传统量子化学方法在模拟大尺度体系时面临显著挑战，由于其计算量随体系增大急剧增长，它们难以应用于处理含数百原子的大尺度体系。为解决这一难题，我们开发了两种新型线性标度算法，能够将精确的从头算量子化学计算拓展至上万原子的大尺度分子体系及复杂的周期性凝聚相材料。 
      “分子中的簇”（CIM）局域相关方法. CIM方法的核心思想是将大体系的电子相关方程解耦为一系列较小的轨道簇相关方程，而每个轨道簇对应于体系正交定域分子轨道的一个子集[1,2]。体系的总电子相关能可通过对各轨道簇的贡献加和得到。由于不同轨道簇的电子相关计算可在不同计算节点并行处理，该特点使CIM区别于其它局域相关方法，可实现含数千原子的大尺度复杂体系的高精度耦合簇计算[3,4]。CIM-MP2（二阶Møller-Plesset微扰理论）解析能量梯度的开发，为大尺度分子体系的几何优化提供了高效工具[5-6]。该方法还成功拓展至周期性体系，在post-Hartree–Fock水平实现了晶格能的高精度计算，这对固态与材料科学研究具有重要意义[7,8]。凭借其良好的扩展性、并行效率及在分子/晶体体系中的成功应用，CIM方法被公认为大尺度体系与周期性体系电子相关计算的领先方法[9]。 
      基于能量的分片方法. 该方法的核心思想在于：大分子的基态能量可通过一系列较小子体系基态能量的线性组合计算获得[10]，或通过"静电嵌入"子体系的计算获得[11]。后者被称为广义的能量分片（GEBF）方法，可基于现有量子化学软件在不同理论层级灵活实现。该方法使标准工作站能够完成含数千原子分子的从头算量子化学计算，精确预测基态能量、分子性质、几何结构、振动光谱等性质[12,13]。GEBF方法已成功拓展至周期边界条件（PBC）下的分子晶体与凝聚相体系[14]。通过将PBC-GEBF方法与先进量子化学方法结合，研究者可精确模拟各类凝聚相材料的晶格能、晶体结构、振动光谱及核磁共振谱[15]。该方法为分子与固态化学领域的复杂体系研究提供了强有力的工具。

Representative Publications
[1] Li, S.*, Ma J. and Jiang Y. "Linear scaling local correlation approach for solving the coupled cluster equations of large systems" J. Comput. Chem. 2002, 23, 237. (Times cited: 200)
[2] Li, S.*, Shen, J., Li, W., Jiang Y. “An efficient implementation of the ‘cluster-in-molecule’ approach for local electron correlation calculations” J. Chem. Phys. 2006, 125, 074109. (Times cited: 148)
[3] Guo, Y., Li W., Li S.* "Improved cluster-in-molecule local correlation approach for electron correlation calculation of large systems" J. Phys. Chem. A, 2014, 118, 8996. (Times cited: 48)
[4] Ni, Z., Guo, Y., Neese, F., Li, W., and Li, S.* "Cluster-in-molecule local correlation method with an accurate distant pair correction for large systems", J. Chem. Theory Comput. 2021, 17, 756(Times cited: 44)
[5] Ni, Z., Wang, Y., Li, W., Pulay, P.*, and Li, S.* "Analytical energy gradients for the cluster-in-molecule MP2 method and its application to geometry optimizations of large systems" J. Chem. Theory Comput. 2019, 15, 3623 (Times cited: 18)
[6] Wang, Y., Ni, Z., Li, W.* and Li, S.*, "Analytical Gradient Using Cluster-in-Molecule RI-MP2 Method for the Geometry Optimizations of Large Systems.", J. Chem. Theory Comput., 2024,20,3626 (Times cited: 3)
[7] Zheng, Y.，Ni, Z.，Wang, Y.，Li, W.*，Li, S.*, "Cluster-in-molecule local correlation approach for periodic systems", J. Chem. Theory Comput., 2019,15,2933 (Times cited: 20)
[8] Wang, Y., Ni, Z., Neese, F., Li, W., Guo, Y.* and Li, S.* “Cluster-in-Molecule Method Combined with the Domain-Based Local Pair Natural Orbital Approach for Electron Correlation Calculations of Periodic Systems ” J. Chem. Theory Comput., 2022, 18, 6510.(Times cited: 9)
[9] Li, W., Wang, Y., Ni, Z., Li, S.* “Cluster-in-Molecule Local Correlation Method for Dispersion Interactions in Large Systems and Periodic Systems” Acc. Chem. Res. 2023, 56, 3462. (Times cited: 10)
[10] Li, S.*, Li, W. and Fang, T. “An efficient fragment-based approach for predicting the ground-state energies and structures of large molecules” J. Am. Chem. Soc. 2005, 127, 7215.(Times cited: 229)
[11] Li, W., Li, S.*, Jiang Y. “Generalized energy-based fragmentation approach for computing the ground-state energies and properties of large molecules” J. Phys. Chem. A 2007, 111, 2193. (Times cited: 298)
[12] Hua, W., Fang, T., Li, W., Yu, J.G., Li, S.* “Geometry optimizations and vibrational spectra of large molecules from a generalized energy-based fragmentation approach” J. Phys. Chem. A 2008, 112, 10864. (Times cited: 131)
[13] Li S.*; Li W.; Ma J. "Generalized Energy-Based Fragmentation Approach and Its Applications to Macromolecules and Molecular Aggregates" Acc. Chem. Res. 2014, 47, 2712 (Times cited: 176)
[14] Fang, T.; Li, W.; Gu, F.; Li, S.* "Accurate Prediction of Lattice Energies and Structures of Molecular Crystals with Molecular Quantum Chemistry Methods" J. Chem. Theory Comput. 2015, 11, 91 (Times cited:47).
[15] Li, W.; Dong, H.; Ma, J., and Li, S.* "Structures and spectroscopic properties of large molecules and condensed-phase systems predicted by generalized energy-based fragmentation approach" Acc. Chem. Res. 2021, 54, 169 (Times cited:57).

        传统单参考电子相关方法（如耦合簇理论）因固有的单组态特性，难以准确描述具有多组态特征的强关联体系（如化学键解离过程、过渡金属配合物）。为此，我们发展了以多轨道块（而非轨道）为基本单元的块相关电子相关理论框架[1]。该框架通过将轨道划分为化学直观的块（如成键对、孤对等），并以多电子块态的张量积作为N电子基函数来构建体系的总波函数，在规避传统多参考方法指数标度难题的同时，实现了静态与动态相关的统一描述。依据分块方式与参考态选择的不同，该框架可衍生多种不同的方法：
     CAS-BCCC:基于CASSCF参考态，对小活性空间体系可对解离过程与反应能垒给与精准的描述[2,3]，精度显著优于传统多参考耦合簇方法；
     GVB-BCPT2: 基于广义价键（GVB）参考态构建的二阶微扰理论，在强关联体系中表现超越MP2方法，可合理描述弱/强相关效应[4].
     GVB-BCCC: 采用GVB参考态，突破活性空间规模的限制。基于新算法开发的程序可实现常规分子的便捷GVB计算[5]。通过包含三/四块电子相关，其精度可媲美广为使用的密度矩阵重整化群（DMRG）方法[6-9]。我们也提出了基于GVB的幺正BCCC拟设（GVB-UBCCC），用于在量子计算机上模拟强关联体系[10]。
      对于电子激发态，我们提出运动方程块相关耦合簇方法（EOM-GVB-BCCC）。其中含三块相关的EOM-GVB-BCCC3方法，在大活性空间体系低激发态预测中展现出接近DMRG方法的潜力[11,12]。综上，该系列块相关方法有望成为研究强关联体系基态和激发态电子结构与性质的标准理论工具。
     

Representative Publications
[1] Li, S. “Block-correlated coupled cluster theory: The general formulation and its application to the antiferromagnetic Heisenberg model” J. Chem. Phys. 2004, 120, 5017. (Times cited: 72)
[2] Fang, T., Li, S.* “Block correlated coupled cluster theory with a CASSCF reference function: The formulation and test applications for single bond breaking” J. Chem. Phys. 2007, 127, 204108. (Times cited: 60)
[3] Fang, T., Shen, J., Li, S.* “Block correlated coupled cluster method with a complete active-space self-consistent-field reference function: the formula for general active spaces and its applications for multi-bond breaking systems”. J. Chem. Phys. 2008, 128, 224107. (Times cited: 44)
[4] Xu, E.; Li, S.* "Block correlated second order perturbation theory with a generalized valence bond reference function.", J. Chem. Phys. 2013, 139, 174111. (Times cited: 53)
[5] Wang, Q.; Zou, J.; Xu, E.; Pulay, P.*; Li, S. * "Automatic construction of the initial orbitals for efficient generalized valence bond calculations of large systems ", J. Chem. Theory Comput. 2019, 15, 141 (Times cited: 28)
[6] Wang, Q.; Duan, M,; Xu, E.; Zou, J.; Li, S.*"Describing Strong Correlation with Block-Correlated Coupled Cluster Theory ", J. Phys. Chem. Lett. 2020, 11, 7536(Times cited: 28)
[7] Zou, J., Wang, Q., Ren, X., Wang, Y., Zhang, H., Li, S.* "Efficient Implementation of Block-Correlated Coupled Cluster Theory Based on the Generalized Valence Bond Reference for Strongly Correlated Systems" J. Chem. Theory Comput. 2022, 18, 5276.(Times cited: 13)
[8] Ren, X., Zou, J., Zhang, H., Li, W.,* Li, S.* "Block-Correlated Coupled Cluster Theory with up to Four-Pair Correlation for Accurate Static Correlation of Strongly Correlated Systems." J. Phys. Chem. Lett. 2024, 15, 693 (Times cited: 10).
[9] Ren, X., Zou, J., Li, W.*, Li, S.* "Block-Correlated Coupled Cluster Theory Based on the Generalized Valence Bond Reference for Singlet–Triplet Energy Gaps of Strongly Correlated Systems" J. Phys. Chem. Lett. 2024, 15, 11342.
[10] Hu, J., Wang, Q.*, Li, S.* "Unitary Block-Correlated Coupled Cluster Ansatz based on the Generalized Valence Bond Wave Function for Quantum Simulation " J. Chem. Theory Comput. 2025, 21, 4579.
[11] Zhang, H., Zou, J., Ren, X., Li, S.* “Equation-of-Motion Block-Correlated Coupled Cluster Method for Excited Electronic States of Strongly Correlated Systems” J. Phys. Chem. Lett. 2023, 14, 6792 (Times cited: 3)
[12] Zhang, H., Zou, J., Ren, X., Li, S.* “Equation-of-Motion Block-Correlated Coupled Cluster Method with up to Three-Block Correlation for Excited Electronic States of Strongly Correlated Systems” J. Phys. Chem. Lett. 2025, 16, 4635.

  理论计算是现代化学研究的基石。本课题组工作的核心目标之一是通过原子层面的机理研究，阐明关键化学转化的反应机制，为实验现象提供微观解释；同时致力于新型化学反应与催化体系的计算设计与虚拟筛选，并通过实验验证发现新的化学反应或催化剂。为加速反应发现，我们开发了自动化反应路径探索与机理分析的先进方法。
     小分子活化的新机制 在惰性分子（如烷烃、H₂、N₂等）活化领域，我们的研究揭示了这类高难度转化的基本规律。针对单核表面Ta(III)中心介导的N₂还原反应，计算表明[(≡SiO)₂TaH]络合物中N₂的罕见侧配位模式对稳定后续氢转移步骤的过渡态至关重要，最终实现N≡N键断裂[1]。此外，对膦-硼烷受阻路易斯酸碱对（FLP）活化H₂的理论研究，证实了路易斯酸碱协同活化的反应机理[2]。这一机制现已成为领域共识，并指导了FLP催化剂在温和条件下活化CO₂、烷烃等惰性底物的理性设计。
    计算驱动的反应发现 通过理论计算，我们发现两分子4-氰基吡啶的协同催化作用可促进B₂(pin)₂中B–B键均裂，生成稳定的吡啶-硼基自由基中间体[3]，得到了实验验证。该活化模式为后续多样化催化转化奠定了基础[4-7]。基于机理认知，我们拓展了硼介导催化体系：利用B(C₆F₅)₃催化剂发展了苯酚与1,3-二烯的区域选择性氢芳基化反应[8]，以及通过硅烷调控实现端炔单/双氢硅烷化的化学选择性策略[9]。另外，我们建立了Ni(cod)₂/PMe₃/KHMDS体系催化的硅基导向邻位C(sp²)–H硼化反应[10]。在不对称催化方向，通过研究BINOL-铝催化的杂芳基酮氢硼化反应，我们的计算和实验结果提出了金属中心手性诱导的新机制[11]，突破了传统认知框架，为BINOL-金属催化体系的立体控制提供了新模式。
    反应设计的计算工具 我们开发了结合分子动力学与坐标驱动（MD/CD）的方法，可自动搜索气相与液相化学反应路径[12-14]，为均相新反应与催化剂的设计提供了技术平台。

Representative Publications
[1] J. Li, S. Li* "Energetics and Mechanism of Dinitrogen Cleavage at a Mononuclear Surface Tantalum Center: A New Way of Dinitrogen Reduction" Angew. Chem. Int. Ed. 2008, 47, 8040.
[2] Y. Guo, S. Li* "Unusual Concerted Lewis Acid-Lewis Base Mechanism for Hydrogen Activation by a Phosphine-Borane Compound " Inorg. Chem. 2008, 47, 6212.
[3] G. Wang, H. Zhang, J. Zhao, W. Li, J. Cao, C. Zhu*, and S. Li* "Homolytic Cleavage of a B−B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification ",Angew. Chem. Int. Ed. 2016, 55, 5985.
[4] G. Wang, J. Cao, L. Gao, W. Chen, W. Huang, X. Cheng,* S. Li* "Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study" J. Am. Chem. Soc., 2017, 139, 3904.
[5] J. Cao, G. Wang, L. Gao, X. Cheng, and S. Li* “Organocatalytic reductive coupling of aldehydes with 1,1-diarylethylenes using an in situ generated pyridine-boryl radical", Chem. Sci. 2018, 9, 3664
[6] J. Cao, G. Wang, L. Gao, H. Chen, X. Liu, X. Cheng and S. Li* “Perfluoroalkylative pyridylation of alkenes via 4-cyanopyridine-boryl radicals” Chem. Sci. ,2019, 10, 2767.
[7] L. Gao, G. Wang, J. Cao, H. Chen, Y. Gu, X. Liu, X. Cheng, J. Ma, and S. Li* “Lewis Acid-Catalyzed Selective Reductive Decarboxylative Pyridylation of N-Hydroxyphthalimide Esters: Synthesis of Congested Pyridine-Substituted Quaternary Carbons” ACS Catal. 2019, 9, 10142.
[8] G. Wang, L. Gao, H. Chen, X. Liu, J. Cao, S. Chen, X. Cheng, and S. Li*, “Chemoselective Borane-Catalyzed Hydroarylation of 1,3-Dienes with Phenols”, Angew. Chem. Int. Ed. 2019, 58, 1694.
[9] G. Wang, X. Su, L. Gao, X. Liu, G. Li and S. Li*, “Borane-catalyzed selective dihydrosilylation of terminal alkynes: reaction development and mechanistic insight” Chem. Sci. 2021, 12, 10883
[10] X. Su, G. Li, L. He, S. Chen, X. Yang, G. Wang*, S. Li*, “Nickel-Catalyzed, Silyl-Directed, Ortho-Borylation of Arenes via an Unusual Ni(II)/Ni(IV) Catalytic Cycle” Nat. Commun. 2024, 15 , 7549.
[11] Z. Li, P. Chen, Z. Ni, L. Gao, Y. Zhao, R. Wang, C. Zhu, G. Wang*, S. Li*, “NAn Unusual Chiral-at-Metal Mechanism for BINOL-Metal Asymmetric Catalysis” Nat. Commun. 2025, 16, 735.
[12] M. Yang, J. Zou, G. Wang, S. Li,* “Automatic Reaction Pathway Search via Combined Molecular Dynamics and Coordinate Driving Method” J. Phys. Chem. A 2017, 121, 1351.
[13] M. Yang, L. Yang, G. Wang, Y. Zhou,* D. Xie, S. Li,* “Combined Molecular Dynamics and Coordinate Driving Method for Automatic Reaction Pathway Search of Reactions in Solution”J. Chem. Theory Comput. 2018, 14, 5787.
[14] G. Li, Z. Li, L. Gao, S. Chen, G. Wang* and S. Li* “Combined molecular dynamics and coordinate driving method for automatically searching complicated reaction pathways”Phys. Chem. Chem. Phys. 2023, 25, 23696.

                                                                                                                                                                 Top