Redox-Active Glycol Nucleic Acid (GNA) Components: Synthesis and Properties of the Ferrocenyl-GNA Nucleoside, Phosphoramidite, and Semicanonical Dinucleoside Phosphate

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 N 6-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.

Stereo‐Defined Ferrocenyl Glycol Nucleic Acid (Fc‐GNA) Constituents: Synthesis, Electrochemistry, Mechanism of Formation, and Anticancer Activity Studies

“…Conjugation of the redox-active ferrocenyl entity with nucleic acids and their constituents has been proved as an effective approach for bioanalytical applications. [32,33,[50][51][52][53][54] The Fc-XNA oligonucleotides [38] as well as some Fc-GNA [43,44,46] and Fc-PNA [35,55] constituents have also been studied by electrochemistry. To achieve complete spectroscopic characterization with electrochemical data, the compounds (R,R)-1, (S,R)-1, and (R,R)-2 were subjected to cyclic voltammetry (CV).…”

“…Approach I involves the substitution of glycol hydrogen atom in position 3' with either an Fc [44] or a pyrenyl [45] entity, while approach II is based on the introduction of an Fc moiety in position 5 of the base. [46] These approaches allowed us to obtain the redox-active Fc-XNA nucleosides B and D as well as luminescent derivative C. It is worth noting that nucleoside D proved its usefulness in the preparation of semicanonical dinucleoside phosphate E (Figure 1), [46] while pyrenyl nucleoside C was used for HeLa cell imaging with confocal microscopy. [45] Our expertise in Fc-GNA and bioorganometallic chemistry [47,48] enabled us to further explore the synthetic chemistry of Fc-GNA constituents and study their activity against cancer and noncancerous cells.…”

Acyclic Nucleic Acids with Phosphodiester Linkages—Synthesis, Properties and Potential Applications

“…More recently, Kowalski and coworkers published the synthesis of a ferrocenyl-labeled analog of the nucleoside GNA-U (GNA-Fc U, 24, Chart 7) [55]. Cyclic voltammetry studies of a chimeric dinucleoside phosphate (GNA-Fc U)p(rA 2 ,3 -O,O-isopropylidene ) revealed the presence of a one-electron ferrocenyl-centered redox wave.…”

Replacement of the phosphodiester backbone between canonical nucleosides with a dirhenium carbonyl “click” linker—a new class of luminescent organometallic dinucleoside phosphate mimics

“…Therefore, we attempted to synthesize this new class of compounds as part of our research on the chemistry and biology of organometallic nucleic acid components. 49,50…”