Which of the following substitutions would still yield an active cholinergic agonist albeit weaker?

• A. Replacement with arsenic, phosphorus, or sulfur
• B. Replacement with neon
• C. Replacement with oxygen
• D. Replacement with carbon

Answer: (A)

The key idea is that the cholinergic receptor–activating motif can tolerate some variation in the acyl linkage while still resembling acetylcholine enough to activate receptors, though potency may drop. Replacing the acetyl oxygen with heavier nonmetals such as sulfur, phosphorus, or arsenic can preserve the general binding features (shape and electronic distribution) of the molecule, forming thioester or phosphoester–type analogs that still act as agonists but more weakly due to altered binding and reactivity. In contrast, introducing neon would break bonding altogether, and substituting with carbon or simply duplicating oxygen would not maintain the same key features needed for receptor activation. Therefore, substitutions to arsenic, phosphorus, or sulfur best preserve activity, albeit with reduced potency.