Instruments and rules: R. B. Woodward and the tools of twentieth-century organic chemistry

The paper illustrates how organic chemists dramatically altered their practices in the middle part of the twentieth century through the adoption of analytical instrumentation — such as ultraviolet and infrared absorption spectroscopy and nuclear magnetic resonance spectroscopy — through which the difficult process of structure determination for small molecules became routine. Changes in practice were manifested in two ways: in the use of these instruments in the development of ‘rule-based’ theories; and in an increased focus on synthesis, at the expense of chemical analysis. These rule-based theories took the form of generalizations relating structure to chemical and physical properties, as measured by instrumentation. This ‘Instrumental Revolution’ in organic chemistry was two-fold: encompassing an embrace of new tools that provided unprecedented access to structures, and a new way of thinking about molecules and their reactivity in terms of shape and structure. These practices suggest the possibility of a change in the ontological status of chemical structures, brought about by the regular use of instruments. The career of Robert Burns Woodward (1917–1979) provides the central historical examples for the paper. Woodward was an organic chemist at Harvard from 1937 until the time of his death. In 1965, he won the Nobel Prize in Chemistry.     

Die Sofortwirkung des Thyroxins und ihre klinische Bedeutung

Summary Former investigations have shown, that Thyroxine does not accelerate directly oxidations but the fermentations and that combustions are increased by the breakdown products only. That is why Thyroxine cannot act from the blood, for on the surface of the cells fermentations are stopped by the oxidations because of the Pasteur reaction. Therefore Thyroxine must reach the O₂-poor interior of cells by means of the peripheral nerves. If it is so then in case of the damage of the cells—which is followed as known by the paralysis of the Pasteur reaction—Thyroxine must act directly from the blood without any latency, for then fermentations are no longer stopped at the surface of the cells. The experiments have shown indeed, that if you produce by anemia on white rats a lack of oxygen, Thyroxine increases the oxidations up to 50% already in about 30 minutes which in the case of normal animals cannot be expected before 24 hours. It is probable that in the case of the general damage of cells (serious anemia, uncompensated heart defects, tumors) the noticeable loss in weight and cachexia are conditioned by that Thyroxine which circulates in the blood-stream and they may be cured by remedies such as Thiouracil or Thermothyrine.     

Chemical explanation and physical dynamics: Two research schools at the First Solvay chemistry conferences, 1922–1928

The convening of the first three Solvay Chemistry Conferences in Brussels from 1922–1928 marked an important turning point for the discipline of chemistry. Whereas much of nineteenth-century chemical endeavour had focused on compositional and functional analysis of chemical compounds, many leaders in chemistry were turning to questions of molecular dynamics by the early twentieth century. Two competing schools of chemical dynamics, which were represented at the Solvay Conferences, were a predominantly English group (Lowry, Lapworth, Robinson, Ingold) who worked out electron and ionic interpretations of organic reaction mechanisms, and a French group (Perrin, Job) who developed a generalized radiation hypothesis of reaction activation. While differences in conceptual and stylistic approach separated the two schools, they agreed on the need to apply contemporary physical theory to old chemical problems, and to develop a theoretical chemistry complementary to theoretical physics.     

Enzymatic hydroxylation of aromatic compounds

Selective hydroxylation of aromatic compounds is among the most challenging chemical reactions in synthetic chemistry and has gained steadily increasing attention during recent years, particularly because of the use of hydroxylated aromatics as precursors for pharmaceuticals. Biocatalytic oxygen transfer by isolated enzymes or whole microbial cells is an elegant and efficient way to achieve selective hydroxylation. This review gives an overview of the different enzymes and mechanisms used to introduce oxygen atoms into aromatic molecules using either dioxygen (O₂) or hydrogen peroxide (H₂O₂) as oxygen donors or indirect pathways via free radical intermediates. In this context, the article deals with Rieske-type and α-keto acid-dependent dioxygenases, as well as different non-heme monooxygenases (di-iron, pterin, and flavin enzymes), tyrosinase, laccase, and hydroxyl radical generating systems. The main emphasis is on the heme-containing enzymes, cytochrome P450 monooxygenases and peroxidases, including novel extracellular heme-thiolate haloperoxidases (peroxygenases), which are functional hybrids of both types of heme-biocatalysts. Received 11 August, 2006; received after revision 28 September 2006; accepted 9 November 2006     

生物催化的Baeyer-Villiger氧化反应研究

生物转化具有底物选择性、立构选择性、化学选择性、对映选择性等一般化学反应中不具备的优点，在精细化工中占有很大的优势，其中Baeyer-Villiger氧化反应在生物转化中占有很重要的地位，产生的许多中间体或产物可以被用来生产多种化学产品和药物，在工业生物催化中有很好的应用前景。本文主要对生物转化中的Baeyer-Villiger氧化反应在利用酶或细胞作为催化剂时存在的问题和解决方法以及基因技术的运用近况进行了综述。     

Paper tools in experimental cultures

The paper studies various functions of Berzelian formulas in European organic chemistry prior to the mid-nineteenth century from a semiotic, historical and epistemological perspective. I argue that chemists applied Berzelian formulas as productive ‘paper tools’ for creating a chemical order in the ‘jungle’ of organic chemistry. Beginning in the late 1820s, chemists applied chemical formulas to build models of the binary constitution of organic compounds in analogy to inorganic compounds. Based on these formula models, they constructed new classifications of organic substances. They further applied Berzelian formulas in a twofold way to experimentally investigate organic chemical reactions: as tools which supplemented laboratory tools and as tools for constructing interpretive models of organic reactions. The scrutiny of chemists' performances with chemical formulas on paper also reveals a dialectic which contributed considerably to the formation of the new experimental culture of synthetic carbon chemistry that emerged between the late 1820s and the early 1840s. In an unintended and unforeseen way, the tools reacted back on the goals of their users and contributed to conceptual development and a shift of scientific objects and practices (‘substitution’) which transcended the originally intended chemical order.     

Microbial energetics applied to waste repositories

Summary Through their catalytic abilities microbes can increase rates of chemical reactions which would take a very long time to reach equilibrium under abiotic conditions. Microbes also alter the concentration and composition of chemicals in the environment, thereby creating new conditions for further biological and chemical reactions. Rates of degradation and possible indirect consequences on leaching rates in waste repositories are a function of the presence or absence of microbes and of the conditions which allow them to become catalytically active.Microbially mediated reactions are no exception to the rule that all chemical processes are basically governed by thermodynamic laws. Naturally occurring processes proceed in the direction that leads to the minimal potential energy level attained when equilibrium is reached. A continuous supply of energy to an ecosystem in the form of biochemically unstable compounds maintains non-equilibrium conditions, a prerequisite for all chemotrophic life. Energy is released as a chemical reaction progresses towards equilibrium. Microbes scavenge that portion of the free energy of reaction (G_r) which can be converted into biochemically usable forms during the chemical oxidation processes. As electrontransfer catalysts, the microorganisms mediate reactions which are thermodynamically possible thereby stimulating reaction rates. Decomposition and mineralization in systems without a continuous supply of substrates and oxidants will lead to equilibria with minimal free energy levels at which point further microbial action would cease. The differences in the free energy levels of reactions (G_r), represent the maximal energy which is available to microorganisms for maintenance and growth. How much of the released free energy will be conserved in energy-rich bonds, compounds (e.g. ATP), and chemical potentials (e.g. emf) useful for biosynthesis and biological work is characteristic for the microbes involved and the processes and metabolic routes employed.Materials whose elements are not present in the most oxidized form attainable in the oxic environment of our planet are potentially reactive. Microbial activities are associated only with chemical reactions whose free energy changes are exergonic. This should be kept in mind for all investigations related to the role of microbes in repositories or in the layout of proper waste storage conditions. Rigorous application of thermodynamic concepts to environmental microbiology allows one to develop models and design experiments which are often difficult to conceive of in complex natural systems from physiological information alone. Thermodynamic considerations also aid in selecting proper deposition conditions and in carrying out thoughtful experiments in areas related to microbial ecology of waste repositories.     

Maternal signals for progeny prevention against allergy and asthma

Allergy and asthma are chronic inflammatory diseases which result from complex gene–environment interactions. Recent evidence indicates the importance of prenatal and postnatal developmental processes in terms of maturation of balanced immune responses. According to the current view, gene–environment interactions during a restricted time frame are responsible for programming of the immune system in favor of allergic immune mechanisms later in life. The interaction between genes and environment is complex and only partially understood; however, heritable epigenetic modifications including chemical additions in and alternative packaging of the DNA have been shown to play a crucial role in this context. Novel data indicate that epigenetic mechanisms contribute to the development of T-helper cell function. Environmental factors, including diesel exhaust particles (DEP), vitamins and tobacco smoke, operate through such mechanisms. Furthermore, the role of environmental microbes provides another and maybe even more important group of exogenous exposures which operates in this critical time frame.     

The CorA family: Structure and function revisited

The CorA family is a group of ion transporters that mediate transport of divalent metal ions across biological membranes. Metal ions are essential elements in most cellular processes and hence the concentrations of ions in cells and organelles must be kept at appropriate levels. Impairment of these systems is implied in a number of pathological conditions. CorA proteins are abundant among the prokaryotic organisms but homologues are present in both human and yeast. The activity of CorA proteins has generally been associated with the transport of magnesium ions but the members of the CorA family can also transport other ions such as cobalt and nickel. The structure of the CorA from Thermotoga maritima, which also was the first structure of a divalent cation transporter determined, has opened the possibilities for understanding the mechanisms behind the ion transport and also corrected a number of assumptions that have been made in the past.     

New insights into copper monooxygenases and peptide amidation: structure, mechanism and function

Many bioactive peptides must be amidated at their carboxy terminus to exhibit full activity. Surprisingly, the amides are not generated by a transamidation reaction. Instead, the hormones are synthesized from glycine-extended intermediates that are transformed into active amidated hormones by oxidative cleavage of the glycine N-C alpha bond. In higher organisms, this reaction is catalyzed by a single bifunctional enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The PAM gene encodes one polypeptide with two enzymes that catalyze the two sequential reactions required for amidation. Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) catalyzes the stereospecific hydroxylation of the glycine alpha-carbon of all the peptidylglycine substrates. The second enzyme, peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL; EC 4.3.2.5), generates alpha-amidated peptide product and glyoxylate. PHM contains two redox-active copper atoms that, after reduction by ascorbate, catalyze the reduction of molecular oxygen for the hydroxylation of glycine-extended substrates. The structure of the catalytic core of rat PHM at atomic resolution provides a framework for understanding the broad substrate specificity of PHM, identifying residues critical for PHM activity, and proposing mechanisms for the chemical and electron-transfer steps in catalysis. Since PHM is homologous in sequence and mechanism to dopamine beta-monooxygenase (DBM; EC 1.14.17.1), the enzyme that converts dopamine to norepinephrine during catecholamine biosynthesis, these structural and mechanistic insights are extended to DBM.     

The autonomy of models and explanation: anomalous molecular rearrangements in early twentieth-century physical organic chemistry

During the 1930s and 1940s, American physical organic chemists employed electronic theories of reaction mechanisms to construct models offering explanations of organic reactions. But two molecular rearrangements presented enormous challenges to model construction. The Claisen and Cope rearrangements were predominantly inaccessible to experimental investigation and they confounded explanation in theoretical terms. Drawing on the idea that models can be autonomous agents in the production of scientific knowledge, I argue that one group of models in particular were functionally autonomous from the Hughes–Ingold theory. Cope and Hardy’s models of the Claisen and Cope rearrangements were resources for the exploration of the Hughes–Ingold theory that otherwise lacked explanatory power. By generating ‘how-possibly’ explanations, these models explained how these rearrangements could happen rather than why they did happen. Furthermore, although these models were apparently closely connected to theory in terms of their construction, I argue that partial autonomy issued in extra-logical factors concerning the attitudes of American chemists to the Hughes–Ingold theory. And in the absence of a complete theoretical hegemony, a degree of consensus was reached concerning modelling the Claisen rearrangement mechanism.     

The literature and the science of ‘two cultures’ historiography

This paper discusses the historiography of the ‘two cultures’ controversy. C. P. Snow’s lament about the ‘two cultures’, literary and scientific, has inspired a wide range of comment—much of which begins by citing Snow and his thesis, before going on to discuss very different things. This paper focuses upon one strand of this commentary, the historical analysis of the controversy itself. A ‘historical’ analysis is defined here as one that resists the impulse to enter the argument on behalf of Snow or Leavis, to conceive of their argument in the terms that Snow defined, or to invoke their argument as a precursor to some contemporary issue. Instead, a historical interpretation registers distance between that day and this, takes the controversy itself as its object of study, and explores the tensions and associations that came to be packed into those now familiar terms. As the fiftieth anniversary of Snow’s Rede Lecture nears, this approach—rather than the repetition of clichés about the bridging of cultures—offers both analytical perspective on the controversy and interpretive possibilities for its examination.     

Ludwig Boltzmann and his influence on science

The life of Ludwig Boltzmann (20 February 1844–5 September 1906) and his influence on science is reviewed. This great Austrian scientist was not only the founder of statistical mechanics and a gifted experimentalist, but his pioneering ideas influenced all the physical sciences. In his honour, many Austrian research institutes carry his name. He had great influence on Albert Einstein whose first papers were, according to his own words, in the spirit of Boltzmann, and intended to proved the reality and the size of certain atoms using the molecular fluctuations postulated by Boltzmann. Max Planck was converted from a ‘Saulus’ to a ‘Paulus’ when he had to use Boltzmann's method to derive his famous law of radiation. In fact, Boltzmann had already used discrete energy levels as early as 1872. Yet his work was heavily criticized by the neopositivists around Ernst Mach and seemed to receive very little attention in the last years of his life when a great number of physicists did not believe in atoms. It is the tragedy of Boltzmann's life that he did not experience the glorius victory of his ideas, but died under the gloomy vision that the work of his whole life was doomed to oblivion.     

Atomism, Poincaré and Planck

Planck's change in attitude to the question of whether atomic hypotheses were scientifically accessible, is discussed. It is argued contra Holton, that Planck's change in attitude to this question did not signal a methodological shift towards realism. The point of doing this is not just to investigate a significant episode in the history of quantum theory, but also to use the episode as a case study in support of a broader historical thesis. This thesis is that there was a widespread late-nineteenth century methodological tradition which motivated the change in status of certain ontological claims — e.g., that atoms exist — from ‘inaccessible to science’ to ‘scientifically acceptable’ even though those claims were not strictly ‘observable’. This methodological tradition is a hybrid of positivist and realist views. Thus, contrary to one popular view, the fin de siécle triumph of atomism is not to be seen as a triumph for a realist view of science Poincare's views are also used as an illustration.     

Molecular recognition in applied enzyme chemistry

Molecular recognition impinges upon many fields of biological chemistry, especially those involving catalytic processes. This review gives examples from studies at Strathclyde of both small and macromolecular systems. Mechanism-based enzyme inhibitors are described with reference to dihydrofolate reductase, dihydroorotate dehydrogenase, and cholesterol metabolism. Applications of molecular recognition related to synthetic transformations are discussed in terms of aromatic substitution, chemically modified papain, and catalytic antibodies for Diels-Alder reactions.     

Molecular recognition in applied enzyme chemistry.

Molecular recognition impinges upon many fields of biological chemistry, especially those involving catalytic processes. This review gives examples from studies at Strathclyde of both small and macromolecular systems. Mechanism-based enzyme inhibitors are described with reference to dihydrofolate reductase, dihydroorotate dehydrogenase, and cholesterol metabolism. Applications of molecular recognition related to synthetic transformations are discussed in terms of aromatic substitution, chemically modified papain, and catalytic antibodies for Diels-Alder reactions.     

Collecting airs and ideas: Priestley’s style of experimental reasoning

It has often been claimed that Priestley was a skilful experimenter who lacked the capacities to analyze his own experiments and bring them to a theoretical closure. In attempts to revise this view some scholars have alluded to Priestley’s ‘synoptic’ powers while others stressed the contextual role of British Enlightenment in understanding his chemical research. A careful analysis of his pneumatic reports, privileging the dynamics of his experimental practice, uncovers significant yet neglected aspects of Priestley’s science. By focusing on his early experimental conduct and writing on nitrous air, I demonstrate how his methodological and rhetorical devices, far from being consequences of compulsive writing or theoretical naïveté, were deeply entwined with his chemical research. I employ the notion of ‘style of experimental reasoning’ (SER)—derived from A. C. Crombie and I. Hacking—to shed light on the intersection at which Priestley’s unique method, literary style, and epistemology converged to generate scientific knowledge. Establishing Priestley’s SER advances a finer understanding of the interactive character of his pneumatic experimentalism, peculiar dimensions of which have evaded both traditional as well as revisionist scholarship, thus infusing the longstanding historiographic debate over his scientific merits.     

Energy flow and community structure in freshwater ecosystems

The goal of this article is twofold: 1) It aims at providing an overview on some major results obtained from energy flow studies in individuals, populations, and communities, and 2) it will also focus on major mechanisms explaining community structures. The basis for any biological community to survive and establish a certain population density is on the one hand energy fixation by primary producers together with adequate nutrient supply and the transfer of energy between trophic levels (bottom-up effect). On the other hand, predator pressures may strongly control prey population densities one or more trophic levels below (top-down effect). Other interpopulation effects include competition, chemical interactions and evolutionary genetic processes, which further interact and result in the specific structuring of any community with respect to species composition and population sizes.