Dendrimer multifunctional

Figure 5.29. PAMAM dendrimer multifunctional conjugates for cancer treatment. The FA group is a folic acid cancer cell target, and FITC is fluorescein isothiocyanate, used as an imaging agent. Also shown (bottom) is the molecular structure for the anticancer drug, taxol, denoting the -OH group that covalently attaches to the dendrimer. Reproduced with permission from Majoros, I. J. Myc, A. Thomas, T Mehta, C. Baker, J. R. Biomacromolecules, 2006, 7, 572. Copyright 2006 American Chemical Society.

PAMAM dendrimers are synthesized in a multistep process. Starting from a multifunctional amine (for example ammonia, ethylenediamine, or tris(2-amino-ethyl)amine) repeated Michael addition of methylacrylate and reaction of the product with ethylenediamine leads to dendrimers of different generation numbers [1,9]. Two methylacrylate monomers are added to each bifunctional ethylenediamine generating a branch at each cycle. Unreacted ethylenediamine has to be completely removed at each step to prevent the initiation of additional dendrimers of lower generation number. Excess methylacrylate has also to be removed. Bridging between two branches of the same or of two different dendrimers by ethylenediamine can also be a problem, and has to be avoided by choosing appropriate reaction conditions. 

A potential source of structural imperfection is the rapid increase of reactive groups as growth is pursued. Their incomplete conversion leads to defects inside the molecule [27]. In convergent-iterative syntheses these problems are avoided by directing the dendritic growth from the surface inwards to a focal point. In a final step several dendrons are connected with a multifunctional core to yield the desired dendrimer (Fig. 9). 

Highly non-linear homopolymers can even be synthesized exclusively from monomers of functionality higher than 2. Dendrimers (from ancient Greek "SavSpov" — tree) are obtained when all the reaction sites of each branch links to another one and when all branches exhibit the same length. Whereas, hyperbranched (HB) polymers result from incomplete reaction of each multifunctional monomer, see Figure 9. 

Islam, M.T., Majoros, I.J., and Baker Jr., J.R. (2005) HPLC analysis of PAMAM dendrimer based multifunctional devices. J. Chrom. B822, 21-26. 

Dendrimers represent a model for compact multifunctional precursor of polymer networks. Polymer networks prepared by crosslinking of dendrimers were suggested several years ago [64]. Since then, some experimental work has been performed, but there are still many points in structural interpretation of network formation and network properties that are not well understood. 

Linear-dendritic star copolymers [5], most frequently obtained via processes in which dendrimers function as multifunctional initiator cores for the poly-... 

Dendrimer synthesis involves a repetitive building of generations through alternating chemistry steps which approximately double the mass and surface functionality with every generation as discussed earlier [1-4, 18], Random (statistical) hyperbranched polymer synthesis involves the self-condensation of multifunctional monomers, usually in a one-pot single series of covalent formation events [31], Random hyperbranched polymers and dendrimers of comparable molecular mass have the same number of branch points and terminal units, and any application requiring only these two characteristics could be satisfied by either architectural type. Since dendrimer synthesis requires many defined synthetic and process purification steps while hyperbranched synthesis may involve a one-pot synthetic step with no purification, the dendrimers will necessarily be a much more expensive material to produce. 

The future will undoubtedly show considerable activity in the field of (metal-lo)dendrimers, not only because of the beauty of the structures and the synthetic challenge their preparation involves, but also because of their usefulness in fundamental applications and applied science. Finally, while we are learning to design, synthesize and apply these multimetallic catalytic objects (either soluble or insoluble), other challenges may include preparation of multifunctional catalytic prototypes by including, e.g. a substrate recognition function next to the catalytically active site. 

Its design versatility, as generic dendrons may be prepared to be used later as building blocks in conjunction with other reactive molecules, or coupled to a multifunctional core to afford functional dendrimers, dendritic-linear hybrids, dendronized polymers, etc. This may be a particularly significant advantage if the coupled reactive or core molecule is itself sensitive to the reaction conditions used in the multiple steps of the iterative synthesis of a dendrimer. 

Majoros IJ, Myc A, Thomas T, Mehta CB, Baker JR (2005). Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy. J. Med Chem. 48 5892-5899. 

Dendrimers have a star-like centre (functionality e.g. 4) in contrast to a star however, the ends of the polymer chains emerging from the centre again carry multifunctional centres that allow for a bifurcation into a new generation of chains. Multiple repetition of this sequence describes dendrimers of increasing generation number g. The dynamics of such objects has been addressed by Chen and Cai [305] using a semi-analytical treatment. They treat diffusion coefficients, intrinsic viscosities and the spectrum of internal modes. However, no expression for S(Q,t) was given, therefore, up to now the analysis of NSE data has stayed on a more elementary level. 

Figure 13.13 Multifunctional anticancer poly(amido amine) (PAMAM) dendrimers. Clockwise from top diol, taxol, fluorescein isothiocyanate, foUc acid, and acetyl groups.

Vutukuri DR, Sivanandan K, Tha3uimanavan S. Synthesis of dendrimers with multifunctional periphery using an ABB monomer. Chem Commun 2003 796-797. 

Different architectures, such as block copolymers, crosslinked microparticles, hyperbranched polymers and dendrimers, have emerged (Fig. 7.11). Crosslinked microparticles ( microgels ) can be described as polymer particles with sizes in the submicrometer range and with particular characteristics, such as permanent shape, surface area, and solubility. The use of dispersion/emulsion aqueous or nonaqueous copolymerizations of formulations containing adequate concentrations of multifunctional monomers is the most practical and controllable way of manufacturing micro-gel-based systems (Funke et al., 1998). The sizes of CMP prepared in this way vary between 50 and 300 nm. Functional groups are either distributed in the whole CMP or are grafted onto the surface (core-shell, CS particles). 

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