Physical Chemistry meets Organic Chemistry: Special Issue on Physical Organic Chemistry in ChemPhysChem.

Physical organic chemistry is broadly defined and of fundamental importance for the development of interdisciplinary areas that link together chemical synthesis and biological and material sciences with theoretical and physical chemistry. In its classical sense, physical organic chemistry can be defined as the study ofmechanism, reactivity, structure, and binding in organic systems, which leads to the quantitative understanding of their properties at the molecular level. Modern physical organic chemistry also encompasses a wider range of contexts and interactions, which extend beyond reaction pathways. Some important current topics include supramolecular interactions and molecular recognition, aggregation and reactivity, computation of reaction pathways, reactions and catalysis in biology, materials where molecular structure controls function, structure activity correlations, mechanisms in synthesis and catalysis, and interactions and reactivity in organised assemblies and interfaces. The program of the Gordon Research Conference on Physical Organic Chemistry (conference title: Understanding Chemical Reactivity – New Concepts and Applications), which was held in June 2013 at the Holderness School, New Hampshire, USA, spanned the wide area of modern physical organic chemistry. This Research Front on physical organic chemistry is dedicated to this highly interdisciplinary field by showcasing research that ranges from mechanistic organic and bio-organic chemistry to materials chemistry. Fluorescence spectroscopy is a powerful method for monitoring conformational changes in proteins and protein–protein associations. Petersson and co-workers describe in their review strategies for labelling proteins with fluorescence probes with a particular focus on evaluating the balance between size and utility of the fluorophores, since large sizes can be disruptive to the protein’s fold or function, but on the other hand provides valuable characteristics such as visible wavelength absorption and emission or brightness. Formation of C–C bonds mediated by transition metals are amongst the most important reactions in organic synthesis. The search for new types of reactions requires a detailed understanding of the mechanism of these reactions. O’Hair and colleagues have used multi-stage mass spectrometric techniques to obtain mechanistic insight of the cobalt-mediated Glaser-type decarboxylative homocoupling of alkynyl carboxylic acids. These studies revealed that dinuclear cobalt clusters are superior to mononuclear complexes at promoting both decarboxylation steps as well as the reductive coupling itself. Reversible bond formation and dissociation of radical species (p-dimers) in solution phase can be applied to control the mechanical motion of molecules. Nishinaga and co-workers studied the diradical character of benzoand naphtho-annelated thiophene-pyrrole mixed oligomer dications and their application in p-dimer based supramolecular chemistry. Organic semiconductors have become increasingly important as substitutes for conventional inorganic materials. Jeffries-EL and co-workers have explored the optoelectronic properties of two-dimensional cross-shaped ‘cruciform’ molecules possessing two extended conjugation axes, which enable independent manipulation of the HOMO and LUMO levels by incorporating electron-donating and -withdrawing substituents at different positions along the two axes. This selection of invited papers in this Research Front is just a snapshot of the variety of research that is currently being performed under the broad category ‘physical organic chemistry’. It is this diversity of science and the constant developments that will keep this field exciting in the future.

Professor William I. Higuchi: Teacher and Scientist

The effects of substitution on reaction rates are at the heart of both physical chemistry and organic chemistry. In this paper, we present a computational laboratory module to explore the effects of group substitution and isotopic substitution on reaction rates by using a readily accessible graphical interface, a computational engine, and spreadsheet software. The module focuses on simple unimolecular isomerization reactions, often used as a classic example for kinetics in first-year, organic, and physical chemistry courses. In the context of a physical or physical organic chemistry course, the module is used to illustrate substituent and/or isotope effects on reaction rates, as well as chemical reaction rate calculations.

Physical organic chemistry – the study of the interplay between structure and reactivity in organic molecules – underpins organic chemistry, and we cannot imagine organic chemistry as a subject without knowledge of mechanism and reactivity. It is sometimes thought that the golden age of ‘physical organic chemistry’ was in the 20th century, when systematic information about mechanism first burst onto the scene. Certainly the impact of early knowledge of mechanism of fundamental aliphatic substitution reactions, among others, was enormous, but our knowledge of reactivity and mechanism has continued to progress and deepen enormously ever since and this has been reflected in a number of Nobel Prizes in Chemistry. In an area of particular interest to me, the transformation of radical chemistry from being an almost impenetrable area to one that can be usefully harnessed even in synthetic applications, has been extraordinary – this transformation has been relatively recent and has been principally dependent on the accurate determination of kinetics of radical reactions. Applications to complex reactions in biology, polymer chemistry and electronic materials are ever more prevalent, and add to contributions in ‘small molecule’ chemistry. Novel experimental techniques combined with the revolution in computational chemistry give new impetus to physical organic chemistry and contribute to its continuing importance, an importance that is reflected in the large number of international meetings in physical organic chemistry in the past two years. I am privileged to act as Guest Editor for this Thematic Series of the Beilstein Journal of Organic Chemistry, and hope that you enjoy the papers that form this issue. I am grateful to the contributors for their contributions. John A. Murphy Glasgow, November 2010

The techniques and thought processes of the field of physical organic chemistry, focused on small organic molecule structure and reactivity, have been taken up by numerous other fields, including, but not limited to, sensor design, organometallics, organic materials, organocatalysis, and supramolecular chemistry. The unifying principles of each field stem from physical organic chemistry pursuits. The insights, terminology, and lessons, as well as the experimental and computational techniques of physical organic chemistry currently permeate nearly all fields of organic chemistry. Thus, although the number of individuals that call themselves physical organic chemists is dwindling, we should recognize this as the inevitable outcome, revealing the strength of the discipline—it is so powerful that all areas of organic chemistry have adopted it, and therefore, we are all physical organic chemists at heart. This manuscript sets forth to highlight this conclusion by showing how several recent studies in fields not historically recognized as physical organic can be described as being so. The message is upbeat; organic chemists have a common background and language that emanates from physical organic chemistry, irrespective of the titles we each associate ourselves with.

Physical organic chemistry (POC) and reactive intermediate chemistry (RIC) belong to the core subjects of organic chemistry. During the 1990s and 2000s both had become increasingly less fashionable, and in many countries, the mass of active researchers working in POC and RIC was in danger of becoming subcritical. Consequently, in 2003, the Whitesides-Report on the status of chemistry in Great Britain pointed out shortcomings in POC. These shortcomings bore implications reaching beyond academia: in chemical industry, chemists with excellent skills in mechanistic organic chemistry are needed for many tasks, but an insufficient number were being educated. As a consequence of the Whitesides-Report, the Engineering and Physical Sciences Research Council of the UK (EPSRC) funded two Centres for Physical Organic Chemistry, one in Cardiff, and one in Glasgow, and launched two calls for research proposals in POC. Research into reactive intermediates has historically been part of the work involved in product studies. In order to characterise a reactive intermediate, it had to be trapped. Thus, in order to characterise a carbene, for example, one would intercept it with an alkene and isolate the resulting cyclopropane. Using internal quenchers (molecular clocks) providing well-defined competing reactions, product studies can even yield accurate values for the kinetics of intermolecular quenching reactions of reactive intermediates. More recent techniques to characterise reactive intermediates include matrix isolation spectroscopy, where a reactive intermediate is generated in a cryogenic noble-gas matrix and hence can be studied for an extended period of time; or laser flash photolysis, where the reactive intermediate is generated by a very short pulse of laser light, and can be investigated in real time; or specialised mass-spectrometric techniques such as ion cyclotron resonance MS. Due to the exponential increase in computing power available to researchers, much of the mechanistic work nowadays is done using the tools of quantum chemistry. In particular, the various flavours of density functional theory have proven valuable in this respect, but high-level correlated methods such as CCSD(T) also have their place. This Thematic Series of the Beilstein Journal of Organic Chemistry is meant to highlight recent developments in the chemistry of reactive intermediates, and to illustrate the current state of the art in a number of very varied research fields. Gotz Bucher Glasgow, March 2013

The sub-discipline of physical organic chemistry, a hybrid of organic and physical chemistry, made the study of the mechanisms of chemical reactions its task, using kinetics as the main tool. Perusal of the monograph by N. V. Sidgwick, Organic Chemistry of Nitrogen, which fulfils an explicit research programme in physical organic chemistry, serves here as an index to the status of this sub-discipline at the turn of the twentieth century. Many among the major concepts not only were fully formed, they were operative too. Sidgwick's book is at the root of the organized study of organic reaction mechanisms. This paternity begs to be more generally recognized. That this is not yet the case is due to Sidgwick's name having been associated almost exclusively to his later work, when he helped to usher in quantum chemical ideas. It is thus concluded that the mechanistic paradigm was already in place by 1910.

Original documents by L. P. Hammett and C. K. Ingold are presented which elucidate the origin of physical organic chemistry in the late 1920s and early 1930s. The field gained fast popularity, and within four decades created the presently accepted mechanistic model of organic chemistry. As the focus of research in organic chemistry shifted to synthesis around 1970, physical organic chemistry lost visibility, though mechanistic investigations became integral aspects of synthetic method development. While important subdisciplines of physical organic chemistry, e. g., supramolecular chemistry or mechanistic enzymology, continued to develop under separate headings, the systematic use of newly developed techniques (gas phase chemistry, laser spectroscopy, matrix isolation) is expected to lead to a renaissance of classical physical organic chemistry.

The 15th International Conference on Physical Organic Chemistry (ICPOC 15) was held on the west coast of Sweden in the heart of Scandinavia in central Göteborg on 8–13 July 2000 in the middle of the summer. The conference was the first in the series to be held in the Nordic countries of Europe. IUPAC Conferences on Physical Organic Chemistry are for physical organic chemists working in all fields of science and its applications. ICPOC 15 covered progress in physical organic chemistry and emphasized its interaction with other sciences.In particular, those ways in which physical organic chemistry has crept into some "hot "fields were highlighted. The conference attracted 268 active participants and 51 accompanying persons. The program comprised 14 plenary lectures, 30 invited lectures, 75 oral contributions, 119 poster presentations, and 3 after-lunch concerts. The organizers are grateful for support from IUPAC, The Royal Swedish Academy of Sciences through its Nobel Institute for Chemistry, The Swedish National Committee for Chemistry, The Swedish Chemical Society, and Organic Chemistry at Göteborg University. Per Ahlberg Chairman, ICPOC 15

Chemical Biology: Powerful Synergy Between Two Cultures

Abstract

The 19th IUPAC Conference on Physical Organic Chemistry (ICPOC-19) was held at the University of Santiago de Compostela, Santiago, Spain, 13-18 July 2008 under the local auspices of the Universities of Santiago, A Coruña, and Vigo. About 400 delegates attended ICPOC-19 from 39 countries, to participate in a scientific program comprising 11 plenary lectures, 22 invited lectures, 102 oral communications, and 224 posters. Physical organic chemistry, the study of the interrelationships between structure and reactivity in organic molecules, is a relatively young subfield of organic chemistry. At the end of the 20th century, there was a perception by some that chemists thoroughly understood organic reactivity and that there were no important problems left. This view ignores the fact that while the rigorous treatment of structure and reactivity in organic structures that is the field‚Äôs hallmark continues, physical organic chemistry has expanded to encompass other disciplines. In fact, the application of quantitative tools taken (historically) from physical chemistry to the solution of problems in mechanisms or in understanding properties has evolved to complex molecular problems, and is now being applied in studying catalysis, biochemistry, photochemistry, reactivity in the vapor phase, surface science, materials sciences, and other areas. Indeed, when considering a nice article on molecular biology, drug design, nanosystems, and catalysis, we observe that the experimental interpretation is based on a physical organic chemistry approach. This issue of Pure and Applied Chemistry contains 15 contributions corresponding to plenary and invited lectures presented at ICPOC-19: Symmetry of hydrogen bonds (C. Perrin, USA); Stabilizing reactive intermediates through site isolation (C. Copéret, France); Divalent carbon(0) compounds (G. Frenking, Germany); NMR spectroscopy and ion pairing: Measuring and understanding how ions interact (P. Pregosin, Switzerland); Photochemical routes to metal nanoparticles (J. Scaiano, Canada); Proton transfers in aromatic systems. How aromatic is the transition state? (C. Bernasconi, USA); How to predict changes in solvolysis mechanisms (H. Mayr, Germany); Kinetics and mechanism of the aminolysis of thioesters and thiocarbonates in solution (E. Castro, Chile); Understanding solvation (O. El Seoud, Brazil); Steric and electronic effects in SN2 reactions (E. Uggerud, Norway); Design of carborane molecular architectures with electronic structure computations: From endohedral and polyradical systems to multidimensional networks (J. Oliva, Spain); Mapping catalytic promiscuity in the alkaline phosphatase superfamily (F. Hollfelder, UK); DNA nucleobases properties and photoreactivity: Modeling environmental effects (L. Serrano-Andrés, Spain); Molecular organization and recognition properties of amphiphilic cyclodextrins (R. de Rossi, Argentina); Ionic liquids: Solvation ability and polarity (C. Chiappe, Italy). The conference program, as reflected both by the plenary and invited lectures as well as the oral communications, illustrates both the old and the new trends covering different research areas such as: reaction mechanisms, computational chemistry, synthetic chemistry, catalysis, gas-phase reactions, surface chemistry, molecular machines, organometallic chemistry, nanoscience, green chemistry, colloidal chemistry, supramolecular chemistry, and biochemistry. Papers presented in this issue of Pure and Applied Chemistry are representative of the different topics covered by the conference. We hope that they will serve as a stimulus for work by future generations of physical organic chemists. Luis Garcia-Rio Conference Editor

Celebration of Inorganic Lives: Interview with F. Albert Cotton

Advances in Physical Organic Chemistry

The 18th International Conference on Physical Organic Chemistry (ICPOC-18) took place at the Gromada Hotel in Warsaw, Poland on 20-25 August 2006 under the local auspices of Warsaw University and the Polish Chemical Society. It was organized by a local Organizing Committee from the Department of Chemistry of Warsaw University led by Prof. Tadeusz M. Krygowski. Although physical organic chemistry began in the 1930s and at the beginning was concerned mostly with the mechanisms and kinetics of organic reactions and their dependence on structural and medium effects, a great extension of the field toward bioorganic, organic, organometallic, theoretical, catalytic, supramolecular, and photochemistry has been observed for decades now. Representative topics for modern physical organic chemistry include: reaction mechanisms; reactive intermediates; bioprocesses; novel structures; reactivity relationships; solvent, substituent, isotope, and solid-state effects; long-lived charges; sextet or open-shell species; magnetic, nonlinear optical, and conducting molecules; and molecular recognition. Contributions from all of these fields were presented. About 220 researchers, representing 31 countries, participated in the conference. The following eight plenary lectures were presented: R. Huber (Nobel laureate, Germany): "Molecular machines in biology" A. Yonath (Israel): "The spectacular ribosomal architecture: Nascent proteins voyage towards folding via antibiotics binding-pockets" P. Coppens (USA): "Time-resolved diffraction studies of molecular excited states and beyond" K. S. Kim (South Korea): "De novo design based on nano-recognition: Functional molecules/materials and nanosensors/nanodevices" I. P. Beletskaya (Russia): "Mechanistic aspects and synthetic application of carbon-carbon and carbon-heteroatom bonds formation in substitution and addition reactions catalyzed by transition-metal complexes" S. Fukuzumi (Japan): "New development of electron-transfer catalytic systems" D. Braga (Italy): "Making crystals from crystals: A green route to crystal engineering and polymorphism" L. Latos-Grażyński (Poland): "Carbaporphyrinoids: Exploring metal ion-arene interaction in a macrocyclic environment" Additionally, 17 invited talks and, during two parallel sessions, 51 oral communications were presented. There were more than 100 poster presentations. I am pleased to introduce a representative selection of outstanding papers based on plenary and invited lectures delivered at ICPOC-18. In addition to the contributions mentioned above, this volume contains: a discussion of modern understanding of aromaticity (P. Fowler, UK); fascinating studies of new mechanisms focused on reactive intermediates (R. Moss, USA); interpretation of acidity, basicity, and hydride affinity by the trichotomy paradigm (Z. Maksić, Croatia); a quantum approach to proton transfer across hydrogen bond (F. Fillaux, France); a discussion of self-assembly of nickel(II) pseudorotaxene nanostructures on Au surface (R. Bilewicz, Poland); a discussion of synthesis and properties of macrocyclic receptors for anions (J. Jurczak, Poland); a description of novel organic-inorganic frameworks (J. Klinowski, UK); an application of microemulsions as microreactors (J. R. Leis, Spain); a discussion of silicon rehybridization and molecular rearrangements in hypercoordinate silicon dichelates (D. Kost, Israel); and a description of solvation in pure and mixed solvents (O. El Seoud, Brazil). All of these papers exemplify the broad range and diversity of interests of the participants and characterize the present and future challenges in physical organic chemistry. The social program of the conference included: a welcome reception; a Chopin music concert organized in cooperation with the Frederic Chopin Society; conference excursions, including Warsaw Old Town and Żelazowa Wola, the house where Chopin was born; the Warsaw Uprising (1944) Museum and the Heroes of Ghetto Memorial; and folk music dances during the conference dinner. Because ICPOC-18 was attended by quite a number of young chemists from all over the world, it can be expected that the next conference in this series, ICPOC-19, which will be held in July 2008 and is being organized by Profs. J. Ramon Leis from the University of Santiago de Compostela and A. Santaballa from the University of A Coruna (Spain), will not only reflect recent developments and the rich potential of physical organic chemistry, but will also demonstrate the aspirations of younger generations of scientists in this field. Krzysztof Woźniak Conference Editor