Polyamines, hyperbranched

Hyperbranched aromatic polyesters, synthesis of, 116-118 Hyperbranched aromatic polymers, 286 Hyperbranched polyamine, synthesis of, 519-520... 

Suzuki et al. [14] reported the Pd-catalyzed ring-opening polymerization of a cyclic carbamate in the presence of an initiator, which also acts as a core molecule, to afford a hyperbranched polyamine. The polymerization was proposed to be an in situ multibranching process, wherein the number of propagating chain ends increase with the progress of the polymerization. 

Commercially available hyperbranched polymers are Polyglycerol (aliphatic polyether polyol) and Polyethylenimine (aliphatic polyamine) both from Hyperpolymers, Boltom (aliphatic polyesters) from Perstorp and Hybrane (aromatic polyester amide) from DSM. 

In an earlier investigation by the authors (3) hyperbranched polyamides were prepared by condensing adipic acid with polyamines at 150°C. 

This review deals with the syntheses of various hyperbranched polyamines that are prepared through a one-step polymerization process. Furthermore, we present the current status of polyamines as gene carriers and describe their versatility, and their properties such as structure-property dependency, gene transfection efficiency, and cytotoxicity profiles of hyperbranched polyamines. 

Keywords Applications Cytotoxicity profile Gene delivery Hyperbranched polyamines Poly(amido amine) Poly(amido ester) Poly(ethylene imine) Polyglycerol amines Structure-property dependence Synthesis Transfection efficiency... 

From the structural point of view, polyamines used for gene transfection vary widely in their structures, which range between linear [24, 29-35], branched [12, 30, 32], hyperbranched, and perfect branched dendrimers [36]. In this chapter we present a general overview of the research reported so far using dendritic polyamines in gene delivery applications. Particular focus is made on hyperbranched... 

Fig. 2 Structurally controlled polymers (a) dendrimer, (b) dendron, (c) random hyperbranched, and (d) dendrigrafts. The metabolism of the polyamine is still unclear. Reproduced with permission from [37]. Copyright 2001 Elsevier...

Our group described a simple access to well-defined hyperbranched polyamines from hyperbranched PEI with different molecular weights, narrow molecular weight distributions, and an adjustable degree of branching [91]. According to this protocol fully branched analogs of polypropyleneimine (PPI) and polyamidoa-mine (PAMAM) dendrimers can be derived from hyperbranched PEI (Mw = 5,000, and 25,000 g mol-1) in a two-step synthetic process (Scheme 2). 

Scheme 2 Synthesis pathway of hyperbranched polyamines, PEI/PAMAM and PEI/PPI based on hyperbranched PEI (a) PEI/PAMAM (1) CH2=CHCOOMe, THF, 25°C, 4 days, (2) CH2=CHOOMe, 25°C, 8 days, and finally (3) H2NCH2CH2NH2, 50°C, 8 days, THF (b) PEI/ PPI (1) CH2=CHCN in water, 25°C, 2 days and (2) LiAlfVAlCb, in THF, 25°C, 1 day. Reproduced with permission from [91]. Copyright 2004 Wiley...

Reichert and Mathias prepared related branched aramids, to those of Kim,t5-34] from 3,5-dibromoaniline (23) under Pd-catalyzed carbonylation conditions (Scheme 6.7). These brominated hyperbranched materials (24) were insoluble in solvents such as DMF, DMAc, and NMP, in contrast to the polyamine and polycarboxylic acid terminated polymers that Kim synthesized, which were soluble. This supports the observation that surface functionality plays a major role in determining the physical properties of hyperbranched and dendritic macromolecules J4,36 A high degree of cross-linking could also significantly effect solubility. When a four-directional core was incorporated into the polymerization via tetrakis(4-iodophenyl)adamantanc,1371 the resultant hyperbranched polybromide (e.g., 25) possessed enhanced solubility in the above solvents, possibly as a result of the disruption of crystallinity and increased porosity. 

Suzuki et al.[57 explored the Pd-catalyzed ring-opening of the monomer 5,5-dimethyl-6-ethenylperhydro-l,3-oxazin-2-one to give a hyperbranched polyamine. The polymerization was conducted at ambient temperature in THF and catalyzed with Pd2(dba)3-2 dppe, affording after the evolution of carbon dioxide, the desired hyperbranched polyamine. NMR spectroscopy confirmed the high yield conversion of the monomer. The degree of branching was ascertained (from NMR data) as the ratio of tertiary amine units to the total of secondary and tertiary moieties. 

Poly(ethylene terephthalate) functionalized with hyperbranched polyamine cations was prepared by Rao [3] and used to splay layered materials in a matrix in polymer-layered nanotubes. 

In industry, several dendrimers are already being synthesized on a hundred kilogram scale. The hopes for effective solubilizing systems suitable for medical applications may, however, not be justified. Phenolic ether or polyamine compounds are both normally not biodegradable so that major problems are foreseeable. An alternative is the employment of hydrolysable polyesters. One such compound already reported, is the imperfectly hyperbranched dendrimer which is easily accessible via thermal self-condensation of 3,5-bis(trimethyl-siloxyjbenzoyl chloride. This one-step procedure leads to a dendritic polyester... 

A number of hyperbranched systems have been prepared. These include polyimides with methacryloyl groups at the chain ends, methacrylated polyamine esters, " polyurethane acrylates, polyester acrylates and polyisoph-thalate esters. All materials exhibit 3D sphere like structures with excellent properties. 

The potential loading capacity of these hyperbranched polymers is similarly high as for dendrimers (5-14 mmol g ) and some hyperbranched polymers are even commercially available [13,121]. The use of these commercial materials as supports for organic synthesis, however, is hmited due to the chemical stability of the respective polymer backbone (e.g. polyamines, polyesters) and the relatively broad molecular weight distributions (typically PD>2) [13]. Therefore, new hyperbranched species have been developed. 

The dominant contribution of simultaneous chain growth from all the chain ends, controlled by the deprotonation level of the initiator, leads to relatively narrow MWD B 1.1-1.4) while maintaining branching levels typical of random polycondensation reactions (degree of branching a 0.5, Eq. 30.7) [70]. The SCROP technique has also been used to synthesize hyperbranched polyglycerols [70], polyethers [71], and polyamines [72]. 

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