Photochemistry of some steroidal bicyclo[3.1.0]hexenones

The photochemistry of five 11-hydroxy-1,5-cyclopregn-3-en-2-ones (‘lumi’ products from the corresponding pregna-1,4-dien-3-ones) has been investigated. In all cases the photoproducts were 1,11-oxy derivatives, resulting from intramolecular attack of the hydroxyl group to the incipient positive charge at C-1. When a fluorine atom was present at C-6, HF elimination took place concurrently with the nucleophilic addition and led to linearly conjugated dienones, rather than the enones obtained in the other cases. Quantum yields were in the range 0.06-0.2, the lower values applying when a fluorine atom was present in position 6 (not in position 9). The results add new evidence on the role of zwitterionic intermediates in the photochemistry of cross-conjugated dienones and the corresponding lumi photoproducts.     

Physico-chemical characterization of nanofiltration membranes.

This study presents a methodology for an in-depth characterization of six representative commercial nanofiltration membranes. Laboratory-made polyethersulfone membranes are included for reference. Besides the physical characterization [molecular weight cut-off (MWCO), surface charge, roughness and hydrophobicity], the membranes are also studied for their chemical composition [attenuated total reflectance Fourier spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS)] and porosity [positron annihilation spectroscopy (PAS)]. The chemical characterization indicates that all membranes are composed of at least two different layers. The presence of an additional third layer is proved and studied for membranes with a polyamide top layer. PAS experiments, in combination with FIB (focused ion beam) images, show that these membranes also have a thinner and a less porous skin layer (upper part of the top layer). In the skin layer, two different pore sizes are observed for all commercial membranes: a pore size of 1.25-1.55 angstroms as well as a pore size of 3.20-3.95 angstroms (both depending on the membrane type). Thus, the pore size distribution in nanofiltration membranes is bimodal, in contrast to the generally accepted log-normal distribution. Although the pore sizes are rather similar for all commercial membranes, their pore volume fraction and hence their porosity differ significantly.     

Electrochemically induced ring-closing of photochromic 1,2-dithienylcyclopentenes

An unprecedented combination of photochromism and electrochromism is observed for two 1,2-bis(dithienyl)cyclopentene derivatives; the ring-opening reactions are photochemically driven while the ring-closing reactions can be triggered by electrochemical oxidation.     

GnRH binding RNA and DNA Spiegelmers: a novel approach toward GnRH antagonism

Mirror-image oligonucleotide ligands (Spiegelmers) that bind to the pharmacologically relevant target gonadotropin-releasing hormone I (GnRH) with high affinity and high specificity have been identified using the Spiegelmer technology. GnRH is a decapeptide that plays an important role in mammalian reproduction and sexual maturation and is associated with several benign and malignant diseases. First, aptamers that bind to D-GnRH with dissociation constants of 50-100 nM were isolated out of RNA and DNA libraries. The respective enantiomers of the DNA and RNA aptamers were synthesized, and their binding to L-GnRH was shown. These Spiegelmers bind to L-GnRH with similar affinity to that of the corresponding aptamers that bind to D-GnRH. We further demonstrated dose-dependent inhibition of GnRH-induced Ca(2+) release in Chinese hamster ovary cells that were stably transfected with the human GnRH receptor.     

Characterisation of combinatorial libraries of mucin-2 antigen peptides by high-resolution mass spectrometry

An epitope motif, TX(1)TX(2)T, of mucin-2 glycoprotein was identified by means of a mucin-2-specific monoclonal antibody, mAb 994, raised against a synthetic mucin-derived 15-mer peptide conjugate. For determination of the epitope sequence recognised with highest affinity by mAb 994, a combinatorial approach was applied using the portioning-mixing technique excluding Cys. Antibody binding of libraries was most profound when Gln was at the X(1) position. Analytical characterisation of the TQTX(2)T library was conducted by amino acid analysis and matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) and electrospray ionisation Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometric methods. Control libraries were prepared by mixing 19 individual peptides corresponding to the TQTX(2)T sequence. Thus, mixtures of 6, 10 and 19 pentapeptides were analysed and compared with the combinatorial mixture. MALDI-TOFMS was able to detect only partially the components in the 6- and 10-member mixtures, but failed to characterise a more complex 19-member mixture. In contrast, ESI-FTICRMS resolved all mixtures of higher complexity and provided direct identification at monoisotopic resolution, such as for a peptide library containing 'isobaric' lysine and glutamine (Delta m = 0.0364 Da). The results of this study suggest that ESI-FTICRMS is a powerful tool for characterisation of combinatorial peptide libraries of higher complexity.     

High-performance liquid chromatography with post-column derivatisation and fluorescence detection for sensitive determination of aflatoxin M1 in milk and cheese

A new HPLC method with fluorescence detection using pyridinium hydrobromide perbromide as a post-column derivatising agent has been developed to determine aflatoxin M1 in milk and cheese. The detection limits were 1 ng/kg for milk and 5 ng/kg for cheese. The calibration curve was linear from 0.001 to 0.1 ng injected. The method includes a preliminary C18-SPE clean-up and the average recoveries of Aflatoxin M1 from milk and cheese, spiked at levels of 25-75 ng/kg and 100-300 ng/kg, respectively, were 90 and 76%; the precision (RSDr) ranged from 1.7 to 2.6% for milk and from 3.5 to 6.5% for cheese. The method is rapid, easily automatable and therefore useful for accurate and precise screening of aflatoxin M1 in milk and cheese.     

Theoretical investigations on the solvation process

A model to facilitate the computation of the most stable conformer of associated M · H₂O (M being a polar molecule) which depends upon the electrostatic interaction energy between the two associated molecules is proposed and tested. SCF electrostatic potentials for the M molecule and a suitable point charge distribution for H₂O were employed in the model computations. Energies predicted by the model are found to be in good agreement with those resulting from an ab initio minimal STO basis SCF treatment of some conformations of the H₂O dimer.

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Zusammenfassung Ein Modell zur Durchführung der Berechnung des stabilsten Konformeren eines Assoziationskomplexes M · H₂O, wobei M ein polares Molekül ist, wird vorgeschlagen und untersucht. Es basiert auf der elektrostatischen Wechselwirkung zwischen beiden Partnern, und zwar wird für das Molekül M der elektrostatische Anteil seines SCF-Potentials und für H₂O eine angemessene Punktladungsverteilung zugrunde gelegt. Die resultierenden Energien sind in guter Übereinstimmung mit denen, die sich bei einer ab initio Rechnung mit minimaler STO Basis ergeben.

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Work performed with the financial support of the Consiglio Nazionale delle Ricerche, through its Laboratorio di Chimica Quantistica ed Energetica Molecolare.     

Synthesis of a Glyoxalase I Inhibitor from Streptomyces griseosporeus NIIDAet OGASAWARA

The pseudolactones 6 and 12 were prepared in a straightforward way from methyl α-D -glucopyranoside and methyl α-D -mannopyranoside, respectively. The pseudolactone 6 reacted with tert-butyl lithioacetate to give the protected, trihydroxylated cyclohexenone carboxylate 7 (51 %). The sterically hindered, L-ribo-configurated pseudolactone 12 reacted with diethyl ethylphosphonate and dimethyl methylphosphonate to give the protected trihydroxycyclohexenones 17 (49 %) and 18 (62 %), respectively. The hydroxymethylated cyclohexenone 21 was obtained from 18 by treatment with Me₂AlSPh and then formaldehyde, oxidation of the product 19 , and elimination. Deprotection of 21 gave 2 , identical with KD16-Ul. Esterification of 2 gave 1 , identical with the title compound. Alternatively, 1 was obtained in higher yields by esterification of 21 , followed by deprotection of the hydroxy groups. This synthesis gave 1 and 2 from methyl α-D -mannopyranoside in an overall yield of 18 and 20 %, respectively, confirming their absolute configuration.     

Deoxy-nitrosugars 12th communication Synthesis of isosteric mono-phosphonate analogues of β-and α-D-fructose 2,6-bisphosphate

A synthesis of the isosteric mono-phosphonate analogues 2a and 19 of the β-and α-D -fructose 2,6-bisphosphate, respectively, is described. Chain elongation of the 1-deoxy-1-nitro-D -arabinose 3 (Scheme 1) by a Henry reaction with paraformaldehyde followed by protection of the resulting alcohol (methoxymethyl ether) and a radical-chain substitution by nitromethane anion gave the key intermediates, the gluco-anhydroalditol 6 and the manno-anhydroalditol 7 . These products equilibrated under basic conditions. Conversion of 7 to the aldehyde 9 , Abramov reaction of 9 with diphenyl phosphite followed by deoxygenation according to Barton gave the phosphonate 11 (Scheme 2). Selective hydrogenolysis of 11 , phosphorylation and deprotection gave 2 which was converted to the tetrasodium salt 2a . Similarly, 6 was transformed into the isosteric phosphonate analogue 19 of the α-D -fructose 2,6-bisphosphate (Scheme 3).     

Phase-space invariants for aggregates of particles: hyperangular momenta and partitions of the classical kinetic energy

Rigorous definitions are presented for the kinematic angular momentum K of a system of classical particles (a concept dual to the conventional angular momentum J), the angular momentum L(xi) associated with the moments of inertia, and the contributions to the total kinetic energy of the system from various modes of the motion of the particles. Some key properties of these quantities are described-in particular, their invariance under any orthogonal coordinate transformation and the inequalities they are subject to. The main mathematical tool exploited is the singular value decomposition of rectangular matrices and its differentiation with respect to a parameter. The quantities introduced employ as ingredients particle coordinates and momenta, commonly available in classical trajectory studies of chemical reactions and in molecular dynamics simulations, and thus are of prospective use as sensitive and immediately calculated indicators of phase transitions, isomerizations, onsets of chaotic behavior, and other dynamical critical phenomena in classical microaggregates, such as nanoscale clusters.