Lance J. Twyman

Catalysis inside dendrimers.

Catalytic sites can be placed at the core, at interior positions or at the periphery of a dendrimer. There are many examples of the use of peripherally functionalized dendrimers in catalysis and this subject has been thoroughly reviewed in the recent literature. This review is concerned only with dendrimer based catalysis involving catalytic sites at the core of a dendrimer and within the interior voids. In covering the significant achievements in this area, we have concentrated on examples that highlight key features with respect to positive and/or negative catalytic activity.

Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives

This paper describes the synthesis of three neutral water soluble poly(amidoamine) (PAMAM) dendrimer derivatives. The ability of the two larger dendrimers to bind small acidic hydrophobic molecules is reported. Spectroscopic data and pH behaviour suggested that the acidic hydrophobes were forming stable ion pairs with the dendrimers internal, basic tertiary nitrogens. With respect to forming 1:1 and 2:1 substrate/dendrimer complexes, both of the larger dendrimers were equally efficient at binding. All dendrimer/substrate complexes were completely miscible with water in all proportions (i.e. infinitely water soluble). When the bound substrates are drug moieties, then the resulting complexes could be considered as potential drug delivery systems. Flow calorimetry demonstrated that the dendrimers were able to release their hydrophobic guests when in contact with a biological cell.

THE SYNTHESIS OF WATER SOLUBLE DENDRIMERS, AND THEIR APPLICATION AS POSSIBLE DRUG DELIVERY SYSTEMS

The synthesis of two water soluble dendrimers is described. The formation of water soluble inclusion complexes with a variety of small, hydrophobic guest molecules is also described. Moreover, when these guest molecules are drug moieties, then the resulting drug/dendrimer complexes can be considered ideal candidates for use as novel drug delivery systems.

The Synthesis of Chiral Dendritic Molecules Based on the Repeat Unit L-Glutamic Acid

Abstract The convenient synthesis of a glutamate based dendrimeric molecule is reported. This chiral unsymmetrical dendrimer, contains 15 chiral centres all with identical configurations (L).

A short synthesis of the β-amyloid (Aβ) aggregation inhibitor 3-p-Toluoyl-2-[4′-(3-diethylaminopropoxy)-phenyl]-benzofuran

A short and convenient synthesis of 3-p-toluoyl-2-[4′-(3-diethylaminopropoxy)-phenyl]-benzofuran, an inhibitor of the aggregation of β-amyloid, which is thought to be the underlying cause of Alzheimers disease, is described. A short and convenient synthesis of 3-p-toluoyl-2-[4′-(3-diethylaminopropoxy)-phenyl]-benzofuran, an inhibitor of the aggregation of β-amyloid protein is described.

New evidence that the Alzheimer β-amyloid peptide does not spontaneously form free radicals: An ESR study using a series of spin-traps

The direct formation of free radicals from Abeta has been suggested to be a key neurotoxic mechanism in Alzheimers disease (AD). We have explored the possibility of the spontaneous formation of peptide-derived free radicals during the incubation of Abeta 1-40 by ESR spectroscopy using N-tert-butyl-alpha-phenylnitrone (PBN), 5,5-dimethyl-1-pyrroline N-oxide (DMPO), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), and 3,5-dibromo-4-nitrosobenzenesulfonic acid sodium salt (DBNBS) as spin traps. Employing PBN, we observed spectra during the incubation of beta-amyloid peptide, at 37 degrees C, which included adducts of 2-methyl-2-nitrosopropane (MNP), despite rigorous purification of the PBN before incubation. The formation of some of these adducts was found to be enhanced by ambient laboratory light. Our experiments have led us to propose a hypothesis that PBN undergoes hydrolysis and decomposition in the presence of oxidants, which explains the origin of all of the PBN and MNP adducts observed (even when the PBN is highly purified). Hydrogen peroxide, formed during incubation, could play a major role as an oxidant in these experiments. Of the other three spin traps, only DMPO gave (very weak) spectra, but these could be assigned to its hydroxyl radical adduct, formed as an artifact by the nucleophilic addition of water to DMPO, catalyzed by trace levels of iron ions. Thus, while spectra are observed during our experiments, none of them can be assigned to adducts of radicals derived from the peptide and, therefore, our data do not support the suggestion that radicals are spontaneously formed from beta-amyloid peptide.

Dendrimers and Supramolecular Chemistry

This review details the combination of supramolecular chemistry and dendrimer chemistry. The use of supramolecular chemistry in the synthesis and modification of dendrimers, along with the application of dendrimers in supramolecular chemistry, is described. Many excellent examples exist within these areas; this review includes key examples intended to illustrate the main principles involved, and demonstrate the large number of possibilities presented through combining supramolecular and dendrimer chemistry.

Reversing the stereochemistry of a Diels–Alder reaction: use of metalloporphyrin oligomers to control transition state stability

A cyclic Zn-porphyrin trimer with ethyne and butadiyne links stabilises the thermodynamically disfavoured endo transition state and product of a reversible Diels–Alder reaction; at 30°C the endo adduct is formed rapidly and almost exclusively. Linear porphyrin dimers containing ethyne or butadiyne links show related stereochemical preferences to the corresponding cyclic trimers; substantial rate accelerations are observed despite rotational freedom around the linkers. A qualitative correlation is observed between rate acceleration (i.e., transition state binding) and product binding, and the results are rationalised in terms of host geometry and flexibility.

The synthesis of unsymmetrical PAMAM dendrimers using a divergent/divergent approach

The synthesis of unsymmetrical dendrimers possessing terminal methyl ester groups on one face, and iso-butylamide groups on the opposite face is reported. The final unsymmetrical dendrimers are obtained in high purity and therefore do not require complicated or excessive purification procedures.

Acceleration of an aminolysis reaction using a PAMAM dendrimer with 64 terminal amine groups

Abstract When compared to an equivalent amine concentration (N-acetylethylene diamine, 64 equivalents), the initial rate of a simple deacylation reaction in water was found to be greatly enhanced when using a PAMAM dendrimer with 64 terminal amine groups. This increase in initial rate is largely due to the hydrophobic binding of the substrate within the outer region of the dendrimer. As a consequence of this binding, the substrate is held in close proximity to the reactive amine groups on the surface of the dendrimer. It is this increase in effective molarity that results in an increase in the observed initial rate.