Synthesis of indolizidines from dialkylated isocyanides: a novel radical cyclisation/N-alkylation/ring closing metathesis approach

Two dialkylated isocyanides were first synthesised from simple starting materials and then used as building blocks for the synthesis of indolizidines via a novel radical cyclisation/N-alkylation/ring closing metathesis strategy. Several functionalised indolizidines were accessed in good to excellent yields.     

Formation of heavy and superheavy elements by reactions with massive nuclei

The effects of the entrance channel and shell structure on the experimental evaporation residues have been studied by analyzing the ³²S + ¹⁸²W, ⁴⁸Ti + ¹⁶⁶Er and ⁶⁰Ni + ¹⁵⁴Sm reactions leading to ²¹⁴Th^*; the ⁴⁰Ar + ¹⁸¹Ta reaction leading to ²²¹Pa^*; the ⁴⁸Ca + ²⁴³Am, ²⁴⁸Cm, ²⁴⁹Cf reactions leading to the ²⁹¹115, ²⁹⁶116 and ²⁹⁷118 superheavy compound nuclei, respectively. The fusion mechanism and the formation of evaporation residues of heavy and superheavy nuclei have been studied. In calculations of the excitation functions for capture, fusion and evaporation residues we used such characteristics as mass asymmetry of nuclei in the entrance channel, binding energies and shape of colliding nuclei, potential energy surface, driving potential, partial-fusion cross-sections and survival probability of the compound nucleus, ratio at each step along the de-excitation cascade of the compound nucleus. The calculations have allowed us to make useful conclusions about the mechanism of the fusion-fission process, which is in competition with the quasifission process, and the production of the evaporation residues.Received: 22 April 2003, Revised: 26 June 2003, Published online: 18 December 2003PACS: 25.70.Gh Compound nucleus - 25.70.-z Low and intermediate energy heavy-ion reactions - 27.80. + w - 27.90. + b      

Seminormality and upper semicontinuity in optimal control

This paper concerns the concept of upper semicontinuity of variable sets, precisely the variant of Kuratowski's definition of upper semicontinuity that Cesari has denoted as property (Q). This concept has been used by Cesari in most of his papers on existence theorems for optimal solutions, and later used by Olech, Lasota and Olech, Brunovsky, Baum, Suryanarayana, and Angell. First, criteria are given for property (Q) in addition to those which had been already given previously. Then, it is shown that a slight restriction in the concept can be expressed in a form which is similar to Tonelli's concept of seminormality for free problems of the calculus of variations. Thus, the property (Q) appears to be a generalization to Lagrange problems of control of the well-known concept of seminormality for free problems.This research was partially supported by AFOSR Research Project No. 69-1662.     

Analysis of dihydropyridine calcium channel blockers using negative ion photoionization mass spectrometry

The fragmentation of dihydropyridine calcium-channel antagonists are compared by electrospray ionization (ESI) and atmospheric pressure photonization (APPI). The results demonstrate that in ESI the preferred ionization process is in positive mode, with the mass spectra of [M+H]+ showing base peak ions probably formed by loss of alcohols from carboxyl groups. Conversely, in APPI, a high intense peak is observed in negative mode due to deprotonated molecule [M-H]- after two serial 1, 2-hydride shifts leading to a rearranged deprotonated molecule [M-H]-. These ions undergo another 1,2-hydride shifts to produce a nitro-phenyl product ion of m/z 122. The APPI is also used to develop a method for the quantitation of dihydropyridines (e.g., nifedipine) in human plasma.     

Modal analysis and intensity of acoustic radiation of the kettledrum

The acoustical features of kettledrums have been analyzed by means of modal analysis and acoustic radiation (p/v ratio) measurements. Modal analysis of two different kettledrums was undertaken, exciting the system both by a hammer and a shaker. Up to 15 vibrational modes were clearly identified. Acoustic radiation was studied using two ways. Based on previous experiments of other researchers, a new parameter, called intensity of acoustic radiation (IAR), has been defined and measured. Results show a strict relationship between IAR and the frequency response function (FRF, which is the v/F ratio), and IAR also strongly relates the modal pattern to acoustic radiation. Finally, IAR is proposed for vibro-acoustical characterization of kettledrums and other musical instruments such as strings, pianos, and harpsichords.     

Site-specific interactions of Cu(II) with alpha and beta-synuclein: bridging the molecular gap between metal binding and aggregation

The aggregation of alpha-synuclein (AS) is a critical step in the etiology of Parkinson's disease (PD) and other neurodegenerative synucleinopathies. Protein-metal interactions play a critical role in AS aggregation and might represent the link between the pathological processes of protein aggregation and oxidative damage. Our previous studies established a hierarchy in AS-metal ion interactions, where Cu(II) binds specifically to the protein and triggers its aggregation under conditions that might be relevant for the development of PD. In this work, we have addressed unresolved structural details related to the binding specificity of Cu(II) through the design of site-directed and domain-truncated mutants of AS and by the characterization of the metal-binding features of its natural homologue beta-synuclein (BS). The structural properties of the Cu(II) complexes were determined by the combined application of nuclear magnetic resonance, electron paramagnetic resonance, UV-vis, circular dichroism spectroscopy, and matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). Two independent, noninteracting copper-binding sites with significantly different affinities for the metal ion were detected in the N-terminal regions of AS and BS. MALDI MS provided unique evidence for the direct involvement of Met1 as the primary anchoring residue for Cu(II) in both proteins. Comparative spectroscopic analysis of the two proteins allowed us to deconvolute the Cu(II) binding modes and unequivocally assign the higher-affinity site to the N-terminal amino group of Met1 and the lower-affinity site to the imidazol ring of the sole His residue. Through the use of competitive chelators, the affinity of the first equivalent of bound Cu(II) was accurately determined to be in the submicromolar range for both AS and BS. Our results prove that Cu(II) binding in the C-terminal region of synucleins represents a nonspecific, very low affinity process. These new insights into the bioinorganic chemistry of PD are central to an understanding of the role of Cu(II) in the fibrillization process of AS and have implications for the molecular mechanism by which BS might inhibit AS amyloid assembly.     

λ-Symmetries for the Reduction of Continuous and Discrete Equations

In this work we present results on the construction of λ-symmetries for ordinary differential equation using ideas derived from the notion of nonlocal symmetries and Jacobi last multiplier. We then apply the results obtained to the case of ordinary difference equations.