Triazine dendrimers

Crampton H, HoUink E, Perez LM, Simanek EE. A divergent route towards single-chemical entity triazine dendrimers with opportunities for structural diversity. New J Chem 2007 31 1283-1290. 

In recent years cationic dendritic structures such as carbosilane-based [215], triazine-based [216], polyester [217] and amphiphilic dendrimers [218] have been investigated for transfection purposes with promising results, thus offering novel alternatives to the exploration of dendrimer-based nucleic acid delivery. 

These features of these materials spurred the scientific community to utilize them in biomedical applications [49]. In particular, the synergy between their multivalency and size on the nanoscale enables a chemical smartness along their molecular scaffold that achieves environmentally sensitive modalities. These functional materials are expected to revolutionize the existing therapeutic practice. Dendritic molecules, such as polyamidoamine, polylysine, polyester, polyglycerol (PG), and triazine dendrimers, have been introduced for biomedical applications to amplify or multiply molecularly pathopharmacological effects [73]. 

Other related dendrimers of the first [279] and second [280] generation based on the 1,3,5-triazine unit and tolane arms were also reported by Lee and Yamamoto. The dendrimers of the first generation bearing two chains exhibit a Colh phase as expected. Surprisingly, the members of the second generation also showed a Colh phase between 130 and 150 up to 170-230 °C, despite of the grafting of only one terminal chain per peripheral arm. 

Interest in the Staudinger reaction of phosphines with azides, and the Mit-sunobu reaction involving nucleophilic attack by phosphorus at nitrogen in esters of diazodicarboxylic acids, has continued. Systems of the type (205) have been obtained from the reactions of secondary arylphosphines with azides. Treatment of these with butyllithium results in deprotonation to form the diaminophosphonium diazaylides (206). Phosphazenes have been prepared from azido-quinolines and -triazines, and also from diazoketones " and polycyanocyclopropanes. The Staudinger reaction has been employed in the synthesis of phosphorus-containing dendrimers, and in new approaches to amide and peptide synthesis. The reaction has also been used in a high-... 

Two novel donor-acceptor phenylazomethine dendrimers with a 5-triazine core and butoxybenzene units have been synthesized <05TL8861>. Three novel nitrogen-rich nanolayered, nanoclustered and nanodendritic carbon nitrides have been prepared from 4,4, 6,6 -tetra(azido)azo-l,3,5-triazine (TAAT) <05AG(E)737>. 

V.J. Venditto, K. Allred, C.D. Allred, E.E. Simanek, Intercepting the synthesis of triazine dendrimers with nucleophilic pharmacophores a general strategy toward drug delivery vehicles, Chem. Commun. 37(2009)5541-5542. 

K.K. Bansal, D. Kakde, U. Gupta, N.K. Jain, Development and characterization of triazine based dendrimers for delivery of antitumor agent, J. Nanosd. Nanotechnol. 10 (12) (2010) 8395-8404. 

S.T. Lo, S. Stem, J.D. Clogston, J. Zheng, P.P. Adiseshaiah, M. Dobrovolskaia, J. Lim, A.K. Patri, X. Sun, E.E. Simanek, Biological assessment of triazine dendrimer toxicological profiles, solution behavior, biodistribution, drug release and efficacy in a PEGylated, paclitaxel construct. Mol. Pharm. 7 (4) (2010) 993-1006. 

Cationic Triazine Dendrimers Synthesis, Characterization, and Biological Applications... 

Interest in dendrimers is predicated in large part on the belief that size, shape, and composition matter. Dendrimers are synthetic polymers that— theoretically—are perfectly branched from a common core, giving rise to descriptions of two-dimensional representations that include tree-like or snowflake-like . As the products of synthesis, the size and composition of a dendrimer can be manipulated by choice of the starting materials. Commonly, triazines can reach protein-sized dimensions with an onset of globular structure. Larger triazine dendrimers that can reach the dimensions of small viruses have been reported. The literature is replete with examples of small dendrimers that can be viewed as floppy, randomly coiled oligomers. 

This chapter focuses on cationic triazine dendrimers—a class of molecules that we have been exploring for almost 15 years. We first focus on design and synthesis, then on characterization, and finally on the biological applications we and collaborators bave described. 

Triazine dendrimers offer properties that distinguish them from other classes of materials. These characteristics include the following (Sections 10.1.2.1-10.1.2.5). 

Triazine dendrimers are stable to a range of pH and thermal conditions. Stability from pH 0 to 14 in aqueous solution is observed. Indeed, the synthesis requires that materials be subjected to a 1 2 mixture of coneentrated aqueous HCl/methanol. These materials are currently presumed to be stable... 

Table 10.1 Summary of G1-G13 triazine (bold) and PAMAM dendrimers. Ends refers to the number of surface groups, MW is the molecular weight in Daltons, (ixEM and (iors refer to the diameter in nanometers measured by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.

Alternatives to triazines exist. These include dendrimers derived from PAMAM, polypropylenimine (PPI), lysine, and phosphorus-containing dendrimers, as shown in Figure 10.2. ... 

Reactions of amines with other reagents can produce cationic dendrimers as well, or temper the degree of cationic character. Triazine dendrimers have been reacted to provide the charged species shown in Figure 10.5. 

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