Binding studies of a protonated dioxatetraazamacrocycle with carboxylate substrates

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• 作者：Sí ; lvia Carvalho ; Rita Delgado ; Michael G.B. Drew ; Vâ ; nia Calisto ; Ví ; tor Fé ; lix
• 关键词：Recognition of anions ; Dioxatetraazamacrocycle ; Binding constants ; Molecular dynamics simulations ; ¹H NMR ; Potentiometry
• 刊名：Tetrahedron
• 出版年：2008
• 期刊代码：107_00404020
• 类别：ch
• 出版时间：26 May 2008
• 卷：64
• 期：22
• 页码：5392-5403
• 文件大小：1870 K

摘要

The tetraprotonated form of the dioxatetraazamacrocycle, 6,19-dioxa-3,9,16,22-tetraaza[22.2.2.2^11,14]triaconta-1(26),11,13,24,27,29-hexaene, (H₄L¹)⁴⁺, was used as the receptor for binding studies with carboxylate anionic substrates of different shapes, sizes, and charges [succinate (suc²⁻), cyclohexanetricarboxylate (cta³⁻), phthalate (ph²⁻), isophthalate (iph²⁻), terephthalate (tph²⁻), and benezenetricarboxylate (btc³⁻)]. Association constants were determined by potentiometry in aqueous solution at 298.2 K and 0.10 M KCl and by ¹H NMR titration in D₂O. The strongest association was found for the btc³⁻ anion at 5–7 pH region. From both techniques it was possible to establish the binding preference trend of the receptor for the different substrates, and the ¹H NMR spectroscopy gave important suggestions about the type of interactions between partners and the location of the substrates in the supramolecular entities formed. The effective binding constants at pH 6 follow the order: btc³⁻>iph²⁻>cta³⁻≈ph²⁻>tph²⁻>suc²⁻. All the studies suggest that the anionic substrates bind to the receptor via N–HOC hydrogen bonds and electrostatic interactions, and the aromatic substrates can also establish π–π stacking interactions. The crystal structures of (H₄L¹)⁴⁺ and its supramolecular assemblies with ph²⁻ and tph²⁻ were determined by X-ray diffraction. The last two structures showed that the association process in solid state occurs via multiple N–HOC hydrogen bonds with the anionic substrate located outside the macrocyclic cavity of the receptor. Molecular dynamics simulations carried out for the association of (H₄L¹)⁴⁺ with tph²⁻ and btc³⁻ in water solution established at atomic level the existence of all interactions suggested by the experimental studies, which act cooperatively in the binding process. Furthermore, the binding free energies were estimated and the values are in agreement with the experimental ones, indicating that the binding of these two anionic substrates occurs into the receptor cavity. However, the tph²⁻ has also propensity to leave the macrocyclic cavity and its molecular recognition can also happen at the top of the receptor.