Linear-dendron (LD) hybrids are macromolecules comprising a linear polymer or oligomer conjugated at one or both termini with branched macromolecules called dendrons. Since their introduction approximately 2 decades ago, tremendous progress has been made in their synthesis, the study of their self-assembly, and toward their application in a variety of fields. This highlight is focused on aqueous assemblies of LD hybrids where function is imparted by the dendron, linear component, or both. These functions include the encapsulation and release of drug molecules, enhancement of cell uptake and targeting of specific tissues, and the stabilization of enzymes for catalysis. In addition, many stimuli-responsive LD hybrids that undergo changes in response to light, enzymes, pH, temperature, redox potential, or even multiple stimuli have been developed. LD hybrids can also be used to form networks via cross-linking reactions. Described here are the structure-property relationships underlying the functions of these materials, along with their potential applications.

The synthesis of arborescent polymers with poly(cbenzyl L-glutamate) (PBG) side chains was achieved through successive grafting reactions. The linear PBG building blocks were produced by the ring-opening polymerization of c-benzyl L-glutamic acid N-carboxyanhydride initiated with n-hexylamine. The polymerization conditions were optimized to minimize the loss of amino chain termini in the reaction. Acidolysis of a fraction of the benzyl groups on a linear PBG substrate and coupling with linear PBG using a carbodiimide/hydroxybenzotriazole promoter system yielded a comb-branched or generation zero (G0) arborescent PBG. Further partial deprotection and grafting cycles led to arborescent PBG of generations G1 to G3. The solvent used in the coupling reaction had a dramatic influence on the yield of graft polymers of generations G1 and above, dimethylsulfoxide being preferable to N,Ndimethylformamide. This grafting onto scheme yielded welldefined (M w /M n 1.06), high molecular weight arborescent PBG in a few reaction cycles, with number-average molecular weights and branching functionalities reaching over 10 6 and 290, respectively, for the G3 polymer. a-Helix to coiled conformation transitions were observed from N,N-dimethylformamide to dimethyl sulfoxide solutions, even for the highly branched polymers.

Amphiphilic copolymers were obtained by grafting arborescent poly(γ‐benzyl l‐glutamate) (PBG) cores of generations G1–G3 with polyglycidol, poly(ethylene oxide) (PEO), or poly(l‐glutamic acid) (PGA) chain segments. The PBG substrates were synthesized by two methods: (1) subjecting PBG samples with a dispersity Đ = Mw/Mn < 1.1 to partial acidolysis of the benzyl ester groups, to produce randomly distributed carboxylic acid functionalities, and (2) using PBG chains containing a glutamic acid di‐tert‐butyl ester initiator fragment in the last grafting cycle of the PBG core synthesis, and selective acidolysis of the tert‐butyl ester groups to obtain substrates with carboxylic acid termini. Linear polymers with Đ < 1.20 and a primary amine terminus were also synthesized to serve as hydrophilic shell materials: Polyglycidol and PEO by anionic polymerization, and PGA by N‐carboxyanhydride ring‐opening polymerization. These polymers, combined with the two different PGB substrate types, allowed the evaluation of the usefulness of random versus chain‐end grafting in producing arborescent copolymers useful as unimolecular micelles in organic and aqueous media. Size exclusion chromatography served to determine the grafting yield, molar mass, dispersity, and branching functionality of the copolymers. Dynamic light scattering measurements provided information on their aggregation behavior in aqueous environments. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1197–1209

A series of arborescent poly(L-glutamic acid)s of generations 0 to 3 (PGA(GY) with Y = 0−3) were randomly labeled with 1-pyrenemethylamine to yield several Py-PGA(GY) constructs with pyrene contents ranging between 2.5 and 22 mol %. The density (ρ) of the interior of the PGA(GY) samples was estimated in N,Ndimethylformamide (DMF) and dimethyl sulfoxide (DMSO) by conducting gel permeation chromatography and dynamic light scattering experiments to determine their molar mass and hydrodynamic diameter, respectively. It was determined that ρ increased with the generation number from PGA(G1) to PGA(G2), which promoted more contacts between the pyrene labels. The increase in the number of pyrene−pyrene contacts was quantified with the parameter N blob obtained by analysis of the fluorescence decays for the Py-PGA(GY) samples in DMF and DMSO. In the analysis, N blob represented the number of structural units, i.e., glutamic acid residues, comprised inside the volume probed by an exited pyrene, termed a blob. Inside a blob, pyrene excimer formation (PEF) could occur upon diffusive encounters between an excited-and a ground-state pyrene label. It was found that N blob increased with the generation number, and larger N blob values were retrieved in DMSO as compared to DMF because the oligo(L-glutamic acid) (OGA) side chains in the PGA(GY) samples underwent partial loss of helicity in DMSO, which increased their hydrodynamic volume and forced the side chains closer to each other, thus resulting in more pyrene−pyrene contacts and larger N blob values. The trends observed for N blob in DMF as a function of the generation number could be correlated theoretically with the degree of polymerization of the OGA side chains used to prepare the PGA(GY) samples and their internal density ρ. The good agreement found between the theoretical and experimental N blob values confirms that pyrene is an excellent probe to study the complex interior of partially structured polypeptides.

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