Recognition of Guests by Water-Stabilized Cavitand Hosts

摘要: Resorcinarenes are versatile modules for modern studies of molecular recognition.1 The monomeric resorcinarene (e.g., 1, Figure 1) and its simple derivatives show recognition properties, but their shallow curvatures cannot provide sufficient surface contacts selecting between targets. Nonetheless, they bind ammonium ions, choline, acetylcholine, carnitine in protic solvents.2 Ideally, a synthetic receptor should congruent chemical complementarity to the target molecule: large fraction be surrounded, how much? Deepened cavitands prepared by fusing four aromatic “walls” resorcinarene.3 This increases curvature cavitand's space. Cavitands with only three walls have been known since 1992,4 properties were discovered Ballester 2006.5 We describe here additional resorcinarene-derived characterize behavior aqueous organic media. Figure 1 Synthesis 3 4 representation vase conformation. Deep benzimidazoles on upper rims allow study events solvents.6 Their vase-like conformations stabilized (rather than disrupted) water or alcohols because hydroxyl functions complete hydrogen bond seam that helps maintain shape receptor. synthesis two- three-walled is low-yielding has led number intriguing applications.7 used hexanitroderivative8 2 prepare cavitand 3. Reduction tin(II) chloride then condensation 5 gave benzimidazole walls, each bearing an ester function. In addition, ethyl-footed analog 3a subsequent saponification water-soluble 4. Although dissolves well CDCl3, 1H NMR spectrum shows broad unassignable signals sharpen upon addition MeOH-d4 (Figure 2).9 two methine resonances at 5.69 (Ha) 5.62 (Hb) ppm indicate conformation10 occupied solvent. fourth proton site missing wall appears 4.20 ppm.11 Folding less pronounced when using D2O-saturated chloroform, presence suitable guest again brings well-resolved signals. Cavitand 3b partially soluble CD2Cl2/CD3OD. It forms folded structure THF-d8/D2O, solvent outcompetes potential guests binding. Figure 2 1H spectra (600 MHz) (a) CDCl3/5% CD3OD, (b) CDCl3/D2O saturated, (c) + 6a saturated. The π-surfaces cavity cations through cation-π CH-π interactions.3,5 Accordingly, we examined various amines, adamantanes (6−13, 3) as guests. Typically, anisotropy imparted eight induces upfield shifts up Alkanes, example, appear region 0 −4 ppm. found both amine/ammonium group bulky aliphatic which properly fills inner space necessary binding (Table 1). Figure 3 Structures 6−13. Table 1 Binding Constants Guests 6-11, Determined NMRa An feature selectivity naturally occurring cations.12 Both choline carnitine, poorly water-saturated taken up, acetylcholine was not. The signatures13 encapsulated modeling studies14 reveal different modes operate depending 4). Primary amines positioned appropriately groups rim. Bulkier such trimethylammonium pyridinium can electrostatic interaction rim if protrude from cavity. Figure 4 Upfield 6a, 8, 13 assignments. Trimethylammonium small hydrophobic regions accommodated deep inside cavity. For these guests, carboxylate bonding interactions unable reach sites. The displays host behavior. Saponification 4, shown ESI-HRMS (see Supporting Information), dissolved D2O, observed spectrum. Four-walled this type display salts; most likely, exist velcrand dimers6c,15 larger, kinetically unstable aggregates 5). Figure 5 Side views simplified model complex 3·2H2O (left) 8 (right) showing orientations adamantyl group. Upon excess 1-adamantanol 6f, sharpened peaks seen. correctly stabilizes conformation breaking providing sharp 1:1 complex. Attempts extend range unsuccessful; not sufficiently strong extract hydrophobics hexane, cyclohexane, isooctane, adamantane into solution, four-walled counterpart can.6c Other adamantane-based 6b, 6d, 6e did fold cavitand, presumably due higher water-solubility. Choline also failed break aggregates, although δ −1 ppm, indicating some dynamic association host. In conclusion, new water-stabilized, recognizes shapes. derivative achieved suitably-sized molecules medium. absence allows promising template more flexible receptors improved biologically relevant These reported earlier5 bridge open-sided receptors16 capsules completely surround guests.17