Volume 82, Issue 8

The 42nd IUPAC Congress was held in Glasgow on 2-7 August 2009, under the patronage of the Royal Society of Chemistry (RSC). More than 2200 delegates convened in the Scottish Exhibition and Conference Centre for this biennial event, evocatively subtitled “Chemistry Solutions” for the occasion. The Organizing Committee, chaired by Prof. Paul O’Brien (Manchester University), was responsible for overall planning and compilation of an outstanding scientific program, and orchestration by the RSC conference team and their management of facilities and activities during the Congress week were widely acclaimed as indispensable factors in ensuring a memorable international celebration of chemistry. For many delegates, this was also an opportunity to discover or renew acquaintance with the proud history and distinctive ambience of this great city, and to enjoy its progressive modern image. The scientific program of the Congress was highlighted by nine inspiring plenary lectures by leading luminaries in various aspects of the chemical sciences. In addition, multi-themed parallel sessions provided a platform for presentation of no less than about 600 lectures, under the following theme titles: - Analysis and Detection - Chemistry for Health - Communication and Education - Energy and Environment - Industry and Innovation - Materials - Synthesis and Mechanism A program of symposia was presented in each of these themes, and catered for all interests from the most fundamental insights and interpretation of current advances in chemistry to the role of chemistry in meeting the growing technological challenges and aspirations of modern society. The scientific program was enriched by the display of over 1200 posters dealing in every imaginable area of pure and applied chemistry, and handsomely representing the contributions of a great number of the young scientists who attended the Congress. Publication coverage of events such as the 42nd IUPAC Congress is challenging. Invited participants are often confronted with competing commitments, and a large multidisciplinary scientific program militates against reconciling a fully representative publication record with the readership appeal of a thematically coherent collection of works. This addition to the illustrious publication record of the Congress series in Pure and Applied Chemistry (PAC) (www.iupac.org/publications/pac/conferences/family/CONGRESS/) adheres to the recent practice of concentrating on more selective publication of certain themes. It is thus a pleasure to introduce a representative collection of works, based upon a seminal plenary presentation by Sir Fraser Stoddart and lectures by a distinguished group of invited contributors to the themes of “Chemistry for Health” and “Synthesis and Mechanism”. The organizers are particularly grateful to these presenters for ensuring that readers of PAC have an opportunity to relive or engage vicariously in an outstanding IUPAC Congress. James R. Bull Scientific Editor

Stereochemistry—in both its static and dynamic variants—has progressed apace now for more than a century to incorporate all aspects of covalent, coordinative, and noncovalent bonding at levels of structure which encompass constitution, configuration, and conformation. The advent of the mechanical bond in more recent times is now providing opportunities for the emergence of new stereochemical tenets and concepts, some of which bear close analogies with those of days gone by in chemistry. Since terminology helps to define and disseminate a discipline, we advocate that the term “mechanostereochemistry” be used to describe the chemistry of molecules with mechanical bonds.

Directed evolution has emerged as a powerful method for engineering essentially any catalytic parameter of enzymes for application in synthetic organic chemistry and biotechnology, including thermostability, substrate scope, and enantioselectivity. Enantioselectivity is especially crucial when applying biocatalysts to synthetic organic chemistry. This contribution focuses on recent methodology developments in laboratory evolution of stereoselective enzymes, hydrolases, and monooxygenases serving as the enzymes. Specifically, iterative saturation mutagenesis (ISM) has been developed as an unusually effective method to evolve enhanced or reversed enantioselectivity, broader substrate scope, and/or higher thermostability of enzymes.

Terpenoid synthases are ubiquitous enzymes that catalyze the formation of structurally and stereochemically diverse isoprenoid natural products. Many isoprenoid coupling enzymes and terpenoid cyclases from bacteria, fungi, protists, plants, and animals share the class I terpenoid synthase fold. Despite generally low amino acid sequence identity among these examples, class I terpenoid synthases contain conserved metal-binding motifs that coordinate to a trinuclear metal cluster. This cluster not only serves to bind and orient the flexible isoprenoid substrate in the precatalytic Michaelis complex, but it also triggers the departure of the diphosphate leaving group to generate a carbocation that initiates catalysis. Additional conserved hydrogen bond donors assist the metal cluster in this function. Crystal structure analysis reveals that the constellation of three metal ions required for terpenoid synthase catalysis is generally identical among all class I terpenoid synthases of known structure.

Cyclization of short hairpin oligonucleotides (ODNs) containing unactivated alkynes and alkyl azides produces triazole-linked products slowly in the absence of Cu I catalysis. The factors affecting the rate of this cycloaddition reaction have been investigated on a variety of hairpin sequences. The reaction proceeds best at intermediate concentrations of sodium chloride, but is inhibited by phosphate and Tris buffers. It is accelerated by increasing the temperature provided that Watson–Crick base pairing can occur. The rationale for these observations is discussed.

The nature of DNA has captivated scientists for more than 50 years. The discovery of the double-helix model of DNA by Watson and Crick in 1953 not only established the primary structure of DNA, but also provided the mechanism behind DNA function. Since then, researchers have continued to further the understanding of DNA structure and its pivotal role in transcription. The demonstration of DNA secondary structure formation has allowed for the proposal that the dynamics of DNA itself can function to modulate transcription. This review presents evidence that DNA can exist in a dynamic equilibrium between duplex and secondary conformations. In addition, data demonstrating that intracellular proteins as well as small molecules can shift this equilibrium in either direction to alter gene transcription will be discussed, with a focus on the modulation of proto-oncogene expression.

Without question, one of the main tasks of the red blood cell (RBC) is to deliver oxygen to various tissues and organs in vivo. However, due to the lack of a nucleus and mito-chondria, the RBC is typically not thought to be a determinant in many diseases or abnormal physiological conditions. Recent efforts by many labs world-wide are resulting in a body of evidence, suggesting that the RBC may serve many other roles in vivo besides that of an oxygen carrier. If so, the RBC may eventually emerge as one of the simplest drug targets and diagnostic tools available. Here, molecular evidence is provided, suggesting that the RBC, via its ability (or inability) to maintain proper levels of adenosine triphosphate (ATP) release in the circulation, may be a major factor in vascular regulation. Moreover, due to the RBC’s response to slight modifications in its normal environment, the use of the RBC as an important diagnostic for early prediction of disease onset is discussed.

Using an in vitro platform technology that combines microfabricated devices with cell culture, we seek to understand the response of the human body to pharmaceuticals and combinations of pharmaceuticals. Computer models of the human body guide the design of in vitro systems we call micro cell culture analogs (μCCAs) or “body-on-a-chip” devices. A μCCA device is a physical representation of a physiologically based pharmacokinetic (PBPK) model and contains mammalian cells cultured in interconnected microchambers to represent key organs linked through a circulatory system. μCCAs can provide inexpensive means for realistic, accurate, and rapid-throughput toxicological studies that do not require experimenting with animals and reveal toxic effects that can result from interactions between organs. As the natural length scale in biological systems is on the order of 10–100 μm, operating on the microscale allows us to mimic physiological relationships more accurately. We summarize proof-of-concept experiments using mixtures of drugs to treat multidrug-resistant (MDR) cancer and colon cancer. We discuss the extension of the μCCA concept to systems that connect barrier tissues with systemic circulation. Examples with models of the gastro-intestinal (GI) tract are provided.

A summary of the reactions involved in the ring-opening polymerization (ROP) of lactide (LA) to give polylactides (PLAs) is presented along with competing reactions. Particular attention is given to the stereoselective polymerization of rac -LA to give heterotactic PLA and meso -LA to give syndiotactic PLA by aluminum Schiff-based catalysts and to the development of highly active group 2 metal single-site catalysts. Melt or solvent-free polymerization is also described along with reactions that lead exclusively to cyclic-polylactides.

IR spectroscopic and X-ray structural data of rhodium and palladium complexes of N- heterocyclic carbene (NHC) and 1 H -pyridin-(2 E )-ylidene (PYE) ligands indicate that both ligand classes exhibit similar electron-donating properties. However, catalytic application of palladium PYE complexes appears to be limited by PYE ligand loss. Density functional theory (DFT) calculations show that the Pd–C NHC σ-bond is very low-lying in energy (HOMO-14 and 15, ca. –11 eV) and a π-backbonding contribution is also present, whereas the Pd-N PYE σ-bond is comparatively high-lying (HOMO-9 and 10, ca. –8 eV) and the highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) gap is also significantly less (4.0 vs. 5.6 eV). Essentially, electronegativity differences between Pd, C, and N render the Pd–N bond much more polarized and susceptible to electrophilic and nucleophilic attack and hence ligand substitution.

The fascinating properties of ionic liquids make it possible to synthesize semiconductor nanostructures via a simple and low-cost electrochemical pathway. The present paper summarizes our recent work on the synthesis of Si, Ge, and Si x Ge 1– x nanostructures from ionic liquids: thin films, nanowires and photonic crystals. We also introduce our first results on the template-assisted electrodeposition of Si x Ge 1– x photonic crystals from 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([EMIm]Tf 2 N) ionic liquid, and some optical measurements on the previously prepared Ge photonic crystals. Our results confirm that electrochemistry in ionic liquids is excellently suited to the synthesis of high-quality semiconductor nanostructures.

Conductive TiC x O 1– x solid solutions were prepared by carbothermic reduction of titanium dioxide. Studies were focused on the possibility of electrochemically dissolving TiC x O 1– x in NaCl–KCl molten salt. The tail-gas from the anode was monitored during the electrolysis. It was discovered that carbon monoxide (CO) or carbon dioxide (CO 2 ) gases were generated, with the process being dependent upon the consumption of the TiC x O 1– x solid solution anode materials. Furthermore, a series of electrochemical methods was used to investigate the valence state of titanium ions dissolved into molten salt when electrolyzing TiC x O 1– x solid solutions. A significant result was that titanium ion species dissolved from the TiC x O 1– x solid solutions, and this is changed between Ti 2+ and Ti 3+ depending on the electrochemically dissolving potentials. The significant result discovered in this paper will be potentially beneficial in the preparation of high-purity titanium by electrorefining TiC x O 1– x solid solutions.

Uranyl(V) species are normally unstable in solutions but are here shown to be stable in high-temperature chloride melts. Reactions leading to the formation of UO 2 Cl 4 3– ions were studied, including thermal decomposition and chemical reduction of uranyl(VI) chloro-species in various alkali chloride melts (LiCl, 3LiCl–2KCl, NaCl–KCl, and NaCl–2CsCl) at 550–850 °C. Decomposition of UO 2 Cl 4 2– species under reduced pressure, with inert gas bubbling through the melt or using zirconium getter in the atmosphere results in the formation of UO 2 Cl 4 3– and UO 2 . Elemental tellurium, palladium, silver, molybdenum, niobium, zirconium, and hydrogen, as well as niobium and zirconium ions were tested as the reducing agents. The outcome of the reaction depends on the reductant used and its electrochemical properties: uranyl(VI) species can be reduced to uranyl(V) and uranium(IV) ions, and to uranium dioxide.

Measurements of δ( 13 C) determined on CO 2 with an isotope-ratio mass spectrometer (IRMS) must be corrected for the amount of 17 O in the CO 2 . For data consistency, this must be done using identical methods by different laboratories. This report aims at unifying data treatment for CO 2 IRMS by proposing (i) a unified set of numerical values, and (ii) a unified correction algorithm, based on a simple, linear approximation formula. Because the oxygen of natural CO 2 is derived mostly from the global water pool, it is recommended that a value of 0.528 be employed for the factor λ, which relates differences in 17 O and 18 O abundances. With the currently accepted N ( 13 C)/ N ( 12 C) of 0.011 180(28) in VPDB (Vienna Peedee belemnite) reevaluation of data yields a value of 0.000 393(1) for the oxygen isotope ratio N ( 17 O)/ N ( 16 O) of the evolved CO 2 . The ratio of these quantities, a ratio of isotope ratios, is essential for the 17 O abundance correction: [ N ( 17 O)/ N ( 16 O)]/[ N ( 13 C)/ N ( 12 C)] = 0.035 16(8). The equation [δ( 13 C) ≍  45 δ VPDB-CO2 + 2 17 R / 13 R ( 45 δ VPDB-CO2 – λ 46 δ VPDB-CO2 )] closely approximates δ( 13 C) values with less than 0.010 ‰ deviation for normal oxygen-bearing materials and no more than 0.026 ‰ in extreme cases. Other materials containing oxygen of non-mass-dependent isotope composition require a more specific data treatment. A similar linear approximation is also suggested for δ( 18 O). The linear approximations are easy to implement in a data spreadsheet, and also help in generating a simplified uncertainty budget.