High Association Constant Research Articles

Sulfated Alkyl Glucopyranans with Potent Antiviral Activity Synthesized by Ring-Opening Copolymerization of Anhydroglucose and Alkyl Anhydroglucose Monomers

Sulfated glucopyranans having long alkyl groups were prepared by the ring-opening copolymerization of benzylated 1,6-anhydroglucopyranose with 3-O-octadecyl 1,6-anhydro-β-d-glucopyranose monomers, and subsequent deprotection and sulfation. Water-soluble sulfated glucopyranans with 2.8 and 4.7 mol% of 3-O-octadecyl group and lower molecular weights ofM-n= 2.5 × 103–5.1 × 103have potent anti-HIV activity at 0.05–1.25 μg/mL, even though sulfated polysaccharides with molecular weights belowM-n= 6 × 103had low anti-HIV activity. The interaction with poly-l-lysine as a model compound of proteins was analyzed by SPR, DSL, and zeta potential, indicating that the sulfated 3-O-octadecyl glucopyranans had high association and low dissociation rate constants, and the particle size increased after addition of poly-l-lysine. The anti-HIV activity was induced by electrostatic interaction between sulfate groups and amino groups of poly-l-lysine and by the synergistic effect of the hydrophobic long alkyl chain and hydrophilic sulfated group.

A novel electrochemical piezoelectric label free immunosensor for aflatoxin B1 detection in groundnut

An electrochemical quartz crystal microbalance (EQCM) based label-free immunosensor has been developed for the quantitative detection of aflatoxin B1 (AFB1) in groundnut. The gold (Au) coated quartz crystal (6 MHz) functionalized with self-assembled monolayer (SAM) of 4-aminothiophenol (4-ATP) has been utilized to immobilize anti-aflatoxin antibodies (aAFB1). The quartz crystal microbalance QCM frequency and EQCM cyclic voltammetry measurements have been used to optimize the deposition of SAM layer on Au electrode (4-ATP/Au), antibody immobilization (aAFB1/4-ATP/Au), bovin serum albumin (BSA) adsorption (BSA/aAFB1/4-ATP/Au) and immuno interaction (AFB1/BSA/aAFB1/4-ATP/Au). Interestingly, the EQCM studies conducted on this immunoelectrode provide wider linear range of 0.1–4.0 ng mL−1 and higher sensitivity than those obtained using under identical condition. The high association constant of 9.4 × 10−2 ng mL−1 of the EQCM immunosensor can be attributed to molecularly oriented self assembled monolayer of 4-ATP on QCM gold electrode that acts as a nanowire between aAFB1 and electrode through amide linkage formed by the NH2 group of 4-ATP and COOH group of Fc part of aAFB1. This linkage also helps to project paratope part of aAFB1 to interact with AFB1. The developed label free EQCM based immunosensor was tested for the AFB1 detection in the extract of contaminated groundnut and the results were compared with Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The comparative results demonstrate the suitability of this sensor for routine screening of groundnut and the percent error is found to be ±12%.

Oxo-anion recognition by mono- and bisurea pendant-arm macrocyclic complexes.

The novel macrocyclic copper(II) complexes [2](2+) and [3](2+), carrying one or two (nitrophenyl)urea fragments appended to an azacyclam or diazacyclam framework, exploit the hydrogen-bond-forming abilities of the urea subunits, along with the metal-ligand interaction, in the recognition of anionic species. Equilibrium studies in acetonitrile performed on [2](2+) and [3](2+) show that (nitrophenyl)urea pendant arms strongly interact with anionic species such as carboxylates and phosphates, which display both coordinating tendencies toward copper(II) and good affinity toward urea subunits. Stability constants of the adducts are considerably higher than those determined for the interaction of the same anions with a "plain urea" reference compound, confirming the synergistic action of metallomacrocyclic and urea subunits. Complex [2](2+) forms 1:1 adducts with acetate, benzoate, hydrogendiphosphate, and dihydrogen phosphate, while complex [3](2+) interacts with the same anions according to both 1:1 and 1:2 stoichiometries, with the exception of hydrogendiphosphate, which forms only the 1:1 adduct with a distinctly high association constant (log K > 7). Spectrophotometric investigations suggest that oxoanionic species interact with the complexes according to a "bridged" mode, inducing the macrocyclic systems to adopt a scorpionate-like conformation, as confirmed by crystallographic studies on the [3](2+)/succinate adduct.

Interaction of palmitic Acid with metoprolol succinate at the binding sites of bovine serum albumin.

The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. The binding of metoprolol succinate to bovine serum albumin (BSA) was studied by equilibrium dialysis method (ED) at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 10(5) M(-1)) with low capacity (n1 = 2) and low affinity association (k2 = 4.0×10(5) M(-1)) constant with high capacity (n2 = 8) at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10(-5) M to 16×10(-5) M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

Pillar[10]arene-based size-selective host-guest complexation and its application in tuning the LCST behavior of a thermoresponsive polymer.

A new molecular recognition motif between a water soluble pillar[10]arene (WP10) and 1,10-phenanthrolinium guest (G) in water is established. Mainly driven by the cooperativity of multiple electrostatic interactions, hydrophobic interactions, and π-π stacking interactions between WP10 and G, this host-guest complex exhibits a high association constant in water, which is about 17 times higher than that between WP10 and paraquat (PQ). Furthermore, this size selective host-guest complexation is employed to tune the lower critical solution temperature behavior of a random copolymer with PQ derivative pendants.

ChemInform Abstract: Stimuli‐Responsive Host‐Guest Systems Based on the Recognition of Cryptands by Organic Guests

AbstractReview: 76 refs.

ChemInform Abstract: Coordination Chemistry‐Assembled Multicomponent Systems Built from a Gable‐Like Bis‐Porphyrin: Synthesis and Photophysical Properties

AbstractReview: 64 refs.

Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries.

Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ΔG for guest binding and the guest's surface area: the change in ΔG for binding is 0.3 kJ mol(-1) Å(-2), corresponding to 5 kJ mol(-1) for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation. The highest association constant is K = 1.2 × 10(6) M(-1) for cycloundecanone, whose volume is approximately 50% of the cavity volume; for larger C12 and C13 cyclic ketones, the association constant progressively decreases as the guests become too large. For a series of C10 aliphatic ketones differing in shape but not size, ΔG for guest binding showed no correlation with surface area. These guests are close to the volume limit of the cavity (cf. Rebek's 55% rule), so the association constant is sensitive to shape complementarity, with small changes in guest structure resulting in large changes in binding affinity. The most flexible members of this series (linear aliphatic ketones) did not bind, whereas the more preorganized cyclic ketones all have association constants of 10(4)-10(5) M(-1). A crystal structure of the cage·cycloundecanone complex shows that the guest carbonyl oxygen is directed into a binding pocket defined by a convergent set of CH groups, which act as weak hydrogen-bond donors, and also shows close contacts between the exterior surface of the disc-shaped guest and the interior surface of the pseudospherical cage cavity despite the slight mismatch in shape.

A quinoline derivative as an efficient sensor to detect selectively Al³⁺ ion.

A quinoline-based Schiff base 1 has been utilized as a fluorescence chemosensor for the selective detection of Al(3+). The receptor 1 exhibited a high association constant (3.67 × 10(5) M(-1)) with submicromolar detection limit (0.18 ppm) towards Al(3+) in CH3CN solution.

Influence of H‐Bonding on Self‐Assembly and Tunable Dual‐Emission of Carbazole‐Based Zn(II)‐Terpyridine Metallocycles

Two carbazole derivatives with terpyridine units attached to the 3,6‐positions are synthesized, 1 with a hydrogen at the 9‐position and 2 bearing a dodecyl chain there, to evaluate the influence of H‐bonds on their self‐assembly behavior with metal ions. The unalkylated derivative 1 assembles with zinc ions to form a single product identified by NMR, electrospray ionisation mass spectrometry (ESI‐MS), and X‐ray photoelectron spectroscopy (XPS) as a pentametric metallocycle (Zn‐1), whereas 2 forms a mixture of two assemblies (Zn‐2). The pentamer Zn‐1 shows tunable dual emission in the blue and green regions by varying the solvent and excitation wavelength, and molecular packing studies by powder X‐ray diffractometry (XRD), transmission electron microscopy (TEM), polarising optical microscopy (POM), and atomic force microscopy (AFM) reveals a high propensity to form ordered layers. A fluorescence quenching experiment of electron‐rich Zn‐1 with C60 shows a high association constant of Ksv = 3.2 × 105m−1, suggesting effective charge transfer between Zn‐1 and C60 molecules. image

Water-Soluble Pillar[7]arene: Synthesis, pH-Controlled Complexation with Paraquat, and Application in Constructing Supramolecular Vesicles

By the introduction of 14 anionic carboxylate groups at its two rims, a water-soluble pillar[7]arene (WP7) was synthesized. Its pH-controlled complexation with paraquat G1 in water was investigated. Host WP7 and guest G1 formed a 1:1 [2]pseudorotaxane with a high association constant of (2.96 ± 0.31) × 10(9) M(-1) in water. Furthermore, we took advantage of this novel molecular recognition motif to fabricate a supra-amphiphile based on WP7 and an amphiphilic paraquat derivative G2. The morphologies and sizes of self-assemblies of G2 and WP7⊃G2 were identified by transmission electron microscopy and dynamic light scattering.

Phenothiazine-Bridged Cyclic Porphyrin Dimers as High-Affinity Hosts for Fullerenes and Linear Array of C60in Self-Assembled Porphyrin Nanotube

Free-bases and a nickel(II) complex of phenothiazine-bridged cyclic porphyrin dimers bearing self-assembling 4-pyridyl groups (M2-Ptz-CPDPy(OCn); M = H2 or Ni, OCn = OC6 or OC3) at opposite meso-positions have been prepared as host molecules for fullerenes. The free-base dimer (H4-Ptz-CPDPy(OC6)) includes fullerenes with remarkably high association constants such as 3.9 ± 0.7 × 10(6) M(-1) for C60 and 7.4 ± 0.8 × 10(7) M(-1) for C70 in toluene. This C60 affinity is the highest value ever among reported receptors composed of free-base porphyrins. The nickel dimer (Ni2-Ptz-CPDPy(OC6)) also shows high affinities for C60 (1.3 ± 0.2 × 10(6) M(-1)) and C70 (over 10(7) M(-1)). In the crystal structure of the inclusion complex of C60 within H4-Ptz-CPDpy(OC3), the C60 molecule is located just above the centers of the porphyrins. The two porphyrin planes are almost parallel to each other and the center-to-center distance (12.454 Å) is close to the optimal separation (∼12.5 Å) for C60 inclusion. The cyclic porphyrin dimer forms a nanotube through its self-assembly induced by C-H···N hydrogen bonds between porphyrin β-CH groups and pyridyl nitrogens as well as π-π interactions of the pyridyl groups. The C60 molecules are linearly arranged in the inner channel of this nanotube.

Functionalization at the Central Position of Vinyl Polymer Chains: Highly Associable Multipoint Hydrogen Bonds for Complementary Self‐Assemblies

This paper deals with the precision introduction of a multiple hydrogen-bonding site of a high association constant at the central position of a vinyl polymer chain for complementary self-assemblies. The interactive site consists of an array of hydrogen donors (D) and acceptors (A) to induce a multiple and highly associable interaction with a complementary counterpart. A bifunctional initiator (Cl-DADDAD-Cl) for metal-catalyzed living radical polymerization is thus designed and synthesized to embed a "Hamilton receptor" (DADDAD) between two terminal chlorides (Cl). In the presence of a ruthenium complex, the dichloride gives controlled polymers (Cl∼∼∼DADDAD∼∼∼Cl, ∼ ∼ ∼: polymer backbone) of narrow molecular weight distributions (Mw/Mn < 1.2) from common monomers such as styrene and methyl methacrylate (MMA). The receptor-decorated polystyrene recognizes complementary associable molecules and polymers carrying an ADADA unit (ADADA-Anthracene and ADADA-PMMA) to form self-assemblies where the association constant is as high as K(ass) ≈ 8000 m(-1).

Syntheses of amide based anion receptors and investigation of their associations with anions and their molecular structures using proton NMR titration and DFT methods

The synthesized disubstituted isophthalamide and pyridine-2,6dicarboxamide derivatives of nine compounds were prepared. Their association constants with tetrabutylammonium fluoride (TBA·F), tetrabutylammonium chloride (TBA·Cl), tetrabutylammonium bromide (TBA·Br), tetrabutylammonium dihydrogenphosphate (TBA·H2PO4), tetrabutylammonium hydrogensulphate (TBA·HSO4) and tetrabutylammonium nitrate (TBA·NO3) were obtained by 1H NMR titration technique. The optimized structures of compounds 1–9 and their association with F−, Cl−, Br−, H2PO4-, HSO4- and NO3- were obtained using the B3LYP/6-31+G(d) method. The most favorable complex of compound 3 with Br− was found. The high association constants of complexes 1–6 with F− are expected. Associations of all receptors with anions are exothermic and spontaneous reactions. Thermodynamic properties of all associations obtained using B3LYP/6-31+G(d) method are reported.

Supramolecular Assembly of Multicomponent Photoactive Systems via Cooperatively Coupled Equilibria

Here, we show that the synergistic interplay between two binding equilibria, acting at different sites of a (Zn)phthalocyanine-amidine molecule (Pc1), enables the dissociation of the photoinactive phthalocyanine dimer (Pc1)2 into a three-component system, in which a sequence of light harvesting, charge separation, and charge shift is successfully proven. The aforementioned dimer is assembled by dual amidine-Zn(II) coordination between neighboring Pc1 molecules and gives rise to high association constants (KD ≈ 10(11) M(-1)). Such extraordinary stability hampers the individual binding of either carboxylic acid ligands through the amidine group or pyridine-type ligands through the Zn(II) metal atom to (Pc1)2. However, the combined addition of both ligands, which cooperatively bind to different sites of Pc1 through distinct noncovalent interactions, efficiently shifts the overall equilibrium toward a photoactive tricomponent species. In particular, when a fullerene-carboxylic acid (C60A) and either a dimethylamino-pyridine (DMAP) or a phenothiazine-pyridine ligand (PTZP) are simultaneously present, the photoactivity is turned on and evidence is given for an electron transfer from photoexcited Pc1 to the electron-accepting C60A that affords the DMAP-Pc1(•+)-C60A(•-) or PTZP-Pc1(•+)-C60A(•-) radical ion pair states. Only in the latter case does a cascade of photoinduced electron transfer processes afford the PTZP(•+)-Pc1-C60A(•-) radical ion pair state. The latter is formed via a thermodynamically driven charge shift evolving from PTZP-Pc1(•+)-C60A(•-) and exhibits lifetimes that are notably longer than those of DMAP-Pc1(•+)-C60A(•-).

The interaction of photoactivators with proteins during microfabrication

Abstract Micron-scale protein cross-linking or microfabrication has been carried out using an Nd 3+ –YAG laser as the excitation source. Fabrication is carried out by the excitation of photoactivators (Rose Bengal, methylene blue and 9-fluorenone-2-carboxylic acid) with the ultimate goal of creating stable structures that will serve as models for various applications (drug delivery and tissue engineering). Experimental parameters have been adjusted to minimize photodamage and maximize cross-linking efficiency. The higher than ideal photon flux and peak power necessitates the use of high protein concentrations to minimize photodamage. Rose Bengal and methylene blue are binding to proteins with high association constants ( K a ≈ 10 6 M −1 ) and both Rose Bengal and both 9-fluorenone-2-carboxylic acid are showing changes to their excited states in presence of proteins at cross-linking concentrations. Molecular docking studies show that Rose Bengal binds close to the tryptophan with Δ G = −6.15 kcal/mol.

A highly selective fluorescence turn-on and reversible sensor for Al3 + ion

A simple Schiff-base receptor 1 was prepared. It exhibits an “off–on-type” mode with high sensitivity in the presence of Al3+ and shows a high association constant (5.89×106M−2) toward Al3+ in DMSO–H2O (4:6 v/v) solution. The addition of EDTA to receptor 1·Al3+ complex quenches the fluorescent intensity, indicating that receptor 1 serves as a reversible chemosensor.

A novel sensitive doxorubicin impedimetric immunosensor based on a specific monoclonal antibody–gold nanoaprticle–sol–gel modified electrode

In this work, ultrasensitive electrochemical doxorubicin impedance immunosensor was investigated based on immobilization of a specific monoclonal antibody on gold nanoparticles (GNPs) associated with a thiol base sol-gel (TBSol-Gel) modified gold electrode. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed for characterization of the various layers that were formed at the electrode surface. The redox couples of 1.0 mmol L(-1), Fe(CN)6(4-/3-) species on the electrode surface was followed to study the layers formation and determination process, using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). After optimization of analytical parameters, the relative charge transfer resistance (Rct) increases linearly with doxorubicin concentration in the ranges of 0.1-1.0 and 2.5-50.0 pg mL(-1), with a detection limit of 0.09 pg mL(-1). A high association constant of 1.4 × 10(11) L mol(-1) was obtained for the affinity of doxorubicin toward the immobilized antibody on the electrode surface. The capability of the proposed immunosensor for the determination of doxorubicin in spiked human serum and urine samples was examined by standard addition method, and the results show that the immunosensor is a useful tool for the determination of doxorubicin in the biological samples.

Coordination Chemistry‐Assembled Multicomponent Systems Built from a Gable‐Like Bis‐Porphyrin: Synthesis and Photophysical Properties

Multiporphyrinic assemblies were quantitatively formed, in one step, from a gable-like zinc(II) bis-porphyrin ZnP2 and free-base porphyrins bearing pyridyl groups. The different fragments are held together by axial 4'-N(pyridyl)-Zn interactions. Formation of a macrocycle ZnP2 •(4'-cisDPyP) and a bis-macrocycle (ZnP2 )2 •(TPyP) is discussed. The macrocycle and the bis-macrocycle were crystallized and studied by X-ray diffraction, which confirmed the excellent complementarity between the various components. Spectrophotometric and spectrofluorimetric titrations and studies reveal high association constants for both multiporphyrinic assemblies due to the almost perfect geometrical match between the interacting units. As expected, energy transfer from the zinc porphyrin component to the free-base porphyrin quenches the fluorescence of the zinc porphyrin components in both compounds. But while in ZnP2 •(4'-cis DPyP) sensitization of the emission of the free-base porphyrin was observed, in (ZnP2)2 •(TPyP) excitation of the peripheral Zn porphyrin units does not lead to quantitative sensitization of the luminescence of the free-base porphyrin acceptor. An unusual HOMO-HOMO electron transfer reaction from ZnP2 to the excited TPyP unit was detected and studied.

Quantum Chemical Challenges for the Binding of Simple Alkanes to Supramolecular Hosts

Binding of hydrocarbon guests to supramolecular hosts can lead to unusual geometric changes such as bending or coiling of guests upon encapsulation. Cucurbiturils (CBs) are classic cation binders that were recently used for the selective binding of small-membered hydrocarbons with a very high association constant (Ka ≈ 10(6) M(-1)). In this study, we have systematically investigated the binding of some alkanes to CB-[6] using a series of quantum chemical methods. The calculated binding free energies are very strong and are largely influenced by guest orientations inside the host and reorganization of host and guests. The computed (1)H NMR chemical shifts of the encapsulated alkanes agree with the experimental estimates thus confirming guest encapsulation. Further, we have shown that although binding of both cyclopentane and neopentane have very strong binding affinities (>20 kcal mol(-1)), the selectivity of cyclopentane to neopentane at CB-[6] is a kinetically driven process through the computation of approximate transition state structures of both alkanes to CB-[6]. The calculated binding affinities with dispersion corrected density functionals (DFs) are very close to the experimental estimates, whereas DFs that lack dispersion correction predict that alkane binding to CB-[6] is largely unfavorable. Finally, we have investigated the binding of some long chain alkanes to several supramolecular hosts using dispersion corrected semiempirical methods which cannot be routinely studied through density functional theory methods due to the larger size of the system.