Pyrrolo-dC Metal-Mediated Base Pairs in the Reverse Watson-Crick Double Helix: Enhanced Stability of Parallel DNA and Impact of 6-Pyridinyl Residues on Fluorescence and Silver-Ion Binding

Reverse Watson–Crick DNA with parallel‐strand orientation (ps DNA) has been constructed. Pyrrolo‐dC (PyrdC) nucleosides with phenyl and pyridinyl residues linked to the 6 position of the pyrrolo[2,3‐d]pyrimidine base have been incorporated in 12‐ and 25‐mer oligonucleotide duplexes and utilized as silver‐ion binding sites. Thermal‐stability studies on the parallel DNA strands demonstrated extremely strong silver‐ion binding and strongly enhanced duplex stability. Stoichiometric UV and fluorescence titration experiments verified that a single 2pyPyrdC–2pyPyrdC pair captures two silver ions in ps DNA. A structure for the PyrdC silver‐ion base pair that aligns 7‐deazapurine bases head‐to‐tail instead of head‐to‐head, as suggested for canonical DNA, is proposed. The silver DNA double helix represents the first example of a ps DNA structure built up of bidentate and tridentate reverse Watson–Crick base pairs stabilized by a dinuclear silver‐mediated PyrdC pair. Base pairs in reverse mode: The highly fluorescent pyrrolo[2,3‐d]pyrimidine 2'‐deoxyribonucleoside (2pyPyrdC) forms a tremendously stable silver‐mediated base pair that incorporates two silver ions in the parallel‐stranded double helix (see figure; dA=2'‐deoxyadenosine, dC=2'‐deoxycytidine, dG=2'‐deoxyguanosine, dT=2'‐deoxythymidine, meiCd=5‐methyl‐2'‐deoxyisocytidine, iGd=2'‐deoxyisoguanosine, Tm=melting temperature).