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

The antitumor drugs 1-nitro-9-[(2-(dialkylamino)ethyl) amino] acridine s (alkyl = Me, A(1); Et, A(2)) with platinum(II) give tridentate coord ination compounds in which the two nitrogens of the ethylenediamine si de chain and the C(8) carbon atom of the acridine ring system act as d onor atoms. An excess of triphenylphosphine displaces the residual chl oride coordinated to platinum but leaves unaltered the tridentate acri dine ligand. The structures of [Pt(A(1)-H)Cl], 1, and [Pt(A(1)-H)(PPh( 3))]Cl, 3, have been solved by single-crystal X-ray diffraction. 1 . C HCl3 crystallizes in the orthorhombic system, space group P2(1)2(1)2(1 ) (no. 19), with a = 8.715(1) Angstrom, b = 11.045(2) Angstrom, c = 22 .609(4) Angstrom, Z = 4, R = 0.0559, and R(w) = 0.0561 for 1502 reflec tions with F > 3 sigma(F). 3 . 1/2CH(2)Cl(2) crystallizes in the monoc linic system, space group P2(1)/c (no. 14), with a = 13.418(3) Angstro m, b = 14.053(3) Angstrom, c = 18.918(4) Angstrom, beta = 97.21(3)degr ees, Z = 4, R = 0.0591, and R(w) = 0.0611 for 3608 reflections with F > 4 sigma(F). In both complexes the acridine ligand adopts an imino-ty pe configuration with the proton of the exocyclic g-amino group shifte d on N(10). Because of a severe steric interaction between the nitro g roup 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 av erage angle between outer rings of 12 degrees. Moreover, the acridine aromatic moiety and the platinum coordination planes are twisted, form ing a dihedral angle of ca. 20 degrees. The steric repulsion between t he nitro and the diamine groups appears to provide the driving force t o metalation. The H(10) proton has a great tendency to be engaged in I I-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.