Pure and Applied Chemistry

Published by De Gruyter
Online ISSN: 1365-3075
Print ISSN: 0033-4545
The discovery and development of the asymmetric rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and exogenous alkynes to form indolizinone and quinolizinone scaffolds is described. This methodology has been expanded to include substituted alkenes and dienes, a variety of sterically and electronically diverse alkynes, and carbodiimides in place of the isocyanate. Through X-ray analysis of Rh(cod)/phosphoramidite complexes, additives that modify the enantio-determining step, and other experimental data, a mechanism has been proposed that explains lactam, vinylogous amide, and pyridone products and the factors governing their formation. Finally, we have applied this methodology to the synthesis of (+)-lasubine-II and (-)-209D.
Deprotonation of carbon and decarboxylation at enzyme active sites proceed through the same carbanion intermediates as for the uncatalyzed reactions in water. The mechanism for the enzymatic reactions can be studied at the same level of detail as for nonenzymatic reactions, using the mechanistic tools developed by physical organic chemists. Triosephosphate isomerase (TIM) catalyzed interconversion of D-glyceraldehyde 3-phosphate and dihydroxyacetone phosphate is being studied as a prototype for enzyme catalyzed proton transfer, and orotidine monophosphate decarboxylase (OMPDC) catalyzed decarboxylation of orotidine 5'-monophosphate is being studied as a prototype for enzyme-catalyzed decarboxylation. (1)H NMR spectroscopy is an excellent analytical method to monitor proton transfer to and from carbon catalyzed by these enzymes in D2O. Studies of these partial enzyme-catalyzed exchange reactions provide novel insight into the stability of carbanion reaction intermediates, that is not accessible in studies of the full enzymatic reaction. The importance of flexible enzyme loops and the contribution of interactions between these loops and the substrate phosphodianion to the enzymatic rate acceleration are discussed. The similarity in the interactions of OMPDC and TIM with the phosphodianion of bound substrate is emphasized.
A research program has applied the tools of synthetic organic chemistry to systematically modify the structure of DNA and RNA oligonucleotides to learn more about the chemical principles underlying their ability to store and transmit genetic information. Oligonucleotides (as opposed to nucleosides) have long been overlooked by synthetic organic chemists as targets for structural modification. Synthetic chemistry has now yielded oligonucleotides with 12 replicatable letters, modified backbones, and new insight into why Nature chose the oligonucleotide structures that she did.
The nature of DNA has captivated scientists for more than fifty 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.
Tunicamycin inhibits capillary endothelial cell proliferation 1.6 × 10 4 cells in EMEM containing 10% fetal bovine serum in 200 μ l were plated in 96 well plates. After 24 h, the cells were synchronized and treated with tunicamycin (1 μ g/ml) 
Tunicamycin-treated cells are less likely to form colonies 
Tunicamycin-treated cells undergo nuclear fragmentation 
Raman Spectroscopy of capillary endothelial cells after 3 h of culturing in the absence or presence of tunicamycin 
Raman Spectroscopy of capillary endothelial cells after 12 h of culturing in the absence or presence of tunicamycin 
Asparagine-linked protein glycosylation is a hallmark for glycoprotein structure and function. Its impairment by tunicamycin [a competitive inhibitor of N-acetylglucosaminyl 1-phosphate transferase (GPT)] has been known to inhibit neo-vascularization (i.e., angiogenesis) in humanized breast tumor due to an induction of ER stress-mediated unfolded protein response (UPR). The studies presented here demonstrate that (i) tunicamycin (i) inhibits capillary endothelial cell proliferation in a dose dependent manner; (ii) treated cells are incapable of forming colonies upon its withdrawal; and (iii) tunicamycin treatment causes nuclear fragmentation. Tunicamycin-induced ER stress-mediated UPR event in these cells was studied with the aid of Raman spectroscopy, in particular, the interpretation of bands at 1672, 1684 and 1694 cm(-1), which are characteristics of proteins and originate from C=O stretching vibrations of mono-substituted amides. In tunicamycin-treated cells these bands decreased in area as follows: at 1672 cm(-1) by 41.85% at 3 h and 55.39% at 12 h; at 1684 cm(-1) by 20.63% at 3 h and 40.08% at 12 h; and also at 1994 cm(-1) by 33.33% at 3 h and 32.92% at 12 h, respectively. Thus, in the presence of tunicamycin, newly synthesized protein chains fail to arrange properly into their final secondary and/or tertiary structures, and the random coils they form had undergone further degradation.
A route to unsymmetrical polyene dialdehydes is described. The utility of these intermediates is illustrated by a synthesis of okenone. The stereochemistry assigned to methyl natural bixin has been confirmed by preparation of the cis-4 isomer. Support has been obtained for the cis-6 formulation of natural cis-crocetin. Oxidation of astacene with manganese dioxide yields violaxanthin. The synthesis of stereoisomers of alloxanthin and crocoxanthin has confirmed the structures of these acetylenic carotenoids, and identified the principal cis isomers formed on stereomutation. The synthesis has been achieved of racemic forms of the allenic ketone from grasshoppers, and of an allenic degradation product from fucoxanthin.
The cobalt–carbon bond in alkylcobaloximes and in alkylcobalt derivatives of related chelates is reductively cleaved by thiols in mildly acidic medium, or by carbon monoxide, dithionite and stannite in alkaline solution. The reductants interact initially by trans attack of the cobalt atom, followed by the rate-determining cleavage of the Co–C bond. Cobalt-bound methyl groups are converted into methyl carbanions, or species with the reactivity of methyl carbanions, which react with protons of the medium to form methane. In the presence of CO2 detectable amounts of acetic acid are formed, in accord with this mechanism. The reductive cleavage of organocobalt complexes, derived from vitamin B12 or vitamin B12 model compounds, by thiols is correlated with available enzymological evidence on ribonucleotide reductase of Lactobacillus leichmannii. microbial methane biosynthesis of Methanobacillus omelianskii and acetate biosynthesis by Clostridium thermoaceticum. All three enzymatic processes are envisaged to involve reductive Co–C bond cleavage reactions of coenzyme–substrate intermediates as part of the catalytic cycle.
A continuing search for tumor inhibitors from plant sources has yielded over two hundred extracts with reproducible growth-inhibitory activity. Systematic fractionation, guided by assay in cell culture and animal tumor systems, has led to the isolation of the active principles of more than sixty plants. Chemical studies of novel sesquiterpene lactones, diterpenoid quinone methides, steriod lactones and other terpenoid tumour inhibitors are discussed.
The characterization of air pollution)in a particular area is connected with the acquisition of a series of statistically significant data. The actual case referred to is a sampling campaign developed in a station in an urban area (Rome), throughout a period of 12 months. For controlling the behaviour of aerosol pollution according to a most complete characterization the three following apparatuses have been employed: (a) continuous impact sampler (Hirst Spore Trap) (b) continuous filtration sampler (Aisi Sampler) (c) differential 4-stage sampler (Mammarella). Through comparison of data resulting from the three series of sampling it has been possible to analyze: (i) the behaviour of pollution in its complexity (ii) the rate of pollution due to coarse aerosol particles (iii) the median diameters of different fractions of aerosols.
The importance of classification of aerosols according to diametric size is well known. In fact it is possible to find a series of differential devices working on this principle ' x2018;Cascade Impactors’ of May, Orr, Lippman, ' x2018;Eolic Classificator’ of Zurlo, ' x2018;Centripeter Impactor’ of Hounam and Sherwood, etc.). The big interest in this field has led us to devise a four-stage aerosol differential sampler with the following principal characteristics: (i) high efficiency and selectivity, (ii) simplicity of use and function, (iii) possibility of sampling high air volumes without conglomeration of particles in sampling surfaces, (iv) employment of usual collecting surfaces (microscope slides). The sampler gives satisfactory responses from all the above points of view.
The discovery of microbial metabolites—macrotetrolides, siderochromes and boromycin—is reviewed. The structures of these and related compounds provide instructuve examples of how Nature has solved the problem of complexing certain rarer elements, such as potassium, iron and boron. The common structural features of these highly specific, natural complexing agents are briefly discussed.
A collaborative multidisciplinary research project is described in which new natural product anticancer drug leads are obtained from a diverse group of organisms, constituted by tropical plants, aquatic cyanobacteria, and filamentous fungi. Information is provided on how these organisms are collected and processed. The types of bioassays are indicated in which crude extracts of these acquisitions are tested. Progress made in the isolation of lead bioactive secondary metabolites from three tropical plants is discussed.
The blackness index of an air sample, measured by reflectance on an air sample filter, is an indication of the mean darkness of the particles collected on such a medium. As the presence of polycyclic hydrocarbons in air samples is associated with soot or carbon particles, it seemed reasonable to find out if a correlation between these two measurements could be established. The current availability of analytical methods of sufficient sensitivity allowed us to make accurate measurements of the two hydrocarbons. The polycyclic levels found were then compared with the measurements of particular matter and the blackness index to discover the best correlation. These correlations have been established for air samples from three different North American cities, and for different stations within the cities.
Some current methods for the determination of both particulate and gaseous compounds of fluorine, present in air as pollutants, are described and compared. The operation included sampling of the air, the separation of fluoride from interfering substances and its final determination. Results obtained for the separation of fluoride by distillation and by other techniques of micro-diffusion are presented, as well as those obtained by the application of different methods to the subsequent determination of fluoride. The analytical method used by the authors is described, giving some results obtained in its application to the control of air pollution caused by an aluminium smelting plant.
One of the major challenges in contemporary synthetic organic chemistry is the design and development of new tactics and strategies and their application to concise and efficient syntheses of biologically active natural products. Strategies that utilize reactions that enable the rapid assembly of the skeletal framework of such targets are thus especially attractive. In this context, we have developed novel applications of imine chemistry in Mannich and related reactions, cascade processes, and multicomponent reactions to rapidly assemble structural subunits common to diverse families of alkaloids. The practical utility of these chemistries is evidenced by their use in the execution of facile total syntheses of (±)-epilupinine (1), (±)-tashiromine (2), (-)-epimyrtine (3), and (±)-roelactamine (4) as well as other nitrogen heterocycles of potential biological interest.
Scheme 10 Proposed regioselectivity of nickellacycle formation in the catalytic coupling reaction of alkenes and isocyanates. 
Several reactions of simple, unactivated alkenes with electrophiles under nickel(0) catalysis are discussed. The coupling of olefins with aldehydes and silyl triflates provides allylic or homoallylic alcohol derivatives, depending on the supporting ligands and, to a lesser extent, the substrates employed. Reaction of alkenes with isocyanates yields N-alkyl acrylamides. In these methods, alkenes act as the functional equivalents of alkenyl- and allylmetal reagents.
Structure of the lipid A and inner core region of LPS from Burkholderia pyrrocinia [13].  
Attachment of 4-amino-4-deoxy-l-arabinose to phosphates or sugar hydroxyl groups of lipopolysaccharide contributes to bacterial resistance against common antibiotics. For a detailed study of antigenic properties and binding interactions, Ara4N-containing inner core ligands related to Burkholderia and Proteus LPS have been synthesized in good yields. Glycosylation at position 8 of allyl glycosides of oct-2-ulosonic acids (Ko, Kdo) has been accomplished using an N-phenyltrifluoroacetimidate 4-azido-4-deoxy-l-arabinosyl glycosyl donor followed by azide reduction and global deprotection. The β-l-Ara4N-(1→8)-α-Kdo disaccharide was further extended into the branched β-l-Ara4N-(1→8)[α-Kdo-(2→4)]-α-Kdo trisaccharide via a regioselective glycosylation of a protected triol intermediate. Synthesis of Ara4N-modified lipid A - part structure occurring in the LPS of Burkholderia, Pseudomonas and Klebsiellla strains was accomplished using the H-phosphonate approach. The stereocontrolled assembly of the phosphodiester linkage connecting glycosidic centres of two aminosugars was elaborated employing an anomeric H-phosphonate of cyclic silyl-ether protected 4-azido-4-deoxy-β-l-arabinose which was coupled to the hemiacetal of the lipid A GlcN-disaccharide backbone. Conditions for global deprotection which warrant the integrity of "double anomeric" phosphodiester linkage were successfully developed. Introduction of thiol-terminated spacer at the synthetic ligands allows both coupling to BSA and immobilization on gold nanoparticles as well as generation of glycoarrays.
Inhibition of the relaxation activity of recombinant LdTopIB by acid 2 (a) and the corresponding plot of the relaxation activity (%) of the LdTopIB enzyme versus concentration (μM) of the acetylenic fatty acid 2 (b). One unit of recombinant LdTopI was assayed in a plasmid DNA relaxation assay for 30 min at 37°C in the presence of 3.1−150 μM acid 2. Reaction products were resolved in agarose gel and subsequently visualized by ethidium bromide staining. The relative position of the negatively supercoiled DNA substrate is indicated by Sc, N is the nicked DNA, whereas the ladder of relaxed DNA topoisomer bands is in between. Reactions were stopped with a mixture of 1% SDS and 6.1 μg of proteinase K. Lane 1 contains 0.2 μg of pHOT plasmid DNA.  
Comparison of the inhibition of the relaxation activity of human TopIB (left) and recombinant LdTopIB by acid 1. One unit of recombinant LdTopIB was assayed in a plasmid DNA relaxation assay for 30 min at 37°C in the presence of 3.125−100 μM acid 1. Reaction products were resolved in agarose gel and subsequently visualized by ethidium bromide staining. The relative position of the negatively supercoiled DNA substrate is indicated by Sc, N is the nicked DNA, whereas the ladder of relaxed DNA topoisomer bands is shown in between. Reactions were stopped with a mixture of 1% SDS and 6.1 μg of proteinase K. Lane 1 contains 0.2 μg of pHOT plasmid DNA and lane 2 DMSO.  
The lowest-energy structures of NH 4 +… C 2 H x [x = 2(a), 4(b), 6(c)] at MP2/aug-cc-pVTZ level of theory.  
Scheme 1. Synthesis of (±)-2-methoxy-6-heptadecynoic acid (2) and the (±)-2-methoxy-6Z- heptadecenoic acid (1).  
Scheme 2. Synthesis of the (±)-2-methoxyheptadecanoic acid (3).  
The fatty acids (±)-2-methoxy-6Z-heptadecenoic acid (1), (±)-2-methoxy-6-heptadecynoic acid (2) and (±)-2-methoxyheptadecanoic acid (3) were synthesized and their inhibitory activity against the Leishmania DNA topoisomerase IB enzyme (LdTopIB) determined. Acids 1 and 2 were synthesized from 4-bromo-1-pentanol, the former in ten steps and in 7% overall yield, while the latter in seven steps and in 14% overall yield. Acid 3 was prepared in six steps and in 42% yield from 1-hexadecanol. Acids 1-3 inhibited the LdTopIB enzyme following the order 2 > 1 ⪢ 3, with 2 displaying an EC(50) = 16.6 ± 1.1 μM and 3 not inhibiting the enzyme. Acid 1 preferentially inhibited the LdTopIB enzyme over the human TopIB enzyme. Unsaturation seems to be a prerequisite for effective inhibition, rationalized in terms of weak intermolecular interactions between the active site of LdTopIB and either the double or triple bonds of the fatty acids. Toxicity towards Leishmania donovani promastigotes was also investigated resulting in the same order 2 > 1 > 3, with 2 displaying an EC(50) = 74.0 ± 17.1 μM. Our results indicate that α-methoxylation decreases the toxicity of C(17:1) fatty acids towards L. donovani promastigotes, but improves their selectivity index.
Chemical structures of NH 2 ICG and structural comparison with its analogs ICGCO 2 H, ICG and Cypate.  
Absorption and emission spectra of NH 2 ICG in 20% aq. DMSO. Absorption and shorter wavelength emission curves are normalized to the same intensity of the principal emission band. Emission taken at absorbance of 0.10 at . Actual short-wavelength emission intensity is comparable to principal emission at the optimal excitation wavelength.  
Comparative emission spectra of NH 2 ICG and ICG excited at -20 nm and -120 nm. Emission of ICG at -20 nm excitation (curve 3) is normalized to the same intensity of emission of NH 2 ICG at -20 nm excitation (Curve 1). For comparative purpose, emission of ICG at -120 nm excitation (curve 4) is normalized by the same factor as in the normalization of the emission at -20 nm excitation. Curve 2 is NH 2 ICG emission at -120 nm excitation.  
Fluorescence has advanced our understanding in various aspects of biological processes. Fluorescence in the near infrared (NIR) region avoids background autofluorescence from biological samples leading to improved image quality. In searching for indocyanine green (ICG) analogs that can be attached to biomolecules, we observed that dichromic fluorescence manifested in some mono reactive-group functionalized ICG analogs. The two emission bands are distinctively separate from each other, making it a unique feature of fluorescent probes found in biological studies. We further demonstrated that the dichromism comes from the structure and is transferable from dye to its bioconjugates. In this paper, we used Resonance Theory and Molecular Orbital Theory to explain the fluorophore photochemistry in an effort to understand the general fluorescence feature of ICG analogs and provide understanding of the secondary emission band.
Echinomycin producing Streptomyces cultures (X-53 or X-63) grown in the presence of quinazol-4-one-3-acetic acid yield an analogue in which one of the two quinoxaline-2-carboxyl residues is replaced by a quinazol-4-one-3-acetyl moiety. This analogue has been designated quinazomycin. Cell-free extracts of culture X-63. synthesize echinomycin in the presence of precursors, ATP, Mg2+ and mercaptoethanol. Replacement of quinoxaline-2-carboxylic acid in this solution with quinazol-4-one-3-acetic acid yields an echinomycin analogue with two quinazol-4-one-3-acetyl residues, designated biquinazomycin.
Analytical studies of the environment have dealt primarily with toxic materials that may affect the health of man. Studies may also be made to evaluate nuisance effects and economic factors associated with corrosion, staining and damage to plant and animal life. It is important to note that many so-called pollutants are also essential trace elements. Analytical studies of the environrment therefore, should provide a broad background of knowledge for a true evaluation of the nature of the environment and changes that are taking place. A brief review of toxic and carcinogenic materials reveals that there are many hazards to man that are present in the environment. Analytical methods for studying water quality and ambient atmospheres are of critical importance. The analytical problems are very complex and there is great need for a concerted effort to develop suitable analytical procedures and to collect reliable analytical data. It may surprise many to learn that although waters have been analysed for many centuries, no one has yet truly determined the nature and amount of all inorganic species in natural waters, let alone the various organic species that must be present. The study of air pollution is similarly deficient in methodology. A review of the current status of analytical chemistry as applied to air and water pollution studies is made. Some important deficiencies in our present knowledge are pointed out.
Top-cited authors
Kenneth Richard Seddon
  • Queen's University Belfast
Henry Ralph Rawls
  • University of Texas Health Science Center at San Antonio
Jean Rouquerol
  • Aix-Marseille Université, Marseille, and French National Centre for Scientific Research (CNRS)
Nicola Pernicone
  • Ma.Tec. Materials Technologies