Skip to content

References

If you use Q2MM in your research, please cite the relevant publications below. Citing these works helps support continued development and gives proper credit to the contributors.

Core method

  1. Norrby, P.-O. Selectivity in Asymmetric Synthesis from QM-Guided Molecular Mechanics. J. Mol. Struct. (THEOCHEM) 2000, 506, 9–16. DOI: 10.1016/S0166-1280(00)00398-5

    Introduces the foundational Q2MM approach — using quantum mechanical reference data to parameterize molecular mechanics force fields for predicting stereoselectivity in asymmetric catalysis.

  2. Norrby, P.-O. Deriving Force Field Parameters for Coordination Complexes. Coord. Chem. Rev. 2001, 212, 79–109. DOI: 10.1016/S0010-8545(00)00296-4

    Methodology for deriving MM force field parameters from QM data, covering coordination complexes and the gradient-based optimization approach used in Q2MM.

  3. O. Nilsson Lill, S.; Forbes, A.; Donoghue, P.; Verdolino, V.; Wiest, O.; Rydberg, P.; Norrby, P.-O. Application of Q2MM to Stereoselective Reactions. Curr. Org. Chem. 2010, 14, 1629–1645. DOI: 10.2174/138527210793563224

    Review of the Q2MM workflow — objective function construction, reference data types, and optimization strategies — with applications to stereoselective reactions.

  4. Limé, E.; Norrby, P.-O. Improving the Q2MM Method for Transition State Force Field Modeling. J. Comput. Chem. 2015, 36, 244–250. DOI: 10.1002/jcc.23797

    Introduces Hessian eigenvalue handling methods (C, D, and E) for transition states. q2mm implements curvature inversion (Method C).

  5. Hansen, E.; Rosales, A. R.; Tutkowski, B.; Norrby, P.-O.; Wiest, O. Prediction of Stereochemistry using Q2MM. Acc. Chem. Res. 2016, 49, 996–1005. DOI: 10.1021/acs.accounts.6b00037

    Comprehensive review of Q2MM methodology, covering the theoretical framework, parameter optimization workflow, and successful predictions of stereochemical outcomes in catalytic reactions.

  6. Rosales, A. R.; Quinn, T. R.; Wahlers, J.; Tomberg, A.; Zhang, X.; Helquist, P.; Wiest, O.; Norrby, P.-O. Application of Q2MM to Predictions in Stereoselective Synthesis. Chem. Commun. 2018, 54, 8294–8311. DOI: 10.1039/C8CC03695K

    Demonstrates application of Q2MM to predict stereoselectivity across diverse reaction types, validating the method's generality and predictive power.

Seminario method

  1. Seminario, J. M. Calculation of Intramolecular Force Fields from Second-Derivative Tensors. Int. J. Quantum Chem. 1996, 60, 1271–1277. DOI: 10.1002/(SICI)1097-461X(1996)60:7<1271::AID-QUA8>3.0.CO;2-W

    The foundational method for extracting bond and angle force constants from a QM Hessian matrix. Projects Cartesian second-derivative sub-blocks onto internal coordinates via eigendecomposition, producing initial force constant estimates without any MM calculations. Q2MM uses this as Stage 1 of the pipeline (see q2mm.models.seminario).

QFUERZA

  1. Farrugia, M.; Helquist, P.; Norrby, P.-O.; Wiest, O. Rapid FF Generation via Hessian-Informed Initial Parameters and Automated Refinement. J. Chem. Theory Comput. 2025, 22, 469–476. DOI: 10.1021/acs.jctc.5c01751

    Builds on the Seminario/FUERZA projection method by substituting known-problematic force constants — particularly hydrogen angle bends, which Seminario overestimates by ~2× — with empirical defaults (0.5 mdyn·Å/rad²). QFUERZA is the default strategy for estimate_force_constants(). Starting from QFUERZA parameters leads to faster optimizer convergence and fewer local-minimum traps. Tested on cis-platinum (ground state) and Rh-enamide (transition state). See theory.

MM3 force field

  1. Allinger, N. L.; Yuh, Y. H.; Lii, J. H. Molecular Mechanics. The MM3 Force Field for Hydrocarbons. 1. J. Am. Chem. Soc. 1989, 111, 8551–8566. DOI: 10.1021/ja00205a001

    Foundational MM3 force field paper. Q2MM uses the MM3 functional forms (cubic bond stretch, sextic angle bend) defined here; see q2mm.models.constants.

Applications

  1. Donoghue, P. J.; Helquist, P.; Norrby, P.-O.; Wiest, O. Development of a Q2MM Force Field for the Asymmetric Rhodium Catalyzed Hydrogenation of Enamides. J. Chem. Theory Comput. 2008, 4, 1313–1323. DOI: 10.1021/ct800132a

    The original Rh-enamide Q2MM force field — the primary benchmark system used throughout this codebase.

  2. Hansen, E.; Limé, E.; Norrby, P.-O.; Wiest, O. Anomeric Effects in Sulfamides. J. Phys. Chem. A 2016, 120, 3677–3682. DOI: 10.1021/acs.jpca.6b02757

    Ground-state force field for sulfamides, using Q2MM to implicitly parameterize coupled anomeric effects via torsional energy scans. Demonstrates Q2MM beyond transition-state applications.

  3. Rosales, A. R.; Wahlers, J.; Limé, E.; Meadows, R. E.; Leslie, K. W.; Savin, R.; Bell, F.; Hansen, E.; Helquist, P.; Munday, R. H.; Wiest, O.; Norrby, P.-O. Rapid Virtual Screening of Enantioselective Catalysts using CatVS. Nat. Catal. 2019, 2, 41–45. DOI: 10.1038/s41929-018-0193-3

    Introduces CatVS, a virtual screening platform that uses Q2MM-derived transition state force fields to rapidly evaluate catalyst libraries for enantioselectivity.

  4. Burai Patrascu, M.; Pottel, J.; Pinus, S.; Bezanson, M.; Norrby, P.-O.; Moitessier, N. From Desktop to Benchtop with Automated Computational Workflows for Computer-Aided Design in Asymmetric Catalysis. Nat. Catal. 2020, 3, 574–584. DOI: 10.1038/s41929-020-0468-3

    Integrates Q2MM with machine learning to predict enantioselectivity for a broader range of reactions and catalyst types.

  5. Rosales, A. R.; Ross, S. P.; Helquist, P.; Norrby, P.-O.; Sigman, M. S.; Wiest, O. Transition State Force Field for the Asymmetric Redox-Relay Heck Reaction. J. Am. Chem. Soc. 2020, 142, 9700–9707. DOI: 10.1021/jacs.0c01979

    Develops a Q2MM transition state force field for the asymmetric redox-relay Heck reaction, accurately predicting both enantio- and site-selectivity.

  6. Wahlers, J.; Maloney, M.; Salahi, F.; Rosales, A. R.; Helquist, P.; Norrby, P.-O.; Wiest, O. Stereoselectivity Predictions for the Pd-Catalyzed 1,4-Conjugate Addition. J. Org. Chem. 2021, 86, 5660–5667. DOI: 10.1021/acs.joc.0c02918

    Applies Q2MM to predict stereoselectivity in palladium-catalyzed conjugate additions, demonstrating transferability to new reaction classes.

  7. Wahlers, J.; Margalef, J.; Hansen, E.; Bayesteh, A.; Helquist, P.; Diéguez, M.; Pàmies, O.; Wiest, O.; Norrby, P.-O. Proofreading Experimentally Assigned Stereochemistry through Q2MM Predictions. Nat. Commun. 2021, 12, 6508. DOI: 10.1038/s41467-021-27065-2

    Uses Q2MM predictions to identify and correct experimentally misassigned stereochemistry, demonstrating the method's value as a validation tool.

  8. Quinn, T. R.; Patel, H. N.; Koh, K. H.; Haines, B. E.; Norrby, P.-O.; Helquist, P.; Wiest, O. Automated Fitting of Transition State Force Fields for Biomolecular Simulations. PLOS ONE 2022, 17, e0264960. DOI: 10.1371/journal.pone.0264960

    Extends Q2MM automation for biomolecular systems, enabling transition state force field fitting for enzymatic reactions.

  9. Wahlers, J.; Rosales, A. R.; Berkel, N.; Forbes, A.; Helquist, P.; Norrby, P.-O.; Wiest, O. A Quantum-Guided Molecular Mechanics Force Field for the Ferrocene Scaffold. J. Org. Chem. 2022, 87, 12334–12341. DOI: 10.1021/acs.joc.2c01553

    Develops specialized MM3* force field parameters for ferrocene-based ligands used in asymmetric catalysis.

  10. Maloney, M. P.; Stenfors, B. A.; Helquist, P.; Norrby, P.-O.; Wiest, O. Interplay of Computation and Experiment in Enantioselective Catalysis. ACS Catal. 2023, 13, 14285–14299. DOI: 10.1021/acscatal.3c03706

    Reviews the synergy between computational (Q2MM) and experimental approaches in developing enantioselective catalysts.