Dendron Building Blocks for Click Chemistry

Dendrimers offer a new possibility to derivatize small molecules, surfaces or biopharmaceuticals with a monodisperse macromolecule and alter in this way properties like solubility and hydrophilicity. Immunogenicity and pharmacokinetics of pharmaceuticals will be improved. The synthetic approach for designing these dendrons of different generations is based on 2,2-bis(hydroxymethyl) propionic acid, which is a non-toxic and biocompatible building block.

The size can be designed from 250 g/mole for 1st generation dendrons to over 4400 g/mole with 5th generation compounds. Dendrimers can be designed reaching even a molecular weight of some 10.000 Da. As focal point alkyne and azido functions are used with appropriate counter parts in any type of click chemistry reaction. Olefinic functions offer the possibility for addition reaction or conjugation by metathesis reactions or photo reactions with the aid of UV light. For the modification of Gold surfaces sulphur bearing dendrons can be used, they also conjugate with biologicals via disulfide bridge formation.

Hydroxyl and acetonide functions are available as terminal groups. Thus the surface can be designed as either hydrophilic or hydrophobic. In particular the hydrophobic acetonide variations offers through its amphiphilic nature interesting properties, as the centre is still polar and hydrophilic. This improves solubility in biological liquids. The hydrophobic surface helps to interact with lipids, cell surfaces, and hydrophobic enzymes, like lipases. Furthermore, the acetonides offer another advantages for chemical diversity. They can be removed and thus be a temporary protecting group for further derivatization of the dendritic surface.