Singlet oxygen generating luminescent lanthanide complexes with naphthalimide-based and oligothiophene-based sensitizers
Luminescent lanthanide (LnIII) complexes that also generate singlet oxygen (1O2) are of interest to medical, biological, and analytical fields, as they can provide cytotoxicity and luminescence using light excitation. Because of the interest in these compounds, systematic studies were used to help understand structure-property relationships. This work aims to synthesize and characterize multiple families of LnIII complexes that incorporate 1O2 generator moieties, specifically oligothienyl or 1,8-naphthalimidyl, to better understand the energetic consequences of combining luminescence and 1O2 generation. This was done by monitoring the emission efficiency of both LnIII-centered luminescence and 1O2 phosphorescence, metal-centered emission lifetimes, the energy of the ligands' excited states, and their overall solution stability. The complex with the highest luminescence efficiency for EuIII was for [Eu(1Tcbx)3]3+ (25.0%), for YbIII was [Yb(2Tcbx)2]3+ (0.69% without simultaneous 1O2 generation), for NdIII was [Nd(2Tcbx)2]3+ (0.20% without simultaneous 1O2 generation), and for ErIII was [Er(2Tcbx)2]3+ (0.02% without simultaneous 1O2 generation). The luminescent complex with the highest 1O2 generation efficiency reported is [Nd(Nap-cbx)3]3+ with 1O2 generation efficiency of 64%.Water-soluble compounds were further investigated by probing their emission in vitro, determining their phototoxicity and dark toxicity, and the resulting cell death mechanism. With these combined data, the usefulness of these compounds as potential therapeutics with dual activity can be assessed and optimized. The complex with the highest luminescence efficiency for EuIII was [Eu(1Tdpa)3]3- (41.0%), for YbIII was [Yb1Thept(COO)4]- (0.50%), and for NdIII was [Nd2Thept(COO)4]- (0.45%). None of the water-soluble ligands could sensitize ErIII luminescence. The luminescent complex with the highest 1O2 generation efficiency is [Eu2Thept(COO)4]- (16%) The most potent compounds for each family were [Gd(2Tdpa)3]3- (4.2 uM) and [Nd2Thept(COO)4]- (15.2 uM). The cell death mechanism for all compounds of this study indicated both apoptotic and necrotic pathways.
dual functionality, lanthanides, luminescence, singlet oxygen
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