Dendrimers Clicked Together Divergently

ABSTRACT: Dendrimers containing 1,4-triazole linkages between each generation were grown divergently via the Click chemistry inspired Huisgen 1,3-dipolar cycloaddition reaction in the presence of a Cu(I) catalyst. The monomeric unit (1-propargylbenzene-3,5-dimethanol) contained the alkyne functionality, while the core (1,2-bis(2-azidoethoxy)ethane) and growing dendrimers presented the azide groups necessary for this type of Click reaction. The first generation dendrimer was also functionalized with alkyne termini to demonstrate an alternative pathway allowed by this chemistry. Synthesis and characterization, with infrared (IR), 1H and 13C NMR spectroscopies, high-resolution mass spectrometry, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), are reported for these divergently grown dendrimers

PEGylated polymers for medicine: from conjugation to self-assembled systems

Synthetic polymers have transformed society in many areas of science and technology, including recent breakthroughs in medicine. Synthetic polymers now offer unique and versatile platforms for drug delivery, as they can be “bio-tailored” for applications as implants, medical devices, and injectable polymer-drug conjugates. However, while several currently used therapeutic proteins and small molecule drugs have benefited from synthetic polymers, the full potential of polymer-based drug delivery platforms has not yet been realized. This review examines both general advantages and specific cases of synthetic polymers in drug delivery, focusing on PEGylation in the context of polymer architecture, self-assembly, and conjugation techniques that show considerable effectiveness and/or potential in therapeutics

Preparation of orthogonally-functionalized core Click cross-linked nanoparticles

The preparation of well-defined core cross-linked polymeric nanoparticles is reported, utilizing multi-functional dendritic cross-linkers that allow for the effective stabilization of supramolecular polymer assemblies and the simultaneous introduction of reactive groups within the core domain. Amphiphilic diblock copolymers of poly(acrylic acid)-b-poly(styrene) (PAA-b-PS) that contained alkynyl functionality, partially incorporated throughout the hydrophobic PS block segment, were utilized as Click-readied precursors for the formation of polymer micelles. Divergently-grown dendrimers of the zero, first, second and third generations, having increasing numbers of azide terminating groups ((N3)2-[G-0], (N3)4-[G-1], (N3)8-[G-2], and (N3)16-[G-3], respectively), were investigated as cross-linkers via Click reactions with the polymer alkynyl groups to form covalent linkages throughout the micellar core domains, thus forming core cross-linked nanoparticles. All four generations of dendrimers were found to cross-link the micelle core effectively and afford robust nanostructures, whilst simultaneously introducing Click-readied functionalities throughout the hydrophobic domain, which are proposed to be readily available for further chemical modification