Abstract
New thiophene-dipicolinato-based compounds, K2nTdpa (n = 1, 2), were isolated. Their anions are sensitizers of lanthanide ion (LnIII) luminescence and singlet oxygen generation (1O2). Emission in the visible and near-infrared regions was observed for the LnIII complexes with efficiencies (φLn) φEu = 33% and φYb = 0.31% for 1Tdpa2- and φYb = 0.07% for 2Tdpa2-. The latter does not sensitize EuIII emission. Fluorescence imaging of HeLa live cells incubated with K3[Eu(1Tdpa)3] indicates that the complex permeates the cell membrane and localizes in the mitochondria. All complexes generate 1O2 in solution with efficiencies (φO12) as high as 13 and 23% for the GdIII complexes of 1Tdpa2- and 2Tdpa2-, respectively. [Ln(nTdpa)3]3- (n = 1, 2) are phototoxic to HeLa cells when irradiated with UV light with IC50 values as low as 4.2 μM for [Gd(2Tdpa)3]3- and 91.8 μM for [Eu(1Tdpa)3]3-. Flow cytometric analyses indicate both apoptotic and necrotic cell death pathways.
| Original language | English |
|---|---|
| Pages (from-to) | 7724-7734 |
| Number of pages | 11 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 64 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jun 10 2021 |
Funding
The National Science Foundation (CHE-1800392 to AdBD) is gratefully acknowledged for financial support. Shanti Rawat and Prof. Jorge H.S.K. Monteiro are acknowledged for their support and guidance. Janina S. Ruprecht is acknowledged for collecting mass spectra. This work was carried out with support from the Coordination for the Improvement of Higher Education Personnel, (CAPES-Brazil) Process (88881.186961/2018-01 to CVSR-Capes Scholar—Brazil). Research reported in this publication used the Cellular and Molecular Imaging (CMI) core facility supported by the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103650.