Volume 84, Issue 1

The European Carbohydrate Organization (ECO), under the auspices of IUPAC and the cosponsorship of the Italian Chemical Society, organized the 16th European Carbohydrate Symposium (Eurocarb-16), in Sorrento (Napoli), Italy on 3-7 July 2011, during the International Year of Chemistry. More than 700 participants representing 46 different countries participated; the scientific program covered all the chemical, biological, biophysical, and biotechnological aspects of carbohydrates; and more than 150 oral communications, 28 invited lectures, 10 plenary lectures, and 2 awarded plenary lectures, as well as 400 poster contributions were presented. Following the tradition of the previous meetings, the Emil-Fischer Carbohydrate Award and the Carbohydrate Research Award were presented during the opening ceremony. The papers published in this issue of Pure and Applied Chemistry ( PAC ) give a good cross-section of the topics covered at Eurocarb-16, including: synthetic procedures developed on multifunctional molecules such as carbohydrates; design and synthesis of bioactive carbohydrates of pharmaceutical interest; structural studies on very complex carbohydrate molecules and their dynamic interactions; carbo hydrate-based tools for biological applications such as PNA-sugar conjugates; and carbohydratebased synthetic ion transporters and glyco-nanoparticles. These are just some examples of the contributions presented. We are grateful to the contributors, who permit the readers to have an idea of how carbohydrate chemistry can concur with the development of chemistry in different and multidisciplinary areas, with relevant applications of social interest. Eurocarb-17 will take place in Tel Aviv 7-11 July 2013. Rosa Lanzetta and Francesco Nicotra Conference Co-chairs and Editors

In this contribution, a brief survey of the multiple synthetic opportunities offered by the I 2 /Et 3 SiH combined system is presented. Both reagents are cheap and easy to handle, and their combination allows HI to be quickly formed in situ. A suitable stoichiometry of the mixture can be addressed to a set of very useful transformations of carbohydrate chemistry ranging from glycosidation reactions to functional group manipulation of sugars.

Attachment of 4-amino-4-deoxy-L-arabinose (Ara4N) to phosphates or sugar hydroxyl groups of lipopolysaccharide (LPS) 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 centers 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 bovine serum albumin (BSA) and immobilization on gold nanoparticles as well as generation of glycoarrays.

The combination of lithiated alkoxyallenes with carbohydrate-derived nitrones constitutes a flexible entry to highly functionalized enantiopure 1,2-oxazine derivatives. They can be used as precursors for acyclic and cyclic carbohydrate-like products such as amino sugar alcohols, azetidine and pyrrolidine derivatives. The Lewis acid-promoted rearrangement of 1,3-dioxolanyl-substituted 1,2-oxazines to bicyclic compounds allows an efficient route to novel amino pyran and oxepane derivatives. After subsequent transformations, new carbohydrate mimetics or “real” carbohydrates were obtained in good yield and often in a stereodivergent fashion. These compounds have already been employed for the preparation of unusual di- and trisaccharide derivatives. Several of the products prepared showed interesting biological activities, e.g., as L- and P-selectin inhibitors with IC 50 values in the subnanomolar range.

Starting materials of phosphasugars, 1-phenyl-2-phospholene 1-oxides, were prepared from dienes and phenylphosphonous dichloride (dichlorophenylphosphine). Several substituted novel phosphasugars (3- or 4-halo-substituted)-1-phenyl-2-phospholene 1-oxides as well as 1-phenyl-2-phospholane 1-oxides were prepared from 2-phospholenes. The synthesized compounds were evaluated for their antitumor activities against the leukemia cell lines (U937 and K562) by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 2,3,4-Tribromo-3-methyl-1-phenylphospholane 1-oxide showed superior antitumor activity against U937 and K562 cell lines in a comparative evaluation with Glivec. The analysis by flow cytometry implied that 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide induced apoptosis to leukemia cell lines.

The interaction of a variety of saccharides and mimetics thereof with lectin receptors has been studied using a combination of molecular modeling protocols and NMR spectroscopy techniques. It is shown that both methods complement each other in a synergistic manner to provide a detailed perspective of the conformational and structural features of the recognition process.

The study of the relationship between the complex structures and numerous physiological functions of the glycosaminoglycans (GAGs) heparin and heparan sulfate (HS) has continued to thrive in the past decade. Though it is clear that the monosaccharide sequences of these polysaccharides must determine their ability to modulate the action of growth factors, morphogens, chemokines, cytokines, and many other extracellular proteins, the exact details of this dependence still prove elusive. Sequence determines the 3D structure of GAGs at more than one level; detailed sequences of highly sulfated regions may influence affinity for specific proteins in some cases, but in addition attention has been called to the importance of the length and spacing of these highly sulfated sequences, which are separated by unsulfated domains. Within the sulfated “S-domains”, the internal dynamics of the conformationally flexible iduronate pyranose ring have continued to interest NMR spectroscopists and molecular modelers. New studies of the relative degrees of flexibility of sulfated and unsulfated domains lead to an overall model of heparin/HS in which protein-binding, highly sulfated S-domains with well-defined conformations are separated by more flexible NA-domains.

Multivalent carbohydrate–lectin interactions are essential for a multitude of biological recognition events. Much effort has been spent in the synthesis of potent multivalent scaffolds in order to mimic or inhibit biological carbohydrate–protein interactions. However, the defined spatial presentation of carbohydrates remained a challenging task. Peptide nucleic acid (PNA)- and DNA-based double helices are useful scaffolds that enable the controlled display of carbohydrate ligands in a modular approach. The hybridization of PNA-sugar conjugates with complementary DNA strands provides multivalent complexes with defined spatial presentation of carbohydrates, which facilitates the spatial screening of carbohydrate–lectin interactions with Ångström-scale precision.

Artificial ion transporters are synthetic molecules mimicking at a functional level the activity of naturally occurring ion channels or carriers. In the frame of cyclodextrin mimicry, we recently described the synthesis and conformational properties of new carbohydrate-based macrocycles having the glucoside units connected through 4,6-linked phosphodiester linkages, named CyPLOS (cyclic phosphate-linked oligosaccharides). The cyclic dimer was then adopted as a versatile synthetic platform to obtain a variety of analogs, carrying long linear alkyl or polyether chains. Diverse, jellyfish-shaped amphiphilic CyPLOS were thus obtained, with the compound carrying four tetraethylene glycol (TEG) tentacles acting as good ion transporter through lipid bilayers. A fine tuning of the properties and complexation abilities of these amphiphilic analogs was realized by introducing special reporter groups at the extremities of the TEG tentacles. Through the design of an azido-TEG functionalized key intermediate, a fluorescently labeled CyPLOS derivative was synthesized, showing a markedly increased ionophore activity, with the fluorescent tag also allowing the investigation of its mechanism of action and localization within the phospholipid bilayers. Incorporation of a spin label at the CyPLOS tentacles—to provide further insight into the study of their interactions with phospholipid membranes by electron spin resonance (ESR) spectroscopy—was also profitably achieved through a postsynthetic functionalization approach.

Toll-like receptor 4 (TLR4), the receptor of bacterial endotoxins in mammalians, plays a pivotal role in the induction of innate immunity and inflammation. TLR4 activation by bacterial lipopolysaccharide (LPS) is achieved by the coordinate and sequential action of three other proteins, the lipopolysaccharide binding protein (LBP), the cluster differentiation antigen CD14, and the myeloid differentiation protein (MD-2) receptors, that bind LPS and present it in a monomeric form to TLR4 by forming the activated [TLR4·MD-2·LPS] 2 complex. Small molecules and nanoparticles active in modulating the TLR4 signal by targeting directly the MD-2·TLR4 complex or by interfering in other points of the TLR4 signaling are presented in this paper. These compounds have great pharmacological interest as vaccine adjuvants, immunotherapeutics, anti-sepsis, and anti-inflammatory agents.

This document deals with the characterization of porous materials having pore widths in the macropore range of 50 nm to 500 μm. In recent years, the development of advanced adsorbents and catalysts (e.g., monoliths having hierarchical pore networks) has brought about a renewed interest in macropore structures. Mercury intrusion–extrusion porosimetry is a well-established method, which is at present the most widely used for determining the macropore size distribution. However, because of the reservations raised by the use of mercury, it is now evident that the principles involved in the application of mercury porosimetry require reappraisal and that alternative methods are worth being listed and evaluated. The reliability of mercury porosimetry is discussed in the first part of the report along with the conditions required for its safe use. Other procedures for macropore size analysis, which are critically examined, include the intrusion of other non-wetting liquids and certain wetting liquids, capillary condensation, liquid permeation, imaging, and image analysis. The statistical reconstruction of porous materials and the use of macroporous reference materials (RMs) are also examined. Finally, the future of macropore analysis is discussed.

This document describes the application of the syntax, semantic rules, and format of the Nomenclature for Properties and Units (NPU) terminology for coded dedicated kinds-of-property in the various subject fields of the clinical laboratory sciences. The document sums up considerations and reasoning by the Committee and Subcommittee on Nomenclature for Properties and Units (C-SC-NPU) and collects the experience with the system through some eight years of application in electronic health communication. Access to the NPU terminology in English is currently at <www.labterm.dk>, via the English download files from the Danish Release Centre under the National Board of Health. Updates to the terminology are usually presented once a month.

Errata: Metallic materials for biomedical applications: Laboratory and clinical studies (Ingrid Milošev). Pure Appl. Chem. 83, 309–324 (2011); http://dx.doi.org/10.1351/PAC-CON-10-07-09