Porphyrin-Fullerene Based Donor-Acceptor Conjugates for Photocontrol of Cell Membrane Potentials

   Optical control of cellular functions is a promising approach for therapeutic application because it can realize precise control with resolutions of submicrosecond temporally and submicrometer spatially.¹ Among various key factors for controlling cellular functions, cell membrane potential is one of the most important ones because it triggers various biological events such as neuron fire and cell signaling. For maintaining membrane potentials, ion channels play crucial roles to keep or to change cell membrane potentials. Therefore, artificial control of cell membrane potential and selective inhibition/activation of ion channels are considered to be promising therapeutic approach.²

   Meanwhile, in electron donor-acceptor linked molecules, photoirradiation triggers intramolecular electron transfer and then charge separated (CS) state is generated. The molecules in CS state demonstrate high oxidizing and reducing abilities, and may induce large dipole which can generate large electric field in nanometer scale. Our group has focused on the photoinduced CS states in the donor-acceptor linked molecules because it may perturb an environment in the cell membrane and may influence function of the proteins therein. Recently, we have reported that such molecules can induce depolarization in the membrane potential of PC12 cells as well as inhibition of the potassium ion flow across the membrane by illumination.³

   In this study, a series of amphiphilic electron donor-acceptor linked molecules based on fullerene and porphyrin were systematically designed, synthesized and investigated for photocontrol on cell membrane potentials. Their molecular structures and unique aggregate structures revealed their characteristic photoinduced excited states of the molecules. Utilizing fullerene moiety was found to be a key for formation of the unique aggregates in highly polar solvent and introduction of porphyrin moiety provides a benefit for using light energy efficiently. Successful design of a CS molecule was found to suppress photocytotoxicity of the molecule remarkably and demonstrated its ability for modulation on the membrane potentials which can increase the frequency of the action potential and trigger neuron firing in rat hippocampal neurons by photo irradiation.

References:

[1] (For a review) Briele, C. et al. Angew. Chem. Int. Ed. 2012, 51, 8446.

[2] (For a review) Wulff, H. et al. Nat. Rev. 2009, 8, 982.

[3] Takano, Y. et al. J. Am. Chem. Soc. 2012, 134, 6092.