Alan E. Enciso

Rapid, semi-automated convergent synthesis of low generation triazine dendrimers using microwave assisted reactions

Microwave assisted synthesis allows for the rapid access of low generation triazine dendrimers in high yields. Products include a macromonomer and alkyne functionalized dendrimers from generation one to three. Using a microwave assisted, convergent synthetic approach, two nucleophilic aromatic substitution reactions are executed on cyanuric chloride in 10 min at 60 °C using primary amines. Substitution of the resulting monochlorotriazine with a diamine requires 95 °C for 30 min. Purifications are accomplished using an automated chromatography system such that the generation three dendrimer can be prepared from the starting materials in less than one day.

Dendrimers Terminated with Dichlorotriazine Groups Provide a Route to Compositional Diversity

Triazine dendrimers terminated with either four or eight dichlorotriazines can be prepared in high yields by reacting an amine-terminated dendrimer with cyanuric chloride. These materials exist as white powders and are stable to storage at room temperature. Sequential nucleophilic aromatic substitution with two different amine nucleophiles yields compounds that display the desired compositional diversity. Reaction conditions for the substitution were developed using a model dichlorotriazine with amine nucleophiles at -20, 0, and 25 °C. Selective substitution is favored at lower temperatures and with more nucleophilic amine groups.

Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers

Triazine and PAMAM dendrimers of similar size and number of cationic surface groups were compared for their ability to promote platelet aggregation. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa–130 kDa and in surface groups 16–256. PAMAM dendrimers selected for comparison included G3 (7 kDa, 32 surface groups) and G6 (58 kDa, 256 surface groups). The treatment of human platelet-rich plasma (PRP) with low generation triazine dendrimers (0.01–1 µM) did not show any significant effect in human platelet aggregation in vitro; however, the treatment of PRP with larger generations promotes an effective aggregation. These results are in agreement with studies performed with PAMAM dendrimers, where large generations promote aggregation. Triazine dendrimers promote aggregation less aggressively than PAMAM dendrimers, a factor attributed to differences in cationic charge or the formation of supramolecular assemblies of dendrimers.

Influence of linker groups on the solubility of triazine dendrimers

Eight triazine dendrimers were prepared to probe the impact of linker choice on water solubility. Three different linkers were assessed including two hydrophobic diamines that show high reactivity, piperazine and trismethylene bispiperidine, as well as a hydrophilic diamine, 4,7,10-trioxotridecane-1,14-diamine, which is less reactive. Dendrimers 1–8 share a common, generation two, hydrophobic core, 1. Dendrimer 1 is insoluble in water. Of the three generation four dendrimers, 2–4, that were prepared, 2 is also insoluble in water, but substitution of one or two of the hydrophobic linkers with 4,7,10-trioxotridecane-1,14-diamine yields sparingly soluble 3 and more soluble 4, respectively. Molecular dynamics simulations of dendrimers 2–4 in water provide additional insight into their shape, hydration and hydrophobicity. Generation six targets, 5–8, are also sensitive to choice of interior and surface groups. Dendrimer 5 is insoluble in water, but replacing one or two hydrophobic linkers with 4,7,10-trioxotridecane-1,14-diamine yields dendrimers 6 and 7 with modest affect unless the double substitution occurs in tandem at the periphery to yield 8 which shows high solubility in water. The solubility trends suggest that the choice of cationic surface group is critical, and that piperazine groups on the periphery and interior do little to promote solubility of triazine dendrimers in water compared with the hydrophilic amine 4,7,10-trioxotridecane-1,14-diamine.

Accelerated synthesis of large generation triazine dendrimers using microwave assisted reactions: a 24 hour challenge

The expedited synthesis of odd generation triazine dendrimers up to generation 9 can be executed in high yields using microwave irradiation. The efforts commence from commercially-available and inexpensive materials. Execution is facilitated by automated chromatography.

Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers

The synthesis and solubility behaviors of four generation five (G5) triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related to a liquid-liquid phase transition with a lower critical solution temperature (LCST) and is explained by differences in composition, notably, the hydrophobic nature of the terminal groups. Interestingly, the water solubility of the acetylated dendrimer is affected by the addition of selected metal ions. Titrating solutions of acetylated dendrimer at temperatures below the LCST with gold or palladium ions promoted precipitation, but platinum, iridium, and copper did not. Gold nanoparticles having diameters of 2.5 ± 0.8 nm can be obtained from solutions of the acetylated dendrimer at concentrations of gold less than that required to induce precipitation by treating the solution with sodium borohydride.

CHAPTER 10:Cationic Triazine Dendrimers: Synthesis, Characterization, and Biological Applications

Triazine dendrimers—globular polymers ranging from small-molecule to viral dimensions—have lived up to the claim of “if it can be cartooned, it can be made”, as illustrated in the diversity in sizes and compositions that have been produced. While largely unexplored in applications associated with regenerative medicine, their potential as scaffolding materials and in the display of ligands or other bioactive agents suggest future opportunities. This chapter summarizes 15 years of efforts in this field with the desire to inspire new uses for this versatile class of materials. With rare and noted exceptions, triazine dendrimers are cationic.