AM1 study of a β-carboline set. Part III: substituent effects

Abstract

Substituent effects on the protonation and deprotonation processes of the β-carboline ring possessing different degrees of aromaticity have been studied from both an experimental and a theoretical point of view. NO₂, Cl, MeO and NH₂ groups have been selected. N-7 protonation and N-1 deprotonation enthalpies have been calculated theoretically using the AM1 semiempirical method. Some of the methoxy and nitro derivatives have been synthesized and their acidity constants for the processes mentioned earlier have been determined in aqueous media. From the pK values and the theoretical gas-phase free energy, ΔG_gp°, the solvation contribution has been calculated. Substituent effects on the β-carboline system are quite independent of the aromaticity of the ring and the general trends observed in other aromatic systems (such as benzoic acids and phenoxides) for each particular substituent are also found in the β-carboline rings. Some experimental facts on the reactivity of these molecules are discussed in connection with the reactivity indices arising from the wavefunctions.