Dendrimers are repeatedly branched
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
s. The huge number of papers on dendritic architectures such as dendrimers, dendronized, hyperbranched and brush-polymers has generated a vast variety of inconsistent terms and definitions making a clear and concise unfolding of this topic highly difficult. The purpose of this section is to provide the vocabulary required for the description of chemical and physical phenomena as well as application aspects associated with the research in the area of dendritic molecules.
Dendritic molecules are repeatedly branched species that are characterised by structural perfection. This is based on the evaluation of both symmetry and polydispersity. The field of dendritic molecules can roughly be divided into low-molecular weight and high-molecular weight species. The first category includes dendrimers and dendrons, and the second includes dendronised polymers, hyperbranched polymers and brush-polymers (called also bottle-brushes).
The name comes from the
GreekGreek , an independent branch of the Indo-European family of languages, is the language of the Greeks. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. In its ancient form, it is the language of classical...
"δενδρον"/
dendron, meaning "tree". Synonymous terms are arborols and cascade molecules. Dendrimer is an internationally accepted term.
Dendrimers and dendrons are repeatedly branched, monodisperse and usually highly symmetric compounds. There is no apparent distinction between the definitions dendrimer and dendron. A dendron usually contains a single chemically addressable group called the focal point.
Because of the absence of molar mass distribution, high-molar-mass dendrimers and dendrons are macromolecules but not polymers.
The first dendrimers were synthesised divergently by Vögtle in 1978, by Denkewalter and coworkers at Allied Corporation as polylysine dendrimers in 1981, by Tomalia at Dow Chemical in 1983 and in 1985, and by Newkome in 1985. In 1990 a convergent synthesis was introduced by Fréchet. Dendrimers then experienced an explosion of scientific interest because of their unique molecular architecture (Fig 1). This resulted in more than 5,000 scientific papers and patents published by the end of 2005.
Properties and applications
The properties of dendrimers are dominated by the functional groups on the molecular
surfaceIn mathematics, specifically in topology, a surface is a two-dimensional topological manifold. The most familiar examples are those that arise as the boundaries of solid objects in ordinary three-dimensional Euclidean space R
3 — for example, the surface of a ball...
, however, there are examples of dendrimers with internal functionality .Dendritic encapsulation of functional molecules allows for the isolation of the active site, a structure that mimics the structure of active sites in biomaterials because dendritic scaffolds separate internal and external functions.. For example, a dendrimer can be water-soluble when its
end-groupAn end-group in polymer chemistry is a constitutional unit that is an extremity of a macromolecule or oligomer molecule. For example the end-group of a PET polyester may be an alcohol group or a carboxylic acid group...
is a hydrophilic group, like a
carboxyl groupA carboxyl group is a set of four atoms bonded together and present in carboxylic acids, including amino acids. Usually abbreviated as either CO2H or COOH, this set of atoms constitutes a functional group. In every carboxyl group the carbon atom is attached to an oxygen atom by a...
. It is theoretically possible to design a water-soluble dendrimer with internal hydrophobicity, which would allow it to carry a hydrophobic
drugA drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
in its interior. Recently it has been shown that redox-active nanoparticles can be synthesized, placing the redox molecules between the nanoparticle core and the dendritic wedges; despite their isolation, some of the redox molecules (COOH in this case) remained uncoupled, and thus still reactive.
Another property is that the volume of a dendrimer increases when it has a positive charge. If this property can be applied, dendrimers can be used for drug delivery systems (DDS) that can give medication to the affected part inside a patient's body directly.
Photonic excited molecules
The inside of a dendrimer has a unique chemical environment because of its high
densityThe density of a material is defined as its mass per unit volume. The symbol of density is ρ .- Formula :Mathematically:where: is the density, is the mass, is the volume....
. From this property, it has been discovered that
azobenzeneAzobenzene is a chemical compound composed of two phenyl rings linked by a N=N double bond. The term 'azobenzene' or simply 'azo' is often used to refer to a wide class of molecules that share the core azobenzene structure, with different chemical functional groups extending from the phenyl rings. ...
is
photoisomerizedIn chemistry, photoisomerization is molecular behavior in which structural change between isomers is caused by photoexcitation. Both reversible and irreversible photoisomerization reactions exist. However, the word "photoisomerization" usually indicates a reversible process...
by very weak
infraredInfrared radiation is electromagnetic radiation whose wavelength is longer than that of visible light , but shorter than that of terahertz radiation and microwaves...
rays when covered by a dendrimer . Through the discovery of a function that catches light and conveys this
energyIn physics, energy is a scalar physical quantity that describes the amount of work that can be performed by a force, an attribute of objects and systems that is subject to a conservation law...
using
excitationExcitation or excitement can refer to:* The excited state of an atom* The excitation provided with an electrical generator or alternator* in ethology, provoking of the emotional state of excitement or agitation**Psychomotor agitation...
of the molecule, attempts have recently been made to synthesize dendrimers that insert
porphyrinPorphyrins are a group of organic compounds of which many occur in nature, most well-known as the pigment in red blood cells. They are heterocyclic macrocycles characterised by the presence of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges...
, absorb light, and
photosynthesizePhotosynthesis is a process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of Bacteria, but not in Archaea...
artificially. In addition, the development of
organic electroluminescent deviceAn organic light emitting diode , also light emitting polymer and organic electro luminescence , is a light-emitting diode whose emissive electroluminescent layer is composed of a film of organic compounds. The layer usually contains a polymer substance that allows suitable organic compounds to...
s and their applications has been undertaken by researchers all over the world.
Synthesis
In the
synthesisIn chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
of dendrimers,
monomerA monomer is a small molecule that may become chemically bonded to other monomers to form a polymer...
s lead to a
monodisperseA collection of objects are called monodisperse, or monosized, if they have the same size, and shape when discussing particles, and the same mass, when discussing polymers...
polymer, tree-like, or generational structure. There are two defined methods of dendrimer synthesis,
divergent synthesisIn chemistry a divergent synthesis is a strategy with the aim to improve the efficiency of chemical synthesis. It is often an alternative to convergent synthesis or linear synthesis....
and
convergent synthesisIn chemistry a convergent synthesis is a strategy that aims to improve the efficiency of multi-step chemical synthesis, most often in organic synthesis...
. Divergent syntheses assemble the molecule from the core, extending radially to the periphery and in contrast convergent methods start at the surface and proceed inwards, before the attachment of pre-synthesised dendrons to the core.
However, because a repeated
reactionReaction may refer to:*Response to another event*Adverse drug reaction*Chemical reaction*Light reaction*Nuclear reaction*Reaction , as defined by Newton's third law*Reflex reaction*Emotional reaction*Reactionary, a political tendency...
which consists of many steps is needed to protect the
active siteThe active site of an enzyme contains the catalytic and binding sites. The structure and chemical properties of the active site allow the recognition and binding of the substrate....
, it is difficult to synthesize dendrimers even if both methods are used. This is why there are obstacles to the synthesis of large quantities of dendrimers. Up to date, there are only a few companies that sell dendrimers; Polymer Factory commercializes biocompatible bis-MPA dendrimers and Dendritech is the only kilogram-scale producers of PAMAM dendrimers.
The original Newkome dendrimer or
arborol (1985) started by
nucleophilic substitutionIn organic and inorganic chemistry, nucleophilic substitution is a fundamental class of substitution reaction in which an "electron rich" nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom attached to a group or atom called the leaving group; the...
of 1-bromopentane by
triethyl sodiomethanetricarboxylate in
dimethylformamideDimethylformamide is the organic compound with the formula
2NCH. Commonly abbreviated DMF , this colourless liquid is miscible with water and the majority of organic liquids. DMF is a common solvent for chemical reactions...
and
benzeneBenzene, or benzol, is an organic chemical compound with the molecular formula C6H6. It is sometimes abbreviated Ph–H. Benzene is a colorless and highly flammable liquid with a sweet smell and a relatively high melting point...
. The
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
groups were then reduced by
lithium aluminium hydrideLithium aluminium hydride , commonly abbreviated to LAH, is a reducing agent used in organic synthesis. It is more powerful than the related reagent sodium borohydride due to the weaker Al-H bond compared to the B-H bond...
to a
triolIn chemistry, an alcohol is any organic compound in which a hydroxyl group is bound to a carbon atom of an alkyl or substituted alkyl group. An important group of acohols is formed by the simple acyclic alcohols, the general formula for which is C
nH
2n+1OH...
in a deprotection step. Activation of the chain ends was achieved by converting the alcohol groups to tosylate groups with tosyl chloride and
pyridinePyridine is a simple aromatic heterocyclic organic compound with the chemical formula C
5H
5N used as a precursor to agrochemicals and pharmaceuticals, and is also an important solvent and reagent. It is structurally related to benzene, wherein one CH group in the aromatic...
. The tosyl group then served as
leaving groupIn chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br-, and I-, and sulfonate esters,...
s in another reaction with the tricarboxylate, forming generation two.
This sequence can be repeated many times.
Click chemistry
Dendrimers have been prepared via
click chemistryClick chemistry is a chemical philosophy introduced by K. Barry Sharpless in 2001 and describes chemistry tailored to generate substances quickly and reliably by joining small units together...
employing
Diels-Alder reactionThe Diels-Alder reaction is an organic chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can proceed even if some of the atoms in the newly-formed ring are not carbon...
s , thiol-ene reactions and azide-alkyne reactions . An example is the synthesis of certain polyphenylene dendrimers :