基于罗丹明的钌(II)配合物的设计、合成和光物理性质研究

重原子效应促进了系间窜越，从而有利于三重激发态的产生。而长寿命激发态的存在有利于能量转移或电子转移过程，该过程能够被应用于光催化和光动力治疗。在本论文中，我们研究了一系列含罗丹明基团的钌(II)配合物，在可见光照射下，这些化合物会由基态转变成长寿命的激发态，通过电子转移过程能够产生超氧阴离子自由基，或者通过能量转移过程产生单线态氧。首先，我们设计并合成了四个含有罗丹明基团的三（双齿配体）钌(II)配合物。由于罗丹明基团的引入，四个配合物均展现出了长寿命的三重罗丹明激发态。除此之外，与不含罗丹明的对照化合物相比，它们拥有更强的 活性氧 的产生能力 ， 这 些 化合物 当 中 的 [Ru(phen)2(Rhobpy)][PF6]3 具高达 0.85 的单线态氧量子产率。同时，我们还设计并合成了含有罗丹明基团的双（三齿配体）钌(II)配合物。[Ru(tpy)2]2+寿命极短并且 不 会 产 生 活 性 氧 ， 但 是 罗 丹 明 的 引 入 不 仅 可 延 长 激 发 态 寿 命 ，[Ru(tpy)(Rho-tpy)][PF6]3 和[Ru(Rho-tpy)2][PF6]4 的激发态寿命分别为 1.09 μs和 311 ns ； 罗丹明 的引入 还 可 以 显 著 地 提 高 化 合 物 的 活 性 氧 产 量 ，[Ru(tpy)(Rho-tpy)][PF6]3 和[Ru(Rho-tpy)2][PF6]4 的单线态氧产率分别为 0.85和 0.60。进一步地，具有更加完美八面体构型的[Ru(tpy)(Rho-dqp)][PF6]3 拥有更高的激发态寿命，这使得其活性氧产生能力得到进一步增强。这两类化合物如此出色的活性氧生成能力使它们成为潜在的光动力治疗试剂。

[1] ASHFORD D L, GLASSON C, NORRIS M R, et al. Controlling Ground and Excited State Properties through Ligand Changes in Ruthenium Polypyridyl Complexes[J]. Inorganic Chemistry, 2014, 53(11):5637-5646.
[2] AL-RAWASHDEH N A F, CHATTERJEE S, KRAUSE J A, et al. Ruthenium bis-diimine complexes with a chelating thioether ligand: delineating 1, 10-phenanthrolinyl and 2, 2’-bipyridyl ligand substituent effects[J]. Inorganic Chemistry, 2014, 53(1): 294-307.
[3] RILLEMA D P, TAGHDIRI D G, JONES D S, et al. Structure and redox and photophysical properties of a series of ruthenium heterocycles based on the ligand 2, 3-bis(2-pyridyl) quinoxaline[J]. Inorganic Chemistry, 1987, 26(4): 578-585.
[4] ANDERSON P A, KEENE F R, MEYER T J, et al. Manipulating the properties of MLCT excited states[J]. Journal of the Chemical Society, Dalton Transactions, 2002: 3820-3831.
[5] ZHOU Q X, LEI W H, SUN Y, et al. [Ru(bpy)3-n(dpb)n]2+: Unusual photophysical property and efficient DNA photocleavage activity[J]. Inorganic Chemistry, 2010, 49(11): 4729-4731.
[6] SUN Q, MOSQUERA-VAZQUEZ S, SUFFREN Y, et al. On the role of ligand-field states for the photophysical properties of ruthenium(II) polypyridyl complexes[J]. Coordination Chemistry Reviews, 2015, 282: 87-99.
[7] JURIS A, BALZANI V, BARIGELLETTI F, et al. Ru(II) polypyridine complexes: photophysics, photochemistry, eletrochemistry, and chemiluminescence[J]. Coordination Chemistry Reviews, 1988, 84: 85-277.
[8] THOMPSON D W, ITO A, MEYER T J. [Ru(bpy)3]2+* and other remarkable metal-to-ligand charge transfer (MLCT) excited states[J]. Pure and Applied Chemistry, 2013, 85(7): 1257-1305.
[9] DONGARE P, MYRON B D B, WANG L, et al. [Ru(bpy)3]2+∗ revisited. Is it localized or delocalized? How does it decay[J]. Coordination Chemistry Reviews, 2017, 345: 86-107.
[10] JURIS A, BALZANI V, BELSER P, et al. Characterization of the excited state properties of some new photosensitizers of the ruthenium(polypyridine) family[J]. Helvetica Chimica Acta, 1981, 64(7): 2175-2182.
[11] MARCUS R A. Chemical and electrochemical electron-transfer theory[J]. Annual Review of Physical Chemistry, 1964, 15(1): 155-196.
[12] ARNAUT L, BURROWS H. Chemical kinetics: from molecular structure to chemical reactivity[M]. Elsevier, 2006.
[13] SOUPART A, ALARY F, HEULLY J L, et al. Recent progress in ligand photorelease reaction mechanisms: Theoretical insights focusing on Ru(II) 3MC states[J]. Coordination Chemistry Reviews, 2020, 408: 213184.
[14] WHITE J K, SCHMEHL R H, TURRO C. An overview of photosubstitution reactions of Ru(II) imine complexes and their application in photobiology and photodynamic therapy[J]. Inorganica Chimica Acta, 2017, 454: 7-20.
[15] LIU Y, HAMMITT R, LUTTERMAN D A, et al. Ru(II) complexes of new tridentate ligands: unexpected high yield of sensitized 1O2[J]. Inorganic Chemistry, 2009, 48(1): 375-385.
[16] ROQUE III J A, COLE H D, BARRETT P C, et al. Intraligand excited states turn a ruthenium oligothiophene complex into a light-triggered Ubertoxin with anticancer effects in extreme hypoxia[J]. Journal of the American Chemical Society, 2022, 144(18): 8317-8336.
[17] TANG M C, LI L K, LAI S L, et al. Design strategy towards horizontally oriented luminescent tetradentate-ligand-containing gold(III) systems[J]. Angewandte Chemie, 2020, 132(47): 21209-21217.
[18] LINCOLN R, KOHLER L, MONRO S, et al. Exploitation of long-lived 3IL excited states for metal–organic photodynamic therapy: verification in a metastatic melanoma model[J]. Journal of the American Chemical Society, 2013, 135(45): 17161-17175.
[19] KOIKE T, AKITA M. Visible-light radical reaction designed by Ru and Ir-based photoredox catalysis[J]. Inorganic Chemistry Frontiers, 2014, 1(8): 562-576.
[20] PRIER C K, RANKIC D A, MACMILLAN D W C. Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis[J]. Chemical Reviews, 2013, 113(7): 5322-5363.
[21] BELL J D, MURPHY J A. Recent advances in visible light-activated radical coupling reactions triggered by (i) ruthenium, (ii) iridium and (iii) organic photoredox agents[J]. Chemical Society Reviews, 2021, 50(17): 9540-9685.
[22] ARIAS-ROTONDO D M, MCCUSKER J K. The photophysics of photoredox catalysis: a roadmap for catalyst design[J]. Chemical Society Reviews, 2016, 45(21): 5803-5820.
[23] GLASER F, WENGER O S. Recent progress in the development of transition-metal based photoredox catalysts[J]. Coordination Chemistry Reviews, 2020, 405: 213129.
[24] LI K, WAN Q, YANG C, et al. Air-stable blue phosphorescent tetradentate platinum(II) complexes as strong photo-reductant[J]. Angewandte Chemie, 2018, 130(43): 14325-14329.
[25] CABRERA-AFONSO M J, LU Z P, KELLY C B, et al. Engaging sulfinate salts via Ni/photoredox dual catalysis enables facile Csp2–SO2R coupling[J]. Chemical Science, 2018, 9(12): 3186-3191.
[26] YANG Q, ZHANG L, YE C, et al. Visible-light-promoted asymmetric cross-dehydrogenative coupling of tertiary amines to ketones by synergistic multiple catalysis[J]. Angewandte Chemie International Edition, 2017, 56(13): 3694-3698.
[27] RÖSSLER S L, JELIER B J, TRIPET P F, et al. Pyridyl radical cation for C-H amination of arenes[J]. Angewandte Chemie International Edition, 2019, 58(2): 526-531.
[28] RUFFONI A, JULIÁ F, SVEJSTRUP T D, et al. Practical and regioselective amination of arenes using alkyl amines[J]. Nature Chemistry, 2019, 11(5): 426-433
[29] JUNG H, KEUM H, KWEON J, et al. Tuning triplet energy transfer of hydroxamates as the nitrene precursor for intramolecular C(sp3)–H amidation[J]. Journal of the American Chemical Society, 2020, 142(12): 5811-5818.
[30] MAHMOOD Z, HE J, CAI S, et al. Tuning the photocatalytic performance of ruthenium(II) polypyridine complexes via ligand modification for visible-light-induced phosphorylation of tertiary aliphatic amines[J]. Chemistry-A European Journal, 2023, 29(1): e202202677.
[31] LEE S K, KONDO M, OKAMURA M, et al. Function-integrated Ru catalyst for photochemical CO2 reduction[J]. Journal of the American Chemical Society, 2018, 140(49): 16899-16903.
[32] HAN G, LI G, HUANG J, et al. Two-photon-absorbing ruthenium complexes enable near infrared light-driven photocatalysis[J]. Nature Communications, 2022, 13(1): 2288.
[33] ZHAO X, LIU J, FAN J, et al. Recent progress in photosensitizers for overcoming the challenges of photodynamic therapy: from molecular design to application[J]. Chemical Society Reviews, 2021, 50(6): 4185-4219.
[34] PHAM T C, NGUYEN V N, CHOI Y, et al. Recent strategies to develop innovative photosensitizers for enhanced photodynamic therapy[J]. Chemical Reviews, 2021, 121(21): 13454-13619.
[35] PAPROCKA R, WIESE-SZADKOWSKA M, JANCIAUSKIENE S, et al. Latest developments in metal complexes as anticancer agents[J]. Coordination Chemistry Reviews, 2022, 452: 214307.
[36] MONRO S, COLON K L, YIN H, et al. Transition metal complexes and photodynamic therapy from a tumor-centered approach: challenges, opportunities, and highlights from the development of TLD1433[J]. Chemical Reviews, 2018, 119(2): 797-828.
[37] ROQUE III J A, COLE H D, BARRETT P C, et al. Intraligand excited states turn a ruthenium oligothiophene complex into a light-triggered ubertoxin with anticancer effects in extreme hypoxia[J]. Journal of the American Chemical Society, 2022, 144(18): 8317-8336.
[38] QIAO L, LIU J, HAN Y, et al. Rational design of a lysosome-targeting and near-infrared absorbing Ru(II)–BODIPY conjugate for photodynamic therapy[J]. Chemical Communications, 2021, 57(14): 1790-1793.
[39] PAUL S, SAHOO S, SAHOO S, et al. Bichromophoric BODIPY and biotin tagged terpyridyl ruthenium(ii) complexes for cellular imaging and photodynamic therapy[J]. European Journal of Inorganic Chemistry, 2022: e202200487.
[40] ZHANG Q, WONG K M C. Photophysical, ion-sensing and biological properties of rhodamine-containing transition metal complexes[J]. Coordination Chemistry Reviews, 2020, 416: 213336.
[41] BÜHLER B, SCHOKOLOWSKI J, BENDEROTH A, et al. Avidity-based bright and photostable light-up aptamers for single-molecule mRNA imaging[J]. Nature Chemical Biology, 2023,19: 478-487.
[42] ZHENG Y, YE Z, ZHANG X, et al. Recruiting rate determines the blinking propensity of rhodamine fluorophores for super-resolution imaging[J]. Journal of the American Chemical Society, 2023, 145(9): 5125-5133.
[43] KOMPA J, BRUINS J, GLOGGER M, et al. Exchangeable HaloTag ligands for super-resolution fluorescence microscopy[J]. Journal of the American Chemical Society, 2023, 145(5): 3075-3083.
[44] GHOSH I, KÖNIG B. Chromoselective photocatalysis: controlled bond activation through light-color regulation of redox potentials[J]. Angewandte Chemie International Edition, 2016, 55(27): 7676-7679.
[45] BRANDL F, BERGWINKL S, ALLACHER C, et al. Consecutive photoinduced electron transfer (conPET): The mechanism of the photocatalyst rhodamine 6G[J]. Chemistry–A European Journal, 2020, 26(35): 7946-7954.
[46] SHIGEMITSU H, TANI Y, TAMEMOTO T, et al. Aggregation-induced photocatalytic activity and efficient photocatalytic hydrogen evolution of amphiphilic rhodamines in water[J]. Chemical Science, 2020, 11(43): 11843-11848.
[47] LIU C, ZHOU L, WEI F, et al. Versatile strategy to generate a rhodamine triplet state as mitochondria-targeting visible-light photosensitizers for efficient photodynamic therapy[J]. ACS Applied Materials & Interfaces, 2019, 11(9): 8797-8806.
[48] ZHOU L, WEI F, XIANG J, et al. Enhancing the ROS generation ability of a rhodamine-decorated iridium(III) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy[J]. Chemical Science, 2020, 11(44): 12212-12220.
[49] SULLIVAN B P, SALMON D J, MEYER T J. Mixed phosphine 2,2'-bipyridine complexes of ruthenium[J]. Inorganic Chemistry, 1978, 17(12): 3334-3341.
[50] WACHTER E, HEIDARY D K, HOWERTON B S, et al. Light-activated ruthenium complexes photobind DNA and are cytotoxic in the photodynamic therapy window[J]. Chemical Communications, 2012, 48(77): 9649-9651.
[51] ARDO S, SUN Y, STANISZEWSKI A, et al. Stark effects after excited-state interfacial electron transfer at sensitized TiO2 nanocrystallites[J]. Journal of the American Chemical Society, 2010, 132(19): 6696-6709.
[52] O’DONNELL R M, SAMPAIO R N, LI G, et al. Photoacidic and photobasic behavior of transition metal compounds with carboxylic acid group(s)[J]. Journal of the American Chemical Society, 2016, 138(11): 3891-3903.
[53] ITO A, KOBAYASHI N, TEKI Y. Low-energy and long-lived emission from polypyridyl ruthenium(II) complexes having a stable-radical substituent[J]. Inorganic Chemistry, 2017, 56(7): 3794-3808.
[54] WEBER J M, RAWLS M T, MACKENZIE V J, et al. High energy and quantum efficiency in photoinduced charge separation[J]. Journal of the American Chemical Society, 2007, 129(2): 313-320.
[55] FAVEREAU L, MAKHAL A, PROVOST D, et al. Tris-bipyridine based dinuclear ruthenium(ii)–osmium(iii) complex dyads grafted onto TiO2 nanoparticles for mimicking the artificial photosynthetic Z-scheme[J]. Physical Chemistry Chemical Physics, 2017, 19(6): 4778-4786.
[56] SHELDRICK G M. A short history of SHELX[J]. Acta Crystallographica Section A: Foundations of Crystallography, 2008, 64(1): 112-122.
[57] REDMOND R W, GAMLIN J N. A compilation of singlet oxygen yields from biologically relevant molecules[J]. Photochemistry and Photobiology, 1999, 70(4): 391-475.
[58] NAM J S, KANG M G, KANG J, et al. Endoplasmic reticulum-localized iridium(III) complexes as efficient photodynamic therapy agents via protein modifications[J]. Journal of the American Chemical Society, 2016, 138(34): 10968-10977.
[59] SETSUKINAI K, URANO Y, KAKINUMA K, et al. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species* 210[J]. Journal of Biological Chemistry, 2003, 278(5): 3170-3175.
[60] LEE L C C, LO K K W. Luminescent and photofunctional transition metal complexes: From molecular design to diagnostic and therapeutic applications[J]. Journal of the American Chemical Society, 2022, 144(32): 14420-14440.
[61] RYAN R T, STEVENS K C, CALABRO R, et al. Bis-tridentate N-heterocyclic carbene Ru(II) complexes are promising new agents for photodynamic therapy[J]. Inorganic Chemistry, 2020, 59(13): 8882-8892.
[62] LIU B, GAO Y, JABED M A, et al. Lysosome targeting bis-terpyridine ruthenium(II) complexes: photophysical properties and in vitro photodynamic therapy[J]. ACS Applied Bio Materials, 2020, 3(9): 6025-6038.
[63] PAUL S, KUNDU P, KONDAIAH P, et al. BODIPY-ruthenium(II) bis-terpyridine complexes for cellular imaging and type-I/-II photodynamic therapy[J]. Inorganic Chemistry, 2021, 60(21): 16178-16193.
[64] WINKLER J R, NETZEL T L, CREUTZ C, et al. Direct observation of metal-to-ligand charge-transfer (MLCT) excited states of pentaammineruthenium(II) complexes[J]. Journal of the American Chemical Society, 1987, 109(8): 2381-2392.
[65] BROWN D G, SANGUANTRAKUN N, SCHULZE B, et al. Bis(tridentate) ruthenium–terpyridine complexes featuring microsecond excited-state lifetimes[J]. Journal of the American Chemical Society, 2012, 134(30): 12354-12357.
[66] PARADA G A, FREDIN L A, SANTONI M P, et al. Tuning the electronics of bis(tridentate) ruthenium(II) complexes with long-lived excited states: modifications to the ligand skeleton beyond classical electron donor or electron withdrawing group decorations[J]. Inorganic Chemistry, 2013, 52(9): 5128-5137.
[67] RUPP M T, SHEVCHENKO N, HANAN G S, et al. Enhancing the photophysical properties of Ru(II) complexes by specific design of tridentate ligands[J]. Coordination Chemistry Reviews, 2021, 446: 214127.
[68] PAL A K, HANAN G S. Design, synthesis and excited-state properties of mononuclear Ru(II) complexes of tridentate heterocyclic ligands[J]. Chemical Society Reviews, 2014, 43(17): 6184-6197.
[69] HAMMARSTRÖM L, JOHANSSON O. Expanded bite angles in tridentate ligands. Improving the photophysical properties in bistridentate Ru(II) polypyridine complexes[J]. Coordination Chemistry Reviews, 2010, 254(21-22): 2546-2559.
[70] RAUCHFUSS T. Inorganic Syntheses[M]. John Wiley & Sons, 2010.
[71] SULLIVAN B P, CALVERT J M, MEYER T J. Cis-trans isomerism in (trpy)(PPh3)RuC12. Comparisons between the chemical and physical properties of a cis-trans isomeric pair[J]. Inorganic Chemistry, 1980, 19(5): 1404-1407.
[72] MAGHACUT K A, WOOD A B, BOYKO W J, et al. Structural, electronic and acid/base properties of [Ru(tpy)(tpyOH)]2+ and [Ru(tpyOH)2]2+(tpy= 2,2':6',2''-terpyridine, tpyOH= 4’-hydroxy-2,2':6',2''-terpyridine)[J]. Polyhedron, 2014, 67: 329-337.
[73] MAESTRI M, ARMAROLI N, BALZANI V, et al. Complexes of the ruthenium(II)-2,2':6',2''-terpyridine family. Effect of electron-accepting and-donating substituents on the photophysical and electrochemical properties[J]. Inorganic Chemistry, 1995, 34(10): 2759-2767.