Coordination and peri-Carbon Metalation of 1-Nitro-9-[(2-aminoethyl)amino]acridines toward Platinum(II). Evidences for Hydrogen Bonding between Endocyclic N(10)H and Chloride Ion

Article abstract of DOI:10.1021/ic950804t

The antitumor drugs 1-nitro-9-[(2-(dialkylamino)ethyl)amino]acridines (alkyl = Me, A₁; Et, A₂) with platinum-(II) give tridentate coordination compounds in which the two nitrogens of the ethylenediamine side chain and the C(8) carbon atom of the acridine ring system act as donor atoms. An excess of triphenylphosphine displaces the residual chloride coordinated to platinum but leaves unaltered the tridentate acridine ligand. The structures of [Pt(A₁-H)Cl], 1, and [Pt(A₁-H)(PPh₃)]Cl, 3, have been solved by single-crystal X-ray diffraction. 1·CHCl₃ crystallizes in the orthorhombic system, space group P2₁2₁2₁ (no. 19), with a = 8.715(1) A?, b = 11.045(2) A?, c = 22.609(4) A?, Z = 4, R = 0.0559, and R_w = 0.0561 for 1502 reflections with F > 3σ(F). 3·1/2CH₂Cl₂ crystallizes in the monoclinic system, space group P2₁/c (no. 14), with a = 13.418(3) A?, b = 14.053(3) A?, c = 18.918(4) A?, β = 97.21(3)°, Z = 4, R = 0.0591, and R_w = 0.0611 for 3608 reflections with F > 4σ(F). In both complexes the acridine ligand adopts an imino-type configuration with the proton of the exocyclic 9-amino group shifted on N(10). Because of a severe steric interaction between the nitro group in the 1-position and the chelate diamine chain in the 9-position, the acridine moiety is folded about the C(9)-N(10) vector with an average angle between outer rings of 12°. Moreover, the acridine aromatic moiety and the platinum coordination planes are twisted, forming a dihedral angle of ca. 20°. The steric repulsion between the nitro and the diamine groups appears to provide the driving force to metalation. The H(10) proton has a great tendency to be engaged in H-bonding as shown by X-ray and solution studies. The formation of a H-bond with a rather poor acceptor such as the chloride ion can cause a downfield shift of the H-resonance as large as 6 ppm.