Tuning the Reactivity of Micellar Nanoreactors by Precise Adjustments of the Amphiphile and Substrate Hydrophobicity

Abstract

Polymeric assemblies, such as micelles, are gaining increasing attention due to their ability to serve as nanoreactors for the execution of organic reactions in aqueous media. The ability to conduct organic transformations, which have been traditionally limited to organic media, in water is essential for the further development of important fields ranging from green catalysis to bioorthogonal chemistry. Considering the recent progress that has been made to expand the range of organometallic reactions conducted using nanoreactors, we aimed to gain a deeper understanding of the roles of the hydrophobicity of both the core of micellar nanoreactors and the substrates on the reaction rates in water. Toward this goal, we designed a set of five metal-loaded micelles composed of polyethylene glycol–dendron amphiphiles and studied their ability to serve as nanoreactors for a palladium-mediated depropargylation reaction of four substrates with different log P values. Using dendrons as the hydrophobic block, we could precisely tune the lipophilicity of the nanoreactors, which allowed us to reveal linear correlations between the rate constants and the hydrophobicity of the amphiphiles (estimated by the dendron’s cLog P ). While exponential dependence was obtained for the lipophilicity of the substrates, a similar degree of rate acceleration was observed due to the increase in the hydrophobicity of the amphiphiles regardless of the effect of the substrate’s log P . Our results demonstrate that while increasing the hydrophobicity of the substrates may be used to accelerate reaction rates, tuning the hydrophobicity of the micellar nanoreactors can serve as a vital tool for further optimization of the reactivity and selectivity of nanoreactors.

Developing Pd(ii) based amphiphilic polymeric nanoparticles for pro-drug activation in complex media

“…39 However, they are often employed as implants near the tumour tissue which may need to be surgically removed after treatment. 11 To cope with this issue, metal complexes can be loaded into the hydrophobic domain of polymeric scaffolds to form homogeneous systems such as micelles [40][41][42] , dendrimers 43 , polymerosomes 44 , star polymers 45 , or polymeric nanoparticles. [46][47][48][49] They offer the possibility of systemic administration and can be localised to tumour tissues by EPR-mediated passive and RGD or NGR-based active targeting.…”

Polymeric architecture as a tool for controlling the reactivity of palladium(ii) loaded nanoreactors

“…The two substrates para -nitrophenyl propargyl ether ( PNPPE ) 26 and N-para -nitrophenyl O -propargyl carbamate ( PNACAPE ) 39 with propargyl ether and propargyl carbamate protecting groups, respectively, were synthesized as previously reported. The depropargylation reactions were conducted by adding the substrate, PNPPE (300 μM) and PNACAPE (150 μM) to micellar solutions containing 150 μM and 75 μM Pd II respectively.…”

Amphiphilic Polymer Hydrogel‐supported Catalysts: Tuning the Accessibility to the Catalytic Site by Molecular Jacketing

“…Furthermore, specifically designed dendrimeric systems have been used successfully to prepare a variety of other interesting single‐molecule catalytic systems [7–12] . Recently, amphiphilic dendron‐based block copolymer micelles have been used to demonstrate a strong correlation between reaction rate and the partitioning efficiency of the reactants into the hydrophobic core that carries the Pd catalyst [13] …”

“…[7][8][9][10][11][12] Recently, amphiphilic dendron-based block copolymer micelles have been used to demonstrate a strong correlation between reaction rate and the partitioning efficiency of the reactants into the hydrophobic core that carries the Pd catalyst. [13] In contrast to traditional highly crosslinked polymeric supports, some recent efforts have focussed on developing swellable, lightly crosslinked polymers for anchoring catalysts. Such swellable systems can be fine-tuned to realize optimal outcomes; for instance, they can provide site homogeneity and solution-like kinetics, while at the same time they are readily separable and recyclable.…”