This manuscript focuses on the routes, methods and reagents used to synthesize triazinebased dendrimers. Our pursuit of macromolecular architectures for drug deliverydendrimers based on triazines-has been an ongoing effort for 8 years. To date, we have produced complex dendrimers with diverse peripheries as proof-of-concept, less complex molecules tailored for specific applications including DNA and RNA delivery and drugdecorated dendrimers for potential therapeutic applications including infectious disease and cancer. These syntheses have been executed at scales that range from high milligrams to over a kilogram. The routes, reagents and diversity displayed by a target anchors it in time. Early targets derive from convergent synthetic routes while later targets are prepared using divergent syntheses. The core of early dendrimers was a simple diamine, including piperazine, yielding the so-called bow-tie structures, middle period targets boast either a trispiperazinyltriazine core or a 'super-core' with six piperazine groups. Later targets return to the trispiperazinyltriazine core. The choice of linking diamine has also changed. Over time, p-aminobenzylamine was replaced by piperazine and then by aminomethylpiperidine with more exotic diamines sprinkled in throughout. Peripheral group choice has undergone similar variations: from AB 2 to AB 4 to, more recently, AB 3 . The diversity communicated by these groups yields dendrimers ranging from those with a common surface to examples where two groups were presented to those where four orthogonally reactive groups appear. Over time, these groups have grown in complexity from protected amines to tags for biodistribution and drugs like paclitaxel. Herein, strategies adopted and lessons learned are reviewed, intuitions relayed and future directions forecast.

Alkali-stable, high-pI isoelectric membranes have been synthesized from quaternary ammonium derivatives of cyclodextrins and poly(vinyl alcohol), and bifunctional cross-linkers, such as glycerol-1,3-diglycidyl ether. The new, high-pI isoelectric membranes were successfully applied as cathodic membranes in isoelectric trapping separations in place of the hydrolytically more labile, polyacrylamide-based cathodic isoelectric membranes, and permitted the use of catholytes as alkaline as 1 M NaOH. The new high-pI isoelectric membranes have shown excellent mechanical stability, low electric resistance and long life times, even when subjected to electrophoresis with current densities as high as 80 mA/cm2.

Hydrolytically stable, low-pI isoelectric membranes have been synthesized from low-pI ampholytic components, poly(vinyl alcohol), and a bifunctional cross-linker, glycerol-1,3-diglycidyl ether. The low-pI ampholytic components used contain one amino group and at least two weakly acidic functional groups. The acidic functional groups are selected such that the pI value of the ampholytic component is determined by the pK(a) values of the acidic functional groups. When the concentration of the ampholytic component incorporated into the membrane is higher than a required minimum value, the pI of the membrane becomes independent of variations in the actual incorporation rate of the ampholytic compound. The new, low-pI isoelectric membranes have been successfully used as anodic membranes in isoelectric trapping separations with pH < 1.5 anolytes and replaced the hydrolytically less stable polyacrylamide-based isoelectric membranes. The new low-pI isoelectric membranes have excellent mechanical stability, low electric resistance, good buffering capacity, and long life time, even when used with as much as 50 W power and current densities as high as 33 mA/cm(2) during the isoelectric trapping separations.

The synthesis and characterization of second-and third-generation triazine dendrimers bearing carboxylic acid groups on the periphery are reported. These materials were synthesized by exhaustive succinylation of amine-terminated dendrimers. 1 H and 13 C NMR spectra are consistent with the desired products, but these techniques are limited by degeneracy in signals. MALDI-TOF mass spectrometry confirms the presence of the desired material. These materials display pHdependent solubility in water. Capillary electrophoresis proves to be valuable in multiple elements of this work, and general protocols emerge that appear to be useful for the characterization of lower-generation anionic dendrimers. Specifically, capillary electrophoresis provides a convenient method for monitoring the removal of excess succinic anhydride/succinic acid and offers additional clues to the chemical nature of the impurities in these samples. Optimization of the background electrolyte and instrumental parameters allows for the assessment of the purity of these triazine targets as well as comparison with two sets of commercially available anionic poly(amidoamine) (PAMAM) dendrimers. Corroborative information from the different orthogonal analytical techniques employed supports the hypothesis that triazine dendrimers exist as very narrowly disperse mixtures of macromolecules approaching, in some cases, single chemical entities.