Eumitrins F-H: three new xanthone dimers from the lichen Usnea baileyi and their biological activities.

The lichen Usnea baileyi is a fruticose lichen belonging to the Usnea genus. It is well known as a rich source of natural xanthone dimers and possesses various bioactivities. Nevertheless, the chemical investigation on this type of lichen is still rare as most of researches reported its components without structural elucidation. Herein, in the continuous study on this type of lichen, we further isolate xanthone dimers from the dichloromethane extract and explore three new xanthone dimers, eumitrins F - H (1 - 3). Their structures were elucidated unambiguously by spectroscopic analyses, including high resolution electrospray ionisation mass spectrometry (HRESIMS), 1 D and 2 D nuclear magnetic resonance spectroscopy (1 D and 2 D NMR), and DP4 probability. All compounds were evaluated for their enzyme inhibition against α-glucosidase, tyrosinase, and antibacterial activity. They revealed moderate antimicrobial and weak tyrosinase inhibition. For α-glucosidase inhibition, compound 3 displayed the most significant inhibitory against α-glucosidase possessing an IC50 value of 64.2 µM.

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Fluorinated Candidates as PI3K Inhibitors: Targeting Fluorophilic Binding Sites.

Highly fluorinated candidates containing anticancer pharmacophores like thiosemicarbazone (5a-e) and its cyclic analogues hydrazineylidenethiazolidine (6a-e), 2-aminothiadiazole (7a-e), and 2-hydrazineylidenethiazolidin-4-one (8a-e) were synthesized, and their cytotoxic activity was assayed against 60 tumor cell lines. Compounds 6c, 7b, and 8b displayed the most potent activity with lower toxic effects on MCF-10a. In vitro phosphatidylinositol 3-kinase (PI3K) enzyme inhibition was performed. Compound 6c displayed half-maximal inhibitory concentration (IC50, µM) values of 5.8, 2.3, and 7.9; compound 7b displayed IC50 values of 19.4, 30.7, and 73.7; and compound 8b displayed IC50 values of 77.5, 53.5, and 121.3 for PI3Kα, ß, and δ, respectively. Moreover, cell cycle progression caused cell cycle arrest at the S phase for compounds 6c and 8b and at G1/S for compound 7b, while apoptosis was induced. In silico studies; molecular docking; physicochemical parameters; and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis were performed. The results showed that compound 6c is the most potent one with a selectivity index (SI) of 39 and is considered as a latent lead for further optimization of anticancer agents.

A fluorinated chitosan-based QuEChERS method for simultaneous determination of 20 organophosphorus pesticide residues in ginseng using GC-MS/MS.

In this study, a new fluorinated methacrylamide (MACF) was synthesized and evaluated as an adsorbent in the dispersive solid-phase extraction for the effective determination and extraction of 20 organophosphorus pesticides (OPPs) from ginseng samples using the QuEChERS (quick, easy, cheap, effective, rugged, safe) method coupled with GC-MS/MS. The properties of MACF were characterized using Fourier-transform infrared spectroscopy, elemental analysis, and high-resolution 19 F NMR. MACF, chitosan, primary and secondary amine, octadecylsilane, graphitized carbon black, Z-Sep, Z-Sep+ , and EMR-Lipid were compared in terms of extraction efficiency. The best results were obtained when MACF was used. Matrix-matched calibration was employed for quantification. All the OPPs exhibited good linearity (r2 > 0.9969) with the concentration at their respective concentration ranges. The limits of detection were 1.5-3.0 µg/kg, and the limits of quantification were 5.0-10.0 µg/kg. The trueness of the 20 pesticides at four spiked levels ranged from 86.1 to 111.1%, and the relative standard deviation was less than 11.3%. The modified QuEChERS method using MACF as the adsorbent was sensitive, reliable, and cost-effective and could be used for the determination of 20 OPP residues in ginseng.

Phosphorus-mediated sp2-sp3 couplings for C-H fluoroalkylation of azines.

Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence almost all metrics associated with their pharmacokinetic and pharmacodynamic profile1-4. Drug candidates increasingly contain trifluoromethyl (CF3) and difluoromethyl (CF2H) groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect and plant life5,6. New fluoroalkylation reactions have undoubtedly stimulated this shift; however, methods that directly convert C-H bonds into C-CF2X groups (where X is F or H) in complex drug-like molecules are rare7-13. Pyridines are the most common aromatic heterocycles in pharmaceuticals14, but only one approach-via fluoroalkyl radicals-is viable for achieving pyridyl C-H fluoroalkylation in the elaborate structures encountered during drug development15-17. Here we develop a set of bench-stable fluoroalkylphosphines that directly convert the C-H bonds in pyridine building blocks, drug-like fragments and pharmaceuticals into fluoroalkyl derivatives. No preinstalled functional groups or directing groups are required. The reaction tolerates a variety of sterically and electronically distinct pyridines, and is exclusively selective for the 4-position in most cases. The reaction proceeds through initial formation of phosphonium salts followed by sp2-sp3 coupling of phosphorus ligands-an underdeveloped manifold for forming C-C bonds.

Low Dose Curcumin Administered in Hyaluronic Acid-Based Nanocapsules Induces Hypotensive Effect in Hypertensive Rats.

BACKGROUND: Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. METHODS: The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic - DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. RESULTS: In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur - based treatment changes in SBP, DBP and MAP amounted to -2.0±0.8 mmHg, -3.9±0.7 mmHg and -3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19F NMR technique after a single intragastric administration. CONCLUSION: These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.

Influence of Fluorine Substituents on the Electronic Properties of Selenium-N-Heterocyclic Carbene Compounds.

N-heterocyclic carbenes (NHCs) are common ancillary ligands in organometallic compounds that are used to alter the electronic and steric properties of a metal centre. To date, various NHCs have been synthesised with different electronic properties, which can be done by modifying the backbone or changing the nitrogen substituents group. This study describes a systematic modification of NHCs by the inclusion of fluorine substituents and examines the use of selenium-NHC compounds to measure the π-accepting ability of these fluorinated NHC ligands. Evaluation of the 77Se NMR chemical shifts of the selenium adducts reveals that fluorinated NHCs have higher chemical shifts than the non-fluorinated counterparts, IMes and IPh. Higher 77Se NMR chemical shifts values indicate a stronger π-accepting ability of the NHC ligands. The findings of this study suggest that the presence of fluorine atoms has increased the π-accepting ability of the corresponding NHC ligands. This work supports the advantage of the 77Se NMR chemical shifts of selenium-NHC compounds for assessing the influence of fluorine substituents on NHC ligands.

Targeted copper supplementation oriented theranostic for fluorescence and 19F NMR detection of tumors.

Alteration of the levels of copper is a promising approach for cancer therapy. Herein, we develop a dual-mode copper vehicle, M985. The biotin-tailed M985 can exert tumor-directed copper supplementation and undergo self-immolative cleavage in living cancerous cells, resulting in the liberation of F542 along with the generation of excess reactive oxygen species. Thus, fluorescence and 19F NMR detection is realized to specifically discriminate cancer cells. F542 acts as a fluorescence reporter and a potent cytotoxic agent, facilitating the visualization of molecular release and distribution, as well as confirming the ER autophagy-induced apoptosis. Therefore, we present a promising dual-mode theranostic M985 for the efficient detection and therapy of cancer.

Powerful, transferable representations for molecules through intelligent task selection in deep multitask networks.

Chemical representations derived from deep learning are emerging as a powerful tool in areas such as drug discovery and materials innovation. Currently, this methodology has three major limitations - the cost of representation generation, risk of inherited bias, and the requirement for large amounts of data. We propose the use of multi-task learning in tandem with transfer learning to address these limitations directly. In order to avoid introducing unknown bias into multi-task learning through the task selection itself, we calculate task similarity through pairwise task affinity, and use this measure to programmatically select tasks. We test this methodology on several real-world data sets to demonstrate its potential for execution in complex and low-data environments. Finally, we utilise the task similarity to further probe the expressiveness of the learned representation through a comparison to a commonly used cheminformatics fingerprint, and show that the deep representation is able to capture more expressive task-based information.

Quantification of Uncoupled Spin Domains in Spin-Abundant Disordered Solids.

Materials often contain minor heterogeneous phases that are difficult to characterize yet nonetheless significantly influence important properties. Here we describe a solid-state NMR strategy for quantifying minor heterogenous sample regions containing dilute, essentially uncoupled nuclei in materials where the remaining nuclei experience heteronuclear dipolar couplings. NMR signals from the coupled nuclei are dephased while NMR signals from the uncoupled nuclei can be amplified by one or two orders of magnitude using Carr-Meiboom-Purcell-Gill (CPMG) acquisition. The signal amplification by CPMG can be estimated allowing the concentration of the uncoupled spin regions to be determined even when direct observation of the uncoupled spin NMR signal in a single pulse experiment would require an impractically long duration of signal averaging. We use this method to quantify residual graphitic carbon using 13C CPMG NMR in poly(carbon monofluoride) samples synthesized by direct fluorination of carbon from various sources. Our detection limit for graphitic carbon in these materials is better than 0.05 mol%. The accuracy of the method is discussed and comparisons to other methods are drawn.

Chemical behavior of fluorine and phosphorus in chemical looping gasification using phosphogypsum as an oxygen carrier.

In China, the amount of phosphogypsum (PG) has exceeded 250 million tons with more than 55 million tons of growth rates each year. As the micro constituent, fluorine and phosphorus restrict the resourceful disposal of PG. This paper focused on chemical looping gasification (CLG) which used PG as an oxygen carrier, systematically investigated the gasification performance and chemical behavior of fluorine and phosphorus contained in PG during CLG process. Main conclusions are as follows. The main pollutant of chemical looping gasification process was HF, which was transformed from NaF. Phosphorus transformed from water-soluble phosphorus (Ca(H2PO4)2, Ca(HPO4)) into insoluble Ca3(PO4)2.20 reducing-oxidizing cycles were investigated, and a less and less fluorine content in oxygen carrier was found because its phase transformation from solid NaF to gaseous HF, and the phosphorus content in oxygen carrier changed slightly under the current conditions. The Ca3(PO4)2 particle layers existed in both the middle of the reduced solid particles and the middle of the cycled oxygen carrier particles, confirmed to actually act as a glue between the particles. Furthermore, transformation routes of fluorine and phosphorus during the CLG process were discussed and the generation of syngas in CLG process needed to be purified.

Tritiodefluorination of alkyl C-F groups.

A straightforward methodology of fluorine substitution by tritium/deuterium is reported. The described method is selective towards the F─C (sp3 ) group and leaves both the aromatic F─C (sp2 ) and F2 ─C (sp3 ) moieties unaffected. Alkylfluorides, readily synthesized from appropriate alcohols by treatment with diethylaminosulfur trifluoride (DAST) reagent in an overall yield up to 76%, undergoes activation with the boron-based Lewis acid B(C6 F5 )3 , and stoichiometric in situ reduction with a tritide/deuteride reagent-the [TMP2(3) H][2(3) HB(C6 F5 )3 ] system of frustrated Lewis pair. This methodology provides an isolated yield of up to 93% of regio-specifically labeled small organic compounds with superior 2 H-enrichment of over 95%. The specific activity of prepared 1-(2-[3 H]-ethyl)naphthalene was determined at 29.0 Ci/mmol. The site selectivity of the Lewis acid/ [TMP2(3) H][2(3) HB(C6 F5 )3 ] approach is orthogonal to currently used methods and allows for isotopic labeling of complementary positions in molecules. Reported labeling methodology proceeds well at ultra-mild reaction conditions (220 mbar of T2 ), allowing very low consumption of the radioactive source (4.2 Ci/156 GBq), and producing limited amount of radioactive waste.

Novel fluorine-containing chiral hydrazide-hydrazones: Design, synthesis, structural elucidation, antioxidant and anticholinesterase activity, and in silico studies.

In this study, a series of fluorine-containing chiral hydrazide-hydrazone derivatives [III-XII] from ʟ-cysteine ethyl ester hydrochloride was synthesized as new antioxidant and anticholinesterase agents. The antioxidant activity of these derivatives was evaluated by ABTS+· and DPPH· scavenging and CUPRAC assays and the anticholinesterase activity by the Ellman method spectrophotometrically. The results of the antioxidant assay showed that compounds V, IX, and X exhibited higher activity than BHT and α-tocopherol used as positive standards. Among the synthesized derivatives, compound IX (IC50 : 2.3 ± 1.6 µM) exhibited higher acetylcholinesterase inhibitory activity than galantamine (IC50 : 4.5 ± 0.8 µM). Compounds XI (IC50 : 9.6 ± 1.0 µM), IX (IC50 : 12.5 ± 1.6 µM), III (IC50 : 16.0 ± 1.6 µM), X (IC50 : 17.2 ± 1.8 µM), VI (IC50 : 20.2 ± 0.8 µM), XII (IC50 : 21.5 ± 1.0 µM), and VII (IC50 : 24.6 ± 0.6 µM) displayed better butyrylcholinesterase inhibitory activity than galantamine (IC50 : 46.03 ± 0.14 µM). ADME-Tox analysis was used to probe the drug-like properties of the compounds. Molecular docking studies were also applied to understand the interactions between compounds and targets. The docking calculations were supported by the experimental data. In particular, compound IX, having better activity than galantamine against acetylcholinesterase and butyrylcholinesterase enzymes, was visualized using molecular docking.

UV and Visible Light-Driven Production of Hydroxyl Radicals by Reduced Forms of N, F, and P Codoped Titanium Dioxide.

The photocatalytic activities of reduced titanium dioxide (TiO2) materials have been investigated by measuring their ability to produce hydroxyl radicals under UV and visible light irradiation. Degussa P25 TiO2 was doped with nitrogen (N), fluorine (F), and/or phosphorus (P) and then subjected to surface modification employing a thermo-physicochemical process in the presence of reducing agent sodium borohydride (NaBH4). The reduced TiO2 materials were characterized by a number of X-ray, spectroscopic and imaging methods. Surface doping of TiO2 was employed to modulate the band gap energies into the visible wavelength region for better overlap with the solar spectrum. Hydroxyl radical generation, central to TiO2 photocatalytic water purification applications, was quantitated using coumarin as a trap under UV and visible light irradiation of the reduced TiO2 materials. At 350 nm irradiation, the yield of hydroxyl radicals generated by the reduced forms of TiO2 was nearly 90% of hydroxyl radicals generated by the Degussa P25 TiO2. Hydroxyl radical generation by these reduced forms of TiO2 was also observed under visible light irradiation (419 and 450 nm). These results demonstrated that simple surface modification of doped TiO2 can lead to visible light activity, which is important for more economical solar-driven applications of TiO2 photocatalysis.

Switchable up-conversion luminescence bioimaging and targeted photothermal ablation in one core-shell-structured nanohybrid by alternating near-infrared light.

In photothermal therapy (PTT), simultaneous achievement of imaging and hyperthermia mediated by a single laser inevitably risks damaging normal tissues before treatment. Herein, a core-shell-structured GdOF:Yb/Er@(GNRs@BSA) nanohybrid was designed and fabricated by conjugating gold nanorods (GNRs) on the surfaces of GdOF:Yb/Er nanoparticles by a facile procedure. By alternating near-infrared (NIR) light appropriately, high photothermal efficiency for PTT and good up-conversion luminescence (UCL) imaging can be achieved in this structure, which can substantially solve the heat-induced risk during the theranostic process. Furthermore, good biocompatibility and phagocytosis can be realized by modifying bovine serum albumin (BSA) on the surface of the GNRs, and the conjugation of folic acid (FA) endows this nanohybrid with targeting function. It is noted that the size of the GNRs prepared by the one-pot method is much smaller than that by the seed-mediated method, which is not only conducive to uniform heat distribution during intratumoral therapy, but also contributes to the nanohybrid metabolic decomposition and fluorescence tracing after treatment. Moreover, this product can also be utilized as a good magnetic resonance imaging (MRI) and computed tomography (CT) contrast agent, which can provide versatile imaging properties in the field of cancer clinical treatment.

Toward 19F magnetic resonance thermometry: spin-lattice and spin-spin-relaxation times and temperature dependence of fluorinated drugs at 9.4 T.

OBJECTIVE: This study examines the influence of the environmental factor temperature on the 19F NMR characteristics of fluorinated compounds in phantom studies and in tissue. MATERIALS AND METHODS: 19F MR mapping and MR spectroscopy techniques were used to characterize the 19F NMR characteristics of perfluoro-crown ether (PFCE), isoflurane, teriflunomide, and flupentixol. T1 and T2 mapping were performed, while temperature in the samples was changed (T = 20-60 °C) and monitored using fiber optic measurements. In tissue, T1 of PFCE nanoparticles was determined at physiological temperatures and compared with the T1-measured at room temperature. RESULTS: Studies on PFCE, isoflurane, teriflunomide, and flupentixol showed a relationship between temperature and their physicochemical characteristics, namely, chemical shift, T1 and T2. T1 of PFCE nanoparticles was higher at physiological body temperatures compared to room temperature. DISCUSSION: The impact of temperature on the 19F NMR parameters of fluorinated compounds demonstrated in this study not only opens a trajectory toward 19F MR-based thermometry, but also indicates the need for adapting MR sequence parameters according to environmental changes such as temperature. This will be an absolute requirement for detecting fluorinated compounds by 19F MR techniques in vivo.

Microbiological and Cellular Evaluation of a Fluorine-Phosphorus-Doped Titanium Alloy, a Novel Antibacterial and Osteostimulatory Biomaterial with Potential Applications in Orthopedic Surgery.

Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both of which are associated with high morbidity and substantial costs for patients and health systems. The development of a biomaterial that is capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. We report antibacterial and osteostimulatory effects in a novel fluorine-phosphorus (F-P)-doped TiO2 oxide film grown on Ti-6Al-4V alloy with a nanostructure of bottle-shaped nanotubes (bNT) using five bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia) and MCT3T3-E1 osteoblastic cells. The interaction between the bacteria and bNT Ti-6Al-4V was complex, as the adhesion of four bacterial species decreased (two staphylococcus species, E. coli, and S. maltophilia), and the viability of staphylococci and S. maltophilia also decreased because of the aluminum (Al) released by bNT Ti-6Al-4V. This released Al can be recruited by the bacteria through siderophores and was retained only by the Gram-negative bacteria tested. P. aeruginosa showed higher adhesion on bNT Ti-6Al-4V than on chemically polished (CP) samples of Ti-6Al-4V alloy and an ability to mobilize Al from bNT Ti-6Al-4V. The cell adhesion and proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 and 168 h, as did the matrix mineralization of these cells and the gene expression levels of three of the most important markers related to bone differentiation. According to our results, the bNT Ti-6Al-4V alloy could have clinical application, preventing infection and stimulating bone growth and thus preventing the two main causes of joint prosthesis failure.IMPORTANCE This work evaluates F-P-doped bNT Ti-6Al-4V from microbiological and cellular approaches. The bacterial results highlight that the antibacterial ability of bNT Ti-6Al-4V is the result of a combination of antiadhesive and bactericidal effects exerted by Al released from the alloy. The cell results highlight that F-P bNT Ti-6Al-4V alloy increases osseointegration due to modification of the chemical composition of the alloy resulting from P incorporation and not due to the nanostructure, as reported previously. A key finding was the detection of Al release from inside the bNT Ti-6Al-4V nanostructures, a result of the nanostructure growth during the anodizing process that is in part responsible for its bactericidal effect.

De novo transcriptome assembly of fluorine accumulator tea plant Camellia sinensis with fluoride treatments.

Tea plant (Camellia sinensis) is a typical fluoride (F) hyperaccumulator enriching most F in old leaves. There is association between the risk of fluorosis and excessive consumption of teas prepared using the old leaves. It is meaningful to develop methods for controlling F levels in tea leaves. We generated a comprehensive RNA-seq dataset from tea plants grown at various F levels for different durations by hydroponics, aiming at providing information on mechanism of F metabolism in tea plant. Besides raw reads of the RNA-seq dataset, we present assembled unigenes and aligned unigenes with annotations versus the Gene Ontology (GO) databases, Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases, and Nonredundant (Nr) protein databases with low e-values. 69,488 unigenes were obtained in total, in which 40,894 were given Nr annotations.

Fluorine Grafted Cu7S4-Au Heterodimers for Multimodal Imaging Guided Photothermal Therapy with High Penetration Depth.

We report the multifunctional nanocomposites (NCs) consisting of 19F-moieties grafted Cu7S4-Au nanoparticles (NPs) for negligible background 19F-magnetic resonance imaging (19F-MRI) and computed tomography (CT) imaging guided photothermal therapy. The localized surface plasmon resonance (LSPR) absorption can be reasonably tuned to the in vivo transparent window (800-900 nm) by coupling Au (<10 nm, LSPR ∼530 nm) with Cu7S4 (<15 nm, LSPR ∼1500 nm) into Cu7S4-Au heterodimers. The in vivo photothermal tests show that Cu7S4-Au show deeper light penetration with 808 nm irradiation, better photothermal efficacy, and less damage to normal tissues than Cu7S4 with 1500 nm irradiation. Moreover, compared to traditional 1H-MRI, the 19F-MRI based on these NCs demonstrates much better sensitivity due to the negligible background. This work offers a promising strategy for multimodal imaging guided photothermal therapy of deep tissue with good efficacy.

A Hollow NaGdF4 /AFn Nanosystem Based on "Relay Race" Release for Therapy.

To develop a multifunctional nanomaterial for dual-mode imaging and synergetic chemotherapy, curcumin (CUR) was physically entrapped into hollow upconversion NaGdF4 nanomaterial, then apoferritin (AFn) loaded with doxorubicin (DOX) was attached to the NaGdF4 surface. Subsequent modification with the targeting reagent folic acid (FA) led to generation of the CUR/NaGdF4 -DOX/AFn-FA conjugate for cancer treatment. X-ray diffraction, scanning (SEM) and transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy demonstrated the successful preparation of hexagonal-phase NaGdF4 and NaGdF4 -AFn-FA. Moreover, no toxicity was observed for NaGdF4 -AFn-FA. In vitro and in vivo experiments demonstrated that the two drugs are sequentially released from the nanocomposites. This two-drug system showed strong growth inhibitory effects on MCF-7 cells. Upconversion luminescence imaging and magnetic resonance (MR) imaging of NaGdF4 -AFn-FA were carried out. The results of this study show that NaGdF4 -AFn-FA can be used for targeted anticancer drug delivery as well as imaging, a novel multi-pronged theranostic system for tumor treatment.

Synthesis and antiviral evaluation of fluorinated acyclo-nucleosides and their phosphoramidates.

A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.