Working tools for theoretical chemistry: Polanyi, eyring, and debates over the "semiempirical method"

Following along with the development of electron theory and quantum mechanics in the 1910s and 1920s, physical chemists began incorporating these new theories and approaches in their studies of activation energies, transition states, and chemical reactions for simple atomic and molecular systems. Among these chemists was Michael Polanyi, one of the founders of modern chemical dynamics, who collaborated with Henry Eyring in the development in the 1930s of a theory of the activated transition state and absolute reaction rates using potential energy surfaces and a semiempirical methodology. This paper examines the circumstances of their collaborative work, its reception, and its implications for further chemical research.     

Guest Editorial: The Professional Status of European Chemists and Chemical Engineers

Which country pays its chemists and chemical engineers the highest salaries? Where can I find a new job quickest? Which chemical sub‐discipline offers most jobs? Reliable answers for these and other questions have been derived from the first European employment survey for chemists and chemical engineers, which was carried out in 2013. Here we publish the first general evaluation of the results of this survey.     

Design and Application of an Easy to Use Oligonucleotide Mass Calculation Program

With the development of new synthesis procedures, an ever increasing number of chemical modifications can now be incorporated into synthetic oligonucleotides, representing new challenges for analytical chemists to efficiently identify and characterize such molecules. While conventional mass spectrometry (MS) has proven to be a powerful tool to study nucleic acids, new and improved methods and software are now needed to address this emerging challenge. In this report, we describe a simple yet powerful program that affords great flexibility in the calculation of theoretical masses for conventional as well as modified oligonucleotide molecules. This easy to use program can accept input oligonucleotide sequences and then calculate the theoretical mass values for full length products, process impurities, potential metabolites, and gas phase fragments. We intentionally designed this software so that modified nucleotide residues can be incorporated into oligonucleotide sequences, and corresponding mass values can be rapidly calculated. To test the utility of this program, two oligonucleotides that contain a large number of chemical modifications were synthesized. We have analyzed these samples using a Q-TOF mass spectrometer and compared the calculated masses to the observed ones. We found that all of the data matched very well with less than 30 ppm mass errors, well within the expectation for our instrument operated in its current mode. These data confirmed the validity of calculations performed with this new software.

Open-access liquid chromatography/mass spectrometry in a drug discovery environment

The use of open-access mass spectrometry to monitor synthetic chemistry reactions, and also the integrity and purity of new chemical entities, has been a part of the medicinal chemist's tool-box for more than 5 years. Originally in our group at Wyeth Research there were two open-access methods available to the chemists, flow injection analysis (FIA) and liquid chromatography/mass spectrometry (LC/MS). The FIA method was approximately 3 min long, while the LC/MS method was approximately 20 min long (including an 8 min gradient). Within the first 2 years, the total number of open-access analyses increased by approximately 125%. It is interesting, however, that the number of LC/MS analyses increased by more than 285%. This is attributed to the fact that the chemists began using the LC/MS data to monitor reactions and also to check final product integrity and purity. In addition, the number of chemists performing parallel synthesis reactions has increased; thus, individual chemists can produce sample sets of up to 100 vials. This paper describes the implementation of new methodology, which accommodates the need for much faster run times and also the ability to acquire alternating positive and negative ion spectra within the same run. In addition, the instrument has been configured to e-mail the resulting processed data report to the submitting chemist. Several methods have been developed, including structure elucidation using in-source collision-induced dissociation (CID) and night-time analysis. The LC/MS methods for this system are described herein and are applicable to both industrial and academic synthetic chemistry optimization efforts.     

Nuclear reactions: The forefront of nuclear science

The development of new heavy-ion accelerators has enabled a wider range of short-lived isotopes to be produced. To measure yields of these isotopes and study nuclear reaction mechanisms has demanded fast on-line chemical separations from chemists. This article reviews some of the techniques that have been introduced in recent years to achieve this. Reference is made to the use of on-line mass separators, helium gas jets and more classical methods carried out in second time scales.     

Online UV–visible spectroscopy and multivariate curve resolution as powerful tool for model-free investigation of laccase-catalysed oxidation

The laccase-catalysed transformation of indigo carmine (IC) with and without a redox active mediator was studied using online UV–visible spectroscopy. Deconvolution of the mixture spectra obtained during the reaction was performed on a model-free basis using multivariate curve resolution (MCR). Thereby, the time courses of educts, products, and reaction intermediates involved in the transformation were reconstructed without prior mechanistic assumptions. Furthermore, the spectral signature of a reactive intermediate which could not have been detected by a classical hard-modelling approach was extracted from the chemometric analysis. The findings suggest that the combined use of UV–visible spectroscopy and MCR may lead to unexpectedly deep mechanistic evidence otherwise buried in the experimental data. Thus, although rather an unspecific method, UV–visible spectroscopy can prove useful in the monitoring of chemical reactions when combined with MCR. This offers a wide range of chemists a cheap and readily available, highly sensitive tool for chemical reaction online monitoring.     

Solving chemical problems of environmental importance using cavity ring-down spectroscopy

Cavity ring-down (CRD) is a sensitive variant of traditional absorption spectroscopy that has found increasing use in a number of chemical measurement applications. This review focuses on applications of cavity ring-down spectroscopy that will be of interest to environmental chemists and analytical chemists working on environmental problems. The applications are classified into direct monitoring approaches, indirect analysis methods and ancillary studies and a differentiation is made between field-tested instruments and proof of principle studies.     

Microreaction Technology for Synthetic Chemistry

Microreaction technology as an emerging tool for synthetic chemistry has been extensively applied in academic and industrial researches. Normally, synthetic chemists used to running reactions in the classical glassware for centuries are unfamiliar and unaccustomed to use microreaction technology for routine synthetic work. This review tries to give a general introduction of the capabilities of microreaction technology. After introducing the origin and history of microreaction technology, we review and discuss mainly several synthetic examples of high T‐P reactions, hazardous reactions, flash chemistry, polymerization, photochemistry, electrochemistry and multistep API's syntheses to demonstrate the capabilities of microreactors. A summary and perspectives on microreactor technology are also given in this paper. It is anticipated that more and more chemists will understand the capabilities and limitations of microreaction technology, and could work together with chemical engineers for the synergic development of chemistry and chemical engineering.     

The atomic number revolution in chemistry: a Kuhnian analysis

This paper argues that the field of chemistry underwent a significant change of theory in the early twentieth century, when atomic number replaced atomic weight as the principle for ordering and identifying the chemical elements. It is a classic case of a Kuhnian revolution. In the process of addressing anomalies, chemists who were trained to see elements as defined by their atomic weight discovered that their theoretical assumptions were impediments to understanding the chemical world. The only way to normalize the anomalies was to introduce new concepts, and a new conceptual understanding of what it is to be an element. In the process of making these changes, a new scientific lexicon emerged, one that took atomic number to be the defining feature of a chemical element.     

A Biocompatible Alkene Hydrogenation Merges Organic Synthesis with Microbial Metabolism

Organic chemists and metabolic engineers use orthogonal technologies to construct essential small molecules such as pharmaceuticals and commodity chemicals. While chemists have leveraged the unique capabilities of biological catalysts for small‐molecule production, metabolic engineers have not likewise integrated reactions from organic synthesis with the metabolism of living organisms. Reported herein is a method for alkene hydrogenation which utilizes a palladium catalyst and hydrogen gas generated directly by a living microorganism. This biocompatible transformation, which requires both catalyst and microbe, and can be used on a preparative scale, represents a new strategy for chemical synthesis that combines organic chemistry and metabolic engineering.     

Issues in mass spectrometry between bench chemists and regulatory laboratory managers: summary of the roundtable on mass spectrometry held at the 123rd AOAC International Annual Meeting

At the 123rd AOAC International Annual Meeting in Philadelphia, PA, 45 residue chemists gathered for a roundtable discussion of mass spectrometry (MS) used for regulatory chemical residues analysis. The session was conceived to address current technical and communication issues about MS between "bench chemists and their bosses". The topics covered a range of practical, routine, and recurring issues on capabilities and limitations of MS techniques, and suggestions on how chemists may better communicate their MS results with customers. The customers in this sense include laboratory managers, quality assurance officers, laboratory clients, regulatory officials, policy-makers, lawyers, and others who have interest in the data. The stated goals devised by the roundtable panelists were to provide independent advice, describe limitations, give practical tips, help set realistic expectations, and answer questions from the attendees. The panelists divided the topics into three main themes: practical aspects in routine analysis using MS, choice of MS technique depending on the purpose for analysis, and qualitative identification and confirmation concepts. This report was written to summarize and expand upon the discussion, frame the current issues, and provide advice on handling common situations in MS analysis and reporting of results. Topics included LODs, data quality objectives, quantification and reporting results, matrix effects, calibration, terminology, differences in performance across MS platforms, proficiency testing, qualitative analysis, and laboratory accreditation. Conclusions are presented as a set of questions for structuring a dialog between bench chemists and laboratory managers.     

InfVis--platform-independent visual data mining of multidimensional chemical data sets

The tremendous increase of chemical data sets, both in size and number, and the simultaneous desire to speed up the drug discovery process has resulted in an increasing need for a new generation of computational tools that assist in the extraction of information from data and allow for rapid and in-depth data mining. During recent years, visual data mining has become an important tool within the life sciences and drug discovery area with the potential to help avoiding data analysis from turning into a bottleneck. In this paper, we present InfVis, a platform-independent visual data mining tool for chemists, who usually only have little experience with classical data mining tools, for the visualization, exploration, and analysis of multivariate data sets. InfVis represents multidimensional data sets by using intuitive 3D glyph information visualization techniques. Interactive and dynamic tools such as dynamic query devices allow real-time, interactive data set manipulations and support the user in the identification of relationships and patterns. InfVis has been implemented in Java and Java3D and can be run on a broad range of platforms and operating systems. It can also be embedded as an applet in Web-based interfaces. We will present in this paper examples detailing the analysis of a reaction database that demonstrate how InfVis assists chemists in identifying and extracting hidden information.     

Microwave-Assisted Synthesis: Can Transition Metal Complexes Take Advantage of This “Green” Method?

Microwave-assisted synthesis is considered environmental-friendly and, therefore, in agreement with the principles of green chemistry. This form of energy has been employed extensively and successfully in organic synthesis also in the case of metal-catalyzed synthetic procedures. However, it has been less widely exploited in the synthesis of metal complexes. As microwave irradiation has been proving its utility as both a time-saving procedure and an alternative way to carry on tricky transformations, its use can help inorganic chemists, too. This review focuses on the use of microwave irradiation in the preparation of transition metal complexes and organometallic compounds and also includes new, unpublished results. The syntheses of the compounds are described following the group of the periodic table to which the contained metal belongs. A general overview of the results from over 150 papers points out that microwaves can be a useful synthetic tool for inorganic chemists, reducing dramatically the reaction times with respect to traditional heating. This is often accompanied by a more limited risk of decomposition of reagents or products by an increase in yield, purity, and (sometimes) selectivity. In any case, thermal control is operative, whereas nonthermal or specific microwave effects seem to be absent.     

Chemistry and Dual Use: From Scientific Integrity to Social Responsibility

Ethical aspects of chemical activity are often exclusively located in the field of scientific integrity and good scientific practice. Yet, there is another dimension of ethics in chemistry that is not covered by research ethics: the impact of chemical scientific and technological progress on society and environment. Here, especially, the dual character of manifestations of chemical progress (new compounds, materials, and processes) is discussed. This essay aims at clarifying the roles, responsibilities, and chances of chemists to contribute to the assessment and management of dual use risks. Its main argument is that the framework for an efficient risk assessment has been established in science and technology governance, based on the sustainability concept. Without having to worry about exceeding their core competences too much – as in ‘Ethics is not my business!’ – chemists’ expertise and knowledge plays a crucial role in tackling the most urging issues of our times as part of a larger interdisciplinary endeavour.     

The Use of One-Electron Quantum Numbers to Describe Polyelectronic Systems

Atomic states are rigorously characterized by the total orbital angular momentum and the total spin angular momentum, but chemists persist in the use of electron configurations based on one-electron quantum numbers and simplified rules for predicting ground state configurations. This practice is defended against two lines of criticism, and its use in teaching chemistry is encouraged with the claim that the inductive approach of Mendeleev and the deductive approach initiated by Schrödinger compose the consummate example of that interaction of empirical and rational epistemologies that defines how chemists think.     

Artificial Signal Transduction

Communication between and inside cells as well as their response to external stimuli relies on elaborated systems of signal transduction. They all require a directional transmission across membranes, often realized by primary messenger docking onto external receptor units and subsequent internalization of the signal in form of a released second messenger. This in turn starts a cascade of events which ultimately control all functions of the living cell. Although signal transduction is a fundamental biological process realized by supramolecular recognition and multiplication events with small molecules, chemists have just begun to invent artificial models which allow to study the underlying rules, and one day perhaps to rescue damaged transduction systems in nature. This review summarizes the exciting pioneering efforts of chemists to create simple models for the basic principles of signal transduction across a membrane. It starts with first attempts to establish molecular recognition events on liposomes with embedded receptor amphiphiles and moves on to simple transmembrane signaling across lipid bilayers. More elaborated systems step by step incorporate more elements of cell signaling, such as primary and secondary messenger or a useful cellular response such as cargo release.     

Switch in Selectivity for Formal Hydroalkylation of 1,3-Dienes and Enynes with Simple Hydrazones

Controlling reaction selectivity is a permanent pursuit for chemists. Regioselective catalysis, which exploits and/or overcomes innate steric and electronic bias to deliver diverse regio-enriched products from the same starting materials, represents a powerful tool for divergent synthesis. Recently, the 1,2-Markovnikov hydroalkylation of 1,3-dienes with simple hydrazones was reported to generate branched allylic compounds when a nickel catalyst was used. As part of the effort, shown here is that a complete switch of Markovnikov to anti-Markovnikov addition is obtained by changing to a ruthenium catalyst, thus providing direct and efficient access to homoallylic products exclusively. Isotopic substitution experiments indicate that no reversible hydro-metallation across the metal-π-allyl system occurred under ruthenium catalysis. Moreover, this protocol is applicable to the regiospecific hydroalkylation of the distal C=C bond of 1,3-enynes.     

The application of ToF-SIMS to the analysis of herbicide formulation penetration into and through leaf cuticles

Understanding the movement of the active ingredient in relation to the other formulation components following application is crucial to an overall understanding of herbicide performance. We describe the novel use of time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a tool for following the movement of herbicide formulation components into and across plant cuticles. This technique provides new insights since it provides both high (sub-micron) spatial resolution combined with the chemical specificity associated with organic mass spectrometry. The components studied include the oligomeric ethoxylate surfactants Synperonic A7 and A20 and active ingredient Sulfosate (trimesium glyphosate). The movement of these molecules, both separately and when combined in a simple formulation, into the surface of Prunus laurocerasus leaves and across the isolated plant cuticle was investigated and clear differences in penetration/diffusion behaviour were identified. ToF-SIMS was uniquely able to (simultaneously) spatially resolve all the species involved, including the anion and cation components of the active ingredient. Also, using spectral reconstructions from the imaging raw data streams, the behaviour of individual oligomers within the surfactant distributions, could be assessed. The observations are discussed with reference to the action of surfactants identified in parallel micro-structural studies and the current understanding of herbicide uptake.     

Connecting the philosophy of chemistry,green chemistry,and moral philosophy

This paper aims to connect philosophy of chemistry, green chemistry, and moral philosophy. We first characterize chemistry by underlining how chemists: (1) co-define chemical bodies, operations, and transformations; (2) always refer to active and context-sensitive bodies to explain the reactions under study; and (3) develop strategies that require and intertwine with a molecular whole, its parts, and the surroundings at the same time within an explanation. We will then point out how green chemists are transforming their current activities in order to act upon the world without jeopardizing life. This part will allow us to highlight that green chemistry follows the three aforementioned characteristics while including the world as a partner, as well as biodegradability and sustainability concerns, into chemical practices. In the third part of this paper, we will show how moral philosophy can help green chemists: (1) identify the consequentialist assumptions that ground their reasoning; and (2) widen the scope of their ethical considerations by integrating the notion of care and that of vulnerability into their arguments. In the fourth part of the paper, we will emphasize how, in return, this investigation could help philosophers querying consequentialism as soon as the consequences of chemical activities over the world are taken into account. Furthermore, we will point out how the philosophy of chemistry provides philosophers with new arguments concerning the key debate about the ‘intrinsic value’ of life, ecosystems and the Earth, in environmental ethics. To conclude, we will highlight how mesology, that is to say the study of ‘milieux’, and the concept of ‘ecumeme’ proposed by the philosopher and geographer Augustin Berque, could become important both for green chemists and moral philosophers in order to investigate our relationships with the Earth.