The purpose of this article is to provide an overview of the latest applications of organophosphorus compounds (OPs) that exhibit biological activity.

5-trifluoromethanesulfonyl-uracil (OTfU), a recently proposed radiosensitizer, is decomposed in the gas-phase by attachment of low-energy electrons. OTfU is a derivative of uracil with a triflate (OTf) group at the C₅-position, which substantially increases its ability to undergo effective electron-induced dissociation. We report a rich assortment of fragments formed upon dissociative electron attachment (DEA), mostly by simple bond cleavages (e.g., dehydrogenation or formation of OTf⁻). The most favorable DEA channel corresponds to the formation of the triflate anion alongside with the reactive uracil-5-yl radical through the cleavage of the O–C₅ bond, particularly at about 0 eV. Unlike for halouracils, the parent anion was not detected in our experiments. The experimental findings are accounted by a comprehensive theoretical study carried out at the M06-2X/aug-cc-pVTZ level. The latter comprises the thermodynamic thresholds for the formation of the observed anions calculated under the experimental conditions (383.15 K and 3 × 10⁻¹¹ atm). The energy-resolved ion yield of the dehydrogenated parent anion, (OTfU–H)⁻, is discussed in terms of vibrational Feshbach resonances arising from the coupling between the dipole bound state and vibrational levels of the transient negative ion. We also report the mass spectrum of the cations obtained through ionization of OTfU by electrons with a kinetic energy of 70 eV. The current study endorses OTfU as a potential radiosensitizer agent with possible applications in radio-chemotherapy.

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

In the present work, we report convenient methods for the synthesis and biological evaluation of phosphate tricyclic coumarin derivatives as potential steroid sulfatase inhibitors. The described synthesis includes the straightforward preparation of 7-hydroxy-2,3-dihydro-1H-cyclopenta[c]chromen-4-one, 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]chromen-6-one modified with various phosphate moieties. The inhibitory effects of the synthesized compounds were tested on STS isolated from human placenta as well as the MCF-7, MDA-MB-231 and MDA-MB-435S cancer cell lines. Most of the new STS inhibitors possessed IC₅₀ values between 21 to 159 μM. In the course of our investigation, the largest inhibitory effects in the STS enzyme assays were observed for the three compounds 9p, 9r and 9s, with IC₅₀ values of 36.4, 37.8 and 21.5 μM, respectively (IC₅₀ value of 1.0 μM for the 665-COUMATE used as a reference). The compound 9r, exhibited the highest potency against MCF-7, an estrogen receptor positive (ER+) cell line, with a GI₅₀ value of 24.7 μM. The structure-activity relationships of the synthesized coumarin derivatives with the STS enzyme are discussed.