Noncovalent Interactions within a Synthetic Receptor Can Reinforce Guest Binding

详细信息    查看全文

• 作者：Zaida Rodriguez-Docampo ; Sofia I. Pascu ; Stefan Kubik ; Sijbren Otto
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：August 30, 2006
• 年：2006
• 卷：128
• 期：34
• 页码：11206 - 11210
• 全文大小：175K
• 年卷期：v.128,no.34(August 30, 2006)
• ISSN：1520-5126

文摘

Structural and thermodynamic data are presented on the binding properties of anion receptorscontaining two covalently linked cyclopeptide subunits that bind sulfate and iodide anions with micromolaraffinity in aqueous solution. A synchrotron X-ray crystal structure of the sulfate complex of one receptorrevealed that the anion is bound between the peptide rings of the biscyclopeptide. Intimate intramolecularcontacts between the nonpolar surfaces of the proline rings of the individual receptor moieties in the complexsuggest that hydrophobic interactions within the receptor that do not directly involve the guest contributeto complex stability. This finding is supported by a microcalorimetric analysis of the solvent dependence ofcomplex stability, which showed that increasing the water content of the solvent has only a weak influenceon the Gibbs energy of binding. Hence, the increasing amount of energy required for desolvating the bindingpartners in solutions containing more water is almost compensated by the increasingly favorable hydrophobicinteractions. Further observations that suggest that guest-induced intra-receptor interactions contribute toguest binding are (i) anion binding of a monomeric cyclopeptide lacking the covalent linkage between thetwo rings leads to the formation of 2:1 complexes; (ii) in the crystal structure of the 2:1 iodide complex ofthis monotopic receptor, a similar arrangement of the two cyclopeptide rings has been found as in thesulfate complex of the biscyclopeptide; (iii) complex formation of the monomeric cyclopeptide in aqueoussolution is highly cooperative with a large stability constant corresponding to the formation of the 2:1complexes from relatively instable 1:1 complexes; (iv) the monomeric cyclopeptide forms only 1:1 anioncomplexes in DMSO where hydrophobic interactions do not take place; and (v) introducing polar hydroxygroups on the proline rings of the monomeric cyclopeptide disrupts cooperativity causing the formation ofonly 1:1 complexes even in aqueous solution. Taken together these observations demonstrate that, inaddition to direct receptor-substrate interactions, noncovalent interactions between the two subunits ofsuch biscyclopeptides contribute significantly to anion complex stability. Reinforcement of molecularrecognition through intra-receptor interactions should be an attractive new strategy to boost host-guestaffinities.