Synthesis, structure, and function of internally functionalized dendrimers

Abstract

The past three decades have witnessed an exponential increase in the structural diversity and applications of dendrimers, spanning across drug delivery and diagnostics, protein, and enzyme mimicry, solubility enhancement, coatings, light harvesting, and catalysis. The dendrimer community has recently focused on internally functionalized dendrimers (IFDs) owing to their advanced design and functionality. The synthesis of IFDs relies on advanced orthogonal chemistries and/or (de)protection schemes, as well as careful purification to minimize polydispersity of composition and molecular weight. The studies published on IFDs, however, lay scattered across the chemical literature, and a comprehensive presentation of structural rationale, synthetic procedures, and technologically relevant applications is missing. To address this need, this review presents a comprehensive collection and discussion of all available studies on IFDs, detailing their methods of synthesis and their structure-function correlations. The wide variety of internal functionalities, including hydroxyl, amine, carboxylic acid, allyl, alkyne, and imidazole groups, enables myriad applications in biochemistry, chemical and biomedical engineering, and material science. Particular focus is given to IFDs that are amenable to modular synthetic strategies, which promote higher synthetic yield and scalability, and therefore possess stronger translational and commercial potential. As such, this review guides research groups pursuing the difficult task of IFD rational design and synthesis providing them a concise roadmap to their mission.

Peptide Multimerization as Leads for Therapeutic Development

“…The construction of these molecules can be achieved in a number of ways but most have a well-defined structure consisting of a central core, an inner shell and outer shell. The central core can consist of a central atom or group of atoms such as a benzene ring [61] or an ethylene diamine [62]. This can branch to multiple layers within the inner shell structure, where each concentric layer is normally referred to as generations with the first being abbreviated as G1 and each subsequent layer G2, G3 and so forth [63] (see Figure 6).…”

Dendrimers as Non-Viral Vectors in Gene-Directed Enzyme Prodrug Therapy

“…The limited drug incorporation into dendrimer cavities, cytotoxicity and inability to control the rate of drug release are among their disadvantages [ 118 ]. For example, in vivo, the use of PAMAM-NH 2 was negatively influenced by their strong cytotoxicity [ 154 ].…”

Unsymmetrical Growth Synthesis of Nontraditional Dendrimers

“…Incorporation of functional groups at the interior branches is one intriguing way to fully exploit the potential of dendrimers. Nevertheless, reports on internally functionalized dendrimers are still exiguous, which might be mainly due to the difficult preparation of building blocks as well as tedious approaches to the targets. − In this context, we envisage the fabrication of nontraditional dendrons from linear ABB-type monomers in an unsymmetrically growing fashion, which will enable the facile distribution of multifunctionality at both of the exterior and interior layers (Scheme B). Additionally, with proper design of initial building blocks, dendrimers assembled from these dendrons probably exhibit diverse three-dimensional forms beyond sphericity.…”