Fluorescence self-quenching of a mannosylated poly(p-phenyleneethynylene) induced by concanavalin A

We report that static quenching of a mannosylated conjugated polymer (sugar-PPE) by Concanavalin A is positively dependent upon sugar-PPE concentration, that is, the recorded Stern-Volmer constants increase with increasing sugar-PPE concentration. Comparison with data obtained from isothermal titration calorimetry (ITC) display the increased sensitivity of the quenching method when compared to ITC. The proposed mechanism suggests the interaction of two or more chains of PPE with one Con A molecule leading to a quenched sugar-PPE-Con A construct.     

Ferrocene conjugates with mannose: synthesis and influence of ferrocene aglycon on mannose‐mediated adhesion of Escherichia coli

Bacterial adhesion, mediated through interaction of bacterial lectins with carbohydrate structures presented on the surface of the host cells, is a prerequisite for infection. Anti‐adhesion therapy, based on the inhibition of lectins by suitable carbohydrates, has been considered as a weapon for the combat of microbial diseases. Structural alteration of aglycon portions of mannose derivatives strongly influences their inhibitory potency toward type 1 fimbriated Escherichia coli. Thus several conjugates of mannose‐containing ferrocene aglycon moieties were synthesized and tested. The novel ferrocene conjugates 10, 12 and 14 were obtained by esterification of O‐mannosylated propionic acid 1 with ferrocene alcohols R‐Fn‐(CH₂)_n‐OH (Fn = 1,1'‐ferrocenylene; 2, n = 1, R = COOMe; 7, n = 1, R = NHBoc; 8, n = 2, R = H) in the presence of Boc₂O/DMAP with subsequent debenzylation of the intermediate O‐protected esters. Performed hemagglutination inhibitory tests showed that the examined bioorganometallics exhibit better inhibitory activity than known inhibitor methyl α‐d ‐mannoside. Thus ferrocene–mannose conjugate 14 with the dimethylene spacer between ferrocene core and chiral linker displayed the best inhibitory efficiency. Copyright © 2012 John Wiley & Sons, Ltd.     

Ferrocene–β‐Cyclodextrin Conjugates: Synthesis,Supramolecular Behavior,and Use as Electrochemical Sensors

Ferrocene with a β‐cyclodextrin unit bound to one or both cyclopentadienyl rings through the secondary face were conveniently synthesized by regiospecific copper(I)‐catalyzed cycloaddition of 2‐O‐propargyl‐β‐cyclodextrin to azidomethyl or bis(azidomethyl)ferrocene. The supramolecular behavior of the synthesized conjugates in both the absence and presence of bile salts (sodium cholate, deoxycholate, and chenodeoxycholate) was studied by using electrochemical methods (cyclic and differential pulse voltammetry), isothermal titration calorimetry, and NMR spectroscopy (PGSE, CPMG, and 2D‐ROESY). These techniques allowed the determination of stability constants, mode of inclusion, and diffusion coefficients for complexes formed with the neutral and, in some cases, the oxidized states of the ferrocenyl conjugates. It was found that the ferrocenyl conjugate with one β‐cyclodextrin unit forms a redox‐controllable head‐to‐head homodimer in aqueous solution. The ferrocene–bis(β‐cyclodextrin) conjugate is present in two distinguishable forms in aqueous solution, each one having a different half‐wave oxidation potential for the oxidation of the ferrocene. By contrast, only one distinguishable form for the oxidized state of the ferrocene–β‐cyclodextrin conjugate is detectable. The redox‐sensing abilities of the synthesized conjugates towards the bile salts were evaluated based on the observed guest‐induced changes in both the half‐wave potential and the current peak intensity of the electroactive moiety.     

Linear Precision Glycomacromolecules with Varying Interligand Spacing and Linker Functionalities Binding to Concanavalin A and the Bacterial Lectin FimH

A series of precision glycomacromolecules is prepared following previously established solid phase synthesis allowing for controlled variations of interligand spacing and the overall number of carbohydrate ligands. In addition, now also different linkers are installed between the carbohydrate ligand and the macromolecular scaffold. The lectin binding behavior of these glycomacromolecules is then evaluated in isothermal titration calorimetry (ITC) and kinITC experiments using the lectin Concanavalin A (Con A) in its dimeric and tetrameric form. The results indicate that both sterical and statistical effects impact lectin binding of precision glycomacromolecules. Moreover, ITC results show that highest affinity toward Con A can be achieved with an ethyl phenyl linker, which parallels earlier findings with the bacterial lectin FimH. In this way, a first set of glycomacromolecule structures is selected for testing in a bacterial adhesion–inhibition study. Here, the findings point to a one‐sugar binding mode mainly affected by sterical restraints of the nonbinding parts of the respective glycomacromolecule.     

Synthesis, cyclic voltammetry, and UV–Vis studies of ferrocene-dithiafulvalenes as anticipated electron-donor materials

Abstract  

New ferrocenyl ketones were obtained as precursors of novel π-conjugated ferrocene-dithiafulvalene (Fc-DTF) and π-extended-ferrocenedithia-fulvalenes (π-exFc-DTF) as electron-donor conducting materials from ferrocene by a direct aroylation process using the Friedel–Crafts reaction. Novel Fc-DTF conjugates were synthesized using the Wittig–Horner reaction and their structures were determined. The redox behavior of the ferrocenyl carbonyl compounds Fc-DTF and Fc-π-exDTF was investigated in comparison to the parent ferrocene by means of cyclic voltammetry. A one-electron redox behavior was observed for carbonylferrocenes as one wave potential, while a two-electron process was observed as two oxidation waves for the conjugates. Introduction of electron-withdrawing groups led to increasing E _pa values and decreasing ΔE _p values. The UV–Vis spectra of some compounds were studied in comparison with ferrocene. The absorption spectra showed a red-shift with a slight increase in the absorption intensities.     

Fluorescence Turn‐On Sensing of Lectins with Mannose‐Substituted Tetraphenylethenes Based on Aggregation‐Induced Emission

The synthesis of mannose‐substituted tetraphenylethenes (TPEs) and their aggregation‐induced emission (AIE) behavior, induced by interactions with concanavalin A (Con A), are reported. A mixture of the mannose‐TPE conjugates and Con A in a buffer solution displays an intense blue emission on agglutination within a few seconds, which serves as a “turn‐on” fluorescent sensor for lectins. The sensing is also selective: the conjugates act as a sensor for Con A, but do not sense a galactose‐binding lectin, PNA. Con A‐recognition is not affected even in the presence of other proteins in a mixture. The conjugates also exhibit high sensitivity to detect Con A. An increased sensitivity of the conjugates results if mannopyranoside substituents are linked to the TPE‐core unit with a flexible chain and/or when the number of mannose residues increases.     

Synthesis,cyclic voltammetry,and UV–Vis studies of ferrocene-dithiafulvalenes as anticipated electron-donor materials

Abstract  New ferrocenyl ketones were obtained as precursors of novel π-conjugated ferrocene-dithiafulvalene (Fc-DTF) and π-extended-ferrocenedithia-fulvalenes (π-exFc-DTF) as electron-donor conducting materials from ferrocene by a direct aroylation process using the Friedel–Crafts reaction. Novel Fc-DTF conjugates were synthesized using the Wittig–Horner reaction and their structures were determined. The redox behavior of the ferrocenyl carbonyl compounds Fc-DTF and Fc-π-exDTF was investigated in comparison to the parent ferrocene by means of cyclic voltammetry. A one-electron redox behavior was observed for carbonylferrocenes as one wave potential, while a two-electron process was observed as two oxidation waves for the conjugates. Introduction of electron-withdrawing groups led to increasing E _pa values and decreasing ΔE _p values. The UV–Vis spectra of some compounds were studied in comparison with ferrocene. The absorption spectra showed a red-shift with a slight increase in the absorption intensities. Graphical abstract        

1,2-disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarial agents

This work presents a new family of organometallic antimalarial compounds consisting of ferrocene bearing a chloroquine-derived moiety as well as a 1,2;3,5-diisopropylidene glucofuranose moiety at a cyclopentadienyl scaffold in a 1,2-substitution pattern. The synthetic route proceeds via a stereoselective functionalization of ferrocene carboxaldehyde to the 1,2-disubstituted conjugates. After complete characterization of these new, trifunctional conjugates, they were examined for their cytotoxicity in two cancerous cell lines (MDA-MB-435S and Caco2) and one non-cancerous cell line (MCF-10A), showing that increased cytotoxicity can be observed for the chloroquine ferrocenyl conjugates compared to their carbohydrate-substituted precursors. The antiplasmodial activity of the conjugates in a chloroquine-sensitive strain of Plasmodium falciparum (D10) and a chloroquine-resistant strain (Dd2) was determined. Monosubstituted conjugates 13, 14 and 15 exhibit decreasing activity with increasing alkyl chain length between the ferrocene and quinoline moiety, bifunctional conjugates 16, 17, 18 show constant activity, performing better than chloroquine in the Dd2 strain.     

功能化纳米金增强的谷胱苷肽电化学检测和巯基识别

以冠有大量二茂铁的纳米金微粒/抗生蛋白链菌素结合物为标记物,将其标记于生物素修饰的巯基识别试剂上,制成了具有电化学活性和纳米金放大作用的传感器.首先将双官能团的羟基琥珀酰亚胺酯自组装于电极表面上,借助两步交联反应固定含巯基的蛋白质,并且引入巯基识别试剂标记生物素的马来酰亚胺,随后利用生物素与链霉抗生物素之间的特异性吸附作用,引入功能化的纳米金.采用伏安法测定修饰在纳米金上的二茂铁,可识别和测定表面固定的蛋白质,还原型谷胱苷肽在5μmol/L～0.1mmol/L浓度范围内存在线性关系,检测限可达到1nmol/L.     

A new triferrocenyl-tris(hydroxymethyl)aminomethane derivative as a highly sensitive electrochemical marker of biomolecules: application to the labelling of PNA monomers and their electrochemical characterization

We have designed and synthesised a new organometallic molecule containing three ferrocene groups for use as a highly sensitive electrochemical marker in biological assays. This trisferrocene derivative was conjugated to different PNA monomers, and the electrochemical activities of the conjugates were extensively investigated in organic solvents, in view of their potential diagnostic applications. The results showed that the introduction of a trisferrocene unit on the PNA monomer triples the current signal in comparison with the monoferrocene-labelled one. Despite their greater molecular complexity, trisferrocene-conjugated PNA monomers are even more electrochemically active than the reference ferrocene. By using differential pulse voltammetry (DPV), the detection limit can reach 10(-8) M in acetonitrile solution. These results are a good premise for the use of the trisferrocene unit as an effective electrochemical probe for biomolecules.     

Enhanced guest affinity and enantioselectivity through variation of the Gd3+ [15-metallacrown-5] side chain

Supramolecular hosts that bind guests reversibly are investigated for potential catalysis and separations applications. Chiral Ln(3+)[15-Metallacrown-5] metallocavitands bind carboxylate guests in hydrophobic cavities generated by their ligand side chains. A thermodynamic study on Gd(3+)[15-metallacrown-5] hosts with ligands bearing phenyl side chains containing 0, 1, and 2 methylene spacers (1-pgHA, 1-pheHA, 1-hpheHA, respectively) is presented to quantitatively assess how guest affinity and chiral selectivity can be enhanced through changes to the ligand side chain. Guest binding affinity was measured with cyclic voltammetry using ferrocene carboxylate as a redox probe. K(a) values between ferrocene carboxylate and 1-pgHA and 1-pheHA were 4800 ± 400 M(-1) and 4400 ± 700 M(-1), respectively. Significantly stronger binding affinity of 12,100 ± 700 M(-1) was measured with 1-hpheHA, a result of the longer side-chains more completely encapsulating the guest. A similar trend was observed with benzoate. The side chain also influenced enantioselectivity, as K(S)/K(R) values of up to 2.2 ± 0.6 were measured. The side chain dependent guest binding supports the development of highly selective Ln(3+)[15-Metallacrown-5] hosts for use in catalysis and separations through careful ligand design.     

Donor–acceptor perylenediimide–ferrocene conjugates: synthesis,photophysical, and electrochemical properties

Donor–acceptor, perylenediimide–ferrocene conjugates have been synthesized by Suzuki, and Sonogashira coupling reactions. The photophysical and electrochemical properties of these conjugates are discussed. It has been shown that fluorescence as well as the electron affinity of the perylenediimide can be tuned by attaching the appropriate ferrocenyl derivatives.     

A bioorganometallic approach for the electrochemical detection of proteins: a study on the interaction of ferrocene-peptide conjugates with papain in solution and on Au surfaces

In this paper, a new bioorganometallic approach for the detection of proteins using surface-bound ferrocene-peptide conjugates is presented. Specifically, a series of peptide conjugates of 1'-aminoferrocene-1-carboxylic acid (ferrocene amino acid, Fca) is synthesized: Boc-Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OMe (2), Thc-Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OMe (3), Thc-Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OH (4), Boc-Fca-Gly-Gly-Arg(Mtr)-Tyr-OMe (7), Thc-Fca-Gly-Gly-Arg(Mtr)-Tyr-OMe (8), Thc-Fca-Gly-Gly-Arg(Mtr)-Tyr-OH (9), Thc-Fca-Gly-Gly-Arg-Tyr-OH (10). The peptide is conjugated to the C-terminal side of Fca and compounds 4, 7-10 possess a thiostic acid linked to the N-terminal side of Fca in order to facilitate formation of thin films on gold substrates. Competitive inhibition towards papain was determined for Thc-Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OH (4), Thc-Fca-Gly-Gly-Arg(Mtr)-Tyr-OH (9) and Thc-Fca-Gly-Gly-Arg-Tyr-OH (10). The binding interaction between the peptide modified substrates and papain enzyme was studied using real-time surface plasmon resonance (SPR) imaging. Peptide 10 showed the strongest binding affinity to papain. Adsorption/desorption rate constants were ka = 1.75+/-0.05 x 10(5) M(-1) s(-1) and kd = 2.90 +/- 0.05 x 10(-2) s(-1). Interactions of papain with Fca-peptide 10 were investigated by cyclic voltammetry. The interaction results were also verified by measuring the electrochemical response of the peptide-papain interaction as function of increasing enzyme concentration. A linear relationship was observed for papain concentration of up to 80 nM. Shifting to higher potentials as well as decrease in the overall signal intensity was observed. The detection limit was 4 x 10(-9) M.     

Modified expanded corrole-ferrocene conjugates: syntheses, structure and properties

Syntheses, characterization and properties of expanded corrole-ferrocene conjugates are reported. Ferrocenyl group are covalently linked to the corrole macrocycle through three different spacers groups. The synthetic strategy involved prior insertion of ferrocene with spacers to the dipyrromethane unit followed by a "3+2" acid-catalyzed oxidative coupling methodology. The optical and emission data of the expanded corrole-ferrocene conjugates depend on the nature and length of the spacer groups and the maximum effects are seen where ferrocene is directly linked to the meso carbon of macrocycle. The single crystal X-ray structure of two expanded corrole-ferrocene conjugates; [22]pentaphyrin (1.1.0.1.0) with different meso substituents, clearly reveal shortening of the C-C bond length linking the meso carbon and the aryl substituent containing the ferrocene moiety relative to meso aryl substituents without ferrocene. The results suggest that an electronic interaction between the two pi systems. Electrochemical data reveal harder oxidation for the ferrocene unit in the conjugates relative to free ferrocene; this suggests the electron donating nature of the ferrocene. The first corrole ring oxidation shows easier oxidation relative to 1 and the magnitude of shifts in potential is inversely proportional to the length of spacer. The molecular first hyperpolarizabilities (beta) measured at 1064 nm by HRS method vary in the range 20-32x10(-30) esu and imply that the beta values can be increased by enhancing the number of mobile electrons in the conjugation. The conjugates form 1:1 metal complex with the Rh(I) where rhodium is coordinated to one amino and one imino nitrogen of the dipyrromethane unit.     

Metal-organic frameworks post-synthetically modified with ferrocenyl groups: framework effects on redox processes and surface conduction

Metal-organic framework (MOF) materials based on zinc(II) and aluminium(III) dicarboxylate frameworks with covalently attached ferrocene functional redox groups were synthesised by post-synthetic modification and investigated by voltammetry in aqueous and non-aqueous media. In the voltammetry experiments, ferrocene oxidation occurs in all cases, but chemically reversible and stable ferrocene oxidation without decay of the voltammetric response requires a "mild" dichloroethane solvent environment. The voltammetric response in this case is identified as "surface-confined" with fast surface-hopping of electrons and without affecting the bulk of MOF microcrystals. In aqueous media a more complex pH-dependent multi-stage redox process is observed associated with chemically irreversible bulk oxidation and disintegration of the MOF framework. A characteristic 30 mV per pH unit dependence of redox potentials is observed attributed to a "framework effect": the hydroxide-driven MOF framework dissolution.     

Synthesis of boron-dipyrromethene-ferrocene conjugates

Synthesis, spectral, electrochemical and photophysical properties of four BODIPY-ferrocene conjugates in which one or two ferrocenyl groups were covalently connected either directly to boron-dipyrromethene framework or to meso-phenyl group of boron-dipyrromethene unit are described. The BODIPY-ferrocene conjugates were prepared by adopting different synthetic routes. The absorption studies indicated the presence of charge transfer band in BODIPY-ferrocene conjugates in which the ferrocenyl group(s) were directly connected to boron-dipyrromethene framework. The electrochemical studies on conjugates indicated that ferrocenyl group was difficult to oxidize whereas boron-dipyrromethene unit was easier to reduce. The conjugates were non-fluorescent due to electron transfer from ferrocene to boron-dipyrromethene unit. However, when ferrocene was oxidized to ferrocenium ion with an oxidizing agent, the conjugates exhibited fluorescence with decent quantum yields (0.17-0.31) and lifetimes (3.8-5.2 ns).     

Achieving High Affinity towards a Bacterial Lectin through Multivalent Topological Isomers of Calix[4]arene Glycoconjugates

A family of seven topologically isomeric calix[4]arene glycoconjugates was prepared through the synthesis of a series of alkyne‐derivatised calix[4]arene precursors that are suitable for the attachment of sugar moieties by microwave‐assisted copper(I)‐catalysed azide–alkyne cycloaddition (CuAAC). The glycoconjugates thus synthesised comprised one mono‐functionalised derivative, two 1,2‐ or 1,3‐divalent regioisomers, one trivalent and three tetravalent topoisomers in the cone, partial cone or 1,3‐alternate conformations. The designed glycoconjugates were evaluated as ligands for the galactose‐binding lectin PA‐IL from the opportunistic bacterium Pseudomonas aeruginosa, a major causative agent of lung infections in cystic fibrosis patients. Binding affinities were determined by isothermal titration calorimetry (ITC), and the interaction with the lectin was shown to be strongly dependant on both the valence and the topology. Whereas the trivalent conjugate displayed enhanced affinity when compared to a monosaccharide model, the tetravalent conjugates are to‐date the highest‐affinity ligands measured by ITC. The topologies presenting carbohydrates on both faces of calixarene are the most potent ones with dissociation constants of approximately 200 nM . Molecular modelling suggests that such a multivalent molecule can efficiently chelate two of the binding sites of the tetrameric lectin; this explains the 800‐fold increase of affinity achieved by the tetravalent molecule. Surface plasmon resonance (SPR) experiments confirmed that this glycoconjugate is the strongest inhibitor for binding of PA‐IL to galactosylated surfaces for potential applications as an anti‐adhesive agent.     

Synthesis,crystal structure,electronic spectroscopy,electrochemistry and biological studies of carbohydrate containing ferrocene amides

A series of four new ferrocene–carbohydrate amides was prepared from pentose and hexose sugar derivatives. These include (5‐amino‐5‐deoxy‐1,2‐O‐isopropylidene‐α‐d ‐xylofuranose)‐1‐ferrocene carboxamide (2a), (5‐amino‐3‐O‐benzyl‐5‐deoxy‐1,2‐O‐isopropylidene‐α‐d ‐xylofuranose)‐1‐ferrocene carboxamide (2b), (methyl‐6‐amino‐6‐deoxy‐2,3‐O‐isopropylidene‐β‐d ‐ribofuranoside)‐1‐ferrocene carboxamide (2c) derived from furanose sugars and (6‐amino‐6‐deoxy‐1,2:3,4‐di‐O‐isopropylidene‐α‐d ‐galactopyranose)‐1‐ferrocene carboxamide (2d) derived from pyranose sugar. The compounds were characterized by spectroscopic means and the structure of amide derived from α‐d ‐xylofuranose (2a) was determined by X‐ray crystallography. The electronic and optical properties of the compounds were studied by means of cyclic voltammetry and absorption spectroscopy. The UV and electrochemical studies of these compounds, performed in aqueous solutions under physiological conditions (at pH 7.4), confirmed their stability. These results indicated that the compounds were suitable for conducting biological studies. The CD spectral analysis displays the effect of sugar substituents on the compounds. The cytotoxicity and antimicrobial activity of these conjugates were investigated on different cancer cell lines and microbes respectively. The degree of inhibition varied over a broad spectrum of Gram‐ positive and Gram‐negative bacteria. In addition, the compounds also exhibited antioxidant properties. Copyright © 2012 John Wiley & Sons, Ltd.     

Amino Acid Chirality and Ferrocene Conformation Guided Self‐Assembly and Gelation of Ferrocene–Peptide Conjugates

The self‐assembly and gelation behavior of a series of mono‐ and disubstituted ferrocene (Fc)–peptide conjugates as a function of ferrocene conformation and amino acid chirality are described. The results reveal that ferrocene–peptide conjugates self‐assemble into organogels by controlling the conformation of the central ferrocene core, through inter‐ versus intramolecular hydrogen bonding in the attached peptide chain(s). The chirality controlled assembling studies showed that two monosubstituted Fc conjugates FcCO–L FL FL A‐OMe and FcCO–L FL FD A‐OMe form gels with nanofibrillar network structures, whereas the other two diastereomers FcCO–D FL FL A‐OMe and FcCO–L FD FL A‐OMe exclusively produced straight nanorods and non‐interconnected small fibers, respectively. This suggests the potential tuning of gelation behavior and nanoscale morphology by altering the chirality of constituted amino acids. The current study confirms the profound effect of diastereomerism and no influence of enantiomers on gelation. Correspondingly, the diastereomeric and enantiomeric Fc[CO‐FFA‐OMe]₂ were constructed for the study of chirality‐organized structures.     

A comparison of biological and calorimetric analyses of multivalent glycodendrimer ligands for concanavalin A

The cluster glycoside effect — the observation that multivalent glycosides bind to their polyvalent protein receptors with apparent affinities greater than those that can be rationalized solely on the basis of valency — is by now a well established phenomenon. As part of a continuing effort to provide a molecular basis for the cluster glycoside effect, we report here the synthesis of two series of mannosylated dendritic ligands and their performance in a range of competitive and non-competitive binding assays, including hemeagglutination inhibition (HIA), enzyme-linked lectin assays (ELLA) and isothermal titration microcalorimetry (ITC). The first series of ligands contained a semi-rigid glycylglycine spacer and showed no significant performance enhancement in any binding studies. The second series of ligands contained a flexible tetraethylene glycol spacer; these ligands showed marked enhancements at tetravalent and hexavalent levels in both HIA (IC₅₀=3 and<0.8 μM, respectively) and ITC (K_A=6.2×10⁴ and 1.5×10⁶ M⁻¹, respectively) studies. In all cases, the thermodynamic parameters of association are consistent with non-specific aggregation rather than enhanced lectin–ligand affinity. This conclusion is reinforced by the lack of enhancements in ligand activity observed in ELLA studies.