ACS Publications. Most Trusted. Most Cited. Most Read

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Med. Chem. 2007, 50, 19, 4642-4647
RETURN TO ISSUEPREVArticleNEXT

Use of Density Functional Calculations To Predict the Regioselectivity of Drugs and Molecules Metabolized by Aldehyde Oxidase

View Author Information
Department of Molecular Systems, Merck Research Laboratories, Rahway, New Jersey 07065, Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19468, and Department of Chemistry, Washington State University, Pullman, Washington 99164
Cite this: J. Med. Chem. 2007, 50, 19, 4642–4647
Publication Date (Web):August 25, 2007
https://doi.org/10.1021/jm0703690
Copyright © 2007 American Chemical Society
Request reuse permissions

    Article Views

    1368

    Altmetric

    -

    Citations

    64
    LEARN ABOUT THESE METRICS
    Read OnlinePDF (197 KB)
    Get e-Alerts
    SUBJECTS:

    Abstract

    Abstract Image

    Aldehyde oxidase is a molybdenum hydroxylase that catalyzes the oxidation of aldehydes and nitrogen-containing heterocycles. The enzyme plays a dual role in the metabolism of physiologically important endogenous compounds and the biotransformation of xenobiotics. Using density functional theory methods, geometry optimization of tetrahedral intermediates of drugs and druglike compounds was examined to predict the likely metabolites of aldehyde oxidase. The calculations suggest that the lowest energy tetrahedral intermediate resulting from the initial substrate corresponds to the observed metabolite ≥90% of the time. Additional calculations were performed on a series of heterocyclic compounds where the products resulting from metabolism by xanthine oxidase and aldehyde oxidase differ in many instances. Again, the lowest energy tetrahedral intermediate corresponded to the observed product of aldehyde oxidase metabolism ≥90% for the compounds examined, while the observed products of xanthine oxidase were not well predicted.

    *

     To whom correspondence should be addressed. For R.A.T.:  phone, 509-335-1516; e-mail, [email protected]. For K.R.K.:  e-mail, [email protected]. For J.P.J.:  phone, 509-335-5983; e-mail, [email protected].

    †

     Department of Molecular Systems, Merck Research Laboratories.

    ‡

     Washington State University.

    §

     Department of Drug Metabolism, Merck Research Laboratories.

    Abbreviations:  AO, aldehyde oxidase; XO, xanthine oxidase; MoCo, molybdenum pyranopterin cofactor; ALS, amyotrophic lateral sclerosis; DFT, density functional theory.

    Cited By

    This article is cited by 64 publications.

    1. Mario Öeren, Peter J. Walton, James Suri, David J. Ponting, Peter A. Hunt, Matthew D. Segall. Predicting Regioselectivity of AO, CYP, FMO, and UGT Metabolism Using Quantum Mechanical Simulations and Machine Learning. Journal of Medicinal Chemistry 2022, 65 (20) , 14066-14081. https://doi.org/10.1021/acs.jmedchem.2c01303
    2. Jihui Zhao, Rongrong Cui, Lihao Wang, Yingjia Chen, Zunyun Fu, Xiaoyu Ding, Chen Cui, Tianbiao Yang, Xutong Li, Yuan Xu, Kaixian Chen, Xiaomin Luo, Hualiang Jiang, Mingyue Zheng. Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model. Journal of Medicinal Chemistry 2020, 63 (12) , 6523-6537. https://doi.org/10.1021/acs.jmedchem.9b01895
    3. Sheng Han, Yali Sang, Yan Wu, Yuan Tao, Christophe Pannecouque, Erik De Clercq, Chunlin Zhuang, Fen-Er Chen. Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. ACS Infectious Diseases 2020, 6 (5) , 787-801. https://doi.org/10.1021/acsinfecdis.9b00229
    4. Nenad Manevski, Lloyd King, William R. Pitt, Fabien Lecomte, Francesca Toselli. Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery. Journal of Medicinal Chemistry 2019, 62 (24) , 10955-10994. https://doi.org/10.1021/acs.jmedchem.9b00875
    5. Jayaraman Chandrasekhar, Ryan Dick, Joshua Van Veldhuizen, David Koditek, Eve-Irene Lepist, Mary E. McGrath, Leena Patel, Gary Phillips, Kassandra Sedillo, John R. Somoza, Joseph Therrien, Nicholas A. Till, Jennifer Treiberg, Armando G. Villaseñor, Yelena Zherebina, Stephane Perreault. Atropisomerism by Design: Discovery of a Selective and Stable Phosphoinositide 3-Kinase (PI3K) β Inhibitor. Journal of Medicinal Chemistry 2018, 61 (15) , 6858-6868. https://doi.org/10.1021/acs.jmedchem.8b00797
    6. Gabriele Cruciani, Nicolò Milani, Paolo Benedetti, Susan Lepri, Lucia Cesarini, Massimo Baroni, Francesca Spyrakis, Sara Tortorella, Edoardo Mosconi, and Laura Goracci . From Experiments to a Fast Easy-to-Use Computational Methodology to Predict Human Aldehyde Oxidase Selectivity and Metabolic Reactions. Journal of Medicinal Chemistry 2018, 61 (1) , 360-371. https://doi.org/10.1021/acs.jmedchem.7b01552
    7. Marco Montefiori, Flemming Steen Jørgensen, and Lars Olsen . Aldehyde Oxidase: Reaction Mechanism and Prediction of Site of Metabolism. ACS Omega 2017, 2 (8) , 4237-4244. https://doi.org/10.1021/acsomega.7b00658
    8. Yuan Xu, Liang Li, Yulan Wang, Jing Xing, Lei Zhou, Dafang Zhong, Xiaomin Luo, Hualiang Jiang, Kaixian Chen, Mingyue Zheng, Pan Deng, and Xiaoyan Chen . Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: A Combined Computational and Experimental Study. Journal of Medicinal Chemistry 2017, 60 (7) , 2973-2982. https://doi.org/10.1021/acs.jmedchem.7b00019
    9. Leena Patel, Jayaraman Chandrasekhar, Jerry Evarts, Aaron C. Haran, Carmen Ip, Joshua A. Kaplan, Musong Kim, David Koditek, Latesh Lad, Eve-Irene Lepist, Mary E. McGrath, Nikolai Novikov, Stephane Perreault, Kamal D. Puri, John R. Somoza, Bart H. Steiner, Kirk L. Stevens, Joseph Therrien, Jennifer Treiberg, Armando G. Villaseñor, Arthur Yeung, and Gary Phillips . 2,4,6-Triaminopyrimidine as a Novel Hinge Binder in a Series of PI3Kδ Selective Inhibitors. Journal of Medicinal Chemistry 2016, 59 (7) , 3532-3548. https://doi.org/10.1021/acs.jmedchem.6b00213
    10. Russ Hille, James Hall, and Partha Basu . The Mononuclear Molybdenum Enzymes. Chemical Reviews 2014, 114 (7) , 3963-4038. https://doi.org/10.1021/cr400443z
    11. Fionn O’Hara, Aaron C. Burns, Michael R. Collins, Deepak Dalvie, Martha A. Ornelas, Alfin D. N. Vaz, Yuta Fujiwara, and Phil S. Baran . A Simple Litmus Test for Aldehyde Oxidase Metabolism of Heteroarenes. Journal of Medicinal Chemistry 2014, 57 (4) , 1616-1620. https://doi.org/10.1021/jm4017976
    12. Jeffrey P. Jones and Kenneth R. Korzekwa . Predicting Intrinsic Clearance for Drugs and Drug Candidates Metabolized by Aldehyde Oxidase. Molecular Pharmaceutics 2013, 10 (4) , 1262-1268. https://doi.org/10.1021/mp300568r
    13. David J. St. Jean,Jr. and Christopher Fotsch . Mitigating Heterocycle Metabolism in Drug Discovery. Journal of Medicinal Chemistry 2012, 55 (13) , 6002-6020. https://doi.org/10.1021/jm300343m
    14. Angelica Linton, Ping Kang, Martha Ornelas, Susan Kephart, Qiyue Hu, Mason Pairish, Ying Jiang, and Chuangxing Guo . Systematic Structure Modifications of Imidazo[1,2-a]pyrimidine to Reduce Metabolism Mediated by Aldehyde Oxidase (AO). Journal of Medicinal Chemistry 2011, 54 (21) , 7705-7712. https://doi.org/10.1021/jm2010942
    15. Vaibhav A. Dixit and Prasad V. Bharatam . Toxic Metabolite Formation from Troglitazone (TGZ): New Insights from a DFT Study. Chemical Research in Toxicology 2011, 24 (7) , 1113-1122. https://doi.org/10.1021/tx200110h
    16. David C. Pryde, Deepak Dalvie, Qiyue Hu, Peter Jones, R. Scott Obach, and Thien-Duc Tran . Aldehyde Oxidase: An Enzyme of Emerging Importance in Drug Discovery. Journal of Medicinal Chemistry 2010, 53 (24) , 8441-8460. https://doi.org/10.1021/jm100888d
    17. Sebastian Metz and Walter Thiel. A Combined QM/MM Study on the Reductive Half-Reaction of Xanthine Oxidase: Substrate Orientation and Mechanism. Journal of the American Chemical Society 2009, 131 (41) , 14885-14902. https://doi.org/10.1021/ja9045394
    18. Sanja Gruenewald, Bettina Wahl, Florian Bittner, Helen Hungeling, Stephanie Kanzow, Joscha Kotthaus, Ulrike Schwering, Ralf R. Mendel and Bernd Clement . The Fourth Molybdenum Containing Enzyme mARC: Cloning and Involvement in the Activation of N-Hydroxylated Prodrugs. Journal of Medicinal Chemistry 2008, 51 (24) , 8173-8177. https://doi.org/10.1021/jm8010417
    19. Joshua F. Alfaro and Jeffrey P. Jones. Studies on the Mechanism of Aldehyde Oxidase and Xanthine Oxidase. The Journal of Organic Chemistry 2008, 73 (23) , 9469-9472. https://doi.org/10.1021/jo801053u
    20. Yuto Shiotake, Yu Takano, Toru Saito. Semi-empirical and machine learning-based prediction of site of metabolisms mediated by aldehyde oxidase. Chemical Physics Letters 2023, 833 , 140942. https://doi.org/10.1016/j.cplett.2023.140942
    21. Nicholas A. Meanwell. The pyridazine heterocycle in molecular recognition and drug discovery. Medicinal Chemistry Research 2023, 32 (9) , 1853-1921. https://doi.org/10.1007/s00044-023-03035-9
    22. Mengting Huang, Keyun Zhu, Yimeng Wang, Chaofeng Lou, Huimin Sun, Weihua Li, Yun Tang, Guixia Liu. In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase. Metabolites 2023, 13 (3) , 449. https://doi.org/10.3390/metabo13030449
    23. Aziz Belkadi, Gaurav Thareja, Fatemeh Abbaszadeh, Ramin Badii, Eric Fauman, Omar M.E. Albagha, Karsten Suhre. Identification of PCSK9-like human gene knockouts using metabolomics, proteomics, and whole-genome sequencing in a consanguineous population. Cell Genomics 2023, 3 (1) , 100218. https://doi.org/10.1016/j.xgen.2022.100218
    24. Usman Ali Ashfaq, Farah Shahid, Samman Munir. Computational approaches for drug-metabolizing enzymes: Concepts and challenges. 2022, 29-72. https://doi.org/10.1016/B978-0-323-95120-3.00001-4
    25. Somaieh Soltani, Somayeh Hallaj-Nezhadi, Mohammad Reza Rashidi. A comprehensive review of in silico approaches for the prediction and modulation of aldehyde oxidase-mediated drug metabolism: The current features, challenges and future perspectives. European Journal of Medicinal Chemistry 2021, 222 , 113559. https://doi.org/10.1016/j.ejmech.2021.113559
    26. David C. Pryde, Dharmendra B. Yadav, Rajib Ghosh. Aldehyde and Xanthine Oxidase Metabolism. 2021, 248-277. https://doi.org/10.1039/9781788016414-00248
    27. Erickson M. Paragas, Kanika Choughule, Jeffrey P. Jones, John T. Barr. Enzyme Kinetics, Pharmacokinetics, and Inhibition of Aldehyde Oxidase. 2021, 257-284. https://doi.org/10.1007/978-1-0716-1554-6_10
    28. Pranav Shah, Vishal B. Siramshetty, Alexey V. Zakharov, Noel T. Southall, Xin Xu, Dac-Trung Nguyen. Predicting liver cytosol stability of small molecules. Journal of Cheminformatics 2020, 12 (1) https://doi.org/10.1186/s13321-020-00426-7
    29. Phillip R. Lazzara, Terry W. Moore. Scaffold-hopping as a strategy to address metabolic liabilities of aromatic compounds. RSC Medicinal Chemistry 2020, 11 (1) , 18-29. https://doi.org/10.1039/C9MD00396G
    30. Christine Beedham. Aldehyde oxidase; new approaches to old problems. Xenobiotica 2020, 50 (1) , 34-50. https://doi.org/10.1080/00498254.2019.1626029
    31. Narges Cheshmazar, Siavoush Dastmalchi, Mineko Terao, Enrico Garattini, Maryam Hamzeh-Mivehroud. Aldehyde oxidase at the crossroad of metabolism and preclinical screening. Drug Metabolism Reviews 2019, 51 (4) , 428-452. https://doi.org/10.1080/03602532.2019.1667379
    32. Jiang Wei Zhang, Hai Bing Deng, Chun Ye Zhang, Jing Quan Dai, Qian Li, Qian Gang Zheng, Hui Xin Wan, Hong Ping Yu, Feng He, Yao Chang Xu, Sylvia Zhao, Ji Yue Jeff Zhang. In Vitro Metabolism by Aldehyde Oxidase Leads to Poor Pharmacokinetic Profile in Rats for c-Met Inhibitor MET401. European Journal of Drug Metabolism and Pharmacokinetics 2019, 44 (5) , 669-680. https://doi.org/10.1007/s13318-019-00557-9
    33. Deepak Dalvie, Li Di. Aldehyde oxidase and its role as a drug metabolizing enzyme. Pharmacology & Therapeutics 2019, 201 , 137-180. https://doi.org/10.1016/j.pharmthera.2019.05.011
    34. Marco Montefiori, Casper Lyngholm-Kjærby, Anthony Long, Lars Olsen, Flemming Steen Jørgensen. Fast Methods for Prediction of Aldehyde Oxidase-Mediated Site-of-Metabolism. Computational and Structural Biotechnology Journal 2019, 17 , 345-351. https://doi.org/10.1016/j.csbj.2019.03.003
    35. Jiang Wei Zhang, Wen Xiao, Zhen Ting Gao, Zheng Tian Yu, Ji Yue (Jeff) Zhang. Metabolism of c-Met Kinase Inhibitors Containing Quinoline by Aldehyde Oxidase, Electron Donating, and Steric Hindrance Effect. Drug Metabolism and Disposition 2018, 46 (12) , 1847-1855. https://doi.org/10.1124/dmd.118.081919
    36. Cristiano Mota, Catarina Coelho, Silke Leimkühler, Enrico Garattini, Mineko Terao, Teresa Santos-Silva, Maria João Romão. Critical overview on the structure and metabolism of human aldehyde oxidase and its role in pharmacokinetics. Coordination Chemistry Reviews 2018, 368 , 35-59. https://doi.org/10.1016/j.ccr.2018.04.006
    37. Raj Kumar, Gaurav Joshi, Harveen Kler, Sourav Kalra, Manpreet Kaur, Ramandeep Arya. Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases. Medicinal Research Reviews 2018, 38 (4) , 1073-1125. https://doi.org/10.1002/med.21457
    38. Susan Lepri, Martina Ceccarelli, Nicolò Milani, Sara Tortorella, Andrea Cucco, Aurora Valeri, Laura Goracci, Andreas Brink, Gabriele Cruciani. Structure–metabolism relationships in human- AOX: Chemical insights from a large database of aza-aromatic and amide compounds. Proceedings of the National Academy of Sciences 2017, 114 (16) https://doi.org/10.1073/pnas.1618881114
    39. Mohammad-Reza Rashidi, Somaieh Soltani. An overview of aldehyde oxidase: an enzyme of emerging importance in novel drug discovery. Expert Opinion on Drug Discovery 2017, 12 (3) , 305-316. https://doi.org/10.1080/17460441.2017.1284198
    40. Tim Cernak, Kevin D. Dykstra, Sriram Tyagarajan, Petr Vachal, Shane W. Krska. The medicinal chemist's toolbox for late stage functionalization of drug-like molecules. Chemical Society Reviews 2016, 45 (3) , 546-576. https://doi.org/10.1039/C5CS00628G
    41. Kanika V. Choughule, Carolyn A. Joswig-Jones, Jeffrey P. Jones. Interspecies differences in the metabolism of methotrexate: An insight into the active site differences between human and rabbit aldehyde oxidase. Biochemical Pharmacology 2015, 96 (3) , 288-295. https://doi.org/10.1016/j.bcp.2015.05.010
    42. Li Di. The role of drug metabolizing enzymes in clearance. Expert Opinion on Drug Metabolism & Toxicology 2014, 10 (3) , 379-393. https://doi.org/10.1517/17425255.2014.876006
    43. Patrik Rydberg, Flemming Steen Jørgensen, Lars Olsen. Use of density functional theory in drug metabolism studies. Expert Opinion on Drug Metabolism & Toxicology 2014, 10 (2) , 215-227. https://doi.org/10.1517/17425255.2014.864278
    44. Nigel J. Waters, Michelle K. Dennehy. Computational Approaches in Drug Biotransformation Studies: Metabolite Prediction. 2014, 1-24. https://doi.org/10.1002/9781118541203.xen0019
    45. John T. Barr, Kanika Choughule, Jeffrey P. Jones. Enzyme Kinetics, Inhibition, and Regioselectivity of Aldehyde Oxidase. 2014, 167-186. https://doi.org/10.1007/978-1-62703-758-7_9
    46. Kanika V. Choughule, John T. Barr, Jeffrey P. Jones. Evaluation of Rhesus Monkey and Guinea Pig Hepatic Cytosol Fractions as Models for Human Aldehyde Oxidase. Drug Metabolism and Disposition 2013, 41 (10) , 1852-1858. https://doi.org/10.1124/dmd.113.052985
    47. Enrico Garattini, Mineko Terao. Aldehyde oxidase and its importance in novel drug discovery: present and future challenges. Expert Opinion on Drug Discovery 2013, 8 (6) , 641-654. https://doi.org/10.1517/17460441.2013.788497
    48. James Matthew Hutzler, Ronald Scott Obach, Deepak Dalvie, Michael A Zientek. Strategies for a comprehensive understanding of metabolism by aldehyde oxidase. Expert Opinion on Drug Metabolism & Toxicology 2013, 9 (2) , 153-168. https://doi.org/10.1517/17425255.2013.738668
    49. John T. Barr, Jeffrey P. Jones. Evidence for Substrate-Dependent Inhibition Profiles for Human Liver Aldehyde Oxidase. Drug Metabolism and Disposition 2013, 41 (1) , 24-29. https://doi.org/10.1124/dmd.112.048546
    50. Robert S. Foti, Dan A. Rock, Larry C. Wienkers, Jan L. Wahlstrom. Mechanisms of Drug Metabolism. 2012, 1-68. https://doi.org/10.1002/9780470921920.edm027
    51. Deepak Dalvie, Hao Sun, Cathie Xiang, Qiyue Hu, Ying Jiang, Ping Kang. Effect of Structural Variation on Aldehyde Oxidase-Catalyzed Oxidation of Zoniporide. Drug Metabolism and Disposition 2012, 40 (8) , 1575-1587. https://doi.org/10.1124/dmd.112.045823
    52. Yin Cheong Wong, Shuai Qian, Zhong Zuo. Regioselective biotransformation of CNS drugs and its clinical impact on adverse drug reactions. Expert Opinion on Drug Metabolism & Toxicology 2012, 8 (7) , 833-854. https://doi.org/10.1517/17425255.2012.688027
    53. Mladen Litvić, Maja Regović, Karolina Šmic, Marija Lovrić, Mirela Filipan-Litvić. Remarkably fast and selective aromatization of Hantzsch esters with MoOCl4 and MoCl5: A chemical model for possible biologically relevant properties of molybdenum-containing enzymes. Bioorganic & Medicinal Chemistry Letters 2012, 22 (11) , 3676-3681. https://doi.org/10.1016/j.bmcl.2012.04.043
    54. Frederick A Villamena, Amlan Das, Kevin M Nash. Potential implication of the chemical properties and bioactivity of nitrone spin traps for therapeutics. Future Medicinal Chemistry 2012, 4 (9) , 1171-1207. https://doi.org/10.4155/fmc.12.74
    55. Tobias Hartmann, Mineko Terao, Enrico Garattini, Christian Teutloff, Joshua F. Alfaro, Jeffrey P. Jones, Silke Leimkühler. The Impact of Single Nucleotide Polymorphisms on Human Aldehyde Oxidase. Drug Metabolism and Disposition 2012, 40 (5) , 856-864. https://doi.org/10.1124/dmd.111.043828
    56. David C. Pryde, Thien-Duc Tran, Peter Jones, Jonathan Duckworth, Martin Howard, Iain Gardner, Ruth Hyland, Rob Webster, Tracey Wenham, Sharan Bagal, Kiyoyuki Omoto, Richard P. Schneider, Jian Lin. Medicinal chemistry approaches to avoid aldehyde oxidase metabolism. Bioorganic & Medicinal Chemistry Letters 2012, 22 (8) , 2856-2860. https://doi.org/10.1016/j.bmcl.2012.02.069
    57. Takafumi Akabane, Nicolas Gerst, Yoichi Naritomi, Jeffrey N. Masters, Kouichi Tamura. A Practical and Direct Comparison of Intrinsic Metabolic Clearance of Several Non-CYP Enzyme Substrates in Freshly Isolated and Cryopreserved Hepatocytes. Drug Metabolism and Pharmacokinetics 2012, 27 (2) , 181-191. https://doi.org/10.2133/dmpk.DMPK-11-RG-097
    58. Russ Hille, Takeshi Nishino, Florian Bittner. Molybdenum enzymes in higher organisms. Coordination Chemistry Reviews 2011, 255 (9-10) , 1179-1205. https://doi.org/10.1016/j.ccr.2010.11.034
    59. Siamak Cyrus Khojasteh, Harvey Wong, Cornelis E. C. A. Hop. Drug Metabolizing Enzymes. 2011, 17-46. https://doi.org/10.1007/978-1-4419-5629-3_2
    60. Selina C. Wang, Peter A. Beal, Dean J. Tantillo. Covalent hydration energies for purine analogs by quantum chemical methods. Journal of Computational Chemistry 2010, 31 (4) , 721-725. https://doi.org/10.1002/jcc.21364
    61. Johannes M. Dieterich, Hans-Joachim Werner, Ricardo A. Mata, Sebastian Metz, Walter Thiel. Reductive half-reaction of aldehyde oxidoreductase toward acetaldehyde: Ab initio and free energy quantum mechanical/molecular mechanical calculations. The Journal of Chemical Physics 2010, 132 (3) https://doi.org/10.1063/1.3280164
    62. Joshua F. Alfaro, Carolyn A. Joswig-Jones, Wenyun Ouyang, Joseph Nichols, Gregory J. Crouch, Jeffrey P. Jones. Purification and Mechanism of Human Aldehyde Oxidase Expressed in Escherichia coli. Drug Metabolism and Disposition 2009, 37 (12) , 2393-2398. https://doi.org/10.1124/dmd.109.029520
    63. Lin Xu, Bruce Adams, Valentina V. Jeliazkova-Mecheva, Laird Trimble, Gloria Kwei, Andreas Harsch. Identification of Novel Metabolites of Colchicine in Rat Bile Facilitated by Enhanced Online Radiometric Detection. Drug Metabolism and Disposition 2008, 36 (4) , 731-739. https://doi.org/10.1124/dmd.107.019463
    64. A.-K. Duhme-Klair. Bioinorganic chemistry. Annual Reports Section "A" (Inorganic Chemistry) 2008, 104 , 455. https://doi.org/10.1039/b717519c
    Download PDF

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect