Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(2'R,5'S-)-cis-5-Fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine (524W91) is a nucleoside analog with potent anti-human immunodeficiency virus and anti-human hepatitis B virus activities in vitro. The pharmacokinetics and bioavailability of 524W91 after oral dosing were studied in mice dosed with 10, 100, and 600 mg of 524W91 per kg of body weight by the oral and intravenous routes. Cynomolgus monkeys were dosed with 10 and 80 mg of 524W91 per kg. In both species, the clearance of 524W91 was rapid, via the kidney, and was independent of dose. In monkeys, the total body clearance of 10 mg of 524W91 per kg was 0.7 +/- 0.1 liter/h/kg, and the volume of distribution at steady state was 0.8 +/- 0.02 liter/kg. The terminal elimination half-life was 1.0 +/- 0.2 h. The absolute bioavailability after oral dosing was 63% +/- 4% at 10 mg/kg. Concentrations of 524W91 in the cerebrospinal fluid were 4% +/- 0.7% of the corresponding levels in plasma. In mice, the total clearance of 10 mg of 524W91 per kg was 2.3 liters/kg/h, and the volume of distribution at steady state was 0.9 liter/kg. Absolute bioavailability in mice after oral dosing was 96% at a dose of 10 mg/kg. The metabolism of orally administered [6-3H]524W91 was studied in cynomolgus monkeys at a dose of 80 mg/kg and in mice at a dose of 120 mg/kg. Monkeys excreted 41% +/- 6% of the radioactive dose in the 0- to 72-h urine, 33% +/- 10% in the feces, and 10% +/- 7% in the cage wash. Unchanged 524W91 was 64% of the total radiolabeled drug recovered in the urine. The glucuronide was a minor urinary metabolite. 5-Fluorouracil was not detected (less than 0.02% of the dose). Mice dosed orally with 120 mg of [6-3H]524W91 per kg excreted 67% +/- 7% of the radiolable in the )- to 48-h urine. Small amounts of the 3' -sulfoxide and glucuronide metabolites were observed in the urine, but 5-fluorouracil was not detected. Good bioavailability after oral dosing and resistance to metabolism recommend 524W91 for further preclinical evaluation.
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PMID:Pharmacokinetics, oral bioavailability, and metabolism in mice and cynomolgus monkeys of (2'R,5'S-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine, an agent active against human immunodeficiency virus and human hepatitis B virus. 769 53

The synthesis of gallophosphate cloverite in the presence of aluminium leads to a partial substitution of Ga by Al. 27Al and 19F magic-angle spinning nuclear magnetic resonance (MAS NMR) studies on this material confirm this substitution. 27Al MAS NMR shows a broad line at 30 ppm which can be attributed to tetrahedrally coordinated Al in the solid. The 19F MAS NMR results are more complex. The spectrum presents five lines between -68 ppm and -95 ppm which can be assigned to fluorine in D4Rs with variable composition in Ga and Al. Two other lines, at -145.6 ppm and -178.2 ppm, may correspond to impurities and to a fluorine atom in a pseudo-sodalite cage environment, respectively.
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PMID:Use of 19F nuclear magnetic resonance spectroscopy for probing substitution of Al for Ga in cloverite. 782 78

The penetration of a proton into the prenucleation building unit of a microporous gallophosphate and its interaction with an encapsulated fluorine anion have been investigated by means of DFT calculations. The inorganic part of the fluorinated gallophosphate ULM-18 has been modeled by a neutral, double four-ring (D4R) unit of formula [(GaOH)4(HPO4)4-H2O] encapsulating the fluorine ion. Assuming the cage to be rigid and to retain throughout the calculations the geometry determined from X-ray diffraction (XRD), the position of F(-) has been optimized, either as an isolated guest species or in the presence of an incoming proton. In agreement with the XRD structure, the fluorine atom has been shown to occupy in both cases a nonsymmetric position in the cage, being attached to three gallium atoms out of four. The distribution of the molecular electrostatic potential inside and outside the (F(-))@[(GaOH)4(HPO4)4-H2O] system has provided indications concerning the pathways that could be used by an incoming proton to penetrate the D4R unit and to approach the fluorine anion. The migration of a proton from an external site of fixation to the interior of the D4R unit has been found possible through two faces out of six. In both cases, the process has been found exothermic by approximately 0.17 eV and the energy barrier was estimated to approximately 0.8 eV. Inside the gallophosphate cage, the proton first adopts a position typical of a strong F...H...O bond made possible through an important shift of the fluorine anion away from the tripod of bonded gallium atoms. Then, the F(-)...H(+) system can easily evolve back and forth on a flat potential curve between one of the F...H...O bonded conformations and a situation characterized by the cleavage of the H...O link and the formation of a moderately activated F-H molecule, with the fluorine still attached to three gallium atoms.
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PMID:Trapping of an activated HF molecule inside a double four-ring unit: a quantum chemical model of the microporous fluorinated gallium phosphate ULM-18. 1127 7

Direct fluorination of dimethyl bicyclo[1.1.1]pentane-1,3-dicarboxylate, obtained from [1.1.1]propellane prepared by an improved synthetic procedure, furnished esters of 14 of the 15 possible bridge-fluorinated bicyclo[1.1.1]pentane-1,3-dicarboxylic acids, isolated by preparative GC. Calculated geometries reflect the substitution pattern in a regular fashion compatible with Bent's rules. Considerable additional strain is introduced into the bicyclo[1.1.1]pentane cage by polyfluorination; it is calculated to be as high as 33-35 kcal/mol for hexasubstitution. Three arrangements of the fluorine substituents are especially strain-rich: geminal, proximate, and W-related. The (1)H, (13)C, and (19)F NMR spectra exhibit a striking variety of chemical shifts and long-range coupling constants. These are in good agreement with results calculated with neglect of the bridgehead substituents for all of the chemical shifts by the GIAO-RHF/6-31G//RHF/6-31G and GIAO-RHF/6-31G//MP2/6-31G methods and for many of the coupling constants by the EOM-CCSD/6-311G//MP2/6-311G method. The proximate (4)J(FF) constants are particularly large (50-100 Hz) and show an inverse linear dependence on the calculated F-F distance in the range 2.43-2.58 A.
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PMID:Partially bridge-fluorinated dimethyl bicyclo[1.1.1]pentane-1,3-dicarboxylates: preparation and NMR spectra. 1147 20

The C-F...M(+) interaction was investigated by observation of the NMR spectroscopic changes and complexation studies between metal cations and the cage compounds 1 and 2 which have fluorobenzene units as donor atoms. As a result, the interaction was detected with all of the metal cations which form complexes with 1 and 2. The stability of the complexes of 1 and 2 was determined by the properties of the metal cations (ionic radii and degree of hydrolysis), not by the hard-soft nature of the cations. Crystallographic analyses of Tl(+) subset 1 and La(3+) subset 2 provided structural information (interatomic distances and bond angles), and the bond strengths, C-F...M(+), O...M(+), and N...M(+), were estimated by Brown's equation based on the structural data. Short C-F...Tl(+) (2.952-3.048 A) distances were observed in the complex Tl(+) subset 1. The C-F bond lengths in the complexes, Tl(+) subset 1 and La(3+) subset 2, are elongated compared to those of the metal-free compounds. Interestingly, no solvent molecules including water molecules were coordinated to La(3+) in the La(3+) subset 2. The stabilization energy of cation-dipole interaction was calculated on the basis of the data from X-ray crystallographic analysis, and it is roughly consistent with the (-)Delta H values estimated in solution. Thus, the C-F...M(+) interaction can be expressed by the cation-dipole interaction. This result explains the fact that compound 1 which has fluorine atom as hard donor strongly binds soft metals such as Ag(+) and Tl(+). Furthermore, it was concluded that the fluorobenzene unit has a poor electron-donating ability compared to that of ether oxygen or amine nitrogen, and thus the ratio of the coordination bond in C-F...M(+) is small. The specific and remarkable changes in the (1)H, (13)C, and (19)F NMR spectra were observed accompanied by the complexation between M(+) and the hosts 1 and 2. These spectral features are important tools for the investigation of the C-F...M(+) interaction. Furthermore, F.Tl(+) spin couplings were observed at room temperature in the Tl(+) subset 1, 2 (J(F-Tl) = 2914 Hz for Tl(+) subset 1 and 4558 Hz for Tl(+) subset 2), and these are clear and definitive evidence of the interaction.
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PMID:A study of C-F...M(+) interaction: metal complexes of fluorine-containing cage compounds. 1156 11

Two pathways have been considered in the fluorination of CB(5)H(6)(-) and CB(9)H(10)(-) by HF. In the ionic HF fluorination pathway, the monocarborane anion cage is first protonated in a BBB face followed by H(2) elimination and fluoride anion addition. In the covalent HF fluorination pathway, HF is first coordinated through hydrogen to the BBB face. Next, the fluorine can add to either an axial or equatorial boron atom which opens the cage to a nido structure with an endo fluoride substituent. Endo to exo rearrangement occurs with a small activation barrier followed by H(2) elimination. In both pathways, fluorination at the equatorial boron position is predicted to have smaller activation barriers even though substitution at the axial position leads to the more stable products.
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PMID:Proposed fluorination mechanism of CB(5)H(6)(-) and CB(9)H(10)(-) with HF. Evidence of kinetic control in the formation of 2-CB(5)H(5)F(-) and 6-CB(9)H(9)F(-). 1159 61

The gradient corrected Perdew-Burke-Ernzerhof density functional in conjunction with a 3-21G basis set and periodic boundary conditions was employed to investigate the geometries and energies of C(2)F fluorinated armchair single wall carbon nanotubes (F-SWNT's) with diameters ranging from 16.4 to 4.2 A [(12,12) to (3,3)] as well as a C(2)F graphene sheet fluorinated on one side only. Using an isodesmic equation, we find that the thermodynamic stability of F-SWNT's increases with decreasing tube diameter. On the other hand, the mean bond dissociation energies of the C-F bonds increase as the tubes become thinner. The C-F bonds in the (5,5) F-SWNT's are about as strong as those in graphite fluoride (CF)(n)() and are also covalent albeit slightly (<0.04 A) stretched. Whereas a fluorine atom is found not to bind covalently to the concave surface of [60]fullerene, endohedral covalent binding is possible inside a (5,5) SWNT despite a diameter similar to that of the C(60) cage.
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PMID:Thermochemistry of fluorinated single wall carbon nanotubes. 1174 43

Three hundred, day-old broiler chicks, with an average initial weight of 41.8 +/- 1.79 g, were used in a 15-day study (10 birds per battery cage) to characterize their performance and fluorine status when dicalcium phosphate (DCP) was replaced by Busumbu rock phosphate (BRP) as the source of phosphorus in the chicks' ration. The treatments comprised a standard ration with BRP replacing 0, 25%, 50%, 75% or 100% of DCP. Replacing DCP with BRP significantly reduced the final weight of the chicks (p < 0.01), feed intake (p < 0.01), weight gains (p < 0.01) and dry matter digestibility (p < 0.05) but increased (p < 0.05) the feed-to-gain ratio. True phosphorus absorption and the percentage of phosphorus in the tibia were not affected by increasing amounts of BRP in the diet. Increasing levels of BRP in the diet linearly reduced (p < 0.01) the percentage bone ash, calcium, Ca:P ratio, ultimate breaking force, bending moment, stress, and modulus of elasticity. Leg stiffness, lameness, reduced feed intake, and a decline in general health were recorded in 10-40% of the chicks on 75% and 100% BRP, respectively. These results suggest that excessive ingestion of fluorine from the BRP caused the reduction in the chicks' performance.
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PMID:The effects of replacing dicalcium phosphate with Busumbu rock phosphate on performance and the mechanical properties of bone in growing chicks. 1216 36

In a toluene/CDCl3 solution at room temperature, the C1 isomer of C60F36 rearranges into the C3 isomer over a period of four days, as a result of a unique 1,3-shift of fluorine; this rare example of addend migration across a fullerene cage surface is accelerated by air.
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PMID:Fluorine takes a hike: remarkable room-temperature rearrangement of the C1 isomer of C60F36 into the C3 isomer via a 1,3-fluorine shift. 1251 Mar 19

The first hexabenzylhexaazaisowurtzitane cage compounds with trifluoromethyl and azide groups, as well as those with fluorine atoms in the 3- and 4-positions, have been prepared and fully characterized. A study of the substituent influence on the benzene ring regarding the formation of the hexaazaisowurtzitane polycycle in either the 2- or 4-position with CF(3), F, and N(3) revealed an interesting difference. In all cases with CF(3), F, and N(3) substituents in the 4-position, the corresponding hexabenzylhexaazaisowurtzitanes were isolated. The corresponding hexabenzylhexaazaisowurtzitanes were also formed when these substituents were in the 2-position; however, in addition with azide in 2-position a novel type of polycycle was isolated and identified. (15)N NMR data and crystal structures of hexabenzylhexaazaisowurtzitane derivatives were obtained and are discussed in detail.
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PMID:Synthesis and structures of trifluoromethyl-, fluoro-, and azido-substituted hexabenzylhexaazaisowurtzitanes and isolation of a novel hexaazaisowurtzitane-based polycycle. 1256 61


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