Synthesis and DNA binding properties of bioorganometallic (η5-pentamethylcyclopentadienyl)iridium(iii) complexes of the type [(η5-C<SUB>5</SUB>Me<SUB>5</SUB>)Ir(Aa)(dppz)]n+ (dppz = dipyrido[3,2-a:2',3'-c]phenazine, n = 1–3), with S-coordinated amino acids (Aa) or peptides

The DNA binding of cationic complexes of the type [(η⁵-C₅Me₅)Ir(Aa)(dppz)](CF₃SO₃)_n (dppz = dipyrido[3,2-a:2',3'-c]phenazine; n = 1, Aa = AccysOH <compoundref>7</compoundref>; n = 2, Aa = AcmetOMe <compoundref>4</compoundref>, H₂cysOMe <compoundref>8</compoundref>; n = 3, Aa = H₂metOMe <compoundref>5</compoundref>) containing S-coordinated amino acids (HmetOH = methionine, HcysOH = cysteine) has been studied by UV-vis titration, 2D-NOESY and gel electrophoresis. The observed steady decrease in absorbance at maxima between 350 and 400 nm on UV-vis titration with CT DNA and the bathochromic shifts of these absorption maxima are consistent with stable intercalative DNA binding for these complexes. An increase in the binding constant K_b from 8.80(6) × 10⁴ for the monocation of <compoundref>7</compoundref> through 2.30(4) × 10⁵ and 7.04(5) × 10⁵ for the dications of <compoundref>8</compoundref> and <compoundref>4</compoundref> to 2.62(3) × 10⁶ M⁻¹ for the 3+ cation of <compoundref>5</compoundref> clearly reflects the strengthening of the electrostatic interaction with the negatively charged phosphodiester backbone of DNA with increasing cation charge. Analogous values of 2.81(7) × 10⁵ and 1.26(5) × 10⁶ M⁻¹ were obtained for the (η⁵-C₅Me₅)Rh^III complexes <compoundref>14</compoundref> (n = 2, Aa = H₂cysOMe) and <compoundref>13</compoundref> (n = 3, Aa = H₂metOMe). Binding site sizes for the organometallic Ir^III and Rh^III complexes on CT DNA lie in the range 1.5–2.1 base pairs. NOE cross peaks for the 1 ∶ 1 complex formed between <compoundref>5</compoundref> and d(GTCGAC)₂ are consistent with intercalation adjacent to T₂ from the major groove. Complexes <compoundref>4</compoundref>, <compoundref>5</compoundref> and [(η⁵-C₅Me₅)Ir(HglyglymetOH)(dppz)](CF₃SO₃)₂ <compoundref>6</compoundref> (HglyOH = glycine) cleave the supercoiled plasmid pBluescript II KS+, on irradiation for 30–180 s with a high pressure Hg lamp, to afford nicked circular and linear DNA forms. X-Ray structural analyses are reported for [(η⁵-C₅Me₅)IrCl(dppz)](CF₃SO₃) <compoundref>3</compoundref> and [(η⁵-C₅Me₅)Ir(9-Etgua)(phen)] (CF₃SO₃)₂ <compoundref>16</compoundref> (9-Etgua = 9-ethylguanine).