We report that the Piers-Rubinsztajn reaction enables rapid deprotection of aryl alkyl ethers under ambient conditions. This chemistry leverages tris(pentafluorophenyl)borane and silyl hydrides to convert aryl methyl ethers to siloxanes, which can then be cleaved using 1 % HCl in EtOH. We examined 26 derivatives and routinely obtained yields > 85 %, even in the presence of sterically demanding groups and complex substrate structures. Other alkyl ethers including ethyl, propyl, isopropyl, tert-butyl, and benzyl groups were also easily removed.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are ongoing global health burdens. Glomerular filtration rate (GFR) is the gold standard measure of kidney function, with clinical estimates providing a global assessment of kidney health without spatial information of kidney- or region-specific dysfunction. The addition of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to the anatomical imaging already performed would yield a ‘one-stop-shop’ for renal assessment in cases of suspected AKI and CKD. Towards urography by DCE-MRI, we evaluated a class of nitrogen-centered organic radicals known as verdazyls, which are extremely stable even in highly reducing environments. A glucose-modified verdazyl, glucoverdazyl, provided contrast limited to kidney and bladder, affording functional kidney evaluation in mouse models of unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN). Imaging outcomes correlated with histology and hematology assessing kidney dysfunction, and glucoverdazyl clearance rates were found to be a reliable surrogate measure of GFR.

In North America, intravascular optical coherence tomography (IV-OCT) is performed every few minutes to evaluate atherosclerotic plaques and guide stent placement. Currently, IV-OCT is limited to anatomical imaging, providing structural information about atherosclerotic plaque morphology, thrombus and dissection. Earlier detection and risk stratification would be possible through molecular characterization of endothelium, but necessitates a purpose-engineered IV-OCT contrast agent. We developed gold superclusters (AuSC) tailored to clinical instrumentation and integrated into clinically relevant workflows. AuSC are aqueously dispersible clusters of closely packed small gold nanoparticles, affording plasmon hybridization to maximize light scattering at the IV-OCT laser line (~1350 nm). A polymer coating fosters AuSC uniformity and provides a functionalizable handle, which we targeted to intravascular P-selectin, an early vascular endothelial marker of inflammation. In a rat model of intravascular inflammation, P-selectin-targeted AuSC facilitated IV-OCT molecular imaging, where the strength of the signal correlates with the severity of vascular inflammation. AuSC thus enable in vivo molecular imaging, advancing IV-OCT into the molecular age.