Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)–cobalt(III) bimetallic complex

Holbrook, Robert J.; Weinberg, David J.; Peterson, Mark D.; Weiss, Emily A.; Meade, Thomas J.

doi:10.1021/jacs.5b00342

Title: Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)–cobalt(III) bimetallic complex

Journal Article · Wed Feb 11 00:00:00 EST 2015 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.5b00342· OSTI ID:1345974

Holbrook, Robert J. ^[1]; Weinberg, David J. ^[1]; Peterson, Mark D. ^[1]; Weiss, Emily A. ^[1]; Meade, Thomas J. ^[1]

Northwestern Univ., Evanston, IL (United States)

In this paper, we describe a mechanism of light activation that initiates protein inhibitory action of a biologically inert Co(III) Schiff base (Co(III)-sb) complex. Photoinduced electron transfer (PET) occurs from a Ru(II) bipyridal complex to a covalently attached Co(III) complex and is gated by conformational changes that occur in tens of nanoseconds. Reduction of the Co(III)-sb by PET initiates displacement of the inert axial imidazole ligands, promoting coordination to active site histidines of α-thrombin. Upon exposure to 455 nm light, the rate of ligand exchange with 4-methylimidazole, a histidine mimic, increases by approximately 5-fold, as observed by NMR spectroscopy. Similarly, the rate of α-thrombin inhibition increases over 5-fold upon irradiation. Finally, these results convey a strategy for light activation of inorganic therapeutic agents through PET utilizing redox-active metal centers.

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Research Organization:: Northwestern Univ., Evanston, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC05-06OR23100

OSTI ID:: 1345974

Journal Information:: Journal of the American Chemical Society, Vol. 137, Issue 9; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 24 works

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References (46)

Metallodrugs in Medicinal Inorganic Chemistry Mjos, Katja Dralle; Orvig, Chris Chemical Reviews, Vol. 114, Issue 8 https://doi.org/10.1021/cr400460s	journal	January 2014
100 years of metal coordination chemistry: from Alfred Werner to anticancer metallodrugs Barry, Nicolas P. E.; Sadler, Peter J. Pure and Applied Chemistry, Vol. 86, Issue 12 https://doi.org/10.1515/pac-2014-0504	journal	December 2014
CHEMISTRY: Metal-Based Therapeutics Hambley, T. W. Science, Vol. 318, Issue 5855 https://doi.org/10.1126/science.1150504	journal	November 2007
Photoactivated chemotherapy (PACT): the potential of excited-state d-block metals in medicine Farrer, Nicola J.; Salassa, Luca; Sadler, Peter J. Dalton Transactions, Issue 48 https://doi.org/10.1039/b917753a	journal	January 2009
Redox activation of metal-based prodrugs as a strategy for drug delivery Graf, Nora; Lippard, Stephen J. Advanced Drug Delivery Reviews, Vol. 64, Issue 11 https://doi.org/10.1016/j.addr.2012.01.007	journal	August 2012
Facile Preparation of Mono-, Di- and Mixed-Carboxylato Platinum(IV) Complexes for Versatile Anticancer Prodrug Design Zhang, Jenny Z.; Bonnitcha, Paul; Wexselblatt, Ezequiel Chemistry - A European Journal, Vol. 19, Issue 5 https://doi.org/10.1002/chem.201203159	journal	December 2012
Photoactivatable metal complexes: from theory to applications in biotechnology and medicine Smith, Nichola A.; Sadler, Peter J. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol. 371, Issue 1995 https://doi.org/10.1098/rsta.2012.0519	journal	July 2013
Cellular Accumulation, Lipophilicity and Photocytotoxicity of Diazido Platinum(IV) Anticancer Complexes Pizarro, Ana M.; McQuitty, Ruth J.; Mackay, Fiona S. ChemMedChem, Vol. 9, Issue 6 https://doi.org/10.1002/cmdc.201402066	journal	May 2014
[Ru(bpy) ₂ (5-cyanouracil) ₂ ] ²⁺ as a Potential Light-Activated Dual-Action Therapeutic Agent Garner, Robert N.; Gallucci, Judith C.; Dunbar, Kim R. Inorganic Chemistry, Vol. 50, Issue 19 https://doi.org/10.1021/ic201615u	journal	October 2011
Coordination of Hydroxyquinolines to a Ruthenium Bis-dimethyl-phenanthroline Scaffold Radically Improves Potency for Potential as Antineoplastic Agents Heidary, David K.; Howerton, Brock S.; Glazer, Edith C. Journal of Medicinal Chemistry, Vol. 57, Issue 21 https://doi.org/10.1021/jm501043s	journal	October 2014
Strained Ruthenium Complexes Are Potent Light-Activated Anticancer Agents Howerton, Brock S.; Heidary, David K.; Glazer, Edith C. Journal of the American Chemical Society, Vol. 134, Issue 20 https://doi.org/10.1021/ja3009677	journal	May 2012
Control and utilization of ruthenium and rhodium metal complex excited states for photoactivated cancer therapy Knoll, Jessica D.; Turro, Claudia Coordination Chemistry Reviews, Vol. 282-283 https://doi.org/10.1016/j.ccr.2014.05.018	journal	January 2015
Effect of Electronic Structure on the Photoinduced Ligand Exchange of Ru(II) Polypyridine Complexes Garner, Robert N.; Joyce, Lauren E.; Turro, Claudia Inorganic Chemistry, Vol. 50, Issue 10 https://doi.org/10.1021/ic102482c	journal	May 2011
Cobalt derivatives as promising therapeutic agents Heffern, Marie C.; Yamamoto, Natsuho; Holbrook, Robert J. Current Opinion in Chemical Biology, Vol. 17, Issue 2 https://doi.org/10.1016/j.cbpa.2012.11.019	journal	April 2013
Spectroscopic Elucidation of the Inhibitory Mechanism of Cys ₂ His ₂ Zinc Finger Transcription Factors by Cobalt(III) Schiff Base Complexes Heffern, Marie C.; Kurutz, Josh W.; Meade, Thomas J. Chemistry - A European Journal, Vol. 19, Issue 50 https://doi.org/10.1002/chem.201301659	journal	November 2013
Inhibition of thermolysin and human α-thrombin by cobalt(III) Schiff base complexes Takeuchi, Toshihiko; Böttcher, Arnd; Quezada, Cindy M. Bioorganic & Medicinal Chemistry, Vol. 7, Issue 5 https://doi.org/10.1016/S0968-0896(98)00272-7	journal	May 1999
Selective Inhibition of Human α-Thrombin by Cobalt(III) Schiff Base Complexes Takeuchi, Toshihiko; Böttcher, Arnd; Quezada, Cindy M. Journal of the American Chemical Society, Vol. 120, Issue 33 https://doi.org/10.1021/ja981191x	journal	August 1998
Kinetics and thermodynamics of irreversible inhibition of matrix metalloproteinase 2 by a Co(III) Schiff base complex Harney, Allison S.; Sole, Laura B.; Meade, Thomas J. JBIC Journal of Biological Inorganic Chemistry, Vol. 17, Issue 6 https://doi.org/10.1007/s00775-012-0902-3	journal	May 2012
Targeted inhibition of Snail family zinc finger transcription factors by oligonucleotide-Co(III) Schiff base conjugate Harney, A. S.; Lee, J.; Manus, L. M. Proceedings of the National Academy of Sciences, Vol. 106, Issue 33 https://doi.org/10.1073/pnas.0906423106	journal	August 2009
Targeted Inactivation of Snail Family EMT Regulatory Factors by a Co(III)-Ebox Conjugate Harney, Allison S.; Meade, Thomas J.; LaBonne, Carole PLoS ONE, Vol. 7, Issue 2 https://doi.org/10.1371/journal.pone.0032318	journal	February 2012
Specific Inhibition of the Transcription Factor Ci by a Cobalt(III) Schiff Base–DNA Conjugate Hurtado, Ryan R.; Harney, Allison S.; Heffern, Marie C. Molecular Pharmaceutics, Vol. 9, Issue 2 https://doi.org/10.1021/mp2005577	journal	January 2012
Irreversible enzymatic inhibition by cobalt chelate complexes Böttcher, Arnd; Gray, Harry B.; Meade, Thomas J. Journal of Inorganic Biochemistry, Vol. 59, Issue 2-3 https://doi.org/10.1016/0162-0134(95)97327-M	journal	August 1995
Photoinduced Electron Transfer from PbS Quantum Dots to Cobalt(III) Schiff Base Complexes: Light Activation of a Protein Inhibitor Peterson, Mark D.; Holbrook, Robert J.; Meade, Thomas J. Journal of the American Chemical Society, Vol. 135, Issue 35 https://doi.org/10.1021/ja4065393	journal	August 2013
Axial Ligand Exchange of N -heterocyclic Cobalt(III) Schiff Base Complexes: Molecular Structure and NMR Solution Dynamics Manus, Lisa M.; Holbrook, Robert J.; Atesin, Tulay A. Inorganic Chemistry, Vol. 52, Issue 2 https://doi.org/10.1021/ic302379j	journal	January 2013
Rational design of [Co(acacen)L2]+ inhibitors of protein function Matosziuk, Lauren M.; Holbrook, Robert J.; Manus, Lisa M. Dalton Transactions, Vol. 42, Issue 11 https://doi.org/10.1039/c2dt32565a	journal	January 2013
Spectroscopy and Electrochemistry of Cobalt(III) Schiff Base Complexes Böttcher, Arnd; Takeuchi, Toshihiko; Hardcastle, Kenneth I. Inorganic Chemistry, Vol. 36, Issue 12 https://doi.org/10.1021/ic961146v	journal	June 1997
Photochemistry and photophysics of Ru(II)polypyridine complexes in the Bologna group. From early studies to recent developments Balzani, Vincenzo; Juris, Alberto Coordination Chemistry Reviews, Vol. 211, Issue 1 https://doi.org/10.1016/S0010-8545(00)00274-5	journal	January 2001
Spectroelectrochemical identification of charge-transfer excited states in transition metal-based polypyridyl complexes Brown, Allison M.; McCusker, Catherine E.; McCusker, James K. Dalton Trans., Vol. 43, Issue 47 https://doi.org/10.1039/C4DT02849J	journal	January 2014
Electrochemistry, spectroelectrochemistry, and photochemistry of a series of new covalently linked tris(2,2-bipyridine)ruthenium(II)/diquat complexes Elliott, C. Michael; Freitag, Ruth A.; Blaney, David D. Journal of the American Chemical Society, Vol. 107, Issue 16 https://doi.org/10.1021/ja00302a009	journal	August 1985
Ruthenium−Manganese Complexes for Artificial Photosynthesis: Factors Controlling Intramolecular Electron Transfer and Excited-State Quenching Reactions Abrahamsson, Malin L. A.; Baudin, Helena Berglund; Tran, Anh Inorganic Chemistry, Vol. 41, Issue 6 https://doi.org/10.1021/ic0107227	journal	March 2002
Intramolecular Electron Transfer from Manganese(II) Coordinatively Linked to a Photogenerated Ru(III)−Polypyridine Complex: A Kinetic Analysis Berglund-Baudin, Helena; Sun, Licheng; Davidov, Roman The Journal of Physical Chemistry A, Vol. 102, Issue 15 https://doi.org/10.1021/jp9731866	journal	March 1998
Intramolecular, Photoinduced Electron Transfer in Ruthenium(II) Bipyridine-Quinone Complexes Opperman, Kimberly A.; Mecklenburg, Sandra L.; Meyer, Thomas J. Inorganic Chemistry, Vol. 33, Issue 23 https://doi.org/10.1021/ic00101a022	journal	November 1994
Gated electron transfer: when are observed rates controlled by conformational interconversion? Hoffman, Brian M.; Ratner, Mark A. Journal of the American Chemical Society, Vol. 109, Issue 21 https://doi.org/10.1021/ja00255a003	journal	October 1987
Electron flow through metalloproteins Gray, Harry B.; Winkler, Jay R. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1797, Issue 9 https://doi.org/10.1016/j.bbabio.2010.05.001	journal	September 2010
Photoinduced electron transfer and back electron transfer within binuclear complexes of ruthenium(II) and cobalt(III) Yoshimura, Akio; Nozaki, Koichi; Ikeda, Noriaki Journal of the American Chemical Society, Vol. 115, Issue 16 https://doi.org/10.1021/ja00069a069	journal	August 1993
Single-Ion Reorganization Free Energy of Aqueous Ru(bpy) ₃ ^2+/3+ and Ru(H ₂ O) ₆ ^2+/3+ from Photoemission Spectroscopy and Density Functional Molecular Dynamics Simulation Seidel, Robert; Faubel, Manfred; Winter, Bernd Journal of the American Chemical Society, Vol. 131, Issue 44 https://doi.org/10.1021/ja9047834	journal	November 2009
Theoretical Analysis of Mechanistic Pathways for Hydrogen Evolution Catalyzed by Cobaloximes Solis, Brian H.; Hammes-Schiffer, Sharon Inorganic Chemistry, Vol. 50, Issue 21 https://doi.org/10.1021/ic201842v	journal	November 2011
Electron transfer in ruthenium-modified proteins Winkler, Jay R.; Gray, Harry B. Chemical Reviews, Vol. 92, Issue 3 https://doi.org/10.1021/cr00011a001	journal	May 1992
Photoinduced short-range electron transfer in DNA with fluorescent DNA bases: lessons from ethidium and thiazole orange as charge donors Prunkl, Christa; Berndl, Sina; Wanninger-Weiß, Claudia Phys. Chem. Chem. Phys., Vol. 12, Issue 1 https://doi.org/10.1039/B914487K	journal	January 2010
Base pair motions control the rates and distance dependencies of reductive and oxidative DNA charge transfer Valis, L.; Wang, Q.; Raytchev, M. Proceedings of the National Academy of Sciences, Vol. 103, Issue 27 https://doi.org/10.1073/pnas.0600957103	journal	June 2006
Charge on the move: how electron-transfer dynamics depend on molecular conformation Benniston, Andrew C.; Harriman, Anthony Chem. Soc. Rev., Vol. 35, Issue 2 https://doi.org/10.1039/B503169A	journal	January 2006
Light-Induced Electron Transfer in Pyropheophytin−Anthraquinone and Phytochlorin−Anthraquinone Dyads: Influence of Conformational Exchange Tkachenko, N. V.; Tauber, A. Y.; Grandell, D. The Journal of Physical Chemistry A, Vol. 103, Issue 19 https://doi.org/10.1021/jp983765q	journal	May 1999
Photoinduced charge separation in a porphyrin-tetraviologen supramolecular array Batteas, James D.; Harriman, Anthony; Kanda, Yu Journal of the American Chemical Society, Vol. 112, Issue 1 https://doi.org/10.1021/ja00157a020	journal	January 1990
Photoinduced electron transfer in α-helical polypeptides: dependence on conformation and electron donor–acceptor distance Jones II, Guilford; Zhou, Xin; Vullev, Valentine I. Photochem. Photobiol. Sci., Vol. 2, Issue 11 https://doi.org/10.1039/B306490E	journal	January 2003
Protease-activated receptors in hemostasis, thrombosis and vascular biology Coughlin, S. R. Journal of Thrombosis and Haemostasis, Vol. 3, Issue 8 https://doi.org/10.1111/j.1538-7836.2005.01377.x	journal	August 2005
Role of thrombin and thromboxane A2 in reocclusion following coronary thrombolysis with tissue-type plasminogen activator. Fitzgerald, D. J.; Fitzgerald, G. A. Proceedings of the National Academy of Sciences, Vol. 86, Issue 19 https://doi.org/10.1073/pnas.86.19.7585	journal	October 1989

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Designing metallodrugs with nuclease and protease activity Agbale, Caleb Mawuli; Cardoso, Marlon Henrique; Galyuon, Isaac Kojo Metallomics, Vol. 8, Issue 11 https://doi.org/10.1039/c6mt00133e	journal	January 2016
Vicinal Diol‐Tethered Nucleobases as Targets for DNA Redox Labeling with Osmate Complexes Havranová‐Vidláková, Pavlína; Krömer, Matouš; Sýkorová, Veronika ChemBioChem, Vol. 21, Issue 1-2 https://doi.org/10.1002/cbic.201900388	journal	August 2019
Heterodinuclear Pt( iv )–Ru( ii ) anticancer prodrugs to combat both drug resistance and tumor metastasis Ma, Lili; Ma, Rong; Wang, Zhigang Chemical Communications, Vol. 52, Issue 71 https://doi.org/10.1039/c6cc04354b	journal	January 2016
Metal‐Mediated Functionalization of Natural Peptides and Proteins: Panning for Bioconjugation Gold Ohata, Jun; Martin, Samuel C.; Ball, Zachary T. Angewandte Chemie International Edition, Vol. 58, Issue 19 https://doi.org/10.1002/anie.201807536	journal	May 2019
Physical properties, ligand substitution reactions, and biological activity of Co( iii )-Schiff base complexes King, A. Paden; Gellineau, Hendryck A.; MacMillan, Samantha N. Dalton Transactions, Vol. 48, Issue 18 https://doi.org/10.1039/c8dt04606a	journal	January 2019
Supramolecular Photoinduced Electron Transfer between a Redox-Active Hexanuclear Metal-Organic Cylinder and an Encapsulated Ruthenium(II) Complex Yang, Lu; He, Cheng; Liu, Xin Chemistry - A European Journal, Vol. 22, Issue 15 https://doi.org/10.1002/chem.201504975	journal	February 2016
Polymetallic Complexes for Applications as Photosensitisers in Anticancer Photodynamic Therapy Felder, Patrick S.; Keller, Sarah; Gasser, Gilles Advanced Therapeutics, Vol. 3, Issue 1 https://doi.org/10.1002/adtp.201900139	journal	November 2019
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“Chemistry-on-the-complex”: functional Ru ^II polypyridyl-type sensitizers as divergent building blocks Mede, Tina; Jäger, Michael; Schubert, Ulrich S. Chemical Society Reviews, Vol. 47, Issue 20 https://doi.org/10.1039/c8cs00096d	journal	January 2018

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