The characterization of dendronized poly(ethylene glycol)s and poly(ethylene glycol) multi-arm stars using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (original) (raw)
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Dendrimers, dendrons, and hyperbranched polymers are gaining popularity as novel drugs, imaging agents, and drug delivery systems. They present advantages of well-defined molecular weight, multivalent surfaces, and high drug carrying capacity. Moreover, it is emerging that such architectures can display unique endocytic properties. As poly(ethylene glycol) (PEG) is widely used for protein and drug conjugation, the aim of this study was for the first time to synthesize novel, branched PEG-based architectures, to define their cytotoxicity and, via preparation of Oregon green (OG) conjugates define the effect of structure on their cellular uptake. Five PEG-based dendrons were synthesized using monodisperse Fmoc-amino PEG propionic acid (M w) 840) as a monomer, and cadaverine, tris(2-aminoethyl)amine or lysine as the branching moieties. These were diamino,bisPEG (M w) 1300); tri-amino,trisPEG (Mw) 1946); tetraamino,tetraPEG (M w) 3956); monocarboxy,diamino,bisPEG (M w) 1346); and monocarboxy,tetraamino,tetraPEG (M w) 3999). These products had NH 2 or both NH 2 and COOH terminal groups and the identity was verified by amino group analysis and ESI-TOF mass spectroscopy. Purity was determined by HPLC. Representative structures were not toxic towards an endothelial-like cell line (ECV304) at concentrations up to 4 mg/mL (over 72 h). At 37 °C, all of the OG-labeled PEG dendrons showed progressive uptake by ECV304 cells, but tetraamino,tetraPEG showed the greatest rate of internalization over the first 20 min. Cellular uptake was inhibited at 4 °C, and PEG dendron localization to perinuclear vesicles was confirmed by fluorescence microscopy. These well-defined novel architectures have potential for further development as targetable drug delivery systems or tools for construction of structurally defined modified surfaces.
Polymers, 2012
Pegylation using heterotelechelic poly(ethylene glycol) (PEG) offers many possibilities to create high-performance molecules and materials. A versatile route is proposed to synthesize heterobifunctional PEG containing diverse combinations of azide, amine, thioacetate, thiol, pyridyl disulfide, as well as activated hydroxyl end groups. Asymmetric activation of one hydroxyl end group enables the heterobifunctionalization while applying selective monotosylation of linear, symmetrical PEG as a key step. The azide function is introduced by reacting monotosyl PEG with sodium azide. A thiol end group is obtained by reaction with sodium hydrosulfide. The activation of the hydroxyl end group and subsequent reaction with potassium carbonate/thioacetic acid yields a thioacetate end group. The hydrolysis of the thioester end group by ammonia in presence of 2,2′-dipyridyl disulfide provides PEG pyridyl disulfide. Amine terminated PEG is prepared either by reduction of the azide or by nucleophilic substitution of mesylate terminated PEG using ammonia. In all cases, >95% functionalization of the PEG end groups is achieved. The PEG derivatives particularly support the development of materials for biomedical applications. For example, grafting up to 13% of the Na-alg monomer units with α-amine-ω-thiol PEG maintains the gelling capacity in presence of calcium ions but simultaneous, spontaneous disulfide bond formation reinforces the initial physical hydrogel.
Macromolecular Symposia, 2000
The design, synthesis and solution properties of dendritic-linear hybrid macromolecules is described. The synthetic strategy employs living ring-opening polymerization in combination with selective and quantitative organic transformations for the preparation of new molecular architectures similar to classical star polymers and dendrimers. The polymers were constructed from high molecular weight poly(e-caprolactone) initiated from the surface hydroxyl groups of dendrimers derived from bis(hydroxymethyl) propionic acid (bis-MPA) in the presence of stannous 2-ethyl hexanoate (Sn(Oct)2). In this way, star and hyperstar poly(e-caprolactones) were elaborated depending on the generation of dendrimer employed. The ROP from these hydroxy groups was found to be a facile process leading to controlled molecular weight, low dispersity products (Mw/Mn) < 1.15). In addition to the use of dendrimers as building blocks to star polymers, functional dendrons derived from bis-MPA were attached to chain ends of the star polymers, yielding structures that closely resemble that of the most advanced dendrimers. Measurements of the solution properties (hydrodynamic volume vs. molecular weight) on the dendritic-linear hybrids show a deviation from linearity, with a lower than expected hydrodynamic volume, analogous to the solution properties of dendrimers of high generation number. The onset of the deviation begins with the polymers initiated from the second generation dendrimer of bis-MPA and becomes more exaggerated with the higher generations. It was found that polymerization amplifies the nonlinear solution behavior of dendrimers. Small angle neutron scattering (SANS) measurements revealed that the radius of gyration scaled with arm functionality (f) as f 2/3 , in accordance with the Daoud-Cotton model for many arm star polymer.
Dendronized polymers with tailored surface groups
Journal of Polymer Science Part A: Polymer Chemistry, 2005
A series of polymers tethered with bis-MPA dendrons was synthesized by a combination of divergent growth and atom transfer radical polymerization (ATRP). Macromonomers of first and second generation were synthesized utilizing the acetonide protected anhydride of bis-MPA as the generic esterfication agent. The macromonomers were polymerized in a controlled fashion by ATRP utilizing Cu(I)/Cu(II) and N-propyl-2-pyridylmethanamine as the halogen/ligand system. The end-groups of these polymers were further tailored to achieve hydroxyl, acetate, and aliphatic hexadecyl functionality. With this approach all polymers will emanate from the same backbone, enabling for an evaluation of both the generation and end-group dependent properties. Furthermore, a dendronized tri-block copolymer was synthesized. All materials were analyzed by 1 H and 13 C NMR, as well as size-exclusion chromatography (SEC). The SEC analysis revealed that the molecular weights of the divergently grown dendronized polymers increased with increasing generation while the polydispersity (PDI) was kept low. V
Effect of Polyethylene Glycol Chain Length on PEGylation of Dendrimers
Asian Journal of Pharmaceutics, 2017
Aim: To check the effect of polyethylene glycol (PEG) chain length on PEGylation of dendrimers. Materials and Methods: In the present work, we have synthesized different PEGylated polyamidoamine dendrimers using six different PEG chains, i.e., PEG - 200, 300, 400, 600, 2000, and 6000. The PEGylated dendrimers were evaluated for color reaction ultraviolet, infrared, and nuclear magnetic resonance studies and compared with standard data. Results and Discussion: The plain dendrimers give violet color due to free NH2 groups. The intensity of violet color of 4.0 G dendrimers decreases on PEGylation, due to attachment of PEG chain on free NH2 groups which is responsible for violet color. The change in λmax values from 283 to 353 nm was observed, which shows the change in structure of dendrimers. On comparing, it was found that PEG 400 and 600 shows value near their expected values, i.e., 19,150 and 19,780, respectively. Conclusion: From the results of the present study, it can be conclude...