A new catalytic manifold that merges photoredox with nickel catalysis in aqueous solution is presented. Specifically, the combination of a highly active, yet air-stable, nickel precatalyst with a new electron-deficient pyridyl carboxamidine ligand was key to the development of a water-compatible nickel catalysis platform, which is a crucial requirement for the preparation of DNA-encoded libraries (DELs). Together with an iridium-based photocatalyst and a powerful light source, this dual catalysis approach enabled the efficient decarboxylative arylation of α-amino acids with DNA-tagged aryl halides. This C(sp 2 )−C(sp 3 ) coupling tolerates a wide variety of functional groups on both the amino acid and the aryl halide substrates. Due to the mild and DNA-compatible reaction conditions, the presented transformation holds great potential for the construction of DELs. This was further evidenced by showing that well plate-compatible LED arrays can serve as competent light sources to facilitate parallel synthesis. Lastly, we demonstrate that this procedure can serve as a blueprint toward the adaptation of other established nickel metallaphotoredox transformations to the idiosyncratic requirements of a DEL.

The synthesis of a supramolecular double hydrophilic glucose responsive block copolymer (DHBC) held together by cucurbit [8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. The supramolecular block copolymer assembly consists of poly(Nisopropylacrylamide) (PNIPAAm) and poly(acrylamidophenyl boronic acid) (PAAPBA) as temperature and glucose responsive blocks, respectively, and poly(dimethylacrylamide) (PDMAAm) as a hydrophilic block. Drug release studies of insulin-loaded micelles using three external triggers were studied with release of insulin achieved by changing temperature, glucose concentration or by adding a competitive guest for CB[8]. This system offers good control over the release of insulin under physiological conditions (pH 7.4, 37 C). These exciting results suggest that this system could be a model for a clinically relevant drug delivery vehicle for diabetic treatment. Fig. 1 Formation of the boronic acid-glucose complex.

DNA encoded libraries (DEL) have shown promise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on‐DNA chemistries to incorporate medicinally relevant and C−S, C−P and N−S linkages into DELs, which are underrepresented in the canonical methods.

The on-DNA synthesis of highly substituted cyclobutanes was achieved through a photocatalytic [2 + 2] cycloaddition reaction in aqueous solution. Readily available DNA-tagged styrene derivatives were reacted with structurally diverse cinnamates in the presence of an iridium-based photocatalyst, Ir(ppy) 2 (dtbbpy)PF 6 , to forge two new C(sp 3 )−C(sp 3 ) bonds. This transformation was demonstrated to have excellent functional group tolerance and allowed for the facile installation of a variety of heteroaromatic substituents on a densely functionalized cyclobutane scaffold.

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