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Solutions For An Introduction to Medicinal Chemistry Chapter 13 Problem 15Q

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Solution 1

The ability of an atom to act as a hydrogen bond acceptor depends on the readiness with which it can contribute a lone pair to the partially positively hydrogen atom of the hydrogen bond donor group. Hence, given these criteria, the potential the three structures have as hydrogen bond acceptors can be gauged.

The first structure is likely to be the weakest hydrogen bond acceptor. It is part of an aromatic ring, and hence its electron density will be adversely affected due to the electron delocalization caused by the resonance effect. Additionally, the atom is covalently bound to another alkyl or aryl group that is likely to have an even more detrimental effect on its electron density.

The second structure is likely to be the strongest hydrogen bond receptor. As it is not a core part of the aromatic ring of the structure, the resonance of the structure has a less detrimental effect on its electron density. Additionally, a lot of its electron density will be affected by the groups it is attached to. It is possible that one or both the groups attached to the atom may enhance its electron density.

The third structure is likely to be in the middle as far as its potency as a hydrogen bond acceptor is concerned. It is a part of an aromatic ring hence its electron density will be affected as a result of structural resonance. However, it will not be subjected to any further weakening of its electron density as no other groups are bound to it.

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Solutions For Problems in Chapter 13