Investigating Metal and Fluorophore Controlled Intracellular Localization in Noble Metal Thiosemicarbazone Complexes

Transition metal complexes have been widely utilized as cellular imaging tools. To impart organelle specificity, ligand architecture is usually modified to modulate properties like overall charge and lipophilicity. In many such designs, the metal identity and its intrinsic properties are often ignored. To address this gap, in this study, we explored the effects of changing the metal center on the localization patterns of isostructural complexes. To this end, we employed the thiosemicarbazone Dp44mT to synthesize coumarin-conjugated complexes of Au(III), Pt(II), and Pd(II). Although the metal centers in these compounds share a formal d⁸ configuration, they differ in properties such as ionic radius, charge density, and ligand exchange rates, which can affect their subcellular localization patterns. In addition, we synthesized a second set of analogous complexes using BODIPY as the conjugating fluorophore to assess the influence of using a different dye on the cellular distribution. Confocal imaging revealed that the complexes exhibited distinct intracellular distributions. For instance, while the coumarin-conjugated Pt(II) complex localized specifically in lysosomes, the corresponding lipophilic Pd(II) complex lacked this specificity and instead followed a diffusely cytosolic distribution. Similarly, the more lipophilic BODIPY conjugated complexes were non-specific in their cellular distribution as well. Overall, the findings of this study highlight the interplay of metal identity and lipophilicity in determining the localization patterns of Dp44mT-based metal complexes, offering fresh insights into the design of new metal-based imaging tools.