方酰胺衍生物及其在离子识别中的应用

方酰胺骨架具有芳香性的四元环状刚性结构,作为双氢键受体和双氢键给体能与许多客体物种结合,是一类重要、理想的氢键给/受体单元,同时该类给/受体的功能化设计为离子识别行为的检测提供了方便。本文综述了近年来方酰胺化合物的结构特性、衍生化方法,及其在超分子中对阴离子、阳离子与两性离子的识别,实现对离子的跨膜传输、分离与萃取、凝胶响应等功能,以及其在有机小分子催化反应中稳定离子型中间体实现对反应底物催化的功能,并展望了方酰胺化合物在离子识别中的发展前景。     

Recognition of Anions by Synthetic Receptors in Aqueous Solution

Natural anion binding systems achieve high substrate affinity and selectivity most often by arranging converging binding sites inside a cavity or cleft that is well shielded from surrounding solvent molecules by the folded peptide chain. Types of interactions employed for anion recognition are electrostatic interactions, hydrogen-bonding, and coordination to a Lewis-acidic metal center. In this review, successful strategies aimed at the development of synthetic receptors active in water or aqueous solvent mixtures are described. It is shown that considerable progress has been made during recent years in the development of potent anion receptors and that for every type of interaction used in nature for anion binding, corresponding synthetic models exist today. Representative examples of these systems are presented with a special emphasis on synthetic receptors whose characterization involved a detailed thermodynamic analysis of complex formation to demonstrate the important interplay between enthalpy and entropy for anion recognition in water.This revised version was published online in July 2005 with a corrected issue number.     

Syntheses,Characterization, and DNA Binding Studies of a Series of Copper(II), Nickel(II), Platinum(II) and Zinc(II) Complexes Derived from Schiff Base Ligands

Three series of metal salophen complexes derived from Zn²⁺, Cu²⁺, Pt²⁺ and Ni²⁺ have been synthesized and their interaction with quadruplex DNA has been evaluated. The compounds differ on the number of ethyl piperidine substituents. They have been characterized by ¹H NMR, IR and UV-visible spectroscopies and by HR-mass spectrometry. Their luminescent properties have been also evaluated and we can observe that, as expected, Zn²⁺ and Pt²⁺ complexes are those displaying more interesting luminescence with an emission band red-shifted with respect to the corresponding uncoordinated ligand. DNA interactions with G4 and duplex DNA were evaluated by FRET melting assays (for the Zn²⁺, Cu²⁺ and Ni²⁺ complexes) and by emission titrations (for one Pt²⁺ complex) which indicated that the disubstituted compounds 2-Ni and 2-Pt are the only ones that display good affinity for G4 DNA structures.     

A Bambusuril Macrocycle that Binds Anions in Water with High Affinity and Selectivity

Synthetic receptors that function in water are important for the qualitative and quantitative detection of anions, which may act as pollutants in the environment or play important roles in biological processes. Neutral receptors are particularly appealing because they are often more selective than positively charged receptors; however, their affinity towards anions in pure water is only in range of 1–10³ L mol^?1. The anion‐templated synthesis of a water‐soluble bambusuril derivative is shown to be an outstanding receptor for various inorganic anions in pure water, with association constants of up to 10⁷ L mol^?1. Furthermore, the macrocycle discriminates between anions with unprecedented selectivity (up to 500 000‐fold). We anticipate that the combination of remarkable affinity and selectivity of this macrocycle will enable the efficient detection and isolation of diverse anions in aqueous solutions, which is not possible with current supramolecular systems.     

Metal Recognition Driven by Weak Interactions: A Case Study in Solvent Extraction

Tuning the affinity of a medium for a given metallic cation with the sole modification of weak interactions is a challenge for molecular recognition. Solvent extraction is a key technique employed in the recovery and purification of valuable metals, and it is facing an increased complexity of metal fluxes to deal with. The selectivity of such processes generally relies on the use of specific ligands, designed after their coordination chemistry. In the present study, we illustrate the possibility to employ the sole control of weak interactions to achieve the selective extraction of Pd^II over Nd^III: the control over selectivity is obtained by tuning the self‐assembly of the organic phase. A model is proposed, after detailed experimental analysis of molecular (XRD, NMR) and supra‐molecular (SAXS) features of the organic phases. We thus demonstrate that Pd^II extraction is driven by metal coordination, whereas Nd^III extraction requires aggregation of the extractant in addition to metal coordination. These results are of general interest for the applications which rely on the stabilization of metals in organic phases.     

A Flexible Solution to Anion Transport: Powerful Anionophores Based on a Cyclohexane Scaffold

Transmembrane anion carriers (anionophores) have potential for biological activity, including the treatment of channelopathies such as cystic fibrosis. A new family of anionophores has been synthesized, in which three thiourea groups are mounted on a cyclohexane‐based scaffold. Though conceptually related to earlier polycyclic systems, these molecules are simpler and far more accessible. Preorganization is somewhat reduced compared to earlier systems, and anion affinities are correspondingly lower. However, transport activities set new records. This surprising performance suggests a role for controlled flexibility in the design of transmembrane anion carriers.     

Molecular Recognition by Zn(II)-Capped Dynamic Foldamers

Two α-aminoisobutyric acid (Aib) foldamers bearing Zn(II)-chelating N-termini have been synthesized and compared with a reported Aib foldamer that has a bis(quinolinyl)/mono(pyridyl) cap (BQPA group). Replacement of the quinolinyl arms of the BQPA-capped foldamer with pyridyl gave a BPPA-capped foldamer, then further replacement of the linking pyridyl with a 1,2,3-triazole gave a BPTA-capped foldamer. Their ability to relay chiral information from carboxylate bound to Zn(II) at the N-terminus to a glycinamide-based NMR reporter of conformational preference at the C-terminus was measured. The importance of the quinolinyl arms became readily apparent, as the foldamers with pyridyl arms were unable to report on the presence of chiral carboxylate in acetonitrile. Low solubility, X-ray crystallography and ¹H NMR spectroscopy suggested that interfoldamer interactions inhibited carboxylate binding. However changing solvent to methanol revealed that the end-to-end relay of chiral information could be observed for the Zn(II) complex of the BPTA-capped foldamer at low temperature.     

Size-specific, colorimetric detection of counteranions by using helical poly(phenylacetylene) conjugated to L-leucine groups through urea acceptors

A colorimetric detection susceptible to the dimensions of guest counteranions has been demonstrated by using poly(phenylacetylene) with L-leucine and urea functionalities (poly-PA-Leu). Poly-PA-Leu was prepared from N-(4-ethynylphenylcarbamoyl)-L-leucine ethyl ester (PA-Leu) by using [Rh(+){eta(6)-C(6)H(5))B(-)(C(6)H(5))(3)}(2,5-norbornadiene)] as a catalyst. The biased helical conformation of poly-PA-Leu was demonstrated through Cotton effects in the circular dichroism (CD) spectra. The addition of ammonium salts, including tetra-n-butylammonium acetate, tetra-n-butylammonium chloride, and tetra-n-butylammonium bromide anions (CH(3)COO(-), Cl(-), and Br(-)), into the poly-PA-Leu solution intensified the CD responses of poly-PA-Leu, which is indicative of the chiral adjustability of anion recognition by using urea groups. In addition, the combination of poly-PA-Leu with the CH(3)COO(-), Cl(-), and Br(-) anions promoted large redshifts in the absorption spectra, thus providing dramatic color changes from pale yellow to red. Guest dependency in the CD and UV/Vis spectra was clearly correlated with the size of the counteranions. Fundamentally, the addition of tetra-n-butylammonium nitrate, tetra-n-butylammonium hydrogen sulfate, tetra-n-butylammonium perchlorate, tetra-n-butylammonium azide, tetra-n-butylammonium fluoride, and tetra-n-butylammonium iodide anions (NO(3) (-), HSO(4) (-), ClO(4) (-), N(3) (-), F(-), and I(-)) has no effect on either the CD or UV/Vis profiles of poly-PA-Leu. The guest specificity observed in the CD and UV/Vis spectra clearly demonstrated the guest-dimension selectivity of poly-PA-Leu in counteranion recognition.     

Custom‐Fit Ruthenium(II) Metallopeptides: A New Twist to DNA Binding With Coordination Compounds

A new bipyridine building block has been used for the solid‐phase synthesis of dinuclear DNA‐binding ruthenium(II) metallopeptides. Detailed spectroscopic studies suggest that these compounds bind to the DNA by insertion into the DNA minor groove. Moreover, the potential of the solid‐phase peptide synthesis approach is demonstrated by the straightforward synthesis of an octaarginine derivative that shows effective cellular internalization and cytotoxicity linked with strong DNA interaction, as evidenced by steady‐state fluorescence spectroscopy and AFM studies.     

New Host Molecules with Imidazoliums as Functional Arms:Syntheses and Anion Recognition

The bridged tri-imidazoliums 3.3X^--5.3X^-(X^-=PF6^-,Br^-,I^-)and bis-imidazoliums 6.2PF6^- were synthesized by N-quaternization of imidazole derivative 1 in acetonitrile under reflux.UV spectroscopic titration experiments showed that the halide salts and hexafluorophosphate salts of these imidazoliums exhibited good recognition toward anions in water and in acetonitrile,respectively.     

Hetero-Coencapsulation within a Supramolecular Cage: Moving away from the Statistical Distribution of Different Guests

Beside sensing and delivery, another peculiar property arising from confinement in discrete molecular hosts comes from the possibility to have in close proximity, and in defined position, two different molecules (hetero-coencapsulation). This phenomenon can be tuned considering steric and electronic properties of the guests. In this work, a study on the parameters affecting homo- and hetero-coencapsulation processes within a supramolecular cage is reported. In particular, different benzoate guests were bound within a supramolecular cage containing two metal-binding sites and the experimental binding thermodynamics measured. Unexpectedly, from competition experiments it was observed that the maximum concentration of hetero-coencapsulation is achieved if a weakly binding guest is used to partially displace a strongly binding guest.     

Recognition of Free Tryptophan in Water by Synthetic Pseudopeptides: Fluorescence and Thermodynamic Studies

Pseudopeptidic receptors containing an acridine unit have been prepared and their fluorescence response to a series of amino acids was measured in water. Free amino acids, not protected either at the C or the N terminus, were used for this purpose. The prepared receptors display a selective response to tryptophan (Trp) versus the other assayed amino acids under acidic conditions. The macrocyclic nature of the receptor is important as the fluorescence quenching is higher for the macrocyclic compound than for the related open‐chain receptor. Notably, under the experimental acidic conditions used, both the receptor and guest are fully protonated and positively charged; thus, the experimental results suggest the formation of supramolecular species that contain two positively charged organic molecular components in proximity stabilized through aromatic–aromatic interactions and a complex set of cation‐anion‐cation interactions. The selectivity towards Trp seems to be based on the existence of a strong association between the indole ring of the monocharged amino acid and the acridinium fragment of the triprotonated form of the receptor, which is established to be assisted by the interaction of the cationic moieties with hydrogen sulfate anions.     

Polystyrene with Pendant Mixed Functional Ruthenium(II)‐Terpyridine Complexes

A vinyl substituted 2,2′:6′,2″‐terpyridine and a mixed, bifunctional ruthenium(II)‐terpyridine complex bearing a vinyl and a hydroxymethyl group are utilized as comonomers for radical copolymerization with styrene. The resulting polymers are characterized by means of UV‐vis spectroscopy and gel permeation chromatography, coupled with an in‐line diode array spectrophotometer.     

Urea-, squaramide-, and sulfonamide-based anion receptors: a thermodynamic study

In this work, we compare the anion-binding capabilities of receptors 1-5, characterized by similar structures, but possessing different hydrogen-bond-donor moieties (urea, squaramide, and sulfonamide). The presence of chromophoric substituents on the receptor's skeleton allowed the determination of association constants by performing UV/Vis titrations with the investigated anions on solutions of the receptors in pure acetonitrile. Additional quantitative studies of the anion-binding properties of receptors 1-5 were performed by isothermal titration calorimetry (ITC). The experimental results indicated that 1 and 2 formed 1:1 hydrogen-bonded complexes with most of the anions investigated. In the case of receptors 3-5, the formation of the 1:1 adduct was observed only with anions of low basicity (i.e., chloride, bromide, iodide, and hydrogen sulfate). With more basic anions (i.e., acetate and dihydrogen phosphate), both spectrophotometric and ITC titrations accounted for the deprotonation of the sulfonamide group, involving the formation of the conjugated base of the receptor.     

Cation and anion coordination chemistry of palladium(II) with polyazacycloalkanes. Thermodynamic and structural studies

The interaction of PdCl ₄ ^2– with the macrocyclic ligands of the series [3k]aneN _k has been studied both in solution and in the solid state. [18]aneN₆ and [21]aneN₇ form both mono- and binuclear Pd²⁺ complexes, whose stability constants have been determined in 0.5 mol dm^–3 NaCl at 298.15 K. [21]aneN₇ also forms, in solution, a trinuclear species in which an amino group deprotonates to bridge two Pd²⁺ ions, as observed in the solid state. The crystal structure of the complexes [Pd₂([18]aneN₆)Cl₂][ClO₄]₂ and [Pd₃([21]aneN₇)Cl₃][ClO₄]₂ · H₂O have been solved by single crystal X-ray analysis. C₁₂H₃₀N₆Cl₄O₈Pd₂: monoclinic, space group C2/m,a = 10.876(2),b = 18.117(2),c = 7.043(2) Å, = 113.78(2)°,V = 1270(12) ų,Z = 2,D _calc = 1.92 g cm^-3, = 16.94 cm^–1.R = 0.063,R _w = 0.059. C₁₄H₃₆N₇CI₅O₉Pd₃: orthorhombic, space groupPcab,a = 13.125(7),b = 13.213(3),c = 33.570(5) Å,V = 5822(3) ų,Z = 8,D _calc = 2.15 g cm^–3, = 21.20 cm^–1.R = 0.074,R _w = 0.061. In very acidic solutions the polyammonium cations (H _k [3k]aneN _k ) ^k+ interact with PdCl ₄ ^2– forming second sphere coordinated species. These reactions have been followed by a microcalorimetric technique in 2 mol dm^–3 HCl solutions. The slowness of the reactions of (H₁₀[30]aneN₁₀)¹⁰⁺ with PdCl ₄ ^2– has been interpreted in terms of inclusion of the anion into the receptor's cavity as shown by the crystal structure of [(PdCl₄)(H₁₀[30]aneN₁₀)][PdCl₄]₂Cl₄: triclinic, space group PT,a = 7.760(3),b = 11.448(4),c = 13.399(11) Å, = 96.31(8)°, = 104.50(6)°, = 92.30(3)°,Z = 1.R = 0.046 andR _w = 0.039.This paper is dedicated to the memory of the late Dr C. J. Pedersen.