NMR Titration Experiments Research Articles

A Versatile Schiff Base Chemosensor for the Determination of Trace Co2+, Ni2+, Cu2+, and Zn2+ in the Water and Its Bioimaging Applications.

In this work, a simple and versatile Schiff base chemosensor (L) was developed for the detection of four adjacent row 4 metal ions (Co2+, Ni2+, Cu2+, and Zn2+) through colorimetric or fluorescent analyses. L could recognize the target ions in solutions containing a wide range of other cations and anions. The recognition mechanisms were verified with a Job’s plot, HR-MS assays, and 1H NMR titration experiments. Then, L was employed to develop colorimetric test strips and TLC plates for Co2+. Meanwhile, L was capable of quantitatively measuring the amount of target ions in tap water and river water samples. Notably, L was used for imaging Zn2+ in HepG2 cells, zebrafish, and tumor-bearing mice, which demonstrated its potential biological applications. Therefore, L can probably serve as a versatile tool for the detection of the target metal ions in environmental and biological applications.

Halide-free pyridinium saccharinate binary organocatalyst for the cycloaddition of CO2 into epoxides

Cycloaddition of CO2 into epoxides (CCE) reaction was the few chemical processes viable commercially in valorizations of carbon dioxide. The produced cyclic carbonate was valuable in electrolyte of lithium batteries and so on, however, halide anion was monopoly as cocatalyst in catalytic CCE reactions. To avoid the harmful halide in corrosion of process equipment, the detrimental halide in electrolytes, and the waste halide as environmental burden, halide-free catalysis for CCE was highly desirable. In design of halide-free catalytic platform, we propose binary adducts of food sweetener saccharin and strong pyridine base in ionic pair pyridinium saccharinate exemplified by PPy·Sac (3). CCE reaction of epichlorohydrin at mild conditions of 40 °C, 0.1 MPa, by 10 mol% loading of catalyst 3 in 24 h were evaluated. Terminal epoxides including glycidyl ethers, alky epoxides, and styrene oxide were transformed into their corresponding cyclic carbonates by excellent yields (80 to 90% up). Internal epoxides of hexene and stilbene were not viable under these mild conditions. The key role of saccharinate anion in cocatalysis in both the nucleophilic attack on epoxide in initiating the ring-opening, and as good leaving group in ring-closure was validated. 1H NMR titration experiment of PPy·Sac on epoxide verified the activation of the substrate by H-bonding, the capture of intermediates in mass spectroscopy certified the ring-opening by Sac, and the control experiment by switching the cation and anion of PPy·Sac supported the indispensable of the cation and anion in the cocatalysis. In view of the wide application of halide anions in nucleophilic catalysis and substitutional reactions, diversity design of anions of appropriate nucleophilicity and nucleofugality would be useful in practical catalysis.

Structural Insights into Molecular Recognition by Human Chemokine CCL19.

The human chemokines CCL19 and CCL21 bind to the G protein-coupled receptor (GPCR) CCR7 and play an important role in the trafficking of immune cells as well as cancer metastasis. Conserved binding sites for sulfotyrosine residues on the receptor contribute significantly to the chemokine/GPCR interaction and have been shown to provide promising targets for new drug-discovery efforts to disrupt the chemokine/GPCR interaction and, consequently, tumor metastasis. Here, we report the first X-ray crystal structure of a truncated CCL19 (residues 7-70) at 2.50 Å resolution, revealing molecular details crucial for protein-protein interactions. Although the overall structure is similar to the previously determined NMR model, there are important variations, particularly near the N terminus and the so-called 30's and 40's loops. Computational analysis using the FTMap server indicates the potential importance of these areas in ligand binding and the differences in binding hotspots compared to CCL21. NMR titration experiments using a CCR7-derived peptide (residues 5-11, TDDYIGD) further demonstrate potential receptor recognition sites, such as those near the C terminus and 40's loop, which consist of both positively charged and hydrophobic residues that may be important for receptor binding. Taken together, the X-ray, NMR, and computational analysis herein provide insights into the overall structure and molecular features of CCL19 and enables investigation into this chemokine's function and inhibitor development.

Solvent Controlled Colorimetric and Fluorometric Detection of Fe2+ and Cu2+ Ions by Naphthaldimine-Glucofuranose Conjugate.

The sensing properties of naphthaldimine-glucofuranose conjugates 1 and 2 towards metal ions were investigated by 1H NMR titration, Fourier-transform infrared spectroscopy (FTIR), absorbance, and fluorescence spectroscopic methods. The absorbance and fluorescence studies indicated that compound 1 formed coordination with Fe2+ and Cu2+ ions in dimethyl sulfoxide (DMSO) through color changes yellow to brown and colorless, respectively. The Job's plots using absorbance data showed metal-ligand binding ratio is 1:1 for both cases. The formation of 1-Fe2+ and 1-Cu2+ complexes have been analyzed by absorption and emission spectroscopy, high-resolution mass spectrometry (HRMS) data, FTIR, 1H NMR titration experiment, and density functional theory (DFT) calculations. The detection limits of naphthaldimine sugar conjugate 1 towards Fe2+/Cu2+ were calculated from UV-vis and fluorescence data according to the standard method. The sugar-naphthaldimine conjugate 2 has been used to establish the binding mode of 1 with Fe2+ or Cu2+ ions in DMSO.

Anion Recognition by a Pincer-Type Host Constructed from Two Polyamide Macrocyclic Frameworks Jointed by a Photo-Addressable Azobenzene Switch.

A sterically crowded light-responsive host 1 was synthetized with a 93% yield by applying a post-functionalization protocol utilizing the double amidation of 4,4′-azodibenzoyl dichloride with a readily available 26-membered macrocyclic amine. X-ray structures of two hydrates of trans-1 demonstrate a very different alignment of the azobenzene linkage, which is involved in T-shape or parallel-displaced π⋯π stacking interactions with the pyridine-2,6-dicarboxamide moieties from the macrocyclic backbone. Despite the rigidity of the macrocyclic framework, which generates a large steric hindrance around the azobenzene chromophore, the host 1 retains the ability to undergo a reversible cis⟷trans isomerization upon irradiation with UVA (368 nm) and blue (410 nm) light. Moreover, thermal cis→trans back-isomerization (ΔG0 = 106.5 kJ∙mol−1, t½ = 141 h) is markedly slowed down as compared to the non-macrocyclic analog. 1H NMR titration experiments in DMSO-d6/0.5% water solution reveal that trans-1 exhibits a strong preference for dihydrogenphosphate (H2PO4−) over other anions (Cl−, MeCO2−, and PhCO2−), whereas the photogenerated metastable cis-1 shows lower affinity for the H2PO4− anion.

A near-infrared fluorescent probe targeting mitochondria for real-time visualization of SO2/formaldehyde in living cells, zebrafish

Sulfur dioxide (SO2) is a gas signal molecule, and SO2 and formaldehyde (HCHO) jointly maintain the internal homeostasis of organisms in the complex signal transduction process. Many fluorescent probes have been designed to detect SO2. However, the response of most probes to SO2 was irreversible, and they are not suitable for studying the dynamic interaction between SO2 and HCHO. In this text, we designed a reversible near-infrared fluorescent probe NIR-BN-Acrylate. Benzopyrylium was used as a fluorophore because of its specific site for SO2 reaction (the double bond of the benzopyrylium unit). The detector exhibited near-infrared emission at 665 nm. In addition, NIR-BN-Acrylate had been successfully applied to target mitochondria to detect SO2 in HepG-2 cells and zebrafish. We also monitored the dynamic changes of SO2 and HCHO over time by the fluorescence intensity of NIR-BN-Acrylate. Unexpectedly, through a series of spectrometric titration experiments and NMR titration experiments, we found that the double bond site on the benzopyrylium group was highly reactive and particularly sensitive to SO2, while the other reactive sites had relatively low reactivity and hardly reacted with any substance.

Aromatic stacking and the self-assembly of perylene monoimide diester homodimers

The self-assembly properties of two novel perylene monoimide diester homodimers have been investigated by concentration-dependent UV–Vis and 1H NMR titration experiments and steady-state fluorescence and SEM techniques. It was found that, as a result of different positioning of the perylene monoimide diester subunits in these structures, the cooperativity and binding-models for their chain growth processes differ significantly in dichloromethane (DCM) and dimethyl sulfoxide (DMSO) due to a change in efficiency of the π- π stacking. The mechanism of aggregation in each case was determined by the application of Goldstein–Stryer nucleation − elongation model to the concentration-dependent data. Because of different aggregation propensities of the respective monomers in DCM, scanning electron microscopy revealed different morphologies for the assemblies.

Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of N-alkylbenzamides.

A mechanistic study on the α-arylation of N-alkylbenzamides catalyzed by a dual nickel/photoredox system using aryl bromides is reported herein. This study elucidates the origins of site-selectivity of the transformation, which is controlled by the generation of a hydrogen atom transfer (HAT) agent by a photocatalyst and bromide ions in solution. Tetrabutylammonium bromide was identified as a crucial additive and source of a potent HAT agent, which led to increases in yields and a lowering of the stoichiometries of the aryl bromide coupling partner. NMR titration experiments and Stern–Volmer quenching studies provide evidence for complexation to and oxidation of bromide by the photocatalyst, while elementary steps involving deprotonation of the N-alkylbenzamide or 1,5-HAT were ruled out through mechanistic probes and kinetic isotope effect analysis. This study serves as a valuable tool to better understand the α-arylation of N-alkylbenzamides, and has broader implications in halide-mediated C–H functionalization reactions.

Squaramide-naphthalimide conjugates – Exploiting self-aggregation effects in acetate recognition

The synthesis of three squaramide-containing bis-naphthalimide conjugates (1–3) are reported where the structures differ by the length of the carbon chain between the squaramide core and the 1,8-naphthalimide fluorophores. All compounds displayed weak fluorescence properties and self-aggregation as studied by UV/Vis, 1H NMR spectroscopy and Scanning Electron Microscopy (SEM), however it was shown that aggregation can be disrupted by increased temperature. Anion binding experiments displayed colourimetric and spectroscopic modulations in response to a variety of anions where more basic anions resulted in receptor deprotonation. However, selectivity was observed in the case of H-bonding to OAc- with binding measured by 1H NMR titration experiments. No fluorometric changes were observed for any of the anions tested and we propose that the squaramide is capable of disrupting eximer formation resulting in a reduction of emission from these systems.

Host-guest chemistry of a bidentate silyl-triflate bis-Lewis acid – complex complexation behaviour unravelled by diffusion NMR spectroscopy

Solution and solid state are markedly different for the adducts of different bipyridines to bidentate silyl-triflate bis-Lewis acids; the solution was studied by diffusion NMR titration experiments and reveals complex aggregates.

Anion Recognition through Multivalent C-H Hydrogen Bonds: Anion-Induced Foldamer Formation and Transport across Phospholipid Membranes.

A series of triazole-cyanostilbene receptors were designed and synthesized. The receptor binds with the anions through various CH···anion hydrogen bonding interactions, where strong binding was observed for SO42- anions followed by Cl-, Br-, NO3-, and I-, calculated from the 1H NMR titration experiment. The NOESY NMR experiment of the receptor confirmed the formation of anion-induced folded conformation. The CH···anion hydrogen bonding interaction-mediated anion recognition and foldamer formation were further confirmed from geometry optimization studies of the anion-bound complex. The receptor transports Cl- anions efficiently compared to SO42- anions across the lipid bilayer membrane via a mobile carrier mechanism.

Antibacterial potentials of pillar[5]arene, pillar[4]arene[1]quinone derivative and their isatin inclusion complexes

ABSTRACT Host–guest complexation of decamethoxypillar[5]arene and difunctionalized pillar[4]arene[1]quinone with isatin were demonstrated by 1H NMR titration experiments. The antibacterial potentials of isatin, decamethoxypillar[5]arene, difunctionalized pillar[4]arene[1]quinone and their isatin inclusion complexes were evaluated against both Gram-positive and Gram-negative bacteria by the well-diffusion method. The results of the antibacterial assay revealed that decamethoxypillar[5]arene displayed very good antibacterial activity than the difunctionalized pillar[4]arene[1]quinone. Isatin inclusion complex of decamethoxypillar[5]arene showed very good antibacterial activity as that of chloramphenicol with S. aureus, P. aeruginosa, K. pneumoniae and E. coli. Checkerboard assay revealed synergic effects of P[5]A and isatin combinations against selected microorganisms. In silico toxicity predictions suggested the potential of isatin, decamethoxypillar[5]arene and the difunctionalized pillar[4]arene[1]quinone as prospective drug candidates.

The synthesis of a new aromatic polycarboxylic acid and its property as fluorescence-colorimetric chemosensor

In this paper, a new “turn-on” aromatic polycarboxylic fluorescent probe L was designed and synthesized based on 4,4′-diaminobiphenyl-2,2′-dicarboxylic acid and salicylaldehyde. The probe L could not only be used as a fluorescent probe to detect Al3+ ions in various solvents, but also be used to detect Fe3+ ions by naked eyes. The detection limits were 5.34 × 10−8 and 1.38 × 10−6 M, respectively. Job′s plot, 1H NMR titration experiments and ESI mass spectrometry proved that the coordination ratio of L and Al3+ ions was 1:1, and Al3+ ions were coordinated with hydroxyl oxygen atoms on the carboxyl groups of probe L. The mechanism could be deduced as chelation enhanced fluorescence.

Strong Bidentate Coordination for Surface Passivation and Ligand-Shell Engineering of Lead Halide Perovskite Nanocrystals in the Strongly Quantum-Confined Regime

The surface of lead halide perovskite nanocrystals (PNCs) is unique compared to conventional metal chalcogenide or pnictogenide semiconductor nanoparticles for its ionic character and the dynamic ligand layer, which makes them unstable in stock solutions and hinders the development of surface engineering strategies. This work employs a chelating strategy to form stable coordination on the PNC surface. Through screening a series of heterocyclic aromatic carboxylates, we found the best ligand, picolinate (PIC), with exceptional passivation effect to the surface traps of CsPbBr3 PNCs in the strongly quantum confined regime, resulting in > 0.8 photoluminescence quantum yields. The exciton lifetime in the passivated PNC approaches the radiative decay limit in various solvents. From an NMR titration experiment, the binding affinity of PIC is estimated to be at least 15 to 30 folds stronger than the original ligand from synthesis. The NMR and FTIR spectroscopic data and first-principles calculations elucidate the bidentate nature of the PIC coordination at the surface Pb site and the coadsorption of the ammonium-PIC ion pair. In apolar solvents, such as cyclohexane, the binding of PIC is stoichiometric to the available surface sites, suggesting the structure as a potent candidate for anchoring functional molecular structures to the PNC surface. In polar solvents, the strong affinity of PIC on the PNC surface provides protection for carrying out the precipitation-redissolution purification procedure that removes synthetic residual from the as-synthetic PNC samples. By modifying the purification procedure, we also develop a cation exchange procedure to replace the original oleylammonium cation with desired structures that consist of an ammonium anchoring group. Our results provide a direction for constructing strong interactions to protect the vulnerable surface of PNCs and pave the road for developing surface engineering strategies to functionalize these nanoparticles.

Fluorescent naphthalimide-based supramolecular gel system for detection phosgene, sulfoxide chloride and oxalyl dichloride

A novel naphthalimide-based gelator ( 1 ) was designed and synthesized, which could form fluorescent gels in six kinds of solvents for all the solvents we tested. The self-assembly process of molecule 1 in six solvents was studied by different technologies. Under the main driving force of hydrogen bonding and π-π stacking, different self-assembly structures were obtained in the self-assembly process, which were all hydrophobic with the contact angles of 103°-140°. Interestingly, compound 1 exhibited sensitive response ability towards high active acyl chlorides due to its weak nucleophilicity of amino at 4-position in naphthalimide. Phosgene, sulfoxide chloride and oxalyl dichloride could be detected via compound 1 in solution, gel and xerogel states, and expressed the change of fluorescence, color and gel state. Especially for three kinds of acyl chlorides gases, xerogel 1 could detect phosgene, sulfoxide chloride and oxalyl dichloride with their corresponding low limits of detection of 23 ppb, 0.25 ppm and 0.19 ppm, respectively. 1 H NMR titration and HRMS experiments well explained the detection mechanism, which was that the reaction between acyl chloride and 4-amino group of molecule 1 weakened or prohibited the original ICT process, and further brought its fluorescent change and affected the noncovalent interaction. This research will bring a new way for construction multi-functional self-assembly system for detection of acyl chlorides.

Gold Nanocluster Functionalized with Peptide Dendron Thiolates: Acceleration of the Photocatalytic Oxidation of an Amino Alcohol in a Supramolecular Reaction Field

Herein, we report the synthesis of gold nanoclusters (AuNCs) functionalized by peptide dendron thiolate ligands forming a hydrogen bonding supramolecular reaction field. The prepared AuNCs act as efficient photocatalysts that promote the oxidative cyclization of an amino alcohol to afford the oxazolidine product. Circular dichroism (CD) spectroscopy and 1H NMR titration experiments revealed that the dynamic transformation of interdendron hydrogen bonds into intermolecular hydrogen bonds between the ligand and the substrate is the key to accelerating the photocatalytic reaction. This work introduces a concept for tuning the reactivities and selectivities of metal nanocluster catalysts that use supramolecular reaction fields created with dendritic thiolate ligands.

1H NMR spectroscopic characterization of inclusion complex of desferrioxamine B chelator and β-cyclodextrin

In this work the complexation between desferioxamine B (DFOB), and β-Cyclodextrin (β-CD) in solution was investigated using 1H NMR spectroscopy. Inclusion compound formation was confirmed by the upfield shifts of H3 and H5 protons, located inside the cavity of β-CD, and downfield shifts of some of the methylene protons of DFOB, observed during NMR titration experiments. Using the continuous variation method, we determined a 1:1 stoichiometry and the association constant was calculated using a nonlinear least-square regression analysis implemented in CONSTEQ, a software developed in our group. A theoretical molecular docking study was additionally performed to ascertain possible conformations of the inclusion complex.

Naphthalimide appended isoquinoline fluorescent probe for specific detection of Al3+ ions and its application in living cell imaging

Herein, a novel Schiff base fluorescent probe NIQ based on naphthalimide and iso-quinoline units has been readily prepared for the selective detection of Al3+ ions. The obviously visible color changes and prominent fluorescence enhancement were observed upon the addition of Al3+ to NIQ, which could be attributed to the complexation of NIQ with Al3+ and thus leading to the inhibition of photo-induced electron transfer (PET) and the chelation-enhanced fluorescence (CHEF) progress. The limit of detection (LOD) was 52 nM that was far below the standard recommended by the WHO. Binding ratio (1:1) of NIQ with Al3+ ions was supported by Job’s plot. The binding constant of NIQ for Al3+ were calculated to be 3.27 × 105 M−1 on the basis of benesi-Hildebrand plot. The plausible binding mechanism for NIQ towards Al3+ ions was evidenced by the density functional theory (DFT) and 1H NMR titration experiment. Furthermore, this “turn-on” probe NIQ has been successfully applied as a biomarker for imaging the Al3+ ions in living cells.

A novel Hamilton receptor monomer for the stoichiometric molecular imprinting of barbiturates

New molecularly imprinted polymers (MIPs) for the recognition of barbiturates were synthesised by “bulk” polymerisation. These polymers were prepared using pentobarbital as the template in combination with a novel Hamilton receptor functional monomer. The solution binding properties of the monomer were assessed by NMR titration experiments, showing high affinity for barbiturates and lower affinity for related compounds lacking the ability to form as many hydrogen bonds. The properties of the MIP were assessed via equilibrium rebinding experiments and in the chromatographic mode, and compared to the behaviour of a control non-imprinted polymer (NIP). The MIP showed a far higher population of binding sites with higher affinity than the NIP which was reflected in the chromatographic evaluation, where the template and a related barbiturate were not eluted from the MIP within 60 min, while their retention was weak on the NIP, leading to extremely high imprinting factors. Other analytes were weakly retained by MIP and NIP, with those presented an acceptor-donor-acceptor array of hydrogen bonding sites most retained. Preliminary molecular modelling studies support the hypothesis that the presence of the template in the MIP synthesis “chooses” the conformation of the functional monomer that is “locked in” during the polymerisation.

Synthesis, crystal structure, CN– ion recognition property and computational studies of a novel hydrazinyl-dihydroimidazole Schiff base

A novel hydrazinyl-dihydroimidazole receptor, (E)-2-(2-(thiophen-2-ylmethylene)hydrazinyl)-4,5-dihydro-1H-imidazol-3-ium bromide (L) has been presented as a colorimetric chemosensor for rapid and selective and sensitive detection of CN– ions in aqueous medium. L has been characterized by FTIR, UV–Vis, 1H NMR, 13C NMR, EI-MS spectrometry, elemental analyses and single crystal X-ray diffraction studies. Interaction of L with CN– ion provides remarkable color change from colorless to yellow along with change in the absorption maxima, enabling naked-eye sensing without the use of any expensive instrument. 1:1 binding stoichiometry of chemosensor L towards cyanide ion has been confirmed by Job’s plot analysis. The limit of detection the chemosensor L has been found 0.89 µM, which is lower than the maximum permissible level of CN– in drinking water set by WHO. The other competitive anions (OAc-, F-, Cl-, Br-, I-, H2PO4-, NO2-, NO3-, SO42-, HSO4- and N3-) showed negligible interference for detection of cyanide ion. The sensing mechanism has been accounted by deprotonation from the exocyclic –NH site of the receptor L, which was confirmed by an 1H NMR titration experiment and DFT studies. L can be successfully applied in colorimetric test kit experiment and for the determination of CN− ions in real samples.