Photochemical Synthesis of Polycyclic Phosphonium Salts as Efficient Anticancer and Antibacterial Agents

Abstract

Phosphorus-containing functional materials have diverse applications in optoelectronics and bioscience owing to their unique properties. However, polycyclic π-conjugated phosphonium salts have been rarely explored due to their complex synthesis. In this work, a facile and efficient method for constructing polycyclic π-conjugated phosphonium salts (TBPIMe derivatives) is proposed, based on the photocyclization of phosphindolium salts (TPPIMe derivatives). Systematic experimental and theoretical investigations reveal the changed photophysical and photochemical properties when TPPIMe derivatives are converted to TBPIMe derivatives. Notably, the novel polycyclic π-conjugated phosphonium salt p-MOTBPIMe exhibits improved reactive oxygen species generation ability and much stronger specific affinity toward DNA than phosphindolium salts p-MOTPPIMe. Moreover, in vitro experiments demonstrate that p-MOTPPIMe can also be efficiently converted into p-MOTBPIMe under 405 nm laser irradiation in living cells, accompanied by the migration from cytoplasm to nucleus to enhance the photodynamic effect. Additionally, p-MOTBPIMe shows superior antibacterial activity against not only Gram-positive drug-resistant bacteria but also fungi, by leveraging both dark and light cytotoxicity. This work opens up a new chemical toolkit for novel polycyclic π-conjugated phosphonium salts, which are promising for developing advanced theranostic agents with satisfactory accuracy and efficacy.

Keywords

antibacterial activity / phosphindolium salt / photocyclization / photodynamic therapy / polycyclic phosphonium salt

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2024 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.