半夹心三氮唑硫氨酰肼配体的MII(cym)Cl (cym = η6-p-cymene; M = Ru, Os)配合物已经展示出口服抗癌活性剂的潜力。为了研究用磷供体配体替换亲核氯配体对其抗增殖特性的影响，三苯基膦(PPh3)和1,3,5-三氮基-7-磷巨藻烷 (pta) 类似物被制备并通过光谱技术进行表征，其中几个配合物的分子结构被通过X-衍射分析确定。有趣的是，分子结构中包含PCA配体去质子化，这可能是由于配合物整体电荷的减少所驱动的。密度泛函理论 (DFT) 计算表明质子化和去质子化形式之间存在微小的能量差异。通过代表性示例的1H NMR光谱研究了水稳定性和对氨基酸L-组氨酸和L-半胱氨酸的反应性。最有效的抗癌药物具有Ru或Os中心和PPh3配体，并对四种癌细胞株显示亚微米级的IC50值。这表明抗增殖活性主要依赖于膦配体的亲脂性质，其中PPh3的clog P值明显高于pta。Copyright © 2023 Elsevier Inc. All rights reserved.

Half-sandwich MII(cym)Cl (cym = η6-p-cymene; M = Ru, Os) complexes of pyridinecarbothioamide (PCA) ligands have demonstrated potential as orally active anticancer agents. In order to investigate the impact of the substitution of the labile chlorido ligand with phosphorous donor ligands on the antiproliferative properties, the triphenylphosphine (PPh3) and 1,3,5-triaza-7-phophaadamantane (pta) analogues were prepared and characterized by spectroscopic techniques and the molecular structures of several complexes were determined by X-diffraction analysis. Interestingly, the molecular structures contained the PCA ligand deprotonated, presumably driven by the reduction in overall charge of the complex. Density Functional Theory (DFT) calculations suggested minor energy differences between the protonated and deprotonated forms. The aqueous stability and the reactivity with the amino acids l-histidine and l-cysteine were investigated by 1H NMR spectroscopy of representative examples. The most potent anticancer agents featured Ru or Os centers and a PPh3 ligand and showed IC50 values in the submicromolar range against four cancer cell lines. This suggests that the antiproliferative activity was mainly dependent on the lipophilic properties of the phosphine ligand with PPh3 having a significantly higher clog P value than pta.Copyright © 2023 Elsevier Inc. All rights reserved.