Electrochemical detection of nucleic acids using pentaferrocenyl phosphoramidate α-oligonucleotides

Abstract

International audienceWe report the synthesis of α-oligonucleotides exhibiting five phosphoramidate linkages bearing a ferrocenyl (Fc) moiety. Three different linkers: ethyl, propyl and 4-methyl-1-ethyl-1,2,3-triazol between the ferrocene (Fc) residue and the phosphoramidate function have been studied. We demonstrated that these Fc5-α-DNA conjugates exhibit similar or even better stability than the wild type β-DNA when hybridized to their complementary β-DNA. Their electrochemical behavior studied in solution by cyclic voltammetry showed that this original structure leads to a strong difference in the Fc environment when the probe is alone or hybridized with a complementary strand. These preliminary electrochemical analyses are very encouraging and augur a good sensitivity of these probes for DNA detection after grafting on an electrode microsystem

Hybridization potential of oligonucleotides comprising 3′-O-methylated altritol nucleosides

“…The UV melting curve analysis method was used to calculate the melting temperature (Tm) values, ΔH°, ΔS° and ΔG°3 10 of folded duplexes. This method necessitates to calculate first the fraction of the single strand state and duplex state at each temperature (α(T)) from the UV melting curves [36,37]. The complete method is described in the experimental section.…”

Metal–Carbon Bonds in Biopolymer Conjugates: Bioorganometallic Nucleic Acid Chemistry

“…23,24 Recently, click chemistry has been used to add multiple ferrocene moieties to DNA at both the 5¤-position 5 25 and the backbone, with the latter approach yielding up to five adjacent ferrocenes. 26 A more unusual example of the postsynthetic incorporation of an organometallic moiety into DNA was shown by Jäschke and co-workers, 27 whose DNA dieneiridium(I) system was shown to enantioselectively catalyze allylic amination reactions.…”

Sandwich Complex‐Containing Macromolecules: Property Tunability Through Versatile Synthesis

“…Irrespective of the spacer between the ferrocenyl moiety and the phosphorus atom, all pentaferrocenylphosphoramidate α‐oligonucleotides exhibited similar electrochemical behavior. Further, the presence of a complementary oligonucleotide was found to induce high response on the ferrocene electrochemical signal whereas a non‐complement oligonucleotide did not induce a signal variation (Figure ) . This result suggests the potential application of these macromolecules as electrochemical probe for DNA detection.…”

“…The redox property, as well as the low cost of some sandwich complexes such as ferrocene, has been exploited in the design of probes for electrochemical detection . By means of “click chemistry” and/or oxidation reaction, ferrocene‐containing α‐oligonucleotide was designed with good sensitivity for detection of nuclei acids . The oligonucleotides were synthesized via a solid‐phase synthetic approach that includes phosphoramidite chemistry and H ‐phosphonate chemistry.…”