Ethylenediamine dendrimer core

Molecular properties of ethylenediamine (EDA) core PAMAM dendrimers... 

The first true dendrimers were the polyamidoamines (PAMAMs). They are also known as starburst dendrimers, and the term starburst is a trademark of the Dow Chemical Company, who have commercialized these materials for a range of applications. These dendrimers use ammonia as the core molecule, and this is reacted with methyl acrylate in the presence of methanol, after which ethylenediamine is added. This is shown in Scheme 9.2. 

The addition of ammonia to excess methyl acrylate (a linear monomer), followed by amidation with excess ethylenediamine afforded the resultant cascade molecule, and thus Tomalia [37] created the commercially available PAMAM starburst series of dendrimers (2, Fig. 2). Related core molecules such as ethylenediamine and aminoalcohols and other functionalizable groups such as thiol moieties were used to prepare similar dendrimers [38]. This methodology is applicable to most primary amines, resulting in a 1 —> 2 branching pattern. Recently, examples of related Si-, [39] P-, [40] and metallo systems [41], which follow this linear monomer protocol have been reported. 

Add 50 pi of the NHS-PEGg-maleimide solution to the 1ml dendrimer solution and mix thoroughly to dissolve. This represents approximately a 14-fold molar excess of crosslinker over the quantity of dendrimer present, if a G-3 PAMAM dendrimer is used with an ethylenediamine core. The optimum molar ratio of crosslinker-to-dendrimer should be determined experimentally for best performance of the resultant conjugate in its intended application. If enough material is available, doing a series of experiments at different mole ratios of crosslinker-to-dendrimer will help to optimize the resultant conjugate. 

Scheme 9. (A) Different dendrimers as macromolecular scaffolds for MRI contrast agents ethylenediamine cored polyamido amine, generation 4 (PAMAM G4), top hyperbranched, ethylenediamine cored polyethylene imine (HB-PEI), bottom left hyperbranched, amino functionalized polyglycerol (HB-PG), bottom right. (B) Different moieties attached to the respective dendrimers via amide or thiourea bonds.

PAMAM dendrimers, and in the binding of probes to PAMAM dendrimers with an ethylenediamine core [23]. 

Comparative evaluation of anti-human thyroid stimulating hormone (hTSH) antibody, bound to the fifth-generation ammonia core (N5) or the fifth-generation ethylenediamine core (E5) dendrimer (1), did not show any differences in either the effective protein concentrations or the shape of the dose-dependent response curves (calibration curves) as determined from the recovery of standard controls. All the other experiments described here were thus carried out with the fifth-generation (i.e. dia. = 70 A) particles of ethylenediamine core (E5) de-ndrimers. The later particles were selected for their ability to be produced reproducibly on a large scale. 

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. 

Fig. 4.7 Synthesis of PAMAM dendrimers — with tetrafunc-tional ethylenediamine core (according to Tomalia et al.)...

In their quest for large molecular cavities capable of binding molecules or ionic guests, Vogtle and coworkers 1 synthesized non-cyclic polyaza compounds via a repetitive stepwise process (one-directional case Scheme 4.2). The use of two-directional cores (Scheme 4.5), e.g., ethylenediamine, 2,6-di(aminomethyl)pyridine (8) or l,3-di(amino-methyl)benzene, with acrylonitrile afforded the tetranitrile 9, which was reduced with Co(n)-catalyzed borohydride to produce hexaamine 10. This terminal tetraamine was subsequently treated with excess acrylonitrile to generate the octanitrile 11 although the process was terminated at this stage, a foundation of dendrimer construction was established. 

Table 2. Size measurements on poly(amidoamine)PAMAM dendrimers (ethylenediamine core) from computer analysis of TEM images...

Poly(amidoamine) dendrimers such as 91, which differ only in the presence of an ethylenediamine (instead of ammonia) core, were used to host the electron transfer reaetion between photoexcited polycyelic aromatic hydrocarbons (PAHs) and ni-tromethane [169]. Quenching studies in aqueous solution indicate that the PAHs associate with the dendrimer, residing in the interior region, far from the charged surface. It was also found that within the dendrimer structure, nitromethane quenches alternant PAHs, while nonalternant PAHs are not quenched. This selective behavior of nitromethane parallels that commonly observed in solution, while in the presence of traditional micelles both classes of PAHs are quenched by nitromethane. 

The poly(imine) dendrimers form a special type of polymer. The dendrimers have different physical properties from linear polymers, and some have been used for biomedical applications. Dendrimers typically start with a core molecule. Ammonia can be used for this purpose. In the presence of methanol, ammonia reacts with methyl acrylate forming N(CH2CH2COOCH3)3. The resulting molecule can react further with ethylenediamine or other diamines forming N(CH2CH2CONHCH2CH2NH2)3- At the end of each branch is a free amino group that can react with two methyl acrylate monomers and further with two ethylenediamine molecules. The continuation of the process leads to a dendrimer (polyamidoamine or PAMAM) [2]. A different dendrimer is poly(propylene imine), which has butylenediamine as a core molecule. 

Three representative dendrimers, with different numbers of generations, are shown in Fig. 3.7-7. They are a poly(amidoamine) dendrimer (PAMAM) synthesized by D.A. Tomalia, which incorporates an ethylenediamine core and terminal amino groups (Fig. 3.7-7a), a poly(propyleneamine) product (POPAM) reported by... 

In a typical example, Tomalia [42] etal. describes a system involving Michael addition of methyl acrylate to ammonia to give the initiator core and then reaction with ethylenediamine. Then again methyl acrylate addition followed by reaction with ethylenediamine. This is repeated many times to finally give the Starburst oligomer or dendrimers shown below in the preparation which follows. 

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