Basicities of some 9-substituted acridine-4-carboxamides: A density functional theory (DFT) calculation

Acid-base properties of drugs are important in understanding the behaviour of these compounds under physiological condition. In order to understand such behaviour the proton affinities of acri-dine 4-carboxamides with substitution (R) at the 9-position are theoretically studied, and considered for the basic sites of both the heterocyclic ring as well as side chain nitrogens. In 9-amino acridine 4-carbox-amide, the -NH₂ group is observed to be an additional basic site. The heterocyclic nitrogen of substituted carboxamides (R =-NH₂, -O-methyl, -O-ethyl, and -O-phenyl) is more basic than the side chain nitrogen, however, side chain nitrogen corresponds to more basic site for some carboxamides (R = -OH and-Cl) and the -NH₂ group represents the least basic site of 9-amino acridine 4-carboxamide. In addition to presenting the basicities of these drugs an indication of another hydrogen-bond between heterocyclic ring N and carboxamide chain O is observed. The difference of basicities with substituents at 9-position are very narrow and carboxamides with substituents at 9-position are found to be suitable for studying intramolecular H-bonds between the heterocyclic N and carboxamide O. The resultant stabilization of a configuration due to such H-bonding is determined