Oehlsen Michael E, Hegmans Alexander, Qu Yun, Farrell Nicholas
Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA.
J Biol Inorg Chem. 2005 Aug;10(5):433-42. doi: 10.1007/s00775-005-0009-1. Epub 2005 Sep 23.
In this study, the reactions of N-acetyl-L-methionine (AcMet) with {trans-PtCl(NH(3))(2)}(2)-mu-H(2)N(CH(2))(6)NH(2)(2) (BBR3005: 1,1/t,t 1) and its cis analog [{cis-PtCl(NH(3))(2)}(2)-mu-{H(2)N(CH(2))(6)NH(2)}]Cl(2) (1,1/c,c 2) were analyzed to determine the rate and reaction profile of chloride substitution by methionine sulfur. The reactions were studied in PBS buffer at 37 degrees C by a combination of multinuclear ((195)Pt, {(1)H-(15)N} HSQC) magnetic resonance (NMR) spectroscopy and electrospray ionization time of flight mass spectrometry (ESITOFMS). The diamine linker of the 1,1/t,t trans complex was released as a result of the trans influence of the coordinated sulfur atom, producing trans-PtCl(AcMet)(NH(3))(2) (III) and trans-Pt(AcMet)(2)(NH(3))(2) (IV). In contrast the cis geometry of the dinuclear compound maintained the diamine bridge intact and a number of novel dinuclear platinum compounds obtained by stepwise substitution of sulfur on both platinum centers were identified. These include (charges omitted for clarity): [{cis-PtCl(NH(3))(2)}-mu-NH(2)(CH(2))(6)NH(2)-{cis-Pt(AcMet)(NH(3))(2)}] (V); [{cis-Pt(AcMet)(NH(3))(2)}(2)-mu-NH(2)(CH(2))(6)NH(2)] (VI); [{cis-PtCl(NH(3))(2)}-mu-NH(2)(CH(2))(6)NH(2)-{PtCl(AcMet)NH(3)] (VII); [{PtCl(AcMet)(NH(3))}(2)-mu-NH(2)(CH(2))(6)NH(2)] (VIII); [{trans-Pt(AcMet)(2)(NH(3))}-mu-NH(2)(CH(2))(6)NH(2)-{PtCl(AcMet)(NH(3))] (IX) and the fully substituted [{trans-Pt(AcMet)(2)(NH(3))}(2)-mu-{NH(2)(CH(2))(6)NH(2)] (X). For both compounds the reactions with methionine were slower than those with glutathione (Inorg Chem 2003, 42:5498-5506). Further, the 1,1/c,c geometry resulted in slower reaction than the trans isomer, because of steric hindrance of the bridge, as observed previously in reactions with DNA and model nucleotides.
在本研究中，分析了N - 乙酰 - L - 蛋氨酸（AcMet）与{反式 - PtCl(NH₃)₂}₂ - μ - H₂N(CH₂)₆NH₂₂（BBR3005：1,1/t,t 1）及其顺式类似物[{顺式 - PtCl(NH₃)₂}₂ - μ - {H₂N(CH₂)₆NH₂}]Cl₂（1,1/c,c 2）的反应，以确定蛋氨酸硫取代氯的速率和反应过程。通过多核（¹⁹⁵Pt，{¹H - ¹⁵N} HSQC）磁共振（NMR）光谱和电喷雾电离飞行时间质谱（ESITOFMS）相结合的方法，在37℃的磷酸盐缓冲盐溶液（PBS）中研究了这些反应。由于配位硫原子的反位影响，1,1/t,t反式配合物的二胺连接体被释放，生成反式 - [PtCl(AcMet)(NH₃)₂]⁺（III）和反式 - [Pt(AcMet)₂(NH₃)₂]²⁺（IV）。相比之下，双核化合物的顺式结构保持二胺桥完整，并且鉴定出了通过在两个铂中心逐步取代硫而获得的许多新型双核铂化合物。这些化合物包括（为清晰起见省略电荷）：[{顺式 - PtCl(NH₃)₂} - μ - NH₂(CH₂)₆NH₂ - {顺式 - Pt(AcMet)(NH₃)₂}]（V）；[{顺式 - Pt(AcMet)(NH₃)₂}₂ - μ - NH₂(CH₂)₆NH₂]（VI）；[{顺式 - PtCl(NH₃)₂} - μ - NH₂(CH₂)₆NH₂ - {PtCl(AcMet)NH₃}]（VII）；[{PtCl(AcMet)(NH₃)}₂ - μ - NH₂(CH₂)₆NH₂]（VIII）；[{反式 - Pt(AcMet)₂(NH₃)} - μ - NH₂(CH₂)₆NH₂ - {PtCl(AcMet)(NH₃)}]（IX）以及完全取代的[{反式 - Pt(AcMet)₂(NH₃)}₂ - μ - {NH₂(CH₂)₆NH₂}]（X）。对于这两种化合物，与蛋氨酸的反应都比与谷胱甘肽的反应慢（《无机化学》2003年，42：5498 - 5506）。此外，由于桥的空间位阻，1,1/c,c结构导致的反应比反式异构体慢，这与之前在与DNA和模型核苷酸的反应中观察到的情况一致。
