Anion-triggered substituent-dependent conformational switching of salicylanilides. New hints for understanding the inhibitory mechanism of salicylanilides
- 化学化工－已发表论文 
A series of salicylanilides (1a - h) bearing varied substituents at the 3'- or 4'-position of the anilino moiety (substituent = p-OCH3, p-CH3, m-CH3, H, p-Cl, m-Cl, p-CO2CH3, and p-CN) were synthesized. In acetonitrile all of the substituted salicylanilides 1a - h predominantly adopt the '' closed-ring '' conformation facilitated by a strong intramolecular OH center dot center dot center dot O=C hydrogen bond. In the presence of H2PO4-, the conformation of 1a - h was found to be modulated by the substituent. With our proposed proton-transfer fluorescence probing method, we were able to show that the conformation of 1a - f bearing a not highly electron-withdrawing substituent was switched to the '' open-ring '' form by H2PO4-, whereas 1h bearing a highly electron-withdrawing substituent, p-CN, remained in the '' closed-ring '' conformation. The significance of these findings for understanding, from a molecular structural point of view, the mechanism of salicylanilide-based inhibitors for inhibiting the protein tyrosine kinase epidermal growth factor receptor was discussed.