Macrotricyclic quaternary tetraammonium receptors: halide anion recognition and interfacial activity at an aqueous interface. A molecular dynamics investigation

We report a molecular dynamics study of the halide inclusion complexes X(-) subset L(4+) of a macrotricyclic tetrahedral receptor L(4+) built from four quaternary ammonium sites connected by six (CH(2))(n) chains. The hydrophilic/hydrophobic character of the complexes is investigated at a water/chloroform interface, represented explicitly and, despite their +3 charge and "spherical" shape, they are found to display amphiphilic behavior and to concentrate at the interface. The more lipophilic N-substituted CH(2)phi derivative, as well as less charged models are more surface active than the N-Me substituted host. In relation with the Hofmeister series, I(-) exo neutralizing counterions are compared with Cl(-) anions and are found to sit closer to the interface, which becomes more neutral. The "macrocyclic interfacial effect" is investigated by a comparison of L(4+) complexes with their acyclic counterparts. Finally, we address the question of anion binding selectivity by L(4+) and its L(1) (4+) and L(2) (4+) topological isomers. F(-) is too small for these three hosts, while I(-) is too big. According to free energy perturbation calculations, Cl(-) is preferred to Br(-), but somewhat more by L(1) (4+) than by L(4+).     

LEP Higgs boson searches beyond the standard model and minimum supersymmetric standard model

Ever since the center-of-mass energy was increased in 1995 above the Zℴ resonance, the four LEP experiments (ALEPH, DELPHI, OPAL and L3) have renewed their effort to search for the Higgs boson. Data taking ended in the year 2000 with about 130 pb⁻¹ of data collected per experiment above 206 GeV ine ⁺ e ⁻¹ collisions but the data analysis is still very active. Most recently, the wealth of theoretical models and predictions has stimulated new analyses and model interpretations which go beyond the standard model and minimal supersymmetric standard model. These include the searches for charged Higgs bosons, models with two Higgs field doublets, searches for ‘fermiophobic’ Higgs decay, invisible Higgs boson decays, decay-mode independent searches, and limits on Yukawa and anomalous Higgs couplings. I review the searches done by the four LEP experiments and present the LEP combined results when they exist.     

Characterization of pure high-grade DCIS on magnetic resonance imaging using the evolving breast MR lexicon terminology: can it be differentiated from pure invasive disease?

Magnetic resonance imaging (MRI) is now a recognized method of imaging the breast. Unfortunately, there is lack of standardization in the MRI terminology used to characterize the appearance of breast lesions. Moreover, cases of mixed histologies are often imaged. We retrospectively identified cases of pure high-grade ductal carcinoma in situ (DCIS) using the recently introduced breast MRI lexicon and characterized the lesions in order to try and identify features that might distinguish high-grade DCIS from invasive disease. Five-year review of our institution's database revealed 637 patients underwent gadolinium-enhanced breast MRI examination. Twenty patients had histologically proven pure high-grade DCIS. After excluding patients with previous chemotherapy or inadequate MRI examination, 13 patients were analyzed and compared to the 13 most recent cases of pure invasive breast carcinoma. The morphological and dynamic features were then compared. High-grade DCIS cases were significantly more likely to show focal branching pattern (P=.03) and to have an irregular contour (P=.03), compared with invasive disease. Although of marginal statistical significance, DCIS lesions are more likely to have a lower morphological score than invasive carcinoma (P=.06), whilst the latter is more likely to show ring enhancement (P=.07). Use of breast MRI for staging at our institution shows that pure DCIS and pure invasive cancers are both rare entities. Despite the relatively limited numbers, we identified features that would help to differentiate high-grade DCIS from invasive carcinoma on MRI.     

A tandem metal carbene cyclization-cycloaddition approach to the pseudolaric acids

An approach toward the synthesis of the antifungal and cytotoxic pseudolaric acids based on the tandem metal carbene cyclization-cycloaddition reaction is described. Using this strategy, the advanced intermediate 3a bearing three of the four stereocenters of the target molecules has been synthesized. The substrate-controlled diastereoselectivity of the tandem carbene cyclization-cycloaddition was preferential for the undesired diastereomer, but reagent control through the use of Hashimoto's chiral rhodium catalyst Rh(2)(S-BPTV)(4) reversed the selectivity in favor of 3a. Ring opening of the oxabicyclic nucleus to give a hydroxycycloheptene has been demonstrated in a model study.     

Cationic,Methylene‐Bridged,Intramolecular Donor‐Acceptor Systems Based on Zirconium and Hafnium and Phosphino‐methanides

A new access to cationic zirconium and hafnium compounds [L₂MCH₂PR₂][MeB(C₆F₅)₃] (L = Cp, Ind; R = iso‐Pr, tert‐Bu; M = Zr, Hf) exhibiting an intramolecular donor‐acceptor system was established by treating the precursors L₂M(Me)CH₂PR₂ with B(C₆F₅)₃ (BCF). Precursors 1 – 6 [L₂M(Me)CH₂PR₂ with L = Cp, Ind; R = iso‐Pr, tert‐Bu; M = Zr, Hf] were fully characterized. The crystal structures of these compounds revealed large M–CH₂–P bond angles with values of about 134° indicating the absence of interactions between the Lewis‐acid and Lewis‐base. The cationic compounds [L₂MCH₂PR₂][MeB(C₆F₅)₃] ( 7 – 12 ) were obtained by treatment of 1 – 6 with BCF. They were characterized by NMR spectroscopy, mass spectrometry, and elemental analyses; in H/D‐scrambling experiments with H₂/D₂ mixtures 7 – 12 disclosed their reactivity towards cleavage of hydrogen.     

Challenges associated with the synthesis of unusual o-carboxamido stilbenes by the Heck protocol: Intriguing substituent effects, their toxicological and chemopreventive implications

The syntheses of fourteen unusual o-carboxamido stilbenes by the Heck protocol revealed surprising complexity related to intriguing substituent effects with mechanistic implications. The unexpected cytotoxic and chemopreventive properties also seem to be substituent dependent. For example, although stilbene 15d (with a 4-methoxy substituent) showed cytotoxicity on HT29 colon cancer cells with an IC(50) of 4.9 μM, the 3,4-dimethoxy derivative (15c) is inactive. It is interesting to observe that the 3,5-dimethoxy derivative (15e) showed remarkable chemopreventive activity in WRL-68 fetal hepatocytes, surpassing the gold standard, resveratrol. The resveratrol concentration needed to be 5 times higher than that of 15e to produce comparable elevation of NQO1.     

Synthetic UDP-furanoses as potent inhibitors of mycobacterial galactan biogenesis

UDP-galactofuranose (UDP-Galf) is a substrate for two types of enzymes, UDP-galactopyranose mutase and galactofuranosyltransferases, which are present in many pathogenic organisms but absent from mammals. In particular, these enzymes are involved in the biosynthesis of cell wall galactan, a polymer essential for the survival of the causative agent of tuberculosis, Mycobacterium tuberculosis. We describe here the synthesis of derivatives of UDP-Galf modified at C-5 and C-6 using a chemoenzymatic route. In cell-free assays, these compounds prevented the formation of mycobacterial galactan, via the production of short "dead-end" intermediates resulting from their incorporation into the growing oligosaccharide chain. Modified UDP-furanoses thus constitute novel probes for the study of the two classes of enzymes involved in mycobacterial galactan assembly, and studies with these compounds may ultimately facilitate the future development of new therapeutic agents against tuberculosis.     

Synthesis of a new hydrophilic poly(ethylene glycol)-ionic liquid and its application in peptide synthesis

The synthesis of a new hydrophilic ammonium-based poly(ethylene glycol)-ionic liquid (PEG-IL) is reported; the structure was assigned by NMR ((1)H, (13)C) and MALDI mass spectrometry. The viscosity and thermal stability were also studied, as well as its polarity. Its application as an alternative solvent in the synthesis of dipeptides under microwave irradiation is also described.     

Chemoselective Catalysis with Organosoluble Lewis Acidic Polyoxotungstates

The preparation of new organosoluble Lewis acidic polyoxometalates (POMs) is reported. These complexes were prepared by the incorporation of Zr, Sc, and Y atoms into the corresponding monolacunary Dawson [P₂W₁₇O₆₁]^10? and Keggin [PW₁₁O₃₉]^7? polyoxotungstates. The catalytic activity of these compounds was evaluated for C? C bond formation in the Diels–Alder, Mannich, and Mukaiyama‐type reactions. Comparisons with previously described Lewis acidic POMs are reported. Competitive reactions between imines and aldehydes or between various imines demonstrated that fine tuning of the reactivity could be reached by varying the metal atom incorporated into the polyanionic framework. A series of experiments that employed pyridine derivatives allowed us to distinguish between the Lewis and induced Brønsted acidity of the POMs. These catalysts activate imines in a Lewis acidic way, whereas aldehydes are activated by indirect Brønsted catalysis.     

Ultrafast and bias-free all-optical wavelength conversion using III-V-on-silicon technology

Using a 7.5 μm diameter disk fabricated with III-V-on-silicon fabrication technology, we demonstrate bias-free all-optical wavelength conversion for non-return-to-zero on-off keyed pseudorandom bit sequence (PRBS) data at the speed of 10 Gbits/s with an extinction ratio of more than 12 dB. The working principle of such a wavelength converter is based on free-carrier-induced refractive index modulation in a pump-probe configuration. We believe it to be the first bias-free on-chip demonstration of all-optical wavelength conversion using PRBS data. All-optical gating measurements in the pump-probe configuration with the same device have revealed that it is possible to achieve wavelength conversion beyond 20 Gbits/s.