When drawing the wedge diagram for transplatin, for example, you would represent the platinum atom as a square in the middle with bonds to ammonia and chloride ions. Bonds in wedge diagrams are depicted using:

• Dashed lines: These indicate bonds going into the plane of the paper, like the bonds to certain chlorides.
• Solid lines: Straight lines show bonds in the plane of the paper.
• Wedges: These show bonds projecting out of the plane, helping visualize the spatial arrangement of atoms.

For transplatin, ammonia molecules are attached using solid lines, whereas chlorine atoms use a dash and wedge to highlight their opposite positions. Cisplatin, on the other hand, has chlorine and ammonia on adjacent rather than opposite sides, altering how it interacts chemically.

Reactivity and Effectiveness

The concepts of reactivity and effectiveness are crucial when considering why certain compounds work better as medication. Reactivity refers to how readily a chemical species undergoes a reaction. Effectiveness, in a medicinal context, describes how well a compound can achieve a desired therapeutic effect.

In the case of transplatin, its configuration allows it to be more reactive. The trans arrangement, with chlorine atoms on opposite ends, makes it easier for these atoms to leave the compound and engage in further chemical reactions. However, reactivity isn’t the only factor in determining the success of a chemotherapy drug. Cisplatin's cis arrangement allows it to engage more successfully with DNA structures.

The unique positioning of its atoms enables cisplatin to form tight DNA cross-links, which effectively disrupt cancer cell processes. Transplatin, although reactive, cannot form these links as effectively, limiting its therapeutic prowess.

DNA Cross-Linking

DNA cross-linking involves the binding or linking together of two DNA strands. This process is crucial in understanding the effectiveness of certain cancer medications like cisplatin.

When cisplatin enters a cancerous cell, it binds and distorts the cell's DNA at two adjacent sites. This distortion causes the DNA to become kinked or bent, impeding the replication process and triggering cellular damage responses.

• Activating DNA repair mechanisms
• Possibly leading to cell death

Cisplatin’s ability to form these cross-links makes it a powerful anti-cancer drug because it effectively disrupts cell division.

Transplatin, on the contrary, places reactive groups on opposite ends, missing the opportunity to bind as effectively to DNA. This lack of effective binding reduces its ability to incite repair mechanisms that can lead to cell apoptosis, making it less effective as a chemotherapy agent compared to cisplatin.