Functional mono- and dinuclear peptide complexes featuring chemospecific κS- or η6-coordination of organometallic half-sandwich fragments

Influence of the Polypyridyl (pp) Ligand Size on the DNA Binding Properties, Cytotoxicity and Cellular Uptake of Organoruthenium(II) Complexes of the Type [(η6‐C6Me6)Ru(L)(pp)]n+ [L = Cl, n = 1; L = (NH2)2CS, n = 2]

“…Thermal denaturation studies for CT DNA can provide simple a means of gauging the efficacy of polypyridyl intercalation for organometallic complexes [4][5][6][7] such as 1-8, provided that electrostatic and hydrogen-bonding interactions with the biopolymer may be regarded as remaining effectively unchanged by pp ligand variation. The ∆T m values listed in Table 2 for the monocations of 1-5 and the dications of 6-8 were recorded under equilibrium conditions in a phosphate buffer, (pH = 7.2) for r = 0.1 and are indicative of strong DNA intercalation for the dppz ligand of 4 (∆T m = 20°C), and 7 (∆T m = 25°C).…”

“…[1][2][3] We have recently established that organometallic half-sandwich compounds of the types [(η 5 -Cp*)Ir (amino acid-κS)(dppz)] n+ (n = 1-3, dppz = dipyrido[3,2-a:2Ј,3Ј-c]phenazine) [4][5][6] and [(η 6 -arene)Ru(amino acid-κS)(dppz)] n+ (n = 1-3, arene = C 6 H 6 , Me 3 C 6 H 3 , C 6 Me 6 ), [7] with a thioether-coordinated methionine-containing amino acid or peptide, exhibit strong intercalative binding into DNA. In these complexes and in [(η 5 -Cp*)Ru(dppz)(NO)] (CF 3 SO 3 ) 2 , [8] the magnitudes of the binding constants K b (8.8 ϫ 10 4 to 5.5 ϫ 10 6  -1 ) are clearly dependent on the overall cation charge n (1-3), i.e.…”

“…[7] properties of compounds of the type [(η 6 -C 6 Me 6 )RuCl(pp)]-(CF 3 SO 3 ) 2 (1)(2)(3)(4)(5) with the diimine ligands phen (1,10-phenanthroline), tap (1,4,5,8-tetraazaphenanthrene), dpq (dipyrido[3,2-f:2Ј,3Ј-h]quinoxaline), dppz and dppn (Scheme 1). The preparation of [(η 6 -C 6 Me 6 )RuCl(phen)]Cl has recently been reported by Süss-Fink et al, [10] who studied the hydrolytic potential of the corresponding dicationic aqua complex [(η 6 -C 6 Me 6 )Ru(H 2 O)(phen)](BF 4 ) 2 for transfer hydrogenation reactions in aqueous solution.…”

Bifunctional Bioorganometallic Iridium(III)–Platinum(II) Complexes Incorporating Both Intercalative and Covalent DNA Binding Capabilities

“…of Ag(CF 3 SO 3 ) and filtration of the resulting AgCl precipitate afforded the starting compound [(η 5 -Cp*)Ir(acetone) 3 ](CF 3 SO 3 ) 2 (1). [17] [(η 5 -Cp*)Ir(dppz)(H-Gly-Met-OH- [16] and [(η 5 -Cp*)Ir(dppz)(H-Gly-Gly-Met-OH-κS)](CF 3 SO 3 ) 2 were prepared from 1 and the relevant peptide in a manner previously described for the latter complex. [14] (Et 4 N) [ [36] [(η 5 -Cp*)Ir(dppz)(H-Gly-Gly-Phe-Met-OH-κS)](CF 3 SO 3 ) 2 (3): The ligand dppz (56.5 mg, 0.2 mmol) was added to 1 (159.8 mg, 0.2 mmol) in CH 3 OH/CH 2 Cl 2 (10 mL) and the resulting solution stirred at reflux for 2 h. After addition of H-Gly-Gly-Phe-Met-OH (82.1 mg, 0.2 mmol) in CF 3 COOH (1.5 mL) and stirring at 50°C for 18 h, the volume was reduced to 3 mL.…”

“…[13] We have recently demonstrated that bioorganometallic metallointercalators of the type [(η 5 -Cp*)Ir(dppz)(peptide)] n+ (n = 1-3) [14] and [(η 6 -arene)Ru(dppz)(peptide)] n+ (n = 1-3; arene = C 6 H 6 , Me 3 C 6 H 3 , C 6 Me 6 ) [15] exhibit strong side-on intercalative binding into DNA with equilibration constants K b of up to 5. [16] H-Gly-Gly-Met-OH, [14] H-Gly-Gly-PheMet-OH (3), H-(Ala) 4 -Met-OH (4)] were prepared as described previously for H-Gly-Met-OH [16] and H-Gly-GlyMet-OH [14] by initially refluxing [(η 5 -Cp*)Ir(acetone) 3 ]-(CF 3 SO 3 ) 2 (1) [17] with dppz in CH 3 OH/CH 2 Cl 2 for 2 h. Addition of the appropriate peptide in CF 3 COOH to the resulting [(η 5 -Cp*)Ir(acetone)(dppz)](CF 3 SO 3 ) 2 solution leads to formation of the desired complexes [(η 5 -Cp*)-Ir(dppz)(peptide-κS)](CF 3 SO 3 ) 2 (Scheme 1). Strongly acidic conditions (CF 3 COOH) are, however, necessary to achieve chemospecific κS coordination of the methionine side chains in the presence of non-protected terminal amino or carboxylate groups.…”