Photoacoustic Probes for Ratiometric Imaging of Copper(II)

Abstract

Photoacoustic tomography has emerged as a promising alternative to MRI and X-ray scans in the clinical setting due to its ability to afford high-resolution images at depths in the cm range. However, its utility has not been established in the basic research arena owing to a lack of analyte-specific photoacoustic probes. To this end, we have developed acoustogenic probes for copper(II)-1 and -2 (APC-1 and APC-2, a water-soluble congener) for the chemoselective visualization of Cu(II), a metal ion which plays a crucial role in chronic neurological disorders such as Alzheimer's disease. To detect Cu(II), we have equipped both APCs with a 2-picolinic ester sensing module that is readily hydrolyzed in the presence of Cu(II) but not by other divalent metal ions. Additionally, we designed APC-1 and APC-2 explicitly for ratiometric photoacoustic imaging by using an aza-BODIPY dye scaffold exhibiting two spectrally resolved NIR absorbance bands which correspond to the 2-picolinic ester capped and uncapped phenoxide forms. The normalized ratiometric turn-on responses for APC-1 and APC-2 were 89- and 101-fold, respectively.

Towards the generalized iterative synthesis of small molecules

“…In fact, there is probably not a household on the planet that is not positively impacted by this class of chemical matter on a daily basis. Small molecules also possess substantial untapped potential to perform many frontier functions, 1 including modulating protein-protein interactions, 2 allosterically modifying protein function, 3 acting as prostheses on the molecular scale, 4,5 serving as next-generation biological probes, 6–9 enabling miniaturized diagnostics, 10 transducing energy, 11–16 emitting light, 17 initiating self-healing, 18 acting as molecular magnets, 19 enabling next generation computing, 20 and superconducting. 21–22 However, largely due to limitations in synthesis, much of this functional potential remains largely untapped.…”

Versatile bimetallic lanthanide metal-organic frameworks for tunable emission and efficient fluorescence sensing

“…In the past few years, various kinds of analytical methods have been explored for the detection of different metal ions. As compared with other detection approaches, fluorescent sensors possess many advantages, such as high sensitivity, good reliability, and real-time detection [13][14][15][16][17] . While some fluorescent metal-organic frameworks (MOFs) showed a promising potential in probing metal ions [18][19][20][21][22] , MOF-based fluorescent platforms for effective and easy detection of different metal ions in aqueous solution have not been well investigated so far.…”

Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications

“…In the past decades, many fluorescent probes have been developed for in vivo detections 114-118. Encouraged by the absorption changes of some PA contrast agents at different conditions, PAI show great potential to monitor or track the environment changes based on the readout intensity of PA signals 119-126. Compared to traditional detection methods (e.g.…”

“…For example, Chan et al developed a PA probe for the chemoselective visualization of Cu 2+ , which is a crucial metal ion in chronic nervous diseases (e.g. Alzheimer's disease) 126. As shown in Figure 9A, the acoustogenic probe for Cu 2+ -2 (APC-2) contains a 2-picolinic ester sensing module that can specifically respond to Cu 2+ .…”

“…(C) PA signal responses of APC-2 to various metal ions. Reproduced with permission 126. Copyright 2015 American Chemical Society.…”