Preorganisation and complementarity

Question 1

What are the chelate and macrocyclic effects?

Answer 1

Thermodynamic effect arising from reduction in degrees of freedom. Chelate effect - stabilising effect as a result of multiple donor atoms complexing to the metal centre simultaneously. Macrocyclic effect - large ring ligands resulting in higher preorganisation of binding sites, offering further stabilisation.

Question 2

What are key example molecules in explaining preorganisation and complementarity?

Answer 2

Crown ethers, acylic crown ether, cryptand, spherand, diaza[18]crown-6, lariat ether

Question 3

How does increasing preorganisation impact binding constants?

Answer 3

Increasing preorganisation increases binding constants as there is a smaller entropic cost in binding.

Question 4

Why do equivalent azamacrocycles have weaker binding constants compared to crown ethers?

Answer 4

Less complementarity due to nitrogen donors - softer donor. HSAB gives an indication of complementarity.

Question 5

Why are lariat ethers significantly weaker binding than the equivalent cryptand?

Answer 5

Lower level of preorganisation as the third bridge not secured to other side of macrocycle.
Less complementarity due to nitrogen donors.

Question 6

What problems may be encountered with spherands and other supermolecules of high preorganisation?

Answer 6

Completely rigid, binding site of very fixed size, so likely to have high steric barriers for binding. This can lead to slow kinetics with selectivity for smaller ions.

Question 7

What are preorganisation effects that arise comparing cryptands, crown ethers and podands?

Answer 7

Cryptands and crown ethers have some relief from the lone pair interactions and lack of solvation. Particularly marked in cryptands with high preorganisation. Significant penalty on binding for podand as lone pairs have very little repulsion and high solvation. Desolvation of lone pairs and specific conformer required for binding.