Dr. Kenneth D. Karlin

Abstract

    Copper ion is a vital constituent of metalloprotein active sites, those required to support the life of aerobic organisms. The biological roles of copper proteins include electron shuttling/trafficking and the processing of the critical small molecule nitrogen oxides NO (nitric oxide; nitrogen monoxide), nitrite (NO₂^–) and nitrous oxide (N₂O).  In the processing of O₂ (molecular oxygen; dioxygen), copper proteins participate in hemolymph O₂-transport, oxygenase activity (i.e., O-atom(s) insertion into organic substrates) and O₂-reduction to hydrogen peroxide or water accompanied by substrate dehydrogenation/oxidation. Functions include pigment production, generation of neurotransmitters and hormones, conversion of methane to methanol, oxidative cleavage of recalcitrant polysaccharides as well as production and scavenging of reactive oxygen species (ROS). Much of the biochemistry of copper surrounds the rich one-electron (e⁻) redox chemistry of copper shuttling within the Cu^II/Cu^I oxidation states. Brief overviews of relevant copper-protein biochemistry will be woven into the presentation of relevant coordination chemistry.

    Our long-term research program on copper-dioxygen chemistry has focused on ligand design, systematic ligand variation and the use of cryogenic solution handling, enabling the generation and investigation of new coordination complexes, ligand-bound Cu^I_n/O_2(g) (n = 1, 2) derived species. Through this approach, one may identify factors such as donor atom type or number, coordination geometry, metal complex redox potential, and second coordination sphere composition, those which significantly contribute to the unique reactivity properties of Cu-metalloprotein active sites, the nature/structure of reactive intermediates and details concerning reaction mechanism(s) involved.

    Prior to our research efforts, no synthetically derived well-characterized Cu^I_n-(O_2(g)) species existed. Success in this area has come from carefully considered ligand design and application of cryogenic solution handling. Use of tripodal tetradentate N₄ ligands leads to the generation of superoxo-copper(II) {(ligand)Cu^II(O₂^•–)} complexes and/or peroxo-dicopper(II) analogs which have been characterized structurally/spectroscopically and have been examined with respect to a variety of reaction types. Binucleating ligands of several types hold two copper(I) ions and exhibit various reactivities, including reversible O_2(g)-binding and/or ‘activation’ of the bound peroxo (O₂^2–) ligand leading to hydroxylation of unactivated arene C–H bonds, chemistry which has relevance to Tyrosinase enzyme reaction mechanism. Use of derived (by arene hydroxylation) binucleating ligand containing phenolato-bridged dicopper complexes leads to new kinds of superoxo, peroxo or hydroperoxo dicopper(II) complexes. We show that these species can be reversibly interconverted with oxidants/reductants and/or acids-bases, thus leading us to elucidate thermodynamic interrelationships; these reveal how differences in ligand properties influence the nature (i.e., reactivity) of the O_2(g)-derived species bound to copper ion(s). Time permitting, presentation of a recently described peroxo-dicopper(II) complex nucleophilic oxidative aldehyde deformylation reaction, that involving dioxygenase chemistry, will be presented.

    Results obtained from the present research presented provides insights into biological copper ion mediated O₂-processing and thus also possibly can apply to practical organic oxidation chemistry and/or energy related fuel-cell technologies.

Recent relevant publications:

Karlin, Kenneth D.; Hota, Pradip Kumar; Kim, Bohee; Panda, Sanjib; Phan, Hai “Synthetic Copper-(Di)oxygen Complex Generation and Reactivity Relevant to Copper Protein O₂-Processing” Bull. Jpn. Soc. Coord. Chem. 2024, 83, 16-27.

Kim, Bohee.; Karlin, Kenneth D. “Ligand–Copper(I) Primary O₂-Adducts: Design, Characterization, and Biological Significance of Cupric–Superoxides” Acc. Chem. Res. 2023, 56, 2197-2212.

Quist, David. A.; Ehudin, Melanie A.; Schaefer, A. W.; Schneider, G. L.; Solomon, Edward I.; Karlin, Kenneth D.
“Ligand Identity-Induced Generation of Enhanced Oxidative Hydrogen Atom Transfer Reactivity for a Cu^II₂(O₂^•−) Complex Driven by Formation of a Cu^II₂(⁻OOH) Compound with a Strong O−H Bond”. J. Am. Chem. Soc. 2019, 141, 12682.

Quist, David A.; Diaz, Daniel E.; Liu, Jeffrey J.; Karlin, Kenneth D. Activation of dioxygen by copper metalloproteins and insights from model complexes. J. Biol. Inorg. Chem. 2017, 22, 253-288.

Biography

Kenneth D. Karlin is the Ira Remsen Professor of Chemistry at Johns Hopkins University in Baltimore, Maryland, USA. He was educated at Stanford University (cum laude, B.S. 1970) and at Columbia University, New York (Ph.D. 1975; Preceptor, Stephen J. Lippard). He was a N.A.T.O. postdoctoral fellow at Cambridge University in England, before being appointed Assistant Professor of Chemistry at the State University of New York at Albany (SUNY Albany) in 1977.  He moved to The Johns Hopkins University as Professor in 1990, where he was appointed as Ira Remsen Chair in Chemistry in 1999. He (recently) led the Johns Hopkins University Chemistry department, serving as Chair from 2014-1017. Dr. Karlin served as Editor-in-Chief of Progress in Inorganic Chemistry (John Wiley & Sons) from 1992-2018 (Volumes 41-59) and has throughout his career has served on various journal Editorial or Advisory Boards. He also has served in advisory or administrative positions with the Society for Biological Inorganic Chemistry (SBIC), the Petroleum Research Fund (PRF) (of the American Chemical Society (ACS)) and the Division of Inorganic Chemistry (DIC) of the ACS, most recently as 2013 DIC Chair (elected)). He is also a Fellow of the American Association for the Advancement of Science and was elected as an ACS Fellow in 2014. For additional research accomplishments/recognitions, he won a 2009 ACS National Award, the F. Albert Cotton Award in Synthetic Inorganic Chemistry. Most recently he was announced as the 2021 winner of the ACS Award for Distinguished Service in the Advancement of Inorganic Chemistry, a recognition for a career full of outstanding research, as well as service to the (bio)inorganic chemistry community. Other recognitions include the 2019 KAIST Distinguished Lectureship Award for 2019 (Dajeon, Korea). The 10^th Sunney Chan Lectureship (2014, Academia Sinica, Taiwan), the Maryland Chemistry of the Year Award (2011) and the ACS Sierra Nevada Distinguished Chemist Award (2009). Dr. Karlin has been Organizer/Chair of a number of international meetings on copper and/or bioinorganic chemistry (2017, 2005, 1992, 1984, 1982), the 1998 Metals in Biology Gordon Research Conference (elected as Chair) and the 1989 International Conference on Bioinorganic Chemistry (ICBIC-4; ~ 750 participants). In the bioinorganic chemistry realm, he has served in various capacities for the Society of Biological Inorganic Chemistry (SBIC), as Treasurer and for 16 years was Chair of the SBIC’s International Organizing Committee, the body that oversees the series of biennial ICBIC meetings. Dr. Karlin’s bioinorganic research focuses on the design, synthesis and study of coordination complexes whose chemistry is relevant to biological processes, mainly metalloenzyme active site chemistry, involving copper and/or heme (porphyrin-iron) complexes and their chemistry with molecular oxygen, its reduced derivatives, and nitrogen oxide compounds. He has published over 380 papers in peer-reviewed journals.