Reversible supramolecular functionalization of surfaces: terpyridine ligands as versatile building blocks for noncovalent architectures

We report on the reversible and selective functionalization of surfaces by utilizing supramolecular building blocks. The reversible formation of terpyridine bis-complexes, based on a terpyridine ligand-functionalized monolayer, is used as a versatile supramolecular binding motif. Thereby, click chemistry was applied to covalently bind an acetylene functionalized Fe(II) bis-complex onto azide-terminated self-assembled monolayers. By decomplexation of the formed supramolecular complex, the ligand modified monolayer could be obtained. These monolayers were subsequently used for additional complexation reactions, resulting in the reversible functionalization of the substrates. The proper choice of the coordinating transition metal ions allows the tuning of the binding strength, as well as the physicochemical properties of the formed complexes and thus an engineering of the surface properties.     

Glycosyl thioimidates as versatile building blocks for organic synthesis

This review discusses the synthesis and application of glycosyl thioimidates in chemical glycosylation and oligosaccharide assembly. Although glycosyl thioimidates include a broad range of compounds, the discussion herein centers on S-benzothiazolyl (SBaz), S-benzoxazolyl (SBox), S-thiazolinyl (STaz), and S-benzimidazolyl (SBiz) glycosides. These heterocyclic moieties have recently emerged as excellent anomeric leaving groups that express unique characteristics for highly diastereoselective glycosylation and help to provide a streamlined access to oligosaccharides.     

Synthesis of formyl-thienylpyrroles: versatile building blocks for NLO materials

Several formyl-substituted 1-alkyl(aryl)-2-(2′-thienyl)pyrroles 3-7 were synthesized by functionalization of the pyrrole or thiophene ring of thienylpyrroles 2 using different methods: Vilsmeier formylation or metalation followed by reaction with DMF.     

Probing the bioactivity-relevant chemical space of robust reactions and common molecular building blocks

In the search for new bioactive compounds, there is a trend toward increasingly complex compound libraries aiming to target the demanding targets of the future. In contrast, medicinal chemistry and traditional library design rely mainly on a small set of highly established and robust reactions. Here, we probe a set of 58 such reactions for their ability to sample the chemical space of known bioactive molecules, and the potential to create new scaffolds. Combined with ~26,000 common available building blocks, the reactions retrieve around 9% of a scaffold-diverse set of compounds active on human target proteins covering all major pharmaceutical target classes. Almost 80% of generated scaffolds from virtual one-step synthesis products are not present in a large set of known bioactive molecules for human targets, indicating potential for new discoveries. The results suggest that established synthesis resources are well suited to cover the known bioactivity-relevant chemical space and that there are plenty of unexplored regions accessible by these reactions, possibly providing valuable "low-hanging fruit" for hit discovery.     

Trifluoromethyl-substituted hydantoins, versatile building blocks for rational drug design

Preparatively simple, one-pot syntheses of trifluoromethyl-substituted hydantoins starting from Boc-protected imines of hexafluoroacetone and trifluoropyruvate are described. They represent valuable building blocks for the construction of constrained peptides or as scaffolds for the synthesis of highly potent VLA-4 antagonists.     

Oligosilsesquioxanes as versatile building blocks for the preparation of self-assembled thin films

A self-assembly approach to the preparation of nanocomposite siliceous thin films by using oligosilsesquioxanes as building blocks is presented. Poly(styrene-4-sulfonate), PSS, and octa(3-aminopropyl)silsesquioxane, NSi8, were layer-by-layer (LbL) assembled onto planar substrates and polystyrene (PS) particles, thus forming composite multilayers. We have clarified the binding properties of NSi8 to PSS by examining the pH influence on film buildup by microelectrophoresis (zeta-potential) and quartz crystal microgravimetry (QCM). The regular growth of PSS/NSi8 multilayers on planar supports was confirmed by surface plasmon resonance (SPR) spectroscopy and QCM. By applying the LbL coating procedure to spherical templates, we prepared compact, microporous hollow silica spheres by calcining PS spheres coated with (poly(allylamine hydrochloride) (PAH)/PSS)(2)/(NSi8/PSS)(n) (n varying from 3 to 12), at 750 degrees C, because of sintering of the octameric clusters (NSi8). Hollow spheres derived from coatings with n = 3 drastically altered in size (relative to the template core), depending on the size of the PS particles used. The novelty of this method for the nanofabrication of siliceous films stems from the use of well-defined and discrete building blocks, such as NSi8, leading to homogeneous organic-silica composite films as well as individual siliceous particles of variable size and shape.     

Sulfo-protected hexosamine monosaccharides: potentially versatile building blocks for glycosaminoglycan synthesis

2,2,2-Trifluorodiazoethane was investigated as a reagent for sulfo group protection on hexosamine monosaccharides. The synthesis of glucosamine and galactosamine building blocks fully differentiated for glycosaminoglycan synthesis and the synthesis of glycosyl donors are described. The compatibility of trifluoroethylsulfonate under a variety of reaction conditions has also been investigated. [structure: see text]     

Perylene bisimide dyes as versatile building blocks for functional supramolecular architectures

Perylene bisimide dyes and their organization into supramolecular architectures through hydrogen-bonding, metal ion coordination and pi-pi-stacking is discussed; further self-assembly leading to nano- and meso-scopic structures and liquid-crystalline compounds is also addressed.     

Electropolymerization as a versatile route for immobilizing biological species onto surfaces

Biosensors based on electronic conducting polymers appear particularly well suited to the requirements of modern biological analysis—multiparametric assays, high information density, and miniaturization. We describe a new methodology for the preparation of addressed DNA matrices. The process includes an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing on their 5′ end a pyrrole moiety. The resulting polymer film deposited on the addressed electrode consists of pyrrole chains bearing covalently linked oligonucleotides (ODN). An oligonucleotide array was constructed on a silicon device bearing a matrix of 48 addressable 50 × 50 μm gold microelectrodes. This technology was successfully applied to the genotyping of hepatitis C virus in blood samples. Fluorescence detection results show good sensitivity and a high degree of spatial resolution. In addition, gravimetric studies carried out by the quartz crystal microbalance technique provide quantitative data on the amount of surface-immobilized species. In the case of ODN, it allows discrimination between hybridization and nonspecific adsorption. The need for versatile processes for the immobilization of biological species on surfaces led us to extend our methodology. A biotinylated surface was obtained by coelectropolymerization of pyrrole and biotin-pyrrole monomers. The efficiency for recognition (and consequently immobilization) of R-phycoerythrin-avidin was demonstrated by fluorescence detection. Copolymerization of decreasing ratios of pyrrole-biotin over pyrrole allowed us to obtain a decreasing scale of fluorescence.     

Synthetic applications of aryl radical building blocks for cyclisation onto azoles

2-(2-Bromophenyl)ethyl groups have been used as building blocks in radical cyclisation reactions onto azoles to synthesise tri- and tetra-cyclic heterocycles. 2-(2-Bromophenyl)ethyl methanesulfonate was used to alkylate azoles (imidazoles, pyrroles, indoles and pyrazoles) for the synthesis of the radical precursors. Cyclisations of the intermediate aryl radicals yield new 6-membered rings attached to the azoles. The aryl radicals undergo intramolecular homolytic aromatic substitution onto the azole rings. Tributylgermanium hydride has been used with success to replace the toxic and troublesome tributyltin hydride. Initial studies show that the protocol can be used on solid phase resins. The molecular and crystal structures of methyl 5,6-dihydroimidazo[5,1-a]iso-quinoline-1-carboxylate and methyl 5,6-dihydroimidazo[2,1-a]isoquinoline-3-carboxylate were determined by X-ray crystallography.     

Boronic acid-substituted metal complexes: versatile building blocks for the synthesis of multimetallic assemblies

Polypyridyl complexes of Ru(II) and Ir(III) incorporating a boronic acid substituent undergo cross-coupling with bromo-substituted complexes, and a sequential coupling-bromination-coupling strategy permits the controlled synthesis of a luminescent Y-shaped heterometallic assembly, in which efficient energy transfer to the terminus occurs.     

Carboranedithiols: building blocks for self-assembled monolayers on copper surfaces

Two different positional isomers of 1,2-dicarba-closo-dodecaboranedithiols, 1,2-(HS)(2)-1,2-C(2)B(10)H(10) (1) and 9,12-(HS)(2)-1,2-C(2)B(10)H(10) (2), have been investigated as cluster building blocks for self-assembled monolayers (SAMs) on copper surfaces. These two isomers represent a convenient system in which the attachment of SH groups at different positions on the skeleton affects their acidic character and thus also determines their reactivity with a copper surface. Isomer 1 exhibited etching of polycrystalline Cu films, and a detailed investigation of the experimental conditions showed that both the acidic character of SH groups and the presence of oxygen at the copper surface play crucial roles in how the surface reaction proceeds: whether toward a self-assembled monolayer or toward copper film etching. We found that each positional isomer requires completely different conditions for the preparation of a SAM on copper surfaces. Optimized conditions for the former isomer required the exposure of a freshly prepared Cu surface to vapor of 1 in vacuum, which avoided the presence of oxygen and moisture. Adsorption from a dichloromethane solution afforded a sparsely covered Cu(0) surface; isomer 1 effectively removes the surface copper(I) oxide, forming a soluble product, but apparently binds only weakly to the clean Cu(0) surface. In contrast, adsorption of the latter, less volatile isomer proceeded better from a dichloromethane solution than from the vapor phase. Isomer 2 was even able to densely cover the copper surface cleaned up by the dichloromethane solution of 1. Both isomers exhibited high capacity to remove oxygen atoms from the surface copper(I) oxide that forms immediately after the exposure of freshly prepared copper films to ambient atmosphere. Isomer 2 showed suppression of Cu film oxidation. A number of methods including X-ray photoelectron spectroscopy (XPS), X-ray Rutherford back scattering (RBS), proton-induced X-ray emission (PIXE) analysis, atomic force microscopy (AFM), cyclic voltammetry, and contact angle measurements were used to investigate the experimental conditions for the preparation of SAMs of both positional isomers on copper surfaces and to shed light on the interaction between these molecules and a polycrystalline copper surface.     

Glycosyl alkoxythioimidates as complementary building blocks for chemical glycosylation

It is reported that S-glycosyl O-methyl phenylcarbamothioates (SNea carbamothioates) have a fully orthogonal character in comparison to S-benzoxazolyl (SBox) glycosides. This complete orthogonality was revealed by performing competitive glycosylation experiments in the presence of various promoters. The results obtained indicate that SNea carbamothioates have a very similar reactivity profile to that of glycosyl thiocyanates, yet are significantly more stable and tolerate selected protecting group manipulations. These features make the SNea carbamothioates new promising building blocks for further utilization in oligosaccharide synthesis.     

Chemistry of epoxysulfones: straightforward synthesis of versatile chiral building blocks

[reaction: see text] Several chiral building blocks have been obtained easily in large quantities from an epoxysulfone (9) that could be obtained in both enantiomeric forms from accessible starting materials.     

Simultaneous tuning of chemical composition and topography of copolymer surfaces: micelles as building blocks.

A simple method is described for controlling the surface chemical composition and topography of the diblock copolymer poly(styrene)-b-poly(dimethylsiloxane)(PS-b-PDMS) by casting the copolymer solutions from solvents with different selectivities. The surface morphology and chemical composition were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively, and the wetting behavior was studied by water contact angle (CA) and sliding angle (SA) and by CA hysteresis. Chemical composition and morphology of the surface depend on solvent properties, humidity of the air, solution concentration, and block lengths. If the copolymer is cast from a common solvent, the resultant surface is hydrophobic, with a flat morphology, and dominated by PDMS on the air side. From a PDMS-selective solvent, the surface topography depends on the morphology of the micelles. Starlike micelles give rise to a featureless surface nearly completely covered by PDMS, while crew-cut-like micelles lead to a rough surface with a hierarchical structure that consists partly of PDMS. From a PS-selective solvent, however, surface segregation of PDMS was restricted, and the surface morphology can be controlled by vapor-induced phase separation. On the basis of the tunable surface roughness and PDMS concentration on the air side, water repellency of the copolymer surface could be tailored from hydrophobic to superhydrophobic. In addition, reversible switching behavior between hydrophobic and superhydrophobic can be achieved by exposing the surface to solvents with different selectivities.     

Tunable supramolecular synthons and versatile, water-soluble building blocks for crystal engineering:

It is shown that the water-soluble dicarboxylic cationic acid [(eta5-C5H4COOH)2Co(III)]+ (1) is an extremely versatile building block for the construction of organometallic crystalline edifices. Removal of one proton from 1 leads to formation of the neutral zwitterion [(eta5-C5H4COOH)(eta5-C5H4COO)Co(III)] (2), while further deprotonation leads to formation of the dicarboxylate monoanion [(eta5-C5H4COO)2Co(III)]- (3). Compounds 1. 2 and 3 possess different hydrogen-bonding capacity and participate in a variety of hydrogen-bonding networks. The cationic form 1 has been characterised as its [PF6]- and Cl- salts 1-[PF6] and 1-Cl.H2O, as well as in its co-crystal with urea, 1-Cl.3(NH2)2CO, and with the zwitterionic form 2, [(eta5-CH4COOH)(eta5-C5H4COO)Co(III)][(eta5-C5H4COOH)2Co(III)]+[PF6]-, 2.1-[PF6]. The neutral zwitterion 2 behaves as a supramolecular crown ether: it encapsulates the alkali cations K+, Rb+ and Cs+ as well as the ammonium cation NH4+ in cages sustained by O-H...O and C-H...O hydrogen bonds to form co-crystalline salts of the type 2(2)-M[PF6] (M = K, Rb, Cs) and 2(2)-[NH4][PF6]. The deprotonated acid 3 has been characterised as its Cs+ salt, Cs+-3.3H2O.     

Decaborane thiols as building blocks for self-assembled monolayers on metal surfaces

Three nido-decaborane thiol cluster compounds, [1-(HS)-nido-B(10)H(13)] 1, [2-(HS)-nido-B(10)H(13)] 2, and [1,2-(HS)(2)-nido-B(10)H(12)] 3 have been characterized using NMR spectroscopy, single-crystal X-ray diffraction analysis, and quantum-chemical calculations. In the solid state, 1, 2, and 3 feature weak intermolecular hydrogen bonding between the sulfur atom and the relatively positive bridging hydrogen atoms on the open face of an adjacent cluster. Density functional theory (DFT) calculations show that the value of the interaction energy is approximately proportional to the number of hydrogen atoms involved in the interaction and that these values are consistent with a related bridging-hydrogen atom interaction calculated for a B(18)H(22)·C(6)H(6) solvate. Self-assembled monolayers (SAMs) of 1, 2, and 3 on gold and silver surfaces have been prepared and characterized using X-ray photoelectron spectroscopy. The variations in the measured sulfur binding energies, as thiolates on the surface, correlate with the (CC2) calculated atomic charge for the relevant boron vertices and for the associated sulfur substituents for the parent B(10)H(13)(SH) compounds. The calculated charges also correlate with the measured and DFT-calculated thiol (1)H chemical shifts. Wetting-angle measurements indicate that the hydrophilic open face of the cluster is directed upward from the substrate surface, allowing the bridging hydrogen atoms to exhibit a similar reactivity to that of the bulk compound. Thus, [PtMe(2)(PMe(2)Ph)(2)] reacts with the exposed and acidic B-H-B bridging hydrogen atoms of a SAM of 1 on a gold substrate, affording the addition of the metal moiety to the cluster. The XPS-derived stoichiometry is very similar to that for a SAM produced directly from the adsorption of [1-(HS)-7,7-(PMe(2)Ph)(2)-nido-7-PtB(10)H(11)] 4. The use of reactive boron hydride SAMs as templates on which further chemistry may be carried out is unprecedented, and the principle may be extended to other binary boron hydride clusters.