Complexation-induced Changes Research Articles

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response.

We herein describe the comprehensive investigation of the complexation behavior of a guanidinium-modified calix[5]arene pentaisohexyl ether (GC5A) with a variety of typical luminescent dyes. Fluorescein, eosin Y, rose bengal, tetraphenylporphine sulfonate and sulfonated aluminum phthalocyanine were employed as classical aggregation-induced quenching dyes. 2-(p-Toluidinyl)naphthalene-6-sulfonic acid and 1-anilinonaphthalene-8-sulfonic acid were selected as representatives of intramolecular charge-transfer dyes. Phosphated tetraphenylethylene was involved as the classical aggregation-induced emission dye. Sulfonated acedan representing one example of two-photon fluorescent probes, was also investigated. A ruthenium(II) complex with carboxylated bipyridyl ligands was included as a representative candidate of luminescent transition-metal complexes. We determined the association constants of the GC5A–dye complexes by fluorescence titration and discuss the complexation-induced photophysical changes. In addition, a comparison of the complexation behavior of GC5A with that of other macrocycles and potential applications according to the diverse photophysical responses are provided.

Interactions of non-charged tadalafil stereoisomers with cyclodextrins: Capillary electrophoresis and nuclear magnetic resonance studies

The single isomer drug R,R-tadalafil (Cialis®) contains two chiral centers thus four stereoisomers (R,R-, S,S-, S,R- and R,S-tadalafil) exist, however, only the most potent inhibitor, the R,R-tadalafil is in clinical use.In our study, over 20 charged cyclodextrin (CD) derivatives were studied for enantiospecific host–guest type interactions in CD-modified capillary electrophoresis. Tadalafil stereoisomers are non-charged; therefore, their electrophoretic separation poses a challenge. Several candidates of both positively and negatively charged hosts were found to be effective for the enantioseparation. Eight out of the beta derivatives and three of alpha derivatives (including sulfated, sulfoalkylated, carboxyalkylated and amino derivatives) resolved all four stereoisomers partially or completely. Cavity size-dependent absolute enantiomer migration order (EMO) reversals were observed in the case of sulfopropyl-alpha (EMO: R,S; S,R; R,R; S,S) and sulfopropyl-beta (S,S; R,R; S,R; R,S) derivatives, while substituent-dependent partial EMO reversals were detected for sulfobutyl-ether-alpha (R,S; S,R; S,S; R,R) and sulfated-alpha-CD (R,R; S,S; R,S; S,R) selectors. Complexation-induced 1H NMR chemical shift changes reflected that the benzodioxole moiety plays a major role in cavity size-dependent EMO reversal.Sulfobutyl-ether-alpha-CD was the only selector that provided the desired EMO in which the clinically applied eutomer R,R-tadalafil migrates last. Finally, an electrophoretic method applying a background electrolyte (BGE) containing 75mM Tris–acetic acid buffer (pH 4.75) and 7mM sulfobutyl-ether-alpha-CD was developed for the baseline resolution of all isomers at 25°C and +25kV applied voltage.

Enhanced Shape-Selective Recognition of Anion Guests through Complexation-Induced Organization of Porphyrin Hosts

We present a fortuitous discovery of enhanced shape-selective recognition of anion guests that stems from a complexation-induced conformational change in porphyrin hosts upon anion binding. Porphyrin hosts reported here exist in a conformation that is not favorable to guest binding. Anions that bind strongly are those that can induce a conformational change in the host to allow guest binding. Furthermore, guests that mimic the shape of the newly formed pocket bind the strongest.

Complex coacervation of pea protein isolate and alginate polysaccharides

Complex coacervation between pea protein isolate (PPI) and alginate (AL) was investigated as a function of pH (1.50–7.00) and mixing ratio (1:1–20:1 PPI:AL) by turbidimetric analysis and electrophoretic mobility during an acid titration. Conformational changes to the secondary structures during coacervation were also studied by Raman spectroscopy. Critical structure-forming events associated with the formation of soluble (pH 5.00) and insoluble (pH 2.98) complexes were found for a 1:1 PPI–AL mixture, with optimal biopolymer interactions occurring at pH 2.10 (pHopt). As mixing ratios increased between 4:1 and 8:1, critical pHs shifted towards higher pH. Maximum coacervate formation at pHopt occurred at a mixing ratio of 4:1. Electrophoretic mobility measurements showed a shift in net neutrality from pH 4.00 in homogenous PPI solutions, to pH 1.55 for the 1:1 mixture. As biopolymer ratios increased towards 8:1 PPI:AL, net neutrality shifted to higher pHs (∼3.80). Raman spectroscopy revealed minimal complexation-induced conformational changes. Findings could aid in the design of pH-sensitive biopolymer carriers for use in functional food and bio-material applications.

Paper-Based Vapor Detection of Hydrogen Peroxide: Colorimetric Sensing with Tunable Interface

Vapor detection of hydrogen peroxide still remains challenging for conventional sensing techniques, though such vapor detection implies important applications in various practical areas, including locating IEDs. We report herein a new colorimetric sensor system that can detect hydrogen peroxide vapor down to parts per billion level. The sensory materials are based on the cellulose microfibril network of paper towels, which provide a tunable interface for modification with Ti(IV) oxo complexes for binding and reacting with H(2)O(2). The Ti(IV)-peroxide bond thus formed turns the complex from colorless to bright yellow with an absorption maximum around 400 nm. Such complexation-induced color change is exclusively selective for hydrogen peroxide, with no color change observed in the presence of water, oxygen, common organic reagents or other chelating reagents. This paper-based sensor material is disposable and one-time use, representing a cheap, simple approach to detect peroxide vapors. The reported sensor system also proves the technical feasibility of developing enhanced colorimetric sensing using nanofibril materials that will provide plenty of room to enlarge the surface area (by shrinking the fiber size), so as to enhance the surface interaction with gas phase.

Naphthyridine amide–urea conjugate: a case toward selective fluorometric sensing of N-acetyl proline carboxylate

A simple neutral naphthyridine-based chemosensor 1, which selectively recognizes the tetrabutylammonium salt of N-acetyl-l-proline over the other N-acetyl-l-amino acid salts studied in CHCl3 containing 0.1% DMSO, has been designed and synthesized. Moreover, the complexation-induced change in emission characteristics of 1 distinguishes the amino acid salts examined from their conjugate acids. Interaction studies were performed by UV–vis, fluorescence and NMR spectroscopic methods. A simple neutral naphthyridine –based chemosensor 1, which selectively recognizes the tetrabutylammonium salt of N-acetyl-l-proline in CHCl3 containing 0.1% DMSO, has been designed and synthesized. The complexation-induced change in emission characteristics of 1 distinguishes the amino acid salts from their conjugate acids.

Solvent Effects on Acridine Polymorphism

1H NMR dilution experiments were used to monitor self-association of acridine in solution in four different solvents. The pattern of complexation-induced changes in chemical shift is similar in chl...

T-dependence of the vibrational dynamics of IBP/diME-β-CD in solid state: A FT-IR spectral and quantum chemical study

Solid inclusion complex of the non-steroidal anti-inflammatory drug Ibuprofen (IBP, (2-[4-(2-methylpropyl)phenyl]-propanoic acid) with (2,6-dimethyl)-β-cyclodextrin (diME-β-CD) has been investigated by Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR spectroscopy) and numerical simulation. The complexation-induced changes in the FTIR-ATR spectrum of IBP have been interpreted by comparison with the theoretical vibrational wavenumbers and IR intensities of dimeric structures of IBP, derived from symmetric hydrogen bonding of the two carboxylic groups, computed by using Density Functional Theory (DFT) calculations. From temperature-dependent studies, the enthalpy change Δ H associated with the binding of IBP with diME-β-CD for 1:1 stoichiometry, in solid phase, has been estimated.

Host-guest complexation-triggered chiroptical change of poly(phenylacetylene)s bearing binaphthocrown ether moieties on the main chain

Diacetylene monomers with respective lengths of the oxyethylene chains were cyclopolymerized with a rhodium catalyst to produce novel poly(phenylacetylene)s bearing a different cavity size of the chiral crown ether in the repeating units (2a–c). In the circular dichroism spectra of the resulting polymers, characteristic Cotton effects were observed in the range from 350 to 500 nm corresponding to the absorption of the conjugated polymer backbone, indicating that the polymers possessed a helical structure with an excess single screw sense induced by the covalently bonded binaphthyl units. The host–guest complexation of 2a–c with achiral guests produced a chiroptical change based on the fluctuation in the main chain conformation. The behavior of the complexation-induced chiroptical change was essentially dictated by the cavity size of the binaphthocrown ether units. Additionally, a chirality-responsive helicity change was observed in the case of the complexation of 2a–c with chiral guests, which also depended on the crown ether size. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1197–1206, 2010

Enantioselective interaction of carbamoylated quinine and (S)-3,5-dinitrobenzoyl alanine: theoretical and experimental circular dichroism study

The interaction between tert-butylcarbamoylquinine selector and (S)-3,5-dinitrobenzoyl alanine selectand was studied experimentally and theoretically by chiroptical methods. Using a combination of experimental and calculated circular dichroism spectra, we present the first work dealing with the interaction of two dissimilar chiral molecules interacting by diverse types of interactions: ion pairing, hydrogen bonding and π-π stacking. Conformational analysis of the free selector, free selectand and the complex of selector with selectand was carried out and the obtained conformers were optimized at the BHandH/6-31+G** and B97d/6-31+G** levels. Consequently, vibrational (VCD) and electronic (ECD) circular dichroism spectra were calculated at the BHandH/6-31+G** and B97d/6-31+G** levels for the VCD and HF/6-31++G** and CAM-B3LYP/6-31++G** levels for the ECD. Spectral patterns of the free selectand and selector together with the complexation-induced spectral changes were compared with experimental data. Despite many simplifications within the theoretical model, the calculated ECD and VCD spectra are in good agreement with experimental data, which proves that the density functional theory (DFT) methods are able to model complicated systems interacting via multiple interactions of different natures.

Synthesis of an anion receptor for acetate based on the frame of ferrocene

An anion receptor was synthesized with ferrocene as binding frame. Anion recognition can be monitored by anion complexation-induced changes in UV-vis absorption spectra. Interaction between the receptor and acetate was described on the basis of 1H NMR experiments.

Use of quantitative 1H NMR chemical shift changes for ligand docking into barnase

(1)H NMR complexation-induced changes in chemical shift (CIS) of HN protons have been used to characterize the complexes of barnase with the deoxyoligonucleotides d(GC) and d(CGAC). Quantitative shift changes are used not only to locate the most probable binding site (using ring-current shifts), but also to determine the orientation of the ligand within the binding site, based on a more complete shift calculation including bond magnetic anisotropies and electric field effects. For both ligands, the guanine is in the same binding site cleft, in the same position as identified in the crystal structure of the d(CGAC) complex. By contrast, a previous X-ray crystal structure of the d(GC) complex showed the ligand in the mouth of the active site, rather than at the guanyl-specific site, implying that the location may be an artifact of the crystallisation process.

Influence of Conformational Flexibility on Complexation-Induced Changes in Chemical Shift in a Neocarzinostatin Protein−Ligand Complex

In this paper is described an analysis of the effects of protein flexibility on the observed CIS values and the impact on the accuracy of 3D structures determined using a (1)H NMR CIS approach. The effects of protein conformational mobility have been investigated by using a set of different protein structures as starting points for the calculation: the unbound X-ray crystal structure, the unbound NMR solution structure, and the bound NMR solution structure of the protein. The results indicated that loop movement does have a significant impact on the quality of the structure generated by the CIS structure determination methodology. The implementation of methods to treat loop flexibility within our protocol, however, did not improve the results for calculations based on the unbound protein frame.

Fluorescent Iminodiacetamide Derivatives as Potential Ionophores for Optical Zinc Ion-selective Sensors

Fluorescent sensor molecules were synthesized by conjugation of iminodiacetamide derivatives with fluorescent moieties of different structures and their UV-visible and fluorescent properties were characterized in acetonitrile solvent. The fluorescent measurements revealed that the N-(2-naphthyl) and N-phenyl derivatives exhibit a distinct zinc ion-selectivity over alkali and alkaline earth metal ions, while N-(anthrylmethyl) and N-(3-methoxyphenyl) derivatives do not possess any ion-selectivities. In contrast to the fluorescent measurements, all ligands show Zn(2+) selectivity over Ca(2+) and Mg(2+) ions in plasticized PVC membranes using potentiometric signal transduction. This observation found for N-(anthrylmethyl) and N-(3-methoxyphenyl) derivatives can be ascribed to the more hindered interaction between the signalling group of the ionophore and the central metal ion in PVC membranes than in acetonitrile solution upon complexation. From the fluorescent measurements it can also be concluded that the ligands with metal ions form complexes mainly with 2:1 stoichiometry (L(2)M). On complex formation a considerable decrease in the fluorescent intensity was observed for all ligands except the N-(anthrylmethyl) derivative, where a 25 - 30 fold fluorescence enhancement was found, which is explained by the photoinduced electron transfer (PET) mechanism. All ionophores exhibited serious hydrogen ion interference, therefore complexation-induced spectral changes were measured in aprotic acetonitrile solution.

Determination of Protein–Ligand Binding Modes Using Complexation-Induced Changes in 1H NMR Chemical Shift

A new method for determining three-dimensional solution structures of protein-ligand complexes using experimentally determined complexation-induced changes in (1)H NMR chemical shift (CIS) is introduced. The method has been validated using the complex formed between the protein antitumor antibiotic neocarzinostatin (NCS) and a synthetic chromophore analogue. The X-ray crystal structure of the unbound protein and the backbone amide proton CIS were the input data used in the determination of the three-dimensional structure of the complex. The experimental CIS values were used in a continuous direct structure refinement process based on genetic algorithms to sample conformational space. The calculated structure of the complex agrees well with the NMR solution structure, indicating the potential of this approach for structure determination.

On the calculations of the nuclear spin–spin coupling constants in small water clusters

The calculations of the nuclear spin–spin coupling constants were carried out for small water clusters (H 2O) n , n = 2–6, 12, and 17, using density functional theory (DFT) and second-order polarization propagator method (SOPPA). A wide range of different standard and modified basis sets was tested to enable the choice of the possibly smallest and most flexible basis set. The changes in the oxygen–proton coupling constants upon the cluster formation between the nuclei involved in hydrogen bonding cover a range of ca. 13 Hz. The range of the calculated changes in intramolecular 1 J OH couplings shows that the simple model of rigid water clusters seems to be sufficient to reproduce properly the sign and to estimate the magnitude of the gas-to-liquid shift. The sign of the complexation-induced changes in the intramolecular 2 J HH coupling constant is different for molecules with a different coordination number. While the sign is positive for the molecules of the single donor–single acceptor (DA) and single donor–double acceptor (DAA) types, it is negative for the double donor–single acceptor (DDA) molecules. In the four-coordinated double donor–double acceptor (DDAA) molecules the sign of Δ 2 J HH varies. The hydrogen-bond transmitted intermolecular coupling constants are substantial: 1h J OH spans the range from 2.8 to 8.4 Hz while 2h J OO varies from −0.6 to 7.5 Hz. The average intermolecular 1h J OH coupling constant decays slowly with the H⋯O distance in the cyclic clusters n = 2–6. The average 2h J OO coupling decreases exponentially with the O⋯O separation for the cyclic clusters n = 2–6.

The Properties of Weak and Strong Dihydrogen‐Bonded DH⋅⋅⋅HA Complexes

The properties of six dihydrogen-bonded (DHB) dimers with the BeH2 molecule as a proton acceptor were calculated by MP2, CCSD(T) and B3LYP methods. The structural, energetic and spectroscopic parameters are presented and analyzed in terms of their possible correlation with the interaction energy and the intermolecular H...H separation. The symmetry-adapted perturbation theory (SAPT) calculations were performed to gain more insight into the nature of the H...H interactions. The studied complexes are divided into three groups based on the calculated intermolecular distances and the interaction energies which range from approximately -1 to -42 kJ mol(-1). The analysis of the interaction energy components indicates that, in contrast to conventional hydrogen bonds, the induction energy is the most important term in the BeH2NH4+ complex. On the other hand, there is no sharp boundary between the DHB complexes classified as hydrogen bonded and van der Waals systems. The complexation-induced changes in vibrational frequencies and in proton shielding constants show a relationship with the interaction energy. The values of the 2hJXH and 3hJBeX coupling constants correlate well with the interaction energy and with the intermolecular distance.

Characterization of the Dense Liquid Precursor in Homogeneous Crystal Nucleation Using Solution State Nuclear Magnetic Resonance Spectroscopy

Crystallization is very complicated, and therefore the control of crystal nucleation has been basically performed by trial and error, so far. This paper provides a novel, basic idea to cope with this problem theoretically on the basis of the experimental data on crystal nucleation. Here, detailed analysis of the homogeneous crystal nucleation of a novel acaricide, amidoflumet, using solution state nuclear magnetic resonance spectroscopy is reported. The dominant interaction between solute molecules was identified by the complexation-induced changes in chemical shift, corrected by the external double reference method. Also, the concentration dependence of the structure of the dense liquid precursor was well characterized by the apparent averaged structure of the solute cluster. Besides the importance of the supersaturation ratio as a relevant parameter to both the energy difference and the transition probability between the solution state and the solid state, the significance of the absolute solution conce...

Assignment of hydrogen-bond structure in a ligand-nucleobase complex inside duplex DNA: Combined use of quantum chemical calculations and 15N NMR experiments

We present a combined experimental and theoretical approach, whereby a comparison of calculated and experimental 15N NMR chemical shifts allows the elucidation of hydrogen-bond structure in a ligand-nucleobase complex inside duplex DNA. In this work, we focus on the highly selective interaction of 2-amino-7-methyl-1,8-naphthyridine (AMND) to cytosine (C) base opposite the abasic site in DNA duplexes, despite the hydrogen-bond array of neutral AMND being fully complementary to guanine (G). Examination of the salt dependence of the binding constants reveals that the effective number of charges on the ligand is +1.0, indicating protonated AMND does bind to C. This is clearly supported by 15N NMR measurements, where the drastic changes in chemical shift are observed for the aromatic nitrogens on the ligand when binding to C. Furthermore, from the complexation-induced changes in chemical shift at 15N1 (83.1 ppm upfield), 15N8 (14.1 ppm upfield), and 15NH2 (18.3 ppm downfield) on AMND, the ligand is found to bind to C via three point hydrogen-bonds. The chemical shifts of the AMND-C complex, calculated by gauge-independent atomic orbital-DFT method, are in fair agreement with the experimental values. These results clearly explain the selective binding of AMND to C over G in abasic site-containing duplex DNA.

Theoretical Investigation of the Anion Binding Affinities of the Uranyl Salophene Complexes

The uranyl salophene complex and its co-complexes with several anions (H[2]PO[4][-], HSO[4][-], NO[2][-], OH[-], Cl[-], F[-]) in the gas phase are investigated theoretically. Equilibrium geometries of relevant species and complexation-induced structural changes are discussed. The [13]C NMR chemical shifts calculated at the gas-phase optimized geometry agree very well with experimental liquid-phase results. The optimized geometry agrees also very well with available crystallographic data. This indicates that the gas-phase structures derived from theoretical calculations can be considered representative also for the condensed phase. For all anions, except H[2]PO[4][-], the calculated gas-phase binding energies correlate well with experimental Gibbs free energies of complexation. The possible role of the solvent in the case of H[2]PO[4][-] complexation is discussed.