Synergistic topological and supramolecular control of Diels-Alder reactivity based on a tunable self-complexing host-guest molecular switch.

Compartmentalization and binding-triggered conformational change regulate many metabolic processes in living matter. Here, we have synergistically combined these two biorelevant processes to tune the Diels-Alder (DA) reactivity of a synthetic self-complexing host-guest molecular switch CBPQT4+ -Fu, consisting of an electron-rich furan unit covalently attached to the electron-deficient cyclobis(paraquat-p-phenylene) tetrachloride (CBPQT4+ , 4Cl- ) host. This design allows CBPQT4+ -Fu to efficiently compartmentalize the furan ring inside its host cavity in water, thereby protecting it from the DA reaction with maleimide. Remarkably, the self-complexed CBPQT4+ -Fu can undergo a conformational change through intramolecular decomplexation upon the addition of a stronger binding molecular naphthalene derivative as a competitive guest, triggering the DA reaction upon addition of a chemical regulator. Remarkably, connecting the guest to a thermoresponsive lower critical solution temperature (LCST) copolymer regulator controls the DA reaction on command upon heating and cooling the reaction media beyond and below the cloud point temperature of the copolymer, representing a rare example of decreased reactivity upon increasing temperature. Altogether, this work opens up new avenues towards combined topological and supramolecular control over reactivity in synthetic constructs, enabling control over reactivity through molecular regulators or even mild temperature variations.

Dual Responsive Regulation of Host-Guest Complexation in Aqueous Media to Control Partial Release of the Host.

The regulation of the concentration of a wide range of small molecules is ubiquitous in biological systems because it enables them to adapt to the continuous changes in the environmental conditions. Herein, we report an aqueous synthetic system that provides an orchestrated, temperature and pH controlled regulation of the complexation between the cyclobis(paraquat-p-phenylene) host (BBox) and a 1,5-dialkyloxynaphthalene (DNP) guest attached to a well-defined dual responsive copolymer composed of N-isopropylacrylamide as thermoresponsive monomer and acrylic acid as pH-responsive monomer. Controlled, partial release of the BBox, enabling control over its concentration, is based on the tunable partial collapse of the copolymer. This colored supramolecular assembly is one of the first synthetic systems providing control over the concentration of a small molecule, providing great potential as both T and pH chromic materials and as a basis to develop more complex systems with molecular communication.

Dopamine-functionalized cyclodextrins: modification of reduced graphene oxide based electrodes and sensing of folic acid in human serum.

A mandatory step in any sensor fabrication is the introduction of analyte-specific recognition elements to the transducer surface. In this study, the possibility to anchor ß-cyclodextrin-modified dopamine to a reduced graphene oxide based electrochemical transducer for the sensitive and selective sensing of folic acid is demonstrated. The sensor displays good electrocatalytic activity toward the oxidation of folic acid. The strong affinity of the surface-confined ß-cyclodextrin for folic acid, together with favorable electron transfer characteristics, resulted in a sensor with a detection limit of 1 nM for folic acid and a linear response up to 10 µM. Testing of the sensor on serum samples from healthy individuals and patients diagnosed with folic acid deficiency validated the sensing capability. Graphical abstract.

Supramolecular Competitive Host-Guest Interaction Induced Reversible Macromolecular Metamorphosis.

In this work, a rational strategy of competitive host-guest complexation between dioxynaphthalene (Naph) and tetrathiafulvalene (TTF) subunits as guests and cyclophane cyclobis(paraquat-p-phenylene) (CBPQT4+ ) module as host is exploited to modify the macromolecular architecture, so-called supramolecular metamorphosis, in aqueous media. The architectures of the polymers can be reversibly transformed from a linear diblock copolymer AB to a linear AC block copolymer or from a linear block copolymer to a comb copolymer by redox switching. Interestingly, as TTF- and Naph-based complexes feature different characteristic colors, it offers a great opportunity to directly observe nanoscaled macromolecular metamorphosis of materials with the naked eye.

Ultrafast Tailoring of Carbon Surfaces via Electrochemically Attached Triazolinediones.

The straightforward coupling between a triazolinedione (TAD) unit and citronellyl derivatives via an Alder-ene reaction has been exploited to tailor the physicochemical surface properties of glassy carbon (GC) surfaces in an ultrafast and additive-free manner. For this purpose, we first covalently grafted a TAD precursor onto GC via electrochemical reduction of an in situ generated diazonium salt, which was then electrochemically oxidized into the desired GC-bonded TAD unit. A kinetic study of the modification of this reactive layer with an electroactive ferrocene probe proved that a complete functionalization was obtained in merely 1 minute. Further modification experiments with a fluorinated probe demonstrated that the surface properties can be swiftly tailored on demand. The different modification steps, as well as the efficiency of this strategy, were investigated by electrochemistry, contact angle goniometry, and X-ray photoelectron spectroscopy analysis.

Antifouling amphiphilic silicone coatings for dairy fouling mitigation on stainless steel.

Pasteurization of dairy products is plagued by fouling, which induces significant economic, environmental and microbiological safety concerns. Herein, an amphiphilic silicone coating was evaluated for its efficacy against fouling by a model dairy fluid in a pilot pasteurizer and against foodborne bacterial adhesion. The coating was formed by modifying an RTV silicone with a PEO-silane amphiphile comprised of a PEO segment and flexible siloxane tether ([(EtO)3Si-(CH2)2-oligodimethylsiloxanem-block-(OCH2CH2)n-OCH3]). Contact angle analysis of the coating revealed that the PEO segments were able to migrate to the aqueous interface. The PEO-modified silicone coating applied to pretreated stainless steel was exceptionally resistant to fouling. After five cycles of pasteurization, these coated substrata were subjected to a standard clean-in-place process and exhibited a minor reduction in fouling resistance in subsequent tests. However, the lack of fouling prior to cleaning indicates that harsh cleaning is not necessary. PEO-modified silicone coatings also showed exceptional resistance to adhesion by foodborne pathogenic bacteria.

Reversible Tethering of Polymers onto Catechol-Based Titanium Platforms.

In this article, we report on the reversible tethering of end-functionalized polymers onto catechol-based titanium platforms by exploiting the reversible Diels-Alder (DA) cycloaddition reaction. For this purpose, furan and maleimide end-functionalized polymers, prepared via reversible addition-fragmentation chain transfer polymerization, were covalently grafted through a DA reaction onto reactive titanium platforms elaborated from catechol-based anchors incorporating either the furan or the maleimide moiety. As a proof of concept, a hydrophilic poly(oligo(ethylene glycol)acrylate) (POEGA) and a hydrophobic poly(2,2,2-trifluoroethyl acrylate) (PTFEA) were grafted onto titanium surfaces and subsequently detached by exploiting the thermoreversible nature of the DA reaction [i.e., retro Diels-Alder (rDA)]. These polymers were interchanged by performing a second DA reaction, thereby allowing the titanium surface wettability to be switched from hydrophobic to hydrophilic on demand. The grafting of furan/maleimide end-functionalized polymers onto functionalized (maleimide/furan, respectively) catechol-based titanium platforms and the subsequent rDA/DA sequence used for switching the titanium surface were evidenced by attenuated total reflectance-Fourier transform-infrared spectroscopy, X-ray photoelectron spectroscopy, and contact angle measurements.

Recognition-Mediated Hydrogel Swelling Controlled by Interaction with a Negative Thermoresponsive LCST Polymer.

Most polymeric thermoresponsive hydrogels contract upon heating beyond the lower critical solution temperature (LCST) of the polymers used. Herein, we report a supramolecular hydrogel system that shows the opposite temperature dependence. When the non-thermosesponsive hydrogel NaphtGel, containing dialkoxynaphthalene guest molecules, becomes complexed with the tetra cationic macrocyclic host CBPQT4+ , swelling occurred as a result of host-guest complex formation leading to charge repulsion between the host units, as well as an osmotic contribution of chloride counter-ions embedded in the network. The immersion of NaphtGel in a solution of poly(N-isopropylacrylamide) with tetrathiafulvalene (TTF) end groups complexed with CBPQT4+ induced positive thermoresponsive behaviour. The LCST-induced dethreading of the polymer-based pseudorotaxane upon heating led to transfer of the CBPQT4+ host and a concomitant swelling of NaphtGel. Subsequent cooling led to reformation of the TTF-based host-guest complexes in solution and contraction of the hydrogel.

Biomimetic Mussel Adhesive Inspired Anchor to Design ZnO@Poly(3-Hexylthiophene) Hybrid Core@Corona Nanoparticles.

The functionalization of zinc oxide (ZnO) nanoparticles by poly(3-hexylthiophene) (P3HT) brush is completed by the combination of a mussel inspired biomimetic anchoring group and Huisgen cyclo-addition "click chemistry." Herein, the direct coupling of an azide modified catechol derivative with an alkyne end-functionalized P3HT is described. This macromolecular binding agent is used to access core@corona ZnO@P3HT with a stable and homogeneous conjugated organic corona. Preliminary photoluminescence measurement proves an efficient electron transfer from the donor P3HT to the acceptor ZnO nanoparticles upon grafting, thus demonstrating the potential of such a combination in organic electronics.

Amplified plasmonic detection of DNA hybridization using doxorubicin-capped gold particles.

We show in this article that doxorubicin-modified gold nanoparticles (Au NP-DOX) can be used for the post-amplification of the wavelength shift of localized surface plasmon resonance (LSPR) signals after DNA hybridization events. We take advantage of the intercalation properties of DOX with guanine-rich oligonucleotides and the plasmon coupling between surface-linked gold nanostructures and Au NP-DOX in solution to detect in a sensitive manner DNA hybridisation events. Post-treatment of double-stranded DNA with Au NP-DOX resulted in a detection limit of ≈600 pM, several times lower than that without post-incubation (LOD ≈ 40 nM).

Elaboration of thermoresponsive supramolecular diblock copolymers in water from complementary CBPQT4+ and TTF end-functionalized polymers.

A well-defined poly(N-isopropyl acrylamide) 1 incorporating at one termini a cyclobis(paraquat-p-phenylene) (CBPQT(4+)) recognition unit is prepared via a RAFT polymerization followed by a copper-catalyzed azide-alkyne cycloaddition (CuAAC). (1)H NMR (1D, DOSY), UV-vis and ITC experiments reveal that polymer 1 is able of forming effective host-guest complexes with tetrathiafulvalene (TTF) end-functionalized polymers in water, thereby leading to the formation of non-covalently-linked double-hydrophilic block copolymers. The effect of the temperature on both the LCST phase transition of 1 and its complexes and on CBPQT(4+)/TTF host-guest interactions is investigated.

Programmable polymer-based supramolecular temperature sensor with a memory function.

A new class of polymeric thermometers with a memory function is reported that is based on the supramolecular host-guest interactions of poly(N-isopropylacrylamide) (PNIPAM) with side-chain naphthalene guest moieties and the tetracationic macrocycle cyclobis(paraquat-p-phenylene) (CBPQT(4+)) as the host. This supramolecular thermometer exhibits a memory function for the thermal history of the solution, which arises from the large hysteresis of the thermoresponsive LCST phase transition (LCST = lower critical solution temperature). This hysteresis is based on the formation of a metastable soluble state that consists of the PNIPAM-CBPQT(4+) host-guest complex. When heated above the transition temperature, the polymer collapses, and the host-guest interactions are disrupted, making the polymer more hydrophobic and less soluble in water. Aside from providing fundamental insights into the kinetic control of supramolecular assemblies, the developed thermometer with a memory function might find use in applications spanning the physical and biological sciences.

Approach for plasmonic based DNA sensing: amplification of the wavelength shift and simultaneous detection of the plasmon modes of gold nanostructures.

In this article, the detection of DNA hybridization taking advantage of the plasmonic properties of gold nanostructures is described. The approach is based on the amplification of the wavelength shift of a multilayered localized surface plasmon resonance (LSPR) sensor interface upon hybridization with gold nanorods and nanostars-labeled DNA. The amplification results in a significant decrease of the limit of detection from ≈40 nM as observed for unlabeled DNA to 0.2 nM for labeled DNA molecules. Furthermore, the plasmonic band, characteristic of the labeled DNA, is different from that of the LSPR interface. Indeed, next to the plasmon band at around 550 nm, being in resonance with the plasmon band of the LSPR interface, additional plasmonic peaks at 439 nm for gold nanostar-labeled DNA and 797 nm for gold nanorod-labeled DNA are observed, which were used as plasmonic signatures for successful hybridization.

Thiol-yne click reactions on alkynyl-dopamine-modified reduced graphene oxide.

The large-scale preparation of graphene is of great importance due to its potential applications in various fields. We report herein a simple method for the simultaneous exfoliation and reduction of graphene oxide (GO) to reduced GO (rGO) by using alkynyl-terminated dopamine as the reducing agent. The reaction was performed under mild conditions to yield rGO functionalized with the dopamine derivative. The chemical reactivity of the alkynyl function was demonstrated by post-functionalization with two thiolated precursors, namely 6-(ferrocenyl)hexanethiol and 1H,1H,2H,2H-perfluorodecanethiol. X-ray photoelectron spectroscopy, UV/Vis spectrophotometry, Raman spectroscopy, conductivity measurements, and cyclic voltammetry were used to characterize the resulting surfaces.

In Vitro and In Vivo Evaluation of a Bio-Inspired Adhesive for Bone Fixation.

Compared to metallic hardware, an effective bone adhesive can revolutionize the treatment of clinically challenging situations such as comminuted, articular, and pediatric fractures. The present study aims to develop such a bio-inspired bone adhesive, based upon a modified mineral-organic adhesive with tetracalcium phosphate (TTCP) and phosphoserine (OPS) by incorporating nanoparticles of polydopamine (nPDA). The optimal formulation, which was screened using in vitro instrumental tensile adhesion tests, was found to be 50%molTTCP/50%molOPS-2%wtnPDA with a liquid-to-powder ratio of 0.21 mL/g. This adhesive has a substantially stronger adhesive strength (1.0-1.6 MPa) to bovine cortical bone than the adhesive without nPDA (0.5-0.6 MPa). To simulate a clinical scenario of autograft fixation under low mechanical load, we presented the first in vivo model: a rat fibula glued to the tibia, on which the TTCP/OPS-nPDA adhesive (n = 7) was shown to be effective in stabilizing the graft without displacement (a clinical success rate of 86% and 71% at 5 and 12 weeks, respectively) compared to a sham control (0%). Significant coverage of newly formed bone was particularly observed on the surface of the adhesive, thanks to the osteoinductive property of nPDA. To conclude, the TTCP/OPS-nPDA adhesive fulfilled many clinical requirements for the bone fixation, and potentially could be functionalized via nPDA to offer more biological activities, e.g., anti-infection after antibiotic loading.

Highly efficient ring-opening reaction of azlactone-based copolymer platforms for the design of functionalized materials.

Azlactone-based homopolymers and copolymers were successfully synthesized using the reversible addition-fragmentation chain transfer (RAFT) process. The functional monomer 2-styryl-4,4-dimethylazlactone (SDA) was first homopolymerized in bulk then copolymerized with styrene, leading to (co)polymers with low polydispersity indices (PDI = 1.10-1.20). The reactive azlactone rings, located along the backbone of the copolymers were subjected to highly efficient ring-opening reactions with functionalized primary amine derivatives incorporating a fluorescent (naphthalene) or an electrochemical (ferrocene) probes, a biological fragment (glutathione), a sugar unit (ß-cyclodextrin), or an oligomeric fluorinated moiety, leading to materials with various interesting properties.

Direct functionalization of nanodiamond particles using dopamine derivatives.

The article reports on the strong linking of dopamine derivatives as a simple and a versatile strategy for the surface functionalization of hydroxyl-terminated nanodiamond (ND-OH) particles. Azide- (ND-N(3)) or poly-N-isopropylacrylamide-terminated (ND-PNIPAM) particles were obtained from ND-OH particles through the reaction with the corresponding dopamine derivatives. The azide-terminated ND particles were further derivatized with a fluorescent probe, alkynyl-pyrene, via copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. The modified ND particles were characterized using transmission Fourier transform infrared (FTIR) spectroscopy, UV-vis spectroscopy, electrochemical measurements, thermogravimetric analysis (TGA), and particle size measurements. The surface loading of ND particles with dopamine was estimated from TGA and UV-vis spectroscopy and was found to be around 0.27 mmol g(-1). Because of its simple, gentle nature and versatility, the chemistry developed in this work can be used as an avenue for the preparation of functional nanodiamond particles for various applications.

In vivo evaluation of a pro-healing polydopamine coated stent through an in-stent restenosis rat model.

Drug-eluting stents have demonstrated efficiency in in-stent restenosis (ISR) but induced a risk of late acute thrombosis by delaying strut re-endothelialization. Polydopamine (PDA), a biocompatible polymer inspired from adhesive proteins of mussels, has been reported to promote endothelial cell (EC) proliferation while limiting SMC proliferation in vitro, thus suggesting the pro-healing potential. This study aimed at evaluating in vivo the impact of the pro-healing PDA-coated stent on ISR and on the quality of the strut re-endothelialization in a rat model. PDA-coated stents demonstrated a significant reduction in ISR in vivo compared to bare metal stents (ratio neointima/media = 0.48 (±0.26) versus 0.83 (±0.42), p < 0.001). Western blot analyses identified a trend towards an increased activation of p38 MAPK phosphorylation and its anti-proliferative effects on vascular SMC that could explain the results observed in morphological analyses. This bioinspired and biocompatible polydopamine layer could intrinsically limit ISR. In addition, according to its latent reactivity, PDA offers the possibility to immobilize some relevant drugs on the PDA-functionalized stent to provide potential synergistic effects.

Tetrathiafulvalene end-functionalized poly(N-isopropylacrylamide): a new class of amphiphilic polymer for the creation of multistimuli responsive micelles.

In this article, we report the formation of micelles from a tetrathiafulvalene (TTF) end-functionalized poly(N-isopropylacrylamide) (poly(NIPAM)) derivative (1). We have determined the critical aggregation concentration (CAC) and average diameter of the micelles using fluorescence spectroscopy and dynamic light scattering experiments, respectively. We have exploited the NIPAM backbone of the polymer to thermally transform the swollen hydrophilic poly(NIPAM) derivative to a more globular hydrophobic state at the lower critical solution temperature (LCST). Finally, we have shown that we can exploit the chemical oxidation and complexation properties of the TTF unit to disrupt the micelle architecture to release the hydrophobic dye Nile Red from the interior of the micelle.