New chlorido(dimethyl sulfoxide)iridium(iii) complexes with n6-substituted adenines – kinetic n(7) versus thermodynamic n(9) coordinated adenine isomers

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DOI: 10.1002/ejic.201000821

New Chlorido(dimethyl sulfoxide)iridium(III) Complexes with N6-Substituted Adenines – Kinetic N(7) versus Thermodynamic N(9) Coordinated Adenine Isomers
Angel García-Raso,*[a] Juan J. Fiol,[a] Francisca M. Albertí,[a] Yolanda Lagos,[a] Marta Torres,[a] Miquel Barceló-Oliver,[a] María J. Prieto,[b] Virtudes Moreno,[b] Ignasi Mata,[c] Elies Molins,[c]Carolina Estarellas,[a] Antonio Frontera,*[a] David Quiñonero,[a] and Pere M. Deyà[a]
Keywords: Iridium / Coordination modes / Amino acids / Structure elucidation / Density functional calculations
New chlorido(dimethyl sulfoxide)iridium(III) complexes with N6-substituted adenine derivatives: [IrIIICl4(DMSO-κS){HAdeCx–κN(7)}]·nH2O [x = 3, n = 3 for 1; x = 4, n = 0.5 and 3 for 2a and 2b,respectively; x = 5, n = 0 for 3; x = 10, n = 0.33 for 4] and [IrIIICl4(DMSO-κS){H-AdeCx–κN(9)}] [x = 3 for 5; x = 4 for 6, x = 5 for 7; x = 10 for 8] have been synthesized and characterized by spectroscopic techniques and by singlecrystal X-ray diffraction studies (1, 2b and 5). In all cases, iridium shows octahedral geometry and is coordinated to four chlorido ligands and one S atom from dimethyl sulfoxide(DMSO-κS). The coordination sphere of the metal is completed by the N6-substituted adenine molecule. Two different coordination modes are observed: (i) the ligand is protonated at N(1) and coordinated through N(7) (complexes 1–4); (ii) the adenine is protonated at N(3) and coordinated through N(9) (complexes 5–8). The kinetic/thermodynamic mechanisms that yield the different coordination productshave been studied by using DFT calculations. Electrophoretic mobility studies and atomic force microscopy (AFM) investigation of the interaction between complexes 1, 5, 8 and plasmid pBR322 DNA have been performed.

Introduction
Organoiridium chemistry is in great development in organic synthesis and catalysis,[1] and iridium(III) cyclometalated compounds have been extensively applied in thedesign and preparation of light-emitting diodes,[2,3] photoactivated agents in redox reactions with DNA[4] or luminescent labels and sensor molecules for biological purposes.[5,6] Furthermore, although several organometallic IrIII compounds with ligands of biological interest have been described,[7–10] few studies of non-organometallic IrIII complexes have been reported.[11–15] On the other hand,RuIII complexes, [LH][trans-RuIIICl4(DMSO-κS)(L)] (L = nitrogenated ligand), such as NAMI-A [ImH][trans-RuIIICl4(DMSO-κS)(Im)] (Im =
[a] Departament de Química, Universitat de les Illes Balears and Inst. Hlth. Sci. Res. IUNICS, Campus UIB, Ctra.Valldemossa, km 7.5, 07122 Palma de Mallorca, Spain Fax: +34-971173426 E-mail: angel.garcia-raso@uib.es toni.frontera@uib.es [b] Departaments de QuímicaInorgànica i Microbiologia, Universitat de Barcelona, Campus de Pedralbes, 08028 Barcelona, Spain [c] Institut de Ciència de Materials de Barcelona (CSIC), Campus UAB, 08193 Bellaterra, Spain
Eur. J. Inorg. Chem. 2010, 5617–5628

imidazole) or KP1019 [IndH][trans-RuIIICl4(Ind)2] (Ind = indazole) show selective antimetastatic properties or specific antitumour action.[16–18] Moreover, several IrIII-and RhIII-related compounds have proved to be potent in vitro cytotoxic agents,[19,20] although similar “NAMI-A”-IrIII or RhIII complexes have been found to be inactive,[11,12,21] which has been related to the lack of lability for ligand substitution and redox properties of the metal centre. In this way, the more inert IrIII compounds could be useful as trace systems to study the route of RuIIIanalogues or designed complexes to deliver an active ligand to a specific receptor. As a continuation of our work on the zwitterionic system [MCl4(DMSO-κS)HL] (M = RuIII, IrIII; L = nitrogenated ligand),[14,22,23] we have explored the synthesis of new iridium(III) complexes with N6-substituted adenines that present cytokinin activity.[24,25] Natural cytokinins (CK) are modified adenine molecules...