Molecular recognition: minimizing the acid–base interaction of a tunable host–guest system changes the selectivity of binding

Two new receptors incorporating a 4-n-butyl aniline moiety has been designed, synthesized and evaluated for their binding properties towards a series of ureido-glycine derivatives. The host design is based on an urea adamantyl host motif known from large generations of poly(propylene imine) dendrimers functionalized with urea adamantyl moieties on the periphery. The design of the host molecules was directed towards a study of the effects of basicity of an amine function versus the effect of molecular recognition on the binding strength as seen from comparing the results obtained in the present work with previously guest–host studies. The guest–host interaction features an electrostatic interaction and multiple hydrogen binding interactions, where the main difference between the hosts described here and previously described is a substitution from an amine to aniline. Anilines are weaker bases than aliphatic amines and they generally give lower binding constants when treated with acidic guest molecules. The association constants have been measured using NMR titrations and the nature of the guest–host system is discussed based on these results. A general decrease in binding affinities is observed upon changing from the trialkyl amine hosts to the dialkyl aniline based hosts. One exception was observed where the weaker base host had stronger affinity to one of the guests. Thus, when the basicity of the host is decreased other factors influence the binding such as a better geometric fit. A crystal structure of one of the receptors has been solved and it shows no intramolecular hydrogen bonding.     

Cyclodextrin-based polymeric materials for the specific recovery of polyphenolic compounds through supramolecular host–guest interactions

While the specific recovery of valuable chemicals from waste streams represents an environmentally-friendly and potentially economically-relevant alternative to synthetic chemical productions, it remains a largely unmet challenge. This is partially explained by the complexity of designing sorption materials able to target one specific compound and able to function in complex matrices. In this work, a series of cyclodextrin-based polymers (CDPs) were designed to selectively extract phenolic compounds from a complex organic matrix that is olive oil mill wastewater (OMW). In order to endow these polymers with selective adsorption properties, several monomers and cross-linkers were screened and selected. The adsorption properties of the CDPs produced were first tested with selected phenolic compounds commonly found in OMW, namely syringic acid, p-coumaric acid, tyrosol and caffeic acid. The selected CDPs were subsequently tested for their ability to adsorb phenolic compounds directly from OMW, which is known to possess a high and complex organic content. It was demonstrated through high-performance liquid chromatography-mass spectroscopy analyses that efficient removal of phenolic compounds from OMW could be achieved but also that two compounds, namely tyrosol and hydroxytyrosol, could be selectively extracted from OMW.     

Simultaneous enhancement of phosphorescence and chirality by host–guest recognition of molecular tweezers

A novel type of host–guest recognition systems have been developed on the basis of a Au(III) molecular tweezer receptor and chiral Pt(II) guests. The complementary host–guest motifs display high non-covalent binding affinity (K_a: ～10⁴ L/mol) due to the participation of two-fold intermolecular π–π stacking interactions. Both phosphorescence and chirality signals of the Pt(II) guests strengthen in the resulting host–guest complexes, because of the cooperative rigidifying and shielding effects rendered by the tweezer receptor. Their intensities can be reversibly switched toward pH changes, by taking advantage of the electronic repulsion effect between the protonated form of tweezer receptor and the positive-charged guests in acidic environments. Overall, the current study demonstrates the feasibility to enhance and modulate phosphorescence and chirality signals simultaneously via molecular tweezer-based host–guest recognition.     

Host–guest system of Vitamin B10 in β-cyclodextrin: characterization of the interaction in solution and in solid state

Conventional drugs are usually formulated for the immediate release of the medicinal substances and for obtaining the desired therapeutic effect. The aim of this paper was to investigate the possible interactions between Vitamin B10 and β-cyclodextrin (β-CD), to determine the physical-chemical characteristics and the interactions present in the corresponding inclusion compound. The so-obtained compounds were characterized by X-ray diffraction, DSC and FTIR spectroscopy. ¹H NMR and UV–vis spectroscopic methods were employed to study the inclusion process in aqueous solution. The X-ray powder diffraction patterns demonstrate the inclusion compound formation, especially for the lyophilized product where the amorphous phase dominates. The existence of the inclusion compounds obtained by different methods was confirmed by comparing with DSC and FTIR data of the pure compounds and the (1:1) Vitamin B10:β-CD physical mixture (pm). ¹H NMR measurements on aqueous solutions of Vitamin B10 and β-CD in D₂O allowed us to establish the corresponding Vitamin B10’s and cyclodextrin’s protons implied in the complexation process. 2D NMR spectroscopy established the geometry of the inclusion complex. ¹H NMR, UV–Vis and fluorescence data were used to obtain the stoichiometry and the stability constant of the complex.     

Synthesis of a hexacationic cyclophane and formation of EDA-type host–guest complexes

A polycationic cyclophane with six cationic sites (three 4,4′-bipyridinium cation units) supported by a rigid cyclic skeleton was synthesized. It formed electron donor–acceptor complexes with electron-rich compounds, and their inclusion properties with pyrene and calixresorcin[4]arene were studied.     

A recipe for new organometallic polymers and oligomers? Synthesis and structure of an oligo- and a polymeric arrangement of P-S anions

A route to organometallic polymers and oligomers is described using metal complexes with P/S-ligands as examples.     

Blind prediction of host–guest binding affinities: a new SAMPL3 challenge

The computational prediction of protein-ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands--i.e., host-guest systems--represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge for host-guest binding affinities, through the incorporation of 11 new host-guest complexes. Ten participating research groups addressed this challenge with a variety of approaches. Statistical assessment indicates that, although most methods performed well at predicting some general trends in binding affinity, overall accuracy was not high, as all the methods suffered from either poor correlation or high RMS errors or both. There was no clear advantage in using explicit versus implicit solvent models, any particular force field, or any particular approach to conformational sampling. In a few cases, predictions using very similar energy models but different sampling and/or free-energy methods resulted in significantly different results. The protonation states of one host and some guest molecules emerged as key uncertainties beyond the choice of computational approach. The present results have implications for methods development and future blind prediction exercises.     

Inter-molecular physiochemical characterization for etodolac-hydroxypropyl-β-cyclodextrin polymeric systems in solid and liquid state

The purpose of this study was to explore the utility of hydroxypropyl-β-cyclodextrin (HP-β-CD) systems in forming inclusion complexes with the anti-rheumatic or anti-arthritic drug, etodolac (EDC), in order to overcome the limitation of its poor aqueous solubility. This inclusion system achieved high solubility for the hydrophobic molecule. The physical and chemical properties of each inclusion compound were investigated. Complexes of EDC with HP-β-CD were obtained using the kneading and co-evaporation techniques. Solid state characterization of the products was carried out using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and Scanning electron microscopy (SEM). Studies in the solution state were performed using UV-Vis spectrophotometry and ¹H-NMR spectroscopy. Phase solubility profiles with HP-β-CD employed was found to be A_L type. Stability constants (K_c) from the phase solubility diagrams were calculated indicating the formation of 1:1 inclusion complex. Stability studies in the solid state and in liquid state were performed; the possible degradation by RP-HPLC was monitored. The dissolution studies revealed that EDC dissolution rate was improved by the formation of inclusion complexes.      

Free-energy calculations of the host–guest association in grafted supramolecular assemblies

Herein, we investigate the impact of grafting macrocyclic hosts with hydrophobic cavities onto a gold surface on the association with a guest molecule of particular importance to applications for molecular machines. We establish that the increase of the grafted alkyl chain length and number of anchor points strengthens the binding of the guest with the β-cyclodextrin host. This is the opposite effect with the p-sulfonatocalix[4]arene host for which the grafting considerably reduces the strength of the host–guest association. The structural and thermodynamic characterizations, carried out with free energy simulations, are combined to rationalize the differences in the association process in both heterogeneous and homogeneous conditions.     

A new electrochemical method for DNA sequence detection with homogeneous hybridization based on host–guest recognition technology

This communication reports on a new electrochemical method to detect the hybridization specificity by using host–guest recognition technique. A hairpin DNA with dabcyl-labeled at its 3′ and NH₂ group at 5′ terminal was combined with CdS nanoparticle to construct a double-labeled probe (DLP), which could selectively hybridize with its target DNA in homogeneous solution. A β-CD modified Poly(N-acetylaniline) glassy carbon electrode was used for capturing the dabcyl label in DLP. When without binding with target DNA, the DLP kept its stem-loop structure which shielded the dabcyl molecule due to the loop of the hairpin DNA and CdS nanoparticle blocking dabcyl enter into the cavity of these β-CD molecules on the electrode. However, in present of complementary sequence, the target-binding DLP was incorporated into double stranded DNA, causing the DLP’s loop-stem structure opened and then the dabcyl was easily captured by the β-CD modified electrode. During electrochemical measurement, the signal from the dissolved Cd²⁺ was used for target DNA quantitative analysis.     

Cooperative binding of an anticancer drug in a guest–host–protein assembly

The supramolecular formation of an anticancer drug (6-mercaptopurine (6-MP)) in an acetate buffer solution was demonstrated through a host–guest interaction with the macrocyclic host cucurbit[7]uril (Q[7]) and bovine serum albumin (BSA). With the help of ultraviolet absorption and fluorescence spectroscopy, it was shown that a binary complex formed between 6-MP and Q[7] and/or BSA, and a specific binding interaction took place between 6-MP and Q[7] in the presence of BSA. The inclusion constants and thermodynamic parameters were determined at different temperatures. The data suggested that the formation of the binary 6-MP–Q[7] complex was driven by enthalpy in the presence of an unfavourable entropy, which was attributed to the van der Waals and hydrophobic interactions. The fluorescence quenching of BSA by 6-MP was a result of the formation of the 6-MP–BSA complex. This quenching occurred by a static quenching mechanism, and hydrophobic forces played predominant roles in the binding process. Moreover, the absorption data suggested that the interaction between 6-MP and Q[7] or BSA was a competitive process. In addition, the effect of 6-MP on BSA conformation was investigated by synchronous and 3D fluorescence spectra.     

Characterization of the inclusion complex of β-cyclodextrin with sorbic acid in the solid state and in aqueous solution

Crystal structure of β-cyclodextrin (β-CD) complexes with sorbic acid, usually as food preservative, has been determined by single-crystal X-ray diffraction at 113 K. The space group of β-cyclodextrin-sorbic acid complex is P1 with unit cell dimensions of a = 15.284(3) Å, b = 15.402(3) Å, c = 17.981(4) Å, α = 99.67(3)°, β = 112.83(3)°, γ = 102.48(3)° and Z = 1. The result indicates that the β-CD molecules form head-to-head dimers which pack in the intermediate mode. Each dimer contains two guest molecules whose methyl groups are located at the dimer interface while the carboxyl groups protrude from the β-CD primary faces. Water molecules (25.5) are distributed outside the cyclodextrin cavity over 31 sites. Furthermore, nuclear magnetic resonance spectroscopy (¹H NMR) has been employed to investigate the inclusion behavior between the host β-CD and guest sorbic acid in aqueous solution. The results obtained enabled us to structurally characterize the β-CD inclusion complex with sorbic acid.     

Preparation of the Ca–diclofenac complex in solid state

Two ONNO type naphtaldehyde derivative Schiff base compounds were reduced and two symmetric phenol-amine ligands containing naphthalene groups were obtained; bis-N,N′[(2-hydroxy-1-naphtyl) methyl]-1,3-propanediamine (NAFL^H) and bis-N,N′[(2-hydroxy-1-naphtyl) methyl]-2,2′-dimetyhyl-1,3-propanediamine (NAFLDM^H). Homotrinuclear Ni(II) complexes of these ligands were prepared. The solid-state molecular structures of representative nickel complex of NAFLDM^H were determined using single crystal X-ray diffraction analysis. The terminal Ni(II) ions were found to be situated in between the donor atoms of the organic ligand. The central Ni(II) ion was observed to be bonded via two different μ-bridges. The phenolic oxygens and carboxylate ion were seen to form two different μ-bridges. TG analysis proved that the compounds have different thermal characteristics than those cited in literature. The complexes showed extreme exothermic degradation reactions in inert atmosphere. The complexes are ruptured with a two stepped exothermic reaction which appears huge heat over 300 °C. The heat appeared in O₂ atmosphere is observed to be higher than the heat appeared in inert atmosphere. Revealed heat is observed to be higher than the conventional explosive materials.     

Comparing of the host–guest interaction in the Hofmann-1,10-diaminodecane and Hofmann-1,12-diaminododecane-type clathrates

M(1,12-diaminododecane)Ni(CN)4.G (M = Co, Ni or Cd; G = chlorobenzene; 1,2-; 1,3- or 1,4- dichlorobenzene) clathrates were prepared in powder form for the first time and their infrared spectra were reported and then compared with M(1,10-diaminodecane)Ni(CN)₄.1,5G (M = Co, Ni or Cd; G = chlorobenzene; 1,2-; 1,3- or 1,4-dichlorobenzene) clathrates. The spectral results suggest that the characteristic ν(CN) and δ(NiCN) frequencies are found to be similar to those known for the Hofmann type compounds, in that prepared compounds are similar in structure to this type compounds and their structures consist of polymeric layers [M–Ni(CN)₄]_∞ with the 1,12-diaminododecane molecule bound to the metal atom (M). Also, the results suggest that the ligand molecule with 10 to 12 of chain length have no effect on vibrational bands of the guest molecules in the similar Hofmann-diam-type clathrates. The normal mode frequencies and corresponding vibrational assignments of chlorobenzene and 1,2-; 1,3- or 1,4-dichlorobenzene in the ground state were calculated by DFT/B3LYP level of theory using the 6-311G(d, p) basis set in Gauss-view. In addition, these theoretical results were compared to the experimental results for the vibrational modes of host molecules.     

Development of a new form for the alpha function of the Redlich–Kwong cubic equation of state

The dependence on temperature and acentric factor of the attractive term of the Redlich–Kwong equation of state has been modified. A new alpha function is expressed in a generalized form. The new equation allows a good representation of vapor pressure data of a great variety of compounds, as well as thermodynamic properties such as the enthalpy of vaporization and the entropy of vaporization.     

Synthesis and characterization of sol–gel-derived molecular imprinted polymeric materials for cholesterol recognition

The sol–gel-derived host matrices are well known for biosensor applications where various types of organic and biological molecules can be immobilized and can act as recognition elements. The molecular imprinting technology is an attractive alternative method where expensive and labile biorecognition elements can be replaced by molecular imprinted polymers (MIPs), which are capable of recognizing a target molecule of an interest. In the present study, hybrid sol–gel MIPs were synthesized in the form of crushed powder (CP) by both non-hydrolytic and hydrolytic method for cholesterol recognition. These MIPs were characterized by scanning electron microscopy (SEM), fourier transform-infrared (FT-IR), liquid chromatography-mass spectrometry (LC–MS) and nitrogen adsorption–desorption isotherm measurements. The template molecule was extracted by means of soxhlet extraction and calcination method. The cholesterol adsorption experiments were performed by using non-imprinted (NI) and extracted crushed powder (ExCP) and the percentage of adsorption was determined by measuring the residual quantity in the analyte solution using Liebermann-Burchard (L-B) reagent. The adsorption studies with non-imprinted crushed powder (NICP) showed interference with L-B reagent as well as non-specific binding between analyte molecules and silica matrix. The percentage of adsorption or rebinding was found to be higher for phenyl triethoxysilane (PhTEOS)-derived ExCP (composition 3) which was synthesized by the aqueous sol–gel processing method at low pH as compared to PhTEOS-derived (composition 1) and 3-aminopropyltriethoxysilane (APTES)-derived ExCP (composition 2) prepared by non-hydrolytic method. The reusability of used ExCP after re-extraction was also investigated. The various factors affecting rebinding of template molecules were discussed along with interference study. The study provided information on molecular imprinting of cholesterol in sol–gel matrix and highlighted the importance of characterization of MIPs before applying it for sensing applications.     

Study of host–guest interaction between ß-cyclodextrin and alkyltrimethylammonium bromides in water

Cyclodextrins were found to play important roles in self-assembly systems of surfactants. The interactions between host molecule ß-cyclodextrin (CD) and model cationic surfactants, alkyltrimethylammonium bromides with different alkyl chain length: dodecyl-(C₁₂TAB), tetradecyl-(C₁₄TAB) and hexadecyl-(C₁₆TAB) are studied by means of conductivity measurements at 313.2 K. The data obtained indicate that inclusion complexes (CD:S⁺) had formed, and apparent critical micelle concentration (CMC*) is equivalent to the combined concentrations of surfactant monomers complexed with the CD and that of a free dissolved monomer in equilibrium with the micellized surfactant without CD. Inclusion complexes were characterized by an equilibrium binding constant K ₁₁, which value increases as the length of alkyl chains, and consequently the hydrophobicity, increases. From mathematical model the concentrations of the uncomplexed cyclodextrin, uncomplexed surfactant ion, and inclusion complex in the submicellar, as well as in the micellar range were calculated. The competition between the micellization and complexation processes leads to the existence of a significant concentration of free CD in equilibrium with the micellar aggregates. The percentage of uncomplexed cyclodextrin in equilibrium with the micelles is independent on cyclodextrin concentration for a particular ternary system and is 31, 37, and 34 % for C₁₂TAB/water/ß-CD, C₁₄TAB/water/ß-CD and C₁₆TAB/water/ß-CD, respectively. By using standard Gibbs free energy for micellization and surfactant complexation by CD, we can explain the observed behavior.     

Solid-state NMR studies of host–guest chemistry in metal-organic frameworks

Metal-organic frameworks (MOFs) are an emerging class of porous materials with potential applications in a wide variety of fields. The knowledge about the detailed interactions between MOFs and guest molecules is critical for the understanding of their structure-property relationships at working conditions. In this review, recent advances for solid-state NMR studies of host–guest chemistry of MOFs in the application fields of gaseous adsorption, chemical separation, drug delivery, chemical sensor, and heterogeneous catalysis were briefly introduced. The adsorption property and dynamic behavior of adsorbed gases confined inside the MOFs channels were elucidated from variable-temperature (VT) solid-state NMR. Moreover, the detailed mechanism of gas-phase and liquid-phase adsorptive separations on MOFs adsorbents was uncovered on the basis of solid-state NMR measurements. Multi-nuclear ¹H, ¹³C, ¹⁵N, and ³¹P MAS NMR was utilized to explore the interactions between drug molecules and MOFs at the atomic scale to monitor the controlled release process of drugs. Furthermore, the investigation of the interactions between guest molecules and MOFs in the application areas of chemical sensor, toxic chemicals removal, and catalysis using solid-state NMR was briefly discussed as well.