Chemistry

Yun Lu

Personal Page

Education:

• Ph.D., Organic Chemistry, 1996, Nankai University
• M.S., Organic Chemistry, 1991, Shanxi University
• B.S., Chemistry, 1986, Shanxi University

Research Interests:

Our recent research focus is to study the enzyme model reactions in solution to attempt to understand the high efficiency of the enzymatic reactions. We compare chemical behaviors of the model reactions with those of the enzymatic reactions to reveal the chemical and physical functions of proteins in catalysis. Of particular interest is about how protein dynamics transiently bring activated reactants to reach their closest contact for chemistry to occur. The enzymatic reactions selected for this purpose are H-transfer reactions. Therefore, we mainly study H-transfer reactions in solution. We use the methodologies that enzymologists use to study the enzymes, which include experiments and computations. Differences and similarities between reactions with and without proteins are compared. Results can also be added to the current debates on the appropriateness of models to describe H-transfer/tunneling reactions in enzymes and solution.

Selected Publications:

• Grishma Singh, Ava Austin, Mingxuan Bai, Joshua Bradshaw, Blake A. Hammann, Daniel E. K. Kabotso, Yun Lu* “Study of the Effects of Remote Heavy Group Vibrations on the Temperature Dependence of Hydride Kinetic Isotope Effects of the NADH/NAD+ Model Reactions” ACS Omega 2024, 18, 20593–20600.
• Amanda Beach, Pratichhya Adhikari, Grishma Singh, Meimei Song, Nicholas DeGroot, Yun Lu * "Structural Effects on the Temperature Dependence of Hydride Kinetic Isotope Effects of the NADH/NAD⁺ Model Reactions in Acetonitrile: Charge-Transfer Complex Tightness Is a Key".  J. Org. Chem. 2024, 89, 3184–3193.
• Mingxuan Bai, Pratap Rijal, Sanaz Salarvand, Yun Lu* "Correlation of Temperature Dependence of Hydride Kinetic Isotope Effects with Donor-Acceptor Distances in Two Solvents of Different Polarities". Org. Biol. Chem. 2023, 21, 5090 – 5097.
• Pratichhya Adhikari, Meimei Song, Mingxuan Bai, Pratap Rijal, Nicholas DeGroot, Yun Lu* “Solvent Effects on the Temperature Dependence of Hydride Kinetic Isotope Effects: Correlation to the Donor–Acceptor Distances” J. Phys. Chem. A 2022, 126, 7675–7686.
• Mingxuan Bai, Shailendra Koirala, Yun Lu*  "Direct Correlation Between Donor-Acceptor Distance and Temperature Dependence of Kinetic Isotope Effects in Hydride-Tunneling Reactions of NADH/NAD+ Analogues"  J. Org. Chem. 2021, 86, 7500–7507.
• Peter Maness, Shailendra Koirala, Pratichhya Adhikari, Nasim Salimfaftar, Yun Lu*  "Substituent Effects on Temperature Dependence of Kinetic Isotope Effects in Hydride-Transfer Reactions of NADH/NAD+ analogues in Solution:  Reaction Center Rigidity Is the Key"  Organic Letters 2020, 22, 5963-5967.
• Yun Lu,* Samantha Wilhelm,^† Mingxuan Bai,^† Peter Maness, and Li Ma “Replication of the Enzymatic Temperature Dependency of the Primary Hydride Kinetic Isotope Effects in Solution: Caused by the Protein Controlled Rigidity of the Donor-Acceptor Centers?” Biochemistry 2019, 58, 4035–4046.
• Li Ma, Nader Sakhaee, Shabnam Jafari, Samantha Wilhelm, Paniz Rahmani, and Yun Lu* “Imbalanced Transition States from α-H/D and Remote β-Type N-CH/D Secondary Kinetic Isotope Effects on the NADH/NAD⁺ Analogues in Their Hydride Tunneling Reactions in Solution” J. Org. Chem. 2019, 84, 5431–5439.
• Nader Sakhaee*, Edward Ackad, and Yun Lu* “Hydride Transfer Tunneling-Ready-State Structure as a Function of Donor-Acceptor Distance: A Full Gating Coordinate for the Vibrational Tunneling-Ready-State” Chemical Physics 2019, 522, 138–146.
• Mortaza Derakhshani-Molayousefi, Sadra Kashefolgheta, James E. Eilers, and Yun Lu*, "Computational Replication of the Primary Isotope Dependence of Secondary Kinetic Isotope Effects in Solution Hydride-Transfer Reactions: Supporting the Isotopically Different Tunneling Ready State Conformations" J. Phys. Chem. A 2016, 120, 4277−4284.
• Binita Maharjan, Mahdi Raghibi Boroujeni, Jonathan Lefton, Ormacinda R. White, Mortezaali Razzaghi, Blake A. Hammann, Mortaza Derakhshani-Molayousefi, James E. Eilers, Yun Lu* "Steric Effects on the Primary Isotope Dependence of Secondary Kinetic Isotope Effects in Hydride Transfer Reactions in Solution: Caused by the Isotopically Different Tunneling Ready State Conformations?" J. Am. Chem. Soc. 2015, 137, 6653-6661.
• Sadra Kashefolgheta, Mortezaali Razzaghi, Blake Hammann, James E. Eilers, Daniel Roston, Yun Lu* "Computational Replication of the Abnormal Secondary Kinetic Isotope Effects in a Hydride Transfer Reaction in Solution with a Motion Assisted H-Tunneling Model" J. Org. Chem. 2014, 79, 1989-1994.
• Blake Hammann, Mortezaali Razzaghi, Sadra Kashefolgheta, Yun Lu* "Imbalanced Tunneling Ready States in Alcohol Dehydrogenase Model Reactions: Rehybridization Lags behind H-Tunneling†" Chemical Communications, 2012, 48, 11337-11339.
• Qi Liu, Yu Zhao, Blake Hammann, James E. Eilers, Yun Lu*, Amnon Kohen* "A Model Reaction Assesses Contribution of H-Tunneling and Coupled Motions to Enzyme Catalysis" J. Org. Chem. 2012, 77 , 6825-6833.
• Yun Lu*, Joshua Bradshaw, Yu Zhao, William Kuester, Daniel Kabotso "Structure - Reactivity Relationship for Alcohol Oxidations via Hydride Transfer to a Carbocationic Oxidizing Agent" J. Phys. Org. Chem. 2011, 24, 1172-1178.
• Yun Lu* ,Fengrui Qu, Yu Zhao, Ashia Small, Joshua Bradshaw, Brian Moore "Kinetics of the Hydride Reduction of an NAD⁺ Analogue by Isopropyl Alcohol in Aqueous and Acetonitrile Solutions: Solvent Effects, Deuterium Isotope Effects and Mechanism" J. Org. Chem. 2009, 74, 6503-6510.
• Yun Lu* , Fengrui Qu, Brian Moore, Donald Endicott, William Kuester "Hydride Reduction of NAD+ Analogues by Isopropyl Alcohol: Kinetics, Deuterium Isotope Effects and Mechanism" J. Org. Chem. (Featured Article) 2008, 73, 4763-4770.
• Yun Lu* , Donald Endicott, William Kuester "Effective Oxidation of Isopropanol by an NAD+ Model." Tetra Lett 2007, 48, 6356-6359.
• Yun Lu* , Jiancheng Liu, Garry Diffee, Diansheng Liu, Bo Liu* "Reduction of Nitroarenes by Hydroxide Ion in Water Catalyzed by β-Cyclodextrin: Enhanced Reactivity of Hydroxide Ion." Tetra Lett 2006, 47, 4597-4599.
• Martin Newcomb*, Runnan Shen, Yun Lu, Minor J. Conn, Paul F. Hollenberg, Daniel A. Kopp, Stephen J. Lippard "Evaluation of norcarane as a probe for radicals in cytochrome P-450 and soluble Methane Monooxygenase- catalyzed hydroxylation reactions" J. Am. Chem. Soc. 2002, 124, 6879-6886.
• Yun Lu , Yixing Zhao, Vernon D. Parker* "Proton-transfer reactions of methylarene radical cations with pyridine bases under non-steady-state conditions. Real kinetic isotope effect evidence for extensive tunneling" J. Am. Chem. Soc. 2001, 123, 5900-5907.
• Jin-Pei Cheng*, Yun Lu, Xiaoqing Zhu, Linjing Mu "Energetics of Multi-step vs. One-step Hydride Transfer Reactions of Reduced Nicotinamide Adenine Dinucleotide (NADH) Models with Organic Cations and p-Quinones" J. Org. Chem. 1998, 63, 6108-6114.

Other publications can be found from my Personal Page