Rollover palladacycles complexes containing pyridinebenzothiazole fragments were synthetized via remote C−H bond activation by PdCl2 in DMF. The structures of these compounds were proposed based on NMR analysis and high‐resolution mass spectrometry; in selected case of compound 1, its molecular structure was corroborated by single crystal X‐ray diffraction experiment. Upon solubilization in acetonitrile and using ESI‐QTOFMS, this complex was found as unusual tricoordinate cationic complex 1‐NCCH3 with acetonitrile attachment via Pd−Cl bond activation. Of note, synthesis success when PdCl2 was used as the starting material and mild heating (60 °C) of the reaction mixture was necessary to obtain the desired compound in a reasonable time (7 days). Evidence is provided that DMF solvent plays a key mechanistic role enabling the formation of organometallic rollover compounds; whereas using another solvent like DMSO, NCCH3 or acetone, a classic coordination complex is obtained.

Cataract is the leading cause of blindness worldwide, and it is caused by crystallin damage and aggregation. Senile cataractous lenses have relatively high levels of metals, while some metal ions can directly induce the aggregation of human γ-crystallins. Here, we evaluated the impact of divalent metal ions in the aggregation of human βB2-crystallin, one of the most abundant crystallins in the lens. Turbidity assays showed that Pb 2+ , Hg 2+ , Cu 2+ , and Zn 2+ ions induce the aggregation of βB2-crystallin. Metal-induced aggregation is partially reverted by a chelating agent, indicating the formation of metal-bridged species. Our study focused on the mechanism of copperinduced aggregation of βB2-crystallin, finding that it involves metal-bridging, disulfide-bridging, and loss of protein stability. Circular dichroism and electron paramagnetic resonance (EPR) revealed the presence of at least three Cu 2+ binding sites in βB2-crystallin, one of them with spectroscopic features typical for Cu 2+ bound to an amino-terminal copper and nickel (ATCUN) binding motif, which is found in Cu transport proteins. The ATCUN-like Cu binding site is located at the unstructured N-terminus of βB2-crystallin, and it could be modeled by a peptide with the first six residues in the protein sequence (NH 2 -ASDHQF-). Isothermal titration calorimetry indicates a nanomolar Cu 2+ binding affinity for the ATCUN-like site. An N-truncated form of βB2-crystallin is more susceptible to Cu-induced aggregation and is less thermally stable, indicating a protective role for the ATCUN-like site. EPR and X-ray absorption spectroscopy studies reveal the presence of a copper redox active site in βB2-crystallin that is associated with metal-induced aggregation and formation of disulfidebridged oligomers. Our study demonstrates metal-induced aggregation of βB2-crystallin and the presence of putative copper binding sites in the protein. Whether the copper-transport ATCUN-like site in βB2-crystallin plays a functional/protective role or constitutes a vestige from its evolution as a lens structural protein remains to be elucidated.