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Vinblastine was investigated in the presence of cyclodextrin derivatives on different cancer cells and it was established that the anticancer activity was unchanged. This was the first step of a long procedure resulting in the dosage of vinblastine together with cyclodextrin or its derivatives to improve the adverse effects. [ABSTRACT FROM AUTHOR]

In this work, reactions between 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-diones with different benzohydrazides were studied. Nucleophilic substitution at C(6) was followed by isomerization and led to α-hydroxy-p-quinone imine derivatives. Synthesized compounds represent a combination of several structural motifs: a benzimidazole core fused with α-hydroxy-p-quinone imine, which contains a benzamide fragment. X-ray crystallography analysis revealed the formation of dimers linked through OH···O interactions and stabilization of the imine form by strong intramolecular NH···N hydrogen bonds. The protonation/deprotonation processes were investigated in a solution using UV–Vis spectroscopy and a 1H NMR titration experiment. Additionally, the electrochemical properties of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its α-hydroxy-p-quinone imine derivative as cathode materials were investigated in acidic and neutral environments using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as a potentially effective active electrode in aqueous electrolyte batteries; however, further optimization is required. [ABSTRACT FROM AUTHOR]

The presence of higher order G-quadruplex-DNA (G4) structures in human cells in guanine-rich DNA sequences has been well established. In cases of G4 helicase impairment or G4 stabilization via association with G4 ligands, it has been determined that arrest and/or termination of DNA transcription/replication occurs because these structures act as physical barriers to both helicase and polymerase mobility along the DNA. Truncation of transcription or replication may result in the loss of genetic material expression leading to disorders. To ameliorate G4-induced barriers, agents that destabilize or "unwind" the quadraplex structures are sought. Earlier work has shown that the cytosine analogue phenylpyrrolocytosine has potential G4-destabilizing ability. It was hypothesized that the unwinding activity was related to its ability to base pair with guanosine. To facilitate the design and evaluation of the hydrogen bonding ability of cytosine analogues, solubility in aprotic, and low-polarity solvents, e.g., deutero-chloroform (CDCl3), is needed; then, determination of association constants (Ka) with guanine via 1H nuclear magnetic resonance (NMR) spectroscopy or isothermal titration calorimetry (ITC) will be possible. Herein, we report on the synthesis of three new chloroform-soluble, cytosine analogues: N1-cyclohexylmethyl-7-phenylimidazolocytosine, N1-cyclohexylmethyl-7-(6-(methoxycarbonyl)pyridin-2-yl)imidazolocytosine, and N1-cyclohexylmethyl-7-(6-carbamoylpyridin-2-yl)imidazolocytosine. We further report the binding interactions of each of these analogues with the guanosine derivative 2′,3′,5′-O-tris(tert-butyldimethylsilyl)guanosine through the use of both ITC and 1H NMR titration experiments in chloroform and compare the binding to persilyated ribo-cytidine. [ABSTRACT FROM AUTHOR]

Inclusion complexes of benzene (Bz) with cyclodextrins (CD) have been investigated so far using non-NMR techniques in various solvents resulting in conflicting data. Here, the first application of NMR spectroscopy in combination with rigorous statistical analysis of the results has allowed us to determine accurately the stoichiometry of complexes and their association constants. Titration measurements have been performed by 1H NMR spectroscopy in D2O at a magnetic field B0 of 14.1 T. αCD and γCD host molecules form weak 1 : 1 complexes with Bz. In contrast, Bz and βCD build 1 : 1 and 2 : 1 complexes coexisting in solution with large binding constants. Binding of second benzene molecule is strongly cooperative. [ABSTRACT FROM AUTHOR]

Bispidines are a family of ligands that plays a pivotal role in various areas of coordination chemistry, with applications in medicinal chemistry, molecular catalysis, coordination polymers synthesis, and molecular magnetism. In the present work, triazole moieties were introduced using the CuAAC click-reaction, with the aim of expanding the number of coordination sites on the bispidine core. The 1,2,3-triazole rings were thus synthesized on propargyl-derived bispidines after reaction with different alkyl azides. The new class of triazole-bispidines was characterized, and their chelation capabilities were evaluated with different metals through NMR titration, ESI-MS spectrometry, and single-crystal X-ray diffraction (SC-XRD). Finally, the suitability of these molecules as metal ligands for the catalytic Henry reaction was demonstrated with copper and zinc. [ABSTRACT FROM AUTHOR]

In this work, reactions between 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-diones with different benzohydrazides were studied. Nucleophilic substitution at C(6) was followed by isomerization and led to α-hydroxy-p-quinone imine derivatives. Synthesized compounds represent a combination of several structural motifs: a benzimidazole core fused with α-hydroxy-p-quinone imine, which contains a benzamide fragment. X-ray crystallography analysis revealed the formation of dimers linked through OH···O interactions and stabilization of the imine form by strong intramolecular NH···N hydrogen bonds. The protonation/deprotonation processes were investigated in a solution using UV–Vis spectroscopy and a 1H NMR titration experiment. Additionally, the electrochemical properties of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its α-hydroxy-p-quinone imine derivative as cathode materials were investigated in acidic and neutral environments using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as a potentially effective active electrode in aqueous electrolyte batteries; however, further optimization is required.

trans-3,4-Dihydroxyselenolane (DHS), a water-soluble cyclic selenide, exhibits selenoenzyme-like unique redox activities through reversible oxidation to the corresponding selenoxide. Previously, we demonstrated that DHS can be applied as an antioxidant against lipid peroxidation and a radioprotector by means of adequate modifications of the two hydroxy (OH) groups. Herein, we synthesized new DHS derivatives with a crown-ether ring fused to the OH groups (DHS-crown-n (n = 4 to 7), 1–4) and investigated their behaviors of complex formation with various alkali metal salts. According to the X-ray structure analysis, it was found that the two oxygen atoms of DHS change the directions from diaxial to diequatorial by complexation. The similar conformational transition was also observed in solution NMR experiments. The 1H NMR titration in CD3OD further confirmed that DHS-crown-6 (3) forms stable 1:1 complexes with KI, RbCl and CsCl, while it forms a 2:1 complex with KBPh4. The results suggested that the 1:1 complex (3·MX) exchanges the metal ion with metal-free 3 through the formation of the 2:1 complex. The redox catalytic activity of 3 was evaluated using a selenoenzyme model reaction between H2O2 and dithiothreitol. The activity was significantly reduced in the presence of KCl due to the complex formation. Thus, the redox catalytic activity of DHS could be controlled by the conformational transition induced by coordination to an alkali metal ion. [ABSTRACT FROM AUTHOR]

A eutectic mixture of L‐menthol and malonic acid, Me/MA (4 : 1), was characterized by calorimetry and other physical measurements. The new deep eutectic solvent (m.p. 6 °C) solvates 338 mg of ibuprofen per mL, and the solution is stable in a wide temperature range. Strategies of NMR titration used in supramolecular chemistry were employed to explore binding forces between the eutectic constituents as well as solute‐solvent interaction in ibuprofen solution. Even in acetonitrile, Me4MA is formed through a hydrogen‐bonding network, where the constituents act as hydrogen donors and acceptors at the same time. The estimated association constant is around 30 M−1; the binding forces are enough to build the eutectic mixture at high concentrations. The aggregate Me4MA forms a molecular complex with ibuprofen in acetonitrile as a result of the cooperative effect of the constituents. In addition, van der Waals interactions are operative between ibuprofen and menthol in the saturated IB‐Me/MA (4 : 1) solution. [ABSTRACT FROM AUTHOR]

Bispidines are a family of ligands that plays a pivotal role in various areas of coordination chemistry, with applications in medicinal chemistry, molecular catalysis, coordination polymers synthesis, and molecular magnetism. In the present work, triazole moieties were introduced using the CuAAC click-reaction, with the aim of expanding the number of coordination sites on the bispidine core. The 1,2,3-triazole rings were thus synthesized on propargyl-derived bispidines after reaction with different alkyl azides. The new class of triazole-bispidines was characterized, and their chelation capabilities were evaluated with different metals through NMR titration, ESI-MS spectrometry, and single-crystal X-ray diffraction (SC-XRD). Finally, the suitability of these molecules as metal ligands for the catalytic Henry reaction was demonstrated with copper and zinc.

Complexation between choline and betaine with acetylated calix[4]pyrogallolarenes was studied in DMSO via 1H-NMR spectroscopy and in the gas phase via electrospray ionization-mass spectrometry (ESI–MS). In the presence of acetylated calix[4]pyrogallolarene, especially if there is an alkyl chain on the lower rim of macrocycle, the formation of a very stable host–guest-type complex was observed. In this way, it was found that the affinity constant between O-acylated-tetra(propyl)calix[4]pyrogallolarene with choline or betaine was 45 or 135, respectively, however the complexation process with acetylated calix[4]pyrogallolarene with aromatic substituent on the lower rim, the results showed that there was a weak interaction with the studied neurotransmitters. From the results, the important role played by the acetyl group in the host–guest interaction with betaine was evident. By contrast, the values of the binding constants of choline were not any higher than unmodified calix[4]pyrogallolarenes. Suitable crystals of O-acylated-tetra(propyl)calix[4]pyrogallolarene were obtained and were characterized through an X-ray crystal structure determination and showed the formation of the inclusion complex O-acylated-tetra(propyl) calix[4]pyrogallolarene·DMSO, which crystallized with two additional molecules of dimethylsulfoxide, additionally the DRX data allowing us to establish that the conformation that it has is of a boat and that it is possibly retained in solution. [ABSTRACT FROM AUTHOR]

A powerful pH-free multicomponent NMR titration method can measure relative acidities, even of closely related compounds, with excellent accuracy. The history of the method is presented, along with details of its implementation and a comparison with earlier NMR titrations using a pH electrode. Many of its areas of applicability are described, especially equilibrium isotope effects. The advantages of the method, some practical considerations, and potential pitfalls are considered.

A powerful pH-free multicomponent NMR titration method can measure relative acidities, even of closely related compounds, with excellent accuracy. The history of the method is presented, along with details of its implementation and a comparison with earlier NMR titrations using a pH electrode. Many of its areas of applicability are described, especially equilibrium isotope effects. The advantages of the method, some practical considerations, and potential pitfalls are considered.

[Display omitted] • NMR titration analysis of diorganotin bis(carboxylate) in basic solution. • Initial in situ analysis considering different base strengths. • In situ formation of distannoxanes via diorganotin bis(carboxylate). • First reaction mechanism for the formation process of distannoxanes. • Distannoxanes blocks for generating complexes with interesting applications. Twelve diorganotin bis(carboxylate) R 2 Sn(O 2 CR') 2 were synthesized using alkyl tin oxide (methyl, n -butyl, and n -octyl), and benzoic acid derivatives with para substituents (NH 2 , H, Cl, and NO 2). Comprehensive characterization through infrared (IR), mass spectrometry (MS), nuclear magnetic resonance (NMR), elemental analysis (EA), and X-ray diffraction confirmed their structures. The diorganotin bis(carboxylate) compounds were placed in situ in an NMR tube under basic conditions with deuterated chloroform as a solvent, forming dimeric distannoxane compounds ([R 2 Sn(O 2 CR')] 2 O) 2. Various bases, such as piperidine, piperazine, aniline, pyridine, sodium hydroxide, and tetrabutyl ammonium hydroxide, were employed. The integration of NMR, MS, and X-ray data provides crucial evidence for the formation of dimeric distannoxanes and their possible reaction mechanism under basic conditions. [ABSTRACT FROM AUTHOR]

trans-3,4-Dihydroxyselenolane (DHS), a water-soluble cyclic selenide, exhibits selenoenzyme-like unique redox activities through reversible oxidation to the corresponding selenoxide. Previously, we demonstrated that DHS can be applied as an antioxidant against lipid peroxidation and a radioprotector by means of adequate modifications of the two hydroxy (OH) groups. Herein, we synthesized new DHS derivatives with a crown-ether ring fused to the OH groups (DHS-crown-n (n = 4 to 7), 1–4) and investigated their behaviors of complex formation with various alkali metal salts. According to the X-ray structure analysis, it was found that the two oxygen atoms of DHS change the directions from diaxial to diequatorial by complexation. The similar conformational transition was also observed in solution NMR experiments. The 1H NMR titration in CD3OD further confirmed that DHS-crown-6 (3) forms stable 1:1 complexes with KI, RbCl and CsCl, while it forms a 2:1 complex with KBPh4. The results suggested that the 1:1 complex (3·MX) exchanges the metal ion with metal-free 3 through the formation of the 2:1 complex. The redox catalytic activity of 3 was evaluated using a selenoenzyme model reaction between H2O2 and dithiothreitol. The activity was significantly reduced in the presence of KCl due to the complex formation. Thus, the redox catalytic activity of DHS could be controlled by the conformational transition induced by coordination to an alkali metal ion.

This is an addendum to our preceding article, 'NMR pD-variation method to determine the proper stabilities of organic electrolyte complexes: case of histidine complexes with a cyclophane acid' Supramolecular Chemistry, which proposes that the species distribution of complexes between organic electrolytes is determined by observing the pD dependence of NMR signals for a mixture of the reactants; the species distribution can be replotted in a pH scale. This addendum demonstrates that the process of data analysis is simplified even more reliably by employing a global fitting method in place of a local, successive method used previously; comparative evaluation was made using Excel® spreadsheets appended. The straightforward global analysis will facilitate the practice of pD-variation NMR titration. The application range is potentially extendable by the use of 13C NMR, which overcomes some weak points of the 1H NMR method. [ABSTRACT FROM AUTHOR]

The complexation of organic electrolytes, like carboxylic acids and amines, is studied usually by spectrometric titration at a constant pH. Obtained stability constants are, however, conditional and dependent on the pH selected, differing from the proper constants. In nuclear magnetic resonance (NMR) titration in D2O, a stability constant determined at a given pD is not directly correlated to other properties observed at a pH in H2O because of difference between acid dissociations in the solvents. To overcome these problems, this report proposes pD-variable NMR spectrometry, which monitors NMR signals of a mixture of the reactants with the variation of pD. This method identifies complexes formed in different pD ranges, and determines the proper stability constants, to yield the species distribution, which can be replotted in pH scale. The usefulness and limitation are examined by simulation of titration curves. An experimental example is presented for complexation of histidine with a cyclophane acid. Excel® files for calculations are available in Supplementary material. [ABSTRACT FROM AUTHOR]

C-2 and C-5 substituted imidazole skeleton was synthesized through a one-pot two-step strategy. Synthesized molecule emits the light on ESIPT (excited-state intramolecular proton transfer). This molecule was utilized for its proton donor ability, and we have observed that fluoride and cyanide ions can be detected selectively. Different cations and anions were selected to observe the response of the synthesized molecule. However, there were not any fluorometric and colorimetric response except for fluoride and cyanide ions. Detection limits of fluoride and cyanide ions were found to be 9.22 μM and 11.48 μM, respectively. 1H-NMR spectra for the solution of the sensor and TBAF (tetrabuthylammoniumfluoride) were used for the identification of [L]−[HF2]− species. 3 equiv. TBAF saturated the solution of the sensor in d6-DMSO, and some of the proton resonances shifted to upfield due to the through-bond effect. The disappearance of NH proton with 0.5 equiv. TBAF or TBACN (tetrabuthylammoniumcyanide) showed that there was a proton abstraction by fluoride and cyanide ions, instead of the hydrogen bond. Solid-state application was utilized, and paper test strips were applied. Emission differences emerged when the sensor loaded strips were reacted with TBAF. Time resolved experiments revealed that solution of the sensor and TBAF in DMSO have multiexponential decay, and one of the lifetime was measured as 13.4 ns. [ABSTRACT FROM AUTHOR]

Halogen bonding represents a powerful tool in the field of noncovalent interactions. However, applications in enantioselective recognition and catalysis remain almost nonexistent, due in part to the distinct features of halogen bonds, including long covalent and noncovalent bond distances and high directionality. Herein, this work presents a novel chiral tetrakis‐iodo‐triazole structure as a neutral halogen bond donor for both chiral anion‐recognition and enantioinduction in ion‐pair organocatalysis. NMR‐titration studies revealed significant differences in anion affinity between the halogen bonding receptor and its hydrogen bonding parent. Selective recognition of chiral dicarboxylates and asymmetric induction in a benchmark organocatalytic reaction were demonstrated using the halogen bond donor. Inversions in the absolute sense of chiral recognition, enantioselectivity, and chiroptical properties relative to the related hydrogen donor were observed. Computational modeling suggested that these effects were the result of distinct anion‐binding modes for the halogen‐ versus hydrogen‐bond donors. [ABSTRACT FROM AUTHOR]

In this article, the presence and effects of polarization‐enhanced hydrogen bonding in 1,8‐dihydroxynaphthalene (1,8‐DHN) were investigated in detail through a series of experimental and computational studies. First, the conformation of 1,8‐DHN, and its ability to make intra‐ and intermolecular hydrogen bonds were investigated in solid state by X‐ray crystallography, in solution by NMR spectroscopy, and computationally by density functional theory. Second, equilibrium binding constants, which were determined by 31P‐NMR titration studies, demonstrated stronger complexation of Ph3PO with 1,8‐DHN compared to mono‐naphthol derivatives 8‐methoxy‐1‐naphthol and 1‐naphthol. In the final section, 1,8‐DHN was observed to be an effective catalyst for the Friedel‐Crafts‐type addition reaction of indoles to β‐nitrostyrenes, and a rationale for this catalytic activity was provided via computational studies. All the findings described in this work support the enhanced hydrogen bond donating ability of 1,8‐DHN due to polarization caused by the six‐membered intramolecular hydrogen bond present in its structure. [ABSTRACT FROM AUTHOR]

The aromatic nucleophilic substitution reaction based synthesis of a three-armed cryptand displaying 2,4,6-triphenyl-1,3,5-triazine units as caps and pyridine rings in the bridges, along with NMR, MS and molecular modelling-based structural analysis of this compound are reported. Appropriate NMR and molecular modelling investigations proved the formation of 1:1 host–guest assemblies between the investigated cryptand and some polynuclear aromatic hydrocarbons or their derivatives.

Some biogenic compounds undergo conformational isomerism, and the isomers may interact distinctively with other substances to form molecular complexes individually with different stabilities. In the present work, such molecular interaction specific to isomers was confirmed for the complexation of cationic glucosamine anomers with benzoate and phthalate anions. The individual stability constants of the anomer complexes were determined by tracing 1H NMR shifts of each anomer in titration with the appropriate carboxylate. In the complexes of benzoate, phthalate and terephthalate, the binding forces in the β-anomer complexes are two to five times as strong as those of the corresponding α-anomer complexes. The formulae of titration curves for determining individual stabilities have been developed in a generalised form to be applicable to the complexation of other unresolvable isomers with different compositions. [ABSTRACT FROM AUTHOR]

Here in, the condensation of boc-glycine with 2,6-anhydro-3,4,5-tri-O-benzyl-D-gluco-heptitol followed by its boc-deprotection to form 2,6-anhydro-3,4,5-tri-O-benzyl-D-gluco-heptitolyl bis-glycinate, which in turn on condensation with succinic acid/pyridine-2,6-dicarboxylic acid led to the formation of sugar-amino acid hybrid macrocyclic compounds 4, 6 and debenzylated marocyclic compound 5, having amide bonds that function as efficient host for polar, hydrogen bond acceptors and carboxylate ions. The anion inclusion capability of synthesized macrocylic hosts has been evaluated by the study of their binding with boc-GlyCOOˉ anion as guest through 1H NMR titration studies in CDCl3. The binding constant (Ka) of boc-GlyCOOˉ guest with macrocyclic hosts 4 and 6 involving succinate and pyridine-2,6-dicarboxylate linkers was found to be 9.201 × 103 and 1.437 × 104 M−1, respectively. The higher binding constant was observed in the complex of boc-GlyCOOˉ with pyridine-dicarboxylate containing host may be due to the extra rigidity & suitable conformation attained by the presence of rigid-aromatic dicarboxylate linker. [ABSTRACT FROM AUTHOR]

Purpose: Cathinone derivatives are new psychoactive substance(s) (NPSs) with amphetamine-like effects and currently represent a great problem for public health. For this reason it is necessary to develop new sensitive, selective fast and inexpensive methods for large-scale screening of NPSs. The purpose of this study was to evaluate the capabilities of 4-tert-butylcalix[4]arene tetra-acetate as a receptor of potentiometric sensor to recognize NPSs based on cathinone derivatives and one aminoindane for comparison. Methods: Potentiometry was used to determine the selectivity of a 4-tert-butylcalix[4]arene tetra-acetate towards cathinone derivatives. Density functional theory (DFT) computations and nuclear magnetic resonance (NMR) titration were used to explain the binding modes of the calix[4]arene derivative towards selected NPSs. Results: The basic binding mode of the calix[4]arene derivative for NPSs, namely a hydrogen bonding towards the NH group, was confirmed using DFT calculations and NMR titration. Importantly, the calix[4]arene derivative as the receptor of the potentiometric sensor provides (1) discrimination between cathinone derivatives themselves and cathinones from aminoindane as well as the (2) possibility of detection of buphedrone in samples containing the mixture of the different NPSs including cathinones (Sr ≤ 0.11). Conclusions: A potentiometric sensor based on calix[4]arene derivative provided a rapid and perspective technique for the detection of cathinone derivatives. These results show that potentiometric sensors can become promising future tools for NPSs detection. [ABSTRACT FROM AUTHOR]

A new family of chiral tetraoxacalix[2]arene[2]triazine receptors (2a–2c) have been synthesized efficiently in 69–73% yields. By 1H NMR spectroscopy, the chiral enantiodiscrimination ability of novel hosts against a series racemic carboxylic acids were examined. The chiral calix[2]arene[2]triazine-based compounds were found to have good enantiomeric recognition ability to racemic carboxylic acids. We also observed that the tetraoxacalix[2]arene[2]triazine derivative 2c is a more versatile chiral solvating agents than 2a and 2b, as 2c shows a better performance for the determination of the enantiomeric excess. The molar ratio of the each enantiomers of guest molecules with receptors were examined by using Job plots, respectively. The graphics show that the hosts form 1:1 complexes with all of the guests. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A macrocyclic bis-urea and two acyclic bis-urea analogues have been synthesized. • NMR titrations indicates that L1 has high selectivity to H 2 PO 4 −. • L1 exhibits higher binding affinity with H 2 PO 4 − than L2 and L3. • XRD analysis shows that L1 have different conformations in solid structure. Abstract A macrocyclic bis-urea receptor (L1) and two acyclic bis-urea analogues (L2 and L3) have been synthesized. The crystal structure of L1 was obtained. The experimental results show that the receptor L1 has high selectivity to H 2 PO 4 −. Meanwhile, compared with the acyclic receptors L2 and L3 , L1 has higher binding ability to H 2 PO 4 −. The results of density functional theory (DFT) calculations deepened our understanding on L1 conformations stability and its anion-binding property. [ABSTRACT FROM AUTHOR]

A series of six new symmetrically functionalized thiourea based indole conjugated ligands (S1–S6) are synthesized in good yields and their anion recognition/sensing ability in the solution as well as in solid state is explored. Chemosensors S1–S6 show selective colorimetric sensing of fluoride by stable NIR signatures at 942 nm, 956 nm, 825 nm, 890 nm, 948 nm, and 1160 nm with corresponding spectral shifts (Δλ) of 592 nm, 588 nm, 603 nm, 485 nm, 610 nm, and 800 nm by virtue of position, conjugation and electronic effect of different functional groups attached to indole unit. To the best of our knowledge the peak shift of a chemosensor by magnitude of 800 nm (from UV to NIR region) in the presence of fluoride represents the highest of its kind. The changes in absorption spectra in the presence of various anions follow the Hofmeister series of anions. All the chemosensors show a bathochromic shift in the absorption spectra of the ligands in the presence of acetate, benzoate, dihydrogen phosphate and hydrogen pyrophosphate due to hydrogen bonding interactions with the indole and thiourea‐NH groups. The single‐crystal X‐ray structures evidence in favour of planar structures of the free sensors (S1, S4, and S5) and strong hydrogen bonding interactions between phosphate anion and indole–thiourea NH groups. Selective sensing of fluoride within a broad NIR window (825 nm to 1160 nm) by prompt visible color changes by six new symmetrically substituted, thiourea based, indole conjugated sensors is demonstrated. Different substituents lead to specific coloration and absorption spectral shifts in the presence of fluoride. This structure‐property correlation could be helpful to design a series of new NIR based sensors with specific colour changes. [ABSTRACT FROM AUTHOR]

The α‐ and β‐cyclodextrins with two dimethylamino groups or two trimethylethylenediamino groups attached to the primary face were synthesized and their pKa values were determined by potentiometric titration. The complexation of the four cyclodextrin analogues with zinc and copper was studied by NMR and showed one or two cyclodextrins bound to the metal. Inclusion of 4‐halophenols in the metal complexes were also studied. The α‐ and β‐cyclodextrins with two dimethylamino groups or two trimethylethylenediamino groups attached to the primary face were synthesized and their pKa values were determined by potentiometric titration. The complexation of the four cyclodextrin analogues with zinc and copper was studied by NMR and showed one or two cyclodextrins bound to the metal. [ABSTRACT FROM AUTHOR]

Abstract Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides isolated from the marine sponge Theonella sp. The inclusion of cholesterol (Chol) or ergosterol in the phosphatidylcholine membrane is known to significantly enhance the membrane affinity for theonellamide A (TNM-A). We have previously revealed that TNM-A stays in a monomeric form in dimethylsulfoxide (DMSO) solvent systems, whereas the peptide forms oligomers in aqueous media. In this study, we utilized 1H NMR chemical shift changes (Δ δ 1H) in aqueous DMSO solution to evaluate the TNM-A/sterol interaction. Because Chol does not dissolve well in this solvent, we used 25-hydroxycholesterol (25-HC) instead, which turned out to interact with membrane-bound TNM-A in a very similar way to that of Chol. We determined the dissociation constant, K D , by NMR titration experiments and measured the chemical shift changes of TNM-A induced by 25-HC binding in the DMSO solution. Significant changes were observed for several amino acid residues in a certain area of the molecule. The results from the solution NMR experiments, together with previous findings, suggest that the TNM-Chol complex, where the hydrophobic cavity of TNM probably incorporates Chol, becomes less polar by Chol interaction, resulting in a greater accumulation of the peptide in membrane. The deeper penetration of TNM-A into the membrane interior enhances membrane disruption. We also demonstrated that hydroxylated sterols, such as 25-HC that has higher solubility in most NMR solvents than Chol, act as a versatile substitute for sterol and could be used in 1H NMR-based studies of sterol-binding peptides. Graphical abstract Unlabelled Image Highlights • Theonellamide A (TNM-A) shows potent antifungal activity in a sterol-dependent manner. • Cholesterol-peptide interaction by solution 1H NMR can be achieved by using hydroxylated sterol and aqueous DMSO. • Unstable complexation of TNM-A with sterol was detected as chemical shift changes in 1H NMR titration. • TNM-A incorporates a sterol molecule in its cavity to strengthen its binding to membrane. [ABSTRACT FROM AUTHOR]

Graphical abstract A new naphthalimide platform based indolium ion functionalized colorimetric as well as fluorometric chemodosimeter (L) has been synthesized which selectively sense CN− ion in aqueous media through nucleophilic addition of CN − in L with low detection limit. Highlights • Novel colorimetric chemodosimeter L is synthesised and characterised. • Visual detection of CN− ion is observed in aqueous media. • Nucleophilic addition of CN− ion in L makes the sensing process irreversible. • L exhibits high sensitivity and selectivity towards CN− ion. Abstract A naphthalimide platform based indolium ion functionalized colorimetric as well as fluorometric chemodosimeter (L) has been synthesized and characterized. This can selectively sense cyanide (CN−) in aqueous medium with a low limit of detection (approximately 0.5 μM), which is around four times lower than the value of 1.9 μM set by WHO. The UV–vis and PL studies have been carried out in 40% aqueous-acetonitrile medium which shows a significant change in the visible region allowing naked eye colorimetric detection of CN¯. The mass spectrometry and 1H NMR spectroscopy are used to characterize the corresponding cyanide adduct which has also been corroborated by time-dependent density functional theory (TD-DFT) during the establishment of the sensing mechanism. [ABSTRACT FROM AUTHOR]

Abstract: We present single crystal structures of unsubstituted oxacalix[4]arene and oxacalix[8]arene macrocycles and investigate the weak supramolecular interactions that govern their packing in the solid state. We further show that the unsubstituted oxacalix[4]arene shows weak complexation with two aromatic guest species, benzoic acid and ferrocene, in CDCl3, whereas the oxacalix[8]arene host does not complex with these guest molecules. We also present NMR titration experiments with non‐aromatic acids and DFT calculations that signify the importance of π‐π interactions for complexation with benzoic acid. Weak complexation is also observed between electron‐rich aromatic guest molecules and the unsubstituted oxacalix[4]arene host. [ABSTRACT FROM AUTHOR]

The binding of monosaccharides and short peptides to lymphocyte receptors (human CD69 and rat NKR-P1A) was first reported in 1994 and then in a number of subsequent publications. Based on this observation, numerous potentially high-affinity saccharide ligands have been synthesized over the last two decades in order to utilize their potential in antitumor therapy. Due to significant inconsistencies in their reported binding properties, we decided to re-examine the interaction between multiple ligands and CD69 or NKR-P1A. Using NMR titration and isothermal titration calorimetry we were unable to detect the binding of the tested ligands such as N-acetyl-d-hexosamines and oligopeptides to both receptors, which contradicts the previous observations published in more than twenty papers over the last fifteen years.

The human telomeric G-quadruplex (G4) is an attractive target for developing anticancer drugs. Natural products protoberberine alkaloids are known to bind human telomeric G4 and inhibit telomerase. Among several structurally similar protoberberine alkaloids, epiberberine (EPI) shows the greatest specificity in recognizing the human telomeric G4 over duplex DNA and other G4s. Recently, NMR study revealed that EPI recognizes specifically the hybrid-2 form human telomeric G4 by inducing large rearrangements in the 5′-flanking segment and loop regions to form a highly extensive four-layered binding pocket. Using the NMR structure of the EPI-human telomeric G4 complex, here we perform molecular dynamics free energy calculations to elucidate the ligand selectivity in the recognition of protoberberines by the human telomeric G4. The MM-PB(GB)SA (molecular mechanics-Poisson Boltzmann/Generalized Born) Surface Area) binding free energies calculated using the Amber force fields bsc0 and OL15 correlate well with the NMR titration and binding affinity measurements, with both calculations correctly identifying the EPI as the strongest binder to the hybrid-2 telomeric G4 wtTel26. The results demonstrated that accounting for the conformational flexibility of the DNA-ligand complexes is crucially important for explaining the ligand selectivity of the human telomeric G4. While the MD-simulated (molecular dynamics) structures of the G-quadruplex-alkaloid complexes help rationalize why the EPI-G4 interactions are optimal compared with the other protoberberines, structural deviations from the NMR structure near the binding site are observed in the MD simulations. We have also performed binding free energy calculation using the more rigorous double decoupling method (DDM); however, the results correlate less well with the experimental trend, likely due to the difficulty of adequately sampling the very large conformational reorganization in the G4 induced by the protoberberine binding.

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson–Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster–Lachmann δ-diagram analysis and Perrin model data linearization.

Solutions of Brønsted acids with bases in aprotic solvents are not only common model systems to study the fundamentals of proton transfer pathways but are also highly relevant to Brønsted acid catalysis. Despite their importance the light nature of the proton makes characterization of acid-base aggregates challenging. Here, we track such acid-base interactions over a broad range of relative compositions between diphenyl phosphoric acid and the base quinaldine in dichloromethane, by using a combination of dielectric relaxation and NMR spectroscopy. In contrast to what one would expect for an acid-base titration, we find strong deviations from quantitative proton transfer from the acid to the base. Even for an excess of the base, multimers consisting of one base and at least two acid molecules are formed, in addition to the occurrence of proton transfer from the acid to the base and simultaneous formation of ion pairs. For equimolar mixtures such multimers constitute about one third of all intermolecular aggregates. Quantitative analysis of our results shows that the acid-base association constant is only around six times larger than that for the acid binding to an acid-base dimer, that is, to an already protonated base. Our findings have implications for the interpretation of previous studies of reactive intermediates in organocatalysis and provide a rationale for previously observed nonlinear effects in phosphoric acid catalysis. [ABSTRACT FROM AUTHOR]

In this contemporary work we designed and synthesized a simple tetra dentate Schiff base, which displays colorimetric and fluorescence “turn on” sensing behavior towards Ag + in aqueous DMF (50%) solution. Benesi Hildebrand–plot reveals 1:2 binding mode between probe and Ag + with limit of detection down to 1.12 μM. Cyclic voltammograms exhibits high anodic shift with Ag + due to the charge transfer from ligand to metal ion. The binding mode was proved by NMR titrations, FE-SEM elemental analysis & advance DFT calculation. Additionally, the subsequent Ag + -complex also shows an extremely selective response to CN − among other anions due to the displacement of Ag + via CN − , forming [Ag(CN) x ] − species into the medium. Probe was used as coated paper test strip which served as mini colorimetric device for detection of Ag + and CN − . [ABSTRACT FROM AUTHOR]

ABSTRACT We report the solution NMR structure of RHE_CH02687 from Rhizobium etli. Its structure consists of two β-sheets that together with two short and one long α-helix form a hydrophobic cavity. This protein shows a high structural similarity to the prokaryotic protein YndB from Bacillus subtilis, and the eukaryotic protein Aha1. NMR titration experiments confirmed that RHE_CH02687, like its homolog YndB, interacted with flavonoids, giving support for a biological function as a flavonoid sensor in the symbiotic interaction between R. etli and plants. In addition, our study showed no evidence for a direct interaction between RHE_CH02687 and HtpG, the R. etli homolog of Hsp90. Proteins 2017; 85:951-956. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The halogen bond (XB) is a topical noncovalent interaction of rapidly increasing importance. The XB employs a `soft' donor atom in comparison to the `hard' proton of the hydrogen bond (HB). This difference has led to the hypothesis that XBs can form more favorable interactions with `soft' bases than HBs. While computational studies have supported this suggestion, solution and solid-state data are lacking. Here, XB soft-soft complementarity is investigated with a bidentate receptor that shows similar associations with neutral carbonyls and heavy chalcogen analogs. The solution speciation and XB soft-soft complementarity is supported by four crystal structures containing neutral and anionic soft Lewis bases. [ABSTRACT FROM AUTHOR]

The present paper explores the complexation ability of methacrylic acid which is one of the most abundant functional monomer for the preparation of molecularly imprinted polymers. Host-guest interactions and the mechanism of complex formation between methacrylic acid and potentially genotoxic 1,3-diisopropylurea were investigated in the pre-polymerization solution featuring both experimental (NMR, IR) and in silico density functional theory (DFT) tools. The continuous variation method revealed the presence of higher-order complexes and the appearance of self-association which were both taken into account during the determination of the association constants. The quantum chemical calculations – performed at B3LYP 6-311 ++G(d,p) level with basis set superposition error (BSSE) corrections – are in agreement with the experimental observations, reaffirming the association constants and justifying the validity of computational investigation of such systems. Furthermore, natural bond orbital analysis was carried out to appraise the binding properties of the complexes. [ABSTRACT FROM AUTHOR]

The peptidyl prolyl isomerase Pin1 has two domains that are considered to be its binding ( WW) and catalytic ( PPIase) domains, both of which interact with phosphorylated Ser/Thr-Pro motifs. This shared specificity might influence substrate selection, as many known Pin1 substrates have multiple sequentially close phosphoSer/Thr-Pro motifs, including the protein interleukin-1 receptor-associated kinase-1 ( IRAK1). The IRAK1 undefined domain ( UD) contains two sets of such neighboring motifs (Ser131/Ser144 and Ser163/Ser173), suggesting possible bivalent interactions with Pin1. Using a series of NMR titrations with 15N-labeled full-length Pin1 (Pin1- FL), PPIase, or WW domain and phosphopeptides representing the Ser131/Ser144 and Ser163/Ser173 regions of IRAK1- UD, bivalent interactions were investigated. Binding studies using singly phosphorylated peptides showed that individual motifs displayed weak affinities (> 100 μ m) for Pin1- FL and each isolated domain. Analysis of dually phosphorylated peptides binding to Pin1- FL showed that inclusion of bivalent states was necessary to fit the data. The resulting complex model and fitted parameters were applied to predict the impact of bivalent states at low micromolar concentrations, demonstrating significant affinity enhancement for both dually phosphorylated peptides (3.5 and 24 μ m for peptides based on the Ser131/Ser144 and Ser163/Ser173 regions, respectively). The complementary technique biolayer interferometry confirmed the predicted affinity enhancement for a representative set of singly and dually phosphorylated Ser131/Ser144 peptides at low micromolar concentrations, validating model predictions. These studies provide novel insights regarding the complexity of interactions between Pin1 and activated IRAK1, and more broadly suggest that phosphorylation of neighboring Ser/Thr-Pro motifs in proteins might provide competitive advantage at cellular concentrations for engaging with Pin1. [ABSTRACT FROM AUTHOR]