Mixed adenine/guanine quartets with three trans-a2Pt II (a=NH3 or MeNH2) cross-links: Linkage and rotational isomerism, base pairing, and loss of NH3

Of the numerous ways in which two adenine and two guanines (N9 positions blocked in each) can be cross-linked by three linear metal moieties such as trans-a2PtII (with a=NH3 or MeNH2) to produce open metalated purine quartets with exclusive metal coordination through N1 and N7 sites, one linkage isomer was studied in detail. The isomer trans,trans,trans-[{Pt(NH3)2(N7-9-EtA-N1) 2}{Pt(MeNH2)2(N7-9-MeGH)}2] [(ClO4)6]·3H2O (1) (with 9-EtA=9-ethyladenine and 9-MeGH=9-methylguanine) was crystallized from water and found to adopt a flat Z-shape in the solid state as far as the trinuclear cation is concerned. In the presence of excess 9-MeGH, a meander-like construct, trans,trans,trans-[{Pt(NH3)2(N7-9-EtA-N1) 2}{Pt(MeNH2)2(N7-9-MeGH)2}] [(ClO4)6]·[(9-MeGH)2]·7 H 2O (2) is formed, in which the two extra 9-MeGH nucleobases are hydrogen bonded to the two terminal platinated guanine ligands of 1. Compound 1, and likewise the analogous complex 1 a (with NH3 ligands only), undergo loss of an ammonia ligand and formation of NH4 + when dissolved in [D6]DMSO. From the analogy between the behavior of 1 and 1 a it is concluded that a NH3 ligand from the central Pt atom is lost. Addition of 1-methylcytosine (1-MeC) to such a DMSO solution reveals coordination of 1-MeC to the central Pt. In an analogous manner, 9-MeGH can coordinate to the central Pt in [D6]DMSO. It is proposed that the proton responsible for formation of NH4 + is from one of the exocyclic amino groups of the two adenine bases, and furthermore, that this process is accompanied by a conformational change of the cation from Z-form to U-form. DFT calculations confirm the proposed mechanism and shed light on possible pathways of this process. Calculations show that rotational isomerism is not kinetically hindered and that it would preferably occur previous to the displacement of NH3 by DMSO. This displacement is the most energetically costly step, but it is compensated by the proton transfer to NH3 and formation of U(-H+) species, which exhibits an intramolecular hydrogen bond between the deprotonated N6H- of one adenine and the N6H2 group of the other adenine. Finally the question is examined, how metal cross-linking patterns in closed metallacyclic quartets containing two adenine and two guanine nucleobases influence the overall shape (square, rectangle, trapezoid) and the planarity of a metalated purine quartet. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This work was supported by the Deutsche Forschungsgemeinschaft (DFG). Funding from the Spanish Ministerio de Economia y Competitividad (CTQ2011–24847/BQU, CTQ2011–27593, and “Ramón y Cajal” program (P.J.S.M.)), the Generalitat de Catalunya (SGR2009–638). M.S. also acknowledges support through the 2011 ICREA Academia award.Peer Reviewe