Structure elucidation of a novel analog of sildenafil detected as an adulterant in a dietary supplement using LC-UV and LC/MS

A sildenafil-related compound was detected in a dietary supplement marketed as an aphrodisiac. The compound was detected during analysis of the dietary supplement using LC-UV and LC/electrospray ionization-MS. The structure of the compound was established using high resolution MS, NMR spectrometry, and X-ray crystal structure analysis. The compound was identified as 5-(5-((3,5-dimethylpiperazin-1-yl)sulfonyl)-2-ethoxyphenyl)-l-methyl-7-((1-methyl-4-nitro-1H-imidazol-5-yl)thio)-3-propyl-1H-pyrazolo[4,3-d] pyrimidine. Based on this structure, the compound was named nitroprodenafil. The dietary supplement was found to contain 90 mg nitroprodenafil/capsule. This article describes the structural characterization of a new sildenafil-related compound. The compound was detected during analysis of a dietary supplement using LC-UV and LC/electrospray ionization (ESI)-MS. The structure was established using high resolution MS (HRMS), NMR spectrometry, and X-ray crystal structure analysis. The structures of methisosildenafil, thiomethisosildenafil, and this new analog, named nitroprodenafil (21), are shown in Figure 1. In the Demizu et al. report, the compound is named mutaprodenafil instead ofnitroprodenafil. Considering the naming right, the authors of this paper think the use of mutaprodenafil is appropriate as the compound name, although nitroprodenafil is used.     

Hydrogen bonding of water in 3-methylpyridine studied by O 1s X-ray emission and absorption spectroscopy

O 1s X-ray emission and X-ray absorption spectroscopy is applied to probe hydrogen bonding of water (D(2)O) in 3-methylpyridine. Owing to element selectivity of X-ray spectroscopies the electronic structure of water in the binary mixture was observed selectively. Based on the observed spectral changes associated with hydrogen bonding in O 1s X-ray emission and X-ray absorption spectra, we have investigated the hydrogen bond of the mixture sample over a wide range of D(2)O concentrations (X(D(2)O) = 0.02-1.0) at room temperature under atmospheric pressure.     

Facile interstrand migration of the hydrocarbon moiety of a dibenzo[a,l]pyrene 11,12-diol 13,14-epoxide adduct at N2 of deoxyguanosine in a duplex oligonucleotide

When a synthesized deoxyribonucleotide duplex, 5'-CCATCGCTACC-3'.5'-GGTAGCGATGG-3', containing a trans 14R dibenzo[a,l]pyrene (DB[a,l]P) adduct, corresponding to trans opening of the (+)-(11S,12R)-diol (13R,14S)-epoxide by N (2) of the central G residue, was allowed to stand for 2-6 days at ambient temperature in neutral aqueous solution, three new products were observed on denaturing HPLC. One of these corresponded to loss of the DB[a,l]P moiety from the original adducted strand to give an 11-mer with an unmodified central dG. The other two products resulted from a highly unexpected migration of the hydrocarbon moiety to either dG5 or dG7 of the complementary strand, 5'-GGTAG5CG7ATGG-3'. Enzymatic hydrolysis of the two 11-mer migration products followed by CD spectroscopy of the isolated adducted nucleosides indicated that, in both cases, the hydrocarbon moiety had undergone configurational inversion at C14 to give the cis 14S DB[a,l]P dG adduct. MS/MS and partial enzymatic hydrolysis showed that the major 11-mer had the hydrocarbon at dG7. Two 11-mer oligonucleotides were synthesized with a single cis 14S DB[a,l]P dG adduct either at G7 or at G5 and were found to be chromatographically identical to the major and minor migration products, respectively. Although HPLC evidence suggested that a small extent of hydrocarbon migration from the trans 14S DB[a,l]P dG diastereomer also occurred, the very small amount of presumed migration products from this isomer precluded their detailed characterization. This interstrand migration appears unique to DB[a,l]P adducts and has not been observed for their fjord-region benzo[c]phenanthrene or bay-region benzo[a]pyrene analogues.     

Retracted and replaced: a flow‐condition‐based interpolation finite element procedure for triangular grids

The following article from the International Journal for Numerical Methods in Fluids ‘A flow‐condition‐based interpolation finite element procedure for triangular grids’ by Haruhiko Kohno and Klaus‐Jürgen Bathe published online on 3 August 2005 in Wiley InterScience ( www.interscience.wiley.com ) and in print on 10 October 2005 in the International Journal for Numerical Methods in Fluids Volume 49 Issue 8 pp. 849–875 has been retracted and replaced by agreement between the authors, the journal editors and John Wiley & Sons, Ltd. The article has been retracted due to printing errors which have been corrected in the replacement article.(DOI: 10.1002/fld.1246 )     

Theory of core-level spectroscopy of rare-earth oxides

A review is presented of the recent development in theoretical studies of X-ray photoemission spectra (XPS) and X-ray absorption spectra (XAS) for rare-earth sesquioxides (R₂O₃) and rare-earth dioxides (RO₂). From the analysis of 3d XPS for R₂O₃ (R = La, Ce,..., Yb) and RO₂ (R = Ce, Pr, Tb) with the impurity Anderson model (without the multiplet coupling effect), we estimate the strength of the covalency hybridization between rare-earth 4f and oxygen 2p states, the charge transfer energy and other physical quantities, and discuss their systematic variation with the change in rare-earth elements. Two possible mechanisms for the splitting of the 3d XPS are pointed out for R₂O₃. One is the initial-state hybridization for R = La, Ce, Pr and Nd; the other is the final-state hybridization for R = Eu and Yb. For RO₂ (R = Ce, Pr, Tb), both of the initial- and final-state hybridizations are essential in explaining the 3d XPS spectra. Then, we study the effect of the intraatomic multiplet coupling on 3d and 4d XPS for La₂O₃, Ce₂O₃, Pr₂O₃, Nd₂O₃, Yb₂O₃ and CeO₂. The multiplet coupling effect is not very important for the 3d XPS, causing only an additional spectral broadening and some minor spectral structures. In the analysis of 4d XPS, however, the interplay between the multiplet coupling and the hybridization plays an essential role. Finally, we study the multiplet structure in 3d and 4d XAS for CeO₂ and PrO₂. It is shown that the original atomic multiplet structure in these XAS is strongly modified by the interatomic hybridization effect, and the experimental multiplet structure is explained consistently with the analysis of 3d and 4d XPS, by the mixed-valence ground state with strong covalency hybridization.     

Performance of the Cr[CH(SiMe3)2]3/SiO2 catalyst for ethylene polymerization compared with the performance of the Phillips catalyst

The catalysis of a silica‐supported chromium system {Cr[CH(SiMe₃)₂]₃/SiO₂} was compared with a silica‐supported chromium oxide catalyst, the Phillips catalyst (CrO₃/SiO₂). This catalyst was prepared by the calcining of the typical silica support used for the Phillips catalyst at 600 °C and by the support of tris[bis(trimethylsilyl)methyl]chromium(III) {Cr[CH(SiMe₃)₂]₃} on the silica. In the slurry‐phase polymerization, this catalyst conducted the polymerization of ethylene at a high activity without organoaluminum compounds as cocatalysts or scavengers. The activity per Cr was about 6–7 times higher than that of the Phillips catalyst. Upon the introduction of hydrogen to the system, the molecular weight of polyethylene did not change with the Phillips catalyst, but it decreased with the Cr[CH(SiMe₃)₂]₃/SiO₂ catalyst. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 413–419, 2003     

Copper(I) tert-butoxide-promoted stereospecific alkylation of β-hydroxymethylvinylsilanes with alkyl halides

Stereospecific alkylation of (Z)-β-hydroxymethylvinylsilanes proceeded by treatment with copper(I) tert-butoxide and alkyl halides. Tri- and tetra-substituted allylic alcohols were obtained with complete retention of configuration.     

Synthesis and hybridization properties of 2'-O-methylated oligoribonucleotides incorporating 2'-O-naphthyluridines

2'-O-(1-Naphthyl)uridine and 2'-O-(2-naphthyl)uridine were synthesized by a microwave-mediated reaction of 2,2'-anhydrouridine with naphthols. Using the 3'-phosphoramidite building blocks, these 2'-O-aryluridine derivatives were incorporated into 2'-O-methylated oligoribonucleotides. Incorporation of five 2'-O-(2-naphthyl)uridines into a 2'-O-methylated RNA sense strand significantly increased the thermostability of the duplex with a 2'-O-methylated RNA antisense strand. Circular dichroism spectroscopy and molecular dynamic simulation of the duplexes formed between the modified RNAs and 2'-O-methyl RNAs suggested that there are π-π interactions between two neighboring naphthyl groups in a sequence of the five consecutively modified nucleosides.     

Theoretical and experimental evidence for a new post-cotunnite phase of titanium dioxide with significant optical absorption

We report the discovery of a post-cotunnite phase of TiO2 by both density-functional ab initio calculations and high-pressure experiments. A pressure-induced phase transition to a hexagonal Fe2P-type structure (space group P62m) was predicted to occur at 161 GPa and 0 K and successfully observed by in situ synchrotron x-ray diffraction measurements at 210 GPa and 4000 K with a significant increase in opacity. This change in opacity is attributed to a reduction of band gap from 3.0 to 1.9 eV across the phase change. The Fe2P-type structure is proved to be the densest phase in major metal dioxides.