Automated synthesis of 3 '-metalated oligonucleotides

We report the first synthesis of a metallonucleoside bound to a solid suppo rt and subsequent oligonucleotide synthesis with this precursor. Large-scal e syntheses of metal-containing oligonucleotides are achieved using a solid support modified with [Ru(bpy)(2)(impy ')](2+) (bpy is 2.2 ' -bipyridine; impy ' is 2 ' -iminomethylpyridyl-2 ' -deoxyuridine). A duplex formed with the metal-containing oligonucleotide exhibits superior thermal stability wh en compared to the corresponding unmetalated duplex (T-m 50 degreesC vs T-m = 48 degreesC). Electrochemical (E-1/2 = 1.3 V vs NHE), absorption (lambda (max) = 480 nm), and emission (lambda (max) = 720 mm, tau = 44 ns, Phi = 0 . 11 X 10(-3)) data for the ruthenium- modified oligonucleotides indicate t hat the presence of the oligonucleotide does not perturb the electronic pro perties of the ruthenium complex. The absence of any change in the emission properties upon duplex formation suggests that the [Ru(bpy)(2)(impy)](2+) chromophore will be a valuable probe for DNA-mediated electron-transfer stu dies. Despite the relatively high Ru(III/II) reduction potential, oxidative quenching of photoexcited [Ru(bpy)(2)(impy)](2+) does not lead to oxidativ e damage of guanine or other DNA bases.