Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C 6 H 8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity
Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C 6 H 8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity
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具有环状 C 6 H 8 主链取代基的双（乙基硫代氨基甲酸酯）铜配合物的配体和连接异构体：合成、表征和抗增殖活性
DOI：
10.1002/ejic.202300447
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发表时间：
2023
影响因子：
2.3
通讯作者：
Grapperhaus, Craig A.
中科院分区：
文献类型：
--
作者：
Bajaj, Kritika;Andres, Sarah A.;Hofsommer, Dillon T.;Chekwube Michael, Okolocha;Mashuta, Mark S.;Bates, Paula J.;Buchanan, Robert M.;Grapperhaus, Craig A.
一系列异构双（烷基硫代氨基甲酸酯）铜配合物已被合成、表征并评估其抗增殖活性。该配合物源自具有 3-甲基戊基 (H2L2) 和环己基 (H2L3) 主链取代基的配体异构体，每个取代基产生一对连接异构体。热力学产物 CuL2a/3a 有两个亚氨基 N 和两个 S 供体，形成三个五元螯合环（555 个异构体）。动力学异构体 CuL2b/3b 具有 1 个亚氨基和 1 个肼基 N 供体和 2 个 S 供体，形成四元环、六元环和五元环（465 个异构体）。与 465 异构体相比，555 异构体具有更容易接近的 CuII/I 电势（E1/2=−811/−768 mV 与二茂铁/二茂铁）和更低的能量电荷转移带（E1/2=−923/−854 mV）。使用 MTT 测定评估针对肺腺癌细胞系 (A549) 和非恶性肺成纤维细胞系 (IMR-90) 的抗增殖活性。 CuL2 对 A549 具有有效 (A549EC50=0.080 μM) 和选择性 (IMR-90EC50/A549EC50=25)。其连接异构体CuL2b具有与A549相当的活性，但选择性较低（IMR-90EC50/A549EC50=12.5）。异构体 CuL3a 和 CuL3b 的 A549EC50 值分别为 1.9 和 0.19 M，其效力较低，而 IMR-90EC50/A549EC50 比率分别为 2.3 和 2.65，选择性较低。还原电位和 A549 抗增殖活性/选择性之间没有相关性。
A series of isomeric bis(alkylthiocarbamate) copper complexes have been synthesized, characterized, and evaluated for antiproliferation activity. The complexes were derived from ligand isomers with 3‐methylpentyl (H2L2) and cyclohexyl (H2L3) backbone substituents, which each yield a pair of linkage isomers. The thermodynamic products CuL2a/3ahave two imino N and two S donors resulting in three five‐member chelate rings (555 isomers). The kinetic isomers CuL2b/3bhave one imino and one hydrazino N donor and two S donors resulting in four‐, six‐, and five‐member rings (465 isomers). The 555 isomers have more accessible CuII/Ipotentials (E1/2=−811/−768 mV vs. ferrocenium/ferrocene) and lower energy charge transfer bands than their 465 counterparts (E1/2=−923/‐854 mV). Antiproliferation activities were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR‐90) using the MTT assay. CuL2awas potent (A549EC50=0.080 μM) and selective (IMR‐90EC50/A549EC50=25) for A549. Its linkage isomer CuL2bhad equivalent A549 activity, but lower selectivity (IMR‐90EC50/A549EC50=12.5). The isomers CuL3aand CuL3bwere less potent withA549EC50values of 1.9 and 0.19 M and less selective withIMR‐90EC50/A549EC50ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.