Coupling Fast Water Exchange to Slow Molecular Tumbling in Gd3+ Chelates: Why Faster Is Not Always Better
Coupling Fast Water Exchange to Slow Molecular Tumbling in Gd3+ Chelates: Why Faster Is Not Always Better
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DOI：
10.1021/ic400308a
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发表时间：
2013-08-05
影响因子：
4.6
通讯作者：
Woods, Mark
中科院分区：
文献类型：
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作者：
Avedano, Stefano;Botta, Mauro;Woods, Mark
动力学对溶液状态结构的影响是化学中广泛被忽视的考虑因素。 Gd3+ 螯合物水合作用随着配位几何结构和解离水交换动力学的变化而变化，显着影响一水合 Gd3+ 螯合物作为 MRI 的 T-1 缩短造影剂的有效性（或弛豫性）。理论表明，弛豫度高度依赖于 Gd3+-水质子距离 (r(GdH))，但在评估 Gd3+ 螯合物作为潜在造影剂的弛豫度时，该距离几乎从未被视为变量。当考虑表现出不同离解水交换动力学的异构 Gd3+ 螯合物的弛豫性时，可以看到这种省略的结果。本文描述的结果表明，具有“最佳”解离水交换动力学的螯合物的弛豫度实际上低于具有“次优”解离水交换动力学的异构螯合物的弛豫度。当这些螯合物的分子翻滚速率减慢时，这是一种长期以来被认为可以增加弛豫度的方法，观察到的弛豫度差异随着更快速交换（“最佳”）螯合物表现出比“次优”交换异构体更低的弛豫度而增加。螯合物之间的差异源于非场相关参数：水合数 (q) 或 r(GdH)。对于溶液态 Gd3+ 螯合物，q 和 r(GdH) 值的变化无法区分。这些参数表达式简单地描述了螯合物的水合状态，即紧密缔合的水分子的数量和位置。螯合物的水合状态 (q/r(GdH)(6)) 与其解离水交换率 k(ex) 有内在联系，在检查 Gd3+ 螯合物的弛豫性时必须考虑这些参数的相互关系。本文提供的数据表明，与改变离解水交换动力学相关的水合参数 (q/r(GdH)(6)) 的变化对弛豫率具有深远影响，并表明在一水合 Gd3+ 螯合物中实现最高弛豫度比简单地“优化”离解水交换动力学更为复杂。
The influence of dynamics on solution state structure is a widely overlooked consideration in chemistry. Variations in Gd3+ chelate hydration with changing coordination geometry and dissociative water exchange kinetics substantially impact the effectiveness (or relaxivity) of monohydrated Gd3+ chelates as T-1-shortening contrast agents for MRI. Theory shows that relaxivity is highly dependent upon the Gd3+-water proton distance (r(GdH)), and yet this distance is almost never considered as a variable in assessing the relaxivity of a Gd3+ chelate as a potential contrast agent. The consequence of this omission can be seen when considering the relaxivity of isomeric Gd3+ chelates that exhibit different dissociative water exchange kinetics. The results described herein show that the relaxivity of a chelate with "optimal" dissociative water exchange kinetics is actually lower than that of an isomeric chelate with "suboptimal" dissociative water exchange. When the rate of molecular tumbling of these chelates is slowed, an approach that has long been understood to increase relaxivity, the observed difference in relaxivity is increased with the more rapidly exchanging ("optimal") chelate exhibiting lower relaxivity than the "suboptimally" exchanging isomer. The difference between the chelates arises from a non-field-dependent parameter: either the hydration number (q) or r(GdH). For solution state Gd3+ chelates, changes in the values of q and r(GdH) are indistinguishable. These parametric expressions simply describe the hydration state of the chelate-i.e., the number and position of closely associating water molecules. The hydration state (q/r(GdH)(6)) of a chelate is intrinsically linked to its dissociative water exchange rate k(ex), and the interrelation of these parameters must be considered when examining the relaxivity of Gd3+ chelates. The data presented herein indicate that the changes in the hydration parameter (q/r(GdH)(6)) associated with changing dissociative water exchange kinetics has a profound effect on relaxivity and suggest that achieving the highest relaxivities in monohydrated Gd3+ chelates is more complicated than simply "optimizing" dissociative water exchange kinetics.