Volume 81, Issue 4

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 S N 2 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

A classic question regarding hydrogen bonds (H-bonds) concerns their symmetry. Is the hydrogen centered or is it closer to one donor and jumping between them? These possibilities correspond to single- and double-well potentials, respectively. The NMR method of isotopic perturbation can answer this question. It is illustrated with 3-hydroxy-2-phenylpropenal and then applied to dicarboxylate monoanions. The 18 O-induced 13 C NMR splittings signify that their intramolecular H-bonds are asymmetric and that each species is a pair of tautomers, not a single symmetric structure, even though maleate and phthalate are symmetric in crystals. The asymmetry is seen across a wide range of solvents and a wide variety of monoanions, including 2,3-di- tert -butylsuccinate and zwitterionic phthalates. Asymmetry is also seen in monoprotonated 1,8-bis(dimethylamino)naphthalenediamines, N , N' -diaryl-6-aminofulvene-2-aldimines, and 6-hydroxy-2-formylfulvene. The asymmetry is attributed to the disorder of the local environment, establishing an equilibrium between solvatomers. The broader implications of these results regarding the role of solvation in breaking symmetry are discussed. It was prudent to confirm a secondary deuterium isotope effect (IE) on amine basicity by NMR titration of a mixture of PhCH 2 NH 2 and PhCHDNH 2 . The IE is of stereoelectronic origin. It is proposed that symmetric H-bonds can be observed in crystals but not in solution because a disordered environment induces asymmetry, whereas a crystal can guarantee a symmetric environment. The implications for the controversial role of low-barrier H-bonds in enzyme-catalyzed reactions are discussed.

This overview describes the reaction of organometallics with oxide surfaces and the formation of highly reactive species. In the case of silica, the surface can be seen as a large siloxy ligand, which helps to stabilize reactive intermediates through site isolations. This is translated into very highly reactive and stable well-defined alkene metathesis catalysts as well as the formation of hydrides species, which display unusual reactivities toward alkanes (e.g., low-temperature hydrogenolysis and metathesis of alkanes). In the case of alumina, it allows the formation of highly reactive, but stable cationic species or masked carbenic species whose structures are unusual by comparison with molecular chemistry.

Quantum chemical studies show that there is a class of carbon compounds with the general formular CL 2 where the carbon atom retains its four valence electrons as two lone pairs. The C-L bonds come from L → C donor-acceptor interactions where L is a strong σ-donor. Divalent C(0) compounds (carbones) are conceptually different from divalent C(II) compounds (carbenes) and tetravalent carbon compounds, but the bonding situation in a real molecule may be intermediate between the three archetypes. There are molecules like tetraaminoallenes which may be described in terms of two double bonds (R 2 N) 2 C=C=C(NR 2 ) 2 where the extraordinary donor strength of the dicoordinated carbon atom comes only to the fore through the interactions with protons and Lewis acids. They may be considered as "hidden divalent C(0) compounds". The donor strength of divalent C(0) molecules has been investigated by calculations of the binding energies with protons and with main-group Lewis acids and the bond dissociation energies (BDEs) of transition-metal complexes.

Pulsed gradient spin-echo (PGSE) diffusion and Overhauser NMR data together with density functional theory (DFT) calculations afford a qualitative estimation of the amount of ion pairing, as well as insight into the structures of a variety of inorganic, organic, and organometallic salts.

The photochemistry of aromatic ketones through the Norrish type I cleavage of benzoins and via photoreduction generates ketyl radicals that readily reduce many metal ions, including silver and gold. Reduction to Au(0) and Ag(0) leads to the spontaneous formation of nanoparticles (NPs) in aqueous or micellar solutions. Careful consideration of kinetic factors to minimize triplet quenching by metal ions can lead to rapid NP generation. These materials are quite stable and have interesting reactivities due to the essentially unprotected characteristics of the surface.

The question as to what extent aromaticity in a reactant or product is expressed in the transition state of a reaction has only recently received serious attention. Inasmuch as aromaticity is related to resonance, one might expect that, in a reaction that leads to aromatic products, its development at the transition state should lag behind bond changes as is invariably the case for the development of resonance in reactions that lead to delocalized products. However, recent experimental and computational studies on proton transfers from carbon acids suggest the opposite behavior, i.e., the development of aromaticity at the transition state is more advanced than the proton transfer. The evidence for this claim is based on the determination of intrinsic barriers that show a decrease with increasing aromaticity. According to the Principle of Nonperfect Synchronization (PNS), this decrease in the intrinsic barrier implies a disproportionately large amount of aromatic stabilization of the transition state. Additional evidence for the high degree of transition state aromaticity comes from the calculation of aromaticity indices such as HOMA, NICS, and the Bird Index. Possible reasons why the degree to which aromaticity and resonance are expressed at the transition state is different are discussed.

Stopped-flow and laser flash techniques have been employed to investigate the individual steps of the solvolysis reactions of benzhydryl (diarylmethyl) halides and carboxylates. In this way, absolute rate constants for the ionization ( k 1 ), recombination of the carbocation with the leaving group ( k -1 ), and subsequent reaction with the solvent ( k SolvOH ) have been determined. As the stabilization of the carbocations increases, the mechanism changes from (a) S N 1 reactions with irreversible ionization through (b) S N 1 reactions with common-ion return and (c) S N 2C + reactions, where the intermediate carbocations accumulate, to (d) the formation of persistent carbocations which do not undergo subsequent reactions under the selected solvolysis conditions. The correlation equation log k = s ( N + E ), where the carbocations are characterized by the electrophilicity parameter E , and leaving groups and solvents are characterized by the nucleophile-specific parameters s and N can be employed to predict the changes of mechanism.

The aminolysis reactions of thioesters and thiocarbonates, in either aqueous solution or in 44 wt % aqueous ethanol at 25 °C, are subjected to a kinetic investigation. The Brønsted-type plots (lg k N vs. amine p K a , where k N is the nucleophilic rate constant) obtained for these reactions can be grouped in three categories: linear plots with slopes 0.8-1, biphasic plots (two linear portions and a curve in between), and linear plots with slopes 0.4-0.6. The two former plots are attributed to stepwise reactions through a zwitterionic tetrahedral intermediate. The latter plots are associated with a concerted mechanism. The fact that some reactions are stepwise and others concerted depends on the stability of the zwitterionic tetrahedral intermediate. This work shows how the experimental data allows one to assess the mechanism of these reactions. Also discussed are the factors that affect the stability of this intermediate, which in turn determines the pathway followed by the reaction. The factors analyzed in this work are (i) the leaving group of the substrate, (ii) the nature of the amine, (iii) the non-leaving group of the substrate, (iv) the electrophilic group of the substrate (CS vs. CO), and (v) the solvent.

The effects of solvents on different chemical phenomena, including reactivity, spectroscopic data, and swelling of biopolymers can be rationalized by use of solvatochromic probes, substances whose UV-vis spectra, absorption, or emission are sensitive to the properties of the medium. Thermo-solvatochromism refers to the effect of temperature on solvatochromism. The study of both phenomena sheds light on the relative importance of the factors that contribute to solvation, namely, properties of the probe, those of the solvent (acidity, basicity, dipolarity/polarizability, and lipophilicity), and the temperature. Solvation in binary solvent mixtures is complex because of "preferential solvation" of the probe by one component of the mixture. A recently introduced solvent exchange model is based on the presence in the binary solvent mixture of the organic component (molecular solvent or ionic liquid), S, water, W, and a 1:1 hydrogen-bonded species (S-W). Solvation by the latter is more efficient than by its precursor solvents, due to probe-solvent hydrogen-bonding and hydrophobic interactions; dimethyl sulfoxide (DMSO)-W is an exception. Solvatochromic data are employed in order to explain apparently disconnected phenomena, namely, medium effect on the pH-independent hydrolysis of esters, 1 H NMR data of water-ionic liquid (IL) mixtures, and the swelling of cellulose.

This article gives an overview of recently published literature on the factors that govern S N 2 reactivity. By comparing reactivity in solution with that in the isolated gas phase, it has become possible to dissect the contribution of the solvent from that of the intrinsic molecular properties. This has proven to be an extremely important and fruitful step forward in obtaining key knowledge not available before. The gas-phase studies have made it clear that organic chemists need to revise radically their concepts and ideas about this crucial reaction type. This is particularly true with regard to the commonly used term "steric effect".

The 12 cage-anchoring points of the very stable icosahedral ortho -, meta -, and para -carborane allow the design of multidimensional architectures provided new self-assembling routes are devised. We provide bases for constructing carborane molecular architectures through high-level quantum chemical computations. We consider ejection mechanisms for the inner atom/ion in endohedral carborane complexes, singlet-triplet energy gaps in carborane biradicals, as well as geometry reorganization in carborane neutral and dianionic triplet states. These features, explored in monomers, are starting points for the design of molecular architectures based on electronic structure properties of carborane assemblies.

"Promiscuous" enzymes possess activities in addition to their native ones. Promiscuous activities could be remnants from an evolutionary ancestor that has been adapted to fulfil a new function following gene duplication. Alternatively, the observation of promiscuity could indicate that an enzyme has the potential to evolve into a new catalyst. Thus, the observation of promiscuity defines functional relationships in enzyme superfamilies. Crosswise promiscuity can provide an additional layer of connectivity between members of a - usually structurally defined - superfamily to establish a system for tracking the emergence and interconversion of enzymatic function. The systematic analysis of measured promiscuous rates may serve as a basis for drawing up phylogenetic relationships based on the potential for catalysis and may be useful for active use in directed evolution, suggesting evolutionary "short cuts". We review recent observations of catalytic promiscuity in members of the alkaline phosphatase (AP) superfamily that exhibit reciprocal relationships of crosswise promiscuity with rate accelerations ( k cat / K M )/ k 2 between 10 6 and 10 18 . Specifically, we focus on the mechanistic features that appear to form the basis of catalytic promiscuity in this superfamily.

The accurate ab initio quantum chemical (QM) method multiconfigurational second-order perturbation (CASSPT2)/complete active space self-consistent field (CASSCF) has been used in conjunction with molecular mechanics (MM) procedures to compute molecular properties and photoinduced reactivity of DNA/RNA nucleobases (NABs) in isolation and within a realistic environment, in which the double helix strand, the aqueous media, and the external counterions are included. It is illustrated that the use of an MM model is helpful both to account for short- and long-range effects of the system surrounding the QM molecular core and to provide the proper structural constraints that allow more accurate QM geometry determinations.

The continuing challenge of using cyclodextrins (CDs) for solubilization and drug targeting has led to the preparation of a wide variety of chemically modified derivatives in order to improve the properties of these host molecules. A possible approach for pharmaceutical applications would be to combine the recognition specificity of CDs with the transport properties of organized structures such as vesicles, liposomes, or micelles. Amphiphilic CDs can be admixed to phospholipid monolayers and to liposomes, and they can be dispersed into nanospheres showing promising properties for drug encapsulation. Monoacylated derivatives of β-CD, Mod-CD (C n ), were synthesized in our laboratory from the reaction of alkenyl succinic anhydride with β-CD. We found that the compound with 10 carbon atoms in the alkenyl chain, Mod-CD (C10), can be incorporated into inverted micelles. We studied their properties in solution and at the air-water interface. In solution they have very low critical micellar concentration, and in the aggregates there are two recognition sites: one is the cavity of the CD and the other is formed by the hydrophobic tails. The alkenyl chain interacts with the cavity, but this is not an obstacle for the association with external guests such as 1-amino adamantane, phenolphthalein, or Prodan. Mod-CD (C n ) with n equal to 10, 14, and 16 ( n indicates the number of carbons in the alkenyl chain), form stable monolayers at the air-water interface and they adopt an organization very different from those found for persubstituted CDs. The differences are attributed to the higher conformational flexibility of these compounds, which allows the organization of the CD units with the cavity perpendicular to the interface.

The role of ionic liquids (ILs) as solvents in chemistry is limited by the poor understanding of the solvation phenomenon in these media. The usual classification criteria used for molecular solvents through various experimental measurements fail to insert ILs into a univocal classification for ILs. Here, we first discuss the unsuitability of the usual interpretative scheme for molecular liquids and elucidate schematically the mechanism of solvation in ILs, pointing out the peculiarities that differentiate them with respect to molecular liquids. Second, we focus on reactivity and reaction kinetics in ILs, underlining the many problems that the complexity of these media reflects on the interpretation of kinetic data and some possible approaches to understand qualitatively the (often not trivial) kinetic problems for reactions performed in ILs.

Synthesis of natural products and analogs using multiple Pd-catalyzed transformations (Lutz F. Tietze and Tom Kinzel). Pure Appl. Chem. 79 , 629-650 (2007); doi:10.1351/pac200779040629.

Dispersity in polymer science (IUPAC Recommendations 2009) (R. G. Gilbert, M. Hess, A. D. Jenkins, R. G. Jones, P. Kratochvíl, and R. F. T. Stepto). Pure Appl. Chem. 81 , 351-353 (2009); doi:10.1351/PAC-REC-08-05-02.