Starburst poly dendrimer

D. Page and R. Roy, Synthesis and biological properties of mannosylated starburst Poly(amidoamine) dendrimers, Bioconjug. Chem., 8 (1997) 714—723. 

Electrophoresis is normally run in aqueous media, hence the analytes must be soluble in water. Presently only three types of water-soluble dendrimers have been successfully analyzed using gel electrophoresis techniques. The list includes Starburst PAMAM dendrimers [21], nucleic acid dendrimers [21] and poly(lysine) dendrimers [23, 24] (see Figures 10.2, 10.4 and 10.6). However, in each case appropriate water solubilizing terminal groups are required (i.e. -NH2, -OH or C02H groups) for suitable electrophoretic analysis. 

Hyper-branched starburst poly(siloxysilane) polymers are synthesized through hydrosi-lylation-polymerization of CH2=CHSi(OSiMe2H)3 (269) and HSi(OSiMe2CH=CH2)3 (270). The polymer from 269 has Si—H moieties on the surface of the dendrimer, while that arising from 270 possesses vinyl groups on the outer sphere264. 

Fig. 27. Corey-Pauling-Koltun (CPK) models of Starburst poly(ethyleneimine) dendrimers of generations 0-5...

Reaction of various primary amine-terminated dendrimers with either inorganic or organic acids allows the preparation of a wide variety of crystalline derivatives. One such intermediate was implicated in the development of lyotropic phases [156] when octanoic acid was combined with Starburst poly(ethylenimine) (generation-3). 

Tomalia-type poly(amidoamine) (PAMAM) dendrimers and their use as precise, fundamental building blocks to form poly(dendrimers) or so-called starburst polymers. These poly(dendrimers) are now referred to as megamers [35,36] and are described in more detail later. Other pioneers in the dendritic polymer field include Vogtle, New-kome, Frechet, and others. These historical contributions have been reviewed recently [33],... 

The upper mass range of a polymer that can be analyzed by MALDl-MS is dependent on the polymer type. For example, Danis et al. reported the detection of water-soluble poly(styrenesulfonic acid) with a molecular mass just below 400000 [122], and the detection of a poly(methyl methacrylate) sample with a molecular mass of about 256000 [17]. Multiply charged ions from a starburst polyamidoamine dendrimer with a molecular mass as high as 1.2 milbon has been reported by Savickas [123]. Yalcin et al. showed that polybutadienes of narrow polydispersity with masses up to 300000 Da, and polyisoprenes of narrow polydispersity with masses up to 150 000 Da, can also be analyzed [42]. 

Some attention has arisen to consider dendrimers as building blocks for the construction of nanoarchitectures possessing higher complexity and dimensions beyond the dendrimer. In an early paper, Tomalia et al referred to their starburst polymers as a class of macromolecules obtained from the chemical bridging of starburst dendrimers. These macromolecules have been termed megamers, which have been defined as architectures derived from the combination of two or more dendritic macromolecules or poly(dendrimers). Many examples of randomly assembled as well as structure-controlled megamers have been reported, such as oligomeric covalent assemblies of dendrimers (i.e., dimers, trimers) referred... 

More recently, non-traditional polymerization strategies have evolved to produce a fourth new major polymer architecmral class, now referred to as dendritic polymers [43]. This new architectural polymer class consists of four major subsets (1) random hyperbranched, (2) dendrigrafts, (3) dendrons and (4) dendrimers. Dendrimers, the most extensively studied subset were discovered by the Tomalia group while in The Dow Chemical Company laboratories (1979) and represent the first example of synthetic, macromolecular dendritic architecture [43,44]. First use of the term dendrimer appeared in preprints for the first SPSJ International Polymer Conference, held in Kyoto, Japan in 1984 [45]. The following year, a full article in Polymer Journal [46] (Fig. 8) described the first preparation of a complete family of Tomalia-type poly(amidoamine) (PAMAM) dendrimers (G = 1-7) and their use as precise, fundamental building blocks to form poly (dendrimers) or so-called starburst polymers. These poly(dendrimers) are now referred to as megamers [47, 48] and are described in more detail later in Sect. 6.4.3. Other pioneers in the dendritic polymer field include Vogtle, Newkome, Frechet, Majoral, and others. These historical contributions have been reviewed recently [52]. ... 

Brief definitions of starburst polymers, dendrimers, and dendrons are as follows, and the reader is referred for detailed descriptions to Tomalia s excellent reviews [1]. Starburst is a the trademark name of poly(amide-amine)s, as shown in Scheme 1, and was presented by Tomalia. Recently, dendrimers and dendrons have been defined in general terms for a class of hyperbranched polymers. Dendrimers are systematically constructed to form regularly branched treelike structures. Under ideal conditions, the molecular architecture is very uniform, as shown in Figure 1. A dendron is one of the major subdivisions of a dendrimer. For example. Figure 1 shows the division of a dendrimer into three separate dendrons, labeled A, B, and C. Further subdivisions are also possible, with each of the three dendrons dividing into two subdendrons, each of which then divides into two subdendrons, etc. Thus, one of the major differences between linear polymers and dendrimers is this branched architecture. 

Roberts, J., Bhalgat, M. and Zera, R. T. (1996) Preliminary evaluation of poly-amidoamine (PAMAM) starburst dendrimers. J. Biomedical. Materials Res., 30, 53 (1996). 

Dendrimers, or arborols, or cascade, or cauliflower, or starburst polymers, were first synthesized in the early 1980s [3,4]. In 1985 Tomalia et al. [5] and Newkome et al. [6] presented the first papers dealing with dendrimers. A multitude of dendrimers have been presented in the literature ranging from polyami-doamine [7,8],poly(propylene imine) [9,10], aromatic polyethers [11-13] and polyesters [14, 15], aUphatic polyethers [16] and polyesters [17], polyalkane [18-19], polyphenylene [20], polysilane [21] to phosphorus [22] dendrimers. Combinations of different monomers as well as architectural modifications have also been presented. For example, chirality has been incorporated in dendrimers [23,24]. Copolymers of linear blocks with dendrimer segments (dendrons) [25-27] and block-copolymers of different dendrons have been described [28]. 

Cationic polymer is also frequently examined to increase the potential of a gene drug. Large molecular weight cationic polymers can condense pDNA more efficiently than cationic liposomes. They include poly-L-lysine (PLL), poly-L-omithine, polyethyleneimine (PEI), chitosan, starburst dendrimer and various novel synthetic polymers. These polymers can enhance the cellular uptake of pDNA by nonspecific adsorptive endocytosis. 

Figure 14.1 Common commercially available dendrimers. Top left Polypropylene imine) dendrimer (G5). Top right Poly(amido amine) dendrimer (G3). Bottom Poly(amido amine) ( Starburst ) dendrimer (G5). Each generation is marked with a circle (reproduced by permission of The Royal Society of Chemistry).

Hall and Polis 7 prepared a series of polyarylamines using an aromatic nucleophilic substitution-reduction sequence (Scheme 4.20). Hence, 2,4-dinitrofluorobenzene 66 was treated with />-diaminobenzene to afford tetranitro 67, which was reduced to give the corresponding first generation, diamine 68. Repetition of this sequence afforded the second generation tetradecaamine 69. These starburst polyarylamines were complexed with iodine to form semiconducting materials and were the first dendrimers to be examined by cyclic voltammetry. 

These methods were used extensively for structure verification of dendrimers prepared by the divergent initiator core method such as Starburst PAMAM [124] poly(ether) [82], and poly(ethylenimine) dendrimers [2], as well as poly(siloxane), poly(phosphonium), poly (ary lalkyl)ether, poly(arylene) and poly(arylester) dendrimers. In many cases, small-molecule model systems were used for process optimization, defect identification, and stoichiometry studies. 

More recent work has shown that this GDS strategy may be used to produce all hydrocarbon, poly (styrene) type dendrimers that the authors refer to as being derived from arborescent grafting [181]. Hybridization of Starburst/Cascade architecture with Comb-burst dendrimer structure, has been reported by our group very recently [182], thus clearly establishing the vast breadth and scope of GDS techniques for the construction and design of nanoscopically sized macromolecules (i.e., 1-100 nm in diameter). 

Molecular modelling techniques are a powerfiil tool for obtaining a very detailed insight in the three-dimensional structure of dendrimer molecules at the atomic level. They have been applied to calculate sizes of the poly(propylene imine) dendrimers and radial density profiles in order to estimate the amount of free volume inside the dendrimers, and to make a prediction about the starburst-dense packed generation. The molecular modelling work by Coussens et al. [33,34] was focussed on the generations 1-5 of the DAR-dendr- CH) and DAB-c(e c(r-(NH2) (n = 4, 8, 16, 32, 64). 

Li, Y. Dubin, P.L. Spindler, R. Tomalia, D.A. Complex formation between poly(dimethyldiallylammonium chloride) and carboxylated starburst dendrimers. Macromolecules 1995, 28, 8426-8428. 

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