EDA dendrimers

This increase has two-fold implications. First, it implies that the fractured dendrimer is more flexible than the intact dendrimer and second, that the fractured dendrimer may expand due to an increase in positive charge at lower pH, a quantity that was described as essential for PEI mediated transfection. Indeed, when branched PEI was subjected to the same set of experiments, the same three-fold increase in viscosity was observed, lending support to the idea that PAMAM dendrimers act as proton sponges. Evidence of lysosomal buffering capability of PAMAM dendrimers was shown by Kukowska-Latallo et al. (1996) when they observed that the efficiency of G5-EDA dendrimers was enhanced by the addition of chloroquine, while the same molecule could not enhance transfection of G10-EDA dendrimers, which contain 40-fold more surface amine groups for proton absorption. 

Figure 7.1 The synthesis of a PAMAM-type dendrimer proceeds from a diamine core [e.g., ethylene diamine (EDA)] by initial addition of the amines to the double bonds of methacrylate. Subsequent reaction of the methyl ester groups with EDA produces a G-0 dendrimer with four pendent amine groups. Another round of methacrylate and EDA additions results in a G-l PAMAM dendrimer containing eight primary amines.

Figure 10.2 Schematic illustration of synthesis of (EDA) core PAMAM dendrimers (E 0-2). Higher generations can be obtained by successive reiterations.

Figure 10.3 Electrophoretogram of several generations of (EDA-core) PAMAM dendrimers (E 0-10). The unlabeled smear in the middle of the gel is a conventional polydispersed linear poly(lysine) sample as a comparison...

Figure 14.1 Energy minimized CPK models of generation 0 through 4 PAMAM and PPI dendrimers. EDA ethylene diamine DAB diamino butane G generation number numbers of end groups given in parentheses...

Figure 14.8 Generational dependence of relative viscosity, tv, on solution volume fraction for the first six generations, G, of PAMAM dendrimers in ethylenediamine (EDA) in comparison with theoretical predictions of Krieger (A), Eiler (B) and Mooney (C) hard sphere models (according to ref. [5])...

Within the temperature range from 10 to 40°C, both PAMAM dendrimers in EDA [5] and PPI dendrimers in water [22] showed a linear relationship between In r and /T, in good agreement with the kinetic rate theory of flow [46]. The apparent activation energies of flow (En) were constant and independent of temperature, and it was shown for PAMAM/EDA systems that the dependence of En on solution concentration was linear for all generations examined [5]. This was considerably different from the typical relationships for the solutions of linear and/or randomly branched chain polymers, where a break in the slope of... 

Table 18.1 Physical characteristics of PAMAM dendrimers (EDA core)...

The number of surface groups (Z), branch cells (BC) and molecular weights for a dendrimer series can be calculated with the math expressions shown below. These parameters, as well as hydrodynamic dimensions for the series [EDA](G 0-10)de dn-PAMAM-(NH2)n are presented in Figure 25.1. The experimental procedures are general for a wide range of alkylenediamine initiator cores (e.g., NH2-(CH2)-nNH2). Characterization data for dendri-PAMAMs derived from these cores are included, where n = 2, 3,4, 5, 6. 

All PAMAM dendrimers (both NH3 and EDA core G = 0-12) were provided by Dendritic Sciences, Inc., Mt. Pleasant, Michigan. Efforts were made to utilize several different generational lot samples for the mass spectral data. 

Step (a) To a 500 mL round bottom flask containing a stir bar was added shell reagent (Y) G = 3.5 methyl ester PAMAM dendrimer, EDA core, (32 g, 2.6 x 10-3 mol, 164 mmol ester, 25 equivalents per core dendrimer (X) and 32 g of methanol. This mixture was stirred until homogeneous. To this mixture was added lithium chloride (7 g, 166 mmol, 1 equivalent per ester) and stirred until homogenous. To this mixture was added (drop-wise) PAMAM dendrimer, EDA core, G = 6 (6 g, 1.0 x 10-4 mol) in 20g of methanol in 10 min. This mixture was warmed to 25 °C and placed in a constant temperature bath at 40 °C for 25 days. 

The divergent method is illustrated in Fig. 2-22 for the synthesis of polyamidoamine (PAMAM) dendrimers [Tomalia et al., 1990]. A repetitive sequence of two reactions are used—the Michael addition of an amine to an a,P-unsaturated ester followed by nucleophilic substitution of ester by amine. Ammonia is the starting core molecule. The first step involves reaction of ammonia with excess methyl acrylate (MA) to form LXIII followed by reaction with excess ethylenediamine (EDA) to yield LXIV. LXV is a schematic representation of the dendrimer formed after four more repetitive sequences of MA and EDA. 

Uppuluri, S., Keinath, S. E., Tomalia, D. A., Dvornic, P. R., Rheology of dendrimers. I. Newtonian flow behavior of medium and highly concentrated solutions of polyamidoamine (PAMAM) dendrimers in ethylenediamine (EDA) solvent. Macromolecules 1998, 31, 4498-4510. 

Fig. 3 Synthesis of a PAMAM dendrimer exhaustive Michael addition of amino groups with methyl acrylate, followed by amidation of the resulting esters with EDA. (From Ref. , 2001 Elsevier Science.)...

Experimental measurements of the hydrodynamic radius of PAMAM dendrimers with ammonia or EDA cores by size exclusion chromatography and vis-... 

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