Carbohydrate-appended 3-hydroxy-4-pyridinone complexes of the [M(CO)3]+ core (M) Re, 99mTc, 186Re)
Carbohydrate-appended 3-hydroxy-4-pyridinone complexes of the [M(CO)3]+ core (M) Re, 99mTc, 186Re)
复制标题
DOI：
10.1021/bc060085e
复制
发表时间：
2006-09-20
影响因子：
4.7
通讯作者：
Orvig, Chris
中科院分区：
文献类型：
--
作者：
Ferreira, Cara L.;Bayly, Simon R.;Orvig, Chris
本工作描述了在制备新型Tc（I）和Re（I）葡萄糖缀合物的背景下，3-羟基-4-吡啶酮配体用于结合[M（CO）（3）]（+）核心（M）Re，Tc）的用途。在宏观标度（M）Re）和示踪标度（M = Tc-99 m，Re-186）上，五个带有侧链糖基的吡啶酮配体HL 1 -5与[M（CO）（3）]（+0）核配位.在宏观尺度上，通过质谱、红外光谱、紫外可见光谱、元素分析和1D/2D核磁共振光谱对配合物ReL 1 -5（CO）（3）（H\O-2）进行了彻底表征。表征证实了吡啶酮的二齿配位和碳水化合物的悬垂性质，并表明在第六个配位位点存在水分子。在初步的生物学评价中，配体和配合物都被评估为潜在的底物或己糖激酶抑制剂，但没有显示出活性。经[Tc-99 m（CO）（3）（H2O）（3）]（+）前体标记，得到高放化产率的（TcL_（1 -5））-Tc-99 m（CO）（3）（H2O）示踪物。当用Re-186标记时，通过在HL 1 -5存在下原位制备[Re-186（CO）（3）（H2O）（3）]（+）物质得到（ReL 1 -5）-Re-186（CO）（3）（H2O），促进了类似的高放射化学产率。在过量半胱氨酸和组氨酸存在下孵育（TcL 1 -5）-Tc-99 m（CO）（3）（H2O）的稳定性挑战证实了长达24 h的复合物稳定性。
This work describes the use of 3-hydroxy-4-pyridinone ligands for binding the [M(CO)(3)](+) core ( M) Re, Tc) in the context of preparing novel Tc( I) and Re( I) glucose conjugates. Five pyridinone ligands bearing pendent carbohydrate moieties, HL1-5, were coordinated to the [M(CO)(3)](+0) core on the macroscopic scale ( M) Re) and on the tracer scale (M) = Tc-99m, Re-186). On the macroscopic scale the complexes, ReL1-5(CO)(3)(H\O-2), were thoroughly characterized by mass spectrometry, IR spectroscopy, UV-visible spectroscopy, elemental analysis, and 1D/2D NMR spectroscopy. Characterization confirmed the bidentate coordination of the pyridinone and the pendent nature of the carbohydrate and suggests the presence of a water molecule in the sixth coordination site. In preliminary biological evaluation, both the ligands and complexes were assessed as potential substrates or inhibitors of hexokinase, but showed no activity. Labeling via the [Tc-99m(CO)(3)(H2O)(3)](+) precursor gave the tracer species (TcL1-5)-Tc-99m(CO)(3)(H2O) in high radiochemical yields. Similar high radiochemical yields when labeling with Re-186 were facilitated by in situ preparation of the [Re-186( CO)(3)(H2O)(3)](+) species in the presence of HL1-5 to give (ReL1-5)-Re-186(CO)(3)(H2O). Stability challenges, incubating (TcL1-5)-Tc-99m(CO)(3)(H2O) in the presence of excess cysteine and histidine, confirmed complex stability up to 24 h.