Dendrimers are nano-sized, radially symmetric molecules well-defined, homogeneous and monodisperse structure Consisting of tree-like arms or branches

Dendrimer is based on the Greek words dendron meaning tree or branch and meros meaning part Dendrimers have a globular configuration with monomer units branching out from a center cord. The structure is highly defined and organized. .. The number of branches increases exponentially extending from core to the periphery. The branching would come to a stop when the steric hindrance stopped any further growth. The multi-functionalized core (initiator core) forms the heart of the molecules; all branches emanate from this core.

The monomers that attach to the core form the first branches (The First Generation). On the successive generations, two monomers will attach to the ends of the monomers in the previous generation. At the terminating generation, a terminal functional group is added to the tail of the monomer. Most of the chemical properties of the molecule depend on types of terminal groups. The physical properties of the molecules, such as solubility and viscosity are also affected by the terminal groups.

. Some of these dendrimers have diameters that are greater than ten nm. The molecular weights range from about 50,000 to 200,000 g/mol. The outer surface area of the molecule increases with the number of generations.

There is a significant of void space within the molecule. These voids consist of channels and cavities. These unique geometries give the molecule special properties such as adhesiveness and ability to entrap foreign molecules. SYNTHESIS OF DENDIMERS Divergent Growth Method This type of synthesis involves two steps:

The activation of the functional surface groups The addition of branching monomer units. The reaction starts at the core.

The initiator core contains several reaction sites. The first generation monomer units react with the core readily. Once all reactive sites are taken, the addition stops. Since the end groups on the first generation are protected, addition of monomers to the end chain is impossible. The end groups must be activated before any further addition. The passive functionalities on the end groups are removed by a secondary reaction.
Additional monomers are attached to the molecule. Steps are repeated for synthesizing higher generations. One can control the structure and molecular weight of the molecule precisely. Divergent growth method is labor intensive and repetitive. In successive generation growth, side reactions and incomplete additions become more apparent attributed to steric hindrance. In each step, the desire products must be purified. The overall yield is considerably small. .. One of the great advantages of this method is the ability to modify the surface of the dendrimer molecule. By changing the end groups at the outermost generation, the overall chemical and physical properties of the dendrimer can be configured to specific needs It is due to this versatility that sparked the interest in dendrimer research. PAMAM dendrimers were synthesized using divergent method, starting with an initiator core and expanding to the periphery

In PAMAM dendrimer synthesis it is observed after tenth generation. The rate of reaction drops suddenly and further reactions of the end groups cannot occur. The tenth generation PAMAM contains 6141 monomer units and has a diameter of about 124 .. Convergent Growth Method This method was first introduced by Frechet. The reaction starts at the periphery and proceeds to the core. Similar to divergent growth, it involves two steps: The attachment of the outermost functional groups to an inner generation The attachment of the inner generations to the core The structural units before the final attachment to the core is called the "wedge." Three to four wedges attach to the core. Each wedge can have different functional groups at the periphery. Thus, the making of unsymmetrical dendrimers is possible. This modification is useful in monolayer formation at the organic-aqueous interface. Half of the dendrimer is submerged in the water phase, while the other half is in the organic phase

..

 Dendritic copolymers are a specific group of dendrimers. There are two different types of copolymers: Segment-block dendrimers: are built with dendritic segments of different constitution. They are obtained by attaching different wedges to one polyfunctional core molecule. Layer-block dendrimers consist of concentric: spheres of differing chemistry. They are the result of placing concentric layers around the central core .

 Pharmaceutical Application Dendrimers Drug Delivery: Targeted And Controlled Release Drug Delivery Dendrimers are considered as a possible drug carriers because of their unique properties. Well dened three-dimensional structure Availability of many functional surface groups Low polydispersity .. Drug molecules can be loaded both in the interior of the dendrimers as well as attached to the surface groups. Dendrimers can function as drug carriers either by encapsulating drugs within the dendritic structure, or by inter-acting with drugs at their terminal functional groups via electrostatic or covalent bonds.

. Structural options for dendrimer based drug delivery. Dendrimers can be synthesized with neutral surfaces and positive or negative charges at the periphery; Dendritic macromolecules, generally when larger than G3, can harbor non-covalently encapsulated drug molecules An alternative strategy for drug delivery is through covalent conjugation of ligands to the surface of the dendrimer The versatility of dendrimers for drug delivery is illustrated by considering that A could be a targeting ligand and the active drug could be encapsulated within the same macromolecule ..

 Synthetic strategies are now available for providing dendritic clusters with extremely high densities of surface ligands and for providing more than one type of surface ligand, either in a random orientation, or in blocks. ..

Requirements for dendrimer-based, cancer-targeted drug delivery. (a) Dendrimers with multiple surface functional groups can be directed to cancer cells by tumor-targeting entities that include folate or antibodies specific for tumor-associated antigens (TAAs). (b) The next step is intake into the cell, which in the case of folate targeting occurs by membrane receptormediated endocytosis. (c) Once inside the cell, the drug generally must be released from the dendrimer, their is simultaneous disintegration of the dendritic scaffold (d). ..

Dendrimers are particularly attractive as they offer a high drug-loading capacity. Methods of dendrimer drug delivery are encapsulation of drugs and dendrimer drug conjugates DNA was complexed with PAMAM dendrimers for gene delivery applications, and hydrophobic drugs and dye molecules were incorporated into various dendrimer cores In dendrimerdrug conjugates, the drug is attached through a covalent bond either directly or via a linker/spacer to the surface groups of a dendrimer Dendrimers have been conjugated to various biologically active molecules such as drugs, antibodies, sugar moieties and lipids. . The drug loading can be tuned by varying the generation number of the dendrimer Release of the drug can be controlled by incorporating degradable linkages between the drug and dendrimer. Conjugates of PAMAM dendrimers with cisplatin, a potent anticancer drug with non-specific toxicity and poor water solubility. The conjugates show increased solubility, decreased systemic toxicity and selective accumulation in solid tumors Poly(lysine) dendrimers is modified with sulfonated naphthyl groups Found to be useful as antiviral drugs against the herpes simplex virus can potentially prevent/reduce transmission of HIV This dendrimer-based nano-drug inhibited early stage virus/cell adsorption Inhibit later stage viral replication by interfering with reverse transcriptase and/or integrase enzyme activities . Dendrimers In Photodynamic Therapy The photosensitizer 5-aminolevulinic acid has been attached to the surface of dendrimers Studied as an agent for PDT of tumorigenic keratinocytes Photo sensitive dyes have been incorporated into dendrimers and utilized in PDT devices This cancer treatment involves the administration of a light- activated photosensitizing drug that selectively concentrates in diseased tissue. The possibility of improving the properties of dendrimers through appropriate unfunctionalization of their periphery makes dendrimers promising carriers for photosensitizers

Dendrimers In Gene Transfection Dendrimers can act as vectors, in gene therapy. PAMAM dendrimers have been tested as genetic material carriers. Dendrimers as non-viral gene transfer agents, enhancing the transfection of DNA by endocytosis and, ultimately, into the cell nucleus A transfection reagent called SuperFectTM consisting of activated dendrimers is commercially available. Activated dendrimers can carry a larger amount of genetic material than viruses. SuperFectDNA complexes are characterized by high stability and provide more efficient transport of DNA into the nucleus than liposomes. PAMAM dendrimers functionalized with cyclodextrin showed luciferase gene expression about 100 times higher than for unfunctionalized PAMAM

Diagnostics Paramagnetic metal chelates such as Gd(III)- N,N,N,N-tetracarboxymethyl-1,4,7,10-tetraazacy-clododecane (Gd(III)-DOTA) and their derivatives used as contrast agents for magnetic resonance imaging (MRI) Dendrimer-based Gd(III) chelates consisting of generations 2 and 6 PAMAM dendrimers with 12 and 192 terminal surface amines conjugated to the chelating ligand 2-(4-isothiocyanatobenzyl)-6- ethyldiethylenetriaminepentaacetic acid through a thiourea linkage were synthesized . These contrast agents exhibited excellent MRI images of blood vessels upon intravenous injection. These dendrimer polychelates were exploited for high-quality MR angiography (MRA) images up to 60 min post injection DNA-dendrimers, which are constructed for routine use in high-throughput functional genomic analysis, and as biosensors for the rapid diagnosis have genetic, and pathogenesis diseases Radiolabelled monoclonal antibodies with high specific activity have been prepared by attachment of PAMAM dendrimers . Dendritic Catalysts / Enzymes The combination of high surface area and high solubility makes dendrimers useful as nanoscale catalysts. Dendrimers have a multifunctional surface and all catalytic sites are always exposed towards the reaction mixture. They can be recovered from the reaction mixture by easy ultra filtration methods Dendritic shells can be used to create a microenvironment favorable for catalysis or provide shielding for functional groups at the dendritic core 1.Metallodendritic catalysts 2. Catalysis with phosphine-based dendrimers 3.Catalysis with (metallo) dendrimers containing chiral ligands 4.Non-metal containing dendrimers CATALYSIS

Industrial Processes

Dendrimers can encapsulate insoluble materials, such as metals transport them into a solvent within their interior. Cooper and co-workers synthesized fluorinated dendrimers, which are soluble in supercritical CO2 and can be used to extract strongly hydrophilic compounds from water into liquid CO2 This may help develop Technologies in which hazardous organic solvents are replaced by liquid CO2 .