Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario K7L 3N6, Canada.
Org Biomol Chem. 2010 Jan 7;8(1):247-52. doi: 10.1039/b915694a. Epub 2009 Nov 6.
The cucurbit[7]uril (CB[7]) host molecule forms very stable host-guest complexes with the local anaesthetics procaine (K(CB[7]) = (3.5 +/- 0.7) x 10(4) dm(3) mol(-1)), tetracaine (K(CB[7]) = (1.5 +/- 0.4) x 10(4) dm(3) mol(-1)), procainamide (K(CB[7]) = (7.8 +/- 1.6) x 10(4) dm(3) mol(-1)), dibucaine (K(CB[7]) = (1.8 +/- 0.4) x 10(5) dm(3) mol(-1)) and prilocaine (K(CB[7]) = (2.6 +/- 0.6) x 10(4) dm(3) mol(-1)) in aqueous solution (pD = 4.75). The stability constants are 2-3 orders of magnitude greater than the values reported for binding by the comparably sized beta-cyclodextrin host molecule. The inclusion by CB[7] raises the first pK(a) values of the anaesthetics by 0.5-1.9 pK units, as the protonated forms are bound more strongly in acidic solution. The complexation-induced chemical shift changes in the guest proton resonances provide an indication of the site(s) of binding and the effects of protonation on the location of the binding sites.
葫芦脲（CB[7]）主体分子与局部麻醉剂普鲁卡因（K(CB[7]) = (3.5 +/- 0.7) x 10(4) dm(3) mol(-1)）、丁卡因（K(CB[7]) = (1.5 +/- 0.4) x 10(4) dm(3) mol(-1)）、普鲁卡因酰胺（K(CB[7]) = (7.8 +/- 1.6) x 10(4) dm(3) mol(-1)）、布比卡因（K(CB[7]) = (1.8 +/- 0.4) x 10(5) dm(3) mol(-1)）和丙胺卡因（K(CB[7]) = (2.6 +/- 0.6) x 10(4) dm(3) mol(-1)）在水溶液中（pD = 4.75）形成非常稳定的主体-客体配合物。稳定常数比具有相似尺寸的β-环糊精主体分子结合的报道值高出 2-3 个数量级。CB[7]的包含物使麻醉剂的第一个 pK(a)值提高了 0.5-1.9 pK 单位，因为质子化形式在酸性溶液中结合得更强。客体质子共振的螯合诱导化学位移变化提供了结合部位的指示以及质子化对结合部位位置的影响。
