Versatile Strategy To Generate a Rhodamine Triplet State as Mitochondria-Targeting Visible-Light Photosensitizers for Efficient Photodynamic Therapy

Abstract

Through the use of a rhodamine-appended chelate, bpy-Rho, a versatile strategy has been demonstrated to readily form mitochondria-targeting photosensitizers via the incorporation of a variety of luminescent transition-metal systems, M-Rho, such as Re(I), Ir(III), Pt(II), and Rh(III). The emission from the rhodamine singlet excited state and the transition-metal triplet excited state is partially quenched by the depopulation of them into the dark rhodamine triplet excited state. The generation of the triplet excited state of a rhodamine moiety endows the complexes with mitochondria-targeting photosensitizing ability to form singlet oxygen ( 1 O 2 ) for use as a photodynamic therapy (PDT) agent upon visible-light irradiation. The combination of the rhodamine organic dye and luminescent transition-metal centers in such hybrid systems exhibits the synergistic merits for the biological applications, including low dark cytotoxicity, selective tumor cell uptake, high molar absorptivity suitable for low-energy excitation in the visible region, and high photostability. The corresponding in vitro photocytotoxicity and in vivo photo-antitumor efficacy have also been studied to demonstrate the potential PDT application of M-Rho.

Enhancing the ROS generation ability of a rhodamine-decorated iridium(iii) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy

“…This population was mainly derived from two sensitization processes: (I) triplet-triplet energy transfer (TTET) from the iridium(III)-based triplet state ðT 0 1 Þ and (II) intersystem crossing (ISC) from the rhodamine singlet state (S 1 ). The occurrence of TTET is rationalized from the lower energy level of T 1 (approximately 1.70 eV) 38 than that of iridium(III)-based T 0 1 (1.89 eV). On the other hand, the luminescence quantum yield (F lum ) from rhodamine uorescence supports the efficient population of T 1 from S 1 .…”

“…The singlet-to-triplet energy transfer from rhodamine singlet state to 3 MLCT excited state is unavoured in Ir-Rho because the energy level of 3 MLCT excited state of [Ir(ppy) 2 (bipy)] + is higher than that of rhodamine singlet state. 38 However, this spin-forbidden energy transfer in Ir-Rho-G2 cannot completely be ruled out, in view of the lower-lying 3 MLCT excited state with dpqx ligand. In contrast, no such ISC was observed in other rhodamine-containing transition metal systems, in that there are no direct interactions between the metal centre and the rhodamine.…”

“…The strategy for improving the singlet oxygen generation ability and organelle targeting behaviour of the rhodamine-containing cyclometallated iridium(III) system was achieved by simply replacing the cyclometallating ligand from 2-phenylpyridine (ppy) to 2,3-diphenylquinoxaline (dpqx) in Ir-Rho-G2. According to the previously reported procedure of Ir-Rho, 38 Ir-Rho-G2 was synthesized from reaction of the corresponding iridium(III) dimeric starting material, [Ir(dpqx)Cl] 2 and the rhodaminetethered bipyridine chelating ligand, bpy-Rho. The characterization of Ir-Rho-G2 was conrmed by 1 H and 13 C NMR and high-resolution mass spectrometry ( Fig.…”

“…36,37 In our previous study, we developed a versatile strategy to generate a series of rhodamine-decorated transition metal complexes of rhenium(I), iridium(III), rhodium(III) and platinum(II) as mitochondria-targeting photosensitizers for efficient PDT. 38 Among these rhodamine-metal complexes, one with an iridium(III) metal centre, ([Ir(ppy) 2 (bpy-Rho)](PF 6 ) 2 (ppy ¼ 2phenylpyridine), named Ir-Rho) (Scheme 1) demonstrated the best performance as a photosensitizer for such organellelocalized PDT. However, Ir-Rho is still in its infancy, and further improvement of ROS generation efficiency is anticipated.…”

A Deep‐Red to Near Infrared (NIR) Fluorescent Probe Based on a Sulfur‐Modified Rhodamine Derivative with Two Spirolactone Rings

“…In order to further red-shift the absorption and fluorescence wavelengths, together with the extension of our ongoing interest in novel rhodamine derivatives [28][29][30] as well as the rhodamine-containing transition metal complexes, [31][32][33][34][35] a novel deep red to NIR fluorescent rhodamine derivative (1-S) was designed and synthesized through a simple one-pot reaction with another reagent of benzene-1,3-dithiol. This compound involves the replacement of the oxygen atoms with sulfur atoms on the xanthene framework and two stereoisomers (cis-1-S and trans-1-S) have been successfully separated and isolated (Scheme 1).…”