High Density Of Functional Groups Research Articles

Synthesis of new soluble dendrimers on poly(ethylene glycole) sublayer

A rational method of synthesis was developed for new soluble dendrimers on poly(ethylene glycole) sublayer with a high density of functional groups applying 2,4,6-trichloro-1,3,5-triazine as a dendron and piperazine as linker and functional group carrier. The density of functional groups in the synthesized soluble dendrimers calculated from the elemental analysis for chlorine was 2.19 mmol of NH groups per 1 g of polymer. These new water-soluble dendrimers can be used not only as convenient soluble polymer sublayers but also for efficient trapping in purification of reaction products from impurities.

Substâncias Húmicas: Possibilidade de um Novo Agente Terapêutico

Substâncias húmicas (SH) são agregados moleculares heterogêneos, possuem estrutura indefinida e constituem a principal fração da matéria orgânica natural. Devido ao elevado número de grupos funcionais presentes em sua estrutura, podem atuar como agentes complexantes, influenciando diretamente o transporte, acúmulo, biodisponibilidade e toxicidade de diferentes substâncias. Dentre os contaminantes ambientais, se destacam os metais, pela sua ampla aplicabilidade em diferentes setores e por não sofrerem degradação química ou biológica. O tratamento de intoxicações por metais potencialmente tóxicos em seres humanos vem sendo realizado por agentes complexantes, como o etilenodiaminotetraácetico (EDTA) e os -aminoácidos. Entretanto, algumas limitações, como a falta de seletividade do EDTA e o elevado custo dos -aminoácidos, têm incentivado a busca por outras substâncias quelantes. Nesse sentido, este artigo aborda as principais propriedades descritas na literatura que tornam as substâncias húmicas uma interessante alternativa como agente terapêutico, em casos de intoxicações por metais potencialmente tóxicos.

Stainless Steel Grafting of Hyperbranched Polymer Brushes with an Antibacterial Activity: Synthesis, Characterization, and Properties

Two strategies were used for the preparation of hyperbranched polymer brushes with a high density of functional groups: (a) the cathodic electrografting of stainless steel by poly[2-(2-chloropropionate)ethyl acrylate] [poly(cPEA)], which was used as a macroinitiator for the atom transfer radical polymerization of an inimer, 2-(2-bromopropionate)ethyl acrylate in the presence or absence of heptadecafluorodecyl acrylate, (b) the grafting of preformed hyperbranched poly(ethyleneimine) onto poly(N-succinimidyl acrylate) previously electrografted onto stainless steel. The hyperbranched polymer, which contained either bromides or amines, was quaternized because the accordingly formed quaternary ammonium or pyridinium groups are known for antibacterial properties. The structure, chemical composition, and morphology of the quaternized and nonquaternized hyperbranched polymer brushes were characterized by ATR-FTIR reflectance, Raman spectroscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. The peeling test confirmed that the grafted hyperbranched polymer films adhered much more strongly to stainless steel than the nongrafted solvent-cast films. The quaternized hyperbranched polymer brushes were more effective in preventing both protein adsorption and bacterial adhesion than quaternary ammonium containing poly(cPEA) primary films, more likely because of the higher hydrophilicity and density of cationic groups.

Dendrimer-grafted cell adhesion peptide-modified PDMS

Surface concentration of cell adhesion peptides is thought to play a role in the interactions between biomaterials and cells. The high density of functional groups at the periphery of dendrimers has been exploited in various applications, but their full potential for generating surfaces with high functional group concentrations has not yet been realized. Poly(dimethylsiloxane) elastomers were surface modified with both polyethylene oxide (PEO) and generation 3 diaminobutane dendrimers. PEO and the dendrimers were subsequently used as linker molecules for surface grafting of cell adhesion peptides. ATR-FTIR, X-ray photoelectron spectroscopy, and water contact angle results confirmed the successful attachment of the polymer linkers and peptides. Peptide grafting density was quantified by means of (125)I radiolabeling. Maximum surface peptide grafting density on dendrimer-modified surfaces was twofold greater than the maximum peptide grafting density achieved via the PEO linker. However, vascular endothelial cell adhesion was significantly greater on surfaces modified with the PEO linker, presumably due to the highly flexible PEO spacer making the peptide more accessible for binding with the cell surface receptors. These results suggest that, although peptide surface density may be important, optimizing surface density may not be sufficient for improving biological interactions.

Reactive patterning via post-functionalization of polymer brushes utilizing disuccinimidyl carbonate activation to couple primary amines

Polymer brushes provide an exceptional route to surface functionalization due to their chemical and mechanical robustness, lack of large-area defects, and high density of functional groups. In spite of these benefits, the synthetic difficulty and complex surface structure associated with polymer brushes have hindered their utilization for constructing multifunctional, patterned surfaces. In this contribution we describe the use of a rapid and highly efficient polymer brush post-functionalization technique as a facile method for controlling surface functionality of polymer brushes. Poly(2-hydroxyethyl methacrylate) (PHEMA) brushes are post-functionalized via activation with N,N′-disuccinimidyl carbonate (DSC) and subsequent coupling to molecules containing α-amine moieties. This post-functionalization effectively tailors surface energy resulting in water contact angles ranging from 40° to 100° using different conjugate molecules. Furthermore, the solvent tolerance, insensitivity to reactant concentration, and rapid reaction time of the aminolysis reaction enable surface energy patterning of the polymer brushes through the use of “reactive” soft lithography. Finally, these surface energy patterns could be “developed” by exposure to gold nanoparticle solutions to yield surfaces with patterned nanoparticle density.

Synthesis of dendrimer–carbon nanotube conjugates

AbstractWe describe the coupling between Carbon Nanotubes (CNTs) and a second‐generation cyanophenyl‐based dendrimer. The goal of our work is the synthesis of highly functionalized CNTs without provoking damage to the conjugated π‐system. One approach is the attachment of dendrimers with a high density of functional groups to the CNTs. These groups serve as anchor points for further reactions. With this aim, we have carried out a primary modification on CNTs by the use of 1,3 dipolar cycloaddition reaction. We have employed Single Wall Carbon Nanotubes (SWNTs) as well as Multi Wall Carbon Nanotubes (MWNTs) obtaining 238 μmol and 511 μmol of pyrrolidine groups per gram, respectively. The amount of amino groups introduced in the system was measured by the Kaiser test as well as thermogravimetric analyses. As a second step, dendrimer incorporation was performed by carbodiimide chemistry. Thermogravimetric Analysis, Raman Spectroscopy and Atomic Force Microscopy characterization techniques are reported for the characterization of the final CNT–dendrimer conjugate.The results show that the dendrimer has been attached covalently to the previously generated amine groups. Morphologically, the attached dendrimer with an estimated theoretical molecular length of 6.4 nm, generates a wrapping of 8 nm thick around the CNTs walls. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Convergent Synthesis of Second Generation AB-Type Miktoarm Dendrimers Using “Click” Chemistry Catalyzed by Copper Wire

Dendrimers synthesized from small molecules form macromolecules of well-defined size and architecture.1 The high density of functional groups on the periphery of the dendrimers makes them useful as carriers for multiple copies of biologically active compounds for drug/vaccine delivery or probe molecules for detection applications.2 However, the typical synthetic procedure for obtaining dendrimers from small molecules limits their size to about 5−15 nm as each new generation is increasingly difficult to add and contributes only to a relatively small increase in dimensions. In addition, traditional dendrimers are difficult to purify and as a consequence costly. Thus, the focus in synthetic dendrimers has shifted from using small molecule to polymeric building blocks made by living radical polymerization.3 However, there is still a need in precise synthetic tools that would allow one to combine polymeric blocks with diverse functionality into one structure to create advanced products for biomedical and coatings applications.

Carbohydrates as Synthetic Tools in Organic Chemistry

While amino acids, terpenes and alkaloids have found broad application as tools in stereoselective organic synthesis, carbohydrates have only lately been recognised as versatile starting materials for chiral auxiliaries, reagents, ligands and organocatalysts. The structural diversity of carbohydrates and the high density of functional groups offer a wide variety of opportunities for derivatization and tailoring of synthetic tools to a specific problem.

Peptidomimetics, Glycomimetics and Scaffolds from Carbohydrate Building Blocks

AbstractSaccharides, due to their high density of functional groups and availability as chiral building blocks are scaffolds for bioactive compound discovery. Pyranosides and iminosugar‐based peptidomimetics have been synthesised as ligands for somatostatin receptors and HIV protease. The synthesis of polyhydroxylated macrolides related to natural products and cyclophanes has been achieved from carbohydrate fragments with a view to investigation of their potential as scaffolds. In addition, the trajectory of aromatic systems grafted to saccharides have been studied and this has led to the synthesis of probes for the study of carbohydrate protein interactions. These compounds include geometrically diverse bivalent glycomimetics derived from scaffolds that are hybrids of sugars and aromatic groups. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers

Highly branched, functionalized polymers have potential to act as efficient drug carrier systems. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups. Using ibuprofen as a model drug, we studied the interaction between the drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with NH 2 functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly forms a complex with PAMAM dendrimers because of the ionic interaction between the NH 2 end groups and the carboxyl group of ibuprofen. On an average, up to 78 molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH 2 with 64 end groups. This complex is stable in deionized water and methanol. The in vitro release of ibuprofen from drug–dendrimer complex is appreciably slower compared to pure ibuprofen. The complexed drug enters A549 cells much more rapidly than pure drug suggesting that dendrimers may be able to carry the complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 OH end groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack of strong interactions between the OH end groups and the drugs prevents complex formation.

Site–site interactions within high-loading PAMAM dendrimer resin beads

Combinatorial chemistry and solid-phase synthesis have revolutionised the process of drug discovery in the last decade. Ever since the concept of split and mix synthesis was introduced in 1988, and in particular the concept of one bead one compound, this approach has been associated with the possibility of generating thousands or millions of compounds in only a relatively small number of synthetic steps. The demand for high loading resins has therefore increased over the last few years. Our research has focussed on bead-loading enhancement via a dendrimerisation process. Dendrimer resin beads have shown compatibility for many chemical conditions, however high functional group density could produce undesirable site–site interactions.

D-Glucose as a multivalent chiral scaffold for combinatorial chemistry

Due to their high density of functional groups and their availability in a variety of diastereomeric forms, monosaccharides are considered attractive scaffolds for combinatorial chemistry that allow the attachment and defined spatial alignment of up to five different pharmacophoric groups. For their application in combinatorial syntheses on solid phase, a set of selectively removable hydroxy protecting groups in combination with a cleavable anchor is required. Herein, we report on the construction and use of a versatile multivalent glucose building block for parallel synthesis on the solid phase.

SPOCC-194, a new high functional group density PEG-based resin for solid-phase organic synthesis.

A novel polymer matrix for solid-phase synthesis, SPOCC(194) resin (1), was designed featuring a backbone of homogeneous tetraethylene glycol (TEG(194)) macromonomer linked by quaternary carbon junctions and terminating in primary alcohol functionality. Beaded SPOCC(194) resin was effectively prepared by suspension polymerization of oxetanylated TEG macromonomer 5 in stirred silicon oil. Mechanically stable and inert to a diverse range of reaction conditions, SPOCC(194) possessed a high hydroxyl group loading (0.9-1.2 mmol/g) for substrate attachment and swelled effectively ( approximately 2-4 mL/g) in a variety of organic and aqueous solvents. Developed for solid-phase synthesis at high reactant concentrations for driving organic and aqueous reactions to completion, SPOCC(194) exhibited high functional group density (mmol/mL) similar to that of low-loaded aminomethylated polystyrene-divinylbenzene copolymer (PS-1%DVB) yet significantly higher than that of PEGA(1900), SPOCC(1500), and TentaGel S. High-resolution MAS NMR spectra of Fmoc-derivatized SPOCC(194) indicate that monitoring of functional group transformation is possible. Moreover, by employment of a nonaromatic resin-linker combination, electrophilic chemistry, such as Lewis acid catalyzed glycosylation and Friedel-Crafts acylation, was selectively performed on substrate bound to SPOCC(194) resin. Such properties make SPOCC(194) resin a promising new polymer matrix for the support-bound construction of small organic molecules by parallel and combinatorial synthesis and the scavenging of solution-phase reactants or byproducts.

Heterocycles through Domino Reactions with Trimethyl Aconitate, a Versatile Synthetic Building Block.

The multitalented synthetic reagent trimethyl aconitate (1) is a renewable raw material with a high density of functional groups that up to now has only been scarcely used as a C6 building block. Domino reactions with 1 consisting of imine additions and intramolecular acylations provide simple access to heteropolycycles in one-pot reactions. For example, 1 reacts with N-methylbenzylidenamine (2) to give the spiro[pyrrolidinone-3,3'-dihydropyrrolinone] 3 in 40 % yield.

Protein adsorption on novel acrylamido-based polymeric ion-exchangers: I. Morphology and equilibrium adsorption

The protein uptake equilibrium and particle morphology are determined for novel polymeric ion-exchange media based on acrylamido monomers with a high density of functional groups and a variety of morphological characteristics. The study considers two anion-exchangers and a cation-exchanger. Physical properties determined experimentally include particle density, ion-exchange capacity, particle size distribution, and equilibrium isotherms for model proteins. The pore structure was evaluated using size exclusion chromatography with neutral probe molecules and transmission electron microscopy. For the anion-exchangers, two types of structures were inferred. The first is comprised of particles that contain a low-density gel supported by denser polymer aggregates. This material had a very low size-exclusion limit for neutral probes, but exhibited an extremely high and reversible protein adsorption capacity (280–290 mg BSA/ml). The second structure is comprised of particles with large, open macropores. While the size-exclusion limit was very high, the protein adsorption capacity was low (60 mg BSA/ml). Moreover, the adsorption was nearly irreversible. The physical structure of the cation-exchanger appeared to be intermediate between those of the anion-exchangers, containing both large pores and smaller pores yielding an intermediate, but reversible, protein uptake capacity (120–130 mg αCHY/ml). The different behavior of these materials with regards to protein adsorption correlates well with their physical structure. For these ion-exchangers, high protein adsorption capacities are attained when a low-density polymer gel with a high concentration of functional groups is present.

The synthesis of sub-micron magnetic particles and their use for preparative purification of proteins

A novel one-step protocol for the preparation of sub-micron magnetic particles as small as 30 nm in diameter has been developed. The surface of the particles was functionalized with carboxyl groups ( approximately 1 COOH per 15A2) to facilitate the attachment of affinity ligands. The high surface area of the resulting beads, combined with the high density of functional groups on the surface, makes them ideally suited for the preparative purification of proteins as was demonstrated by the efficient isolation of trypsin (36 mg per gram of particles) from pancreatic extract.

The synthesis of sub‐micron magnetic particles and their use for preparative purification of proteins

A novel one-step protocol for the preparation of sub-micron magnetic particles as small as 30 nm in diameter has been developed. The surface of the particles was functionalized with carboxyl groups (∼1 COOH per 15Å2) to facilitate the attachment of affinity ligands. The high surface area of the resulting beads, combined with the high density of functional groups on the surface, makes them ideally suited for the preparative purification of proteins as was demonstrated by the efficient isolation of trypsin (36 mg per gram of particles) from pancreatic extract. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 60: 419–424, 1998.

Model Studies Towards a Novel Fragment Coupling for the Synthesis of Mycalamides and Related Natural Products

AbstractThe mycalamides (3) and related natural products contain an α‐hydroxy acid 1 bound via an amide bond to an α‐alkoxy amine. The high density of functional groups in the ‘coupling region’ renders the coupling reactions delicate. Model studies showed that an alternate assembly of the molecular halves is possible using an ‘Umpolung’ of an α‐alkoxy isocyanate, e.g. 13. Thus, combination of the ester 12 with 13 led to the α‐keto amide 16. The further elaboration of 16 to the α‐hydroxy‐amide structure found in the mycalamides is reported.

Surface properties of suspended solids in stratified estuaries (Krka River estuary and Rhône River delta)

Three surface parameters—specific surface area (SSA), heat of wetting (Hw), and cation exchange capacity (CEC)—of estuarine suspended solids were studied in relation to the organic matter (dissolved or particulate). Natural suspended solids were studied in two stratified river mouths—the Krka River estuary and the Rhône River delta. The same studies were performed with model solids, well defined by chemical composition and preparation (controlled pore glass, silanized controlled pore glass and calcite) after exposure to natural water samples from the Krka River estuary. On the basis of the studied parameters, the existence of two types of organic compounds that mediate the surface properties of particulates was indicated: (1) hydrophilic, with high density of functional groups, reactive and degradable, and coinciding with ‘river type organic matter’, and (2) hydrophobic, less reactive and thus more persistent, and coinciding prevalently with ‘marine type organic matter’. Generally, it was found that high Hw values (100–300 μJ cm −2) reflect the influence of surface functional groups that originate primarily from the reactive organics (adsorbed or particulate). An extreme value of Hw (523 μJ cm −2) was found at a location of high biological productivity and high anthropogenic influence.

ChemInform Abstract: De novo Synthesis of Carbohydrates and Related Natural Products

Two synthetic strategies from achiral precutsors especially useful for sugars requiring unusual functional groups, deoxy and branched sugars, as well as partially 0protected sugars, are outlined. One strategy employs inversetype hetero-Diels-Alder reaction with highly functionalized 1-oxa-1,3-dienes. Their reaction with electron rich heterodienophiles (enol ethers, etc.) and subsequent diastereoselective transformation of the CC-double bond in the dihydropyran adducts obtained gives convenient access to deoxy sugars (for instance, Dand L-olivose) and related compounds, which also contain C-branching (for instance, ramulosin). The other versatile strategy starts from racemic or meso-divinyl glycols. Kinetic resolution via Sharpless epoxidation again gives direct access to partially 0protected carbohydrates. This method is exemplified in deoxy sugar synthesis (for instance, Dand L-digitoxose and chalcose) and also in the synthesis of the pheromone exobrevicomin. INTRODUCTION AND STRATEGIES Carbohydrate derivatives and related natural products are mainly synthesized by transformation of readily available sugars (ref. 1). However, the high density of functional groups of comparable reactivity requires regioselective protection and deprotection measures and stereospecific functional group exchange quite often resulting in multistep syntheses. Several methods have been developed in the last years which are useful in the diastereoselective and enantioselective generation of new stereocenters (ref. 2). Therefore novo syntheses or total syntheses of natural products from achiral starting materials have become competitive or even superior (ref. 3-8). For the generation of several subsequent chiral centers two different key step reactions are applicable: (i) stereoselective CC-bond formation and (ii) stereoselective functionalisation of compounds having already the required carbon skeleton. In the de novo synthesis of carbohydrates these two principles, •having led to great progress in natural product synthesis, are especially well illustrated (ref. 5-7). The stereoselective formation of the carbon skeleton is frequently attained by diastereofacial selectivity in carbon nucleophile additions to carbonyl and imine systems where either the nucleophile or the electrophile or both contain chiral groups in order to induce the preferred formation of one enantiomer (ref. 9, 10). Also Diels-Alder reaction has become a powerful tool in natural product synthesis because it combines CC-bond formation with diastereoselectivity at several centers (ref. 11). Due to supra-suprafacial reaction, polarity controlled orientation, and endoor exo-selectivity of diene and dienophile, very often only one pair of enantiomers is obtained out of the maximum of thirty two possible isomers (ref. 7). Recently even enantioselectivity could be incorporated successfully into the Diels-Alder reaction leading to preferential or exclusive formation of one single isomer (ref. 12). Aiming at the pyranose form of sugars hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems which are important targets in the chiron approach * De novo Synthesis of Carbohydrates and Related Natural Products, Part 25. Part 24, see ref. 23.