IONIZATION AND PARTITIONING PROFILES OF ZWITTERIONS - THE CASE OF THEANTIINFLAMMATORY DRUG AZAPROPAZONE

Azapropazone (1) is a non-steroidal anti-inflammatory drug (NSAID) who se chemical structure is markedly different From that of other agents in this class and challenges our understanding of structure-activity a nd structure-permeation relationships, Using a variety of experimental and computational techniques, we studied 1 for its molecular structur e in the gas phase and non-protic polar solvents, protonation/deproton ation equilibria, tautomerism, and pH-lipophilicity profiles (octan-1- ol/H2O and dodecane/H2O). Other NSAIDs and model compounds were also e xamined For comparison. Due to its very low acidic pK(al), 1 exists in the physiological pH range as a zwitterion and as an anion. Some phar macological implications of these findings are discussed.