Endocyclic versus exocyclic N-coordination to platinum(II) of some nitro-9-[(2-dialkylaminoethyl)amino]acridines

The kinetically controlled reaction products between the antitumor drugs 1-nitro-9-[(2-dialkylaminoethyl)amino]acridine (alkyl=Me, A1; Et, A2) or the inactive analogs 3-nitro-9-[(2-dialkylaminoethyl)amino]acridines (alkyl=Me, A3; Et, A4) and three different platinum(II) substrates have been investigated in chloroform and acetone solutions and found to be dependent upon the charge of the metal complex and the position of the tautomeric equilibrium (amino and imino forms) in the free acridine. Anionic ([Pt(η2-C2H4)Cl3]−) and neutral ([PtI2(DMSO)]2) platinum substrates react with the dominant tautomer, either amino or imino, to give the endocyclic and exocyclic N-bonded derivatives, respectively. Positively charged substrates ([Pt(H2O)(Me5dien)]2+ and [Pt(H2O)(dien)]2+) coordinate exclusively to the exocyclic aminic nitrogens and this coordination mode stabilizes the imino form also in the case of 3-nitro acridines, which are present in both solvents as pure amino tautomers. For dien-platinum complexes fast exchange between free and coordinated acridine was observed at room temperature.