CEITEC - Central European Institute of Technology, Masaryk University , Kamenice 5, CZ - 62500 Brno, Czech Republic.
Department of Chemistry, Faculty of Science, Masaryk University , Kamenice 5, CZ - 62500 Brno, Czech Republic.
J Am Chem Soc. 2016 Jul 13;138(27):8432-45. doi: 10.1021/jacs.6b02749. Epub 2016 Jul 5.
Ruthenium-based compounds are potential candidates for use as anticancer metallodrugs. The central ruthenium atom can be in the oxidation state +2 (e.g., RAPTA, RAED) or +3 (e.g., NAMI, KP). In this study we focus on paramagnetic NAMI analogs of a general structure 4-R-pyHtrans-Ru(III)Cl4(DMSO)(4-R-py), where 4-R-py stands for a 4-substituted pyridine. As paramagnetic systems are generally considered difficult to characterize in detail by NMR spectroscopy, we performed a systematic structural and methodological NMR study of complexes containing variously substituted pyridines. The effect of the paramagnetic nature of these complexes on the (1)H and (13)C NMR chemical shifts was systematically investigated by temperature-dependent NMR experiments and density-functional theory (DFT) calculations. To understand the electronic factors influencing the orbital (δ(orb), temperature-independent) and paramagnetic (δ(para), temperature-dependent) contributions to the total NMR chemical shifts, a relativistic two-component DFT approach was used. The paramagnetic contributions to the (13)C NMR chemical shifts are correlated with the distribution of spin density in the ligand moiety and the (13)C isotropic hyperfine coupling constants, Aiso((13)C), for the individual carbon atoms. To analyze the mechanism of spin distribution in the ligand, the contributions of molecular spin-orbitals (MSOs) to the hyperfine coupling constants and the spatial distribution of the z-component of the spin density in the MSOs calculated at the relativistic four-component DFT level are discussed and rationalized. The significant effects of the substituent and the solvent on δ(para), particularly the contact contribution, are demonstrated. This work should contribute to further understanding of the link between the electronic structure and the NMR chemical shifts in open-shell systems, including the ruthenium-based metallodrugs investigated in this account.
钌基化合物是用作抗癌金属药物的潜在候选物。中心钌原子可以处于+2 氧化态（例如 RAPTA、RAED）或+3 氧化态（例如 NAMI、KP）。在这项研究中，我们专注于一般结构 4-R-吡啶 Htrans-Ru(III)Cl4(DMSO)(4-R-吡啶)的顺磁 NAMI 类似物，其中 4-R-吡啶代表 4-取代吡啶。由于顺磁系统通常被认为难以通过 NMR 光谱详细表征，因此我们对含有各种取代吡啶的配合物进行了系统的结构和方法学 NMR 研究。通过温度依赖性 NMR 实验和密度泛函理论 (DFT) 计算，系统地研究了这些配合物的顺磁性对 (1)H 和 (13)C NMR 化学位移的影响。为了了解影响轨道（δ(orb)，与温度无关）和顺磁（δ(para)，与温度有关）对总 NMR 化学位移贡献的电子因素，使用了相对论双分量 DFT 方法。将 (13)C NMR 化学位移的顺磁贡献与配体部分的自旋密度分布以及各个碳原子的 (13)C 各向异性超精细耦合常数 Aiso((13)C)相关联。为了分析配体中自旋分布的机制，讨论并合理化了分子自旋轨道（MSOs）对超精细耦合常数的贡献以及在相对论四分量 DFT 水平上计算的 MSOs 中自旋密度 z 分量的空间分布。证明了取代基和溶剂对 δ(para)，特别是接触贡献的显著影响。这项工作应该有助于进一步了解包括本研究中所研究的基于钌的金属药物在内的开壳体系中电子结构与 NMR 化学位移之间的联系。
