bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organometallic Compounds for Nonlinear Optics—The Search for En‐light‐enment!
Authors: Long Nicholas J. 
Published: January 2004

AbstractThe importance of nonlinear optical phenomena has been known for some time, however, since the mid‐1980s, there has been an explosion of interest in the search for and development of non‐linear optical materials that possess commercial device applications. To date, the systems have been utilized in information processing, optical switching, optical frequency conversion, and telecommunications, and with the advancing development of optotechnology, burgeoning demands for suitable materials are becoming apparent. Of the many systems studied for example inorganic crystals and semiconductors, organic crystalline monomers, and long‐chain polymers with delocalized π electrons, no one species has proved to be all‐encompassing, with advantages for one application being negated by disadvantages for another. This is likely to remain the case for the foreseeable future with the criteria of the application governing the type of material used. However, chemists are gradually elucidating what actually governs second‐ and third‐order nonlinear activity and thereby, tailoring species to show greater effects. In recent years, organometallic compounds, through their unique characteristics such as diversity of metals, oxidation states, ligands, and geometries, have found success and brought a new dimension to the area. This review attempts, with critical appraisal, to bring the discussion of organometallic nonlinear optical systems up to date, as well as giving a brief but general introduction to the field of nonlinear optics.For corrigendum see DOI:10.1002/anie.199508261
Toxins as Tools in Neurochemistry
Authors: Hucho Ferdinand 
Published: January 2004

AbstractNeurotoxins have evolved as molecules targeted specifically against molecules with an important function in the nervous system. Because of their selectivity they have been used as probes for detecting and characterizing key proteins of the nerve cell. Ion channels involved in the propagation of the action potential, proteins of presynaptic neurotransmitter exocytosis, and most importantly, neurotransmitter receptors have been and are presently being analyzed, in some cases already at atomic level by a combination of the tools of neurotoxins, molecular biology, and patch clamp electrophysiology. In this review a selection of these toxins is presented, together with their targets in the nervous system. Special emphasis is given to the recent breakthroughs in our understanding of the mechanism of action of tetanus and botulinum toxins and to the neurotoxins ranging from the plant alkaloid strychnine to the peptide toxins from poisonous snakes, which were fundamental in elucidating ligand‐gated ion channels like the glycine and nicotinic acetylcholine receptors.
Disulfide‐Reductase Inhibitors as Chemotherapeutic Agents: The Design of Drugs for Trypanosomiasis and Malaria
Authors: Schirmer R. Heiner , Müller Joachim G. , Krauth‐Siegel R. Luise 
Published: January 2004

AbstractViewed globally, parasitic diseases such as malaria and Chagas' cardiopathy pose an increasing threat to human health and welfare. Recognition of this problem and the challenge of synthesizing a quinine‐like antimalarial agent sparked off the development of the chemical industry about 100 years ago. Our contribution deals with aspects of drug design, a young branch of pharmaceutical chemistry. As drug targets the flavoenzyme, glutathione reductase, and the recently discovered parasite enzyme, trypanothione reductase, were chosen. Based on the knowledge of the structure of these molecules, the modeling of enzyme inhibitors as potential chemotherapeutic agents against parasites has become possible. In addition, biochemical and clinical observations are considered since chemical principles of biological evolution can serve as guidelines for the pharmaceutical chemists. The picture shows two erythrocytes destroyed by malaria parasites. In the center of the photograph a parasite is just leaving its host cell through the ruptured cell membrane. Its target could be a neighboring healthy erythrocyte.
Atom Economy—A Challenge for Organic Synthesis: Homogeneous Catalysis Leads the Way
Authors: Trost Barry M. 
Published: January 2004

AbstractEnhancing the efficiency of the synthesis of complex organic products constitutes one of the most exciting challenges to the synthetic chemist. Increasing the catalogue of reactions that are simple additions or that minimize waste production is the necessary first step. Transition metal complexes, which can be tunable both electronically and sterically by varying the metal and/or ligands, are a focal point for such invention. Except for catalytic hydrogenation, such methods have been rare in complex synthesis and virtually unknown for CC bond formation until the advent of cross‐coupling reactions. These complexes may orchestrate a variety of CC bond‐forming processes, important for creation of the basic skeleton of the organic structure. Their ability to insert into CH bonds primes a number of different types of additions to relatively nonpolar π‐electron systems. Besides imparting selectivity, they make feasible reactions that uncatalyzed were previously unknown. The ability of these complexes to preorganize π‐electron systems serves as the basis both of simple additions usually accompanied by subsequent hydrogen shifts and of cycloadditions. The ability to generate “reactive” intermediates under mild conditions also provides prospects for new types of CC bond‐forming reactions. While the examples reveal a diverse array of successes, the opportunities for new invention are vast and largely untapped.
Digitalis Research in Berlin–Buch—Retrospective and Perspective Views
Authors: Repke Kurt R. H. , Megges Rudolf , Weiland Jürgen , Schön Rudolf 
Published: January 2004

Abstract“The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.” These declarations, which stem from the famous book “An Account of the Foxglove and some of its Medical Uses” by physician William Withering in 1785 in which he introduced preparations from digitalis leaves in the therapy of dropsy (cardiac failure), are cited here by the senior author because of his awareness of the difficulties in presenting a balanced report on his life‐long research project on the further development of digitalis. His decision to devote himself to digitalis research originated at the bedside, when as a physician he experienced the grim final stages of cardiac failure in which no real help for the patients is possible. Unfortunately, his research project did not fit into the research program decreed by the Ministry of Science of the German Democratic Republic, so that he was ordered to stop the digitalis project in favor of biomembrane studies. Fortunately, he got round the ban simply by labeling the digitalis‐like acting steroids as probes for the cell membrane‐located Na+/K+‐transporting ATPase which he had just recognized as the digitalis target (receptor) enzyme. These and other ventures by the authors are collated here for the first time. The aim of this review is to foster straightforward research for solving a major challenge: the development of steroidal drugs for the prevention and cure of cardiac failure.
Probing Protein Structure and Function with an Expanded Genetic Code
Authors: Cornish Virginia W. , Mendel David , Schultz Peter G. 
Published: January 2004

AbstractA general biosynthetic method has been developed which makes it possible to site‐specifically incorporate unnatural amino acids with novel properties into proteins. In this approach the codon encoding the amino acid of interest is replaced with the “blank” nonsense codon UAG by oligonucleotide‐directed mutagenesis. A suppressor tRNA that recognizes this codon is generated by run‐off transcription and then chemically aminoacylated with the desired unnatural amino acid. Addition of the mutagenized gene and the aminoacylated suppressor tRNA to an in vitro extract capable of supporting protein biosynthesis generates a mutant protein containing the unnatural amino acid at the specified position. This methodology has recently been used to study the stability, specificity, and catalytic properties of a number of proteins. In these studies amino acids and analogues possessing altered hydrogen‐bonding, electronic, and steric properties and unique backbone conformations have all been site‐specifically incorporated into proteins. In addition, photoactivatable amino acids, isotopically labeled amino acids, and amino acids bearing biophysical probes have been inserted site‐specifically. This chemistry increases our ability to carry out detailed physical organic studies on this important class of macromolecules.
Preparative Solid‐State Chemistry with High‐Power CO2 Lasers
Authors: Möhr Sönke , Möller‐Buschbaum Hanskarl 
Published: January 2004

AbstractThe establishment of solid state chemistry as an independent field, which also has had a stimulating effect on material sciences, is a consequence of the experimental skill of chemists. The development of new methods led to an abundance of new compounds, the characteristic properties of which are linked with the solid state. The reaction temperature plays an important role in the synthesis of solid compounds; therefore, it is not surprising that a large number of the newly developed experimental techniques involve methods which can produce high temperatures on the openended temperature scale. Since the development of the CO2 laser, the solidstate chemist has an excellent heat source available, and with the power available today the range of high temperatures possible has been extended considerably. A way is now open for producing metastable, “entropy‐supported” high‐temperature compounds and substances with anomalous oxidation states and with macroscopic defects.
Carbon—Hydrogen Bonds of DNA Sugar Units as Targets for Chemical Nucleases and Drugs
Authors: Pratviel Geneviève , Bernadou Jean , Meunier Bernard 
Published: January 2004

AbstractThis review article focuses on the molecular aspects of DNA cleavage by synthetic chemical nucleases (transition metal complexes endowed with redox properties and DNA affinity) and natural drugs (cytotoxic agents such as bleomycins or enediynes). Unlike deoxyribonucleases, which catalyze the nucleophilic attack of water on the phosphorus atom of a particular phosphodiester entity, these nonhydrolytic DNA‐cleavers are able to oxidize the sugar units, generally by hydrogen atom abstraction. Examples of oxidative attack on each of the five different CH bonds of deoxyribose are known, depending on the nature, structure, type of activation, or mode of DNA interaction of the DNA‐cleaver. Further evolution at the site of the initial lesion leads to the release of bases, oxidized deoxyribose units, or oxidized sugar fragments appended to the base or the terminal phosphate. In most cases the loss of a part (at least) of a nucleoside, with the concomitant loss of one base information, primarily induces the cleavage of the DNA strand. For both types of DNA cleavage reagents studied within the two last decades, the modes of activation and DNA binding are presented, as well as the details on the mechanism of deoxyribose oxidative degration. Because of the need for highly efficient and highly specific reagents, the development of new artificial and selective DNA cleavers, supported by an improved knowledge of these different mechanisms of DNA cleavage, is to‐day a challenging area in the rational design of antitumoral or antiviral agents, as well as in the field of molecular biology.
Model Reactions for Photosynthesis—Photoinduced Charge and Energy Transfer between Covalently Linked Porphyrin and Quinone Units
Authors: Kurreck Harry , Huber Martina 
Published: January 2004

AbstractPhotosynthesis is one of the fascinating fields of current interdisciplinary research. It seems miraculous that nature, in the process of evolution, has managed to bring about the process of photosynthesis. The first step involves a charge separation at the reaction centers, which proceeds with 100% quantum yield from the photoexcited singlet state of the bacteriochlorophyll donor, despite the fact that the wasteful deactivation of the electron into the ground state should be highly favored. Biomimetic model compounds (that is, those which resemble the pigments nature has developed) have been constructed from porphyrins and quinones. These model systems have allowed the study of the factors contributing to the highly efficient charge separation. This report focuses on recent developments in the study of electron transfer in porphyrinoquinones. Some of the results of these investigations may not be not fully understood and are often the subject of controversial discussions.
Anticoagulatory Substances of Bloodsucking Animals: From Hirudin to Hirudin Mimetics
Authors: Dodt Johannes 
Published: January 2004

AbstractBloodsucking animals contain substances in their saliva that specifically interfere with the blood clotting system. These substances are mainly low molecular weight proteins with a molecular mass of between 4 and 50 kDa. Some have become accessible in large quantities with the help of genetic engineering, and as a result their structures and structure—activity relationships have been studied and clinically tested. In the light of what is known about the mode of action of these natural products at the molecular level, new compounds with possible therapeutic effect can be derived. In the last ten years this approach has been tested with the proteinase inhibitor hirudin, obtained from medicinal leeches, and with the thrombin/hirudin complex. The serine protease thrombin plays a central role in the complex pathway of the blood clotting process and its pathophysiological effect finally results in thrombosis. The selectivity of the formation of complexes from hirudin and thrombin lies in the bivalent interaction of the inhibitor with the active site of the enzyme as well as with a substrate recognition site outside of the active site, the so‐called fibrin‐(ogen) binding site (FBS). The knowledge of this mode of action enabled the synthesis of bifunctional thrombin inhibitors based on hirudin peptides. Hirudin and hirudin mimetics in vivo have been shown to be highly potent anticoagulants for the treatment of arterial and venous thrombosis.
Combinatorial Synthesis and Multidimensional NMR Spectroscopy: An Approach to Understanding Protein–Ligand Interactions
Authors: Chen James K. , Schreiber Stuart L. 
Published: January 2004

AbstractCombinatorial chemistry is a laboratory emulation of natural recombination and selection processes. Strategies in this developing discipline involve the generation of diverse, molecular libraries through combinatorial synthesis and the selection of compounds that possess a desired property. Such approaches can facilitate the identification of ligands that bind to biological receptors, promoting our chemical understanding of cellular processes. This article illustrates that the coupling of combinatorial synthesis, multidimensional NMR spectroscopy, and biochemical methods has enhanced our understanding of a protein receptor used commonly in signal transduction, the Src Homology 3 (SH3) domain. This novel approach to studying molecular recognition has revealed a set of rules that govern SH3–ligand interactions, allowing models of receptor–ligand complexes to be constructed with only a knowledge of the polypeptide sequences. Combining combinatorial synthesis with structural methods provides a powerful new approach to understanding how proteins bind their ligands in general.
The Catalytic Oxidative Coupling of Methane
Authors: Lunsford Jack H. 
Published: January 2004

AbstractOne of the great challenges in the field of heterogeneous catalysis is the conversion of methane to more useful chemicals and fuels. A chemical of particular importance is ethene, which can be obtained by the oxidative coupling of methane. In this reaction CH4 is first oxidatively converted into C2H6, and then into C2H4. The fundamental aspects of the problem involve both a heterogeneous component, which includes the activation of CH4 on a metal oxide surface, and a homogeneous gas‐phase component, which includes free‐radical chemistry. Ethane is produced mainly by the coupling of the surface‐generated CH radicals in the gas phase. The yield of C2H4 and C2H6 is limited by secondary reactions of CH radicals with the surface and by the further oxidation of C2H4, both on the catalyst surface and in the gas phase. Currently, the best catalysts provide 20% CH4 conversion with 80% combined C2H4 and C2H6 selectivity in a single pass through the reactor. Less is known about the nature of the active centers than about the reaction mechanism; however, reactive oxygen ions are apparently required for the activation of CH4 on certain catalysts. There is spectroscopic evidence for surface O− or O ions. In addition to the oxidative coupling of CH4, cross‐coupling reactions, such as between methane and toluene to produce styrene, have been investigated. Many of the same catalysts are effective, and the cross‐coupling reaction also appears to involve surface‐generated radicals. Although a technological process has not been developed, extensive research has resulted in a reasonable understanding of the elementary reactions that occur during the oxidative coupling of methane.
Ligand‐Accelerated Catalysis
Authors: Berrisford David J. , Bolm Carsten , Sharpless K. Barry 
Published: January 2004

AbstractThe search for new metal‐catalyzed asymmetric reactions has provided some fascinating insights into the effects imposed on the metal catalysts by chiral ligands. A practical consequence is the discovery of ligand‐accelerated catalysis (LAC). Thus, an existing catalyzed process is improved by the addition of a specific ligand, which leads to a faster, “ligand‐accelerated” reaction. Both homogeneous and heterogeneous catalysts are known to exhibit this behavior. The concept is especially valuable in reactions catalyzed by early transition metals, where dynamic ligand exchange processes require an efficient in situ self‐selection of a highly reactive catalyst from a variety of thermodynamically dictated assemblies. Results of detailed mechanistic studies will be presented, and the significance of LAC phenomena in transformations catalyzed by early and late transition metals will be discussed.
On the Synthesis of the FeMo Cofactor of Nitrogenase: Gene‐Controlled in Nature versus Laboratory‐Produced by Man
Authors: Müller Achim , Krahn Eugen 
Published: January 2004

AbstractOne of the primary challenges of chemistry is the controlled synthesis of compounds with tailor‐made structures and properties. Natural products serve as inspiration in this quest, ranging from biocatalysts with optimal selectivity and activity to “inorganic materials” with exceptional properties, whose generation can be described by the term biomineralization. It is of fundamental importance to comprehend the courses of events at the interface between gene expression and the subsequent processes of epigenesis that are no longer under gene control. Chemistry has been able to achieve many goals; however, in the area of controlled syntheses of highly complex, tailor‐made metal clusters, there is a lack of fundamental theories and principles. This is especially true for the fascinating metal–sulfur cluster of nitrogenase, which, in this enzyme, functions as the active center for the N2 reduction and, so far, has eluded all attempts to be synthesized in the laboratory. To understand the biosynthesis of this cluster, information from genetics and chemistry must be combined.
Basic Principles of Thermoanalytical Techniques and Their Applications in Preparative Chemistry
Authors: Cammenga Heiko Karl , Epple Matthias 
Published: January 2004

AbstractThe investigation of thermodynamic properties and reactivity yields interesting insights into the chemistry of newly synthesized substances. With thermal analysis extensive information can be gained from small samples (often only a few milligrams). In addition, the data obtained by thermal analysis can be used to plan and optimize a synthesis. Among the most important applications are identification and purity analysis, and the determination of characteristic temperatures and enthalpies of phase transitions (melting, vaporization), phase transformations, and reactions. Investigations into the kinetics of consecutive reactions and decomposition reactions are also possible. With the instruments available today such analyses can usually be performed quickly and easily. In this review the fundamentals of thermoanalytical methods are described and illustrated with selected examples of applications to low and high molecular weight compounds.
A Stable Aquairon(III) Complex with S = 1: Structure and Spectroscopic Properties
Authors: Bartos Michael J. , Kidwell Christopher , Kauffmann Karl E. , Gordon‐Wylie Scott W. , Collins Terrence J. , Clark George C. , Münck Eckard , Weintraub Susan T. 
Published: January 2004

AbstractFor corrigendum see DOI:10.1002/anie.199516491
Recent Trends in Photoaffinity Labeling
Authors: Kotzyba‐Hibert Florence , Kapfer Isabelle , Goeldner Maurice 
Published: January 2004

AbstractInvestigation of receptor—ligand interactions remains an inexhaustible challenge for chemists and biologists. Structural exploration of biological receptors is the starting point for a better understanding of how they function. Photoaffinity labeling is a biochemical approach to identify and characterize receptors targeting further structural investigations. The primary structure of a receptor protein was typically obtained by reverse genetics after exhaustive purification and sequencing of the N‐terminal peptide, which allowed the design of the corresponding oligonucleotide probes. Synthesis of these oligonucleotide probes then led to identification of cDNA clones by hybridization. Following this strategy, several membrane neurotransmitter receptors and constituent polypeptides, present in very small quantities in the central nervous system, were identified and their sequence deduced from the cDNA sequence. Since photoaffinity labeling implies the formation of a covalent bond between a radiolabeled ligand analogue and a receptor binding site, it becomes theoretically possible to isolate and sequence radiolabeled peptides and then synthesize the corresponding oligonucleotide probes. Photoaffinity labeling might avoid the critical solubilization and purification steps of the classical approach. To our knowledge, no such example of primary structure determination based on photoaffinity labeling experiments has been reported. However, the extraordinary developments in gene cloning technologies, in particular homology cloning and expression cloning, have made this approach obsolete and raised the question of new perspectives for photoaffinity labeling technology. In this article we present an update on selected original developments, as well as new challenges for this method. Photoaffinity labeling not only gives access to structural elements but is also a potential tool for the investigation of functional aspects of biological receptors, for example their role in signal transduction mechanisms.