Dendrimes

• What are dendrimers?

• How are they formed?

• What are their properties?

• What are the applications?

• How do you characterize

them?

Overview

Dendrimers are the new artificial macromolecules which have the structure

like a tree. consist of a series of chemical shells built on a small core molecule. Each shell consists of two chemicals, always in the same order and is called a

generation

Fig. A: Schematic 2D presentation of dendrimerFig. B: 3D presentation of dendrimer

Properties of

Dendrimers

Properties

Structure Compact and Globular

synthesis Careful and stepwise growth

Structure control Very high

Shape spherical

Crystallinitty Non crystalline, amorphous material, lower glas temperature

Nonpolar solubility high

Aqueous solubility high

viscosity Non liner relationship with molecular weight

reactivity high

.Core Surfa

ce

Interior

Surface: functional peripheral group

Interior: affects host-guest properties

Core: affects 3D shape of dendrimer

- Dendrimers consist of three main components…

Dendrimer Components

- Count branching points as the “generation”

This is a “G2 dendrimer.”Higher generation dendrimers form more dense, dimensional shape.

Types of Dendrimers: - Pamam Dendrimer- PPI Dendrimer- Chiral Dendrimer- Multilingual Dendrimer- Tecto Dendrimer- Hybird Dendrimer- Aruphiphilic Dendrimer- Frecher-Type Dendrimer- Peptide Dendrimer- Pamamos Dendrimer

We make the nanodevice by modeling it first. Modeling then drives synthesis, which produces materials for testing.  Test results, in turn, drive further modeling and synthesis.

How do we make a dendrimer?

Divergent strategy

convergent strategy

Synthesis of Dendrimers

Divergent strategy

http://www.fda.gov/nanotechnology/powerpoint_conversions/chbsa-nanotech-presentation06-05_files/textonly/slide10.html

convergent strategy

Lee J. W., Kim J.H., Kim Byung-Ku. Synthesis of azide-functionalized PAMAM dendrons at the focal point and their application for synthesis of PAMAM-like dendrimers, Tetrahedron Letters, 2006. 47:2683–2686

Organic Synthesis

Dendrimers have been prepared via click chemistry, employing Diels-Alder reactions,thiol-yne reactions and azide-alkyne reactions.An example is the synthesis of certain polyphenylene dendrimers is shown in this figure

http://en.wikipedia.org/wiki/Dendrimer

Supramolecular Dendrimers

Supramolecular systems are rarely designed from first principles. Rather, chemists have a range of well-studied structural and functional building blocks that they are able to use to build up larger functional architectures. Many of these exist as whole families of similar units, from which the analog with the exact desired properties can be chosen. The molecule shown here is a combination of traditional organic synthetic compounds using significant steric hinderence to achieve a particular shape/conformation

Dendrimers (Arborols)

Size scale of Dendrimers of different generations vs. Biological Proteins

Dendrimers vs. Proteins

Similarities

Size

Weight

Well defined chemical structure (known bonding structure)

3 dimensional position of each atom is difficult to determine - yet a consistent specific 3 dimensional structure exists

Difficult to perform chemical analysis

Easy for cell to uptake

Main Difference

Proteins are polymers made from 20 different monomers, while dendrimers are polymers made from two monomers.

This light-harvesting dendrimer performs some functions of artificial photosynthesis. White light is gathered through chain-ends that behave like antennae and funneled into a chromophore in the dendrimer's core that then emits a single color of amplified light

Dendrimer Applications

1- Bioactive Dendrimers

Dendrimer

Dendrimers can be functionalized for surface activity., such as attaching to cells, and using a quantum dot interior core for imaging. Dendrimers can contain metal atoms including gold which can absorb radiation at a particular wavelength, and used in cancer treatment. The relatively short lifetime of a dendrimer enures that it won’t bioaccumulate in the body, or concentrate potentially toxic cadmium (CdS quantum dots).

2- Dendrimer as magnetic resonance imaging contrast agents

Dendrimer based metal chelates act as a magnetic resonance imaging contrast agent. Dendrimers are highly suited and used as image contrast media because of their properties. Many tests carried on dendrimers have shown that dendrimers are stronger contrast agent than conventional ones.

The effect of sepsis on dendrimer-enhanced magnetic resonance imaging (MRI) of the kidney. MRI scans 1, 9, and 17 minutes after intravenous injection of G4 dendrimer. (A) Sham-operated mouse 20 hours after surgery. (B) Cecal ligation and puncture (CLP)-operated mouse 20 hours after surgery.

3- Dendrimers in Antitumor Therapy

Dendrimers molecule has found use as diagnostic reagent for tumour imaging by magnetic resonance imaging and as contrast agent; by varying the size and hydrophilicity and by combining with tumour targeting antibodies, these compounds can be used for a range of specific imaging purpose The drug used should be non-toxic, under non- irradiative condition, thus acting as prodrug when not irradiated.

4- Dendrimers as Gene Transfer agents

Dendrimers as Gene Transfer agents because• Unmodified PAMAM and PPI

dendeimers an form complexes with DNA.

• Partially degraded or fragmented ( activated) dendrumers help transfection efficiency

• Slight excess of primaryamines is benefiocail

5- Dendrimers in targeted drug delivery

Dendrimers have multifunctionality and high potential for drug delivery

applications as they possess high density and wide variety of functional groups on its surface 9-11. Its well defined molecular structure, segmental spherical

construction of dendrimers offers an interesting architecture for dendrimers. If one of these

segments is attached with active drug molecule, the other can be highlighted as targeting group. Due to this double functional group, the plasma level of the drugs will stay at desired level

for longer time period and increase its Pharmaceutical

efficiency.

6- Dendrimers in drug delivery

Dendrimers in drug delivery because • Enhance the aqueous

solubility • Increase circulation half life• Target certain tissue.• Improve transit across

biological barrier .• Slow drug metabolism

7- Dendrimers in transdermal drug delivery

Transdermal drug delivery has come into existence long back. To improve the effectiveness of the drug transdermal drug delivery system was emerged. Drug delivery

through skin to achieve a systematic effect of drug is known as transdermal drug delivery.

8- Dendrimers in oral drug delivery

Oral drug delivery is the most popular and has received more attention in the pharmaceutical field because of ease of production, low cost, convenience of ease of administration and

flexibility in designing of dosage. The oral drug delivery depends on various factors such as type of delivery system, the disease being treated, and the patient, the length of the therapy

and properties of the drug.

9- Dendrimers in ocular drug delivery

10- Dendrimers Fighting the Spread of Diseases

The dendrimer (blue and red) attaches to multiple receptors

(pink) on cell membranes or other biological structures such

as a virus.

The dendrimers (blue and red) in VivaGel interact with

protein structures (yellow) on the surface of HIV, blocking

the interaction of HIV (purple) with healthy human cells

(pink) that results in HIV infection.

11-Dendrimers used for enhancing the solubility

PAMAM dendrimers are expected to have potential applications in enhancing the solubility for drug

delivery systems 1, 2. Dendrimers have hydrophilic exteriors and hydrophilic interiors, which are

responsible for its unimolecular micelle nature.

12- Dendrimers for additives, printing inks and paints

Dendrimers can be used in toners material with additives which require less material than their liquid counterparts. Xerox Corp.

Patented a dry toner compound dendrimers as charge enhancing species in the form of an additive

13- Dendrimers in light harvesting material

14- Dendrimers as Catalyst

15- Supramolecular Architectures

A schematic illustration of supramolecular architectures of self-assembled extended amphiphilic dendrons, developed at Cornell by Ulrich Wiesner, professor of materials science and engineering , and his research team. The illustration shows (A) cubic micelles, (B) two-dimensional lamellar layers, (C) hexagonally arranged cylindrical columns and (D) three-dimensional continuous cubic structures.

16- Dendrimers as a separating agent

A study of variety of compounds synthesized to determine suitability for enhancing boron rejection by reverse osmosis and nanofilteration

membrane to separate born from sea water has been developed. For separation, compound must have amphiphile chemical structure and form micelle in aqueous solution. As a new compound dendrimers with a high

density of functional moiety, is able to form micelle structure which can be easily separated and recovered by ultra filtration membrane.

Dendrimer Superstructures

Dendrimers are repetitively branched molecules. [1] [2] The name comes from the Greek word "δένδρον" (pronounced dendron), which translates to "tree". Synonymous terms for dendrimer include arborols and cascade molecules. However, dendrimer is currently the internationally accepted term. A dendrimer is typically symmetric around the core, and often adopts a spherical three-dimensional morphology. The word dendron is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point. The difference between dendrons and dendrimers is illustrated in figure one, but the terms are typically encountered interchangeably.[3]

Organic Light Emitting Diodes (OLEDs)

• http://www.nature.com/ki/journal/v67/n6/full/4495293a.html#fig1

References

• http://www.chemistry.ohio-state.edu/cgi-bin/brochure?Faculty=parquett

• http://nano.med.umich.edu/Dendrimers.html#dendrimer_introduction

• http://nano.med.umich.edu/Dendrimers.html

• http://www3.interscience.wiley.com/cgi-bin/fulltext/106558159/PDFSTART

• http://www.lbl.gov/Science-Articles/Research-Review/Magazine/2001/Fall/features/02Dendrimers.html

• http://perceco2.chem.upenn.edu/~percec/inthenews/denx.html

• http://www.news.cornell.edu/releases/Sept04/Wiesner.supermolecules.deb.html

• http://www.fda.gov/nanotechnology/powerpoint_conversions .com

• http://www.gade.uni-hd.de/research.php

http://pubs.acs.org/doi/abs/10.1021/nl202220q

• http://www.ncbi.nlm.nih.gov/pubmed/21864902

• http://en.wikipedia.org/wiki/Dendrimers

Thanks for your

listening