Donald A. Tomalia

Formation of silver and gold dendrimer nanocomposites

Structural types of dendrimer nanocomposites have been studied and the respective formation mechanisms have been described, with illustration of nanocomposites formed from poly(amidoamine) PAMAM dendrimers and zerovalent metals, such as gold and silver. Structure of {(Au(0))n−PAMAM} and {(Ag(0))n−PAMAM} gold and silver dendrimer nanocomposites was found to be the function of the dendrimer structure and surface groups as well as the formation mechanism and the chemistry involved. Three different types of single nanocomposite architectures have been identified, such as internal (‘I’), external (‘E’) and mixed (‘M’) type nanocomposites. Both the organic and inorganic phase could form nanosized pseudo-continuous phases while the other components are dispersed at the molecular or atomic level either in the interior or on the surface of the template/container. Single units of these nanocomposites may be used as building blocks in the synthesis of nanostructured materials.

Hydrophobically modified poly(amidoamine) (PAMAM) dendrimers: their properties at the air–water interface and use as nanoscopic container molecules

Tri- and tetra-dendron poly(amidoamine) (PAMAM) dendrimers were nconverted into hydrocarbon-soluble polymers and used as hydrophobic nnanoscopic scaffolding by reacting their primary amino chain ends with nvarious epoxyalkanes. These hydrophobically modified modules performed nwell as nanoscopic transport molecules. They mimicked classical inverse nmicelle behaviour by transporting copper(ii) sulfate from an aqueous nsolution into an organic phase to form homogeneous, transparent, intensely nblue toluene solutions. The modified dendrimers were examined at the nair–water interface both with and without copper guest molecules. A nnumber of critical macromolecular design parameters (CMDPs) such as ngeneration (size), core (shape, topology) and surface groups were varied nto determine their influence on Langmuir film properties.

The synthesis and testing of anti-cancer therapeutic nanodevices

Nanotechnology provides the sized materials that can be synthesized and function in the same general size range and Biologic structures. We have attempted to develop forms of anticancer therapeutics based on nanomaterials. Our project seeks to develop dendritic polymer nanodevices that serve as a means for the detection of cancer cells, the identification of cancer signatures, and the targeted delivery of anti-cancer therapeutics (cis-platin, methotrexate, and taxol) and contrast agents to tumor cells. Initial studies documented the synthesis and function of a targeting module, several drug delivery components, and two imaging/contrast agents. Analytical techniques have been developed and used to confirm the structure of the device. Progress has been made on the specifically triggered release of the therapeutic agent within a tumor using high-energy lasers. The work to date has demonstrated the feasibility of the nano-device concept in actual cancer cells in vitro.

Partial shell-filled core-shell tecto(dendrimers): A strategy to surface differentiated nano-clefts and cusps

Poly(amidoamine) (PAMAM) dendrimer shell reagents possessing either nucleophilic (i.e., primary amines) or electrophilic (i.e., carboxymethyl esters) functional groups have been covalently assembled around appropriate electrophilic or nucleophilic dendrimer core reagents to produce partial shell filled/core-shell tecto(dendrimers). Partial shell-filled products with saturation levels ranging from 28% to 66% were obtained. These metastable, remarkably monodispersed assemblies possess functionally differentiated nano-cusps and clefts that exhibit “autoreactive” behavior. Pacification of these autoreactive products with appropriate alkanolamine reagents produced robust, nonreactive, “hydroxy-amine-differentiated” surfaces that exhibit very active self-assembly properties. Based on the monodispersity, dimensional scaling, and electrophoretic similarities of PAMAM dendrimers to globular proteins, these assemblies may be viewed as crude biomimetics of classical core shell-type protein aggregates. These dimensionally larger, but analogous PAMAM core-shell tecto(dendrimer) architectures extend and complete a similar pattern of autoreactivity and pacification that was observed earlier for traditional mono PAMAM dendrimer core-shell modules possessing unsaturated shell levels.

Dendrimers as reactive modules for the synthesis of new structure-controlled, higher-complexity megamers

Dendrimers are macromolecular, nanoscale objects that are widely recognized as precise, mathematically defined, covalent core-shell assemblies. As such, they are composed of quantized numbers of atoms, monomers, and terminal functional groups relative to the respective shell levels (generations) surrounding their cores. Dendrimers have been referred to as molecular-level analogs of atoms. This perspective arises from their potential to function as precise macromolecular tectons (modules), suitable for the synthesis of structure-controlled complexity beyond dendrimers. We have termed this major new class of generic structures megamers. Our group has now synthesized such megamer complexity in the form of both covalent and supra-macromolecular dendri-catenanes, dendri-macrocycles, dendri-clefts, and dendri-clusters. The covalent dendri-cluster subset of megamers has been coined core-shell tecto(dendrimers). New mathematically defined, covalent bonding rules for tecto(dendrimer) formation are consistent with sterically induced stoichiometry (SIS) predictions and have been verified experimentally.

Architecturally Driven Properties Based on the Dendritic State

This new architectural class of macromolecules has received substantial attention during the past decade. Three dendritic subclasses, which include: (a) random hyperbranched (i.e. one-pot AB x polymerizations), (b) dendritic grafted (i.e. Combburst® polymers) and (c) regular dendrons/dendrimers (e.g., Starburst® dendrimers) have been synthesized and characterized at a well-defined level in our laboratory. It is clear that their precisely controlled, nanoscale dimensions and architecture play critical roles in influencing physical properties and performance characteristics. Furthermore, these parameters have also distinguished dendrimers as fundamental modules for many nanotechnology applications, as well as for the construction of a new class of larger nanoscale entities which we have termed core–shell tecto(dendrimers). This paper will overview these activities and focus on certain unique de Gennes dense packing (or congestion phenomena) and nanoscale container properties that have emerged from this novel architecture.

Dendritic Macromolecules: A Fourth Major Class of Polymer Architecture – New Properties Driven by Architecture

This new architectural class of macromolecules has received substantial attention during the past decade. Three dendritic subclasses, which include (a) random hyperbranched (i.e., one-pot AB x , polymerizations), (b) dendritic grafted (i.e., Combburst® polymers) and (c) regular dendrons/dendrimers (e.g., Starburst® dendrimers) have been synthesized and characterized at a well-defined level in our laboratory. It is clear that their precisely controlled, nanoscale dimensions and architecture play critical roles in influencing physical properties and performance characteristics. Furthermore, these parameters have also distinguished dendrimers as fundamental modules for many nanotechnology applications, as well as for the construction of a new class of larger nanoscale entities which we have termed core-shell tecto(dendrimers) . This account will overview these activities and focus on certain unique de Gennes dense packing (or congestion phenomena) and nanoscale container properties that have emerged from this novel architecture.

The characterization of high generation poly(amidoamine) G9 dendrimers by atomic force microscopy (AFM)

Scanning force microscopy (AFM) has been employed to characterize the generation-9 (G9) poly(amidoamine) (PAMAM) dendrimer packing on a mica surface under various conditions. Well ordered 2-D arrays from hexagonally packed particles of PAMAM (G9) dendrimers (11.4nm in diameter) were deposited on the mica surface. This may be one of the smallest regular monolayer arrays ever observed. The mechanism considered to be responsible for this 2-D array packing is the interaction of forces between the dendrimer and the mica surface and between dendrimer molecules as well. Other factors such as molecular interpenetrating and the rigidity of the branch structure obviously play an important role in the 2-D array formation.

Analysis of polyamidoamine dendrimers by isoelectric focusing

AbstractPolyamidoamine dendrimers have been studied extensively for their potential applications in nanomedicine. Their uses as imaging, drug, and nucleic acid delivery agents are nearing clinical trials. As such, characterization of polyamidoamine dendrimers and their nano-devices is of immense importance for monitoring the efficiency of their synthesis, purity, and quality control of manufactured products as well as their in vivo behavior. We report here the analysis of polyamidoamine dendrimers possessing various cores and surface groups with a simple and inexpensive isoelectric focusing method. The isoelectric points of the dendrimers were readily determined from a calibration plot generated by running proteins with known pI values. The isoelectric points for various surface-modified polyamidoamine dendrimers ranged from 4 to 9. Polyamidoamine dendrimers possessing terminal hydroxyl groups gave a pIu2009>u20097, while those with terminal carboxyl groups exhibit a pIu2009<u20097. Generation number and cores of the dendrimers did not significantly affect their isoelectric points. Isoelectric focusing thus offers another important tool for characterizing these nanomolecules.n FigureIEF of PAMAM dendrimers

Regio-specific size, shape and surface chemistry designed dendrimers based on differentiated dendroid templates

Various generations of zero α,ω-alkylenediamine core poly(amidoamine) PAMAM dendrimers (tetra-amine terminated substrates, A4) were allowed to react with sub-stoichiometric amounts (i.e., 2.0 equivalents) of Boc anhydride to give product mixtures consisting of the symmetrical tetra-Boc product (B4) and four partial Boc protected adducts, namely, (1) the tri-(AB3), (2) di-geminal (A2B2), (3) di-vicinal (A2B2) and (4) mono-Boc (A3B) products. These unprecedented, regio-differentiated Boc cores possess emerging dendritic features and intrinsic “protect–deprotect” function. We refer categorically to these newly differentiated branched cores as differentiated dendroid templates (DDTs). These dendroid templates can be well resolved by thin layer chromatography (TLC). Gram quantities of these Boc adducts were purified using single pass silica gel column chromatography. These partial Boc protected, differentiated dendroid templates (AmBn, m/n = 1–3) were used as “protect–deprotect” functionalized starting substrates (i.e., regio-differentiated cores) for synthesizing higher generation libraries of regio-differentiated PAMAM dendrimers. In principle, the use of differentiated dendroid templates (i.e., regio-functionalized star-branched cores) should be expected to offer broad options for the systematic engineering and control of many diverse organic nanostructures as a function of size, shape and regio-chemistry.