The Challenge of Deciphering Linkage Isomers in Mixtures of Oligomeric Complexes Derived from 9-Methyladenine and trans-(NH3)2PtII Units

Abstract

Metal coordination to N9-substituted adenines, such as the model nucleobase 9-methyladenine (9MeA), under neutral or weakly acidic pH conditions in water preferably occurs at N1 and/or N7. This leads, not only to mononuclear linkage isomers with N1 or N7 binding, but also to species that involve both N1 and N7 metal binding in the form of dinuclear or oligomeric species. Application of a trans-(NH3)2PtII unit and restriction of metal coordination to the N1 and N7 sites and the size of the oligomer to four metal entities generates over 50 possible isomers, which display different feasible connectivities. Slowly interconverting rotamers are not included in this number. Based on 1H NMR spectroscopic analysis, a qualitative assessment of the spectroscopic features of N1,N7-bridged species was attempted. By studying the solution behavior of selected isolated and structurally characterized compounds, such as trans-[PtCl(9MeA-N7)(NH3)2]ClO4⋅2H2O or trans,trans-[{PtCl(NH3)2}2(9MeA-N1,N7)][ClO4]2⋅H2O, and also by application of a 9MeA complex with an (NH3)3PtII entity at N7, [Pt(9MeA-N7)(NH3)3][NO3]2, which blocks further cross-link formation at the N7 site, basic NMR spectroscopic signatures of N1,N7-bridged PtII complexes were identified. Among others, the trinuclear complex trans-[Pt(NH3)2{μ-(N1-9MeA-N7)Pt(NH3)3}2][ClO4]6⋅2H2O was crystallized and its rotational isomerism in aqueous solution was studied by NMR spectroscopy and DFT calculations. Interestingly, simultaneous PtII coordination to N1 and N7 acidifies the exocyclic amino group of the two 9MeA ligands sufficiently to permit replacement of one proton each by a bridging heterometal ion, HgII or CuII, under mild conditions in water.This work was supported by the Deutsche Forschungsgemeinschaft, the Spanish Ministerio de Economía y Competitividad [CTQ2011-27593, “Ramón y Cajal” program (P.J.S.M.), and a postdoctoral fellowship (S.I.)]. We are grateful to Dr. M. Bette (University of Halle) for the structural solution of complex [2][NO3]