Jung, Michael E.

Organic

Jung Michael

Biography

Mike Jung received his Bachelor of Arts in 1969 from Rice University, doing research with Richard Turner, and then his PhD in 1973 from Columbia, where he worked with Gilbert Stork. After a one-year NATO postdoctoral fellowship with Albert Eschenmoser at the ETH in Zurich, he joined the faculty at UCLA in 1974. He has risen through the ranks at UCLA and is now a Distinguished Professor of Chemistry. He has served as a reviewer of proposals for various organizations, e.g., NSF, PRF, NIH Medicinal Chemistry Study Section, Research Corporation and others. He is on the Scientific Advisory Boards of several pharmaceutical firms and consults currently for more than 20 industrial laboratories in both the biotech and big pharma settings. Professor Jung is an authority on synthetic organic and medicinal chemistry and has more than 25 patents arising from both his consulting activities and his own research. His current interests include the easy preparation of hindered systems via both Diels-Alder reactions using a new mixed Lewis acid catalyst and via an unusual formal [3,3]-sigmatropic rearrangement. He has also pioneered the use of epoxide rearrangements in synthesis (e.g., the non-aldol aldol) and has investigated new types of gem-disubstituent effects in synthesis. He has published more than 250 articles in refereed journals and has given over 470 lectures on his research, including lectures in German and French. Finally one of his recent compounds is in Phase 1/2a clinical trials for the treatment of hormone refractory prostate cancer.

Research Interests

Antitumor and Antiviral Agents

At present we are engaged in the total synthesis of a large number of active antitumor and antiviral agents. The current cytotoxic targets include dichlorolissoclimide, tedanolide and 13-deoxytedanolide, aplysiapyranoids A-D, discodermide, dysidiolide, sclerophytin A, cylindramide A, and halomon and its alkene derivatives. The antiviral compounds are oxetanocin A and its analogues, both the carbocyclic ones, e.g., cyclobut-A and G, and the C-oxetanocins (related to oxetanocin H), methylene-expanded oxetanocins, several modified N-nucleosides (2′,3′-dideoxycytidine and analogues, AZT, d4T and their analogues, l-3-TC), carbovir, and the cyclophellitols. We are also investigating new methods for the preparation of l-carbohydrates and their corresponding modified nucleosides, e.g., l-5-F ddC, which have shown strong antiviral activity. As possible reagents for antisense oligonucleotide therapy, we are preparing both l-DNA and l-RNA. Finally we are preparing several isonucleosides and 4′-substituted 2′-deoxynucleosides as potential antiviral agents.

Jung.research

Other Biologically Active Compounds

The synthesis of several biologically active alkaloids is currently under investigation. Included among our synthetic goals are the following: the novel dimeric bis-amino acid isodityrosine, the antitumor agents bouvardin and deoxybouvardin, the ACE inhibitor K-13, the platelet aggregation inhibitor herquline, and the antifungal agent piperazinomycin. We are also pursuing total syntheses of some antiulcer compounds (the plaunol class of clerodane diterpenes), antiinflammatory agents (pseudopterosin A), and the unusual ketosterols xestobergsterol and contignasterol, which are inhibitors of histamine release. We are developing new processes for the efficient synthesis of various cardioactive agents, e.g., ouabain and several naturally occurring natriuretic agents. We have several collaborative programs, e.g., to prepare modified peptides as potential inhibitors of carboxy methyl transferases, to develop a new method of delivering antibacterial agents to resistant bacterial strains, and finally to determine the structures and mechanism of action of several naturally occurring natriuretic agents.

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New Synthetic Methods and Physical Organic Chemistry

We are studying several epoxide rearrangements, e.g., the preparation of asymmetric quaternary aldehydes from tertiary vinyl oxiranes. By this method, we have also determined that a benzylic cation is more stable than an allylic one, e.g., the ethenyl phenyl oxirane gave the single optically active product shown below. We have also developed a new method for the preparation of aldols by a non-aldol process.

Jung.synthetic

Thus conversion of an aldehyde to the epoxy alcohol via Wittig reaction and reduction followed by Sharpless epoxidation generates the substrate for the rearrangement which is effected by treatment with trialkylsilyl triflates and base to give the protected aldol products in high yield. We are now extending this reaction to the synthesis of polypropionates by an iterative process so that compounds such as erythromycin and rifamycin could be prepared.

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We are also studying the use of radical cyclization-fragmentation processes for the synthesis of several natural products of biological interest. Finally, we are investigating the synthetic potential of substituent effects (gem-dialkyl, -dialkoxy, -dithioalkoxy, -dicarboalkoxy, bis(dialkylamino), etc.) and polar solvent effects on cyclizations, including the novel acceleration of the intramolecular Diels-Alder reactions of furfuryl methyl fumarates by the use of polar solvents. Dialkoxy substitution, both gem and vic, allows one to carry out a wide variety of cyclizations, including cyclizations to produce 4- and 8-membered rings. We are also studying the possibility of asymmetric induction in these processes.

The Jung Research Group »

Honors & Awards

  • 2024 MEDI Hall of Fame
  • 2022 IUPAC-Richter Prize
  • 2021 JCCC, Breast Cancer Intramural Award (shared w/ Prof. Cun-Yu Wang, UCLA Dentistry)
  • 2020 UCLA Academic Senate Faculty Research Lectureship
  • 2019 LA BioStar Award, CSU Los Angeles
  • 2019 After Dinner Speaker, UCLA Biomedical and Life Science Innovation Day
  • 2019 American Association for Cancer Research Award for Outstanding Achievement in Chemistry in Cancer Research
  • 2019 Alexander Cruickshank Memorial Lecturer, University of Rhode Island
  • 2019 Keynote Lecturer, UCLA Brain Research Center, NIH SPORE meeting, UCLA
  • 2018 University of California Presidential Chair in Medicinal Chemistry, UCLA
  • 2018 Invited Lecture, Amgen Inventor’s Banquet, Ronald Reagan Presidential Library, Simi Valley, CA
  • 2018 Invited Lecture, Gilbert Stork Memorial Symposium, Columbia University, New York, NY
  • 2018 Keynote Lecture, UCLA Biomedical/Life Science Innovation Day, University of California, Los Angeles, CA
  • 2017 The Inaugural Nguyen and Tarbet Seminar in Translational Research, University of California, Irvine, CA
  • 2017 Plenary Lecturer, The William S. Johnson Symposium, Stanford, CA
  • 2017 The Inaugural Pfizer Oncology Lecture in Medicinal Chemistry, the Scripps Research Institute, La Jolla, CA
  • 2017 Plenary Lecturer, American Chemical Society Medicinal Chemistry Division and European Federation for Medicinal Chemistry Symposium, Philadelphia
  • 2017 Plenary Lecturer, 9th CINVESTAV/Sigma-Merck Symposium, Mexico City, Mexico
  • 2017 Plenary Lecturer, 2017 Sigma Aldrich Symposium, University of Texas Southwestern Medical Center, Dallas, TX
  • 2016 Glenn T. Seaborg Award Medalist, UCLA
  • 2016 Keynote Speaker, Yao Yuan Symposium, Chicago, IL
  • 2016 Richard C. Tolman Award, Southern California Section of the American Chemical Society
  • 2016 Carl M. Franklin Lecturer, University of Southern California
  • 2015 American Association of Cancer Research Team Science Award
  • 2015 National Academy of Inventors Inductee
  • 2012 Keynote Speaker, UCLA Department of Pharmacology Annual Retreat
  • 2011 Visiting Professor, Université Pierre et Marie Curie, Paris, France
  • 2011 Plenary Lecturer, Groupe Etude Chimie Organique Symposium, Aber Wrac’h, France
  • 2011 Plenary Lecturer, First Mexican Meeting on Pure and Applied Chemistry, Mexico City
  • 2011 Plenary Lecturer, USC Stauffer Symposium, Los Angeles, CA
  • 2011 Plenary Lecturer, ACS Award Symposium Award in Industrial Chemistry, Anaheim, CA
  • 2010 Plenary Lecturer, 14th International Congress on Hormonal Steroids, and Hormones and Cancer, Edinburgh
  • 2010 Dr. Paul Janssen Lecture Series in Organic Chemistry Lecturer, Johnson & Johnson Pharmaceeutical R&D, Beerse, Belgium
  • 2009 Herbert Newby McCoy Award Recipient, UCLA
  • 2009 Plenary Lecturer, ZaCh Systems Symposium on Organic Synthesis, Paris
  • 2009 Plenary Lecturer, Center for Cancer Research Eminent Lecture Series, National Cancer
  • 2008 Organic Synthesis Symposium, 43rd Mexican Chemical Society National Meeting, Tijuana, Mexico
  • 2008 Plenary Lecturer, Symposium in honor of Victor Marquez, American Chemical Society National Meeting, Philadelphia, PA
  • 2008 Plenary Lecturer, Chemical Insights into Biological Processes, Center for Cancer Research, National Cancer Institute, Frederick, MD
  • 2008 Plenary Lecturer, Symposium on Organic Synthesis, 91st National Meeting of the Canadian Society for Chemistry, Edmonton, Canada
  • 2007 Wolfrom Award Symposium in honor of Muthiah Manoharan, 234th ACS National Meeting, Boston, MA
  • 2006 Boehringer-Ingelheim Lecturer, University of British Columbia, Vancouver
  • 2004 Plenary Lecturer, Ischia Advanced School of Organic Chemistry, Ischia, Italy
  • 2004 Bristol-Myers Squibb Lecturer, University of Puerto Rico, Rio Piedras, PR
  • 2003 Invited Professor, Université Pierre et Marie Curie, Paris
  • 2002 Auspex Horizon Award, Auspex Pharmaceutical Co., Inc., San Diego, CA
  • 2002 Plenary Lecturer, 60th Anniversary International Symposium on Organic Synthesis, Tokyo, Japan
  • 2001 Plenary Lecturer, First International Symposium on Asymmetric Synthesis, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City
  • 1999 Plenary Lecturer, Japan Pharmaceutical Society, Tokushima, Japan
  • 1999 Plenary Lecturer, Japan Chemical Society, Tokyo, Japan
  • 1998 Plenary Lecturer, 21st Gulf Coast Chemistry Conference, Pensacola, FL
  • 1998 Invited Lecturer, XIII International Round Table on Nucleosides, Nucleotides and Their Biological Applications, Montpellier, France
  • 1998 Invited Lecturer, 19th International Carbohydrate Symposium, La Jolla, CA
  • 1998 Plenary Lecturer, Western Switzerland Lecture Tour
  • 1998 Plenary Speaker, Spring Meeting, French Chemical Society, Paris
  • 1998 Plenary Lecturer, Robert A. Welch Foundation
  • 1997 Plenary Speaker, 2nd AFMC International Medicinal Chemistry Symposium (AIMECS 97), Seoul
  • 1997 Invited Lecturer, 16th International Congress of Heterocyclic Chemistry, Montana State University, Bozeman, MT
  • 1995 American Chemical Society Arthur C. Cope Scholar Award
  • 1995 Plenary Lecturer, Gordon Conference on Purines, Pyrimidines, and Other Related Substances
  • 1995 Plenary Lecturer, 5th French American Chemical Society (FACS) Conference
  • 1992 Hanson-Dow Teaching Award, UCLA
  • 1991 Herbert Newby McCoy Award Recipient, UCLA
  • 1991 Fujii-Ohtsuka Professor, University of Tokushima, Tokushima, Japan
  • 1988 Plenary Lecturer, 3rd Nozaki Conference, Sagamihara, Japan
  • 1987 Glenn T. Seaborg Award Recipient
  • 1987 Plenary Lecturer, Gordon Conference on Natural Products Chemistry
  • 1987 Plenary Lecturer, Gordon Conference on Organic Reactions and Processes
  • 1986 Inaugural UCLA Gold Shield Faculty Prize
  • 1985 Plenary Lecturer, 9th Oxford Symposium on Organic Synthesis, Oxford
  • 1982 Plenary Lecturer, 4th International Conference on Organic Synthesis, Tokyo
  • 1981 Invited Participant, Twelfth Annual Workshop on Organic Synthesis in Natural Products Chemistry, Pingree Park, Colorado
  • 1981 Plenary Lecturer, French Chemical Society Meeting, Paris (Spring)
  • 1980 Fulbright-Hays Grant, U.S. Research Scholar Award
  • 1980 American Cyanamid Young Researcher Award
  • 1980 Plenary Lecturer, Gordon Conference on Organometallic Chemistry
  • 1979 Alfred P. Sloan Foundation Research Fellow
  • 1979 Camille and Henry Dreyfus Teacher-Scholar Grantee
  • 1977 Eli Lilly Grantee
  • 1978 University Distinguished Teaching Award
  • 1978 Invited Speaker, Symposium for Creative Work in Synthetic Organic Chemistry, 175th ACS National Meeting, Anaheim
  • 1978 Plenary Lecturer, 5th Annual Conference on Organosilicon Chemistry
  • 1977 Invited Participant, Eight Annual Workshop on Organic Synthesis in Natural Products Chemistry, Dartmouth College Minary Conference Center, NH
  • 1975 UCLA Summer Faculty Fellow

Representative Publications

[ Selected Publications ]

  • C. Tran, S. Ouk, N. J. Clegg, Y. Chen, P. A. Watson, V. Arora, J. Wongvipat, P. M. Smith-Jones, D. Yoo, A. Kwon, T. Wasielewska, D. Welsbie, C. Chen, C. S. Higano, T. M. Beer, D. T. Hung, H. I. Scher, M. E. Jung, and C. Sawyers,Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate CancerScience, 2009, 324, 787-790. PMID: 19359544. PMCID: 2981508.
  • N. Suree, S. W. Yi, W. Thieu, M. Marohn, R. Damoiseaux, A. Chan, M. E. Jung and R. T. Clubb,Discovery and Structure Activity Relationship Analysis of Staphylococcus aureus Sortase A InhibitorsBioorg. Med. Chem. 2009, 17, 7174-7185. PMID: 19781950. PMCID: 2888031.
  • M. C. Wolf, A. N. Freiberg, T.-H. Zhang, Z. Akyol-Ataman, A. Grock, P. W. Hong, J. Li, N. F. Watson, A. Q. Fang, H. C. Aguilar, M. Porotto, A. N. Honko, R. Damoiseaux, J. P. Miller, S. E. Woodson, S. Chantasirivisal, V. Fontanes, O. A. Negrete, P. Krogstad, A. Dasgupta, A. Moscona, L. E. Hensley, S. P. Whenlan, K. F. Faull, M. R. Holbrook, M. E. Jung, and B. Lee,A Broad-spectrum Antiviral Targeting Entry of Enveloped VirusesProceed. Natl. Acad. Sci. U. S. A. 2010, 107, 3157-3162, S3157/1-S3157/11. PMID 20133606. PMCID: 2840368.
  • M. E. Jung, S. Ouk, D. Yoo, C. L. Sawyers, C. Chen, C. Tran, and J. Wongvipat,Structure-Activity Relationship for Thiohydantoin Androgen Receptor Antagonists for Castration-Resistant Prostate Cancer (CRPC)J. Med. Chem. 2010, 53, 2779-2796. PMID: 20218717. PMCID: 3180999.
  • M. Aghajan, N. Jonai, K. Flick, F. Fu, M. Luo, X. Cai, I. Ouni, N. Pierce, X. Tang, B. Lomenick, R. Damoiseaux, R. Hao, P. N. del Morala, R. Verma, Y. Li, C. Li, K. N. Houk, M. E. Jung, N. Zheng, L. Huang, R. J. Deshaies, P. Kaiser, and J. Huang,Chemical Genetics Screen for Enhancers of Rapamycin Identi-fies a Specific Inhibitor of the SCF Family E3 Ubiquitin LigaseNature Biotechnology 2010, 28, 738-742. PMID: 20581845. PMCID: 2902569.
  • J. Johnson, V. Meliton, W. K. Kim, K. B. Lee, J. Wang, K. L. Nguyen, D. Yoo, M. E. Jung, E. Atti, S. Tetradis, R. Pereira, C. Magyar, T. Nargizyan, T. Hahn, F. Farouz, S. Thies, and F. Parhami,Novel Oxysterols Have Pro-Osteogenic and Anti-Adipogenic Effects In Vitro and Induce Spinal Fusion In VivoJ. Cellular Biochem. 2011, 112, 1673-1684. PMID: 21503957. PMCID: 3080246.
  • M. E. Jung, J.-M. Ku, L. Du, H. Hu, and R. A. Gatti,Synthesis and Evaluation of Compounds that Induce Readthrough of Premature Termination CodonsBioorg. Med. Chem. Lett. 2011, 21, 5842-5848. PMID: 21873052. PMCID: pending.
  • N. J. Clegg, J. Wongvipat, C. Tran, S. Ouk, A. Dilhas, Y. Chen, K. Grillot, E. Bischoff, L. Cai, A. Aparicio, J. Kaufman, V. Arora, G. Shao, J. Qian, H. Zhao, G. Yang, J. Sensintaffar, T. Wasielewska, H. I. Scher, P. Smith-Jones, C. Bonnefous, J. Joseph, D. Darimont, M. Klang, E. De Stanchina, N. Wu, N. D. Smith, O. Ouerfelli, P. Rix, R. A. Heyman, M. E. Jung, C. Sawyers, and J. H. Hager,Discovery and development of ARN-509, a novel Anti-androgen for the Treatment of Prostate CancerCancer Res. 2012, 72, 1494-1503. PMID: 22266222. PMCID: 3306502.
  • F. Stappenbeck, W. Xiao, M. Epperson, M. Riley, A. Priest, D. Huang, K. Nguyen, M. E. Jung, R. S. Thies and F. Farouz,nn Novel Oxysterols Activate the Hedgehog Pathway and Induce OsteogenesisBioorg. Med. Chem. Lett. 2012, 22, 5893-5897. PMID: 22901899. PMCID: pending.
  • R. Kayali, J.-M. Ku, G. Khitrov, M. E. Jung, O. Prikhodko, and C. Bertoni,Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophyHum. Mol. Genet. 2012, 21, 4007-4020. PMID: 22692682. PMCID: 3607466.
  • F. Vigant, J. Lee, A. Hollmann, L. Tanner, Z. Akyol-Ataman, G. Shui, H. Aguilar-Carreno, T. Yun, D. Zhang, D. Meriwether, G. Roman-Sosa, L. Robinson, T. Juelich, H. Buczkowski, S. Chou, M. A.R.B. Castanho, M. C. Wolf, A. Banyard, M. Kielian, S. Reddy, M. R. Wenk, M. Selke, N. C. Santos, A. Freiberg, M. E. Jung, and B. Lee,A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-cell FusionPLOS Pathog. 2013, 9, e1003297. PMID: 23637597. PMCID: 3630091.
  • W. Zhong, J. R. Springstead, R. Al-Mubarak, S. Lee, R. Li, B. Emert, J. A. Berliner, and M. E. Jung,An Epoxyisoprostane is a Major Regulator of Endothelial Cell FunctionJ. Med. Chem. 2013, 56, 8521-8532.
  • E. J. Gillespie, C.-L. Ho, K. Balaji, Z. Li, D. Thomas, D. L. Clemens, G. Deng, Y. Wang, H. Elsaesser, B. Tamilselvam, B. France, B. T. Chamberlain, S. R. Blanke, G. Cheng, D. Brooks, M. E. Jung, M. Manchester, J. Zink, J. Colicelli, R. Damoiseaux, and K. A. Bradley,Selective Inhibitor of Endosomal Trafficking Pathways Exploited by Multiple Toxins and VirusesProc. Natl. Acad. Sci. U.S.A., 2013, 110, E4904-E4912, SE4904/1-SE4904/4. PMCID: 3864319
  • D. L. Sun, S. Poddar, R. D. Pan, E. W. Rosser, E. R. Abt, J. Van Valkenburgh, T. M. LE, V. Lok, J. Capri, S. P. Hernandez, J. Song, J. Li, A. Turlik, X. Chen, C.-A. Cheng, W. Chen, C. E. Mona, A. D. Stuparu, L. Vergnes, K. Reue, R. Damoiseaux, J. I. Zink, J. Czernin, T. R.Donahue, K. N. Houk, M. E. Jung, and C. G. Radu, “Isoquinoline thiosemicarbazone displays potent anticancer activity with in vivo efficacy against aggressive leukemia,” ChemRxiv 2019, 1-12; RSC Medicinal Chemistry 2020, 11 (3), 392-4110. [pdf]
  • S. Poddar, E. Capparelli, E. W. Rosser, R. M. Gipson, L. Wei, T. Le, M. E. Jung, C. Radu, M. Nikanjam, “Development and preclinical pharmacology of a novel dCK inhibitor, DI-87,” Brit. J. Pharmacol. 2020, 172, 113742. [pdf]
  • J. Tsang, L. Urner, G. Kim, K. Chow, L. Baufeld, K. Faull, T. Cloughesy, P. Clark, M. E. Jung, D. Nathanson, “Development of a Potent Brain-Penetrant EGFR Tyrosine Kinase Inhibitor Against Malignant Brain Tumors,” ACS Med. Chem. Lett. 2020, 11(10), 1799-1809. [pdf]
  • X. Xiao, Y. Kim, B. Romartinez-Alonso, K. Sirvydis, D. S. Ory, J. W. R. Schwabe, M. E. Jung, and P. Tontonoz, “Selective Aster inhibitors distinguish vesicular and nonvesicular sterol transport mechanisms,” Proc. Natl. Acad. Sci. U. S. A. 2021, 118(2), e2024149118. [pdf]
  • X. Liu, A. Flores, L. Situ, W. Gu, H. Ding, H. Christofk, W. Lowry, and M. E. Jung, “Development of Novel Mitochondrial Pyruvate Carrier Inhibitors to Treat Hair Loss,” J. Med. Chem. 2021, 64 (4), 2046-2063. [pdf]
  • J. E. Gosschalk, C. Chang, C. K. Sue, S. D. Siegel, C. Wu, M. D. Kattke, S. W. Yi, R. Damoiseaux, M. E. Jung, H. Ton-That, R. T. Clubb, “A Cell-based Screen in Actinomyces oris to Identify Sortase Inhibitors,” Sci. Rep. 2020, 10 (1), 8520. [pdf]
  • H. J. Gim, J. Park, M. E. Jung, and K. N. Houk, “Conformational Dynamics of Androgen Receptors Bound to Agonists and Antagonists,” Sci. Rep. 2021, 11 (1), 15887. [pdf]
  • E. D. Micewicz, R. D. Damoiseaux, G. Deng, A. Gomez, K. S. Iwamoto, M. E. Jung, C. Nguyen, A. J. Norris, J. A. Ratikan, P. Ruchala, J. W. Sayre, D. Schaue, J. P. Whitelegge, and W. H. McBride, “Classes of Drugs that Mitigate Radiation Syndromes,” Front. Phamacol. 2021, 12, article 666776. [pdf]
  • L. M. Urner, G. Y. Lee, J. W. Treacy, A. Turlik, S. I. Khan, K. N. Houk, and M. E. Jung, “Intramolecular NH···F Hydrogen Bonding Interaction in a Series of 4-Anilino-5-Fluoroquinazolines: Experimental and Theoretical Characterization of Electronic and Conformational Effects,” Chem. Eur. J. 2022, 28, e2021031. [pdf]
  • O. E. Martinez, B. J. Mahoney, A. K. Goring, S.-W. Yi, D. P. Tran, D. Cascio, M. L. Phillips, M. M. Muthana, X. Chen, M. E. Jung, J. A. Loo, and R. T. Clubb, “Insight into the molecular basis of substrate recognition by the wall teichoic acid glycosyltransferase TagA,” J. Biol. Chem. 2022, 298(2), 101464. [pdf]
  • S. Li, T. Yokota, P. Wang, J. ten Hoeve, F. Ma, T. M. Le, E. R. Abt, Y. Zhou, R. Wu, M. Nathavongdouangsy, A. Rodriguez, Y. Wang, H. Muranaka, M. Sharpley, D. T. Braddock, V. E MacRae, U. Banerjee, M. Seldin, D. Huang, M. Teitell, I. Gertsman, M. E, Jung, S. J. Bensinger, R. Damoiseaux, K. Faull, M. Pellegrini, A. J. Lusis, T. Graeber, C. G. Radu, and A. Deb, “Extracellular adenine released by the cardiac muscle cell disrupts pyrimidine biosynthesis in non-muscle cells to regulate tissue repair after heart injury,” J. Clin. Invest. 2022, 132(2), e149711. [pdf]

For a complete list of all publications, see: http://www.chem.ucla.edu/~jung/publications.html