Impact of sample history and solvent effects on pathway control in the supramolecular polymerisation of Au(i)-metallopeptide amphiphiles.

We investigate the kinetics of the supramolecular polymerisation of an Au(i)-metallopeptide amphiphile that assembles into exceptionally long and rigid nanofibers. We developed a precise preparation protocol to measure the concentration dependent assembly kinetics which elucidated a nucleation-elongation dominated supramolecular polymerisation process. We show striking differences in the assembly behavior and morphology in aqueous media, even at organic solvent contents as low as 1 vol%, compared to pure buffer.

Cucurbit[7]uril Macrocyclic Sensors for Optical Fingerprinting: Predicting Protein Structural Changes to Identifying Disease-Specific Amyloid Assemblies.

In a three-dimensional (3D) representation, each protein molecule displays a specific pattern of chemical and topological features, which are altered during its misfolding and aggregation pathway. Generating a recognizable fingerprint from such features could provide an enticing approach not only to identify these biomolecules but also to gain clues regarding their folding state and the occurrence of pathologically lethal misfolded aggregates. We report here a universal strategy to generate a fluorescent fingerprint from biomolecules by employing the pan-selective molecular recognition feature of a cucurbit[7]uril (CB[7]) macrocyclic receptor. We implemented a direct sensing strategy by covalently tethering CB[7] with a library of fluorescent reporters. When CB[7] recognizes the chemical and geometrical features of a biomolecule, it brings the tethered fluorophore into the vicinity, concomitantly reporting the nature of its binding microenvironment through a change in their optical signature. The photophysical properties of the fluorophores allow a multitude of probing modes, while their structural features provide additional binding diversity, generating a distinct fluorescence fingerprint from the biomolecule. We first used this strategy to rapidly discriminate a diverse range of protein analytes. The macrocyclic sensor was then applied to probe conformational changes in the protein structure and identify the formation of oligomeric and fibrillar species from misfolded proteins. Notably, the sensor system allowed us to differentiate between different self-assembled forms of the disease-specific amyloid-ß (Aß) aggregates and segregated them from other generic amyloid structures with a 100% identification accuracy. Ultimately, this sensor system predicted clinically relevant changes by fingerprinting serum samples from a cohort of pregnant women.

Facile access to foldable redox-active flavin-peptide conjugates.

A convenient approach for the synthesis of foldable redox-active flavin peptide conjugates was established. A model ß-hairpin oligopeptide motif was utilized to demonstrate that azidolysine side-chains are readily functionalised with an alkyne-bearing flavine derivative. The folding equilibrium of the peptide backbone as well as the redox behaviour of the flavin moieties remains intact after the conjugation.

Impact of NDI-Core Substitution on the pH-Responsive Nature of Peptide-Tethered Luminescent Supramolecular Polymers.

The pH-responsive nature of two self-assembled NDI-peptide amphiphile conjugates is reported. The diethoxy substituted NDI showed a pH-dependent assembly behaviour, as expected. In contrast, the isopropylamino- and ethoxy-substituted NDI based supramolecular polymer was stable at acidic and basic aqueous conditions. This finding highlights how subtle changes in the molecular design of π-stacked chromophore-peptide conjugates have a drastic impact on their equilibrium structure and ultimately functional properties.

Room temperature transmetallation from tris(pentafluorophenyl)borane to cyclometallated iridium(iii).

Transmetallation reactions involving organoboron reagents and transition metals are legion in synthetic organometallic chemistry and homogeneous catalysis. Triarylboranes (BAr3) have been observed to participate in transmetallation reactions with many transition metals, typically following abstraction of an alkyl (R-) or hydride ligand by the Lewis acidic borane. Here, an unusual transmetallation strategy is described where an aryl group from a borane replaces a weakly coordinated PF6- ligand. The precursors Ir(C^N)2(CNAr)(FPF5) (C^N = cyclometallating ligand, CNAr = aryl isocyanide) react smoothly with B(C6F5)3 to give complexes of the type Ir(C^N)2(CNAr)(C6F5), a previously unobserved structure type featuring an unchelated aryl ligand. The reaction tolerates a variety of C^N ligands and a range of electronically and sterically varied aryl isocyanide ancillary ligands. A total of six complexes of this type are described, two of which are characterized by single-crystal X-ray diffraction. All but one of the complexes luminesces at room temperature, with the emission wavelength dependent on the C^N ligand.

Temperature-regulated fluorescence and association of an oligo(ethyleneglycol)methacrylate-based copolymer with a conjugated polyelectrolyte--the effect of solution ionic strength.

Aqueous mixtures of a dye-labeled non-ionic thermoresponsive copolymer and a conjugated cationic polyelectrolyte are shown to exhibit characteristic changes in fluorescence properties in response to temperature and to the presence of salts, enabling a double-stimuli responsiveness. In such mixtures at room temperature, i.e., well below the lower critical solution temperature (LCST), the emission of the dye is strongly quenched due to energy transfer to the polycation, pointing to supramolecular interactions between the two macromolecules. Increasing the concentration of salts weakens the interpolymer interactions, the extent of which is simultaneously monitored from the change in the relative emission intensity of the components. When the mixture is heated above its LCST, the transfer efficiency is significantly reduced, signaling a structural reorganization process, however, surprisingly only if the mixture contains salt ions. To elucidate the reasons behind such thermo- and ion-sensitive fluorescence characteristics, we investigate the effect of salts of alkali chlorides, in particular of NaCl, on the association behavior of these macromolecules before and after the polymer phase transition by a combination of UV-vis, fluorescence, and (1)H NMR spectroscopy with light scattering and small-angle neutron scattering measurements.

A water soluble fluorescent polymer as a dual colour sensor for temperature and a specific protein.

We present two thermoresponsive water soluble copolymers prepared via free radical statistical copolymerization of N-isopropylacrylamide (NIPAm) and of oligo(ethylene glycol) methacrylates (OEGMAs), respectively, with a solvatochromic 7-(diethylamino)-3-carboxy-coumarin (DEAC)-functionalized monomer. In aqueous solutions, the NIPAm-based copolymer exhibits characteristic changes in its fluorescence profile in response to a change in solution temperature as well as to the presence of a specific protein, namely an anti-DEAC antibody. This polymer emits only weakly at low temperatures, but exhibits a marked fluorescence enhancement accompanied by a change in its emission colour when heated above its cloud point. Such drastic changes in the fluorescence and absorbance spectra are observed also upon injection of the anti-DEAC antibody, attributed to the specific binding of the antibody to DEAC moieties. Importantly, protein binding occurs exclusively when the polymer is in the well hydrated state below the cloud point, enabling a temperature control on the molecular recognition event. On the other hand, heating of the polymer-antibody complexes releases a fraction of the bound antibody. In the presence of the DEAC-functionalized monomer in this mixture, the released antibody competitively binds to the monomer and the antibody-free chains of the polymer undergo a more effective collapse and inter-aggregation. In contrast, the emission properties of the OEGMA-based analogous copolymer are rather insensitive to the thermally induced phase transition or to antibody binding. These opposite behaviours underline the need for a carefully tailored molecular design of responsive polymers aimed at specific applications, such as biosensing.