In addition to developing powerful contrast agents, we wanted to extend the use of mvGlu to augment our analyte sensing capabilities. Recently, we developed an acoustogenic ABS probe for Cu(I) (named PACu-1), which we applied to visualize pathological levels of hepatic copper in a Wilson's disease model. PACu-1 is equipped with a tris[(2pyridyl)methyl]amine (TPA) trigger that can be appended to an AB via an ether linkage. Upon coordination to Cu(I), an oxidative cleavage event can then take place which releases the dye. Of note, we selected the TPA trigger in this design because it has been used to develop a variety of sensors for other modalities and can effectively compete against glutathione to access intracellular Cu(I). However, when PACu-1 was employed in an attempt to image breast tumors, most of the probe localized to the liver owing to its hydrophobic properties. This result was disappointing because elevated copper is linked to aggressive breast malignancies and its detection could serve as a diagnostic marker. Moreover, this finding highlights the unpredictable nature of many molecules not equipped with a targeting group. The design of the second-generation copper probe to overcome this challenge is based on the mvGlu-AB3 architecture where one of the anisole rings was replaced with a 2,6-dichlorophenol moiety to provide a site for trigger installation. Synthesis of the proposed probe, multivalent probe for Cu(I) (mvpCu), began with the preparation of 1 and 2, which were accessed from the corresponding chalcone precursors via aldol condensation and Henry reactions (Scheme S4 and S5). The aza-BODIPY dye scaffold was synthesized via Paal-Knorr cyclization of the two precursors, followed by metalation using boron trifluoride etherate in 22% yield over 2-steps. Next, copper-mediated click chemistry with the acetyl protected mvGlu azide (Scheme S7 and S8), yielded the glycoside incorporated aza-BODIPY 5. A Tsuji-Trost deallylation reaction was employed to remove the allyl protecting group on the 2,6-dichlorophenol moiety in 81% yield. The TPA trigger was then installed via nucleophilic substitution. Global deprotection of the acetyl groups with potassium methoxide generated in situ simultaneously exchanged the fluoro substituents with methoxy groups (Scheme 1).