Premium
Stereo‐Defined Ferrocenyl Glycol Nucleic Acid (Fc‐GNA) Constituents: Synthesis, Electrochemistry, Mechanism of Formation, and Anticancer Activity Studies
Author(s) -
Skiba Joanna,
Kowalczyk Aleksandra,
Trzybiński Damian,
Woźniak Krzysztof,
Vrček Valerije,
Gapińska Magdalena,
Kowalski Konrad
Publication year - 2021
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.202100193
Subject(s) - chemistry , hela , nucleoside , ethylene glycol , nucleic acid , nucleotide , stereochemistry , ribonucleoside , rna , organic chemistry , in vitro , biochemistry , gene
In this paper, we report the Yb(OTf) 3 ‐mediated etherification reaction that allowed obtaining R , R and S , R isomers of ferrocenyl glycol nucleic acid (Fc‐GNA) nucleosides from their corresponding stereo‐defined ( S , R ) precursor. The R , R absolute configuration of the chiral carbon atoms in one of the Fc‐nucleoside isomers was assigned by single‐crystal X‐ray diffraction. Density functional theory calculations showed that the stereochemical outcome of the reaction can be explained by an exo attack of ethylene glycol on the pro‐ R ‐ or pro‐ S ‐configured α‐ferrocenyl carbenium ion intermediate. The R , R isomer was transformed into the corresponding nucleotide diethyl ester which is, to the best of our knowledge, the first Fc‐GNA nucleotide ever reported. The obtained compounds feature reversible one‐electron oxidation of the ferrocenyl portion of their molecular structures. Anticancer activity studies showed that the ( S , R ) nucleoside was the most active against HeLa and Ishikawa cancer cells, while it did not show any activity against nontumorigenic L929 cells. The compound induced apoptosis in HeLa cells at IC 50 =66.0 μM concentration upon 72 h of treatment.