Intramacromolecular Conformational Changes in Low Generation PAMAM Dendrimers Probed by Pyrene Excimer Formation.

Pyrene excimer formation (PEF) was used to probe the intramacromolecular conformational change experienced by low generation pyrene-labeled PAMAM dendrimers referred to as PyCX-PAMAM-GY, where (=4, 8, or 12) and (=0, 1, or 2) represent the number of atoms in the pyrenyl linker and the dendrimer generation, respectively. Each sample was studied in ,-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) with and without 5 mM HCl. Global analysis of the monomer and excimer time-resolved fluorescence decays using the model free analysis (MFA) yielded the average rate constant of excimer formation, ⟨⟩, which was compared with the local pyrene concentration ([]) of the PyCX-PAMAM-GY samples calculated by assuming that the oligomeric segments constituting the dendrimer's interior obeyed Gaussian statistics.

Molecular Sieving with PEGylated Dendron-Protein Conjugates.

A series of generation 3-5 dendrons based on a bis(2,2-hydroxymethylpropionic acid) (bis-MPA) scaffold bearing three respective lengths of linear poly(ethylene glycol) at their periphery and a dibenzocyclooctyne unit at their core was prepared. These dendrons were appended to the surface of azide-decorated α-chymotrypsin (α-CT) via strain-promoted azide-alkyne cycloaddition to yield a library of dendron-protein conjugates. These conjugates were characterized by FT-IR and NMR spectroscopy and were imaged using cryo-electron microscopy.

Direct Measure of the Local Concentration of Pyrenyl Groups in Pyrene-Labeled Dendrons Derived from the Rate of Fluorescence Collisional Quenching.

The model-free analysis (MFA) was applied to measure the average rate constant (<>) for pyrene excimer formation (PEF) in a series of pyrene-labeled dendrons referred to as Py-G(), where (= 2) is the number of pyrenyl labels born by a dendron of generation ranging from 1 to 6. <> was measured in four different solvents, namely tetrahydrofuran (THF), toluene, ,-dimethylformamide (DMF), and dimethylsulfoxide (DMSO). <> was found to increase linearly with increasing local pyrene concentration ([]), where [] had been determined mathematically for the Py-G() dendrons.

Globular Polymer Grafts Require a Critical Size for Efficient Molecular Sieving of Enzyme Substrates.

A series of 2,2-bis(hydroxymethyl)propionic acid dendrons of generation 2 through 8 having a strained cyclooctyne at the core and hydroxy groups at the periphery were prepared by a divergent method and used to functionalize azide-decorated α-chymotrypsin. The ability of the appended dendrons to selectively block enzyme activity (through a molecular sieving effect) was investigated using a small molecule substrate (benzoyl-l-tyrosine p-nitroanilide), as well as two proteins of different size (casein and bovine serum albumin). Additionally, the ability of dendrons to block complexation with a chymotrypsin antagonist, α-antichymotrypsin, was investigated, and it was found that the dendron coating effectively prevented inhibition by this antagonist.

Reproducible Dendronized PEG Hydrogels via SPAAC Cross-Linking.

A common issue with hydrogel formulations is batch-to-batch irreproducibility originating from poorly defined polymer precursors. Here, we report the use of dendritic polymer end-groups to address this issue and maintain reproducibility between batches of poly(ethylene glycol) (PEG) hydrogels. Specifically, we synthesized two end-functionalized PEG chains: one with azide-terminated first- and second-generation dendrons and the other with strained cyclooctynes.

Synthesis, Radiolabeling, and In Vivo Imaging of PEGylated High-Generation Polyester Dendrimers.

A fifth generation aliphatic polyester dendrimer was functionalized with vinyl groups at the periphery and a dipicolylamine Tc(I) chelate at the core. This structure was PEGylated with three different molecular weight mPEGs (mPEG160, mPEG350, and mPEG750) using thiol-ene click chemistry. The size of the resulting macromolecules was evaluated using dynamic light scattering, and it was found that the dendrimer functionalized with mPEG750 was molecularly dispersed in water, exhibiting a hydrodynamic diameter of 9.