Oligonucleotides Incorporating Palladacyclic Nucleobase Surrogates

Abstract

An oligonucleotide incorporating a palladacyclic nucleobase has been prepared by ligand-directed metalation of a phenylpyridine moiety. This oligonucleotide hybridized with natural counterparts placing any of the canonical nucleobases opposite to the palladacyclic residue. The palladated duplexes had B-type conformation and melting temperatures comparable to those of respective unmodified duplexes with a single mismatch. In the duplexes placing C, G or T (but not A) opposite to the palladacyclic residue, greatly increased absorptivity suggested formation of a Pd -mediated base pair. Absorptivity and ellipticity of these duplexes persisted even at the highest temperatures applicable in T and CD experiments (90 °C). Evidently the Pd -mediated base pairs do not dissociate under the experimental conditions.

Covalently Palladated Oligonucleotides Through Oxidative Addition of Pd0

“…The equilibrium T m values lie somewhere between these two extremes but the overlapping of the two transitions on the biphasic curves precludes a more detailed analysis. It is worth pointing out, however, that even the lower limits for the “high” T m are higher than the T m of a respective fully matched natural duplex under the same conditions (approximately 50 °C) . Averages of the upper and lower limits would in all cases mean considerable stabilization.…”

“…It is worth pointingo ut, however,t hat even the lower limits for the "high" T m are higher than the T m of ar espective fully matched natural duplex under the same conditions (approximately 50 8C). [2] Averages of the upper and lower limits would in all cases mean considerable stabilization. In contrast, meltingp rofiles of duplexes formed by the unmetalatedo ligonucleotide ON1 b-I were monophasic with T m values of approximately 30 8Ca nd did not exhibit appreciable hysteresis (renaturation curves are presented in the Supporting Information).…”

“…The supernatant was fractioned by RP HPLC under the conditions used for the purification of ON1 b.T he product peak was broad and convoluted, consistent with previous reports on covalently palladated oligonucleotides. [2] Mass spectrometric analysis revealed presence of the desired product ON1 b-Pd in all of the fractions collected but only the one of the highest purity (eluting at 10.7 min) was used in the hybridization experiments. The concentration of this fraction was determined UV spectrophotometrically as described above.…”

“…[1] To widen the scope of the latter application to biological systems, that is, to overcome the scarcity of transition metals available for metal-mediated base pairingi nt he intracellular medium, we have explored the possibility of using oligonucleotides with organometallic nucleobase surrogates. [2,3] We have successfully synthesizeds uch structures by two approaches-eitherd irect mercuration of electron-richs ites on aromatic rings [4] or ligand-directed cyclopalladation of benzylamine or phenylpyridine moieties. [5] Palladationof aromatic rings withoutt he assistance of ad irecting ligand would also be desirable, as the resultingm onodentate organopalladium complexes wouldl eave the palladium center more exposed and amenable to pseudo-linear coordination (Figure 1).…”

Stable Copper(I)‐Mediated Base Pairing in DNA

“…[4] Here,the nucleobases are held together by coordinate bonds to metal ions in the center of the helix, formally replacing the canonical base pairs.B oth natural nucleosides and artificial nucleosides are capable of engaging in metal-mediated base pairing. [6] In this context, artificial nucleosides have as light advantage because they can in principle be designed for selective metal ion coordination. [6] In this context, artificial nucleosides have as light advantage because they can in principle be designed for selective metal ion coordination.…”