An Amphiphilic Pentaaryl Cyclopentadienyl Ruthenium(II) Molecular Rotor with a Luminescent Tag

Abstract

This study presents a chemically modified molecular motor designed for interactions with lipid bilayers. By incorporating long alkyl chains into the anchoring fragment and a rhodamine luminescent tag onto the rotating subunit, we aimed to monitor the position of the motor and to permit its real-time visualization during membrane-perforation experiments. The synthesis of the functionalized tripodal ligand involved a seven-step process, culminating in the formation of a piano-stool Ru(II) complex that exhibits distinctive spectroscopic properties. The luminescence of the rhodamine tag, although slightly quenched upon incorporation in the Ru(II) complex, remains sufficiently strong to permit single-molecule observation using a total-internal-reflection fluorescence microscope.

Key words

molecular rotors - ruthenium complexes - fluorescent tags - amphiphiles - membrane penetration

Publikationsverlauf

Eingereicht: 22. November 2024

Angenommen nach Revision: 16. Dezember 2024

Accepted Manuscript online:
16. Dezember 2024

Artikel online veröffentlicht:
23. Januar 2025

• References and Notes

• 1 Present address: C. J. Martin, Laboratory for Chemistry and Life Science, Institute of Innovative Research, Institute of Science Tokyo, Yokohama 226-8503, Japan.
• 2 Junge W, Sielaff H, Engelbrecht S. Nature 2009; 459: 364
• 3 Blair DF. FEBS Lett. 2003; 545: 86
• 4a Feringa BL. J. Org. Chem. 2007; 72: 6635
• 4b Kassem S, van Leeuwen T, Lubbe AS, Wilson MR, Feringa BL, Leigh DA. Chem. Soc. Rev. 2017; 46: 2592
• 4c Jacquot de Rouville H.-P, Garbage R, Ample F, Nickel A, Meyer J, Moresco F, Joachim C, Rapenne G. Chem. Eur. J. 2012; 18: 8925
• 4d García-López V, Liu D, Tour JM. Chem. Rev. 2020; 120: 79
• 4e Baroncini M, Silvi S, Credi A. Chem. Rev. 2020; 120: 200
• 4f Gisbert Y, Abid S, Kammerer C, Rapenne G. Chem. Eur. J. 2021; 27: 16242
• 5 García-López V, Chen F, Nilewski LG, Duret G, Aliyan A, Kolomeisky AB, Robinson JT, Wang G, Pal R, Tour JM. Nature 2017; 548: 567
• 6 Ayala-Orozco C, Galvez-Aranda D, Corona A, Seminario JM, Rangel R, Myers JY, Tour JM. Nat. Chem. 2024; 16: 456
• 7a Santos AL, Liu D, Reed AK, Wyderka AM, van Venrooy A, Li JT, Li VD, Misiura M, Samoylova O, Beckham JL, Ayala-Orozco C, Kolomeisky AB, Alemany LB, Oliver A, Tegos GP, Tour JM. Sci. Adv. 2022; 8: eabm2055
• 7b Shen J, Ren C, Zeng H. Acc. Chem. Res. 2022; 55: 1148
• 7c Zhu X, Shi Z, Mao Y, Lächelt U, Huang R. Small 2024; 20: 2310605
• 8a Vives G, Rapenne G. Tetrahedron 2008; 64: 11462
• 8b Perera UG. E, Ample F, Kersell H, Zhang Y, Vives G, Echeverria J, Grisolia M, Rapenne G, Joachim C, Hla S.-W. Nat. Nanotechnol. 2013; 8: 46
• 9 Zhang Z, Dao A, Yang X, Pan L, Li W, Lin Y, Zhang X, Huang H. Bioorg. Chem. 2024; 144: 107067
• 10a Abid S, Gisbert Y, Kojima M, Saffon-Merceron N, Cuny J, Kammerer C, Rapenne G. Chem. Sci. 2021; 12: 4709
• 10b Zhang Y, Calupitan JP, Rojas T, Tumbleson R, Erbland G, Kammerer C, Ajayi TM, Wang S, Curtiss LA, Ngo AT, Ulloa SE, Rapenne G, Hla SW. Nat. Commun. 2019; 10: 3742
• 11a Sirven AM, Stefak R, Rapenne G. Heterocycl. Commun. 2015; 21: 5
• 11b Kammerer C, Rapenne G. Eur. J. Inorg. Chem. 2016; 2214
• 11c Erbland G, Gisbert Y, Rapenne G, Kammerer C. Eur. J. Org. Chem. 2018; 4731
• 12a Rüchardt C, Hassmann V. Synthesis 1972; 375
• 12b Rüchardt C, Hassmann V. Liebigs Ann. Chem. 1980; 908
• 13 Gisbert Y, Abid S, Bertrand G, Saffon-Merceron N, Kammerer C, Rapenne G. Chem. Commun. 2019; 55: 14689
• 14 Asato R, Martin CJ, Gisbert Y, Abid S, Kawai T, Kammerer C, Rapenne G. RSC Adv. 2021; 11: 20207
• 15 Höger S, Bonrad K. J. Org. Chem. 2000; 65: 2243
• 16 Techen A, Czapla S, Möllnitz K, Budach D, Wessig P, Kumke MU. Helv. Chim. Acta 2013; 96: 2046
• 17a Gao S, Gisbert Y, Erbland G, Abid S, Kammerer C, Venturini A, Rapenne G, Ventura B, Armaroli N. Phys. Chem. Chem. Phys. 2021; 23: 17049
• 17b Dumartin M, Abid S, Gisbert Y, Saffon-Merceron N, Gao S, Armaroli N, Ventura B, Kammerer C, Rapenne G. Chem. Lett. 2024; 53: upad003
• 18 Joo C, Balci H, Ishitsuka Y, Buranachai C, Ha T. Annu. Rev. Biochem. 2008; 77: 51
• 19 Fluorescence-Tagged Molecular Rotor 10 For other compounds, refer to the Supporting Information. A mixture of compound 9 (295 mg, 160 μmol), alkyne-substituted rhodamine derivative 11 ⁴ (102 mg, 195 μmol), CuI (19 mg, 100 μmol), and TBTA (44 mg, 82 μmol) was suspended in anhyd THF (17 mL), and the resulting mixture was refluxed for 18 h. After removal of volatiles, the crude compound was purified by column chromatography [silica gel, CHCl₃–MeOH (10:1)] to give a brown solid; yield: 71% (270 mg). ¹H NMR (400 MHz, CDCl₃/TMS): δ = 8.38 (br s, 1 H, NH), 8.11 (d, J = 0.8 Hz, 1 H, H_d), 7.93 (s, 3 H, H_d), 7.89 (s, 3 H, H_a), 7.63 (br s, 1 H), 7.56–7.53 (m, 5 H, H_Ar), 7.44–7.42 (m, 2 H, H_Ar), 7.38–7.31 (m, 14 H, H_Ar), 7.28–7.26 (m, 12 H, H_Ar with CHCl₃), 7.11–7.06 (m, 4 H, H_Ar), 7.00–6.96 (m, 12 H, H_Ar), 6.55 (d, J = 9.2 Hz, 2 H, H_xanthene), 6.44 (d, J = 2.0 Hz, 2 H, H_xanthene), 6.33 (d, J = 8.0 Hz, 2 H, H_xanthene), 5.55 (s, 4 H, H_a-b), 4.75 (s, 2 H, H_e), 3.89 (s, 6 H, H_e), 3.35 [q, J = 6.9 Hz, 8 H, NEt (CH₂)], 2.49 (t, J = 7.2 Hz, 6 H, H_f), 1.66–1.58 (m, 14 H, alkyl chains including H₂O), 1.39–1.25 (m, 54 H, CH_{2 Alkyl}), 1.16 [t, J = 7.2 Hz, 12 H, NEt (CH₃)], 0.87 (t, J = 6.8 Hz, 9 H, CH₃). ¹³C NMR (150 MHz, CDCl₃/TMS): δ = 166.2, 153.8, 148.0, 143.6, 140.7, 140.3, 136.8, 134.2, 133.9, 133.9, 133.8, 133.6, 129.2, 128.9, 128.7, 128.5, 127.8, 127.2, 127.1, 124.4, 122.1, 121.9, 120.0, 119.5, 111.3, 108.6, 97.4, 88.2, 88.0, 87.2, 53.8, 44.6, 37.3, 31.9, 29.7, 29.7, 29.6, 29.4, 29.2, 29.0, 22.7, 14.1, 12.5. HRMS (ESI, positive): m/z [M + H]⁺ calcd for C₁₄₃H₁₆₅BN₁₅O₄RuS₃: 2365.1468; found: 2365.1184. UV/Vis (CHCl₃, 10 μM): λ_max (ε) = 550 nm (16270). Emission (λ_exc = 520 nm; CHCl₃, 10 μM): λ_max : 569 nm.