Synthesis of novel, simplified, C-7 substituted eleutheside analogues with potent microtubule-stabilizing activity

The synthesis of a number of novel, simplified, C-7 substituted eleutheside analogues with potent tubulin-assembling and microtubule-stabilizing properties is described, using ring closing metathesis as the key-step for obtaining the 6-10 fused bicyclic ring system. The RCM precursors were synthesized starting from aldehyde 3 [prepared in six steps on a multigram scale from R-(−)-carvone in 30% overall yield] via multiple stereoselective Hafner-Duthaler allyltitanations and/or Brown allylborations. ‘Second generation’ RCM-catalyst 15 gave the desired ring closed ten-membered carbocycles as single Z stereoisomers in good yields. The RCM stereochemical course (100% Z) is likely to reflect thermodynamic control. Molecular mechanics and semi-empirical calculations also show that the Z stereoisomers of these ten-membered carbocycles are consistently more stable than the E. The crucial role of the homoallylic and allylic substituents and of their protecting groups for the efficiency of the RCM reactions is discussed. In particular, we have found that p-methoxyphenyl (PMP) protected allylic alcohols, the products of a stereoselective oxyallylation, are compatible with the RCM reaction and give better yields than the corresponding free allylic alcohols. One of the simplified analogues of the natural product (44, lacking inter alia the C-4/C-7 ether bridge) retains potent microtubule-stabilizing activity. However, the cytotoxicity tests did not parallel the potent tubulin-assembling and microtubule-stabilizing properties: limited cytotoxicity was observed against three common tumor cell lines (human ovarian carcinoma, human colon carcinoma and human leukemia cell lines, IC₅₀ in the μM range), approximately two orders of magnitude less than paclitaxel (IC₅₀ in the nM range). The mechanism of cell cycle arrest induced by compound 44 is similar to that obtained with paclitaxel.     

Amperometric Glucose Determination by Means of Glucose Oxidase Immobilized on a Cellulose Acetate Film: Dependence on the Immobilization Procedures

Glucose microelectrodes were prepared by immobilizing glucose oxidase onto a cellulose acetate film coating a platinum wire. Hexamethylenediamine (HMDA) and Glutaraldehyde (GA) were employed as spacer and coupling agent, respectively. Sensitivities and linear response ranges were studied as a function of the relative amounts of HMDA and GA. The best sensitivity was found when HMDA and GA were 5% and 2.5% in aqueous solutions, respectively. Taking as a reference the functioning of this biosensor, the roles of HMDA and GA percentages appear to be opposed when the extension of the linear response range is considered. Indeed, an increase of one unit in HMDA percentage (from 5 to 6 %) induces an increase in the extension of the linear response range equal to that obtained with a decrease of one unit of GA percentage (from 2.5 to 1.5%).     

On the effect of catalyst status in the quantitative determination of platinum in Pt-Sn/MgO materials

The development of an analytical method for the determination of platinum in MgO based Pt/Sn catalysts is described. Electrothermal atomic absorption spectroscopy (ETAAS) was chosen because of its high sensitivity and robustness against spectral interferences. All the sources of chemical interferences were statistically analyzed and corrections were adopted for the presence of magnesium oxide support. The effectiveness of different mineralization procedures was critically evaluated as a function of the chemical of the solid catalyst. Microwave digestion allowed recovery of metal of 100% for all the catalysts analyzed and exhibited significant better precision values than other digestion methods, which could nevertheless be utilized under proper conditions in selected cases. Received: 31 July 2000 / Revised: 17 October 2000 / Accepted: 24 October 2000     

Polynomials whose coefficients coincide with their zeros

In this paper we consider monic polynomials such that their coefficients coincide with their zeros. These polynomials were first introduced by S. Ulam. We combine methods of algebraic geometry and dynamical systems to prove several results. We obtain estimates on the number of Ulam polynomials of degree N. We provide additional methods to obtain algebraic identities satisfied by the zeros of Ulam polynomials, beyond the straightforward comparison of their zeros and coefficients. To address the question about the existence of orthogonal Ulam polynomial sequences, we show that the only Ulam polynomial eigenfunctions of hypergeometric type differential operators are the trivial Ulam polynomials \(\{x^N\}_{N=0}^\infty \). We propose a family of solvable N-body problems such that their stable equilibria are the zeros of certain Ulam polynomials.     

Quaternionic hyperfunctions on five-dimensional varieties in ℍ2

In this article we introduce a new notion of differential forms to describe the cohomology associated to the sheaf of regular functions in several quaternionic variables. We then use these differential forms to introduce and describe concretely a sheaf of quaternionic hyperfunctions as boundary values of regular functions in two quaternionic variables. We show how these ideas can be generalized to the case of monogenic functions in two vector variables with values in a Clifford algebra.     

Standard Model without elementary scalars and high energy Lorentz violation

If Lorentz symmetry is violated at high energies, interactions that are usually non-renormalizable can become renormalizable by weighted power counting. Recently, a CPT invariant, Lorentz violating extension of the Standard Model containing two scalar-two fermion interactions (which can explain neutrino masses) and four fermion interactions (which can explain proton decay) was proposed. In this paper we consider a variant of this model, obtained suppressing the elementary scalar fields, and argue that it can reproduce the known low-energy physics. In the Nambu–Jona-Lasinio spirit, we show, using a large N _c expansion, that a dynamical symmetry breaking takes place. The effective potential has a Lorentz invariant minimum and the Lorentz violation does not reverberate down to low energies. The mechanism generates fermion masses, gauge-boson masses and scalar bound states, to be identified with composite Higgs bosons. Our approach is not plagued by the ambiguities of approaches based on non-renormalizable vertices. The low-energy effective action is uniquely determined and predicts relations among parameters of the Standard Model.     

Direct l-doublet transitions in the 0110 state of cyanogen chloride and cyanogen bromide

Direct l doublet transitions have been observed for the 01¹0 state of the ³⁵Cl¹²C¹⁴N and ³⁷Cl¹²C¹⁴N isotopic species of cyanogen chloride and the ⁷⁹Br¹²C¹⁴N and ⁸¹Br¹²C¹⁴N isotopic species of cyanogen bromide in the frequency range 4–22 GHz. The l-doubling constants (q⁰, q¹, q²) and the asymmetry parameters (ηeQq_z) of the halogen nuclear quadrupole coupling tensors have been derived. The constants q¹ have been calculated form the vibrational force fields of Whiffen for the four cyanogen halides using the formulation of Watson. Agreement with the observed values is found to be 10% or better and for cyanogen fluoride and cyanogen chloride the isotopic shifts in q¹ are also well predicted.