A Comparative Study of Complexation of β-Cyclodextrin,Calix[4]arenesulfonate and Cucurbit[7]uril with Dye Guests: Fluorescence Behavior and Binding Ability

The complexation behaviors of acridine red (AR), neutral red (NR) and rhodamine B (RhB) dye guest molecules by three kinds of supramolecular hosts, including β-cyclodextrin (β-CD), calix[4]arene tetrasulfonate (C4AS) and cucurbit[7]uril (CB[7]), have been investigated by means of fluorescence spectra in aqueous citrate buffer solution (pH 6.0). The results obtained show that the three hosts, possessing different types of cavity, lead to various complexation-induced fluorescence of dye guests, and present different binding ability and molecular selectivity. The complexation stability constants decrease in the order of NR > AR > RhB for C4AS and CB[7] hosts, while in the order of RhB > AR > NR for β-CD host. Particularly, CB[7] displays the strongest binding ability with NR (K _S = 33300 M^? 1), and provides the molecular selectivity of 4.8 for NR/AR pairs. Although the binding ability of C4AS for present dye guests is weaker than CB[7], but the molecular selectivity of the two hosts are nearly equivalent. β-CD shows stronger binding ability with RhB (K _S = 5880 M^? 1) as comparison with CB[7] and C4AS. Furthermore, the solvent effects and salt effects during the course of complexation have also been investigated.     

胆甾类分子钳对氨基酸衍生物的对映选择性识别

用差紫外光谱滴定法考察了以脱氧胆酸作spacer的手性分子钳1～3对一系列α-氨基酸甲酯的对映选择性识别性能。结果表明,分子钳1和2与客体氨基酸甲酯形成1:1型超分子配合物,并显示较好的手性识别能力。分钳3对所考察的氨基酸甲酯均没有明显的识别作用。讨论了主-客体间尺寸/形状匹配、几何互补等因素对形成超分子配合物的影响,并利用计算机模拟作辅助手段对实验结果和现象进行了解释。     

The Complexation of Some Amino Acids by Isomers of Dicyclohexano-18-Crown-6 and 18-Crown-6 in Methanol

The complexation of some amino acids (glycine, L-alanine,L-leucine, L-valine, and L-serine) by the cis-syn-cisand cis-anti-cis isomers of dicyclohexano-18-crown-6 (DC18C6) in methanol was studied by calorimetric titrationmeasurements. Both isomers exhibited a significant ability to bind the amino acidsmentioned above. The results obtained demonstrate that the structural isomers ofDC18C6 are significantly different in terms of thermodynamics concerning their complexationwith the amino acids. The stability constants and the thermodynamic data forthe reaction of the amino acids under study in protonated form and 18-crown-6 (18C6) are reported.     

荧光标识的环糊精二聚体与小肽衍生物之间的包合行为研究

报道了利用荧光偏振方法研究导硫氰酸盐荧光素（FITC）标识,并由天冬氨酸 、谷氨酸、(1R, 3R)-1-氨基-1,3-二羟基环丁烷和（1R, 3R）-1-氨基-1,3-二 羟基环戊烷衍生物桥联的环糊精二聚体（1～4,作为主体）,在pH = 7.4的水溶液 中与几个低分子量的多肽衍生物:Adm-Lys(Adm)-Arg-Arg 5; Adm-Lys(Adm)-D-Arg- D-Arg 6; Adm-Cha-Arg-Arg 7; Adm-Cha-D-Arg-D-Arg 8（作为客体,其中Arg, Lys, Cha和Adm分别为精氨酸,赖氨酸,β-环已烷丙氨酸和1-羟基金刚烷）之间 的键合常数（K_b)和包合反应的热力学参数（△G°,△H°,△S°）。从主-客体 键合常数的比较、客体嵌入基团的结构与周边环境的考察发现,主、客体之间的键 合能力因客体非进入基团（Arg)空间构型上的变化而有所不同。通过比较主体包结 一对手性异构体的自由能变化增量（-△△G_(DL)°）以及一对手性异构体（L-与 D-）与同一主体的键合常数之比（K_L/K_D),讨论了环糊精二聚体对D-型或L-型多 肽衍生物的手性识别能力。根据各体系T△S°与△H°之间较好的线性关系,探讨 了环糊精二聚体与多肽衍生物之间相互作用的焓-熵补偿行为。     

A theoretical and experimental study of water complexes of m-aminobenzoic acid MABA.(H2O)n (n = 1 and 2)

We report studies of supersonically cooled water complexes of m-aminobenzoic acid MABA.(H(2)O)n (n = 1 and 2) using two-color resonantly enhanced multiphoton ionization (REMPI) and UV-UV hole-burning spectroscopy. Density functional theory calculations are also carried out to identify structural minima of water complexes in the ground state. For the most stable isomers of both complexes, water molecules bind to the pocket of the carboxyl group in a cyclic hydrogen bond network. Vibrational frequency calculations for the first electronically excited state (S(1)) of these isomers agree well with the experimental observation. The addition of water molecules has a major impact on the normal mode that involves local motion of the carboxyl group, while negligible effects are observed for other normal modes. On the basis of the hole-burning experiment, two major isomers for each complex are identified, corresponding to the two conformers of the bare compound. Compared with the other two isomers of aminobenzoic acid, the red shifts of the origin bands due to water complexation in MABA are considerably larger. Similar to p-aminobenzoic acid and different from o-aminobenzoic acid, the existence of the intermolecular stretching mode is ambiguous in the REMPI spectrum of MABA.(H(2)O)n.     

The structure and thermodynamics of calix[n]arene complexes with dipyridines and phenanthroline in aqueous solution studied by microcalorimetry and NMR spectroscopy

The complex stability constants (K(S)) and thermodynamic parameters (DeltaH degrees and TDeltaS degrees) for 1:1 intermolecular complexation of three water-soluble calixarenes, that is, p-sulfonato calix[4]arene (C4AS), p-sulfonato thiacalix[4]arene (TCAS), and p-sulfonato calix[5]arene (C5AS), with dipyridines (4-DPD and 2-DPD) and 1,10-phenanthroline (Phen) have been determined by means of titration microcalorimetry in an acidic buffer solution (pH = 2.0) at 298.15 K, and their binding modes have been investigated by (1)H NMR and 2D ROESY NMR spectroscopy. The results obtained indicate that 4-DPD, 2-DPD, and Phen are included in the cavity of C5AS with the different patterns, this is, accumbent for 4-DPD, acclivitous for 2-DPD and Phen, while Phen is included upright in the cavity of C4AS. The K(S) values decrease with increasing cavity size of host molecules but enhance with extending conjugation degree of guest molecules, and thus C4AS exhibits an exceptionally high Phen/4-DPD selectivity of 22.5. Thermodynamically, the complexation of DPDs/Phen with the water-soluble calixarenes is obviously enthalpy-driven, but the molecular selectivity is mainly governed by the entropy term.     

Synthesis of novel bis(beta-cyclodextrin)s and metallobridged bis(beta-cyclodextrin)s with 2,2'-diselenobis(benzoyl) tethers and their molecular multiple recognition with model substrates

To investigate quantitatively the cooperative binding ability of beta-cyclodextrin dimers, a series of bridged bis(beta-cyclodextrin)s with 2,2'-diselenobis(benzoyl) spacer connected by different lengths of oligo(ethylenediamine)s (2-5) and their platinum(IV) complexes (6-9) have been synthesized and their inclusion complexation behavior with selected substrates, such as Acridine Red, Neutral Red, Brilliant Green, Rhodamine B, ammonium 8-anilino-1-naphthalenesulfonate, and 6-p-toluidino-2-naphthalenesulfonic acid, were investigated by means of ultraviolet, fluorescence, fluorescence lifetime, circular dichroism, and 2D-NMR spectroscopy. The spectral titrations have been performed in aqueous phosphate buffer solution (pH 7.20) at 25 degrees C to give the complex stability constants (K(S)) and Gibbs free energy changes (-DeltaG degrees ) for the inclusion complexation of hosts 2-9 with organic dyes and other thermodynamic parameters (DeltaH degrees and TDeltaS degrees ) for the inclusion complexation of 2-5with fluorescent dyes ANS and TNS. The results obtained indicate that beta-cyclodextrin dimers 2-5 can coordinate with one or two platinum(IV) ions to form 1:1 or 1:2 stoichiometry metallobridged bis(beta-cyclodextrin)s. As compared with parent beta-cyclodextrin (1) and bis(beta-cyclodextrin)s 2-5, metallobridged bis(beta-cyclodextrin)s 6-9 can further switch the original molecular binding ability through the coordinating metal to orientate two beta-cyclodextrin cavities and an additional binding site upon the inclusion complexation with model substrates, giving the enhanced binding constants K(S) for both ANS and TNS. The tether length between two cyclodextrin units plays a crucial role in the molecular recognition with guest dyes. The binding constants for TNS decrease linearly with an increase in the tether length of dimeric beta-cyclodextrins. The Gibbs free energy change (-DeltaG degrees ) for the unit increment per ethylene is 0.32 kJ.mol(-)(1) for TNS. Thermodynamically, the higher complex stabilities of both ANS and TNS upon the inclusion complexation with 2-5 are mainly contributed to the favorable enthalpic gain (-DeltaH degrees ) by the cooperative binding of one guest molecule in the closely located two beta-cyclodextrin cavities as compared with parent beta-cyclodextrin. The molecular binding ability and selectivity of organic dyes by hosts 1-9 are discussed from the viewpoints of the multiple recognition mechanism and the size/shape-fitting relationship between host and guest.     

Structure selective complexation of cyclodextrins with five polyphenols investigated by capillary electrokinetic chromatography

The complexation of five polyphenols, namely trans‐resveratrol, astilbin, taxifolin, ferulic acid, and syringic acid (guest molecules) with α‐, β‐, and γ‐cyclodextrin (host molecules), was investigated by capillary electrokinetic chromatography. The binding constants were calculated based on the effective electrophoretic mobility change of guests with the addition of cyclodextrins into the background electrolyte. Because of cavity size, cyclodextrins showed structure‐selective complexation property to different guest. The stability of the trans‐resveratrol complexes was in the order of β‐ > α‐ > γ‐cyclodextrin. The cavity size of α‐cyclodextrin was too small for astilbin and taxifolin molecules, and thus they could not form complexes. The molecular size of syringic acid was too big for all cyclodextrins cavity, and no cyclodextrin could form complexes with it. Temperature studies showed that the binding constants decreased with the rise of temperature. Enthalpy and entropy values were calculated and the negative values of these parameters indicated that the complexation process was enthalpy‐controlled. Van der Waals force and release of high‐enthalpy water molecules from the cyclodextrins cavity played important roles in the process.     

Host–guest complexation of antioxidative caffeic and ferulic acid amides with a functionalized cyclophane

Host?guest complexation has been studied by ¹H NMR on the benzyl and phenethyl amides of ferulic and caffeic acids as the guests in chloroform and acetonitrile; the counter host is a cyclophane which integrates four phenylene rings, amino and amide groups in the macrocyclic framework and bears four pendant methyl acetate ester arms. CAPE, one of the best known natural antioxidants, also has been studied for comparison. Among the guests studied, ferulic acid benzyl amide shows NMR shifts due to the formation of a host?guest complex in chloroform. The complexation occurs in two steps with the formation constants K ₁?=?[HG]/[H][G]?=?6?M^?1 and β ₂?=?[HG₂]/[H][G]²?=?87?M^?2. Two guest molecules are bound on the surface of the macrocyclic framework of a host molecule by two hydrogen bonds, NH(host amide)···O=C(guest amide) and C=O(host ester)···HO(guest phenol). The latter hydrogen bond may protect the bioactive site, i.e., phenol OH, of guest molecules captured in the complex against undesirable oxidation. This feature is observed only for ferulic acid benzyl amide in chloroform; the cyclophane ester interacts with this amide, distinctively from the other hydroxycinnamic acid derivatives.     

NMR Studies of Host–guest Complexes Between Monocarboxylic Acids and Amide-based Cyclophanes in Chloroform

Formation of host–guest complexes with acetic acid and benzoic acid was studied by NMR for amide-based octaazacyclophanes having pendant methyl ester arms; the cyclophanes were tetramethyl 2,9,18,25-tetraoxo-1,4,7,10,17,20,23,26-octaaza[10.10]paracyclophane-4,7,20,23-tetraacetate, its meta-isomer and analogues. Amide NH proton and CH₂ proton adjacent to amide C = O in every cyclophane host showed down-field NMR shifts in the presence of the guest acids in CHCl₃-d, suggesting the formation of 1:1 complexes in which the carboxyl group of an acid molecule formed two hydrogen bonds with the amide NH and C = O moieties of a host molecule. Since the complex formation competed with the dimerization of the guest acids, the monomer–dimer equilibrium was restudied by NMR and the equilibrium constant was determined to be 330 M^? 1 for acetic acid and 518 M^? 1 for benzoic acid. By using these values, the formation constants of the host–guest complexes were determined to be 8–51 M^? 1. The close contact between the host and guest molecules via hydrogen bonding was consistently confirmed by NMR shifts due to the ring current of aromatic group.     

Binding of a neutral guest to cucurbiturils: photophysics,thermodynamics and molecular modelling

Steady-state and time-resolved fluorescence techniques were used to study the thermodynamics of binding of a neutral polarity-sensitive guest, the methyl 2-naphthalenecarboxylate (2MN), with three cucurbiturils (CBn; n = 6, 7 and 8) in water. Association constants (K) were obtained from nonlinear regression analysis of the fluorescence intensity against [CB] in the 5–45°C range. 2MN complexed with CB7 exhibited a 1:1 stoichiometry (K ≈ 10³ M^? 1 at 25°C); however, it hardly did with CB6 (K < 10 M^? 1) and it did not with the larger CB8 macrocyclic ring. The (1:1) 2MN:CB7 complexation process was accompanied by a small unfavourable enthalpy change and was, therefore, entropically governed. Molecular mechanics and molecular dynamics calculations in the presence of water were also used to study the geometry of the complexes formed and the driving forces responsible for their formation. The results were compared with those previously obtained for the complexation of the same guest, 2MN, with natural α-, β- and γ-cyclodextrins.     

Thermodynamics of Amino Acid Methyl Ester Hydrochlorides—Crown Ether Complexes in Methanol at 25°C

Stability constants, free energies, and enthalpies and entropies of the complexation of L-alanine methyl ester hydrochloride (L-Ala-HCl), L-phenylalanine methyl ester hydrochloride (L-Phe-HCl), and valine methyl ester hydrochloride (L-Val-HCl) with 15-crown-5 (15C5), benzo-15-crown-5 (B15C5), 18-crown-6 (18C6), benzo-18-crown-6 (B18C6), dicyclohexano-18-crown-6 (DC18C6), and dicyclohexano-24-crown-8 (DC24C8) in methanol are reported for 20°C. No significant variation in the stability constants and free energies of complexation is observed, indicating that the various crown ethers are poorly selective in binding the amino acids. However, the nature of the crown ether and the amino acid and their pattern of substitution cause a remarkable variation in the enthalpies and entropies of complexation. This indicates a strong enthalpy–entropy compensation effect. The enthalpy–entropy compensation effect for the crown ether complexes of the amino acid methyl ester hydrochlorides reported herein is compared with that of the crown ethers complexes of the amino alcohols and the free amino acid. It is found that the enthalpy–entropy compensation effect holds equally for the three classes of complexes.     

香豆素衍生物和β环糊精分子络合过程的稳态和时间分辨荧光研究

用稳态和时间分辨荧光光谱法研究某些香豆素衍生物(C_311, C_47, C_102, C_120和C_4)同βCyD在水溶液中的络合过程。观察到这些分子在βCyD水溶液中的荧光峰值兰向位移、强度增加和荧光寿命增大。结果表明CND分子在水溶液中同βCyD分子发生络合作用。测得的CND一βCyD体系的络合常数按下列次序递减; K_311>K_47>K_102>K_120>K_4, 这些事实揭示了客体分子的憎水性及同βCyD分子腔体尺寸医配是影响络合作用的重要因素。     

Synthesis and molecular recognition of novel oligo(ethylenediamino) bridged bis(beta-cyclodextrin)s and their copper(II) complexes: enhanced molecular binding ability and selectivity by multiple recognition

Four bridged bis(beta-cyclodextrin)s tethered by different lengths of oligo(ethylenediamine)s have been synthesized and their inclusion complexation behavior with selected substrates elucidated by circular dichroism spectroscopy and fluorescence decay. In order to study their binding ability quantitatively, inclusion complexation stability constants with four dye guests, that is, brilliant green (BG), methyl orange (MO), ammonium 8-anilino-1-naphthalenesulfonic acid (ANS), and sodium 6-(p-toluidino)-2-naphthalenesulfonate (TNS), have been determined in aqueous solution at 25 degrees C with spectrophotometric, spectropolarimetric, or spectrofluorometric titrations. The results obtained indicate that the two tethered cyclodextrin units might cooperatively bind to a guest, and the molecular binding ability toward model substrates, especially linear guests such as TNS and MO, could be extended. The tether length plays a crucial role in the molecular recognition, the binding constants for ANS and TNS decrease linearly with an increase in the tether length of dimeric cyclodextrin. The Gibbs free energy changes (-deltaGo) for the unit increment per ethylene are 0.99 kJ mol(-1) for ANS and 0.44 kJmol(-1) for TNS, respectively. On the other hand, the presence of a copper(II) ion in metallobis(beta-cyclodextrin)s oligo(ethylenediamino) tethers enhances not only the original binding ability, but also the molecular selectivity through triple or multiple recognition, as compared with the parent bis(beta-cyclodextrin)s.     

Molecular Recognition Studies on Modified Cyclodextrins

This account describes our research progress in recent years in the areas of the molecular recognition studies on modified cyclodextrins, including positively charged cyclodextrins, cyclodextrin derivatives with hydrophobic substituent, and dimeric cyclodextrins. Calorimetric titration and various spectrometric techniques were employed to determine the complex stability constants, as well as the thermodynamic parameters, for their inclusion complexation with diverse guest molecules. The results obtained have been discussed from the viewpoint of size/shape‐matching, induced‐fit, geometric compensation, and multiple recognition. Thermodynamically, the compensatory relationship between ΔH and TΔS was found to be exhibited in the inclusion complexation of modified cyclodextrin.     

Inclusion complexes of dihydroartemisinin with cyclodextrin and its derivatives: characterization,solubilization and inclusion mode

The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of dihydroartemisinin with β-cyclodextrin and its derivatives, sulfobutyl ether β-cyclodextrin (SBE-β-CD), mono[6-(2-aminoethylamino)-6-deoxy]-β-cyclodextrin (en-β-CD) and mono{6-[2-(2-aminoethylamino)ethylamino]-6-deoxy}-β-cyclodextrin (dien-β-CD), were studied using phenolphthalein as a spectral probe. Spectral titration was performed in aqueous buffer solution (pH ca. 10.5) at 25 °C to determine the binding constants. The inclusion complexation behaviors were investigated in both solution and solid state by means of NMR, TG, XRD. The results showed that the water solubility and thermal stability of dihydroartemisinin were significantly increased in the inclusion complex with cyclodextrins (CDs). According to ¹H NMR and 2D NMR spectroscopy (ROESY), the A, B rings of dihydroartemisinin can be included into the cavity of CDs. The enhanced binding ability of CDs towards dihydroartemisinin was discussed from the viewpoint of the size/shape-fit concept and multiple recognition mechanism between host and guest.     

Kinetics and mechanism of cyclodextrin inclusion complexation incorporating bidirectional inclusion and formation of orientational isomers

The kinetics of cyclodextrin (CD) inclusion complexation has been usually analyzed in terms of a one-step reaction or a consecutive two-step reaction involving intracomplex structural transformation as a second step. These schemes presume the inclusion of guest molecules through only one side of the CD cavity and the formation of unidirectional CD complexes. However, there has been increasing experimental evidence for the inclusion of guests through both sides of the CD cavity and the formation of orientational isomers for noncentrosymmetric guest molecules. This article presents a novel parallel reaction scheme for CD inclusion complexation, incorporating bidirectional inclusion and the formation of orientational isomers into the scheme. It is shown that the parallel reaction scheme gives the same concentration versus reaction time relationship as the consecutive two-step reaction scheme. The experimental methods for determining the microscopic directional rate constants are presented. The kinetic parameters of the two-step reaction scheme are expressed as functions of the directional rate constants. The ratios of orientational isomers of alpha-CD-based [2]-pseudorotaxanes and the microscopic directional rate constants of the threading and dethreading reactions are estimated from the reported thermodynamic and kinetics data obtained by using either the one-step or two-step reaction scheme. It is shown that the thermodynamic preference of an isomer over the other is mainly due to the slow dethreading rate of the isomer.     

Phase solubility and FTIR-ATR studies of idebenone/sulfobutyl ether β-cyclodextrin inclusion complex

The favourable accessibility offered by sulfobutyl ether β-cyclodextrin (SBE-β-CD) for the complexation with idebenone (IDE) has been probed, as a function of temperature, in liquid state, by phase solubility study, and, in solid state, by FTIR-ATR technique. The phase solubility results indicated the formation of a IDE/SBE-β-CD inclusion complex with 1:1 molar ratio (A_L type diagram), whose apparent stability constants at T = 300, 310, and 320 K have been estimated according to the Higuchi–Connors method. The formation of the inclusion complex has been confirmed on a freeze-dried and a co-precipitated product by FTIR-ATR spectroscopy, monitoring the changes induced by complexation on some characteristic vibrational bands of IDE. Quantitative studies, performed in a wide T range, from T = 250 K to T = 340 K, allowed us to extract information on the effect of temperature on the different hydrogen-bonded environments involving host, guest, and crystallization water molecules. Again, complexation is proved to enhance the stability of the guest, at least in the explored T range.     

Selective binding behaviors of p-sulfonatocalixarenes in aqueous solution

The complex structures, binding abilities, molecular selectivities, and thermodynamic origin of p-sulfonatocalixarenes upon complexation with kinds of guests are outlined in this review article, including inorganic cations, organic ammonium cations, pyridiniums and viologens, neutral organic molecules, dye molecules, and others. Calorimetric and spectroscopic investigations afford the complex stability constants, thermodynamic parameters and binding manners of the inclusion complexation of p-sulfonatocalixarenes with guest molecules. The π-stacking, hydrophobic and charge interactions are the main driving-forces during the course of the host–guest inclusion complexation. The molecular binding abilities and selectivities are influenced by not only the frameworks of calixarene cavities, structures of guest molecules, and their binding manners but also the conditions of solutions (mainly pH), which are discussed from the correlation between the structural features and molecular-recognition abilities. Moreover, the further applications and potentials of p-sulfonatocalixarenes are briefly described.     

Study of the complexation of 5,17-bis-(N-tolyliminomethyl)-25,27-dipropoxycalix[4]arene with pyridine carboxylic acids by RP HPLC and molecular modelling

Host–guest complexation process of 5,17-bis-(N-tolyliminomethyl)-25,27-dipropoxycalix[4]arene with pyridine carboxylic acids by RP HPLC method (mobile phase – MeCN/H₂O, 86/14 by volume, LiChrosorb RP 18, UV detector, λ = 254 nm) had been studied. The binding constants and Gibbs free energies of the complexes 5,17-bis(N-tolyliminomethyl)-25,27-dipropoxycalix[4]arene with the pyridine carboxylic acids are within 584 to 1914 M^? 1 and ? 15.76 to ? 18.69 kJ/mol, respectively. It was shown by the molecular modelling that the complexes are stabilised by hydrogen bonds between carboxylic groups of the acids and nitrogen atoms of imino groups at the upper rim or oxygen atoms of the hydroxyl groups at the lower rim of the macrocycle. Linear dependence of the binding constants from the acid lipophilicity log P indicates the role of solvophobic interactions during the complexation process.