Preparation and chemistry of phosphoranyl-derived iodanes

The preparation and chemistry of novel phosphoranyl-derived lambda(3)-iodanes is reported. The phosphoranyl-derived phenyliodonium sulfonates were prepared in good yields by the reaction of stabilized phosphonium ylides [1-triphenylphosphoranylidene-2-propanone, methyl(triphenylphosphoranylidene)acetate, (triphenylphosphoranylidene)acetaldehyde, and (triphenylphosphoranylidene)acetonitrile] with the pyridinium complex of iodobenzene ditriflate or with [hydroxy(tosyloxy)iodo]benzene under mild conditions. These compounds represent a potentially useful class of reagents that combine in one molecule synthetic advantages of a phosphonium ylide and an iodonium salt. Specifically, phosphorane-derived phenyliodonium tosylates can react with soft nucleophiles, such as iodide, bromide, benzenesulfinate, and thiophenolate anions, with a selective formation of the respective alpha-functionalized phosphonium ylides, which can be further converted to alkenes by the Wittig reaction with benzaldehyde. The phosphoranyl-derived benziodoxoles can be prepared by the reaction of 1-acetoxybenziodoxole with stabilized phosphonium ylides. An unusual ligand exchange on the iodine(III) center resulting in the substitution of a carbon ligand with an oxygen ligand was observed in the reaction of these compounds with strong acids.     

Synthesis and Conformational Analysis of 1′‐ and 3′‐Substituted 2‐Deoxy‐2‐fluoro‐D‐ribofuranosyl Nucleosides

Convergent syntheses of the 9‐(3‐X‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranosyl)adenines 5 (X=N₃) and 7 (X=NH₂), as well as of their respective α‐anomers 6 and 8 , are described, using methyl 2‐azido‐5‐O‐benzoyl‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranoside ( 4 ) as glycosylating agent. Methyl 5‐O‐benzoyl‐2,3‐dideoxy‐2,3‐difluoro‐β‐D ‐ribofuranoside ( 12 ) was prepared starting from two precursors, and coupled with silylated N⁶‐benzoyladenine to afford, after deprotection, 2′,3′‐dideoxy‐2′,3′‐difluoroadenosine ( 13 ). Condensation of 1‐O‐acetyl‐3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐β‐D ‐ribofuranose ( 14 ) with silylated N²‐palmitoylguanine gave, after chromatographic separation and deacylation, the N⁷‐β‐anomer 17 as the main product, along with 2′‐deoxy‐2′‐fluoroguanosine ( 15 ) and its N⁹‐α‐anomer 16 in a ratio of ca. 42 : 24 : 10. An in‐depth conformational analysis of a number of 2,3‐dideoxy‐2‐fluoro‐3‐X‐D ‐ribofuranosides (X=F, N₃, NH₂, H) as well as of purine and pyrimidine 2‐deoxy‐2‐fluoro‐D ‐ribofuranosyl nucleosides was performed using the PSEUROT (version 6.3) software in combination with NMR studies.     

On the electronic states of macrocycles of the extended porphyrin family and their coordination compounds

The electronic absorption spectra of Ni, Zn and Mg hemiporphyrazine derivatives are presented and discussed together with theoretical results obtained by INDO/S computations. The absorption spectra of all the metal derivatives show marked red shifts of the lowest energy absorption bands with respect to those of the metal free hemiporphyrazine. The possible explanation that in metal derivatives low lying excited states with a fully conjugated π electron system are present is supported by theoretical computations.     

Modified synthesis of Ru–Rh heterobimetallic metallacarboranes based on ruthenium exo-nido complexes and not accompanied by exo-nido → closo rearrangement

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S-Adenosyl methionine/S-adenosyl-L-homocysteine ratio determination by capillary electrophoresis employed as a monitoring tool for the antiviral effectiveness of adenosine analogs

S-Adenosyl-L-homocysteine hydrolase (SAHh) inhibitors have long been used as broad-range antivirals and have been recently evaluated as an experimental therapy of filovirus infections. In response to the need for a rapid laboratory testing method that could assess antiviral potency in vivo, our group developed a capillary electrophoresis (CE) method for the determination of the S-adenosyl-L-homocysteine (SAH) to S-adenosyl-L-methionine (SAM) ratio. After chloroacetaldehyde derivatization, SAH and SAM were detected using laser-induced fluorescence detection with a HeCd laser. Separation and quantitation of both SAH and SAM in human plasma were achieved in less than 1 min. The proposed method is rapid and reliable, and could be easily applied to routine monitoring of clinical and preclinical trials subjects.     

Simplified procedures for the analysis of polycyclic aromatic hydrocarbons in water, sediments and mussels

We describe in this paper simple and robust analytical protocols to determine the 16 polycyclic aromatic hydrocarbons (PAHs) of the US Environmental Protection Agency priority list in water, sediment and mussels. For water samples, eight different solid-phase extraction (SPE) sorbents have been compared and among them, C18 provided highest recoveries and limits of detection of 0.3-15 ng/L. For lyophilized sediments, Soxhlet and ultrasonic extraction were compared, and the last one permitted to recover all analytes with highest repetitivity and was validated by analysing a certified reference material. Finally, the analysis of mussels was undertaken using Soxhlet, ultrasonic and pressurized liquid extraction (PLE) and the performance of several clean-up steps are compared. Whereas for the former two, incomplete recovery or losses of some analytes were evidenced, PLE permitted a more efficient extraction and although alkaline digestion was necessary to remove coextracted compounds, the method gave acceptable recoveries and limits of detection of 0.5-7.7 microg/kg dry mass, as for sediments. In all cases, analysis was performed by gas chromatography coupled to mass spectrometry and internal standard quantification was performed using five deuterated PAHs. Each method performance is discussed for the three matrices analysed and the paper reports advantages and disadvantages of each for their routine application in monitoring programs.     

The first 4,1,10-MC2B10 supraicosahedral metallacarboranes and a route to previously inaccessible 4,1,12-ruthenium arene species

Reduction of 1,12-closo-C2B10H12 or its C,C-dimethyl analogue with sodium in liquid ammonia followed by metallation with {CpCo}2+, {(arene)Ru}2+ or {(dppe)Ni}2+ fragments affords the first examples of 4,1,10-MC2B10 species; thermolysis of these yields the appropriate 4,1,12-MC2B10 isomers, unavailable for (arene)Ru metallacarboranes by similar thermolysis of known 4,1,6-MC2B10 compounds.     

Synthesis and structural characterization of two novel heterometallic clusters: [Rh4Pt2(CO)11(dppm)2] and [Ru2Rh2Pt2(CO)12(dppm)2

Two novel heterometallic octahedral clusters [Rh(4)Pt(2)(CO)(11)(dppm)(2)](1) and [Ru(2)Rh(2)Pt(2)(CO)(12)(dppm)(2)](2) were synthesized by the reaction of [Rh(2)Pt(2)(CO)(6)(dppm)(2)] with [Rh(6)(CO)(14)(NCMe)(2)] and Ru(3)(CO)(12), respectively. Solid state structures of 1 and 2 have been established by a single crystal X-ray diffraction study. Two dppm ligands in 1 are bonded to one platinum and three rhodium atoms, which form an equatorial plane of the Rh(4)Pt(2) octahedron. Two rhodium and two platinum atoms bound to the diphosphine ligands in 2 are nonplanar to give an octahedral C2 symmetric Ru(2)Rh(2)Pt(2)(dppm)2 framework. The (31)P NMR investigation of and (1D, (31)P COSY, (31)P-[(103)Rh] HMQC) and simulation of 1D spectral patterns showed that in both clusters the structures of the M(6)(PP)(2) fragments found in the solid state are maintained in solution.     

Fluoropolyethers end‐capped by polar functional groups. IV. A novel approach to the evaluation of reactivities of hydroxy‐terminated ethoxylated fluoropolyethers in the tin(IV)‐catalyzed reactions with isophorone diisocyanate

The effect of catalyst dibutyltin dilaurate (DBTDL) on the kinetics of urethane formation reactions of α,ω‐bis(hydroxy)‐terminated fluoropolyethers Fomblin® Z‐DOL TXs (FPEs) of various molecular weights and poly(oxyethylene) glycol PEG‐400 with isophorone diisocyanate (IPDI) in hexafluoroxylene (HFX) and tetrahydrofuran (THF) at 40 °C and NCO:OH = 2:1 have been studied in a broad range of catalyst (0.10–9.00) ×10^?4 M and total reagents (10.0–60.1 wt %) concentrations. The rate of tin‐catalyzed second‐order reactions (with respect to diol and diisocyanate) was found to be proportional to the square root of catalyst concentration [DBTDL]^0.5 both in low polar (HFX) and polar (THF) solvents. Effect of catalyst saturation was revealed for all the reaction systems at higher DBTDL concentrations as well as the appearance of the limiting catalyst concentrations C_lim below which the rates of reaction were close to zero. Based on these findings new effective rate coefficients have been derived k = k_cat/(C ? C) that are independent of the total reagent concentration in the range of 10.0–60.1 wt % ([OH] = 0.10–0.91 equiv/L). This new approach highlights that the rate of the tin‐catalyzed urethane formation reactions of α,ω‐bis(hydroxy)‐terminated fluoropolyethers Z‐DOL TXs with IPDI in HFX at 40 °C and NCO:OH = 2:1 increases significantly with increasing MW of FPE from 776 up to 3405. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5354–5371, 2004     

Mechanism of action of 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one, a very active angular furocoumarin-like sensitizer

The molecular structure of 1,4,6,8-tetramethylfuro[2,3-h]quinolin-2(1H)-one (FQ), a recent furocoumarin-like photosensitizer, has been modified with the aim of reducing its strong genotoxicity, by replacing the methyl group at 4 position with a hydroxymethyl one, and so obtaining 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ). This modification gave rise to a strong reduction of lipophilicity and dark interaction with DNA. The formation of monoadducts (MA) was deeply affected, whereas the induction of bifunctional adducts between DNA and proteins (DPC(L>0)) was replaced by an efficient production of DNA-protein cross-links at zero length (DPC(L=0)), probably via guanine damage. Because of its angular molecular structure, HOFQ does not form interstrand cross-links (ISC): therefore, DPC(L=0) and MA represent the main lesions induced by HOFQ in DNA. In comparison with FQ (which induces MA and DPC(L>0)) and 8-methoxypsoralen (8-MOP) (MA, ISC, DPC(L>0)), HOFQ seems to be a more selective agent. In fact, contrary to FQ and 8-MOP, HOFQ, together with a noticeable antiproliferative activity, shows low levels of point mutations in bacteria and of clastogenic effects in mammalian cells. HOFQ is also an efficient apoptosis inducer, especially in comparison with 8-MOP, when tested at equitoxic experimental conditions; this property might be correlated with the complete HOFQ inability of inducing skin erythemas, a well-known side effect of classic furocoumarin photosensitization.