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We discovered a rare phenomenon wherein a thieno-pyrrole fused BODIPY dye (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents. SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this is the first example of such a finding. To establish a structure-photophysical property relationship, we prepared SBDPiR analogs with electron-withdrawing groups at the para-position of the phenyl groups. The electron-withdrawing groups increased the HOMO-LUMO energy gap and singlet oxygen generation. Among the analogs, SBDPiR688, a CF3 analog, had an excellent dual functionality of brightness (82290 m(-1)  cm(-1) ) and phototoxic power (99170 m(-1)  cm(-1) ) comparable to those of Pc 4, due to a high extinction coefficient (211 000 m(-1)  cm(-1) ) and balanced decay (Φflu =0.39 and ΦΔ =0.47). The dual functionality of the lead compound SBDPiR690 was successfully applied to preclinical optical imaging and for PDT to effectively control a subcutaneous tumor.

Photodynamic Therapy Photodynamic therapy (PDT) is a minimally invasive three‐component regimen using light, a photosensitizer (PS), and molecular oxygen. The development of efficient and effective dual‐functioning PSs (i.e., fluorescent PSs) stands to offer a more personalized image‐guided treatment approach. In their Full Paper on page 1335, highlighted on the Back Cover, Youngjae You, Francis D′Souza et al. report on the discovery and identification of key structure–photophysical property relationships within BODIPY dyes that produce singlet oxygen without heavy halogen atom assistance. The exclusion of heavy atoms maintains their high brightness, which was successfully translated in vivo. The authors also demonstrate the phototoxic power of a lead BODIPY compound through optical‐guided photodynamic therapy to effectively control a subcutaneous tumor.

Mitochondria-specific photosensitizers were designed by taking advantage of the preferential localization of delocalized lipophilic cations (DLCs) in mitochondria. Three conjugates, CMP-Rh, CMP-tPP, and CMP-(tPP)2, were successfully synthesized by linking the hydroxy core modified porphyrins (CMP-OH and CMP-(OH)2) to either rhodamine B (Rh B) or one or two triphenyl phosphine (tPP) cations respectively via a saturated hydrocarbon linker. Their ability for delivering photosensitizers to mitochondria was evaluated using dual staining fluorescence microscopy and staining pattern was compared with a mitochondrial specific probe. Fluorescence imaging study suggested that CMP-Rh specifically localized in mitochondria. On the other hand, CMP-tPP and CMP-(tPP)2 showed less significant mitochondrial localization. The conjugation of CMP to Rh and tPP did greatly improve intracellular uptake and in vitro photodynamic activity compared to CMP-OH. In addition, to evaluate the efficiency of the conjugates as photosensitizers, their photophysical properties and in vitro biological activities were studied in comparison to those of CMP-OH. All conjugates were capable of generating singlet oxygen at rates comparable to CMP-OH. This improved photodynamic activity might be primarily due to an enhanced cellular uptake. Our study suggests that Rh B cationic group is better at least for CMP than tPP as a mitochondrial targeting vector. Citation Format: Pallavi Rajaputra, Gregory Nkepang, Ryan Watley, Youngjae You. Synthesis and in vitro evaluation of lipophilic cation conjugated photosensitizers for targeting mitochondria. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1603. doi:10.1158/1538-7445.AM2013-1603