Boronic acid building blocks: tools for self assembly

Dynamic covalent functionality has been acknowledged as a powerful tool for the construction of organised architectures, the reversible nature thermodynamically facilitates self-control and self-correction. The use of boronic acids complexation with diols and their congeners has already shown great promise in realising and developing reversible boron-containing multicomponent systems with dynamic covalent functionality. The structure-directing potential has lead to the development of a variety of self-organisation involving not only macrocycles, cages and capsules, but also porous covalent organic frameworks and polymers. Structure controls as well as remarkable synthesis are highlighted in this feature article.     

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.     

Boronic acid converters for reactive hydrazide amplifiers: polyphenol sensing in green tea with synthetic pores

Multicomponent sensing in complex matrices with synthetic pores became feasible with the introduction of amplifiers. Amplifiers are defined as molecules that can covalently capture undetectable analytes after enzymatic signal generation and drag them into the pore for transduction. Here, we introduce converters as molecules that can shift the reactivity of amplifiers in situ to capture chemoorthogonal analytes. For this purpose, a series of dialkoxynaphthalene (DAN) and dialkoxyanthracene (DAA) hydrazinoboronic acids was prepared in situ from DAN and DAA hydrazides and formylphenylboronic acids. These converted amplifiers efficiently inactivate synthetic pores with internal naphthalenediimide clamps. This pore inactivation by DAN and DAA hydrazinoboronic acids vanishes in the presence of catechols such as (+)-catechin, presumably because the obtained boronate esters are too large to bind within the synthetic beta-barrel pore or because they prefer to partition into the bilayer membrane. The resulting increase in pore activity with increasing catechol concentration at constant amplifier concentration is shown to be compatible with the sensing of polyphenols in green tea.     

Caged phospho-amino acid building blocks for solid-phase peptide synthesis

Three 1-(2-nitrophenyl)ethyl-caged phospho-amino acids have been synthesized for use in standard N(alpha)-fluorenylmethoxycarbonyl-based solid-phase peptide synthesis (SPPS). The most common naturally occurring phospho-amino acids, serine, threonine, and tyrosine, were prepared as protected caged building blocks by modification with a unique phosphitylating reagent. In previous work, caged phospho-peptides were made using an interassembly approach (Rothman, D. M.; Vazquez, M. E.; Vogel, E. M.; Imperiali, B. Org. Lett. 2002, 4, 2865-2868). However, this technique is limited to creating peptides without oxidation sensitive residues C-terminal to the amino acid to be modified and the methodology involves synthetic manipulations on the solid phase that may limit the utilization of the methodology. Herein we report the facile synthesis of N-alpha-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-serine 1, N-alpha-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-threonine 2, and N-alpha-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-tyrosine 3. These building blocks allow the synthesis of any caged phospho-peptide sequence using standard Fmoc-based SPPS procedures.     

Synthesis of new ribosylated Asn building blocks as useful tools for glycopeptide and glycoprotein synthesis

We performed the first synthesis of new Asn derivatives bearing α- or β-ribose as pure anomers, linked by an N-glycosidic bond, on the side chain of the Asn residue orthogonally protected for Fmoc/^tBu SPPS, by an efficient five-step strategy with a global yield of 73% starting from d-ribose. These building blocks are obtained in a large scale and can be useful tools for glycopeptide and glycoproteins synthesis.     

Solid-phase synthesis of new S-glycoamino acid building blocks

Efficient synthesis of unprotected S-glycoamino acid building blocks in the solid phase by coupling a sugar 1-thiolate with iodine activated fluoren-9-ylmethoxycarbonyl (Fmoc) protected amino acids.     

Optimizing biomimetic gelators constructed from amino acid building blocks

This paper reports the use of a range of amino acids to construct diverse gelators, employing structures in which Boc-protected amino acids are attached to either end of an aliphatic diamine spacer chain. The choice of amino acid determines whether nanoscale self-assembly takes place and controls the properties of the resultant material, while the function of the amino acid (e.g., the optical properties of tryptophan) is translated into the self-assembled nanostructured gel.     

Glycomimetic building blocks: a divergent synthesis of epimers of shikimic acid

A divergent synthesis of (-)-4-epi-shikimic acid was developed. This route features a one-pot zinc-mediated reductive ring opening of an arabinofuranose followed by a Barbier reaction and culminates in a ring-closing metathesis. Functionalization of (-)-4-epi-shikimic acid via conjugate addition of a thiol occurs in high diastereoselectivity to afford a product with the features of fucosylated glycans.     

An efficient synthetic route to glycoamino acid building blocks for glycopeptide synthesis

[reaction: see text] Chemical glycopeptide synthesis requires access to gram quantities of glycosylated amino acid building blocks. Hence, the efficiency of synthesis of such building blocks is of great importance. Here, we report a fast and highly efficient synthetic route to Fmoc-protected asparaginyl glycosides from unprotected sugars in three steps with high yields. The glycosylated amino acids were successfully incorporated into target glycopeptides 7 and 8 by standard Fmoc solid-phase peptide synthesis.     

Readily available amino acid building blocks for the synthesis of phosphole-containing peptides

Nucleophilic substitution of a phospholide anion onto protected 3-iodoalanine leads to the formation of an amino acid with an appended phosphole in excellent yield. Manipulation of the protecting groups, leads to building blocks suitable for the synthesis of phosphole-containing polypeptides.     

Synthesis of iduronic acid building blocks for the modular assembly of glycosaminoglycans

The modular synthesis of glycosaminoglycans requires straightforward methods for the production of large quantities of protected uronic acid building blocks. In particular, the preparation of fully differentiated iduronic acids has proven particularly challenging. An efficient route to methyl 3-O-benzyl-1,2-O-isopropylidene-alpha-l-idopyranosiduronate 6 from diacetone glucose in nine steps and 36% overall yield is described. Idopyranosiduronate 6 is useful as a glycosyl acceptor and as an intermediate that may be further elaborated into iduronic acid trichloroacetimidate glycosyl donors for the assembly of glycosaminoglycan structures as illustrated here.     

Polysaccharides as building blocks for nanotherapeutics

The use of polysaccharides as building blocks in the development of nano-sized drug delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, low toxicity and low cost. In addition, the variety of physicochemical properties and the ease of chemical modifications enable the preparation of a wide array of nanoparticles. This tutorial review describes the properties of common polysaccharides, the main mechanisms for polysaccharide based-nanoparticles preparation, and provides examples from the conceptual design towards pre-clinical and clinical applications.     

Benzoderivatives of nucleic acid bases as modified DNA building blocks

The tautomeric properties of benzoderivatives of the canonical nucleic acid bases have been studied by using different computational approaches. Attention has been paid to the impact of the benzene group in altering the tautomeric preferences of the canonical bases both in the gas phase and in aqueous solution. To this end, relative solvation free energies of the tautomers determined from Self-Consistent Reaction Field continuum calculations and Monte Carlo-Free Energy Perturbation are combined with gas-phase tautomerization free energies determined from quantum mechanical calculations. The results provide a detailed picture of the tautomeric preferences of the benzoderivatives of nucleic acid bases. This information is used to examine the recognition properties of the preferred tautomers of the benzo-fused derivatives, paying particular attention to the ability to form Watson-Crick hydrogen-bonding and stacking interactions as well as to the hydrophobic nature of the modified bases. The implications of present results on the potential use of benzo-fused bases as potential building blocks in modified DNA duplexes are examined.     

Core-shell particles: building blocks for advanced polymer materials

Polymer particles with submicrometer dimensions show promising applications in “bottom-to-top approach” to fabrication of materials with periodic structure, function, and composition. A novel approach to producing such materials is proposed, which employs core-shell particles with specific structures and compositions. We report on the synthesis of core-shell particles using interfacial polymerization and heterocoagulation techniques. The compositions of core-forming material and/or the shell-forming polymers were selectively controlled to be make the cores or the shells rigid or fluid, fluorescent or non-fluorescent, organic or inorganic. Several potential applications of nanocomposite materials obtained from these particles are demonstrated, including three-dimensional optical data storage and optical limiting and switching.     

De novo synthesis of uronic acid building blocks for assembly of heparin oligosaccharides

An efficient de novo synthesis of uronic acid building blocks is described. The synthetic strategy relies on the stereoselective elongation of thioacetal protected dialdehydes 12 a and 17. The dialdehydes are prepared from D-xylose, a cheap and commercially available source. A highly stereoselective MgBr(2)OEt(2)-mediated Mukaiyama aldol addition to C4-aldehyde 12 a is performed to obtain D-glucuronic acid building block 16, whereas L-iduronic acid building block 22 is prepared by MgBr(2)OEt(2)-mediated cyanation of C5-aldehyde 17. Synthesis of a heparin disaccharide demonstrates the utility of the de novo strategy for the assembly of glycosaminoglycan oligosaccharides.     

Synthetic protocols and building blocks for molecular electronics

Simple and readily accessible aryl bromides are useful building blocks for thiol end-capped molecular wires. Thus, 4-bromophenyl tert-butyl sulfide and 1-bromo-4-(methoxymethyl)benzene serve as precursors for a variety of oligo(phenylenevinylene) and oligo(phenyleneethynylene) wires via efficient synthetic transformations as presented in this paper.     

Shape-persistent macrocycles: building blocks for complex organic and polymeric architectures

Alkyl- and Oligostyrene substituents were attached to shape-persistent macrocycles based on a phenyl-ethynyl backbone. In good solvents for both the rigid core and the flexible corona no aggregation occurred. Whereas, addition of a solvent that selectively solubilizes the corona induced a solvophobic aggregation. For alkyl substituted rings the experimental data were described by a monomer-dimer equilibrium. In contrast, the oligostyrene substituted rings formed more expanded aggregates which were investigated by scattering and by imaging methods. The superstructures are consequently described as hollow supramolecular cylindrical brushes.     

Benzoylated uronic acid building blocks and synthesis of N-uronate conjugates of lamotrigine

A chemoenzymatic approach towards benzoylated uronic acid building blocks has been investigated starting with benzoylated hexapyranosides using regioselective C-6 enzymatic hydrolysis as the key step. Two of the building blocks were reacted with the antiepileptic drug lamotrigine. Glucuronidation of lamotrigine using methyl (2,3,4-tri-O-benzoyl-α-D-glycopyranosyl bromide)uronate proceeded to give the N2-conjugate. However, lamotrigine-N2-glucuronide was most efficiently synthesised from methyl (2,3,4-tri-O-acetyl-α-D-glucopyranosyl bromide)uronate. Employing nitromethane as solvent with CdCO(3) as a base lamotrigine-N2 glucuronide was prepared in a high yield (41%). Also methyl (2,3-di-O-benzoyl-4-deoxy-4-fluoro-α-D-glucosyl bromide)uronate underwent N-glucuronidation, but the product was unstable, eliminating hydrogen fluoride to give the corresponding enoate conjugate.     

Viruses as building blocks for materials and devices

From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles. They are composed of a small number of different (bio)polymers: proteins and nucleic acids. Many viruses are enveloped in a lipid membrane and all viruses do not have a metabolism of their own, but rather use the metabolic machinery of a living cell for their replication. Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution by taking advantage of their inbuilt colocalization of geno- and phenotypes. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine.     

Boronic acid based peptidic receptors for pattern-based saccharide sensing in neutral aqueous media, an application in real-life samples

The advent of the alternative sweeteners market has signaled a demand for chemosensors which target multiple saccharides and saccharide derivatives, in aqueous media at physiological pH. This demand has largely been unmet as existing molecular receptors for saccharides have generally not shown sufficient degrees of affinity and selectivity in aqueous media. A chemosensor array for saccharides and saccharide derivatives, fully operational in aqueous media at physiological pH, has been developed and is reported herein. Boronic acid based peptidic receptors, derived from a combinatorial library, served as the cross-reactive sensor elements in this array. The binding of saccharides to these receptors was assessed colorimetrically using an indicator uptake protocol in the taste-chip platform. The differential indicator uptake rates of these receptors in the presence of saccharides were exploited in order to identify patterns within the data set using linear discriminant analysis. This chemosensor array is capable of classifying disaccharides and monosaccharides as well as discriminating compounds within each saccharide group. Disaccharides have also been distinguished from closely related reduced-calorie counterparts. This linear discriminant analysis set was then employed as a training set for identifying a specific saccharide in a real-world beverage sample. The methodology developed here augurs well for use in other real-world samples involving saccharides as well as for sensing other desired analytes.