Zaupa Giovanni, Scrimin Paolo, Prins Leonard J
Department of Chemical Sciences, University of Padova, Italy.
J Am Chem Soc. 2008 Apr 30;130(17):5699-709. doi: 10.1021/ja7113213. Epub 2008 Apr 10.
Functionalization of multivalent structures such as dendrimers and monolayer passivated nanoparticles with catalytically active groups results in very potent catalysts, a phenomenon described as the positive dendritic effect. Here, we describe a series of peptide dendrons and dendrimers of increasing generation functionalized at the periphery with triazacyclononane, a ligand able to form a strong complex with Zn(II). Kinetic studies show that these metallodendrimers very efficiently catalyze the cleavage of the RNA model compound HPNPP, with dendrimer D32 exhibiting a rate acceleration of around 80,000 (kcat/k(uncat)) operating at a concentration of 600 nM. A theoretical model was developed to explain the positive dendritic effect displayed by multivalent catalysts in general. A detailed analysis of the saturation profile and the Michaelis-Menten parameters kcat and KM shows that it is not necessary to ascribe the positive dendritic effect to, for instance, changes in the catalytic site, increased substrate binding constant, or changes in the microenvironment. Rather it appears that the efficient catalytic behavior of multivalent catalysts is mainly determined by two factors: the number of catalytic sites occupied by substrate molecules under saturation conditions, and the efficiency of the multivalent system to generate catalytic sites in which multiple catalytic units act cooperatively on the substrate.
用具有催化活性的基团对树枝状聚合物和单层钝化纳米颗粒等多价结构进行功能化，会产生非常有效的催化剂，这一现象被称为正树枝状效应。在此，我们描述了一系列代数递增的肽树枝状分子和树枝状聚合物，其外围用三氮杂环壬烷进行功能化，三氮杂环壬烷是一种能够与Zn(II)形成强络合物的配体。动力学研究表明，这些金属树枝状聚合物能非常有效地催化RNA模型化合物HPNPP的裂解，树枝状聚合物D32在600 nM的浓度下表现出约80,000的速率加速（kcat/k(uncat)）。开发了一个理论模型来解释一般多价催化剂所表现出的正树枝状效应。对饱和曲线以及米氏参数kcat和KM的详细分析表明，没有必要将正树枝状效应归因于例如催化位点的变化、底物结合常数的增加或微环境的变化。相反，多价催化剂的高效催化行为似乎主要由两个因素决定：饱和条件下底物分子占据的催化位点数量，以及多价体系产生多个催化单元协同作用于底物的催化位点的效率。
