Boronated dendrimer

Several dendrimeric borane and carborane systems have been developed for use as boron-delivery agents.147 In vitro tests with a boronated dendrimer-epidermal growth factor bioconjugates indicated that they are endocytosed, resulting in the accumulation of boron in lysosomes. 

Backer, M. V., Gaynutdinov, T. I., Patel V., et al. (2005) Vascular endothelial growth factor selectively targets boronated dendrimers to tumor vasculature. Mol. Cancer. Ther. 4, 1423-1429. 

PAMAM Four G5 conjugated to protein NH2, Cy5.5, and boron, (dendrimer linked to VEGF protein) Cy5.5 VEGF protein Angiogenesis Dual NIR and neutron capture therapy Yes Yes 353... 

The first dendrimeric structures peripherally functionalized with a polyhedral borane were reported by Barth et al. in 1994. For that purpose, zero, first, second, and third generation of amino-terminated PAMAM startbust dendrimers were boronated by their reaction with Na(CH3)3NB,oH8NCO. After that, the boronated dendrimers reacted with the monoclonal antibody MoAb IB16-6, previously derivatized with A-succinimidyl 3-(2-pyridyldithio)propionate, to obtain stable immunoconjugates. 

Synthesis of a few other boronated dendrimers that potentially could be used as boron delivery agents for BNCT were described recently [178,179]. 

Qualmann and Kessels have reported the synthesis of carborane-containing lysine dendrimers (123) (Fig. 72), with a better defined number of boron atoms, for use as protein labels in immunocytochemistry using electron microscopic techniques such as electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI).149... 

Precise placement of metal complexing sites within the infrastructure of a cascade molecule is of importance from a variety of perspectives. In the construction of the above noted Micellane family (cf. Sect. 3.1), we reported the construction of dendrimers with four alkyne moieties at sites equidistant from each other in the interior (17, Fig. 8) [60]. These were treated with decaborane (B10H14) to afford 1,2-dicarba-closo-dodecaboranes (o-carboranes) [71]. Rendering boron clusters soluble in water is of interest because of their use in cancer treatment by Boron Neutron Cancer Therapy. First and second generation water-soluble dendrimers containing four and twelve precisely located boron cluster sites, respectively, were synthesized (e.g., 18). These water soluble dendrimers and their precursors were characterized by 13C-, and nB-NMR spectroscopy (Fig. 8). 

Qualmann, B., Kessels, M.M., Musiol, H.J., Sierralta, W.D., Jungblut, P.W., and Morodeg L. (1996) Synthesis of boron-rich lysine dendrimers as protein labels in electron microscopy. Angew. Chem. Int. 

Shinkai et al. described the synthesis of dendritic saccharide sensors based on a PAMAM dendrimer labeled with eight boronic acid residues [183]. The dendritic compound showed enhanced binding affinity for D-galactose and d-fructose. The fact that the dendritic boronic acid functions as a saccharide sponge is ascribed primarily to the cooperative action of two boronic acids to form an intramolecular 2 1 complex. When one boronic acid binds a saccharide, its counterpart cannot participate in dimer formation and seeks a guest. 

Drug and DNA delivery, photodynamic therapy, boron neutron capture therapy, and magnetic resonance imaging are some areas in which appropriately functionalized dendrimers are being evaluated (Jang and Kataoka 2005 Svenson and Tomalia 2005 Yang and Kao 2006). In one particularly nice example, polylysine... 

We have synthesized and tested an example boron-chelating polymer based on a commercially available dendrimeric poly(amido amine) (PAMAM). Dendrimeric chelants offer several advantages over polymers typically used in PAUF. Foremost among these is the reduced viscosity of dendrimer solutions as compared to solutions of linear polymers[6]. This allows the use of higher polymer concentrations than previously feasible (though in the present study we worked at polymer concentrations of less than 5% due to the expense of the starting dendrimer). In this study, the dendrimeric chelant also serves as a convenient, monodisperse polymer with which to test the mathematical model for boron speciation which is derived from the work of Wise and Weber[l],... 

Within either of the polymer-rich phases, borate esters and diesters of the functional groups are assumed to form with the same association constants as observed for the independent functional groups in aqueous solution. The resulting equations simply describe the borate ester association constants as well as mass balances on boron and polymer-bound functional groups. Wise and Weber used the model to estimate association constants for the borate esters formed with the diols in PVA and to predict the gelation of PVA-borate solutions. As we have independently measured the association constants for the borate esters formed in this work, we have used the model to estimate the radius of gyration of the GP3 dendrimer and to predict both the boron speciation in borate/GP3 solutions and the efficacy of PAUF using these functional dendrimers. 

Polymer-assisted ultrafiltration. The functionalized dendrimer described above was used to remove boron from an aqueous feed stream. With the polymer in the holding cell (see Figure 3), the feed was added at the same rate that the permeate left the system. The differential equation describing the change in total boron concentration in the holding cell as a function of permeate volume is simply d(Bt)... 

Figure 6. Concentration of boron in the permeate (solid squares) as a function of permeate volume as the 1.63 mM boric acid feed (pH 9) was diafiltered through the holding cell containing 100 ml water and 4.755 g GP3 dendrimer. The permeate pH rose from 5.02 at the beginning of the run to 7.75 at the end. Model parameters Rg, 88.5 A K, 6300 K2,105 Mw, 55471 fp, 0.024.

Schliiter et al. successfully accomplished generation-specific incorporation of an individual aryl bromide functionality into poly(benzyl ether) dendrimers. Whatever its position in the dendrimer framework, this bromide function could also be utilised for further chemical modification because it can react with aryl-boronic acid via Suzuki cross-coupling [42]. 

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