Bioorthogonal catalysis using transition-metal-based complexes (TMCs) is a promising approach for converting substrates to desired products in complex cellular media. Notably, the in situ activation ...of prodrugs or synthesis of active drugs with the aim to complement existing treatments in diseases such as cancer has received significant attention. Whereas the focus has initially been on optimizing ligands to enhance the activity and stability of the metal complexes, more recently the benign effects of compartmentalization of the catalyst into homogeneous or heterogeneous scaffolds have been unveiled. Such tailor-made carrier materials not only afford active catalysts but also permit to guide the catalyst to the site of interest in in vivo applications. This review will emphasize the potential of synthetic amphiphilic polymers that form compartmentalized nanostructures for TMCs. The use of amphiphilic polymers is well established in the field of nanomedicine for i.e. drug delivery purposes, but their application as homogeneous carrier materials for TMCs has been less well explored. Since synthetic polymers are readily functionalized with ligands and targeting moieties, they can act as versatile catalysts carriers. After a short overview of the state-of-the-art in bioorthogonal catalysis using ligand-based TMCs, we summarize the advances in using homogeneous natural polymers as scaffolds and synthetic heterogeneous carrier materials for bioorthogonal catalysis. We end this review by highlighting the recent advances of catalysis in complex media using TMCs embedded in nanostructures formed by amphiphilic synthetic polymers. The combination of polymer science and homogeneous catalysis with the field of nanomedicine may open up new opportunities for advancing the exciting field of bioorthogonal catalysis for therapeutic applications.
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•Overview of natural and synthetic polymer scaffolds for embedding transition metals for bio-orthogonal catalysis.•Review of the potential of synthetic amphiphilic polymers for bio-orthogonal catalysis in complex media.•Summary of the challenges to bring bio-orthogonal catalysis from in vitro to in vivo conditions.
A versatile and scalable strategy is reported for the rapid generation of block copolymer libraries spanning a wide range of compositions starting from a single parent copolymer. This strategy ...employs automated and operationally simple chromatographic separation that is demonstrated to be applicable to a variety of block copolymer chemistries on multigram scales with excellent mass recovery. The corresponding phase diagrams exhibit increased compositional resolution compared to those traditionally constructed via multiple, individual block copolymer syntheses. Increased uniformity and lower dispersity of the chromatographic libraries lead to differences in the location of order–order transitions and observable morphologies, highlighting the influence of dispersity on the self-assembly of block copolymers. Significantly, this separation technique greatly simplifies the exploration of block copolymer phase space across a range of compositions, monomer pairs, and molecular weights (up to 50000 amu), producing materials with increased control and homogeneity when compared to conventional strategies.
The hexagonally close-packed (HCP) sphere phase is predicted to be stable across a narrow region of linear block copolymer phase space, but the small free energy difference separating it from ...face-centered cubic spheres usually results in phase coexistence. Here, we report the discovery of pure HCP spheres in linear block copolymer melts with A = poly(2,2,2-trifluoroethyl acrylate) (“F”) and B = poly(2-dodecyl acrylate) (“2D”) or poly(4-dodecyl acrylate) (“4D”). In 4DF diblocks and F4DF triblocks, the HCP phase emerges across a substantial range of A-block volume fractions (circa f A = 0.25–0.30), and in F4DF, it forms reversibly when subjected to various processing conditions which suggests an equilibrium state. The time scale associated with forming pure HCP upon quenching from a disordered liquid is intermediate to the ordering kinetics of the Frank–Kasper σ and A15 phases. However, unlike σ and A15, HCP nucleates directly from a supercooled liquid or soft solid without proceeding through an intermediate quasicrystal. Self-consistent field theory calculations indicate the stability of HCP is intimately tied to small amounts of molar mass dispersity (Đ); for example, an HCP-forming F4DF sample with f A = 0.27 has an experimentally measured Đ = 1.04. These insights challenge the conventional wisdom that pure HCP is difficult to access in linear block copolymer melts without the use of blending or other complex processing techniques.
Enzymatic DNA synthesis (EDS) is a promising benchtop and user-friendly method of nucleic acid synthesis that, instead of solvents and phosphoramidites, uses mild aqueous conditions and enzymes. For ...applications such as protein engineering and spatial transcriptomics that require either oligo pools or arrays with high sequence diversity, the EDS method needs to be adapted and certain steps in the synthesis process spatially decoupled. Here, we have used a synthesis cycle comprising a first step of site-specific silicon microelectromechanical system inkjet dispensing of terminal deoxynucleotidyl transferase enzyme and 3' blocked nucleotide, and a second step of bulk slide washing to remove the 3' blocking group. By repeating the cycle on a substrate with an immobilized DNA primer, we show that microscale spatial control of nucleic acid sequence and length is possible, which, here, are assayed by hybridization and gel electrophoresis. This work is distinctive for enzymatically synthesizing DNA in a highly parallel manner with single base control.
