Semiautomated Transition State Localization for Organometallic Complexes with Semiempirical Quantum Chemical Methods

We present an efficient computational protocol for robust transition state localization that can be routinely applied to complex (organometallic) reactions. The capabilities of the combination of extended tight-binding semiempirical methods (GFNn-xTB) with a state-of-the-art transition state localization algorithm (mGSM) is demonstrated on a modified version of the MOBH35 benchmark set, consisting of 29 organometallic reactions and transition states. Furthermore, for three examples we demonstrate how error-prone the conventional (manual) approach based on chemical intuition can be and how errors are avoided by a semiautomated generation of reaction profiles. The performance of the GFNn-xTB methods is carefully assessed and compared with that of the widely used PM6-D3H4 and PM7 semiempirical methods. The GFNn-xTB methods show much higher success rates of 89.7% (GFN1-xTB) and 86.2% (GFN2-xTB) compared with 72.4% for PM6-D3H4 and 69.0% for PM7. The barrier heights and reaction energies are computed with much better accuracy at reduced computational cost for the GFNn-xTB methods compared with the PMx methods, allowing a semiquantitative assessment of possible reaction pathways already at a semiempirical level. The mean error of GFN2-xTB for the barrier heights (8.2 kcal mol–1) is close to what low-cost density functional approximations provide and substantially smaller than the corresponding error of the competitor methods.

本研究提出一种可稳健定位过渡态（transition state）的高效计算方案，可常规应用于复杂有机金属（organometallic）反应体系。本研究将扩展紧束缚半经验方法（extended tight-binding semiempirical methods，GFNn-xTB）与先进过渡态定位算法（mGSM）相结合，并在修改版MOBH35基准测试集（benchmark set）上验证了该组合方案的性能；该基准测试集包含29个有机金属反应及过渡态。此外，通过三个实例，本研究展示了基于化学直觉的传统（手动）方法存在的易出错性，以及通过半自动化生成反应势能剖面（semiautomated generation of reaction profiles）如何规避此类误差。本研究对GFNn-xTB系列方法的性能进行了严谨评估，并与当前广泛使用的PM6-D3H4、PM7半经验方法进行了对比。GFNn-xTB系列方法展现出更高的成功率：GFN1-xTB为89.7%，GFN2-xTB为86.2%；而PM6-D3H4与PM7的成功率仅为72.4%与69.0%。相较于PMx系列方法，GFNn-xTB系列方法在更低的计算成本下，能以更高精度计算能垒高度与反应能量，使得仅依靠半经验级别计算即可对潜在反应路径进行半定量评估。GFN2-xTB计算能垒高度的平均误差为8.2 kcal mol⁻¹，接近低成本密度泛函近似（density functional approximations）的误差水平，且远低于对比方法的对应误差值。