Synthesis and Hybridization Properties of Covalently Mercurated and Palladated Oligonucleotides

Abstract

Covalent metalation of the base moieties affords a new class of modified oligonucleotides. These organometallic oligonucleotides share many properties, notably increased hybridization affinity conferred by metal-mediated base pairing, with oligonucleotides incorporating coordinative transition-metal complexes. They are, however, set apart by their ability to retain the transition-metal ion even at extreme dilution. Such stability towards dissociation would be desirable in DNA nanotechnology and necessary in therapeutic applications. Herein we describe our efforts towards preparation and characterization of covalently mercurated and palladated oligonucleotides, highlighting in particular our recent contribution on the synthesis and potential applications of oligonucleotides incorporating dimercurated artificial nucleobases.1 Introduction2 Synthesis of Covalently Mercurated and Palladated Oligonucleotides3 Hybridization Properties of Covalently Mercurated and Palladated Oligonucleotides4 Outlook

Synthesis of Organometallic Oligonucleotides through Oximation with Metalated Benzaldehydes

“…We, on the other hand, have recently become interested in an alternative approach in which the metal ion is held in place by an organometallic bond formed by postsynthetic metalation of an oligonucleotide, incorporating an appropriate “hot spot” in a solution. 9 The main advantage of this strategy is that the organometallic complex resists dissociation even at extreme dilution, widening the scope of metal ions usable in intracellular applications from the kinetically inert Pt(II) and Ru(II) to more labile ones, such as Pd(II) and Hg(II). For example, the high thermodynamic stability of kinetically labile metal-mediated base pairs 2,3 could be harnessed to promote hybridization of therapeutic oligonucleotides with their target sequences.…”

“…Oligonucleotides functionalized with transition metal ions are studied intensively for potential applications in DNA nanotechnology − as well as diagnostics and chemotherapy. − Such structures are typically obtained through coordination of the desired metal ion to a high-affinity ligand within the oligonucleotide. We, on the other hand, have recently become interested in an alternative approach in which the metal ion is held in place by an organometallic bond formed by postsynthetic metalation of an oligonucleotide, incorporating an appropriate “hot spot” in a solution . The main advantage of this strategy is that the organometallic complex resists dissociation even at extreme dilution, widening the scope of metal ions usable in intracellular applications from the kinetically inert Pt­(II) and Ru­(II) to more labile ones, such as Pd­(II) and Hg­(II).…”

Organomercury Nucleic Acids: Past, Present and Future

“…Electrophilic aromatic substitution at C5 of cytosine and uracil bases, as well as electron‐rich carbon atoms of artificial nucleoside analogues, by Hg II proceeds under sufficiently mild conditions to be feasible also on oligonucleotides [11] and even longer nucleic acid sequences [4] . The reaction is highly sequence dependent, homopolymers of cytidine and uridine being mercurated much faster than naturally occurring heteropolymers.…”

“…More recently, Hg II ‐mediated base pairing of organomercury nucleobases has been studied as a means to increase the hybridization affinity of oligonucleotide probes in biological media [11] . These studies have involved recording concentration‐dependent 1 H NMR spectra at monomer level and UV melting profiles at the oligomer level and, when applicable, the results have generally been in good agreement.…”

2-Trifluoromethyl-6-mercurianiline Nucleotide, a Sensitive 19F NMR Probe for Hg(II)-mediated Base Pairing

“…They do not require similar external metal ion content and may thus be more applicable in biological systems. 30 − 40 …”