Linear-dendritic Block Copolymers Research Articles

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit.

Background: 4-(n-Octyloxy)aniline is a known component in the elaboration of organic materials with mesogenic properties such as N-substituted Schiff bases, perylene bisimide assemblies with a number of 2-amino-4,6-bis[4-(n-octyloxy)phenylamino]-s-triazines, amphiphilic azobenzene-containing linear-dendritic block copolymers and G-0 monomeric or dimeric dendritic liquid crystals with photochromic azobenzene mesogens. The present ab initio study explores a previously unknown use of 4-(n-octyloxy)aniline in the synthesis, structure and supramolecular behaviour of new dendritic melamines.Results: Starting from 4-(n-octyloxy)aniline, seven G-2 melamine-based dendrimers were obtained in 29–79% overall yields. Their iterative convergent- and chemoselective synthesis consisted of SN2-Ar aminations of cyanuric chloride and final triple N-acylations and Williamson etherifications (→ G-2 covalent trimers) or stoichiometric carboxyl/amino 1:3 neutralisations (→ G-2 ionic trimers). These transformations connected G-1 chloro- and amino-termini dendrons to m-trivalent cores (triazin-2,4,6-triyl and benzene-1,3,5-triyl units) or tripodands (central building blocks), such as N-substituted melamines with 4-hydroxyphenyl or phenyl-4-oxyalkanoic motifs. Owing to the diversity of cores and central building blocks, the structural assortment of the dendritic series was disclosed by solvation effects (affecting reactivity), rotational stereodynamism and self-organisation phenomena (determining a vaulted and/or propeller macromolecular shape in solution). DFT calculations (in solution), (VT) NMR and IR (KBr) spectroscopy supported these assignments. TEM analysis revealed the ability of the title compounds towards self-assembling into homogeneously packed spherical nano-aggregates.Conclusions: The (non)covalent synthesis and step-by-step structural elucidation of novel G-2 melamine dendrimers based on 4-(n-octyloxy)aniline are reported. Our study demonstrates the crucial influence of the nature (covalent vs ionic) of the dendritic construction in tandem with that of its central building blocks on the aptitude of dendrimers to self-organise in solution and to self-assembly in the solid state.

Linear-Dendritic Block Copolymer Containing Fluorescent Groups: An Effective and Environmentally Benign Inhibitor for Calcium Carbonate

Abstract A novel fluorescent-tagged scale inhibitor, the linear-dendritic double hydrophilic block copolymer [acrylic acid (AA)/allyloxy poly(ethylene glycol) polyglycerol (APEG-PG-(OH)n)/8-allyloxy-1,3,6-pyrene trisulfonic acid trisodium salt (PA) (AA/APEG-PG-(OH)n/PA)] was synthesized by polymerisation of AA, APEG-PG-(OH)n and PA. Structures of APEG, APEG-PG-(OH)n and AA/APEG-PG-(OH)n/PA were determined by 1HNMR. The experiments show that the dosage and the n value of AA/APEG-PG-(OH)n/PA play an important role on CaCO3 inhibition. The polymer AA/APEG-PG-(OH)5/PA displays a 90% inhibition of CaCO3 precipitate formation at a dosage of 8 mg/L. The relationship between the fluorescent intensity of AA/APEG-PG-(OH)5/PA and the dosage of this polymer was studied. The correlation coefficient R of AA/APEG-PG-(OH)5/PA's is 0.9995. The effect on formation of CaCO3 was investigated with combination of XRD and SEM analysis. Finally, the significant cause and mechanism for calcium carbonate inhibition were analysed in depth.

End-group modification of linear-dendritic​ block copolymers (LDBCs) as multifunctional carriers for targeted drug delivery

End-group modification of linear-dendritic​ block copolymers (LDBCs) as multifunctional carriers for targeted drug delivery

Introduction to Editorial Board Member: Professor Paula T. Hammond

In this issue of Bioengineering and Translational Medicine, we are pleased to introduce our Editorial Board Member, Professor Paula T. Hammond. Prof. Hammond is the David H. Koch Chair Professor of Engineering and the Head of the Department of Chemical Engineering at the Massachusetts Institute of Technology (MIT). Prof. Hammond received her BS degree from MIT in Chemical Engineering, her MS degree from the Georgia Institute of Technology, and her PhD degree from MIT. Over the past two decades, Professor Hammond's research has made deep and impactful contributions in the fields of synthetic polymers, nanomedicine, and materials assembly. Professor Hammond is a leader in the use of molecular interactions, which include electrostatic and hydrogen-bonding forces, to generate “layer-by-layer” deposited functional materials with highly controlled microscale and nanoscale structures on a broad range of surfaces as a means to create ordered architecture.1-3 Her research has leveraged these nanoscale forces, inherent to many synthetic and natural materials, toward developing a range of new biochemical and electrochemical materials with synergistic functionality that are well beyond the capacity of individual materials. Professor Hammond's research draws on and extends concepts of thermodynamics and self-assembly in which the basis of the approach is the use of secondary, or nonspecific interactions, in combination with steric repulsion and electrostatic interactions, to direct the deposition of molecules and larger scale materials systems onto activated surfaces in a stepwise layer-by-layer approach. She has pioneered the development and application of this technology to generate controlled release thin film coatings for biomedical implants that address tissue regeneration,4 wound healing,5 and transdermal delivery from microneedle platforms,6 to nanoparticle drug carriers for drug, gene, and siRNA delivery.7-9 Professor Hammond has also extended the applications of self-assembled materials to electrochemical energy devices,10 including photovoltaics11 and fuel cells.12 Another major research area in Professor Hammond's group focuses on nanoscale self-assembly through the design of functionalized block copolymers. Block copolymers, which consist of two or more covalently bound polymer segments of different chemical composition, are known for their ability to microphase separate and organize into mesophase structures on nanometer length scales in the bulk state, and at surfaces and interfaces, based on chemical differences between blocks. Professor Hammond's research has demonstrated the role of controlling the molecular architecture on the nanoscale in the ordering of block copolymer morphology, particularly for copolymer systems with asymmetric (irregular or nonlinear) blocks. Professor Hammond's research has investigated the development and application of dendritic-linear block copolymers as nanoencapsulants for targeted drug delivery.13 Professor Hammond has led a remarkable career as a researcher and educator. Her research has been published in over 300 journal articles and book chapters, and has been heavily cited, with more than 21,000 citations. In recognition of these contributions to materials chemistry and nanomedicine, Prof. Hammond has been presented with numerous awards and honors. She has been elected to the National Academy of Engineering (2017), the National Academy of Medicine (2016), and the American Academy of Arts and Sciences (2013). She is an elected Fellow of the American Physical Society, the American Institute of Biological and Medical Engineers, and the American Chemical Society Polymer Division. She is the recipient of the AIChE Charles M. A. Stine Award (2013) in recognition of outstanding contributions to the field of materials science and engineering, and the Alpha Chi Sigma Award (2014) for Chemical Engineering Research. Professor Hammond has been featured numerous times in the top 100 cited materials scientists. In addition to research and teaching excellence, Prof. Hammond has had a deep interest for administrative leadership. At MIT, she co-founded the MIT Institute for Soldier Nanotechnology. She served as the Executive Officer of the Chemical Engineering Department of MIT (2008–2011) and currently serves as the department chair. Professor Hammond describing the spray layer-by-layer technology to President Barack Obama during the President's visit to MIT on October 23, 2009 Source. MIT Spring 2010 Chemical Engineering Newsletter (http://web.mit.edu/cheme/alumni/newsletter/XCurrentsSpring10.pdf) Group photo at the 15 year Hammond Lab reunion on June 4, 2011 Photo courtesy of the Hammond Group

Theory of Linear-Dendritic Block Copolymer Micelles.

A self-consistent field theory is applied to study structural properties of micelles formed upon spontaneous assembly of diblock copolymers comprising soluble dendron block covalently linked to insoluble linear block in selective solvent. The structure of spherical micelles is analyzed as a function of degrees of polymerization of the blocks and number of generations and branching functionality of the dendron block. We demonstrate that for a given molecular mass of blocks both the hydrodynamic dimensions of the micelles and the aggregation number decrease as a function of the degree of branching of the dendron block. However, the number of potentially functionalizable terminal segments of dendrons in the corona exposed to the solution increases compared to the number of terminal groups in the corona of linear diblock copolymer micelle. This result may have important implications for construction of linear-dendritic block copolymer micelles with smart functionalities for targeted drug and gene delivery.

Dendritic poly(benzyl ether)‐b‐poly(N‐vinylcaprolactam) block copolymers: Self‐organization in aqueous media, thermoresponsiveness and biocompatibility

ABSTRACTFour generations of new amphiphilic thermoresponsive linear‐dendritic block copolymers (LDBCs) with a linear poly(N‐vinylcaprolactam) (PNVCL) block and a dendritic poly(benzyl ether) block are synthesized by atom transfer radical polymerization (ATRP) of N‐vinylcaprolactam (NVCL) using dendritic poly(benzyl ether) chlorides as initiators. The copolymers have been characterized by 1H NMR, FTIR, and GPC showing controlled molecular weight and narrow molecular weight distribution (PDI ≤ 1.25). Their self‐organization in aqueous media and thermoresponsive property are highly dependent on the generation of dendritic poly(benzyl ether) block. It is observed for the LDBCs that the self‐assembled morphology changes from irregularly spherical micelles, vesicles, rod‐like large compound vesicles (LCVs), to the coexistence of spherical micelles and rod‐like LCVs, as the generation of the dendritic poly(benzyl ether) increases. The results of a cytotoxicity study using an MTT assay method with L929 cells show that the LDBCs are biocompatible. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 300–308

Linear-Dendritic Block Copolymers Based on N-Isopropylacrylamide and Perfluorinated Polyphenylenegermane: Synthesis and Properties at Various Interfacial Boundaries

It is shown that linear-dendritic block copolymers poly(N-isopropylacrylamide)–block–polyphenylenegermane can be prepared by the polymerization of N-isopropylacrylamide in the presence of bis(pentafluorophenyl)germane followed by activated polycondensation with tris(pentafluorophenyl)germane. The properties of the dilute solutions and Langmuir monolayers of the functional polymers and the linear-dendritic block copolymers of N-isopropylacrylamide are studied.

Synthesis and tunable thermoresponsive solution morphologies of 2,2-bis-methylolpropionic acid dendron-azobenzene-poly(N -isopropyl acrylamide) copolymers

Amphiphilic temperature and photoresponsive linear-dendritic block copolymers comprising second generation acetonide-2,2-bis-methylolpropionic acid (bis-MPA)-based polyester dendron and linear poly(N-isopropyl acrylamide) (PNIPAM) linked by an azobenzene unit were synthesized using ATRP followed by click chemistry. Precursor linear PNIPAM was prepared from an azide-functionalized azobenzene containing ATRP initiator. Two polymers obtained by varying the chain length of PNIPAM block showed different morphologies and LCST values in aqueous solution. Complete change in morphology of the two polymers into large spherical aggregates and nanotubes, respectively, was observed upon heating the micellar solution above LCST. Azobenzene unit was found to undergo trans-cis photoisomerization in the assemblies and caused change in the microenvironment of encapsulated hydrophobic dye without any release. Acetonide groups on the dendron were deprotected to afford hydroxylated polymer that showed well-defined morphologies above the LCST and after heating-cooling cycle while significant dye encapsulation was seen only above LCST.

Linear-dendritic block copolymers as a green scale inhibitor for calcium carbonate in cooling water systems

Water-soluble monomer APEG-PG-(OH)n were produced and the Structure of APEG-PG-(OH)5 were identified by 1H-NMR. APEG-PG-(OH)n were copolymerized with maleic anhydride (MA) to synthesize no phosphate and nitrogen free calcium carbonate inhibitor MA/APEG-PG-(OH)n. The structure and thermal property of MA/APEG-PG-(OH)5 were characterized and measured by 1H-NMR, GPC and TGA. The observation shows that the dosage and n value of MA/APEG-PG-(OH)n plays an important role on CaCO3 inhibition. MA/APEG-PG-(OH)5 displays superior ability to inhibit the precipitation of calcium carbonate, with approximately 97% inhibition at a level of 8 mg/L. The effect on formation of CaCO3 was investigated with combination of SEM and XRD analysis.

Dendrimer‐based nanocarriers: a versatile platform for drug delivery

Advances in nanotechnology have had profound impacts on therapeutic delivery, leading to the development of nanomaterials engineered with large carrying capabilities and targeting functionalities. Among the nanomaterials, dendrimers have garnered particular attention from researchers owing to their well-defined structure, near-monodispersity, and ease of multifunctionalization. As hyperbranched, three-dimensional macromolecules, dendrimers can be engineered to target and deliver a wide range of therapeutic agents, including small molecules, peptides, and genes, reducing their systemic toxicities and enhancing efficacies. In this review, we provide a comprehensive overview of the commonly employed dendrimer-based nanocarrier designs, including dendrimer conjugates, Janus dendrimers, and linear-dendritic block copolymers. The discussion will progress through the basic synthetic strategies of dendrimer-based nanocarriers, followed by the potential clinical applications related to their unique structural properties. Finally, the major challenges that these nanocarriers are currently facing in their clinical translation and possible solutions to address these issues will be discussed, with the aim to provide researchers in the drug delivery field a good understanding of the potential utilities of dendrimer-based nanocarriers. WIREs Nanomed Nanobiotechnol 2017, 9:e1409. doi: 10.1002/wnan.1409 For further resources related to this article, please visit the WIREs website.

A comparative study of linear, Y-shaped and linear-dendritic methoxy poly(ethylene glycol)-block-polyamidoamine-block-poly(l-glutamic acid) block copolymers for doxorubicin delivery in vitro and in vivo

The linear, Y-shaped, and linear-dendritic block copolymers of methoxy poly(ethylene glycol)-block-polyamidoamine-block-poly(l-glutamic acid) (MPEG-b-PAMAM-b-PGA) with one, two, four, and eight PGA arms but similar MPEG/PGA weight ratios (W/W) (named as P1PA, P2PA, P4PA and P8PA, respectively) were synthesized and comparatively investigated for doxorubicin hydrochloride (DOX) delivery. All the obtained block copolymers were highly biocompatible and could efficiently load DOX into nanoparticles (NPs) through electrostatic interaction. The NPs formed by linear (P1PA) or Y-shaped (P2PA) block copolymers and DOX were spherically shaped with smaller sizes, while the NPs formed from linear-dendritic block copolymers (P4PA and P8PA) were irregular in shape and larger in size. The P1PA/DOX and P2PA/DOX NPs exhibited better DOX protection and slower DOX release profile. However, cell cytotoxicity assays indicated that all the DOX-loaded NPs exhibited similar cytotoxicities with free DOX, indicating effective DOX release after cellular uptake. The NPs from linear and Y-shaped block copolymers greatly extended the blood circulation time, and displayed more accumulation in tumor site and less accumulation in the liver and kidney compared with the linear-dendritic counterparts. In addition, the P1PA/DOX and P2PA/DOX NPs also exhibited higher anti-tumor efficacy and less toxicity than the other DOX formulations. All these results indicated that the linear and Y-shaped MPEG-b-PAMAM-b-PGA block copolymers displayed better DOX delivery ability in anti-tumor treatment than the linear-dendritic copolymers. Statement of SignificancePolymeric NPs derived from block copolymers have emerged as effective vehicles for drug delivery. However, the majority of the researches in this field have involved simple linear block copolymers and there are very few comparative studies on the self-assembly, in vitro, and in vivo drug delivery by the block copolymers with similar composition but different architectures. In this study, a series of linear, Y-shaped, and linear-dendritic polypeptide-based block copolymers were prepared and thoroughly investigated for DOX delivery. These block polymers loaded DOX into NPs with different sizes and morphologies, and exhibited different anti-tumor capabilities both in vitro and in vivo. The results indicated that the architecture of the block copolymers played an important role in their drug delivery behaviors.

Synthesis and solution properties of novel thermo- and pH-responsive poly(N-vinylcaprolactam)-based linear–dendritic block copolymers

This study describes the synthesis and solution properties of the novel linear–dendritic block copolymers (LDBCs) based on thermoresponsive poly(N-vinylcaprolactam) (PNVCL) chains and pH-responsive poly(benzyl ether) dendrons.

Self-assembly of thermo and light responsive amphiphilic linear dendritic block copolymers

The synthesis and structural characterization of a new dual responsive linear-dendritic block copolymer (LDBC) is presented. The LDBC is constituted by a thermoresponsive linear block from polymethacrylate of oligo- and diethylene glycol, and a light responsive dendron block of bis-MPA decorated at the periphery with 4-isobutyloxyazobenzene and alkyl chains in a 50:50M ratio. Blocks are coupled together by copper(I) catalyzed alkyne–azide cycloaddition (CuAAC). The ability of the LDBC to form vesicle self-assemblies in water is described, as well as the effect of light and temperature on the vesicles morphology, on the basis of transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV–vis spectroscopy studies. The effect of UV light and temperature on the vesicles structure by SAXS and WAXS conducted on real time is also presented. Finally, the potential use of the vesicles to load and stimuli controlled release of small fluorescent molecules is probed.

Tissue Adhesives: Linear Dendritic Block Copolymers as Promising Biomaterials for the Manufacturing of Soft Tissue Adhesive Patches Using Visible Light Initiated Thiol–Ene Coupling Chemistry (Adv. Funct. Mater. 42/2015)

Tissue Adhesives: Linear Dendritic Block Copolymers as Promising Biomaterials for the Manufacturing of Soft Tissue Adhesive Patches Using Visible Light Initiated Thiol–Ene Coupling Chemistry (Adv. Funct. Mater. 42/2015)

Linear Dendritic Block Copolymers as Promising Biomaterials for the Manufacturing of Soft Tissue Adhesive Patches Using Visible Light Initiated Thiol–Ene Coupling Chemistry

A library of dendritic–linear–dendritic (DLD) materials comprising linear poly(ethylene glycol) and hyperbranched dendritic blocks based on 2,2‐bis(hydroxymethyl) propionic acid is successfully synthesized and postfunctionalized with peripheral allyl groups. Reactive DLDs with pseudo‐generations of 3 to 6 (G3‐G6) are isolated in large scale allowing their thorough evaluation as important components for the development of biomedical adhesives. Due to their branched nature and inherent degradable ester‐bonds, promising biomaterial resins are accomplished with suitable viscosity, eliminating the excessive use of co‐solvents. By utilizing benign high‐energy visible light initiated thiol–ene coupling chemistry, DLDs together with tris[2‐(3‐mercaptopropionyloxy)ethyl] isocyanurate and surgical mesh enable the fabrication of soft tissue adhesive patches (STAPs) within a total irradiation time of 30 s. The STAPs display the ability to create good adhesion to wet soft tissue and encouraging results in cytotoxicity tests. All crosslinked materials are also found to degrade after being stored in human blood plasma and phosphate buffered saline. The proposed benign methodology coupled with the promising features of the crosslinked materials is herein envisioned as a soft tissue adhesive with properties that do not exist in currently available tissue adhesives.

Controlled micellar disassembly of photo- and pH-cleavable linear-dendritic block copolymers

A biocompatible linear-dendritic copolymer comprising photo and pH-cleavable groups at the junction was synthesised and controlled release of drug into cells was demonstrated.

Synthesis, characterization and association behavior of linear-dendritic amphiphilic diblock copolymers based on poly(ethylene oxide) and a dendron derived from 2,2′-bis(hydroxymethyl)propionic acid

Two new amphiphilic linear-dendritic block copolymers have been synthesized and characterized. And their association behaviors have also been studied.

Enhanced photovoltaic performance of inverted polymer solar cells by incorporating graphene nanosheet/AgNPs nanohybrids

A linear-dendritic block copolymer functionalized exfoliated graphene nanosheets/silver nanoparticles was prepared for using as the interfacial layer between the electron-selective layer and photoactive layer in an inverted polymer solar cell.

Conformation of the Linear-Dendritic Block Copolymers of Hyperbranched Polyphenylenegermane and Linear Poly(methylmethacrylate)

Dilute solutions of linear-dendritic block copolymers of linear poly(methylmethacrylate) with hyperbranched polyphenylenegermane were investigated by light scattering methods. The obtained results were compared with characteristics of functionalized poly(methylmethacrylate) with -Ge(C6F5)3 terminal groups, linear poly(methylmethacrylate), and hyperbranched polyphenylenegermane. The investigated samples differ by molar masses of the linear components. It was shown that molecules of functionalized poly(methylmethacrylate) in solution have a conformation that is typical for linear polymers in good solvent, while the linear-dendritic polymers in dilute chloroform solution have compact structure and high density in comparison with linear poly(methylmethacrylate).

Macromol. Rapid Commun. 12/2014

Back Cover: Linear dendritic block co-polymers combine linear and dendritic polymers in the same macromolecule. Synergies between both types of structures can be exploited to achieve hybrid polymers with excellent control of functionality, good processability, and self-assembling properties, both in solution and in bulk. Synthetic approaches are reviewed here, as well as their most important application as stimuli-responsive materials. Further details can be found in the article by E. Blasco, M. Piñol,* and L. Oriol* on page 1090.