Site-specific covalent metalation of DNA oligonucleotides with phosphorescent platinum(ii) complexes

Abstract

Phosphorescent Pt(II) complexes, composed of a tridentate N^N^C donor ligand and a monodentate ancillary ligand, were covalently attached to DNA oligonucleotides. Three modes of attachment were investigated: positioning the tridentate...

Organometallic modification confers oligonucleotides new functionalities

“…The third option is attachment of a previously synthesized organometallic moiety to an appropriately modified oligonucleotide by one of the established conjugation chemistries (Scheme 1(C)), such as peptide coupling, [111][112][113][114][115] Michael addition, 116 oximation 117,118 or azidealkyne cycloaddition. 119,120 The advantage of this approach is that the conditions used for the preparation of the organometallic moiety do not need to be compatible with those of oligonucleotide synthesis. Depending on the intended application, the relatively bulky linkages resulting from most conjugation reactions may be seen as a limitation.…”

“…The properties of some organometallic complexes make them useful as labels to facilitate imaging of oligonucleotides or elucidation of their secondary structures. The field is dominated by studies on ferrocene-labeled electrochemical probes and sensors [73][74][75][76][77] but recently luminescent organometallic labels 119,171 have also received attention.…”

“…As a step towards such applications, the platinacyclic chelate was recently incorporated into short double-helical oligodeoxynucleotides through either DNA- or GNA-type scaffolds pointing it towards the center of the double helix or through uridine-C5, placing it in the major groove. 119 Oligonucleotides placing the platinacycle within the base stack had longer fluorescence lifetimes than those placing it in the major groove and this difference was attributed to shielding from water and triplet oxygen. This interpretation was further borne out by the fact that the shortest lifetimes were observed with corresponding single-stranded oligonucleotides.…”

“…Organometallic compounds are also known for a number of metals but few are sufficiently stable hydrolytically to be useful as modifications of oligonucleotides. So far, organometallic oligonucleotide conjugates have been reported for cobalt, [133][134][135][136] iron, 101 mercury, 106 palladium, 96 platinum 119 and tin. 103,137,138 While this list is likely to expand, it is clear that compared to the coordinative counterparts, modification of oligonucleotides with organometallic complexes is much more limiting in terms of the repertoire of suitable metals.…”

6-Pyrazolylpurine and its deaza derivatives as nucleobases for silver(I)-mediated base pairing with pyrimidines

“…Likewise, the introduction of more than one metal ion per base pair can be achieved [ 11 , 12 ]. Even arrays of metal ions within a DNA duplex [ 13 – 18 ] and organometallic DNA modifications are possible [ 9 , 19 – 21 ]. DNA with metal-mediated base pairs can be applied to modulate the charge transfer ability of nucleic acids [ 22 – 25 ], to generate metal nanoclusters [ 26 ], to devise adaptive and responsive nanosystems [ 27 – 32 ], and to develop sensors for various analytes [ 33 , 34 ].…”