Volume 73, Issue 1

Atomic spectrometry and electrochemistry are usually recognized as independent analytical tools used for different purposes. Here, a brief review is given of the advantages of using electrochemistry in the various fields of atomic spectrometry techniques. In the first part, the application of electrochemical preconcentration before the atomic spectrometry will be addressed and exemplified. Electrochemical preconcentration could be used with flame atomic absorption spectrometry (AAS) or graphite furnace AAS as well as with atomic emission plasma sources. The second area of the applications of electrochemistry will be directly focused on the graphite furnace AAS where the electrodeposition onto the graphite surface of the atomizer could be used for both in situ analyte preconcentration or modification of the surface by noble metals.

The possibilities of using diffusive gradients in thin films (DGT) and anodic stripping voltammetry (ASV) to perform speciation measurements in natural waters are discussed. Both techniques measure labile species, but different approaches have been used to discriminate organic (Corg) and inorganic (Cinorg) metal complexes. In DGT, metals are bound to a resin after passing through a hydrogel that serves as a well-defined diffusion layer. DGT devices with different hydrogels that impede the diffusion of humic substances by different amounts were deployed in solutions of copper and humic substances. Devices with a gel composition that greatly restricted the diffusion of humic substances, but only retarded the diffusion of Cu ions slightly, could be used directly to determine Cinorg. By using different, more open pored gels, which allowed some passage of humic substances, it was possible to determine both Corg and Cinorg. The two separate measurements of Cinorg obtained using the two DGT approaches agreed well. At the high concentrations of Cu used there was good agreement with the predicted distribution from the speciation code WHAM. At the lowest Cu concentration, the proportion of Cinorg estimated using DGT was higher than with WHAM. Possibilities of errors in the DGT or modeling approaches are discussed.

The pH-sensitive chromoionophores brought the dream of the ion-selective membrane scientist close to realization. With the help of these molecules, one can build pH-sensitive, ion-selective electrodes and look into the bulk of solvent polymeric membranes during potentiometric measurements (spectropotentiometry) and image concentration profiles in situ with high spatial and temporal resolution. The combination of electrochemical and optical information helped to interpret non-idealities in the potentiometric responses, suppress or tailor the undesirable transport across sensor membranes, and estimate the residual lifetime of chronically implanted sensors. These novel opportunities provide feedback in membrane optimizations and are expected to lead to sensor systems with picomolar detection limits and superb selectivities.

Disposable, electrochemical DNA-based biosensors have been exploited for the determination of low-molecular-weight compounds with affinity for nucleic acids. The application is related to the molecular interaction between the surface-linked DNA obtained from calf thymus and the target pollutants or drugs, in order to develop a simple device for rapid screening of genotoxic or similar compounds. The determination of such compounds was measured by their effect on the oxidation signal of the guanine peak of the DNA immobilized on the electrode surface and investigated by chronopotentiometric or square-wave voltammetric analysis. The DNA biosensor is able to detect known intercalating and groove-binding compounds such as daunomycin, polychlorinated biphenyls (PCBs), aflatoxin B1, and aromatic amines. Applicability to river and waste water samples is discussed and reported.

Thirty years of ion-selective electrode (ISE) researches at the University of Wales, Cardiff are outlined. They summarize developments of PVC membrane ISEs, first for calcium and then of other systems, including the improved calcium dioctyl-phenyl-phosphate sensor for calcium and those of ion-exchangers, polyalkoxylates, and cyclic and acyclic polyethers for various anions and cations. Electrodes based on polyalkoxylates have interesting properties toward the polyethers themselves. Some ISE failure causes are discussed. Attention is given to applications, including analysis of wash liquors and nonionic surfactants, biomedical roles, and studies of sulfate-reducing bacteria activity. Coated-wire ISEs and ion-selective field effect transistors (ISFETs) are mentioned, as are other modes of ISE deployment. The review concludes with some fundamental features of PVC electrode membranes as determined by radiotracer, applied potential, and potentiostatic approaches.

The steady-state biouptake of metals from complex media is outlined for the case of two different uptake routes. The analysis comprises the limiting situations of inert and labile complexes, and distinguishes between bioinactive and bioactive (lipophilic) complexes. Depending on the dynamic features, fluxes of the different species may be either coupled or uncoupled. The role of the lipophilic ligands may be important in the overall uptake process. Some specific cases are discussed.

Mechanized procedures for chemical analyses are susceptible to systematic errors usually difficult to trace. This holds also for flow analysis that although accepted worldwide may sometimes yield inaccurate results. The present work focused on the development of a simple system able to detect and circumvent sources of inaccuracy. The versatility inherent in the multicommuted flow analyzers was exploited for real-time characterization of the source of inaccuracy and overcoming the problem for every assayed sample. Specific situations where the analytical results are more susceptible to inaccuracy are emphasized.

Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir (PMPA), and disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, and emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir. In addition, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120; (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5; (iii) virus-cell fusion; (iv) viral assembly and disassembly; (v) proviral DNA integration; and (vi) viral mRNA transcription. Also, new NRTIs, NNRTIs, and PIs have been developed that possess respectively improved metabolic characteristics, or increased activity against NNRTI-resistant HIV strains or, as in the case of PIs, a different, nonpeptidic scaffold. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells.

Many early discoveries in the pharmaceutical industry were through serendipity. Later, targets were mainly identified in animals and systematically exploited through the identification of potent and selective molecules. A disease association was normally obtained through the clinical testing of candidate molecules in patients. The technological advances in the last few years offer the possibility of knowing more about the disease, and this is driving the industry toward a disease-based approach where understanding the disease becomes central to the process. This is now possible thanks to the recent explosion in molecular and cellular biology, together with the application of genetics and genomics. New screening technologies have also revolutionized the identification of chemical leads. Now, high-throughput screening allows a wide chemical diversity to be applied in order to obtain tractable leads, which can then be optimized by the medicinal chemist. It is envisaged that these trends of continuously searching for process improvement will continue, being driven by the need to find medicines that add value in treating unmet medical need.

Biotransformation systems, whether used for environmentally benign biocatalysis of synthetic reactions, or bioremediation of pollutants, require suitable biocatalysts and suitable bioreactor systems with particular characteristics. Our research focuses on the bioconversion of organic compounds, many of which are industrial residues, such as phenols, poly-aromatic hydrocarbons, heterocyclic compounds, and polychlorinated biphenyls. The purpose of such biotransformations can be twofold: firstly, to remove them from effluents and convert them to less toxic forms, and secondly, to convert them into products with economic value. We conduct research in utilizing various isolated-enzyme and whole-cell biological agents; bioreactors, including novel membrane bioreactors, are used as a means of supporting/immobilizing, and hence applying, these biocatalysts in continuous systems. In addition, the enzyme systems are characterized biochemically, to provide information which is required in modification, adaptation, and scale-up of the bioreactors. The paper summarizes research on application of biofilms of fungal and bacterial cells and their enzymes, including hydrolases, polyphenol oxidase, peroxidase and laccase, in bioreactor systems including continuously operating membrane bioreactors.

The oxidation of cyclohexane with molecular oxygen in the presence of isobutyraldehyde catalyzed by nanostructured iron and cobalt oxides and iron oxide supported on titania has been studied. Nanostructured cobalt oxide on MCM-41 is found to be efficient for catalytic aerobic epoxidation of olefins.

Higher-valent transition metals react with H 2 O 2 to form peroxometallates, thereby activating the coordinated peroxide. Based on the reaction profiles of peroxometal species, environmentally acceptable newer syntheses of tetrabutylammonium tribromide (TBATB), Bu 4 NBr 3 , cetyltrimethylammonium tribromide (CTMATB), cetyl(Me) 3 NBr 3 , and tetraethyl-ammonium tribromide (TEATB), Et 4 NBr 3 , have been developed from the reactions of the corresponding quaternary ammonium bromides with H 2 O 2 and a catalytic amount of vanadium(V) or molybdenum(VI). Other transition metals capable of activating peroxide give similar results. The quaternary ammonium tribromides (QATBs) thus produced, especially TBATB and CTMATB, very efficiently act as clean and selective brominating agents for a variety of organic substrates. Very facile bromination of organic substrates, including aromatics, is also possible by tetrabutylammonium bromide (TBAB) Bu 4 NBr, either promoted by V 2 O 5 ­H 2 O 2 or catalyzed by MoO 4 2­ ­H 2 O 2 . The scope of the protocols has been underscored, and the relevance to green chemistry has been highlighted.

The use of heterogenization as a method for achieving clean synthesis is discussed. The chemical modification of mesoporous solids can be used to make a range of catalysts, including solid acids and bases, and stable metal complexes for selective oxidations and other reactions. By avoiding an aqueous quench stage in the separation, the heterogenization of catalysts and reagents can lead to substantial reductions in waste produced in organic chemical manufacturing processes.

By learning how to balance natural resource limitations and pollution prevention with economic growth, green chemistry will become the central science of sustainability. The elimination of persistent pollutants is vital for a sustainable civilization. To achieve this, the most important guiding concept is that the elemental composition of technology should be shifted toward the elemental composition of biochemistry. Oxidation chemistry is currently a prolific producer of persistent pollutants. Many arise from the use of chlorine, hypochlorite, or chlorine dioxide in large-scale oxidation processes. Oxidation chemistry can be greened by replacing these with catalyzed alternatives based on Nature's oxidizing agent, hydrogen peroxide. TAML® (TetraAmidoMacrocyclicLigand) iron catalysts, which were invented at Carnegie Mellon University, are widely patented and are being developed to activate H 2 O 2 for commercial applications. TAML activators are water-soluble, easy to use, function well from neutral to basic pH, are not dominated by nonselective Fenton-like reactivity, are straightforward to synthesize, work effectively in minute concentrations, enable peroxide processes to occur at temperatures well below those of the processes targeted for replacement, and are amenable to modification for capturing novel selectivities. TAML activators are "dial-a-lifetime" catalysts: an activator can be chosen exhibiting a lifetime commensurate with the desired task.

Methods are discussed for rapid screening of soluble and polymer-bound homo-geneous catalysts for activity. A polymer-bound phosphine library is synthesized, and a modular tridentate pincer CNC bis-carbene Pd complex is described. The possibility of C-bound His in metalloenzymes is raised.

The concept of chemoremediation in the liquid homogeneous phase using polymer reagents as a green technology is presented and outlined. It is based on the retention of polymer­metal complexes in aqueous solution according to their molecular size by using membrane filtration. The fundamentals of the metal ion interaction with respect to enrichment and separation procedures are discussed, and the role of polymer­metal complexes is assessed. The formation conditions of these polymer­metal complexes as well as major factors influencing the process are investigated. In addition, recent developments using this method are evaluated, and several application examples are highlighted.

Air pollution may have severe long-term as well as short-term health effects. The determination of possible links between pollution levels and impact on human health is, however, not a straightforward task. A key problem is the assessment of human exposure to ambient pollution levels. In later years, the possible role of particulate pollution as a health hazard has drawn major attention and is, therefore, the subject of research projects in many countries including Denmark. The present paper gives a review of recent and ongoing/planned Danish air pollution exposure studies. Furthermore, key results from Danish studies of ultrafine particles from urban traffic are outlined. The exposure studies show that air pollution models may be strong tools in impact assessment studies, especially when used in combination with personal exposure monitoring and application of biomarkers. Personal exposure measurements in Copenhagen indicate that indoor pollution levels may be very important for the personal exposure to fine fraction particles (PM 2.5 ). Measurements with a differential mobility analyzer (DMA) in Danish urban areas show that number concentrations of ultrafine particles (<100 nm) in busy streets are strongly correlated with classic traffic pollutants such as nitrogen oxides and carbon monoxide. The number concentrations in urban Danish streets have decreased considerably between two campaigns in 1999 and 2000, apparently as a result of reductions in sulfur contents in Danish diesel fuels that took place in July 1999.

Dry media reaction under microwaves is an effort toward "green chemistry". Effects of microwaves in dry media organic reactions have shown synthetic utility for the preparation of biodynamic heterocycles.

The liquefaction, gasification, and other chemical modifications of oil shale are challenging goals of chemistry and chemical engineering. The use of new solvent systems, such as supercritical fluids and ionic liquids, represents new avenues in the search of environmentally benign technologies. Supercritical fluid extraction (SFE) with carbon dioxide is particularly effective for the isolation of substances of medium molecular weight and relatively low polarity. At elevated temperatures it is possible to unite the breaking chemical bonds in the kerogen organic matter and convert the former into oil with extraction using supercritical fluids. Quantitative and qualitative information obtained at different temperatures during SFE is providing some insight into the speciation of hydrocarbons in geological samples. Ionic liquids were studied as potential solvents for kerogen extraction. However, these chemical processes are favored at elevated temperatures up to the thermal degradation temperature of kerogen, 400 C. There were observed significant differences in the chemical composition of extracted oil and from the oil from the classical semicoking process of oil shale. An additional application would be a combination of the two methodsthe use of supercritical carbon dioxide to recover nonvolatile organic compounds from room-temperature ionic liquid without using organic solvents.

Typical applications of solvent-free conditions and microwave activation are described. Non-purely thermal specific effects are evidenced and discussed in terms of reaction medium and mechanisms, taking into account the variations in polarity of the systems.

The capabilities of porcine pancreatic lipase (PPL), Candida antarctica lipase (CAL), and Candida rugosa lipase (CRL) were evaluated for enantio- and/or regioselective acetylation/deacetylation of (±)-2,4-diacetoxyphenyl alkyl ketones, (±)-4-alkyl-3,4-dihydro-3-hydroxyalkyl-2 H -1,3-benzoxazines, and d- arabino and d- threo -polyhydroxyalkyltriazoles in organic solvents. PPL in tetrahydrofuran (THF) exhibited high to moderate enantioselectivity during the deacetylation of (±)-2,4-diacetoxyaryl alkyl ketones and acetylation of (±)-3-hydroxyalkyl-2 H -1,3-benzoxazines. Together with enantioselectivity, PPL in THF also showed exclusive regioselectivity for the deacetylation of para -acetoxy over the ortho -acetoxy function, with respect to the nuclear carbonyl group in 2,4-diacetoxyphenyl alkyl ketones. CAL in diisopropyl ether (DIPE) and PPL in THF exhibited exclusive selectivity for the acetylation of primary hydroxyl over secondary hydroxyl group(s) of d- arabino - and d- threo -polyhydroxyalkyltriazoles.

We have modified the current phosphoramidite-based, solid-phase synthesis of antisense oligonucleotides to accommodate principles of green chemistry. In this article, we summarize key accomplishments that reduce or eliminate the use or generation of toxic materials, solvents, and reagents. Also discussed are methodologies that allow reuse of valuable materials such as amidites, solid-support, and protecting groups, thus improving the atom economy and cost-efficiency of oligonucleotide manufacture. Approaches to accident prevention and the use of safer reagents during oligonucleotide synthesis are also covered.

A green analytical method was developed for separation and preconcentration of trace amounts of copper from aqueous samples using aurin tricarboxylic acid-immobilized silica gel (ATA-SG). This was done by determining chemical speciation and stability constant of Cu-ATA complex. The pH-metric studies indicate strong complexation of Cu with ATA (log b Cu2 ATA = 19.56). Species distribution curve for Cu-ATA complex indicates almost 100% complexation of copper, with ATA forming Cu 2 ATA as the predominant species. Considering the selectivity and strong interaction of ATA toward copper, ATA was immobilized on the polymeric matrix of silica gel, and the conditions were optimized for the uptake of copper from the aqueous solutions. The uptake of Cu ions by ATA-SG was studied both by batch and column methods. The method was developed for the estimation of trace amounts of copper in various samples. Molecular modeling studies were also performed on ATA-immobilized silica gel for gaining an insight into the active structure of ATA on the silica surface.

The chemistry of multicomponent reactions (MCRs) and isocyanides belongs to three periods: In the century 1859­1958, isocyanide chemistry was moderately active and was separate from the classical name reactions of the MCRs. In the next period, isocyanides became well available, and MCRs of isocyanides became the most variable way of forming chemical compounds. The year 1993 began a new era of the formation and investigation of the products and the libraries of the Ugi reaction (U-4CR) and higher MCRs of the isocyanides. This chemistry is primarily accomplished in the industrial search and preparation of new pharmaceutical and plant-protecting products.

A solvent-free approach for organic synthesis is described which involves microwave (MW) exposure of neat reactants (undiluted) either in the presence of a catalyst or catalyzed by the surfaces of inexpensive and recyclable mineral supports such as alumina, silica, clay, or "doped" surfaces, namely, Fe(NO 3 ) 3 -clay (clayfen), Cu(NO 3 ) 2 -clay (claycop), NH 2 OH-clay, PhI(OAc) 2 -alumina, NaIO 4 -silica, MnO 2 -silica, and NaBH 4 -clay. A variety of deprotection, condensation, cyclization, oxidation, and reduction reactions are presented including the efficient one-pot assembly of heterocyclic molecules from in situ generated intermediates such as enamines and a-tosyloxyketones. The application of this solvent-free MW approach to multicomponent reactions is highlighted that can be adapted for high-speed parallel synthesis of the library of dihydropyrimidine-2(1 H )-ones and imidazo [1,2-a]annulated pyridines, pyrazines, and pyrimidines.

Owing to present environmental awareness, attempts are being made toward the evolution of environmentally benign processes using solid-supported reagents and microwave-assisted reactions. A newly developed, nonmetallic oxidative reagent, "clayan", has been exploited for various reactions such as deprotection, oxidation, oxidative coupling, and nitration and bromination of activated and deactivated arenes. In another green chemistry endeavor, reactions such as reduction and cyclization have been successfully carried out in dry media under microwave irradiation. The nonsolvent reaction, experimental simplicity, and enhanced selectivity are the main attractive features of the approach.