Aggregation-free and high stability core–shell polymer nanoparticles with high fullerene loading capacity,variable fullerene type,and compatibility towards biological conditions

Fullerenes have unique structural and electronic properties that make them attractive candidates for diagnostic, therapeutic, and theranostic applications. However, their poor water solubility remains a limiting factor in realizing their full biomedical potential. Here, we present an approach based on a combination of supramolecular and covalent chemistry to access well-defined fullerene-containing polymer nanoparticles with a core–shell structure. In this approach, solvophobic forces and aromatic interactions first come into play to afford a micellar structure with a poly(ethylene glycol) shell and a corannulene-based fullerene-rich core. Covalent stabilization of the supramolecular assembly then affords core-crosslinked polymer nanoparticles. The shell makes these nanoparticles biocompatible and allows them to be dried to a solid and redispersed in water without inducing interparticle aggregation. The core allows a high content of different fullerene types to be encapsulated. Finally, covalent stabilization endows nanostructures with stability against changing environmental conditions.

A polymer nanoparticle approach to biorelevant and robust fullerene nanoparticles is presented.     

Surface hydration for antifouling and bio-adhesion

Antifouling properties of materials play crucial roles in many important applications such as biomedical implants, marine antifouling coatings, biosensing, and membranes for separation. Poly(ethylene glycol) (or PEG) containing polymers and zwitterionic polymers have been shown to be excellent antifouling materials. It is believed that their outstanding antifouling activity comes from their strong surface hydration. On the other hand, it is difficult to develop underwater glues, although adhesives with strong adhesion in a dry environment are widely available. This is related to dehydration, which is important for adhesion for many cases while water is the enemy of adhesion. In this research, we applied sum frequency generation (SFG) vibrational spectroscopy to investigate buried interfaces between mussel adhesive plaques and a variety of materials including antifouling polymers and control samples, supplemented by studies on marine animal (mussel) behavior and adhesion measurements. It was found that PEG containing polymers and zwitterionic polymers have very strong surface hydration in an aqueous environment, which is the key for their excellent antifouling performance. Because of the strong surface hydration, mussels do not settle on these surfaces even after binding to the surfaces with rubber bands. For control samples, SFG results indicate that their surface hydration is much weaker, and therefore mussels can generate adhesives to displace water to cause dehydration at the interface. Because of the dehydration, mussels can foul on the surfaces of these control materials. Our experiments also showed that if mussels were forced to deposit adhesives onto the PEG containing polymers and zwitterionic polymers, interfacial dehydration did not occur. However, even with the strong interfacial hydration, strong adhesion between mussel adhesives and antifouling polymer surfaces was detected, showing that under certain circumstances, interfacial water could enhance the interfacial bio-adhesion.

Antifouling properties of materials play crucial roles in many important applications such as biomedical implants, marine antifouling coatings, biosensing, and membranes for separation.     

Light-intensity switch enabled nonsynchronous growth of fluorinated raspberry-like nanoparticles

Raspberry-like (RB) nanoparticles hold potential for diverse applications due to their hierarchical morphology. Here we developed a novel tandem synthetic approach of nonsynchronous growth based on photo-mediated reversible-deactivation radical polymerization, enabling simple, efficient and bottom-up synthesis of RB nanoparticles of uniform sizes at quantitative conversions of fluorinated monomers. Chain transfer agents of different chain lengths, concentrations and chemical compositions were varied to tune the diameter of RB particles. Importantly, fluorinated RB nanoparticles obtained with this method allow facile post modifications via both covalent bond formation and intermolecular physical interactions without disrupting the RB morphology. The facile nature of this method and versatility of the obtained fluorinated RB materials open new opportunities for the development of functional materials using nanoparticles.

Nonsynchronous growth of raspberry-like (RB) nanoparticles in a one-pot and bottom-up fashion, enabling simple post-modification of RB colloids through both covalent bond formation and supramolecular interaction.     

Oxidative regulation of the mechanical strength of a C–S bond

The mechanical strength of individual polymer chains is believed to underlie a number of performance metrics in bulk materials, including adhesion and fracture toughness. Methods by which the intrinsic molecular strength of the constituents of a given polymeric material might be switched are therefore potentially useful both for applications in which triggered property changes are desirable, and as tests of molecular theories for bulk behaviors. Here we report that the sequential oxidation of sulfide containing polyesters (PE-S) to the corresponding sulfoxide (PE-SO) and then sulfone (PE-SO2) first weakens (sulfoxide), and then enhances (sulfone), the effective mechanical integrity of the polymer backbone; PE-S ∼ PE-SO2 > PE-SO. The relative mechanical strength as a function of oxidation state is revealed through the use of gem-dichlorocyclopropane nonscissile mechanophores as an internal standard, and the observed order agrees well with the reported bond dissociation energies of C–S bonds in each species and with the results of CoGEF modeling.

The mechanical strength of individual polymer chains is believed to underlie a number of performance metrics in bulk materials, including adhesion and fracture toughness.     

Dynamic reaction-induced phase separation in tunable,adaptive covalent networks

A series of catalyst-free, room temperature dynamic bonds derived from a reversible thia-Michael reaction are utilized to access mechanically robust dynamic covalent network films. The equilibrium of the thiol addition to benzalcyanoacetate-based Michael-acceptors can be directly tuned by controlling the electron-donating/withdrawing nature of the Michael-acceptor. By modulating the composition of different Michael-acceptors in a dynamic covalent network, a wide range of mechanical properties and thermal responses can be realized. Additionally, the reported systems phase-separate in a process, coined dynamic reaction-induced phase separation (DRIPS), that yields reconfigurable phase morphologies and reprogrammable shape-memory behaviour as highlighted by the heat-induced folding of a predetermined structure.

Dynamic covalent networks comprised of tunable thia-Michael bonds result in phase separated networks with tailorable mechanical and adaptive properties.     

Stimuli-responsive temporary adhesives: enabling debonding on demand through strategic molecular design

Stimuli-responsive temporary adhesives constitute a rapidly developing class of materials defined by the modulation of adhesion upon exposure to an external stimulus or stimuli. Engineering these materials to shift between two characteristic properties, strong adhesion and facile debonding, can be achieved through design strategies that target molecular functionalities. This perspective reviews the recent design and development of these materials, with a focus on the different stimuli that may initiate debonding. These stimuli include UV light, thermal energy, chemical triggers, and other potential triggers, such as mechanical force, sublimation, electromagnetism. The conclusion discusses the fundamental value of systematic investigations of the structure–property relationships within these materials and opportunities for unlocking novel functionalities in future versions of adhesives.

Stimuli-responsive temporary adhesives emerge as next-generation multifunctional materials with advantages that include strong temporary adhesion, debonding on demand, and tunable reactivity.     

Asymmetric synthesis of 1,2-fluorohydrin: iridium catalyzed hydrogenation of fluorinated allylic alcohol

We have developed a simple protocol for the preparation of 1,2-fluorohydrin by asymmetric hydrogenation of fluorinated allylic alcohols using an efficient azabicyclo thiazole-phosphine iridium complex. The iridium-catalyzed asymmetric synthesis of chiral 1,2-fluorohydrin molecules was carried out at ambient temperature with operational simplicity, and scalability. This method was compatible with various aromatic, aliphatic, and heterocyclic fluorinated compounds as well as a variety of polyfluorinated compounds, providing the corresponding products in excellent yields and enantioselectivities.

We have developed a simple protocol for the preparation of 1,2-fluorohydrin by asymmetric hydrogenation of fluorinated allylic alcohols using an efficient azabicyclo thiazole-phosphine iridium complex.     

Pot and time economies in the total synthesis of Corey lactone

The Corey lactone is a highly versatile intermediate for the synthesis of a variety of prostaglandin hormones that natively control a multitude of important physiological processes. Starting from commercially available compounds, we herein disclose a time-economical, one-pot enantioselective preparation of the Corey lactone by virtue of a new diphenylprolinol silyl ether-mediated domino Michael/Michael reaction to afford the substituted cyclopentanone core in a formal (3 + 2) cycloadditive fashion. More broadly, this work advances the on-demand, gram-scale synthesis of high-value targets involving chemically orthogonal transformations, whereby distinct reactions of acids, bases, organometalics, reductants and oxidants can be carried out in a single reaction vessel in a sequential fashion.

The Corey lactone was synthesized by one-pot within 152 minutes from comercially available compounds using organocatalyst.     

Vibrational circular dichroism spectroscopy for probing the expression of chirality in mechanically planar chiral rotaxanes

Mechanically interlocked molecules can exhibit molecular chirality that arises due to the mechanical bond rather than covalent stereogenic units. Developing applications of such systems is made challenging by the absence of techniques for assigning the absolute configuration of products and methods to probe how the mechanical stereogenic unit influences the spatial arrangements of the functional groups in solution. Here we demonstrate for the first time that Vibrational Circular Dichroism (VCD) can be used to not only discriminate between mechanical stereoisomers but also provide detailed information on their (co)conformations. The latter is particularly important as these molecules are now under investigation in catalysis and sensing, both of which rely on the solution phase shape of the interlocked structure. Detailed analysis of the VCD spectra shows that, although many of the signals arise from coupled oscillators isolated in the covalent sub-components, intercomponent coupling between the macrocycle and axle gives rise to several VCD bands.

Through the looking glass: VCD spectroscopy provides unique insight into how a chiral mechanical bond imposes shape on rotaxanes in solution and allows their absolute configuration to be determined.     

Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 5′-hydroxy-6′-deoxy-amanitin

Appreciating the need to access synthetic analogs of amanitin, here we report the synthesis of 5′-hydroxy-6′-deoxy-amanitin, a novel, rationally-designed bioactive analog and constitutional isomer of α-amanitin, that is anticipated to be used as a payload for antibody drug conjugates. In completing this synthesis, we meet the challenge of diastereoselective sulfoxidation by presenting two high-yielding and diastereoselective sulfoxidation approaches to afford the more toxic (R)-sulfoxide.

Elucidating a highly diastereoselective sulfoxidation of S-deoxy-amanitin to afford α-amanitin and a more synthetically accessible analog of near-native toxicity.     

Mechanochemical generation of acid-degradable poly(enol ether)s

In an effort to develop polymers that can undergo extensive backbone degradation in response to mechanical stress, we report a polymer system that is hydrolytically stable but unmasks easily hydrolysable enol ether backbone linkages when force is applied. These polymers were synthesized by ring-opening metathesis polymerization (ROMP) of a novel mechanophore monomer consisting of cyclic ether fused bicyclohexene. Hydrogenation of the resulting polymers led to significantly enhanced thermal stability (T_d > 400 °C) and excellent resistance toward acidic or basic conditions. Solution ultrasonication of the polymers resulted in up to 65% activation of the mechanophore units and conversion to backbone enol ether linkages, which then allowed facile degradation of the polymers to generate small molecule or oligomeric species under mildly acidic conditions. We also achieved solid-state mechano-activation and polymer degradation via grinding the solid polymer. Force-induced hydrolytic polymer degradability can enable materials that are stable under force-free conditions but readily degrade under stress. Facile degradation of mechanically activated polymechanophores also facilitates the analysis of mechanochemical products.

A mechanically responsive polymer system that is hydrolytically stable without stress, but unmasks enol ether backbone linkages under force to allow facile hydrolytic degradation.     

Extraordinary electrochemical stability and extended polaron delocalization of ladder-type polyaniline-analogous polymers

Electrochemical stability and delocalization of states critically impact the functions and practical applications of electronically active polymers. Incorporation of a ladder-type constitution into these polymers represents a promising strategy to enhance the aforementioned properties from a fundamental structural perspective. A series of ladder-type polyaniline-analogous polymers are designed as models to test this hypothesis and are synthesized through a facile and scalable route. Chemical and electrochemical interconversions between the fully oxidized pernigraniline state and the fully reduced leucoemeraldine state are both achieved in a highly reversible and robust manner. The protonated pernigraniline form of the ladder polymer exhibits unprecedented electrochemical stability under highly acidic and oxidative conditions, enabling the access of a near-infrared light-absorbing material with extended polaron delocalization in the solid-state. An electrochromic device composed of this ladder polymer shows distinct switching between UV- and near-infrared-absorbing states with a remarkable cyclability, meanwhile tolerating a wide operating window of 4 volts. Taken together, these results demonstrate the principle of employing a ladder-type backbone constitution to impart superior electrochemical properties into electronically active polymers.

Electrochemical stability and state delocalization critically impact the functions and practical applications of electronically active polymers.     

Cleavable and tunable cysteine-specific arylation modification with aryl thioethers

Cysteine represents an attractive target for peptide/protein modification due to the intrinsic high nucleophilicity of the thiol group and low natural abundance. Herein, a cleavable and tunable covalent modification approach for cysteine containing peptides/proteins with our newly designed aryl thioethers via a S_NAr approach was developed. Highly efficient and selective bioconjugation reactions can be carried out under mild and biocompatible conditions. A series of aryl groups bearing different bioconjugation handles, affinity or fluorescent tags are well tolerated. By adjusting the skeleton and steric hindrance of aryl thioethers slightly, the modified products showed a tunable profile for the regeneration of the native peptides.

A cleavable and tunable covalent modification approach for cysteine by aryl thioethers via a S_NAr approach was developed. The highly efficient and selective bioconjugation reactions can proceed under the mild and biocompatible conditions.     

Isomeric anthracene diimide polymers

N-type semiconducting polymers are attractive for organic electronics, but desirable electron-deficient units for synthesizing such polymers are still lacking. As a cousin of rylene diimides such as naphthalene diimide (NDI) and perylene diimide (PDI), anthracene diimide (ADI) is a promising candidate; its polymers, however, have not been achieved yet because of synthetic challenges for its polymerizable monomers. Herein, we present ingenious synthesis of two dibromide ADI monomers with dibromination at differently symmetrical positions of the ADI core, which are further employed to construct ADI polymers. More interestingly, the two obtained ADI polymers possess the same main-chain and alkyl-chain structures but different backbone conformations owing to varied linking positions between repeating units. This feature enables their different optoelectronic properties and film-state packing behavior. The ADI polymers offer first examples of conjugated polymer conformational isomers and are highly promising as a new class of n-type semiconductors for various organic electronics applications.

Two anthracene diimide (ADI) polymers with the backbone conformational isomerism, new members of aromatic diimide polymers family, have been synthesized as a class of highly promising n-type semiconductors for organic electronics.     

Template effects of vesicles in dynamic covalent chemistry

Vesicle lipid bilayers have been employed as templates to modulate the product distribution in a dynamic covalent library of Michael adducts formed by mixing a Michael acceptor with thiols. In methanol solution, all possible Michael adducts were obtained in similar amounts. Addition of vesicles to the dynamic covalent library led to the formation of a single major product. The equilibrium constants for formation of the Michael adducts are similar for all of the thiols used in this experiment, and the effect of the vesicles on the composition of the library is attributed to the differential partitioning of the library members between the lipid bilayer and the aqueous solution. The results provide a quantitative approach for exploiting dynamic covalent chemistry within lipid bilayers.

Vesicle lipid bilayers have been employed as templates to modulate the product distribution in a dynamic covalent library of Michael adducts formed by mixing a Michael acceptor with thiols.     

Triboluminescence of a new family of CuI–NHC complexes in crystalline solid and in amorphous polymer films

Triboluminescent compounds that generate emission of light in response to mechanical stimulus are promising targets in the development of “smart materials” and damage sensors. Among triboluminescent metal complexes, rare-earth europium and terbium complexes are most widely used, while there is no systematic data on more readily available and inexpensive Cu complexes. We report a new family of photoluminescent Cu–NHC complexes that show bright triboluminescence (TL) in the crystal state visible in ambient indoor light under air. Moreover, when these complexes are blended into amorphous polymer films even at small concentrations, TL is easily observed. Observation of TL in polymer films overcomes the limitation of using crystals and opens up possibilities for the development of mechanoresponsive coatings and materials based on inexpensive metals such as Cu. Our results may also have implications for the understanding of the TL effect''s origin in polymer films.

Triboluminescent compounds that generate emission of light in response to mechanical stimulus are promising targets in the development of “smart materials” and damage sensors.     

Cross dehydrogenative C–O coupling catalysed by a catenane-coordinated copper(i)

Catalytic activity of copper(i) complexes supported by phenanthroline-containing catenane ligands towards a new C(sp³)–O dehydrogenative cross-coupling of phenols and bromodicarbonyls is reported. As the phenanthrolines are interlocked by the strong and flexible mechanical bond in the catenane, the active catalyst with an open copper coordination site can be revealed only transiently and the stable, coordinatively saturated Cu(i) pre-catalyst is quickly regenerated after substrate transformation. Compared with a control Cu(i) complex supported by non-interlocked phenanthrolines, the catenane-supported Cu(i) is highly efficient with a broad substrate scope, and can be applied in gram-scale transformations without a significant loss of the catalytic activity. This work demonstrates the advantages of the catenane ligands that provide a dynamic and responsive copper coordination sphere, highlighting the potential of the mechanical bond as a design element in transition metal catalyst development.

The use of a catenane-supported copper(i) complex for the cross dehydrogenative C–O coupling of phenols and bromodicarbonyls is described.     

Tunable heteroaromatic azoline thioethers (HATs) for cysteine profiling

Here we report a new series of hydrolytically stable chemotype heteroaromatic azoline thioethers (HATs) to achieve highly selective, rapid, and efficient covalent labeling of cysteine under physiological conditions. Although the resulting cysteine–azoline conjugate is stable, we highlight traceless decoupling of the conjugate to afford unmodified starting components in response to reducing conditions. We demonstrated that HAT probes reverse the reactivity of nucleophilic cysteine to electrophilic dehydroalanine (Dha) under mild basic conditions. We demonstrated the umpolung capability of HAT probes for the modification of cysteine on peptides and proteins with various nucleophiles. We demonstrated that HAT probes increase the mass sensitivity of the modified peptides and proteins by 100 fold as compared to the classical methods. Finally, we extended the application of HAT probes for specific modification of cysteines in a complex cell lysate mixture.

Here we report a new series of hydrolytically stable chemotype heteroaromatic azoline thioethers (HATs) to achieve highly selective, rapid, and efficient covalent labeling of cysteine under physiological conditions.     

Room temperature crystallization of amorphous polysiloxane using photodimerization

Bulk crystallization in flexible polymeric systems is difficult to control due to the random orientation of the chains. Here we report a photo cross-linking strategy that results in simultaneous cross-linking and crystallization of polysiloxane chains into millimeter sized leaf-like polycrystalline structures. Polymers containing pendant anthracene groups are prepared and undergo [4+4] photocycloaddition under 365 nm irradiation at room temperature. The growth and morphology of the crystalline structures is studied using polarized optical microscopy (POM) and atomic force microscopy and is found to progress through three unique stages of nucleation, growth, and constriction. The mobility of the individual chains is probed using pulsed-field gradient (PFG) NMR to provide insights into the diffusion processes that may govern chain transport to the growing crystal fronts. The room temperature crystallization of this conventionally amorphous polymer system may allow for a new level of morphological control for silicone materials.

Millimeter sized polymer crystallites grow rapidly when anthracene-containing siloxanes are photocrosslinked using UV light.     

Synthetic glycosidases for the precise hydrolysis of oligosaccharides and polysaccharides

Glycosidases are an important class of enzymes for performing the selective hydrolysis of glycans. Although glycans can be hydrolyzed in principle by acidic water, hydrolysis with high selectivity using nonenzymatic catalysts is an unachieved goal. Molecular imprinting in cross-linked micelles afforded water-soluble polymeric nanoparticles with a sugar-binding boroxole in the imprinted site. Post-modification installed an acidic group near the oxygen of the targeted glycosidic bond, with the acidity and distance of the acid varied systematically. The resulting synthetic glycosidase hydrolyzed oligosaccharides and polysaccharides in a highly controlled fashion simply in hot water. These catalysts not only broke down amylose with similar selectivities to those of natural enzymes, but they also could be designed to possess selectivity not available with biocatalysts. Substrate selectivity was mainly determined by the sugar residues bound within the active site, including their spatial orientations. Separation of the product was accomplished through in situ dialysis, and the catalysts left behind could be used multiple times with no signs of degradation. This work illustrates a general method to construct synthetic glycosidases from readily available building blocks via self-assembly, covalent capture, and post-modification. In addition, controlled, precise, one-step hydrolysis is an attractive way to prepare complex glycans from naturally available carbohydrate sources.

Synthetic glycosidases with a sugar-binding active site and a precisely positioned acidic group hydrolyze oligo- and polysaccharides selectively in hot water to afford desired sugar products in a single step.