Chemically revised conducting polymers with inflammation resistance for intimate bioelectronic electrocoupling.

Conducting polymers offer attractive mixed ionic-electronic conductivity, tunable interfacial barrier with metal, tissue matchable softness, and versatile chemical functionalization, making them robust to bridge the gap between brain tissue and electronic circuits. This review focuses on chemically revised conducting polymers, combined with their superior and controllable electrochemical performance, to fabricate long-term bioelectronic implants, addressing chronic immune responses, weak neuron attraction, and long-term electrocommunication instability challenges. Moreover, the promising progress of zwitterionic conducting polymers in bioelectronic implants (≥4 weeks stable implantation) is highlighted, followed by a comment on their current evolution toward selective neural coupling and reimplantable function. Finally, a critical forward look at the future of zwitterionic conducting polymers for in vivo bioelectronic devices is provided.

A trade-off between antifouling and the electrochemical stabilities of PEDOTs.

Strong nonspecific protein/cell adhesion on conducting polymer (CP)-based bioelectronic devices can cause an increase in the impedance or the malfunction of the devices. Incorporating oligo(ethylene glycol) or zwitterionic functionalities with CPs has demonstrated superior performance in the reduction of nonspecific adhesion. However, there is no report on the evaluation of the antifouling stability of oligo(ethylene glycol) and zwitterion-functionalized CPs under electrical stimulation as a simulation of the real situation of device operation. Moreover, there is a lack of understanding of the correlation between the molecular structure of antifouling CPs and the antifouling and electrochemical stabilities of the CP-based electrodes. To address the aforementioned issue, we fabricated a platform with antifouling poly(3,4-ethylenedioxythiophene) (PEDOT) featuring tri(ethylene glycol), tetra(ethylene glycol), sulfobetaine, or phosphorylcholine (PEDOT-PC) to evaluate the stability of the antifouling/electrochemical properties of antifouling PEDOTs before and after electrical stimulation. The results reveal that the PEDOT-PC electrode not only exhibits good electrochemical stability, low impedance, and small voltage excursion, but also shows excellent resistance toward proteins and HAPI microglial cells, as a cell model of inflammation, after the electrical stimulation. The stable antifouling/electrochemical properties of zwitterionic PEDOT-PC may aid its diverse applications in bioelectronic devices in the future.

Tunable Protein/Cell Binding and Interaction with Neurite Outgrowth of Low-Impedance Zwitterionic PEDOTs.

Zwitterionic poly(3,4-ethylenedioxythiophene) (PEDOT) is an effective electronic material for bioelectronics because it exhibits efficient electrical trade-off and diminishes immune response. To promote the use of zwitterionic PEDOTs in bioelectronic devices, especially for cell alignment control and close electrocoupling, features such as tunable interaction of PEDOTs with proteins/cells and spatially modulating cell behavior are required. However, there is a lack of reliable methods to assemble zwitterionic EDOTs with other functionalized EDOT materials, having different polarities and oxidation potentials, to prepare PEDOTs with the aforementioned surface properties. In this study, we have developed a surfactant-assisted electropolymerization to assemble phosphorylcholine (PC)-functionalized EDOT with other functionalized EDOTs. By adjusting compositions, the interaction of PEDOT copolymers with proteins/cells can be finely tuned; the composition adjustment has an ignorable influence on the impedance of the copolymers. We also demonstrate that the cell-repulsive force generated from PC can spatially guide the neurite outgrowth to form a neuron network at single-cell resolution and greatly enhance the neurite outgrowth by 179%, which is significantly more distinctive than the reported topography effect. We expect that the derived tunable protein/cell interaction and the PC-induced repulsive guidance for the neurite outgrowth can make low-impedance zwitterionic PEDOTs more useful in bioelectronics.

Two-step synthesis of a red-emissive warped nanographene derivative via a ten-fold C-H borylation.

The regioselective ten-fold borylation of warped nanographene (WNG: C80H30) was achieved by modifying the reaction conditions of a previously reported Ir-catalyzed C-H borylation, affording decaborylated WNG in high yield (75%) from pristine WNG. The solid-state structure of decaborylated WNG was confirmed by X-ray crystallography. Corresponding decaarylated WNGs containing electron-withdrawing and -donating groups were synthesized from decaborylated WNG using Suzuki-Miyaura cross-coupling reactions to afford the red-emissive warped nanographene derivative.

Synthesis and structural features of thiophene-fused analogues of warped nanographene and quintuple helicene.

Thiophene-fused analogues of warped nanographene (WNG) and quintuple helicene (QH) were synthesized via a three-step π-extension of corannulene. Similar to the synthetic route to WNG, five hexagons and five heptagons were generated by a Scholl reaction of pentakis(thienylphenyl)corannulene to form pentathiaWNG. In contrast, decathiaWNG could not be obtained from pentakis(thienylthienyl)corannulene, and instead decathiaQH was generated from the photocyclization of the precursor. X-ray crystallography of the products revealed their conformations and packing modes in the solid state. The configurational features of decathiaQH were further examined by DFT calculations. The absorption and fluorescence spectra of the sulfur-containing WNG and QH were shifted relative to those of the corresponding sulfur-free analogues.

A Water-Soluble Warped Nanographene: Synthesis and Applications for Photoinduced Cell Death.

Nanographene, a small piece of graphene, has attracted unprecedented interest across diverse scientific disciplines particularly in organic electronics. The biological applications of nanographenes, such as bioimaging, cancer therapies and drug delivery, provide significant opportunities for breakthroughs in the field. However, the intrinsic aggregation behavior and low solubility of nanographenes, which stem from their flat structures, hamper their development for bioapplications. Herein, we report a water-soluble warped nanographene (WNG) that can be easily synthesized by sequential regioselective C-H borylation and cross-coupling reactions of the saddle-shaped WNG core structure. The saddle-shaped structure and hydrophilic tetraethylene glycol chains impart high water solubility to the WNG. The water-soluble WNG possesses a range of promising properties including good photostability and low cytotoxicity. Moreover, the water-soluble WNG was successfully internalized into HeLa cells and promoted photoinduced cell death.

Palladium-catalyzed direct C-H arylations of dioxythiophenes bearing reactive functional groups: a step-economical approach for functional π-conjugated oligoarenes.

A Pd-catalyzed single-step C-H arylation of dioxythiophene derivatives bearing unprotected reactive functional groups (-OH, -COOH, -N3) in a phosphine-free manner has been developed. Various dioxythiopene-based oligoarenes with extended π-conjugation are obtained with good yields (up to 90%). These oligoarenes display suitable optical properties (absorption and emission maxima, quantum yields) and contain reactive functional groups suitable for further conjugations with bioactive molecules. This new methodology is step economical (fewer synthetic steps) and environmentally friendly (no toxic metal-containing by-products) and the oligoarenes synthesized are potentially applicable for bio-labeling, bioimaging, and biosensing.

Step-Economical Syntheses of Functional BODIPY-EDOT π-Conjugated Materials through Direct C-H Arylation.

Palladium-catalyzed direct C-H arylations of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with 3,4-ethylenedioxythiophene (EDOT) derivatives at relatively low temperature (60 °C) provide moderate to good yields (47%-72%) of products having potential applications in fluorescent bioimaging and organic optoelectronics.

Programming thermoresponsiveness of NanoVelcro substrates enables effective purification of circulating tumor cells in lung cancer patients.

Unlike tumor biopsies that can be constrained by problems such as sampling bias, circulating tumor cells (CTCs) are regarded as the "liquid biopsy" of the tumor, providing convenient access to all disease sites, including primary tumor and fatal metastases. Although enumerating CTCs is of prognostic significance in solid tumors, it is conceivable that performing molecular and functional analyses on CTCs will reveal much significant insight into tumor biology to guide proper therapeutic intervention. We developed the Thermoresponsive NanoVelcro CTC purification system that can be digitally programmed to achieve an optimal performance for purifying CTCs from non-small cell lung cancer (NSCLC) patients. The performance of this unique CTC purification system was optimized by systematically modulating surface chemistry, flow rates, and heating/cooling cycles. By applying a physiologically endurable stimulation (i.e., temperature between 4 and 37 °C), the mild operational parameters allow minimum disruption to CTCs' viability and molecular integrity. Subsequently, we were able to successfully demonstrate culture expansion and mutational analysis of the CTCs purified by this CTC purification system. Most excitingly, we adopted the combined use of the Thermoresponsive NanoVelcro system with downstream mutational analysis to monitor the disease evolution of an index NSCLC patient, highlighting its translational value in managing NSCLC.

Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer.

Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it.

Controlled protein absorption and cell adhesion on polymer-brush-grafted poly(3,4-ethylenedioxythiophene) films.

Tailoring the surface of biometallic implants with protein-resistant polymer brushes represents an efficient approach to improve the biocompability and mechanical compliance with soft human tissues. A general approach utilizing electropolymerization to form initiating group (-Br) containing poly(3,4-ethylenedioxythiophen)s (poly(EDOT)s) is described. After the conducting polymer is deposited, neutral poly((oligo(ethylene glycol) methacrylate), poly(OEGMA), and zwitterionic poly([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), poly(SBMA), brushes are grafted by surface-initiated atom transfer radical polymerization. Quartz crystal microbalance (QCM) experiments confirm protein resistance of poly(OEGMA) and poly(SBMA)-grafted poly(EDOT)s. The protein binding properties of the surface are modulated by the density of polymer brushes, which is controlled by the feed content of initiator-containing monomer (EDOT-Br) in the monomer mixture solution for electropolymerization. Furthermore, these polymer-grafted poly(EDOT)s also prevent cells to adhere on the surface.

Electrical pulse triggered reversible assembly of molecular adlayers.

Reversible adlattice assembly for alkoxy-decorated aromatics is controllable by short electrical pulses.

Enantiotropic nematics from cross-like 1,2,4,5-tetrakis(4'-alkyl-4-ethynylbiphenyl)benzenes and their biaxiality studies.

The theoretically predicted optimum length/breadth/width ratio for maximizing shape biaxiality was investigated experimentally by the facile and successful synthesis of cross-shaped compound 3, which showed enantiomeric nematic phase behavior. This cross-like core structure could alternatively be viewed as two fused V-shaped mesogens, which have recently immerged as a new direction in biaxial nematic research, at the bending tips that can act as a new structure for biaxial investigations. Whilst the thermal analysis data of compound 3 did not meet the expected theoretical values for biaxial nematics, surface-induced biaxiality was evidenced by optical studies. Cluster-size analysis within the nematic phase of compound 3 revealed the formation of meta-cybotactic nematics, which approached the cluster sizes of cybotactic nematics. The split small-angle 2D X-ray diffraction patterns of magnetic-field-aligned samples indicated that the nematic phase was composed of small smectic C-like clusters with the tilting of molecules within the clusters. The wide-temperature-range enantiomeric nematic phase of cross-like compound 3 enabled the molecular skeleton to serve as an alternative skeleton to bent-rod mesogens, which exhibited nematic phases with the potential competition of transitions to higher-order liquid-crystalline phases and crystallization, for future biaxial investigations.

Gearing of molecular swirls: columnar packing of nematogenic hexakis(4-alkoxyphenylethynyl)benzene derivatives.

Through molecular design and straightforward synthesis, incorporating an additional alkoxy chain onto various numbers of peripheral phenyls in nematogenic hexakis(4-alkoxyphenylethynyl)benzene was achieved to generate columnar phases with significantly expanded temperature ranges. For the compound with two decyloxy chains on every peripheral phenyl, scanning tunnelling microscopic studies indicate the molecule adopts a preferred molecular-swirl geometry by restricting the conformational arrangement of the alkoxy side chains. Cooperative packing of the molecular swirls by a lock-in mechanism among columns results in a stable helical column packing evidenced by powder X-ray diffraction.

Synthesis, optical, and mesomorphic properties of self-assembled organogels featuring phenylethynyl framework with elaborated long-chain pyridine-2,6-dicarboxamides.

A series of new organogelators with pi-conjugated phenylethynyl framework featuring long-chain carboxamides have been synthesized. These organgelators have shown great ability to gel a variety of organic solvents to form stable organogels with the minimum gelation concentration as low as 0.1 wt %. Gelation is completely thermoreversible, and it occurs due to the aggregation of the organogelators resulting in the formation of a fibrous network via a combination of intermolecular hydrogen bonding, pi-pi stacking, and van der Waals interactions that is observed for the xerogels by TEM. The influence of sol-to-gel transition has been explored in detail by variable-temperature 1H NMR, UV-vis absorption, and fluorescence spectroscopy. Aggregation-induced enhanced emission has been observed in these organogelator molecules with an order of higher fluorescence quantum yields from solution to gels. In addition, some molecules also exhibit unique liquid crystalline properties over a large temperature range as revealed by DSC and POM studies.