Miktoarm Star Research Articles

Synthesis, characterization and self-assembly of linear and miktoarm star copolymers of exclusively immiscible polydienes

Model linear PB1,4-b-PI3,4 and the corresponding miktoarm star copolymers PB1,4(PI3,4)n=2,3 were synthesized by anionic polymerization/selective chlorosilane chemistry, molecularly characterized and the morphological/thermal properties were reported.

Effects of Asymmetric Molecular Architecture on Chain Stretching and Dynamics in Miktoarm Star Copolymers

We use broad-band dielectric spectroscopy (BDS) and small-angle X-ray scattering (SAXS) to investigate the impact of architectural asymmetry in the miktoarm star copolymer on the dielectric polymer relaxations. The miktoarm copolymers studied contain one or two polystyrene (PS) chains of constant molecular weight and two identical poly(cis-1,4-isoprene) (PI) chains with varied molecular weights. Using the chains in the PI block as dielectric probes, we find that the architecturally asymmetric miktoarm star copolymer systems (PSPI2) feature distributions in chain relaxation times and dielectric relaxation strengths that are not dependent on molecular weight or morphology, in stark contrast to the effects of morphological confinement observed for symmetric diblock systems (PS-b-PI or PS2PI2). Along with evidence from the SAXS measurements regarding phase separation, these results are attributed to influences from chain stretching within the framework of the Gaussian chain model for block copolymer systems. As such, the molecular architecture in block copolymers happens to be a versatile handle to control polymer chain dynamics and, ultimately, the macroscopic physicochemical properties in architecturally complex polymers.

Micellization through complexation of oppositely charged diblock copolymers: Effects of composition, polymer architecture, salt of different valency, and thermoresponsive block

AbstractThe structural and electrical characteristics of polyelectrolyte complex micelles (PCMs) formed by mixing of oppositely charged double hydrophilic copolymers are studied by means of molecular dynamics simulations. In mixtures of linear diblock copolymers we found that the preferential aggregation number Np of PCMs is a universal function of the ratio γ± of the total positive to total negative charges of the mixture. The addition of divalent salts ions induces a secondary micellization. In mixtures of copolymers bearing a common neutral thermoresponsive block, micelles with contracted corona consisting of thermoresponsive blocks and complex polyelectrolyte core are formed at low salt concentration and temperature far away the biphasic regime. At high salt concentration and temperature in the biphasic regime, reversed micelles are obtained. In equimolar mixtures of linear copolymers with miktoarm stars we found that Np of PCMs decreases as the number of charged branches of miktoarm copolymer increases. The shape of micelles progressively changes from spherical to worm‐like with the increase of number of branches of miktoarm copolymers. Our findings are in full agreement with existing experimental and theoretical predictions and provides new and additional insights.

Dendrons and Dendritic Terpolymers: Synthesis, Characterization and Self-Assembly Comparison.

To the best of our knowledge, this is the very first time that a thorough study of the synthetic procedures, molecular and thermal characterization, followed by structure/properties relationship for symmetric and non-symmetric second generation (2-G) dendritic terpolymers is reported. Actually, the synthesis of the non-symmetric materials is reported for the first time in the literature. Anionic polymerization enables the synthesis of well-defined polymers that, despite the architecture complexity, absolute control over the average molecular weight, as well as block composition, is achieved. The dendritic type macromolecular architecture affects the microphase separation, because different morphologies are obtained, which do not exhibit long range order, and various defects or dislocations are evident attributed to the increased number of junction points of the final material despite the satisfactory thermal annealing at temperatures above the highest glass transition temperature of all blocks. For comparison reasons, the initial dendrons (miktoarm star terpolymer precursors) which are connected to each other in order to synthesize the final dendritic terpolymers are characterized in solution and in bulk and their self-assembly is also studied. A major conclusion is that specific structures are adopted which depend on the type of the core connection between the ligand and the active sites of the dendrons.

Miktoarm Star Polymers with Environment-Selective ROS/GSH Responsive Locations: From Modular Synthesis to Tuned Drug Release through Micellar Partial Corona Shedding and/or Core Disassembly.

Branched architectures with asymmetric polymeric arms provide an advantageous platform for the construction of tailored nanocarriers for therapeutic interventions. Simple and adaptable synthetic methodologies to amphiphilic miktoarm star polymers have been developed in which spatial location of reactive oxygen species (ROS) and glutathione (GSH) responsive entities is articulated to be on the corona shell surface or inside the core. The design of such architectures is facilitated through versatile building blocks and selected combinations of ring-opening polymerization, Steglich esterification, and alkyne-azide click reactions. Soft nanoparticles from aqueous self-assembly of these stimuli responsive miktoarm stars have low critical micelle concentrations and high drug loading efficiencies. Partial corona shedding upon response to ROS is accompanied by an increase in drug release, without significant changes to overall micelle morphology. The location of the GSH responsive unit at the core leads to micelle disassembly and complete drug release. Curcumin loaded soft nanoparticles show higher efficiencies in preventing ROS generation in extracellular and cellular environments, and in ROS scavenging in human glioblastoma cells. The ease in synthetic elaboration and an understanding of structure-property relationships in stimuli responsive nanoparticles offer a facile venue for well-controlled drug delivery, based on the extra- and intracellular concentrations of ROS and GSH.

Micellization of amphiphilic host–guest inclusion complexes of polymers based on β–cyclodextrin trimer and adamantane

The present work aims to study the self–aggregation of amphiphlic miktoarm star polymers synthesized via the inclusion complexation of adamantyl terminated poly(methyl methacrylate) (ADM–PMMA) guest, into β–cyclodextrin grafted polyacrylamide (β–CD–PAM) and β–cyclodextrin trimer (3–β–CD) grafted polyacrylamide (3–β–CD–PAM) star polymer hosts, separately. β–CD and 3–β–CD based hosting star polymers have been synthesized through solution polymerization technique and the guest adamantyl terminated poly(methyl methacrylate) through the technique of atom transfer radical polymerization (ATRP) by using an adamantine–based ATRP initiator. Further, the guest polymer has been incorporated into the host polymer via molecular recognition between adamantyl moiety and β–CD. Construction of β–CD–PAM–b–ADM–PMMA and 3–β–CD–PAM–b–ADM–PMMA miktoarm star polymers has been examined by 1H NMR and 2D 1H NOESY NMR spectra. Their critical micellar concentrations have been estimated by using fluorescence spectroscopy. Further, sizes of the self–aggregates have been anticipated by dynamic light scattering and transmission electron microscopic investigations.

Miktoarm Star Polymers: Branched Architectures in Drug Delivery.

Delivering active pharmaceutical agents to disease sites using soft polymeric nanoparticles continues to be a topical area of research. It is becoming increasingly evident that the composition of amphiphilic macromolecules plays a significant role in developing efficient nanoformulations. Branched architectures with asymmetric polymeric arms emanating from a central core junction have provided a pivotal venue to tailor their key parameters. The build-up of miktoarm stars offers vast polymer arm tunability, aiding in the development of macromolecules with adjustable properties, and allows facile inclusion of endogenous stimulus-responsive entities. Miktoarm star-based micelles have been demonstrated to exhibit denser coronae, very low critical micelle concentrations, high drug loading contents, and sustained drug release profiles. With significant advances in chemical methodologies, synthetic articulation of miktoarm polymer architecture, and determination of their structure-property relationships, are now becoming streamlined. This is helping advance their implementation into formulating efficient therapeutic interventions. This review brings into focus the important discoveries in the syntheses of miktoarm stars of varied compositions, their aqueous self-assembly, and contributions their formulations are making in advancing the field of drug delivery.

Preparation of Doxorubicin-Loaded Amphiphilic Poly(D,L-Lactide-Co-Glycolide)-b-Poly(N-Acryloylmorpholine) AB2 Miktoarm Star Block Copolymers for Anticancer Drug Delivery.

Owing to their unique topology and physical properties, micelles based on miktoarm amphiphilic star block copolymers play an important role in the biomedical field for drug delivery. Herein, we developed a series of AB2-type poly(D,L-lactide-co-glycolide)-b-poly(N-acryloyl morpholine) (PLGA-b-PNAM2) miktoarm star block copolymers by reversible addition–fragmentation chain–transfer polymerization and ring-opening copolymerization. The resulting miktoarm star polymers were investigated by 1H NMR spectroscopy and gel permeation chromatography. The critical micellar concentration value of the micelles increases with an increase in PNAM block length. As revealed by transmission electron microscopy and dynamic light scattering, the amphiphilic miktoarm star block copolymers can self-assemble to form spherical micellar aggregates in water. The anticancer drug doxorubicin (DOX) was encapsulated by polymeric micelles; the drug-loading efficiency and drug-loading content of the DOX-loaded micelles were 81.7% and 9.1%, respectively. Acidic environments triggered the dissociation of the polymeric micelles, which led to the more release of DOX in pH 6.4 than pH 7.4. The amphiphilic PLGA-b-PNAM2 miktoarm star block copolymers may have broad application as nanocarriers for controlled drug delivery.

Novel amphiphilic ABC 3-miktoarm star azo-copolymer with polypeptide chain: Synthesis, self-assembly and photo-responsive behavior

Well-defined amphiphilic ABC 3-miktoarm star terpolymer containing hydrophilic methoxy poly(ethylene glycol) (MPEG), hydrophobic poly[6-(4-methoxy-azobenzene-4′-oxy) hexyl methacrylate] (PAzoMA) and poly(γ-benzyl-L-glutamic acid) (PBLG) was synthesized by a combination of copper-mediated atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP). MPEG was modified to bear two different functional groups, which were further modified to the initiator of ATRP and ROP for the preparation of the amphiphilic ABC-type 3-miktoarm star terpolymers (MPEG) (PAzoMA) (PBLG). The spindle-like micelles were formed from the amphiphilic 3-miktoarm star terpolymer through a solution self-assembly due to the rigid ɑ-helical conformation of PBLG block and the π-π interaction between PBLG block with PAzoMA block in the star terpolymer. The investigation of the photo-isomerization behavior of (MPEG) (PAzoMA) (PBLG) in solution and in micellar solution showed that trans–cis isomerization in solution was quicker than that in micellar solution, and H- or J-aggregates of the azobenzene groups in the aggregates did not be observed. On the basis of the experimental results, the formation mechanisms of the spindle-like micelles were suggested and the obtained results may expand the self-assembly research field.

Correction to Supramolecular Four-Armed Star A2B2 Copolymer (Miktoarm Star) via Host–Guest Complexation and Nitroxide-Mediated Radical Polymerization

Correction to Supramolecular Four-Armed Star A₂B₂ Copolymer (Miktoarm Star) via Host–Guest Complexation and Nitroxide-Mediated Radical Polymerization

Alternating Gyroid Network Structure in an ABC Miktoarm Terpolymer Comprised of Polystyrene and Two Polydienes.

The synthesis, molecular and morphological characterization of a 3-miktoarm star terpolymer of polystyrene (PS, = 61.0 kg/mol), polybutadiene (PB, = 38.2 kg/mol) and polyisoprene (PI, = 29.2 kg/mol), corresponding to volume fractions (φ) of 0.46, 0.31 and 0.23 respectively, was studied. The major difference of the present material from previous ABC miktoarm stars (which is a star architecture bearing three different segments, all connected to a single junction point) with the same block components is the high 3,4-microstructure (55%) of the PI chains. The interaction parameter and the degree of polymerization of the two polydienes is sufficiently positive to create a three-phase microdomain structure as evidenced by differential scanning calorimetry and transmission electron microscopy (TEM). These results in combination with small-angle X-ray scattering (SAXS) and birefringence experiments suggest a cubic tricontinuous network structure, based on the I4132 space group never reported previously for such an architecture.

Micellization Behaviour of Linear and Nonlinear Block Copolymers Based on Poly(n-hexyl isocyanate) in Selective Solvents.

Block copolymers have attracted significant scientific and economic interest over the last decades due to their ability to self-assemble into ordered structures both in bulk and in selective solvents. In this work, the self-assembly behaviour of both linear (diblocks, triblocks and pentablocks) and nonlinear (miktoarm stars and a block-graft) copolymers based on poly(n-hexyl isocyanate), PHIC, were studied in selective solvents such as n-heptane and n-dodecane. A variety of experimental techniques, namely static and dynamic light scattering, dilute solution viscometry and atomic force microscopy, were employed to study the micellar structural parameters (e.g., aggregation number, overall micellar size and shape, and core and shell dimensions). The effect of the macromolecular architecture, the molecular weight and the copolymer composition on the self-assembly behaviour was studied. Spherical micelles in equilibrium with clusters were obtained from the block copolymers. Thermally stable, uniform and spherical aggregates were found from the triblock copolymers. The poly(n-hexyl isocyanate)-b-polyisoprene-b-poly(n-hexyl isocyanate),-HIH copolymers tend to adopt closed loop conformation, leading to more elongated cylindrical-type structures upon increasing the concentration. Clustering effects were also reported in the case of the pentablock terpolymers. The topology of the blocks plays an important role, since the poly(n-hexyl isocyanate)-b-polystyrene-b-polyisoprene-b-polystyrene-b-poly(n-hexyl isocyanate), HSISH terpolymer shows intermicellar fusion of spherical micelles, leading to the formation of extended networks. The formation of spherical micelles in equilibrium with clusters was obvious in the case of the miktoarm stars, whereas the block-graft copolymer shows the existence of mainly unimolecular micelles.

Tuning Solvent Quality Induces Morphological Phase Transitions in Miktoarm Star Polymer Films

The ordering and kinetics of self-assembly of miktoarm star polymers of the form (An)k–C–(Bn)k in solution and confined between two surfaces are investigated using a coarse-grained molecular dynamics simulation, with the ultimate goal of developing predictive capabilities for these systems. By systematically changing the relative solvent-block interaction for one block, combined with the effect of confining substrate on one side and vapor on the other side, we observed a number of interesting morphologies for an inherently lamellar miktoarm star polymers in the absence of solvent. Furthermore, we also found that in solution the self-assembly kinetics of miktoarm star polymers into cylindrical and lamellar morphologies is completely different from the self-assembly kinetics of linear block copolymers. The findings from the present study can be used to tailor the film morphology of miktoarm star polymers, playing a leading role in guiding the experimentalists for designing this class of materials for different types of applications.

Supramolecular Four-Armed Star A2B2 Copolymer (Miktoarm Star) via Host–Guest Complexation and Nitroxide-Mediated Radical Polymerization

A supramolecular four-armed star copolymer was prepared from the pseudorotaxane complex of a crown-centered polystyrene and a bis(2,2,6,6-tetramethylpiperidinyl-1-oxy) viologen compound and n-butyl methacrylate (BMA) by nitroxide-mediated polymerization of the latter. Solvent fractionation with dioxane/THF/MeOH removed a small amount of a high molecular weight poly(BMA) homopolymer. The molecular weight increase from its monomodal size exclusion chromatographic trace gives direct evidence of the four-armed star copolymer formation; there is no residual starting polystyrene. NMR spectroscopy shows the two components of the copolymer and confirms the presence of the central [2]rotaxane unit. Differential scanning calorimetry displays two glass-transition temperatures, which correspond closely to those of polystyrene and poly(BMA).

Complex Star Architectures of Well-Defined Polyethylene-Based Co/Terpolymers

Well-defined polyethylene (PE)-based 3-miktoarm star copolymers (PI)2PE-OH, PI2(PI′-b-PE)-OH and terpolymer PI2(PS-b-PE)-OH (PI: polyisoprene, PS: polystyrene), bearing a functional group (−OH) at ...

Versatile Approach for Preparing PVC-Based Mikto-Arm Star Additives Based on RAFT Polymerization

A versatile approach to the synthesis of migration-resistant poly(vinyl chloride) (PVC) additives is described and a preliminary assessment of their properties is presented. The process involves th...

Synthesis and characterization of low molar mass end-functionalized homo- and copolymers with ureidopyrimidone, UPy groups

Anionic polymerization techniques along with functional initiation and/or functional termination reactions were employed for the synthesis of end-functionalized polymers composed from polystyrene (PS), polyisoprene-1,4 (PI), and polybutadiene-1,4 (PBd) chains bearing –OH end groups. Specifically, PS-OH, HO-PS-OH homopolymers, PS-b-PI-OH and PI-b-PS-OH block copolymers, HO-PS-b-PI-b-PS-OH triblock copolymers, and PS(PBd-OH)2 miktoarm star copolymers were prepared. The –OH functions were transformed into 2–ureido–4–pyrimidone, UPy, groups leading to the synthesis of the corresponding functionalized polymers. The UPy groups interact through the formation of strong hydrogen bonds. The aggregation behavior of selected samples was studied by a variety of techniques, such as size exclusion chromatography, dilute solution viscometry, dynamic light scattering, differential scanning calorimetry, thermogravimetric analysis, melt rheology, small angle X-ray scattering, and atomic force microscopy. It was found that in the solid state and in non-polar solvents, the UPy-terminated chains associate leading to the formation of dimers and larger aggregates. This systematic study presents a library of useful materials for potential applications and for fundamental studies linking associations, molecular structure, and macroscopic properties.

Amphiphilic miktoarm star copolymers can self-assemble into micelle-like aggregates in nonselective solvents: a case study of polyoxometalate based miktoarm stars

It is well-known that amphiphilic star-shaped copolymers can self-assemble in selective solvents to form complicated micellar constructs as a synergistic result of both the topological constraints and relative volume fractions of the arms. Although the association phenomena of amphiphilic stars have been observed in nonselective solvents, both the structural detail and formation mechanism of these associates are not clear yet. Moreover, these experimental observations are controversial with respect to molecularly dispersed starlike copolymers in nonselective solvents as is popularly believed. To clarify these issues, we have synthesized a series of polyoxometalate-based polystyrene-poly(ethylene glycol) (PS-PEG) miktoarm star supramolecular copolymers (SEW-1-5) by coupling a Keggin-type polyoxometalate of K4[α-SiW12O40] with 1,2,3-triazolium bridged block copolymers of PSn-b+-PEGmI− (n=17, 26, 39, 57, 81; m=45) through ionic exchange reactions, respectively. TEM imaging, contact angle and 1H NMR studies reveal that SEW-2-5 self-assemble in chloroform, THF, and toluene to create micellelike aggregates ranging from cylinder to sphere with a PS corona and a PEG core, while for SEW-1, reverse bilayers are captured with a PEG corona and a PS core. Among these aggregates, the Keggin clusters of [α-SiW12O40]4− localize at the core-corona interfaces between PS and PEG. In terms of solvent quality, chloroform, THF, and toluene are only slightly poorer for PEG than that for PS with a relative order of chloroform<THF<toluene. These unexpected aggregates originate from the topological constraints of the chemically different arms of PS and PEG in the miktoarm stars, where the weak incompatibility between the PS and PEG arms is intensified appropriately. The presence of the reverse bilayered structures of SEW-1 is due to the magnified steric hindrance of the PEG45 arm with decreasing the molecular weight of the PS17 arm. However, to the best of our knowledge, these are the first examples clearly indicating that miktoarm star copolymers can self-assemble in common good solvents or slightly selective solvents to generate micellelike aggregates. This scenario is not only in sharp contrast to the intuitively considered behavior of unimolecular miktoarm stars in nonselective solvents, but also rather different from the conventional self-assembly behavior of amphiphilic star copolymers in selective solvents.

Synthesis and Self-Assembly of ABn Miktoarm Star Polymers

The stability of tetrahedrally close-packed (TCP) phases in block copolymer melts is predicted by theory to depend on molecular architecture, yet no experimental studies to date have probed its effect. Motivated by this open question, here we report an efficient synthesis of asymmetric ABn miktoarm star polymers using functionalized sugars as cores for orthogonal grafting-from block copolymerizations. A combination of ring-opening and atom transfer radical polymerization produced model low dispersity materials comprising a single A = poly(lactide) (L) and multiple B = poly(dodecyl acrylate) (D) arms that amplify "conformational asymmetry" through two concerted effects: the mikto architecture and disparate block statistical segment lengths. Analyzing the self-assembly of LD2 and LD3 samples resulted in the discovery of two TCP phases, σ and A15, that remained stable to significantly higher A-block volume fractions as the number of B arms increased. These results experimentally establish the importance of conformational asymmetry and molecular architecture as powerful design tools for the self-assembly of block copolymers into nonclassical phases.

Well-Defined DNA-Polymer Miktoarm Stars for Enzyme-Resistant Nanoflares and Carrier-Free Gene Regulation.

Herein, we report a star-architectured poly(ethylene glycol) (PEG)-oligonucleotide nanoconjugate of a well-defined molecular structure. Based upon fullerene C60 cores, each star bears precisely 1 DNA strand and 11 polymer chains. The elevated PEG density provides the DNA with steric selectivity: the DNA is significantly more resistant to nuclease digestion while remaining able to hybridize with a complementary sequence. The degree of resistance increases as the centers of mass for the DNA and fullerene are closer together. Such steric selectivity reduces protein-related background signals of the nanoflares synthesized from these miktoarm star polymers. Importantly, the stars improve cellular uptake and regulate gene expression as a non-cytotoxic, single-entity antisense agent without the need for a transfection carrier.