ESI-MS and thermal melting studies of nanoscale platinum(ii) metallomacrocycles with DNA

The hydrophilic, long-chain diamine PEGda (O,O′-bis(2-aminoethyl)octadeca(ethylene glycol)), when complexed with cis-protected Pt(II) ions afforded water-soluble complexes of the type [Pt(N,N)(PEGda)](NO3)2 (N,N = N,N,N′,N′-tetramethyl-1,2-diaminoethane (tmeda), 1,2-diaminoethane (en), and 2,2′-bipyridine (2,2′-bipy)) featuring unusual 62-membered chelate rings. Equimolar mixtures containing either the 16-mer duplex DNA D2 or the single-stranded D2a and [Pt(N,N)(PEGda)]2+ were analyzed by negative-ion ESI-MS. Analysis of D2-Pt(II) mixtures showed the formation of 1:1 adducts of [Pt(en)(PEGda)]2+, [Pt(tmeda)(PEGda)]2+ and the previously-described metallomacrocycle [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+ with D2; the dinuclear species bound to D2 most strongly, consistent with its greater charge and aromatic surface area. D2 formed 1:2 complexes with the acyclic species [Pt(2,2′-bipy)(Mebipy)2]4+ and [Pt(2,2′-bipy)(NH3)2]2+. Analyses of D2a-Pt(II) mixtures gave results similar to those obtained with D2, although fragmentation was more pronounced, indicating that the nucleobases in D2a play more significant roles in mediating the decomposition of complexes than those in D2, in which they are paired in a complementary manner. Investigations were also conducted into the effects of selected platinum(II) complexes on the thermal denaturation of calf thymus DNA (CT-DNA) in buffered solution. Both [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)64,4′-bipy}2]8+ and [Pt(2,2′-bipy)(Mebipy)2]4+ stabilized CT-DNA. In contrast, [Pt(tmeda)(PEGda)]2+ and [Pt(en)(PEGda)]2+ (as well as free PEGda) caused negligible changes in melting temperature (ΔTm), suggesting that these species interact weakly with CT-DNA.