通过用葫芦[7]脲包裹α-轴向5,6-二甲基苯并咪唑配体来稳定维生素B12和辅酶B12的碱基脱离形式

Stabilization of the base-off forms of vitamin B(12) and coenzyme B(12) by encapsulation of the alpha-axial 5,6-dimethylbenzimidazole ligand with cucurbit[7]uril.

作者信息

Wang Ruibing, Macgillivray Brendan C, Macartney Donal H

机构信息

Department of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.

出版信息

Dalton Trans. 2009 May 14(18):3584-9. doi: 10.1039/b904028e. Epub 2009 Mar 18.

DOI:10.1039/b904028e

PMID:19381421

Abstract

Cucurbit[7]uril (CB[7]) forms very stable complexes with the alpha-axial 5,6-dimethylbenzimidazole (alpha-DMB) nucleotide base when dissociated from the Co(III) center in vitamin B(12) (CNCbl, K(CB[7]) = (7.5 +/- 0.5) x 10(4) dm(3) mol(-1)) and coenzyme B(12) (AdoCbl, K(CB[7]) = (3.02 +/- 0.35) x 10(6) dm(3) mol(-1)). The inclusion of alpha-DMB ligand facilitates its release from the metal center and its subsequent protonation, with significantly higher pK(base-off) values of 3.77 and 6.61, than determined for the free CNCbl (0.11) and AdoCbl (2.67), respectively. Addition of CB[7] to the base-on form of CNCbl at pH 2 provides for a direct measurement of the rate constant for the dissociation of the alpha-DMB ligand from the Co center (k = (4.6 +/- 0.2) x 10(-2) s(-1), DeltaH = 93 +/- 2 kJ mol(-1), DeltaS = +41 +/- 6 J K(-1) mol(-1)). The beta-axial 5'-deoxyadenosyl ligand (beta-Ado) on coenzyme B(12) is bound more weakly by a second CB[7] host (K(CB[7]) = (1.1 +/- 0.2) x 10(3) dm(3) mol(-1)), however inclusion of the beta-Ado ligand has no effect on the kinetics of its heterolytic photodissociation from the Co(III) center.

摘要

葫芦[7]脲（CB[7]）与从维生素B12的Co（III）中心解离出来的α-轴向5,6-二甲基苯并咪唑（α-DMB）核苷酸碱基形成非常稳定的配合物（氰钴胺，K（CB[7]） = （7.5 ± 0.5）×10^4 dm³ mol⁻¹）和辅酶B12（腺苷钴胺，K（CB[7]） = （3.02 ± 0.35）×10^6 dm³ mol⁻¹）。α-DMB配体的包合促进了其从金属中心的释放及其随后的质子化，其pK（碱基脱离）值分别为3.77和6.61，比游离氰钴胺（0.11）和腺苷钴胺（2.67）测定的值高得多。在pH 2下将CB[7]添加到氰钴胺的碱基形式中，可以直接测量α-DMB配体从Co中心解离的速率常数（k = （4.6 ± 0.2）×10⁻² s⁻¹，ΔH = 93 ± 2 kJ mol⁻¹，ΔS = +41 ± 6 J K⁻¹ mol⁻¹）。辅酶B12上的β-轴向5'-脱氧腺苷配体（β-Ado）与第二个CB[7]主体的结合较弱（K（CB[7]） = （1.1 ± 0.2）×10³ dm³ mol⁻¹），然而β-Ado配体的包合对其从Co（III）中心的异裂光解动力学没有影响。