Surface dendrimers

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

Dendrimers are complex but well-defined chemical compounds, with a treelike structure, a high degree of order, and the possibility of containing selected chemical units in predetermined sites of their structure [4]. Dendrimer chemistry is a rapidly expanding field for both basic and applicative reasons [5]. From a topological viewpoint, dendrimers contain three different regions core, branches, and surface. Luminescent units can be incorporated in different regions of a dendritic structure and can also be noncovalently hosted in the cavities of a dendrimer or associated at the dendrimer surface as schematically shown in Fig. 1 [6]. 

Because of their proximity, the various functional groups of a dendrimer may easily interact with one another. Interaction can also occur between dendrimer units and molecules hosted in the dendritic cavities or associated to the dendrimer surface. 

The same group modified the linker by using different numbers of carbon atoms (1, 5, 10) to afford variations of the local saccharide concentrations at the dendrimer surface.418 This study was aimed to determine the influence of this linker parameter on the glycodendrimer-protein interactions, the relationship between structure and water solubility, and to investigate amphiphilic properties. 

Many of the applications of dendrimers involve the covalent coupling of other molecules to the dendrimer surface or to points within the branched structure. These attached molecules... 

Figure 7.9 Amine-containing dendrimers can be activated with SPDP to create thiol-reactive derivatives. Alternatively, the pyridyl dithiol group may be reduced to create free thiols on the dendrimer surface for subsequent conjugation.

Use of sulfo-NHS-LC-SPDP or other heterobifunctional crosslinkers to modify PAMAM dendrimers may be done along with the use of a secondary conjugation reaction to couple a detectable label or another protein to the dendrimer surface. Patri et al. (2004) used the SPDP activation method along with amine-reactive fluorescent labels (FITC or 6-carboxytetramethylrhodamine succinimidyl ester) to create an antibody conjugate, which also was detectable by fluorescent imaging. Thomas et al. (2004) used a similar procedure and the same crosslinker to thiolate dendrimers for conjugation with sulfo-SMCC-activated antibodies. In this case, the dendrimers were labeled with FITC at a level of 5 fluorescent molecules per G-5 PAMAM molecule. 

Figure 7.18 Amine-containing dendrimers can be activated with epibromohydrin to result in the formation of reactive epoxy groups on the dendrimer surface. This reactive intermediate then can be used to conjugate with thiol-containing proteins, such as thiolated alkaline phosphatase. The reaction results in the formation of a thioether bond.

The polyvalent nature of dendrimers has been investigated as vehicles for carrying multiple chelator groups to enhance signals in various imaging applications (Barthand Soloway, 1994 Yoo et al., 1999 Kobayashi et al., 2000, 2001 Sato et al., 2001). In addition, in certain chelate-dendrimer constructs, excess amines on the dendrimer surface can aid in the cellular uptake process through charge-mediated endocytosis. 

The above examples of the dendrimeric Gdm complexes clearly illustrate how flexibility of the macromolecule is important in limiting proton relaxivity. This flexibility can originate from the intrinsic flexibility of the macromolecule itself, or/and from the non-rigid coupling of the chelate to the dendrimer surface. In both cases, the surface chelate benefits only partially from the slow motion of the dendrimer (or other macromolecule). In order... 

It is also possible to decorate the dendrimer surfaces with a variety of functional groups such as halo, cyano, carboxy, amino, hydroxy and thiome-thyl.[441 It stands to reason that surface functional-... 

As a consequence of the excluded volume associated with the core, interior and surface branch cells, steric congestion is expected to occur due to tethered connectivity to the core. Furthermore, the number of dendrimer surface groups, Z, amplifies with each subsequent generation (G). This occurs according to geometric branching laws, which are related to core multiplicity (iVc) and branch cell multiplicity (iVb). These values are defined by the following equation ... 

Dendrimer surface congestion can be appraised mathematically as a function of generation, from the following simple relationship ... 

Figure 1.21 Periodic properties for poly(amidoamine) (PAMAM) dendrimers as a function of generation G = 0-10 (I) flexible scaffolding (G = 0-3) (II) container properties (G = 4-6) and (III) rigid surface scaffolding (G = 7-10) various chemo/ physical dendrimer surfaces amplified according to Z = NCN where Nc = core multiplicity, Nb = branch cell multiplicity, G = generation...

Scheme 1 summarizes four different approaches used to characterize dendrimer structures by photophysical and photochemical probes 1. Non-covalent, inter-molecularly bound interior probes - to study the internal cavities and the encapsulation abilities of dendrimers. 2. Non-covalent, intermolecularly bound surface probes - to study surface characteristics of dendrimers. 3. Covalently linked probes on dendrimer surfaces - to study the molecular dynamics of dendrimers. 4. Covalently linked probes at the dendrimer central core - to study the site isolation of the core moiety and define the hydrodynamic volume of dendrimers by the concentric dendrimer shells. Critical literature in these four categories will be described using representative examples. 

The surface morphologies of PAMAM dendrimers have been studied extensively by Turro and co-workers [16-23]. As shown in Scheme 4, one approach was to study the adsorption of organic dye molecules and metal complexes on the dendrimer surface by UY-Vis and fluorescence spectroscopy another approach took advantages of electron transfer processes between two adsorbed species on a single dendrimer surface or between the adsorbed species on a dendrimer surface and other species in aqueous solution. 

Photoinduced Electron Transfer Processes on Dendrimer Surface... 

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