5-trifluoromethanesulfonyl-uracil (OTfU), a recently proposed radiosensitizer, is decomposed in the gas-phase by attachment of low-energy electrons. OTfU derivative uracil with triflate (OTf) group at C5-position, which substantially increases its ability to undergo effective electron-induced dissociation. We report rich assortment fragments formed upon dissociative electron (DEA), mostly simple bond cleavages (e.g., dehydrogenation or formation OTf-). The most favorable DEA channel...

Abstract The effect of the ionic liquid's (IL) anion type ([BMIM][X], where BMIM=1‐butyl‐3‐methylimidazolium and X=[Br], [PF 6 ], or octylsulfonate [OctSO 4 ]) IL content on morphology, surface properties, photoactivity TiO 2 obtained by solvothermal method has been systematically investigated. Our results revealed that presence [Br] ] anions favor formation anatase phase, whereas causes Ti(OH)PO phase mixtures. highest photocatalytic activity under visible radiation (approximately four...

5-Selenocyanato-2'-deoxyuridine (SeCNdU) is a recently proposed radiosensitizer based on 2'-deoxyuridine (dU) with the electron-affinic selenocyanato (-SeCN) side group attached at C5 position of uracil. Since electron interaction processes may be an important source DNA damage by ionizing radiation, we have studied low-energy dissociative attachment to SeCNdU in gas phase. Negative ion formation has been obtained means mass spectrometry, where rich fragmentation pattern observed even ∼0 eV....

The propensity of 5-selenocyanatouracil (SeCNU) to decomposition induced by attachment electron was scrutinized with the G3B3 composite quantum-chemical method and radiolytic studies. Favorable thermodynamic (Gibbs free reaction energy -13.65 kcal/mol) kinetic activation 1.22 characteristics revealed profile suggest SeCNU be sensitive attachment. title compound synthesized in between uracil selenocyanogen chloride acetic acid. Then, an aqueous deoxygenated solution HPLC purified containing...

Although 5-bromo-2'-deoxyuridine (5BrdU) possesses significant radiosensitizing power in vitro, clinical studies do not confirm any advantages of radiotherapy employing 5BrdU. This situation calls for a continuous search efficient radiosensitizers. Using the proposed mechanism radiosensitization by 5BrdU, we propose series 5-substituted uracils, XYU, that should undergo dissociative electron attachment. The DFT-calculated thermodynamic and kinetic data concerning XYU degradations induced...

Here, we report mechanistic studies on type II thymidine kinase, Thermotoga maritima TmTK, aiming to predict barriers for the enzyme-catalyzed reaction. Extensive umbrella sampling QM/MM MD simulations (PBE/GPW/DZVP-GTH-PBE:AMBER) resulted in a free energy barrier phosphorylation reaction's rate-limiting step of 16.6 kcal·mol–1, which is an excellent agreement with experimentally reported value. An atomistic picture provided by our reveals that reaction follows concerted, dissociative SN2...

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....

Nucleosides, especially pyrimidines modified in the C5-position, can act as radiosensitizers via a mechanism that involves their enzymatic triphosphorylation, incorporation into DNA, and subsequent dissociative electron attachment (DEA) process. In this paper, we report 5-iodo-4-thio-2'-deoxyuridine (ISdU) compound effectively lead to ionizing radiation (IR)-induced cellular death, which is proven by clonogenic assay. The test revealed survival of cells, pre-treated with 10 or 100 µM...

Efficient radiotherapy requires the concomitant use of ionizing radiation (IR) and a radiosensitizer. In present work uracil-5-yl O-sulfamate (SU) is tested against its radiosensitizing potential. The compound possesses appropriate dissociative electron attachment (DEA) characteristics calculated at M06-2X/6-31++G(d,p) level. Crossed electron–molecular beam experiments in gas phase demonstrate that SU undergoes efficient DEA processes, single C–O or S–O bond dissociations account for...

Radiosensitizing properties of substituted uridines are great importance for radiotherapy. Very recently, we confirmed 5-iodo-4-thio-2'-deoxyuridine (ISdU) as an efficient agent, increasing the extent tumor cell killing with ionizing radiation. To our surprise, a similar derivative 4-thio-2'-deoxyuridine, 5-bromo-4-thio-2'-deoxyuridine (BrSdU), does not show radiosensitizing at all. In order to explain this remarkable difference, carried out radiolytic (stationary and pulse) quantum chemical...

Abstract Conjugating an anticancer drug of high biological efficacy but large cytotoxicity with a “transporting” molecule low toxicity constitutes valuable approach to design safe delivery system. In the present study, doxorubicin (DOX) cardiotoxicity was chemically conjugated C 60 -fullerene. The synthesized molecule, fullerene-doxorubicin conjugate (Ful-DOX), characterized using 1 H NMR and MALDI TOF mass spectrometry. absorption fluorescence spectra dynamic light scattering were recorded...

Metronidazole belongs to the class of nitroimidazole molecules and has been considered as a potential radiosensitizer for radiation therapy. During irradiation biological tissue, secondary electrons are released that may interact with surrounding environment. Here, we present study electron attachment metronidazole aims investigate possible reactions in molecule upon anion formation. Another purpose is elucidate effect microhydration on electron-induced metronidazole. We use two crossed...

Modified uridines seem to be able work as hypoxic tumour cell radiosensitisers. Before they sensitise cells ionising radiation, have incorporated into the genomic DNA and latter process has preceded by phosphorylation of modified uridine, which in human is executed thymidine kinase 1 (hTK1). In current study, we present quantitative structure-activity relationship (QSAR) model allowing identify understand molecular features nucleoside derivatives governing hTK1 activity. The developed meets...

Brominated nucleobases sensitize double stranded DNA to hydrated electrons, one of the dominant genotoxic species produced in hypoxic cancer cells during radiotherapy. Such radiosensitizers can therefore be administered locally enhance treatment efficiency within solid tumor while protecting neighboring tissue. When a solvated electron attaches 8-bromoadenosine, potential sensitizer, dissociation bromide leads reactive C8 adenosyl radical known generate range lesions. In current work, we...

Formation of a surface complex between organic molecules and TiO2 is one the possible strategies for development visible light-induced photoactivity. Herein, three ionic liquids (ILs) with same cation different anions (1-butylpirydynium chloride/bromide/iodide) have been applied modification to understand role in activity ILs-TiO2 systems. Photocatalytic screening tests (the measurements phenol photodegradation reaction rate) revealed that anion type affected light (λ > 420 nm) obtained...

Despite its importance in the nucleoside (and prodrug) metabolism, structure of active conformation human thymidine kinase 1 (hTK1) remains elusive. We perform microsecond molecular dynamics simulations inactive enzyme form bound to a bisubstrate inhibitor that was shown experimentally activate another TK1-like kinase, Thermotoga maritima TK (TmTK). Our results are excellent agreement with experimental findings for TmTK closed-to-open state transition. show induces an increase radius...

Intermolecular interactions such as those present in molecule···water complexes may profoundly influence the physicochemical properties of molecules. Here, we carried out an experimental–computational study on doubly deprotonated guanosine monophosphate···water clusters, [dGMP – 2H]2–·nH2O (n = 1–4), using a combination negative anion photoelectron spectroscopy (NIPES) with molecular dynamics (MD) and quantum chemical (QM) calculations. Successive addition water molecules to 2H]2– increases...

Hypoxia—a hallmark of solid tumors—dramatically impairs radiotherapy, one the most common anticancer modalities. The adverse effect low-oxygen state can be eliminated by concomitant use a hypoxic cell radiosensitizer. In present paper, we show that 5-(N-trifluoromethylcarboxy) aminouracil (CF3CONHU) considered as an effective radiosensitizer DNA damage, working under hypoxia. title compound was synthesized in reaction 5-aminouracil and trifluoroacetic anhydride acid. Then, aqueous...

A better understanding of the mechanism oxidative DNA damage requires obtaining a molecular level description nucleotides in various charge states. Herein, we report systematic photoelectron spectroscopy and theoretical investigation electronic geometric structures four doubly deprotonated 2'-deoxynucleoside 5'-monophosphate dianions, smallest quintessential building block. These dianions are intrinsically stable with their adiabatic/vertical detachment energies (ADE/VDE) ranging from...

The UVB irradiation of DNA labeled with 5-bromo-2'-deoxyuridine (BrdU) leads to single-strand breaks (SSBs) as a major photochemical damage. Some time ago, we demonstrated that SSB is secondary damage forming due thermal dissociation 2'-deoxyribonolactone generated photochemically in BrdU. For the first time, study here variation yield SSBs alteration 3'-neighbor nucleobase electron donor (2'-deoxyguanine (dG)) and acceptor (excited BrdU) double-stranded DNA. We showed experimental yields...