Starburst poly

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. 

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]. 

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. 

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).

Scheme 4.7. Method for the construction of starburst poly(ethylene imine) cascades using N-mesylaziridine.

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. 

Starburst polyacrylamines and their semiconducting complexes as potentially electroactive materials. [H. K. Hall, Jr., D. W. Polis, Polym. Bull. 1987, 77(5), 409-416] [ 604]. 

Poly(amidoamine)-(PAMAM-Starburst)-Monodendrons Among the first Starburst (Cascade) syntheses we performed in the early 1980s [83] involved partially masked (differentiated) initiator cores. For example dodecyl-amine, hydroxyalkyl amines or partially protected alkylene diamines were used as initiator cores and submitted to sequential (a) Michael addition with methyl acrylate followed by (b) reaction with an excess of ethylene diamine to give in situ branch cell construction in a divergent manner. The resulting products were core functionalized monodendrons as shown below ... 

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

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. 

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). 

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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