bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Electron Equations for Embedded Electron Density and Their Applications to Study Electronic Structure of Atoms and Molecules in Condensed Phase
Authors: Dulak Marcin , Kevorkyants Ruslan , Tran Fabien , Wesolowski Tomasz A.
Published: June 2006

Recent applications of one-electron equations for embedded electron density introduced originally for multi-level modeling of solvated molecules (T.A. Wesolowski, A. Warshel, J. Phys. Chem. 1993, 97, 8050) are reviewed. The considered applications concern properties
directly related to the electronic structure of molecules (or an atom) in condensed phase such as: i) localized electronic excitations in a chromophore involved in a hydrogen-bonded intermolecular complex; ii) UV/Vis spectra of acetone in water; and iii) energy levels of f-orbitals
for lanthanide cations in a crystalline environment. For each case studied, the embedding potential is represented graphically and its qualitative features are discussed.
Ground and Excited State Density Functional Calculations with the Gaussian and Augmented-Plane-Wave Method
Authors: Iannuzzi Marcella , Chassaing Thomas , Wallman Thomas , Hutter Jürg
Published: June 2006

The calculation of the electronic structure of large systems by methods based on density functional theory has recently gained a central role in molecular simulations. However, the extensive study of quantities like excited states and related properties is still out of reach due to
high computational costs. We present a new implementation of a hybrid method, the Gaussian and Augmented-Plane-Wave (GAPW) method, where the electronic density is partitioned in hard and soft contributions. The former are local terms naturally expanded in a Gaussian basis, whereas the soft
contributions are expanded in plane-waves by using a low energy cutoff, without loss in accuracy, even for all-electron calculations. For the calculation of excitation energies a recently developed, time-dependent density functional response theory (TD-DFRT) technique is joined with the GAPW
procedure. We demonstrate the accuracy of the method by comparison with standard quantum chemistry calculations for a set of small molecules. To highlight the performance and efficiency of GAPW we show calculations on systems with several thousands of basis functions.
The Interplay and Synergism of Experiment and Quantum Chemistry in Research on Reactive Intermediates
Authors: Bally Thomas
Published: June 2006

Three examples from the work of the author's research group on reactive intermediates are used to illustrate how fruitful interaction between experimental and computational chemistry may lead to the solution of problems that neither of the two methods could have solved without the other.
It is shown that computational chemistry has indeed become an indispensable tool for the verification of spectroscopic assignments, the elucidation of reaction mechanisms, and the understanding of the factors that drive chemistry.
Binding Energies of Hydrogen-Bonded cis-Amide and Nucleobase Dimers: An Evaluation of DFT Performance
Authors: Frey Jann A. , Leutwyler Samuel
Published: June 2006

The understanding of biological processes at the molecular level demands accurate knowledge of the nonbonded interactions that control the geometries, binding energies and dynamics of the supramolecular structures involved. High level ab initio methods are still prohibitively
expensive for large systems, but certain density functional (DFT) methods can provide cost-effective alternatives. The performance of six different functionals (BLYP, B3LYP, X3LYP, PBE, PW91, and mPW91) for the calculation of the doubly hydrogen-bonded cis-amide dimers (formamide)2
and (2-pyridone)2 have been tested. Their N-H···O hydrogen bond motifs occur between many nucleobases, peptides, and proteins. Binding energy benchmarks using ab initio MP2 calculations and basis set extrapolations to the complete basis set (CBS) limit
with the Dunning aug-cc-pVXZ (X=D,T,Q) basis set series have been established. These yield D?e = ?14.80 kcal/mol for (formamide)2 and ?22.63 kcal/mol for (2PY)2. Of the six functionals, PW91 consistently gives the
best agreement with the MP2 basis-set limit binding energies, closely followed by PBE. The mPW91, B3LYP and the recently proposed X3LYP functionals are in less good agreement. The BLYP functional underestimates the interaction strengths by 20–25% and is not recommended. As an application
the hydrogen-bond isomerization equilibria for the Sugar-edge, Watson-Crick and Wobble isomers of the dimers 2-pyridone·uracil and 2-pyridone·thymine from first principles are computed and compared to experiment.
The Medicinal Chemist's Dream: Faster Design of Better and Safer Drug Candidates
Authors: Reist Marianne , Novaroli Laura , Daina Antoine , Martel Sophie , Carrupt Pierre-Alain
Published: June 2006

Successful drug research depends on adequate links between therapeutic benefits for the treatment of a disease, pertinent biological targets and suitable chemical compounds. The pharmacochemistry group at EPGL is active in the development of virtual and experimental methods to enhance
these links following a general hit and lead generation strategy to reduce large chemically diverse databases to lead collections. This strategy is based on a careful definition of its numerous steps and on a series of key validation processes. Particular attention is devoted to identify and
improve the usefulness of virtual screening techniques widely used in drug development. The guidelines proposed here to use the best validated tools in the most suitable order will help the medicinal chemist to approach his dream, namely to be faster in the design of better and safer drug
candidates.
Formulation Optimization in a University Hospital: The Example of Pediatric Solutions of the ACE Inhibitor Captopril
Authors: Berger-Gryllaki Markoulina , Podilsky Grégory , Widmer Nicolas , Gloor Stéphane , Testa Bernard , Pannatier André
Published: June 2006

Many major drugs are not available in pediatric form. As a result, hospital pharmacists are often requested to provide the medical staff with liquid formulations for individualized dosage and easy administration to newborn and young patients. Such in-house formulations must of course
fulfil stringent criteria of purity and stability. This paper reports the development of a liquid solution of captopril for pediatric use. A specific HPLC-UV method was developed. A number of formulations described in the literature as affording one-month stability were examined and found
wanting. A simple solution of the drug (1 mg/ml) in purified water containing 0.1% EDTA-Na proved chemically and microbiologically stable at room temperature for two years.
Experimental and Virtual Physicochemical and Pharmacokinetic Profiling of New Chemical Entities
Authors: Martel Sophie , Castella Marc-Etienne , Bajot Fania , Ottaviani Giorgio , Bard Bruno , Henchoz Yveline , Valloton Bénédicte Gross , Reist Marianne , Carrupt Pierre-Alain
Published: June 2006

Physicochemical and pharmacokinetic profiling of new chemical entities (NCEs) allows the rapid identification and elimination of compounds with properties not suitable for further development as drug candidates. Among the complex panel of theoretical and experimental methods available
to predict or measure physicochemical or pharmacokinetic properties, some key techniques developed or tested in the pharmacochemistry group at EPGL are presented. This paper focuses on virtual and experimental approaches dealing with key properties such as ionization, solubility, lipophilicity,
and membrane permeation. In addition, the effect of the third dimension on intramolecular interactions is exemplified by lipophilicity variations in the conformational space of cyclosporin A and with a 3D solvatochromic model able to accurately predict the BBB permeation.
Identification of Novel Multifunctional Compounds for the Treatment of Some Aging Related Neurodegenerative Diseases
Authors: Novaroli Laura , Daina Antoine , Bertolini Francesca , Di Giovanni Saviana , Bravo Juan , Reist Marianne , Carrupt Pierre-Alain
Published: June 2006

Aging related neurodegenerative disorders such as Parkinson disease (PD) and Alzheimer's disease (AD) are the result of multiple pathophysiological pathways that contribute to the neurodegenerative cascade. Hence, multifunctional drug candidates able to interact with several targets
are of great interest for the treatment of such diseases. Therefore, an experimental and virtual screening pathway to generate multifunctional hits showing promise for the treatment of PD or AD was suggested. Moreover, suitable experimental and virtual screening methods to rapidly test pre-focused
compound libraries were developed and validated. In particular, the screening was focused on potential inhibitors of acetylcholinesterase (AChE) and monoamine oxidase B (MAO B) using a combination of in vitro enzymatic tests, docking and scoring approaches and refined molecular modeling
tools.
Synergy at the 'Ecole de Pharmacie Genève-Lausanne': Methodology Developments for the Treatment of Complex Metabolomic Datasets with Data Mining
Authors: Thiocone Aly , Grata Elia , Boccard Julien , Carrupt Pierre-Alain , Rudaz Serge , Wolfender Jean-Luc
Published: June 2006

With the advances in analytical techniques and data mining, the chances to elucidate a plant metabolome and understand the metabolite variation in response to external stimuli such as stress are gradually becoming feasible in a global manner. This approach represents a very important
research challenge because of the structural diversity of the metabolites and the convolute nature of biological matrices. Based on a new collaborative framework emerging from the recent creation of the EPGL, a project aimed at the development of methodology for the treatment of complex metabolomic
datasets with data mining has been initiated with the expertise of different EPGL laboratories. In this paper the strategies used for the study of the metabolic variations in a biological model (the effect of mechanical wounding on Arabidopsis thaliana) are described. Metabolite profiling
based on micro-extraction and LC/MS analysis with various detection methods has been used. Data were parsed in the form of ion maps and treatment of this complex set of MS information was performed with dedicated bioinformatic tools. This approach should enable the evaluation of metabolome
variations in a comprehensive manner for a better understanding of complex biological mechanisms and for the detection of novel bioactive molecules.
The Importance of Phytoestrogens in Food Supplements and Phytopharmaceuticals
Authors: Polasek Johanne , Hostettmann Kurt
Published: June 2006

Different natural products from the plant kingdom including isoflavones, prenylflavones, coumestans, stilbenes, and lignans can cause endocrine perturbations, especially on the estrogenic hormonal pathway because of their structural analogies to estradiol. Several studies report the
presence of such compounds in food, the richest source being soy and soy products. These substances, commonly called phytoestrogens, are known to influence the human hormonal profile and soy preparations are being considered for use as post-menopausal estrogen replacement therapy. Numerous
clinical and epidemiological reports have studied the influence of phytoestrogens on the development of hormone-dependent cancers. The effect on genital development of postnatal phytoestrogen exposure is still under debate. Consumption of phytoestrogens may also influence the incidence of
bone diseases, atherosclerosis, or Alzheimer's disease. This article summarizes the classification of phytoestrogens, their pharmacological evaluation and properties, and the methods used for their identification.
Biomaterials for Injectable Therapeutic Implants
Authors: Jordan Olivier , Rufenacht Daniel A. , Iselin Christophe , Doelker Eric
Published: June 2006

Injectable biomaterials that have the ability to form semi-solid implants in situ are of keen interest for therapeutic applications. The materials may be used to fill in pathological vascular spaces or be designed to possess functional properties such as being radiopaque for
an improved visibility during image-guided minimally invasive interventions, or induce a localized biological activity. Among the variety of solidification principles that may be used to produce implants in situ, the precipitation of water-insoluble polymers driven by solubility changes
shows some particular features that may be valuable for specific therapeutic applications. This paper reviews some of the applications of these implant-forming biomaterials in interventional radiology, urology, and oncology.
Application of Special FTIR ATR Techniques for Quantitative Structural Analysis of Thin Surface Layers
Authors: Baurecht Dieter , Reiter Gerald , Hassler Norbert , Schwarzott Michael , Fringeli Urs Peter
Published: June 2006

FTIR ATR spectroscopy is increasingly used for in situ investigations of processes at or near a surface. Particularly when thin layers (biomembranes, monolayers, thin films) are investigated with respect to surface concentration and molecular structure, very sensitive techniques
have to be applied in order to achieve an adequate signal-to-noise ratio. This may lead to long measuring times due to extended data accumulation and averaging. However, this can cause new problems with respect to the stability of relevant experimental parameters, such as the sample itself,
the spectrometer, and the atmosphere in the spectrometer.In this article we report on two techniques which were developed or improved in our laboratory and successfully applied over past years. Both methods, the so-called single-beam sample reference (SBSR) spectroscopy and the modulation
or modulated excitation (ME) spectroscopy, are well suited to compensate instabilities that occur in the course of an experimental series. The SBSR technique converts a single-beam FTIR spectrometer into a pseudo double-beam instrument. By this technique there is always a reference with the
same age as the sample available. Moreover, by alternating sample and reference measurements within short time periods, varying environmental conditions such as water vapor concentration in the spectrometer are easily compensated. Moreover SBSR technique enables data evaluation in the conventional
single-beam mode (SB) in both the sample (S) and reference (R) channel. This kind of evaluation is important to gain information on the history of S and R. As examples for SBSR and SB applications we report on studies of the interaction of an endotoxin with an immobilized lipid bilayer membrane,
as well as on the interaction of TNF? with a TNF? antibody. ME spectroscopy can be applied to systems that show a (pseudo-) reversible response to a periodic excitation. The response of the system measured with time-resolved FTIR spectroscopy is then processed by phase-sensitive
detection (PSD). ME spectroscopy is able to determine kinetic constants of a system, allows a hardware separation of overlapping absorption bands, and eliminates all disturbing signal components which do not have the same frequency as the excitation itself. This improves the signal-to-noise
ratio dramatically and leads in principal to a stable baseline. The binding of sodium cholate to an adsorbed protein layer of human serum albumin (HSA) is shown as an example that the required sensitivity to study specific molecular interaction is in the ?AU range and can be reached by
FTIR ME spectroscopy. In a second example, the measurement of structural changes of PLL induced by temperature modulation shows the feasibility of band separation and indicates the possible determination of kinetic properties of a system.
Recent Advances in Optical DNA Biosensors Technology
Authors: Kuswandi Bambang , Tombelli Sara , Marazza Giovanna , Mascini Marco
Published: June 2006

Recent advances in nucleic acids-based biosensors have led to the development of DNA biosensors for DNA hybridisation detection and for nucleic acid–ligand binding studies. This review presents a concise description and an evaluation of the optical devices that have been employed
in the development of optical DNA biosensors. Such optical devices include optical fibres, planar waveguide, surface plasmon resonance, resonant mirror and surface-enhanced Raman scattering. The specificity and response of each optical DNA biosensor are discussed. Overall, a rapid growth in
the development of optical DNA biosensor technology will be seen in the near future, which will lead to the establishment of optical DNA biosensor technology as a major tool of analytical biochemistry.
Potentiometric Sensors for Heavy Metals – An Overview
Authors: Gupta Vinod K.
Published: June 2006

An overview of potentiometric sensors that are capable of detecting heavy metal ions is presented. Notwithstanding the tremendous work performed so far, it is obvious that severe limitations still exist in terms of selectivity, limits of detection, dynamic ranges, applicability to specific
problems, and reversibility. A survey of important advances in potentiometric sensors with regard to high selectivity, lower detection limit, fast response time and on-line environmental analysis is given.
Cellular Assays with Multiparametric Bioelectronic Sensor Chips
Authors: Wiest Joachim , Brischwein Martin , Ressler Johann , Otto Angela M. , Grothe Helmut , Wolf Bernhard
Published: June 2006

During recent years, sensor chip-based systems have been developed which monitor functional changes of living cells. Key elements of such cellular assays are silicon or glass chips with integrated sensors for physico-chemical parameters, i.e. pH, pO2, electric impedance
and temperature. Analysis of these primary parameters yields information about cell metabolism, cell growth and adhesion, and cell morphological changes. The operation principles of individual sensor types are described together with examples of experimental results.
Multiple Aspects of R&D Must Be Optimized to Foster Innovation
Authors: Aeschbacher Roger
Published: June 2006

On October 27, 2004, Prof. Dr. Daniel Gygax received the annual award for R&D of the Canton Baselland. This important prize was presented to Daniel Gygax by the minister for education of the canton Baselland, Mr. Urs Wüthrich-Pelloli. In his address the executive politician
highlighted the exemplary role that Daniel Gygax plays in facilitating technology transfer between academia and industry in biotechnology. This is therefore a good reason and a good opportunity to have a closer look both at what biotechnological competences Daniel Gygax has built up at the
Chemistry Department of the University of Applied Sciences in Muttenz (FHBB) and at how R&D of Swiss Universities of Applied Sciences can help foster innovation today.
Modeling of Solvolysis Reaction Mechanism for Cation-Olefin Cyclizations
Authors: Bollot Guillaume , Fouillet Céline C.J. , Mareda Jiri
Published: June 2006

We report on a computational study of cation-olefin cyclization mechanism under solvolytic conditions. The combined explicit-continuum solvent model aimed at providing a complete estimate of media effects is used to investigate the nature, stability, and conformational behavior of cationic
species involved in the reaction. The comparison between the explicit-continuum and leaving group models is also provided. Our study of reactionpath ways shows that protonated cyclopropane is the key intermediate on the potential energy surface of cation-olefin cyclizations.
Synthesis and Characterization of a New Family of Iron Porphyrins
Authors: Meyer Dominik N. , Woggon Wolf-D.
Published: June 2006

A significant tool for better understanding the complex nature of the cofactor of heme thiolate proteins such as Cytochromes P450 is the investigation of model compounds. In this context a new family of iron porphyrins has been synthesized by replacing the native thiolate ligand for
a SO3? group coordinating the heme iron.
Synthetic Diversity and Catalytic Mechanism of Peptide Dendrimers
Authors: Delort Estelle , Darbre Tamis , Reymond Jean-Louis
Published: June 2006

Peptide dendrimers composed of alternating sequences of natural amino acids and branching diamino acids are investigated as synthetic enzyme models. The dendrimers can be prepared by solid-phase peptide synthesis and are obtained pure in yields of 5–35%. Peptide dendrimers with
surface histidine residues catalyze ester hydrolysis reaction with enzyme-like kinetics, including substrate binding (KM), catalytic turnover (kcat), and rate acceleration kcat/kuncat = 1000–20'000. Mechanistic investigation
by substrate variation, pH-profile, and isothermaltitration calorimetry show that the catalytic effect is caused by positive interaction between the histidine side-chains and creation of a hydrophobic microenvironment for substrate binding.
Rational Design of Organo-Ruthenium Anticancer Compounds
Authors: Gossens Christian , Tavernelli Ivano , Rothlisberger Ursula
Published: June 2006

Organometallic ruthenium(II)-arene complexes are currently attracting increasing interest as anticancer compounds with the potential to overcome drawbacks of traditional drugs like cisplatin with respect to resistance, selectivity, and toxicity. Rational design of new potential
pharmaceutical compounds requires a detailed understanding of structure–property relationships at an atomic level. We performed in vacuo density functional theory(DFT) calculations, classical MD, and mixed QM/MM Car-Parrinello MD explicit solvent simulations to rationalize the
binding mode of two series of anticancer ruthenium(II) arene complexes to double-stranded DNA (dsDNA).Binding energies between the metal centers and the surrounding ligands as well as proton affinities were calculated using DFT. Our results support a pH-dependent mechanism for the activity
of the RAPTA [Ru(?6-arene)X2(pta)] (pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) compounds. Adducts of the bifunctional RAPTA and themonofunctional [Ru(?6-p-cymene)Xen]+ series of compounds with the DNA sequence d(CCTCTG*G*TCTCC)/d(GGAGACCAGAGG),
where G* are guanosine bases that bind to the ruthenium compounds through their N(7) atom, have been investigated. The resulting binding sites were characterized in QM/MM molecular dynamics simulations showing that DNA can easily adapt to accommodate the ruthenium compounds.
Porphyrin-Substituted Dinucleotides: Synthesis and Spectroscopy
Authors: Bouamaied Imenne , Stulz Eugen
Published: June 2006

Deoxyuridine, which is substituted with either 5, 15-diphenyl porphyrin (DPP) or 5, 10, 15,20-tetraphenyl porphyrin (TPP) at the 5-position via an alkynyl linker, was dimerised to the homo- and hetero-porphyrin dinucleotide. The synthesis was performed either in solution or on
solid phase in order to compare the reactivity of the phosphoramidite building blocks under both conditions. The absorbance properties reveal electronic interactions in the dimers that are strongly dependent on the nature of the porphyrin. The DPP-containing dimers show significant differences
between the calculated and the measured UV-Vis spectra, whereas in the TPP dimer hardly any difference is observed. Formation of the duplex with the corresponding diadenosine changes the electronic interactions between the chromophores in the heteroporphyrin dimer, as shown by a blue shift
of the absorbance. The low solubility of the DPP dimer in pure chloroform prevented formation of the duplex due to the necessity to add about 10% of methanol. The dimerisation is detectable using MALDI-TOF mass spectrometry for all dinucleotides.
Heterobimetallic Complexes as Catalyst Precursors for the Oppenauer-Type Oxidation of Alcohols
Authors: Gauthier Sébastien , Severin Kay
Published: June 2006

A heterobimetallic Ru(II)-Rh(I) complex has been identified as a potent catalyst precursor for the Oppenauer-type oxidation of alcohols. With 0.1–0.5 mol% of this complex and K2CO3 as the co-catalyst, it is possible to oxidize secondary and primary alcohols
at ambient temperature using acetone as the solvent and oxidation agent.
Oxidosqualene Cyclase (OSC) Inhibitors for the Treatment of Dyslipidemia
Authors: Dehmlow Henrietta , Thoma Ralf , Ruf Armin , Panday Narendra , Von Der Mark Elisabeth , Morand Olivier , Märki Hans Peter , Kansy Manfred , Hartman Peter , Coassolo Philippe , Chucholowski Alexander , Blum-Kaelin Denise , Aebi Johannes , Ackermann Jean , Schulz-Gasch Tanja
Published: June 2006

Novel inhibitors of oxidosqualene cyclase (OSC) for the treatment of dyslipidemia are reported. Starting point for the chemistry program was a set of compounds derived from a fungicide project which, in addition to high affinity for OSC from Candida albicans, also showed high
affinity for the human enzyme (hOSC). Here the evaluation process of different scaffolds is outlined for two representative series, the phenyl substituted benzo[d]isothiazoles and the aminocyclohexanes. The most promising compounds derived from the latter series were further profiled
in vivo and showed promising properties with respect to modulation of lipid parameters.
Is Switzerland Still a Lucrative Place for Manufacturers of Drug Substances to Produce Their Products?
Authors: Bäuerle Hans-Dieter
Published: June 2006

Pharmaceutical manufacturers are coming under increasing pricing pressure as a result of healthcare reforms and are therefore looking to low wage countries in the Far East. Often, the outcome is a process that is not fully mature in economic terms. Contract synthesis manufacturers,
such as Siegfried, offer assistance here with its comprehensive pharmaceutical know-how in order to establish efficient and low-cost processes at an early stage. Siegfried's strengths lie in its many years experience in the pharmaceutical industry and in the network of contacts it has built
up over the years with technical and material suppliers. Therefore, as far as Switzerland as a location for manufacturing is concerned, Siegfried looks to the future with confidence.
Industrial Activity in a Rural Environment
Authors: Zweifel Bernhard O.
Published: June 2006

UCB, a Belgian pharmaceutical/chemical company, founded an industrial site in 1996 in Bulle, Switzerland. Since the time of the creation of the enterprise, industrial activity has been expanded continuously and consists today of three production buildings with more than 70 employees
in production and approx. 180 in total. In a preface to the description of the manufacturing activities some general remarks are made to highlight factors to be considered for a successful site selection. The conclusion is reached that the investment – as of today – has successfully
met the expectations of the investor.
"Times are changing ... and so must we" Integral Logistics and Services for the World-Scale Producer in Switzerland
Authors: Habegger Erich , Kirschbaum Georg , Vollenweider Ivan
Published: June 2006

The chemical distribution business has traditionally consisted of a more or less one-way flow of information and products channeled through the distributor's organization. Changes in the industry require more integral service-oriented models to meet current needs. Distributors become
both the supplier's and the customer's partner in the supply chain management, with an awareness of their partners' key objectives and strategies. The European chemical distribution market is highly fragmented. In order to be able to provide the required broad range of services and to run
the business on a sustainable economic basis, the distribution operations must exceed a critical minimal size. Therefore a consolidation tends to shift towards larger distributors with broader services and product ranges. The competitive supplier in the chemical distribution business must
provide a complete service. The following activities are viewed as essential elements of this integral service: Storage and materials handling, transportation, dispensing and refilling operations (if necessary in clean rooms under cGMP conditions), mixing and blending operations, tailor-made
labeling, recovery and disposal service, quality control support, and last but not least experts advising the customer on chemical, technical, application, safety, logistical and commercial issues. Chemical distributors represent and serve important sectors of the chemical industry's value
chain.
New Methods for Synthesizing DNA, RNA, and Phosphonates
Authors: Caruthers Marvin H.
Published: June 2006

The development of new methods for the synthesis of DNA, RNA, and phosphonates has enabled new applications in biochemistry and biology.
Dialkylzincs in Radical Reactions
Authors: Bazin Samantha , Feray Laurence , Bertrand Michèle P.
Published: June 2006

This review describes recent developments in the use of dialkylzincs in radical reactions. In most of the processes reported therein, dialkylzincs act simultaneously as sources of alkyl radicals, as Lewis acids, and as chain transfer agents. A parallel is drawn with the behaviour of
trialkylboranes in similar reactions.
Molecular Functional Materials: The Spring Meeting of the Swiss Chemical Society, March 10th, 2006, Department of Chemistry, University of Fribourg
Authors: Belser Peter , Daul Claude A.
Published: June 2006

The 2006 Spring Meeting of the Swiss Chemical Society was held at the University of Fribourg on March 10, 2006. The one-day symposium was dedicated to recent advances in Molecular Functional Materials. The four speakers, Tom Ziegler, Dante Gatteschi, Andrew Holmes and J. Fraser Stoddart
covered a wide range of modern functionalized material research.
Multifunctional Materials Based on Tetrathiafulvalene Derivatives with Binding Sites for Metal Ions
Authors: Dolder Stefan , Liu Shi-Xia , Decurtins Silvio
Published: June 2006

Tetrathiafulvalene (TTF) and its derivatives are very well known as reversible, stable two-electron donors and they have found widespread use in the field of organic conductors and superconductors. Further, during the last decades, developments in synthetic TTF chemistry have enabled
the use of TTF and its derivatives as versatile building blocks in new fields of materials and supramolecular chemistry. This brief review relates some recent advances that have been achieved by combining the redox and conducting properties of TTF with other functionalities, such as magnetism
or optical properties. A variety of TTF-based ligand systems and their metal complexes are presented.
Intramolecular Schmidt Reaction: Applications in Natural Product Synthesis
Authors: Nyfeler Erich , Renaud Philippe
Published: June 2006

The intramolecular Schmidt reaction was first described at the beginning of the 1990s and rapidly proved to be a powerful tool for the fast assembly of complex nitrogen-containing heterocycles. This review focuses on the application of this reaction in the synthesis of natural products
and other biologically relevant compounds.
Recent Developments in Enantioselective Phase Transfer Catalysis Using Chiral Ammonium Salts
Authors: Vachon Jérôme , Lacour Jérôme
Published: June 2006

Due to the constant demand for non-racemic molecules in both industrial and academic laboratories, many efforts have been devoted in the last 25 years to the development of enantioselective phase transfer catalyzed (PTC) processes. Much of this chemistry was recently reviewed –
the latest reports were from 2003/2004 and treated essentially the synthesis of non racemic ?-amino acids. After a short historical introduction, this article will thus review enantioselective PTC reactions reported in the last three years (2003–2006) and demonstrate how broad
and active the field is – and this considering ammonium-catalyzed reactions only.
Isomerization Mechanisms of a Labile Co(II) Octahedral Complex
Authors: Riblet Fabrice , Novitchi Ghenadie , Helm Lothar , Gulea Aurélian , Merbach André E.
Published: June 2006

The labile cobalt (II) complex [Co(TUF)2(Pic)2] with 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione (TUF) bidentate and 4-methylpyridine (Pic) monodentate ligands was studied by variable temperature (VT) 19F NMR from 184 to 312 K. In contrast to the solid
state, all the isomers are present in a CD2Cl2 solution. Thermodynamic parameters (?H° and ?S°) of each isomer with reference to the trans(N)-trans(CF3)-trans isomer were obtained from the fitting of experimental mole
fraction values. A kinetics investigation of the isomerization processes was performed by lineshape analysis of the spectra using the Kubo-Sack formalism. The suggested bidentate bond-rupture mechanism involves the breaking of the weakest Co–O bond (closest to the CF3 withdrawing
group) with the TUF ligand.
The Use of N-iPr-2,2'-bipyrrolidine Derivatives as Organocatalysts for Asymmetric Michael Additions
Authors: Mossé Sarah , Andrey Olivier , Alexakis Alexandre
Published: June 2006

The recent rapid growth of organocatalysis has shown a new approach in organic chemistry and presents the obvious advantage in the avoidance of expensive and often toxic metals. Moreover, the organocatalysts are generally easier to make than standard catalytic reagents. Therefore, our
laboratory has synthesized N-alkyl-2,2'bipyrrolidine derivatives as a new class of organocatalysts and applied them to the asymmetric Michael addition of ketones and aldehydes to nitroolefins via an enamine intermediate. We have furthermore developed the first asymmetric Michael addition
of aldehydes to vinyl sulfones catalyzed with our diamines. The 1,4 adducts are obtained in good yields with enantioselectivities up to 80% ee. The determination of absolute configuration allowed us to postulate a Si,Si transition state model, as described previously for nitroolefins.
Minireview: Bacterial Sialyltransferases for Carbohydrate Synthesis
Authors: Schwardt Oliver , Visekruna Tamara , Rabbani Said , Ernst Beat
Published: June 2006

Sialylation catalyzed by sialyltransferases is one of the most interesting enzymatic glycosyl transfer reactions, since chemical sialylations usually give only low yields and lead to poor stereoselectivities. In the last decade, several bacterial sialyltransferases were identified and
found to exhibit broader substrate specificity than their mammalian counterparts. This suggests the potential usefulness of bacterial sialyltransferases in chemo-enzymatic synthesis of natural and non-natural sialooligosaccharides.
Possible Ring Structures of Armchair Single-Walled Carbon Nanotubes
Authors: Tamilmani Venkatachalam , Daul Claude , Jenny Titus
Published: June 2006

Energetics and the electronic structure of various types of single-walled carbon nanotubes have been investigated by using Density Functional Theory. Armchair [n,n], zigzag [n,0] and chiral [n,m] C40H20 nanotubes have been considered. Calculations show that the
armchair isomer is the most stable among the three types and they further reveal the factors that stabilize this isomer. Nucleus-independent chemical shift calculations indicate the aromaticity of the individual hexagonal rings in the carbon nanotubes and explain the extent of electron delocalization
in them.
Chasing an Elusive Alkoxide: Attempts to Synthesize [OC(tBu)(CF3)2]?
Authors: Müller Lutz O. , Scopelliti Rosario , Krossing Ingo
Published: June 2006

The synthesis of the alkoxide [OC(tBu)(CF3)2]? by the reaction of tBuM-reagents (M = Li; MgX) with hexafluoroacetone was attempted. This alkoxide was anticipated to be a good building block for novel weakly coordinating anions. However,
in all attempted syntheses – also supported by theoretical DFT calculations – it was shown that [H]? addition is favored over [tBu]? addition. Thus compounds like [(Li(OC(H)(CF3)2]4·2Et2O
(1) and (CF3)2(H)COMgCl·(OEt2)2 (4) were formed. An unexpected result was the formation of (THF)3LiO(CF3)2OC(H)(CF3)2(2), an addition compound built from [(CF3)2C(H)O]?
and hexafluoroacetone. The alkoxy-alkoxide 2 could be useful for further applications.
Accurate Molecular Structure Determination by Femtosecond Degenerate Four-Wave Mixing
Authors: Kummli Dominique S. , Frey Hans M. , Leutwyler Samuel
Published: June 2006

Femtosecond degenerate four-wave mixing (fs-DFWM) is a Raman scattering type of rotational coherence spectroscopy that can be utilized for the measurement of highly accurate rotational and centrifugal constants of nonpolar molecules. The accuracy of the method has been tested using
cyclopropane (C3H6). The rotational and centrifugal distortion constants of this symmetric-top molecule are known to high accuracy. The fs-DFWM constants are currently only surpassed by those determined by dipole distortion microwave spectroscopy.
Organisation and Solubilisation of Zeolite L Crystals
Authors: Bossart Olivia , Calzaferri Gion
Published: June 2006

Zeolite L is a versatile host material for realising functional photonic antenna systems. Energy can be transferred within dye-loaded zeolite L crystals and means have been found to transport the energy from the crystal inside to the environment or vice versa. In order to direct
the energy to a target, the organisation of the zeolite crystals with respect to the environment is an important issue. Some possibilities of modifying zeolite L crystals according to specific sample requirements are summarised. Zeolite L material with interesting optical properties can be
obtained by controlling the interaction between the crystals and their environment.
Molecular Imprinting with Ruthenium Porphyrin Catalysts
Authors: Burri Estelle , Severin Kay
Published: June 2006

A ruthenium meso-tetra[4-(vinylbenzoxy)benzyl]porphyrin catalyst with four polymerizable side chains was synthesized in three steps from commercially available starting materials. The polymerizable side chains allowed the incorporation of this complex in highly cross-linked mesoporous
co-polymers. A block polymer and a molecularly imprinted polymer were prepared by co-polymerization with ethyleneglycol dimethacrylate using chloroform as the porogen. The imprinted polymer was prepared in the presence of aminodiphenylmethane as a template. Subsequent removal of the template
created a substrate pocket next to the catalytically active center. Both polymers displayed a high catalytic activity for the oxidation of alcohols and alkanes with 2,6-dichloropyridine-N-oxide as the oxidant while the homogeneous catalyst was completely inactive. Furthermore, the imprinted
polymer displayed a significant increase in activity compared to the block co-polymer.
Physical Chemistry of Dust: Weak Intermolecular Interactions in Molecular Nanoparticles
Authors: Signorell Ruth
Published: June 2006

Large weakly bound molecular aggregates are ubiquitous: As atmospheric aerosols they influence the quality of the air and have a significant impact on our climate. Furthermore pharmaceuticals in the form of nanoparticles are required to achieve a targeted drug delivery. In all these
fields, physical-chemical methods play a crucial role for the preparation and characterization of this type of matter. Apart from such experimental efforts, one of the greatest challenges is to understand the properties of large molecular aggregates on a microscopic level.
Direct Ambient Analysis of Pharmaceutical and Ecstasy Tablets
Authors: Leuthold Luc Alexis , Mandscheff Jean-François , Fathi Marc , Giroud Christian , Augsburger Marc , Varesio Emmanuel , Hopfgartner Gérard
Published: June 2006

Desorption electrospray ionization (DESI) is a new ionization technique recently introduced in analytical chemistry for the ambient analysis of surfaces by mass spectrometry. We present here new developments in this field, focusing on their use for the analysis of solid forms, as pharmaceutical
tablets or illicit drug tablets. Results recently published by ourselves are discussed in the context of related publications.
Pyrrolidine Derivatives as New Inhibitors of ?-Mannosidases and Growth Inhibitors of Human Cancer Cells
Authors: Fiaux Hélène , Schütz Catherine , Vogel Pierre , Juillerat-Jeanneret Lucienne , Gerber-Lemaire Sandrine
Published: June 2006

New pyrrolidine-3,4-diol derivatives were prepared from D-(?)- and L-(+)-phenylglycinol and tested for their ability to inhibit 25 commercial glycosidases. The influence of the substitution of the lateral side chain and of the pyrrolidine ring on the enzyme inhibition was evaluated.
(2R,3R,4S)-2-({[(1R)-2-Hydroxy-1-phenylethyl]amino} methyl)pyrrolidine-3,4-diol was a potent and selective inhibitor of ?-mannosidase from jack bean. This compound was derivatized into lipophilic esters in order to allow its internalization by human cancer
cells. In particular, the 4-bromobenzoate derivative demonstrated promising inhibition of glioblastoma and melanoma cells whereas it was less effective on healthy human fibroblasts.
Synthesis of Boron-Bridged Anionic C2-Symmetric Bisoxazolines and Their Application in Asymmetric Catalysis
Authors: Mazet Clément , Köhler Valentin , Roseblade Stephen , Toussaint Aurélie , Pfaltz Andreas
Published: June 2006

Anionic boron-based chiral bisoxazoline ligands, the borabox ligands, are readily prepared from amino alcohols and haloboranes. The highly modular nature of these ligands allows both for electronic and steric tuning of the structure. The high enantioselectivities obtained in various
Cu-catalyzed asymmetric reactions and especially in the kinetic resolution of pyridyl alcohols where bisoxazoline ligands exhibit almost no selectivity, point to a considerable potential of borabox ligands in asymmetric catalysis.
Tricyclic Marine Alkaloids: Synthetic Approaches to Cylindricines, Lepadiformine, and Fasicularin
Authors: Schär Pascal , Cren Sylvaine , Renaud Philippe
Published: June 2006

Cylindricines, lepadiformine, and fasicularin are marine alkaloids with a common novel pyrrolo- and pyrido[1,2-j]quinoline skeleton. They have recently been isolated from various tunicates and have shown interesting cytotoxic effects which could be attributed to covalent interactions
with DNA, as well as cardiovascular effects. The promising biological activities together with the unique structural features make these alkaloids interesting targets for natural product synthesis. This review focuses on the different approaches developed for their synthesis with a particular
emphasis on the key step where the quaternary amino substituted carbon center is created.
The Copper-Catalyzed Asymmetric Allylic Substitution
Authors: Alexakis Alexandre , Malan Christophe , Lea Louise , Tissot-Croset Karine , Polet Damien , Falciola Caroline
Published: June 2006

This mini-review discusses the rapidly growing field of asymmetric copper-catalyzed chemistry. Although the allylic substitution has been less studied than the conjugate addition, recent breakthroughs have made this methodology a very valuable synthetic tool. Thus, a primary allylic
halide or phosphate reacts with Grignard or diorganozinc reagents to afford the SN' product (or ?-product) in high regio- and enantioselectivities. Besides the results of the authors, we present also other, different approaches to this reaction, with emphasis on the organo-metallic
and the type of chiral ligand used.
Recollecting the Institute of Organic Chemistry, ETH Zürich, 1972–1990
Authors: Wintner Claude E.
Published: June 2006

The author recalls several visits to the Institute of Organic Chemistry, ETH Zürich. The faculty and staff of the Institute are remembered. Some circumstances surrounding the history of the publication of the total synthesis of vitamin B12 are mentioned.
Glycosyltransferases: An Efficient Tool for the Enzymatic Synthesis of Oligosaccharides and Derivatives as well as Mimetics Thereof
Authors: Rabbani Said , Schwardt Oliver , Ernst Beat
Published: June 2006

Research over the past two decades has uncovered numerous biological roles for carbohydrates, e.g. in cell adhesion processes, signal transduction, malignant transformation, or viral and bacterial cell-surface recognition. Carbohydrates and structural analogues thereof are therefore
considered as potential new leads. Although the chemical synthesis of carbohydrates is well established, the preparation of particular oligosaccharides still remains a costly and cumbersome challenge. A complementary approach to the chemical synthesis is the use of enzymatic methods. The transfer
of monosaccharide moieties to natural substrates, catalyzed by glycosyltransferases, exhibits excellent chemo-, regio- and stereoselectivity. In addition, enzymatic glycosylations permit the synthesis of carbohydrate derivatives and even carbohydrate mimetics. Our results reveal a remarkable
synthetic potential of fucosyltransferases VI (EC 2.4.1.65) and III (EC 2.4.1.65), and ? (2?3)-sialyltransferase ST3Gal III (EC 2.4.99.6). Their use for the preparative synthesis of oligosaccharides and derivatives as well as mimetics thereof is demonstrated.
Pharmaceutical Care – A New Discipline in the Curriculum: Introducing Pharmacy Students to Medication Non-Compliance
Authors: Hersberger Kurt E. , Arnet Isabelle
Published: June 2006

Pharmaceutical Care (PC) is a new academic discipline with a direct link to patient care. Since 2003 it has been integrated into the Swiss five-year university pharmacy curriculum. This article aims to describe (1) the concept of PC as a systematic process through which a pharmacist
cooperates with the patient and healthcare professionals in designing, implementing and monitoring a therapeutic plan that will produce specific therapeutic outcomes; (2) the didactic concept used for the new discipline; (3) an illustrative example of how to teach pharmacy students the issues
of patient non-compliance.
Pharmacy in Basel
Authors: Kessler Michael
Published: June 2006

The production of pharmaceuticals is one of the foundations of the economy and financial stability of the Basel region. Pharmacy and the city of Basel have been synonymous, and historically entwined, for a considerable time. Probably no other city in the world displays a higher density
of pharmaceutical industry. The historic origins of these developments stem from far back in the Middle Ages. However, the past two hundred years have transformed our medical and pharmaceutical sciences tremendously, and this progress has made deep impressions upon Basel's industry. The predominant
sources and currents that have influenced the foundation and development of the Basel pharmaceutical industry are described in this article. The histories of pharmacy and medicine are definitively connected, and neither subject can be properly understood without the awareness of the relationship
between the two. Pharmacy and medicine were affected by diverse cultural influences and sociological changes, and further by profound advances in the natural sciences and the resultant technological discoveries. Today's pharmaceutical industry in Basel is a living illustration of the combined
complexity of a distant historical past and the technological present working together towards the future.
Computational Pharmaceutical Chemistry – Novel Technologies for Lead Optimization and the Prediction of ADMET Properties
Authors: Lill Markus A.
Published: June 2006

The prediction of affinities of ligands binding to a target protein represents a major challenge in modern computer-aided drug design. To contribute towards this goal, we have developed a new technology to identify feasible binding modes of protein-bound, biomedically interesting molecules
and to compute their binding affinity using multidimensional quantitative structure-activity relationships (QSAR). In our approach, the flexibility of the protein is explicitly simulated. Applications of the underlying technology to G protein-coupled receptors, nuclear receptors and cytochrome
P450 show the ability of this approach to predict the binding affinity of diverse sets of ligands to a common protein, and suggest its potential to predict adverse or toxic effects of drugs and chemicals in silico.