5-Selenocyanato and 5-trifluoromethanesulfonyl derivatives of 2′-deoxyuridine: synthesis, radiation and computational chemistry as well as cytotoxicity

• DOI: 10.1039/c8ra03172j
• Publication Date: 2018-06-12T10:43:58Z
• Authors: Samanta Makurat; Magdalena Zdrowowicz; Lidia Chomicz-Mańka; Witold Kozak; Illia E. Serdiuk; Paweł Wityk; Alicja Kawecka; Marta Sosnowska; Janusz Rak
• Keywords: Deoxyuridine; Bond-dissociation energy

5-Selenocyanato-2'-deoxyuridine (SeCNdU) and 5-trifluoromethanesulfonyl-2'-deoxyuridine (OTfdU) have been synthesized their structures confirmed with NMR MS methods. Both compounds undergo dissociative electron attachment (DEA) when irradiated X-rays in an aqueous solution containing a hydroxyl radical scavenger. The DEA yield of SeCNdU significantly exceeds that 5-bromo-2'-deoxyuridine (BrdU), remaining good agreement the computationally revealed profile electron-induced degradation. radiolysis products indicate, line theoretical predictions, Se-CN bond dissociation as main reaction channel. On other hand, for OTfdU is slightly lower than degradation measured BrdU, despite fact calculated driving force substantially overpasses thermodynamic stimulus BrdU Moreover, suggests induced formation 5-hydroxy-2'-deoxyuridine (OHdU) from OTfdU, while 2'-deoxyuridine (dU) mainly observed experimentally. We explained this discrepancy terms increased acidity resulting efficient deprotonation N3 atom, which brings about domination OTfdU(N3-H)- anion equilibrium mixture. As consequence, addition chiefly leads to dianion, OTfdU(N3-H)˙2-, easily protonates at C5 site. result, C5-O rather O-S undergoes dissociation, leading dU, A negligible cytotoxicity studied toward MCF-7 cell concentrations used labelling calls further studies aiming clinical use proposed derivatives.