Cusumano M, Di Pietro M L, Giannetto A, Romano F
Dipartimento di Chimica Inorganica, Chimica Analitica e Chimica Fisica, University of Messina, Messina, Italy.
Inorg Chem. 2000 Jan 10;39(1):50-5. doi: 10.1021/ic990747u.
The kinetics of substitution of pyridine or 2-methylpyridine, by iodide or thiourea, in the complexes Pt(4'-R'terpy)(2-Rpy)2 (R' = o-tolyl or H; R = H or CH3) has been studied, at 25 degrees C, pH 7, and various ionic strength values, in the presence of and without calf thymus DNA. The reactions occur in one observable step, and plots of kobsd against nucleophile concentration give straight lines with zero intercepts. DNA inhibits all the reactions studied without altering the rate law; the second-order rate constants k2 decrease systematically on increasing DNA concentration and are larger at higher ionic strength values. Partitioning of the ionic reactants in solution on electrostatic grounds can account for this kinetic effect in the reaction with iodide. Iodide is kept off the double helix proximity while the dicationic complexes concentrate on it. The inhibiting effect observed for the uncharged reagent thiourea can be related to the specific binding mode of the complexes to DNA. The complexes studied are effective intercalators to double helix, and this type of interaction, which prevents attack of thiourea at platinum, decreases their actual concentration in solution. The inhibiting effect is larger for [Pt(terpy)(py)]2+ that is a better intercalator. Likewise, the decrease in the rate of substitution of 2-Rpy, at a given [DNA] on decreasing ionic strength, is due to the influence of ionic strength on the complex-DNA interactions.
研究了在25℃、pH值为7以及不同离子强度值的条件下，在有和没有小牛胸腺DNA存在的情况下，碘化物或硫脲取代配合物Pt(4'-R'terpy)(2-Rpy)2（R' = 邻甲苯基或H；R = H或CH3）中吡啶或2-甲基吡啶的动力学。反应以一个可观察到的步骤进行，观察到的速率常数kobsd对亲核试剂浓度的作图给出截距为零的直线。DNA抑制所有研究的反应但不改变速率定律；随着DNA浓度的增加，二级速率常数k2系统性地降低，并且在较高离子强度值时更大。基于静电作用，离子反应物在溶液中的分配可以解释与碘化物反应中的这种动力学效应。碘化物被阻止靠近双螺旋，而二价阳离子配合物则集中在其上。观察到的不带电荷的试剂硫脲的抑制作用可能与配合物与DNA的特定结合模式有关。所研究的配合物是有效的双螺旋嵌入剂，这种相互作用阻止硫脲对铂的进攻，降低了它们在溶液中的实际浓度。对于更好的嵌入剂[Pt(terpy)(py)]2+，抑制作用更大。同样，在给定的[DNA]下，降低离子强度时2-Rpy取代速率的降低是由于离子强度对配合物 - DNA相互作用的影响。
