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Ruthenium Complexes

Photochemical and Biomedical Applications


Edited by

Alvin A. Holder
Lothar Lilge
Wesley R. Browne
Mark A.W. Lawrence
Jimmie L. Bullock Jr.






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Dedicated to Karen with admiration, affection, and respect!!


Dear Karen, we will miss you for your class, humour, and knowledge!!


About the Editors

Alvin A. Holder is an associate professor at Old Dominion University in Norfolk, USA. He graduated from the University of the West Indies (UWI), Mona Campus, Jamaica, with a BSc (special chemistry) in 1989 and acquired his PhD in inorganic chemistry in 1994 with Prof. Tara P. Dasgupta. He was a faculty member at the University of the West Indies, Cave Hill Campus, Barbados, and an assistant professor in chemistry at the University of Southern Mississippi. His current research involves transition metal chemistry and he has published more than 65 articles and several textbooks and book chapters. In 2012, he was awarded an NSF Career Award.

Lothar Lilge is a Senior Scientist at the Princess Margaret Cancer Centre and holds a professorship at the University of Toronto, Canada. He obtained his Diploma in physics from the Johann Wolfgang Goethe University in Frankfurt, Germany, and his PhD in biophysics from the Westfaehlische Wilhelms University in Muenster, Germany. Additional training was provided through the Wellman Laboratories of Photomedicine at Massachusetts General Hospital, Boston, USA, and during a post-doc at McMaster University in Hamilton, Canada. His work is focused on photodynamic therapy including the use of ruthenium-based photosensitizers and optical spectroscopy for diagnostic and risk assessment among a range of other biophotonic application in medicine.

Wesley R. Browne is an associate professor at Stratingh Institute for Chemistry at the University of Groningen, The Netherlands, since 2013. He completed his PhD at Dublin City University, Ireland, with Prof. J. G. Vos in 2002, followed by a post-doc under the joint guidance of Prof. J. G. Vos and Prof. J. J. McGarvey, Queens University Belfast, UK. Between 2003 and 2007 he was a postdoctoral research fellow in the group of Prof. B. L. Feringa at the University of Groningen. He was appointed assistant professor in 2008. His current research interests include transition-metal-based oxidation catalysis, electrochromic materials, and responsive surfaces. He is an advisory board member for the European Journal of Inorganic Chemistry, Particle & Particle Characterization (both Wiley) and Chemical Communications (RSC). He has (co-)authored over 150 research papers, reviews, and book chapters.

Mark A. W. Lawrence was a post-doctoral fellow at Old Dominion University in Norfolk, USA, in the group of Prof. A. Holder. He received his BSc degree in 2006 and his PhD degree in inorganic-physical chemistry in 2011 from the University of the West Indies (UWI), Mona Campus, Jamaica, with Prof. Tara P. Dasgupta. His research interests include synthesis of hydrazones and functionalized pyridyl benzothiazoles, their transition metal complexes and application to catalysis and biological processes.

Jimmie L. Bullock Jr is a PhD student at the University of Kentucky in Lexington, USA, in the department of Chemistry. He received his BSc from Longwood University, Farmville, USA, and his MS in biological inorganic chemistry from Old Dominion University, Norfolk, USA, in 2013 and 2016, respectively. His research interests include studying activation of signaling pathways induced by non-platinum-based chemotherapeutic agents and synthesis of lanthanide sensor molecules.


Ruthenium, a second-row transition metal, continues to attract much attention in scientific research, as it possesses a vast array of novel applications and properties. The enormous chemistry of ruthenium, much of which remains untapped, has been and continues to be investigated by numerous researchers. One such person was an icon, Prof. Karen J. Brewer. Karen, as she was affectionately called by many of her friends and research students, is being honored for her contribution to research on ruthenium with this textbook.

Ruthenium and its compounds are also paramount in catalysis and medicine, so it is not surprising that its biological activities and coordination chemistry remain very active areas of research. Ruthenium-containing complexes have long been known to be well suited for biological applications, and have long been studied as replacements to popular platinum-based drugs.

The textbook entitled “Ruthenium Complexes: Photochemical and Biomedical Applications” focuses on the uses and application of ruthenium-containing complexes in medicine and renewable energy. This title is unique as it discusses potential applications of ruthenium complexes in solving some of the world's foremost problems. While the biological application of ruthenium-containing complexes has been known for years, their application as photosensitizers in the emerging field of photodynamic therapy, also known as photochemotherapy, is of special interest. Photodynamic therapy can be utilized to treat a wide range of medical conditions including macular degeneration and malignant cancers. Ruthenium-containing photosensitizers have been shown to be especially active in the latter, with often minimal dark toxicity. Light-activated ruthenium-containing complexes are also gaining much attention as molecular catalysts in artificial photosynthesis for the production of hydrogen gas in aqueous media, after water oxidation.

Our goal at the outset was to capture the full vibrancy of the biological and coordination chemistry of this very important element called ruthenium and, in this way, to reflect the insight and enthusiasm of the honoree, Karen. To do so, we have divided this textbook into three sections with 15 chapters: (1) Introduction (Chapters 1–2), (2) Artificial Photosynthesis (Chapters 3 and 4), and (3) Applications in Medicine (Chapters 5–15). As such, we invited experts in each of these areas to complete this project by contributing a chapter. The chapters are as follows: Chapter 1: Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon; Chapter 2: Basic Coordination Chemistry of Ruthenium; Chapter 3: Water Oxidation Catalysis with Ruthenium; Chapter 4: Ruthenium- and Cobalt-Containing Complexes and Hydrogenases for Hydrogen Production; Chapter 5: Ligand Photosubstitution Reactions with Ruthenium Compounds: Applications in Chemical Biology and Medicinal Chemistry; Chapter 6: Use of Ruthenium Complexes as Photosensitizers in Photodynamic Therapy; Chapter 7: Photodynamic Therapy in Medicine with Mixed-Metal/Supramolecular Complexes; Chapter 8: Ruthenium Anticancer Agents En Route to the Tumor: From Plasma Protein Binding Agents to Targeted Delivery; Chapter 9: Design Aspects of Ruthenium Complexes as DNA Probes and Therapeutic Agents; Chapter 10: Ruthenium-Based Anticancer Compounds: Insights into Their Cellular Targeting and Mechanism of Action; Chapter 11: Targeting cellular DNA with Luminescent Ruthenium(II) Polypyridyl Complexes; Chapter 12: Biological Activity of Ruthenium Complexes With Quinoline Antibacterial and Antimalarial Drugs; Chapter 13: Ruthenium Complexes as NO Donors: Perspectives and Photobiological Applications; Chapter 14: Trends and Perspectives of Ruthenium Anticancer Compounds (Non-PDT); and Chapter 15: Ruthenium Complexes as Antifungal Agents.

It has been our good fortune to work with so many exceptionally talented contributors from all over the world in compiling a textbook that we believe will be a valuable resource for graduate students, young investigators, and more senior scholars in the field of biological and coordination chemistry. We thank all the contributors for their hard work and their willingness to assist us whenever requested.

July 20, 2017

Alvin Holder
Norfolk, Virginia, USA


This is my acknowledgment which is based on the influence of Professor Karen Brewer on my life as she taught me how to carry out good and sensible chemistry with osmium(II), ruthenium(II), and rhodium(III) complexes. Photodynamic therapeutic studies with pUC18 and pBluescript DNA plasmids and Vero cells were the order of the day! This research catalyzed my career and research in the USA.

The task of working with so many gifted authors has been a real treat for me. The project also presented many challenges. We would not have made it to the finish line without the assistance of so many colleagues. We have not lost any Soldados on this journey. Thank God!!

In an Invited Plenary Talk: 251st ACS National Meeting and Exposition, March 13–17, 2016, San Diego, California. Abstract # INOR-1141. Title: “Light that pleases the world in science: The Karen Brewer's effect on my academic career.” Author: Alvin A. Holder; I learnt about the seven (7) Ps from Professor Mark Richter and the Brew Crew, who attended the ACS conference. They are as follows:

The seven (7) Ps

  1. Proper
  2. Prior
  3. Planning
  4. Prevents
  5. Piss
  6. Poor
  7. Performance

Credit for the seven (7) Ps must be given to my deceased former postdoctoral mentor, Professor Karen J. Brewer. She was a great Lady, who believed in “Family First”!! Please see


I would like to thank the National Science Foundation (NSF) for a National Science Foundation CAREER Award as this material is based upon work supported by the National Science Foundation under CHE-1431172 (formerly CHE – 1151832). I would also like to thank Old Dominion University's Faculty Proposal Preparation Program (FP3), and also for the Old Dominion University start-up package that allowed for the successful completion of this work. Full gratitude to Professor Karen Brewer (R.I.P.), Professor Brenda Winkel, Professor Larry Taylor, Dr Myra Gordon, the research group (The Brew Crew), and all at Virginia Tech.

Personally, I would like to thank Dr. Anne Brennführer, Dr. Eva-Stina Müller, Ramprasad Jayakumar, Anne, Claudia Nussbeck, Dr. Eva-Stina Müller, and Samnaa Srinivas.

Alvin A. Holder

Section I