Metal-Modified Nucleobase Sextet: Joining Four Linear Metal Fragments (trans-a2PtII) and Six Model Nucleobases to an Exceedingly Stable Entity

Abstract

Crosslinking of three different model nucleobases (9-ethyladenine, 9-EtA; 9-ethylguanine, 9-EtGH; 1-methyluracil, 1-MeU) by two linear trans-aPtII (a = NH3 or CH3NH2) entities leads to a flat metal-modified base triplet, trans,trans-[(NH3)2Pt(1-MeU-N3)(mu-9-EtA-N7,N1)Pt(CH3NH2)2(9-EtGH-N7)]3+ (4b). Upon hemideprotonation of the 9-ethylguanine base at the N1 position. 4b spontaneously dimerizes to the metalated nucleobase sextet 5, [(4b)(triple bond)(4b-H)]5+. In this dimeric structure a neutral and an anionic guanine ligand, which are complementary to each other, are joined through three H bonds and additionally by two H bonds between guanine and uracil nucleobases. Four additional interbase H bonds maintain the approximate coplanarity of all six bases. The two base triplets form an exceedingly stable entity (KD = 500 +/- 150 M(-1) in DMSO), which is unprecedented in nucleobase chemistry. The precursor of 4b and several related complexes are described and their structures and solution properties are reported.

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a2PtII: Artificial nucleobase quartets and C—H…N bonds

“…Thus, Scheme 2a is an example for the involvement of a second nucleobase (X ϭ guanine) in self-association (v in Scheme 4), as are compounds V (14) and VI (15) tion (vii in Scheme 4). This pair by far exceeds the normal G,C Watson-Crick pair in strength (47)(48)(49)(50).…”

PtII Binding to N1 of Cytosine: Strengthening the Watson-Crick Pair with Guanine and yet Confining Its pH Existence Range

“…Similarly, the strength of the pair between Pt-CH and 1-MeC exceeds that of the regular G/C pair, even though it does not reach the record value recently observed for the hemideprotonated pair of N7-platinated guanine. [8] Our findings have led us to pursue the idea of creating artificial oligonucleotide analogues that consist of a backbone of metal ions and bridging ligands, with nucleobases attached either through N1 (unsubstituted pyrimidine bases), through N9 (unsubstituted purine bases), or through N7 (N9-substituted purine bases) to the metal centers. These coordination polymers might be considered relatives of purely organic neutral [9] and cationic [10] oligonucleotide analogues.…”

Connectivity patterns and rotamer states of nucleobases determine acid–base properties of metalated purine quartets

“…Three principal arrangements of two hemi-deprotonated adenine ligands in head-head orientation and cross-linked by linear metal ions (M = trans-a 2 Pt II ): N1-Pt-N1, N1-Pt-N7, and N7-Pt-N7 (top to bottom). [73][74][75][76][77][78][79][80][81]. Even with a single purine base applied, e.g., 9MeA [82], yet more so in combinations with a second, different purine base [54], the number of linkage isomers becomes large.…”

“…Typically G-H8 resonances undergo upfield shifts of 0.2-0.25 ppm during N1H deprotonation, whereas A-H8 and A-H2 shift by ca. 0.6 ppm or even more [78,80,[90][91][92]. Changes in nucleobase rotamer states may modify these values further.…”