Tonglei Li

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Multiscale Modeling and Simulation for Drug Development: Over the last few years, we have integrated molecular modeling and simulation with continuum dynamics and pharmacokinetics modeling. For example, one area is to simulate local drug transport and absorption with fluid dynamics and predict system exposure of drug molecules. Another study is to investigate protein stability under hydrodynamic stress. Our research interests lie in integration of macro-, meso-, and microscale modeling and simulation methods for understanding the in vivo fate of drug products. Deep Learning for Drug Discovery and Development: We have exploited the hard and soft acids and bases principle (HSAB) within the conceptual density functional theory (CDFT) framework to characterize the locality and strength of intermolecular interactions. The efforts have led to our recent development of a novel concept to depict molecules in the context of molecular interaction. It allows us to utilize deep learning and develop predictive models of molecular properties and functionalities. The concept also permits de novo design of molecules.

Selected Publications:

Tonglei Li, Shubin Liu, Shaoxin Feng, and Clare E. Aubrey, Face-Integrated Fukui Function: Understanding Wettability Anisotropy of Molecular Crystals from Density Functional Theory, Journal of the American Chemical Society, 127:1364-1365, 2005

Tonglei Li and Shaoxin Feng, Empirically Augmented Density Functional Theory for Predicting Lattice Energies of Aspirin, Acetaminophen Polymorphs, and Ibuprofen Homochiral and Racemic Crystals, Pharmaceutical Research, 23:2326-2332, 2006

Tonglei Li, Paul W. Ayers, Shubin Liu, Matthew J. Swadley, and Clare Aubrey-Medendorp, Crystallization Force: A Density Functional Theory Concept for Revealing Intermolecular Interactions and Molecular Packing in Organic Crystals, Chemistry – A European Journal, 15:361-371, 2009

Sihui Long and Tonglei Li, Controlled Formation of the Acid−Pyridine Heterosynthon over the Acid−Acid Homosynthon in 2-Anilinonicotinic Acids, Crystal Growth & Design, 9:4993–4997, 2009

Sihui Long and Tonglei Li, Enforcing Molecule’s π-Conjugation and Consequent Formation of the Acid-Acid Homosynthon over the Acid-Pyridine Heterosynthon in 2-Anilinonicotinic Acids, Crystal Growth & Design, 10:2465-2469, 2010

Tonglei Li, Alessandra Mattei, and Panpan Zhou, Electronic Origin of Pyridinyl N Being A Better Hydrogen-Bonding Acceptor Than Carbonyl O, CrystEngComm, 13:6356-6360, 2011

Paul W. Ayers, Shubin Liu, and Tonglei Li, Chargephilicity and Chargephobicity: Two New Reactivity Indicators for External Potential Changes from Density Functional Reactivity Theory, Chemical Physics Letters, 480:318-321, 2009

Rongsheng Zhao, Christin P. Hollis, Hua Zhang, Lili Sun, Richard A. Gemeinhart, and Tonglei Li, Hybrid Nanocrystals: Achieving Concurrent Therapeutic and Bioimaging Functionalities Toward Solid Tumors, Molecular Pharmaceutics, 8:1985-1991, 2011

Panpan Zhou, Paul W. Ayers, Shubin Liu, and Tonglei Li, Local Reactivity Descriptors Based on Natural Bond Orbital Occupancy: Natural Orbital Fukui Functions (NOFFs) and their applications in the reaction mechanisms of addition reactions, Journal of Chemical Physics, 14:9890-9896, 2012

Christin P. Hollis, Heidi L. Weiss, Markos Leggas, B. Mark Evers, Richard A. Gemeinhart, and Tonglei Li, Biodistribution and bioimaging studies of hybrid paclitaxel nanocrystals: Lessons learned of the EPR effect and image-guided drug delivery, Journal of Controlled Release, 172:12-21, 2013

Mingtao Zhang and Tonglei Li, Intermolecular Interactions in Organic Crystals: Gaining Insight from Electronic Structure Analysis by Density Functional Theory, CrystEngComm, 16:7162-7171, 2014

Sihui Long, Panpan Zhou, Sean Parkin, and Tonglei Li, From Competition to Commensuration by Two Major Hydrogen-Bonding Motifs, Crystal Growth & Design, 14:27-31, 2014

Hua Zhang, Xueqing Wang, Wenbing Dai, Richard A. Gemeinhart, Qiang Zhang, and Tonglei Li, Pharmacokinetics and Treatment Efficacy of Metastatic Lung Cancer by Camptothecin Nanocrystals, Molecular Pharmaceutics, 11:226-233, 2014

Christin P. Hollis, Heidi L. Weiss, B. Mark Evers, Richard A. Gemeinhart, and Tonglei Li, In vivo Investigation of Hybrid Paclitaxel Nanocrystals with Dual Fluorescent Probes for Cancer Theranostics, Pharmaceutical Research, 31:1450-1459, 2014

Alessandra Mattei, and Tonglei Li, Solution Chemistry and Its Implication on Nucleation of Conformational Polymorphs: A Computational Study of Tolfenamic Acid by Explicit Solvation, Crystal Growth & Design, 14:2709-2713, 2014

Wei Gao, Yan Chen, David H. Thompson, Kinam Park, and Tonglei Li, Impact of Surfactant Treatment of Paclitaxel Nanocrystals on Biodistribution and Tumor Accumulation in Tumor-bearing Mice, Journal of Controlled Release, 237:168-176, 2016

Weiwei Tang, Huaping Mo, Mingtao Zhang, Sean Parkin, Junbo Gong, Jingkang Wang, and Tonglei Li, Persistent Self-Association of Solute Molecules in Solution, Journal of Physical Chemistry B, 121:10118-10124, 2017

Weiwei Tang, Huaping Mo, Mingtao Zhang, Junbo Gong, Jingkang Wang, and Tonglei Li, Glycine’s pH-Dependent Polymorphism: A Perspective from Self-Association in Solution, Crystal Growth and Design, 17:5028−5033, 2017

Lei Xing, Yue Li, and Tonglei Li, Local Concentrating, Not Shear Stress, That May Lead to Possible Instability of Protein Molecules During Syringe Injection: A Fluid Dynamic Study with Two-Phase Flow Model. PDA Journal, 73:260-275, 2019

Weiwei Tang, Yufeng Quan, Junbo Gong, Jingkang Wang, Qiuxiang Yin, and Tonglei Li, Form Selection of Concomitant Polymorphs: A Case Study Informed by Crystallization Kinetics Modeling, AIChE Journal, 2020, DOI: 10.1002/aic.17129.

Peng Hou, Fudan Zheng, Clairissa D. Corpstein, Lei Xing, and Tonglei Li, Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Sensitivity Analysis. Pharmaceutical Research, 38:1011–1030, 2021

Fudan Zheng, Peng Hou, Clairissa D. Corpstein, Lei Xing, and Tonglei Li, Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Model Development. Pharmaceutical Research, 2021 38, 607–624

Fudan Zheng, Peng Hou, Clairissa D Corpstein, Kinam Park, and Tonglei Li, Multiscale pharmacokinetic modeling of systemic exposure of subcutaneously injected biotherapeutics, Journal of Control Release 337:407-416, 2021

Paige N. Zambrana, Peng Hou, Dana C. Hammell, Tonglei Li, and Audra L. Stinchcomb Understanding Formulation and Temperature Effects on Dermal Transport Kinetics by IVPT and Multiphysics Simulation. Pharmaceutical Research, 39:893–905, 2022