Design and synthesis of dendrimers for multipurpose tasks

Monodisperse macromolecules with tailored architecture constitute the key to designing efficient and smart nanomaterials. They offer real potential to achieve this goal, and one of the earlier challenges faced by this novel class of macromolecules has been addressed by the evolutions in their synthetic methodologies. In this thesis, (i) inorganic, organometallic, and organic synthetic routes are employed to construct mono- and bi-functional dendrimers; and (ii) a detailed study including an evaluation of their structure-property relationships using a combination of experiment with theoretical calculations, and their applications in molecular encapsulations and drug delivery, are reported. Geometric characterization of 3,5-dihydroxybenzyl alcohol (DHBA)-based dendrimers, using aminosilanes as linkers was achieved using molecular mechanics MM+ method and the PM3 semi-empirical molecular orbital theory. Optimization of DHBA-based dendrimer generations 1--5 (DG1--5) suggested that DG1--3 have a relatively open structure with no internal spaces of any particular size or shape, while DG4 and 5 assume a more globular structure with well-defined internal cavities. Encapsulation of disperse red 1 (DR1) into the cavities of these dimethylsilyl linked DHBA-based dendrimers led to a blue shift in the lambdamax of DR1, and transmission electron microscopy (TEM) showed a rectangular shape of dendritic aggregates containing DR1. Catalytic activity of (COD)RhCl(PPh2(CH2) 3OH) encapsulated in dendritic aggregates of generations 1--4, indicated a significant decrease in catalytic conversion of 1-decene to decane in dendrimer generation 4 upon going from a concentration below critical aggregation concentration (cac) to above cac. Subsequently, a simple divergent methodology to synthesize 1,3,5-triethynylbenzene (TEB)-based dendrimers, using amino stannanes as linkers, was developed. A theoretical evaluation of their structure suggested that they evolve into a turbine shape with benzene rings arranged in a fashion to create sandwich type cavities. Our results show that the inorganic entities (Me3Sn) in these dendrimers act as electron donors, and can significantly influence their photophysical properties. The versatility of these dendrimers in introducing transition metal centers directly into the backbone is demonstrated by substitution of dimethyltin links with square planar platinum centers, upon reaction with (nBu3P)2PtCl2. This eliminates the need to add a catalyst in the synthesis of such organometallic dendrimers. In an attempt to streamline the synthesis of dendrimers that incorporate organic backbones, we report the synthesis of molecular building blocks that contain azide and alkyne terminated functionalities, suitable for carrying out Cu I catalyzed cycloaddition between alkynes and azides (CuAAC) "click" reaction. We show the versatility of these building blocks in constructing dendritic frameworks with 4, 6 or 12 peripheral acetylene groups, using either the convergent or divergent methodologies. Using the same protocol, we devised an efficient iterative methodology using CuAAC "click" chemistry to construct bifunctional dendrimers which combine imaging and therapeutic functions, and can specifically target lipid droplets. BODIPY, a tracer dye, and the drug, alpha-lipoic acid, are covalently linked in these dendrimers. A detailed evaluation of subcellular distribution of these dendrimers clearly demonstrates that (i) they do not induce marked metabolic abnormalities in human liver cells; (ii) the rate and extent of internalization of dendrimers containing either only the BODIPY or both BODIPY and alpha-lipoic acid, are different from the free dye and drug.