Access to At- andI-radiolabeled compounds in excellent RCCs and RCYs was achieved in just 10 min at room temperature using a Cu catalyst. The reaction conditions are applicable to a broad class of aryl and heteroaryl boronic reagents with varying steric and electronic properties as well as late-stage astatination and iodination of anticancer PARP inhibitors. This protocol eliminates the traditional need for toxic organotin reagents, elevated temperatures, and extended reaction times, providing a more practical and environmentally friendly approach to developing α-emitting radiotherapeutics.

Alpha-emitters can be pharmacologically delivered for irradiation of single cancer cells, but cellular lethality could be further enhanced by targeting alpha-emitters directly to the nucleus. PARP-1 is a druggable protein in the nucleus that is overexpressed in neuroblastoma compared with normal tissues and is associated with decreased survival in high-risk patients. To exploit this, we have functionalized a PARP inhibitor (PARPi) with an alpha-emitter astatine-211. This approach offers enhanced cytotoxicity from conventional PARPis by not requiring enzymatic inhibition of PARP-1 to elicit DNA damage; instead, the alpha-particle directly induces multiple double-strand DNA breaks across the particle track. Here, we explored the efficacy of [ 211 At]MM4 in multiple cancers and found neuroblastoma to be highly sensitive in vitro and in vivo. Furthermore, alpha-particles delivered to neuroblastoma show antitumor effects and durable responses in a neuroblastoma xenograft model, especially when administered in a fractionated regimen. This work provides the preclinical proof of concept for an alphaemitting drug conjugate that directly targets cancer chromatin as a therapeutic approach for neuroblastoma and perhaps other cancers.

Development of CCC-NHC pincer Co complexes via transmetalation from Zr is reported. Formation of these air-stable Co(iii) complexes was achieved through use of a CoCl2 or Co(acac)3in situ or with a discrete CCC-NHC pincer Zr transmetallating agent. Preliminary activity in the hydroboration of styrene is reported. This facile methodology will further the development of CCC-NHC pincer first-row transition metal complexes.

A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 122–25.6 nM) and were highly selective for D3R vs D3R (ranging from 264–905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10–20 minute benchtop C–N cross-coupling methodology, affording a broad range of arylated diazaspiro pre-cursors.

A facile Pd-catalyzed methodology providing an efficient synthetic route to biologically relevant arylpiparazines under aerobic conditions is reported. Electron donating and sterically inducing aryl chlorides were aminated to afford yields up to 97%, with examples using piperazine as solvent, illustrating an eco-friendly, cost-effective synthesis of these privileged structures.