Copper(I) complexes of the types [Cu(N–N)(PPh₃)₂]NO₃ (LC41–LC44) and [Cu(N–N)(PPh₃)(NO₃)] (LC45) carrying 3‐substituted 1‐pyridine‐2‐ylimidazo[1,5‐a]pyridine (N–N) derivatives and triphenylphosphine (PPh₃) ligands have been prepared. The synthesized copper(I)–phosphine complexes were fully characterized by NMR, IR, ESI‐MS and UV–visible spectroscopy as well as by cyclic voltammetry. Selected structures such as LC42, LC43 and LC45 were additionally analysed by single‐crystal X‐ray method, which show that copper(I) centre adopts a highly distorted tetrahedral geometry. The ¹H and ¹³C NMR spectral data of the complexes throw light on the nature of metal–ligand bonding. They display dπ–π* metal‐to‐ligand charge transfer (MLCT) transition and show quasireversible Cu^I/Cu^II metal oxidation. Among the copper(I)–phosphine complexes, LC41–LC44 exhibit moderate cytotoxicity (IC₅₀: 24 h, 67–74 μM; 48 h, 58–70 μM) against human lung epithelial adenocarcinoma A549 cells, whereas LC45 displays the best activity (IC₅₀: 24 h, 42 μM; 48 h, 34 μM) for A549 cancer cell line, which is better than that of the commercial antitumor drug cisplatin. All the complexes also displayed excellent selectivity by being relatively inactive against the human lung epithelial L132 normal cell line with selectivity index (SI) values ranging from 3.4 to 7.4. The complexes block cell cycle progression of A549 cells in G₀/G₁ phase. FACSVerse analyses are suggestive of reactive oxygen species (ROS) generation and apoptotic cell death induced by the LC41, LC43 and LC45. The induction of apoptosis in A549 cells was shown by Annexin V with propidium iodide (PI) and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining methods and established the ability of LC41, LC43 and LC45 to accumulate in the cell nuclei.

中文翻译：

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基于3-取代的1-吡啶-2--2-咪唑并[1,5-a]吡啶的铜（I）-膦复合物的合成，结构，表征和生物学评估，用于抗癌药物筛选

[Cu（N–N）（PPh ₃）₂ ] NO ₃（LC41–LC44）和[Cu（N–N]（PPh ₃）（NO ₃）]（LC45）类型的铜（I）配合物，其3取代的1 -吡啶-2-基咪唑并[1,5-一个]吡啶（N-N）衍生物和三苯基膦（PPH ₃）配位体已经制备。合成的铜（I）-膦配合物已通过NMR，IR，ESI-MS和UV-可见光谱以及循环伏安法进行了全面表征。通过单晶X射线方法对LC42，LC43和LC45等选定结构进行了额外分析，结果表明铜（I）中心采用高度扭曲的四面体几何形状。的¹ H和¹³配合物的13 C NMR光谱数据揭示了金属-配体键合的性质。它们显示出dπ–π *金属到配体的电荷转移（MLCT）跃迁，并显示出准可逆的Cu ^I / Cu ^II金属氧化。之间的铜（I） -膦络合物，LC41-LC44表现出适度的细胞毒性（IC ₅₀：24小时，67-74μM; 48小时，58-70μM）对人肺上皮腺癌A549细胞，而LC45显示最好的活性（IC ₅₀：24小时，42μM; 48小时（34μM）用于A549癌细胞系，优于市售抗肿瘤药顺铂。由于对人肺上皮L132正常细胞系相对无活性，所有复合物还表现出优异的选择性，选择性指数（SI）值在3.4至7.4之间。该复合物阻断了A549细胞在G ₀ / G ₁期的细胞周期进程。FACSVerse分析提示由LC41，LC43和LC45诱导的活性氧（ROS）生成和凋亡细胞死亡。Annexin V用碘化丙锭（PI）和4'，6-二mid基-2-苯基吲哚（DAPI）染色方法显示了A549细胞的凋亡诱导作用，并确定了LC41，LC43和LC45在细胞核中积累的能力。 。