A modular approach to organic, coordination complex and polymer based podand hosts for anions

A range of novel host molecules with various degrees of preorganisation for the supramolecular complexation of anionic guest species are analysed within the context of other recent advances in the field. A modular approach to the design of cationic podands incorporating both organic and coordination compound cores is discussed. Special attention is given to ‘pinwheel’ hosts with functionalities including pyridyl, bipyridyl, aminopyridyl and ureas. The electrochemical and photochemical anion sensing by these functionalised podands is also reviewed. Much larger and more pre-organised calixarene units with consequent alteration of complexation properties, as well as the extension of this work to polystyrene-based and coordination polymer systems and metallogels are also covered.     

A modular "toolbox" approach to flexible branched multimacrocyclic hosts as precursors for multiply interlocked architectures

Tetralactam macrocycles can be functionalized by a variety of cross-coupling reactions. A modular "toolbox" strategy is presented that allows 1) several tetralactam macrocycles to be covalently connected with each other or with a central spacer, 2) the macrocycles to be substituted with or connected to different chromophores, and 3) metal-coordination sites to be attached to the macrocycles. With this approach a series of different oligo-macrocyclic hosts was obtained with great structural diversity and enormous potential for further functionalization. Rotaxanes made on the basis of these macrocycles have been synthesized to demonstrate their utility in building more complex supramolecular architectures.     

Click fleximers: a modular approach to purine base-expanded ribonucleoside analogues

The synthesis of nucleoside analogues incorporating 4-(5-pyrimidinyl)-1,2,3-triazole aglycons as expanded purine nucleobase mimics were accessed using the copper-catalyzed azide-alkyne Huisgen cycloaddition between a ribosyl azide and 5-alkynylpyrimidines. Depending on the nature of the alkyne employed, other nucleoside analogues that possess fluorescence or potential metal-binding properties were prepared. Computational studies were undertaken on the purine analogues and indicate that the heterocycles of the unfused nucleobase prefer a coplanar arrangement and the anti-glycosidic conformer is favoured in most instances.     

Anion sensing by Phenazine-based urea/thiourea receptors

The novel colorimetric receptors 2,3-bis-N-(9,10-diaza-anthracen-1-yl)-N′-phenylurea and 2,3-bis-N-(9,10-diaza-anthracen-1-yl)-N′-phenylthiourea have been prepared by the reaction of 2,3-diaminophenazine with phenylisocyanate and phenylisothiocyanate, respectively, in quantitative yields. The interaction and colorimetric sensing properties of receptor = 2 and 3 with different anions were investigated by naked eye, UV-vis and fluorescence spectroscopy in DMSO. The receptors effectively and selectively recognized biologically important F⁻, CH₃COO⁻, H₂P in the presence of other anions, such as Cl⁻, Br⁻, I⁻ and HS in DMSO.     

Ion sensing coupled to resonance energy transfer: a highly selective and sensitive ratiometric fluorescent chemosensor for Ag(I) by a modular approach

We report a novel dimeric boradiazaindacene dye which can be converted in one step to an efficient resonance energy transfer (RET) dyad. In addition, if this modification is done with appropriate ligands, RET can be coupled to ion sensing. The utility of this approach is demonstrated in a highly selective, emission ratiometric chemosensor for Ag(I).     

Anion recognition by a family of quinoline-functionalised bis-amide hosts in solid state and in solution

The interaction between a series of bidentate, amide-functionalised 8-oxyquinoline receptors and coordinating anions is investigated. Anion recognition properties and conformations were studied by solid-state structures, Hartree–Fock calculations and solution-phase ¹H NMR investigations. Our findings suggest that the amide-oxyquinoline motif coordinates anions and water with a well-defined, consistent geometry involving multiple hydrogen bonds. Solution studies of the neutral receptors reveal the unprotonated oxyquinoline ring to indirectly contribute to anion binding by the adjacent amide NH groups despite being unable to directly participate through hydrogen bonding.     

"Flexiball" toolkit: a modular approach to self-assembling capsules.

We report the synthesis and characterization of new, self-assembling molecular capsules. The modular strategy makes use of glycoluril building blocks available in multigram amounts combined with aromatic spacer elements. The lengthy syntheses encountered with earlier generations of capsules are avoided, and several capsules of nanometer dimensions are now accessible. Single bond attachments between spacers and glycoluril modules result in monomers as dimeric capsules that are less rigid than their earlier counterparts. The host-guest properties of the homo- and heterodimeric capsules were studied using a combination of NMR and ESI-mass spectrometry. They show a less pronounced selectivity for guests of different sizes, and their increased flexibility prevents self-assembly when no rigidifying elements are present on the central spacer unit. Some of the new capsules bear inwardly directed, secondary amide N-H protons. These can be further functionalized, as shown by their methylation to give tertiary analogues. The structures hold broader implications for the placement of functional groups on concave molecular surfaces.     

Tandem modular protein-based hydrogels constructed using a novel two-component approach

Leucine zipper sequences have been widely used to engineer protein-based hydrogels for biomedical applications. Previously, we have used this method to engineer tandem modular protein-based hydrogels as a step toward developing extracellular matrix-mimetic hydrogels. However, the spontaneous self-association of leucine zipper sequences in solution has made it challenging to express and purify tandem modular proteins carrying leucine zipper under native conditions. To obviate this problem, here we report a novel two-component approach to engineer tandem modular protein-based hydrogels. This methodology makes use of two complementary leucine zipper sequences (CCE and CCK), which do not self-associate but self-assemble into heterodimeric coiled-coils at neutral pH, as functional groups to drive the self-assembly of protein hydrogels. The two protein components are bifunctional and trifunctional tandem modular proteins carrying the leucine zipper functional groups. We found that the two proteins carrying CCE or CCK can be expressed and purified under native conditions with high yield. Upon mixing, the aqueous solution of the two proteins readily forms a transparent hydrogel. The resultant hydrogel can undergo reversible sol-gel transitions as a function of temperature, and shows much improved erosion properties. This method provides a new approach to tune the topology and physical properties of the protein hydrogels via genetic engineering, and opens the possibility to systematically explore the use of large native extracellular proteins to engineer extracellular matrix-mimetic hydrogels.     

A modular approach toward block copolymers

A novel methodology for the formation of block copolymers has been developed that combines ring-opening metathesis polymerization (ROMP) with functional chain-transfer agents (CTAs) and self-assembly. Telechelic homopolymers of cyclooctene derivatives end-functionalized with hydrogen-bonding or metal-coordination sites are formed through the combination of ROMP with a corresponding functional CTA. These telechelic homopolymers are fashioned with a high control over molecular weight and without the need for post-polymerization procedures. The homopolymers undergo fast and efficient self-assembly with their complement homopolymer or small molecule analogue to form block-copolymer architectures. The block copolymers show equivalent association constants as their small molecule analogues described in the literature, regardless of size or nature of the complementary unit or the polymer side chain.     

The modular approach to ligand discovery

Identifying specific protein-ligand interactions is a long-standing problem in drug discovery and chemical biology, which is only exacerbated by the abundance of uncharacterized proteins revealed by genomics. Last month in Chemistry Biology, Sem et al. described a powerful technique for rapidly screening protein families for ligands.     

Co-crystallisation as a modular approach to the discovery of spin-crossover materials

Herein we present co-crystallisation as a strategy for materials discovery in the field of switchable spin crossover (SCO) systems. Using [Fe(3-bpp)₂]·2A (where 3-bpp = 2,6-bis(pyrazol-3-yl)pyridine, A = BF₄⁻/PF₆⁻) as a starting point, a total of 11 new cocrystals have been synthesised with five different dipyridyl coformers. Eight of these systems show spin crossover behaviour, and all show dramatically different switching properties from the parent complex. The cocrystals have been studied by variable temperature single-crystal X-ray diffraction and SQUID magnetometry to develop structure–property relationships. The supramolecular architecture of the cocrystals depends on the properties of the coformer. With linear, rigid coformer molecules leading to 1D supramolecular hydrogen-bonded chains, while flexible coformers form 2D sheets and bent coformers yield 3D network structures. The SCO behaviour of the cocrystals can be modified through changing the coformer and thus co-crystallisation presents a rapid, facile and highly modular tool for the discovery of new switchable materials. The wider applicability of this strategy to the design of hybrid multifunctional materials is also discussed.

The switching behaviour of spin crossover cocrystals can be modified through changing the coformer and thus co-crystallisation presents a rapid, facile and highly modular tool for the discovery of new switchable materials.     

Synthesis of bisbenzannulated spiroketals-model studies for a modular approach to rubromycins

[reaction: see text] A highly flexible synthesis of bisbenzannulated spiroketals is described with additions of lithiated methoxyallene to aryl aldehydes and Heck reactions as key steps. Subsequent hydrogenations and ketalizations afforded the desired spiroketals in good yields and with predominating trans-configuration. With model compound 30, already bearing the fully substituted naphthyl core of rubromycins, the ketalization proceeded efficiently providing the expected product 31 and the isopropoxy compound 32. Both products are advanced model compounds of heliquinomycin.     

A modular approach to main-chain organometallic polymers

A highly efficient route to a new class of organometallic polymers containing difunctional N-heterocyclic carbenes has been developed. Bis(imidazolium) halides and divalent group X metals were copolymerized to afford organometallic polymers in up to quantitative yields and with molecular weights up to 10(6) Da, depending on the structure of the N-heterocyclic carbene and the incorporated transition metal. Enhanced solubilities were demonstrated through post-polymerization ligation with phosphines. Finally, selective end-group functionalization and excellent molecular weight control was achieved through the inclusion of monofunctional chain transfer agents during the polymerization.     

Synthesis of the non-classical acetogenin mucocin: a modular approach based on olefinic coupling reactions

A three component modular synthesis of the potent antitumor agent mucocin, based on olefinic coupling reactions, is described. A cross-metathesis on tetrahydropyran and tetrahydrofuran alkene components was used to assemble a stereochemically complex, non-adjacently-linked bicyclic ether. The latter was elaborated to a sulfone and partnered with a butenolide aldehyde component in a Julia-Kocienski olefination to provide the mucocin framework, which was converted to the natural product after hydrogenation and alcohol deprotection.     

Anion recognition and sensing with Zn(II)-dipicolylamine complexes

This critical review covers the developments in anion recognition and sensing using Zn(II)-dipicolylamine functionalized receptors over the past decade with emphasis on recent rapid advances in the last five years.     

Anion chelation-induced porphyrin protonation and its application for chloride anion sensing

The protonation of a simple meso-tetraphenylporphyrin in an organic-aqueous system was found to be induced by the counteranions. During the process of protonation, the counteranion of the proton sources binds with the porphyrin core and thus promotes the complexation of the porphyrin and protons. The interaction of porphyrin and anion was characterized by fluorescence, UV-visible, cyclic voltammetry, (1)H NMR, and IR. Moreover, it could be exploited in selective fluorescent sensing of Cl(-). The sensing mechanism was based on extraction of protons from the aqueous phase into the organic phase by free base porphyrin and simultaneous coextraction of Cl(-), which promoted porphyrin protonation, and hence resulted in significant changes of the porphyrin fluorescence spectra. Selectivity trends turned out to be dependent upon the lipophilicity of anion and the binding affinity and structure complementarity between the protonated porphyrin and anions. The fluorescence enhancement of the porphyrin band at 684 nm showed modest selectivity for Cl(-) and NO(3)(-).     

Education: A modular approach to microfluidics in the teaching laboratory

This article seeks to educate the reader about the role played by the microfluidics teaching lab in the education of science, technology, engineering and mathematics for students of all ages. The discussion is intended to serve as a general guide to educators about the lab philosophy, goals, lab experiments and required equipment and reagents necessary for a successful microfluidics teaching laboratory. We hope that this article will stimulate other groups and companies to describe what they are doing to encourage education in this sector. At LabSmith we have developed a modular approach for teaching and demonstrating microfluidics that allows the end user to tailor the laboratory to course goals without an impact on the package of experimental equipment required and available to them. Thus, it is possible to educate students either in the art of microfluidics or use microfluidics to educate students about fundamental physical, chemical, or biological principles. The laboratory experiments discussed here are for students with educational experience at high school, undergraduate, graduate, and post-graduate levels.     

Cracking the genetic code(s) with a modular determinative degree: An algebraic approach

We introduce a new “modular” (compositional and positional) determinative degree for the four bases U, C, A, and G to define a “Dinucleotide charge number” for the dinucleotides, which discriminates between the two octets of dinucleotides: M₁ and M₂. These two components are exchanged under a transformation, which, we show, implements the Rumer symmetry. We invoke also the base “size index” of Rosen as a complementary determinative degree for the third‐base component of a codon. Next, we define the address functions for the 64 codons (amino acids), which are functions only of the composition and position of these codons in the genetic table. With these ingredients, we build an algebraic classification of the amino acids in the genetic code and some of its nonstandard versions as a preliminary application. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003     

Polysiloxane-bound ligand accelerated catalysis: a modular approach to heterogeneous and homogeneous macromolecular asymmetric dihydroxylation ligands

Polysiloxane acts as a modular scaffold for macromolecular reagent development. Two separate components were covalently integrated into one material, one constituent provided reagent functionality, the other modulated solubility. In particular cinchona alkaloid based ligands used in the osmium tetroxide catalyzed asymmetric dihydroxylation (AD) reaction were covalently attached to commercially available polysiloxane. To enhance the reactivity of these polymeric ligands, multifunctional reagents were designed to include both the cinchona alkaloid and an alkoxyethylester solubilizing moiety providing random co-polymers. While the mono-functional materials led to heterogeneous conditions, the bi-functional polymers resulted in homogeneous reaction mixtures. Although both reagent types provided diol products with excellent yield and selectivity (>99% ee in nearly quantitative yield) the homogeneous analog has nearly twice the reactivity. Every repeat unit in the heterogeneous material was functionalized along the polysiloxane backbone while approximately half of these sites contained ligand in the homogeneous version. This approach led to macromolecular catalysts with high loadings of ligand and therefore materials with very low equivalent weights. Although these polymers are highly loaded they do maintain reactivity on a par with their free ligand counterpart. Using straightforward purification techniques (i.e. precipitation, simple filtration, or ultrafiltration) these polymeric ligands were easily separated from diol product and reused multiple times. Polysiloxane is a viable support for the catalysis of AD reactions and may provide a generally useful backbone for other catalytic systems.     

A modular cross-linking approach for exploring protein interactions

A method is described for the elucidation of protein-protein interactions using novel cross-linking reagents and mass spectrometry. The method incorporates (1) a modular solid-phase synthetic strategy for generating the cross-linking reagents, (2) enrichment and digestion of cross-linked proteins using microconcentrators, (3) mass spectrometric analysis of cross-linked peptides, and (4) comprehensive computational analysis of the cross-linking data. This integrated approach has been applied to the study of cross-linking between the components of the heterodimeric protein complex negative cofactor 2.