Abstract
Ferrocenylated glycol nucleic acid (Fc-GNA) components are rarely studied in the field of xeno nucleic acid (XNA) chemistry. As an attempt to contribute to XNA chemistry, in the present article we report a seven-step synthesis of the first semicanonical dinucleoside containing the Fc-GNA nucleoside linked to the adenosine nucleoside with a phosphodiester bond. First, the nucleoside-bearing ethynylferrocenyl moiety in the C5 position of the uracil nucleobase was obtained. In the following steps, the nucleoside was transformed into the phosphoramidite intermediate that in turn was reacted with N6-benzoyl-2′,3′-O-isopropylideneadenosine to afford the target dinucleoside phosphate with 47% yield. The newly obtained Fc-GNA nucleoside is redox-active, and on the basis of this property (function), it belongs to a new class of functional GNA (fun-GNA) nucleosides. The electrochemistry of the Fc-GNA nucleoside, dinucleoside phosphate, and ferrocenyl furanopyrimidone nucleoside that was obtained as an undesired byproduct of Fc-GNA nucleoside synthesis was investigated by cyclic voltammetry (CV). The CV result showed the presence of a one-electron ferrocenyl-centered redox wave in each case. The half-wave potentials of the Fc-GNA nucleoside and dinucleoside phosphate were 89 and 99 mV, respectively, against the FcH/FcH+ couple. Finally, the activity of the newly obtained Fc-GNA components was studied against the nontumorigenic mouse L929 and human cervix adenocarcinoma HeLa cells. The synthesized compounds showed no cytotoxic activity against the tested cell lines.
Highlights
Xeno nucleic acids (XNAs) are artificial genetic polymers containing canonical nucleobases and phosphodiester bonds but devoid of deoxy-D-ribofuranose or D-ribofuranose as backbone motifs.[1]
Our research has been centered on the chemistry of Fcnucleobase conjugates,[40,42,43,49,50] and recently, we have focused on Fc-XNA nucleoside chemistry.[46,47]
Ferrocenylated canonical oligonucleotides and nucleobases have been used as electrochemical DNA microsensors and probes.[55−58] Ferrocenyl XNA oligonucleotides and nucleosides have been a subject of in-depth electrochemical studies.[42,46−48] With this in mind, we investigated Ferrocenylated glycol nucleic acid (Fc-GNA) nucleoside 4, furanopyrimidone 8, and dinucleoside phosphate 9 by cyclic voltammetry (CV)
Summary
Xeno nucleic acids (XNAs) are artificial genetic polymers containing canonical nucleobases and phosphodiester bonds but devoid of deoxy-D-ribofuranose or D-ribofuranose as backbone motifs.[1]. An alternative synthetic approach was attempted for the synthesis of intermediate 3 It involved the Sonogashira crosscoupling reaction of the fully protected nucleoside 1 with ethynylferrocene, followed by the hydrochloric acid cleavage of the 2,3-O-isopropylidene group (Scheme 2). A comparison of the half-wave E1/20/+ potentials in Table 1 shows that the E1/20/+ value of furanopyrimidone 8 is 43 mV higher than that of Fc-GNA nucleoside 4 This anodic shift can most likely be ascribed to the electron-withdrawing effect of the oxygen atom adjacent to the ferrocenyl moiety in 8. The cytotoxicity activities of Fc-GNA nucleoside 4, furanopyrimidone 8, and dinucleoside phosphate 9 were investigated in vitro on nontumorigenic mouse murine fibroblasts L929 and human cervical epithelioid carcinoma HeLa cells by using the tetrazolium (MTT) assay. This is a desirable effect, as it potentially allows for the use of 4 and 9 as XNA components in living cells and tissues without any toxic side effects
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