Oligo Ethylene Glycol Chains Research Articles

Self-Assembly of Metallo-Supramolecular Amphiphiles Based on Azadipyrromethenes: Consecutive Pathways to Nanodiscs and Nanosheets.

A new class of metallo-supramolecular amphiphilic dyes 1a, b was constructed by using two azadipyrromethene units which were respectively modified with two hydrophobic alkyl and two hydrophilic oligo(ethylene glycol) chains. The spectroscopic and morphological studies revealed the consecutive self-assembly pathways of 1a in EtOH/H2O mixed solvent. The monomers of 1a firstly aggregated into the kinetic-controlled, nanodisc-shaped Agg. I upon cooling and the latter spontaneously transformed into the thermodynamically more stable Agg. II with a nanosheet morphology. While the non-fluorescent Agg. I displayed a broad absorption band (λmax = 594 nm), the Agg. II displayed a more intensive and narrowed J-band (λmax =693 nm) and a fluorescence band with a maximum at 760 nm (Фfl = 0.1), which could be ascribed to the J-aggregation induced emission enhancement. The kinetics of Agg. I to Agg. II transformation was further modulated by seed-initiated supramolecular polymerization with various ratios of Seedagg.II, in which the transformation rate was significantly increased by ca. 2 orders of magnitude compared to the spontaneous process. The supramolecular amphiphile 1b bearing longer hydrophilic chains formed only one type aggregate, which exhibited spectroscopic and morphological properties that were highly comparable with that of Agg. I.

Unprecedented cubic mesomorphic behaviour of crown-ether functionalized amphiphilic cyclodextrins.

Amphiphilic supramolecular materials based on biodegradable cyclodextrins (CDs) have been known to self-assemble into different types of thermotropic liquid crystals, including smectic and hexagonal columnar mesophases. Previous studies on amphiphilic CDs bearing 14 aliphatic chains at the primary face and 7 oligoethylene glycol (OEG) chains at the secondary face showed that the stability of the mesophase can be rationally tuned through implemation of terminal functional groups to the OEG chains. Here, we report the syntheses of first examples of crown ether-functionalized amphiphilic cyclodextrins that unexpectedly form thermotropic bicontinuous cubic phases. This constitutes the first reported examples of cyclodextrins forming such phases, which are potentially capable of 3D ion transport. Lithium composites were made to assess lithium conduction in the material. XRD revealed the added lithium salt destabilizes the cubic phase in favour of the smectic phase. Solid-state NMR studies showed that these materials conduct lithium ions with a very low activation energy.

Design of Cyborg Proteins by Loop Region Replacement with Oligo(ethylene glycol): Exploring Suitable Mutations for Cyborg Protein Construction Using Machine Learning

Abstract We synthesized a “cyborg protein,” wherein a synthetic molecule partially substitutes the main peptide chain by linking two protein domains with a synthetic oligomer. Green fluorescent protein (GFP) served as the model for constructing the cyborg proteins. We prepared circularly permuted GFP (cpGFP) with new termini between β10 and β11, where the original N- and C-termini were linked by a cleavable peptide loop. The cyborg GFP was constructed from cpGFP by linking the β10 and β11 with oligo(ethylene glycol) using maleimide-cysteine couplings, followed by the enzymatic cleavage of the N- and C-termini linking loop by thrombin. With the help of machine learning, we were able to obtain the cpGFP mutants that significantly alter the fluorescence activity (53% increase) by thrombin treatment, which splits cpGFP into two fragments (fragmented-GFP), and by heat shock. When the cyborg GFP was constructed using this mutant, the fluorescence intensity increased by 13% after heat treatment, similar to cpGFP (33% increase), and the behavior was significantly different from that of the fragmented-GFP. This result suggests the possibility that the oligo(ethylene glycol) chain in the cyborg protein plays a similar role to the peptide in the main chain of the protein.

(Invited) Fullerenes for Bio-Applications: The Way of Water

Nano-materials are emerging as important components for a series of bio-applications. In this context, carbon nanostructures such as graphene, carbon nanotubes and fullerenes have unique chemical and physical properties that make them attractive for such applications. Carbon nanomaterials have been used in tissue engineering, biosensing and drug delivery. They have also shown anti-microbial activity. They can be loaded with drugs for controlled local delivery. More importantly, the surface of carbon nanomaterials can be functionalised to enhance their biocompatibility by increasing their water-solubility.In this talk, I will present an update on our work in using fullerenes and their derivatives for developing bio-nanomaterials. I shall focus on the combination of carbon nanostructures and polymeric materials which can result in supramolecular hydrogels with interesting properties. Hydrogels are emerging as important materials in applications such as cellular scaffoldings in regenerative medicine/tissue engineering, tissue replacements, wound dressings, etc.I will present the synthesis of supramolecular hydrogels made from fullerenes of different sizes (C60, C84 and C90–92) that have been hydroxylated and functionalised with hydrophilic oligoethylene glycol chains. To the best of our knowledge, there have been no attempts made at incorporating higher fullerenes and their derivatives into such extended supramolecular structures, before now.I will also show possibilities for extending our approach to endohedral fullerenes such as N@C60. I will show how we can use advanced techniques including AFM to characterise the elasticity of the hydrogels formed. The ability to incorporate endohedral fullerenes in hydrogels may be important in extending the possibility for using these materials as sensors in vitro or even in vivo, exploiting the quantum properties of such molecular systems such as their extended electron and nuclear spin lifetimes.

Self-Assembly of Amphiphilic PDI and NDI Derivatives with Opposite Thermoresponsive Fluorescent Behaviors in Aqueous Solution.

This work presents a study of the thermally induced aggregation of perylene diimide (PDI) and naphthalene diimide (NDI) derivatives modified with oligo ethylene glycol (OEG) chains in aqueous solution. Water-soluble and flexible OEG side chains were introduced into the π-core of glutamate-modified NDI and PDI structures, and the aggregation process was modulated by heating or cooling in water. Interestingly, a rare opposite temperature response of fluorescent behavior from the two amphiphilic chromophores was revealed, in which the PDI exhibited fluorescent enhancement, while fluorescent quenching upon temperature increase was observed from the NDI assembly. The mechanism of thermally induced aggregation is clearly explained by studies with various spectroscopic techniques including UV-visible, fluorescence, 1H NMR, 2D NMR spectroscopy, and SEM observation as well as control experiments operated in DMSO solution. It is found that although similar J-aggregates were formed by both amphiphilic chromophores in aqueous solution, the temperature response of the aggregates to temperature was opposite. The degree of PDI aggregation decreased, while that of NDI increased upon temperature rising. This research paves a valuable way for understanding the complicated supramolecular behaviors of amphiphilic chromophores.

Water-Soluble Trityl Radicals for Fluorescence Imaging.

Stable tris(trichlorophenyl)methyl radicals have gained interest as all-organic bioimaging agents combining fluorescent and paramagnetic properties. However, cellular uptake has so far only been reported for nanoparticles, because molecular hydrophobic trityl radicals are not soluble in aqueous media. Here, we report the synthesis and characterization of new water-soluble tris(trichlorophenyl)methyl radical derivatives exhibiting red doublet emission. Solubility in water is achieved through functionalization with oligoethylene glycol (OEG) chains. The emission behavior of OEG functionalized trityl radicals is studied in polar environments. Donor-functionalization with carbazole evokes a charge-transfer excited state that is efficiently quenched in polar solvents. In contrast, click-reaction mediated attachment of OEG-azide and trityl acetylene furnishes a triazole functionalized radical with locally excited states and emission in water. Confocal fluorescence microscopy proves successful uptake of the material by macrophages in cell culture, showing the potential of our water soluble trityl radical for fluorescence bioimaging.

Functionalized [2.2]Paracyclophanedienes as Monomers for Poly(p-phenylenevinylene)s.

Poly(p-phenylenevinylene)s (PPVs) featuring complex side-chains, to date, have only been synthesized by nonliving polymerization methods which have no control over PPV molecular weights, dispersities, or end groups. [2.2]Paracyclophane-1,9-diene (pCpd) has gained attention as a monomer for its ability to be ring-opened to PPV in a living fashion. pCpd, an organic cyclic scaffold with planar chirality, has seen minimal structural diversity due to the harsh reaction conditions required to afford the highly strained compound. Herein, we introduce a general method to overcome this by targeting the synthesis of a monohydroxy-pCpd via mono-demethylation of a dialkoxy-pCpd. The monohydroxy-pCpd can then be functionalized easily, which we demonstrate using three distinct side-chains with four moieties commonly incorporated in conjugated polymers: an alkyl bromide, an oligo(ethylene glycol) chain, an enantiomerically pure side-chain, and a Boc-protected amine. These monofunctionalized-pCpds were investigated as monomers in the ring-opening metathesis polymerization (ROMP) to afford functionalized PPVs in a living manner. The functional-group-containing PPVs are synthesized with full control over their end groups, repeat units, and dispersities. The feasibility of post-polymerization modifications to incorporate any desired moiety to PPV fabricated by this method was demonstrated using an azide-alkyne click reaction. All synthesized PPVs were soluble in organic solvents and display the same fluorescent emission, indicating their conjugated backbones are unaltered.

(Invited) Fullerenes in Water: The Formation of Hydrogels

Hydrogels are emerging as important materials to achieve medical advances, in applications such as cellular scaffoldings in regenerative medicine/tissue engineering, tissue replacements, wound dressings, and drug/gene/protein/RNA delivery systems among others. This is due to their high-water content and their similarities to the structural form of living tissues. Hydrogels are most useful when they can be compatible with the dynamics of healthy tissues, while at the same time they are able to deliver therapeutic molecules at specified locations.In this talk, I will present our recent work in using fullerenes and their derivatives for biomedical engineering. Fullerenes are attractive for a number of reasons: their surface can be functionalised to enhance their biocompatibility and water solubility; they can encapsulate molecules in endohedral form, and they have shown antiviral, antibacterial and antioxidant activity. The physical properties of fullerenes make them ideal candidates to produce supramolecular structures and hydrogels without the need for an external polymeric matrix. I will show the synthesis of supramolecular hydrogels solely from covalently-functionalised C60. I will also demonstrate the synthesis of new kinds of supramolecular hydrogels made from fullerenes of different sizes (C60, C84 and C90–92) functionalised with hydrophilic oligoethylene glycol chains. Carrying out the reaction on fullerenes of different sizes, including C70, allows us to interrogate the effect of fullerene shape on chemical functionalization, and thus, self-assembly behaviour.We believe these fullerene hydrogels may have biomedical applications. Furthermore, they maybe sought after for electrochemical applications such as next-generation capacitors.

An amphiphilic near-infrared Mn,O-chelated metallo-azadipyrromethene dye: Synthesis, acid-responsive properties, and aggregation pathway control

A new amphiphilic Mn,O-chelated azadipyrromethene dye 1 bearing dodecyl chains at the 1,7-phenyls and oligo(ethylene glycol) chains at the 3,5-phenyls was synthesized and characterized. The dye 1 exhibited an absorption maximum in NIR at 823 nm, which is largely bathochromically shifted as compared with the known aza-BODIPY as well as the B,O-chelated aza-BODIPY dyes. Meanwhile, the electrochemical studies of this dye indicated a lower HOMO-LUMO gap in comparison with the boron-chelated analogues. This dye also displayed the acid-responsive properties, as indicated by the hypsochromical shift of ca. 94 nm of the absorption band as well as the occurrence of fluorescence emission at 751 nm upon adding trifluoroacetic acid (TFA) into the dye 1 solution. Moreover, in highly polar solvent MeOH the amphiphilic dye 1 self-assembled into H-type aggregates, which exhibited a fibrous morphology in AFM studies. Further temperature-dependent UV/Vis absorption spectroscopic studies revealed a cooperative aggregation mechanism of dye 1 in MeOH. Based on the acid-responsive properties of 1, a method of control of the aggregation pathway of dye 1 by using acid and base was proposed and demonstrated by UV/Vis spectroscopic studies.

An amphiphilic molecule with a single fluorophore exhibits multiple stimuli-responsive behavior

Fluorescent materials that respond to multiple stimuli have broad applications ranging from sensing and bioimaging to information encryption. Herein, we report the design and synthesis of a single-fluorophore-based amphiphile DCSO, which shows temperature-, solvent-, humidity-, and radiation-dependent fluorescence. DCSO consists of a dicyanostilbene (DCS) group as a rigid hydrophobic core with oligo(ethylene glycol) (OEG) chains at both ends as a flexible hydrophilic periphery. The DCS group acts as a highly efficient fluorophore, while the OEG chain endows the molecule with thermo-responsiveness. Fluorescent colors can vary from blue to green to yellow in response to external stimuli. On the basis of light radiation, we demonstrate that this system can be applied to time-dependent information encryption, in which the correct information can only be read at a specific time under irradiation. This work further demonstrates the usefulness and application of single-fluorophore-based luminescent materials with multiple stimuli-responsive functions.

Design of Dendritic Promesogenic Ligands for Liquid Crystal-Nanoparticle Hybrid Systems

Liquid crystal-nanoparticle (LC-NP) hybrid systems allow synergistic interactions between LC matrixes with anisotropic alignment and NP dopants with versatile functionalities. A uniform, well-dispersed, and highly stable thermotropic LC-NP mixture paves the way for further applications. In this work, a linear promesogenic ligand and two types of dendritic promesogenic ligands with alkyl or oligo ethylene glycol (OEG) chains are designed and synthesized to facilitate incorporating NPs into the thermotropic 4-cyano-4′-pentylbiphenyl (5CB) LC matrix. A comparison study between the linear and the dendritic ligands on the capability to promote miscibility and stability of NPs in LCs is conducted. Miscibility test results show that the linear ligand and the OEG-chained dendrimer both perform well in uniformly dispersing NPs in LCs. Dynamic assemblies of NPs assisted by dendritic ligands and driven by aligning and equilibrating of mesogens are captured, showing the potential of manipulating the assembly of NPs through external thermal stimuli. The stability test shows that both types of dendrimers can significantly enhance the shelf-life time and thermal stability of NPs compared to the linear ligand. In particular, Au NPs capped with OEG-chained dendrimers are stable in 5CB for 6 months at room temperature and over 10 h at 50 °C. The synthesis of dendritic ligands is highly modulated and can be generalized onto NPs with different dimensions and properties. Tied by the dendritic promesogenic ligands, this LC-NP hybrid system with good uniformity and stability could be further applied to tunable optical displays, responsive materials, etc.

Smart Poly(lactide)-b-poly(triethylene glycol methyl ether methacrylate) (PLA-b-PTEGMA) Block Copolymers: One-Pot Synthesis, Temperature Behavior, and Controlled Release of Paclitaxel.

This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and 1H NMR spectroscopy, were used to characterize the block copolymers, while 1H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications.

Manipulating Host‐Guest Charge Transfer of a Water‐Soluble Double‐Cavity Cyclophane for NIR‐II Photothermal Therapy

AbstractWater‐soluble small organic photothermal agents (PTAs) over NIR‐II biowindow (1000–1350 nm) are highly desirable, but the rarity greatly limits their applications. Based on a water‐soluble double‐cavity cyclophane GBox‐44+, we report a class of host–guest charge transfer (CT) complexes as structurally uniform PTAs for NIR‐II photothermal therapy. As a result of its high electron‐deficiency, GBox‐44+ can bind different electron‐rich planar guests with a 1 : 2 host/guest stoichiometry to readily tune the CT absorption band that extends to the NIR‐II region. When using a diaminofluorene guest substituted with an oligoethylene glycol chain, the host–guest system realized both good biocompatibility and enhanced photothermal conversion at 1064 nm, and was then exploited as a high‐efficiency NIR‐II PTA for cancer cell and bacterial ablation. This work broadens the potential applications of host–guest cyclophane systems and provides a new access to bio‐friendly NIR‐II photoabsorbers with well‐defined structures.

Manipulating Host-Guest Charge Transfer of a Water-Soluble Double-Cavity Cyclophane for NIR-II Photothermal Therapy.

Water-soluble small organic photothermal agents (PTAs) over NIR-II biowindow (1000-1350 nm) are highly desirable, but the rarity greatly limits their applications. Based on a water-soluble double-cavity cyclophane GBox-44+ , we report a class of host-guest charge transfer (CT) complexes as structurally uniform PTAs for NIR-II photothermal therapy. As a result of its high electron-deficiency, GBox-44+ can bind different electron-rich planar guests with a 1 : 2 host/guest stoichiometry to readily tune the CT absorption band that extends to the NIR-II region. When using a diaminofluorene guest substituted with an oligoethylene glycol chain, the host-guest system realized both good biocompatibility and enhanced photothermal conversion at 1064 nm, and was then exploited as a high-efficiency NIR-II PTA for cancer cell and bacterial ablation. This work broadens the potential applications of host-guest cyclophane systems and provides a new access to bio-friendly NIR-II photoabsorbers with well-defined structures.

A temperature-responsive artificial light-harvesting system in water with tunable white-light emission

A tadpole-type amphiphilic monomer containing cyanostilbene and oligo(ethylene glycol) chains has been designed and synthesized, which can be used to construct a thermo-responsive light-harvesting system in water with tunable white-light emission.

Detection of alkali and alkaline earth metal ions using birefringence of hyperswollen lamellar phase.

Chemical sensors have targeted various substances. Most sensors electrically amplify signals. Here, we propose a visual detection system that uses a hyperswollen lamellar phase and detects targets in a solution without electric amplification. Amphiphiles with an oligo(ethylene glycol) chain can catch alkali and alkaline earth metal ions and amplify to macroscopic birefringence.

Halogen-Bonding Heteroditopic [2]Catenanes for Recognition of Alkali Metal/Halide Ion Pairs.

The first examples of halogen bonding (XB) heteroditopic homo[2]catenanes were prepared by discrete Na+ template-directed assembly of oligo(ethylene glycol) units derived from XB donor-containing macrocycles and acyclic bis-azide precursors, followed by a CuI -mediated azide-alkyne cycloaddition macrocyclisation reaction. Extensive 1 H NMR spectroscopic studies show the [2]catenane hosts exhibit positive cooperative ion-pair recognition behaviour, wherein XB-mediated halide recognition is enhanced by alkali metal cation pre-complexation. Notably, subtle changes in the catenanes' oligo(ethylene glycol) chain length dramatically alters their ion-binding affinity, stoichiometry, complexation mode, and conformational dynamics. Solution-phase and single-crystal X-ray diffraction studies provide evidence for competing host-separated and direct-contact ion-pair binding modes. We further demonstrate the [2]catenanes are capable of extracting solid alkali-metal halide salts into organic media.

Halogen‐Bonding Heteroditopic [2]Catenanes for Recognition of Alkali Metal/Halide Ion Pairs

AbstractThe first examples of halogen bonding (XB) heteroditopic homo[2]catenanes were prepared by discrete Na+ template‐directed assembly of oligo(ethylene glycol) units derived from XB donor‐containing macrocycles and acyclic bis‐azide precursors, followed by a CuI‐mediated azide‐alkyne cycloaddition macrocyclisation reaction. Extensive 1H NMR spectroscopic studies show the [2]catenane hosts exhibit positive cooperative ion‐pair recognition behaviour, wherein XB‐mediated halide recognition is enhanced by alkali metal cation pre‐complexation. Notably, subtle changes in the catenanes’ oligo(ethylene glycol) chain length dramatically alters their ion‐binding affinity, stoichiometry, complexation mode, and conformational dynamics. Solution‐phase and single‐crystal X‐ray diffraction studies provide evidence for competing host‐separated and direct‐contact ion‐pair binding modes. We further demonstrate the [2]catenanes are capable of extracting solid alkali‐metal halide salts into organic media.

Impact of Hydrophobic/Hydrophilic Balance on Aggregation Pathways, Morphologies, and Excited-State Dynamics of Amphiphilic Diketopyrrolopyrrole Dyes in Aqueous Media.

We report the thermodynamic and kinetic aqueous self-assembly of a series of amide-functionalized dithienyldiketopyrrolopyrroles (TDPPs) that bear various hydrophilic oligoethylene glycol (OEG) and hydrophobic alkyl chains. Spectroscopic and microscopic studies showed that the TDPP-based amphiphiles with an octyl group form sheet-like aggregates with J-type exciton coupling. The effect of the alkyl chains on the aggregated structure and the internal molecular orientation was examined via computational studies combining MD simulations and TD-DFT calculations. Furthermore, solvent and thermal denaturation experiments provided a state diagram that indicates the formation of unexpected nanoparticles during the self-assembly into nanosheets when longer OEG side chains are introduced. A kinetic analysis revealed that the nanoparticles were obtained selectively as an on-pathway intermediate state toward the formation of thermodynamically controlled nanosheets. The metastable aggregates were used for seed-initiated supramolecular assembly, which allowed establishing control over the assembly kinetics and the aggregate size. The sheet-like aggregates prepared using the seeding method exhibited coherent vibration in the excited state, indicating a well-ordered orientation of the TDPP units. These results underline the significance of fine tuning of the hydrophobic/hydrophilic balance in the molecular design to kinetically control the assembly of amphiphilic π-conjugated molecules into two-dimensional nanostructures in aqueous media.

Unravelling Disorder Effects on Thermoelectric Properties of Semicrystalline Polymers in a Wide Range of Doping Levels.

Thermoelectric (TE) performance of a specific semicrystalline polymer is studied experimentally only in a limited range of doping levels with molecular doping methods. The doping level is finely controlled via in situ electrochemical doping in a wide range of carrier concentrations with an electrolyte ([PMIM]+ [TFSI]- )-gated organic electrochemical transistor system. Then, the charge generation/transport and TE properties of four p-type semicrystalline polymers are analyzed and their dynamic changes of crystalline morphologies and local density of states (DOS) during electrochemical doping are compared. These polymers are synthesized based on poly[(2,5-bis(2-alkyloxy)phenylene)-alt-(5,6-difluoro-4,7-di(thiophene-2-yl)benzo[c][1,2,5]thiadiazole)] by varying side chains: With oligoethylene glycol (OEG) substituents, facile p-doping is achieved because of easy penetration of TFSI- ions into the polymer matrix. However, the charge transport is hindered with longer OEG chains length because of the enhanced insulation. Therefore, with the shortest OEG substituents the electrical conductivity (30.1 S cm-1 ) and power factor (2.88 µW m-1 K-2 ) are optimized. It is observed that all polymers exhibit p- to n-type transition in Seebeck coefficients in heavily doped states, which can be achieved by electrochemical doping. These TE behaviors are interpreted based on the relation between the localized DOS band structure and molecular packing structure during electrochemical doping.