NMR Titration Research Articles

Pyrene-acylhydrazone-based Turn-on Fluorescent Probe for Highly Sensitive Detection Cu2+ and Application in Bioimaging.

The development of highly selective and sensitive, low detection limits, and biocompatible turn-on copper ion fluorescent probes is of great significance for the environment and life sciences. In this study, a novel turn-on fluorescent probe T based on pyrene-acylhydrazone was synthesized via an efficient one-step condensation reaction and characterized by 1H NMR, 13C NMR and HRMS. The probe T exhibited high selectivity with a low detection limit of 0.304 nM towards Cu2+ in DMSO/H2O (v/v = 1 : 1) medium by a PET-TICT dual interplaying sensing mechanisms. Job's plot analysis and HRMS data confirmed the 1 : 1 binding stoichiometry between T and Cu2+ with an association constant of 5.7×103 M-1. Additionally, the binding model was investigated by 1H NMR titration and FT-IR spectra. Furthermore, probe T exhibits low cellular toxicity and excellent membrane permeability, and has been successfully applied for fluorescent imaging of copper ions in live HT-22 cells.

An AIE active imidazole conjugated α-cyanostilbene based sensor for the selective and sensitive detection of picric acid in an aqueous medium

Due to increasing pollution threats, terrorism-sensitive rapid sensing of aromatic nitro explosives (picric acid) has gained predominant significance in environmental safety. Herein, imidazole-derived monofunctional fluorescent sensor 2-(4-aminophenyl)-3-(3-(4,5-diphenyl-1H-imidazol-2-yl)-2-hydroxyphenyl) acrylonitrile (ADHA) was successfully developed for the selective recognition of explosive picric acid. The D-π-A configuration of ADHA facilitates extraordinary photophysical properties with remarkable aggregation-induced emission (AIE). The detection process is induced by the photon-induced electron transfer (PET) and resonance energy transfer (RET) and results in the generation of ADHA+PA complex. The structural relationship and the photophysical properties of ADHA were extensively studied by DFT (Density Functional Theory) methods and spectroscopic analysis. It has been calculated that the detection limit of the formed complex is 6.26 nM. In addition, 1H NMR titrations DFT calculations, and HRMS analysis were performed to understand the detection mechanism better. Test strip-aided detection and invisible ink applications confirmed that ADHA is a versatile sensor for sensitively detecting picric acid without sophisticated instruments. In addition, ADHA was implemented to detect PA in real water samples with remarkable recovery.

Al3+ selective ratiometric fluorescent and colorimetric chemoprobe and its practical applications in foods, test kits and Smartphone

We herein developed an effective colorimetric and ratiometric fluorescent chemoprobe MPIM and successfully revealed its efficiency for naked eye recognition of Al3+ in MeOH/HEPES (6/4, v/v, pH = 7.4). Upon exposure of MPIM to diverse amounts of Al3+, the detection limit values for Al3+ were found as 12.6 µM and 1.82 μM, respectively. The MPIM was practically efficient and excellently selective for Al3+ in the existence of potentially competitive ions. The MPIM could be regenerated from MPIM–Al3+ complex with an appropriate agent of F–. The binding phenomenon of MPIM–Al3+ (2:1) was authenticated using Job's plot, FT–IR, 1H NMR titration and MALDI TOF–MS, and it was supported by DFT. Furthermore, the practical utilities of our prototype chemoprobe were clarified for Al3+ in diverse products, Smartphone and test kits applications without the aid of any sophisticated tool.

Thiophene derived sky-blue fluorescent probe for the selective recognition of mercuric ion through CHEQ mechanism and application in real time samples

A vibrant blue organic luminescent material with enhanced photophysical properties is in great demand for the generation of optoelectronic devices and luminescent sensors. In this context, the thiophene-benzimidazole probe TH-IMI was designed and synthesized by a simple condensation reaction. The synthesized probe has shown excellent photophysical properties like high FL intensity, a high quantum yield of 90% in the solution phase, a low optical bandgap of 2.84 eV, positive solvatochromic effect in emission spectra and Disaggregation Caused Quenching Effect (DCQE). Such a high luminescent probe was employed for the recognition of mercuric ions in the solution phase, solid state detection, and in tracking mercury in green gram sprouts. UV–visible absorption and emission spectra, 1H NMR titration, IR spectroscopic and ESI-MS techniques confirmed that the probe underwent a fluorescence quenching response via the CHEQ effect upon exposure to Hg2+. The stoichiometry was found to be 1:1 through Job’s plot and has a fast response rate and relatively low limit of detection of about 6.13 × 10-11 M in a linear range between 0 and 110 µL.

Hydroxyl-group functionalized phenanthroline diimides as efficient masking agents for Am(III)/Eu(III) separation under harsh conditions

The separation of Lns(III) from radioactive Ans(III) in high-level liquid waste remains a formidable hydrometallurgical challenge. Water-soluble ligands are believed to be new frontiers in the search of efficient Lns/Ans separation ligands to close the nuclear fuel cycles and dealing with current existing nuclear waste. Currently, the development of hydrophilic ligands far lags behind their lipophilic counterparts due to their complicated synthetic procedures, inferior extraction performances, and acid tolerances. In this paper, we have showed a series of hydroxyl-group functionalized phenanthroline diimides were efficient masking agents for Am(III)/Eu(III) separation under high acidity (˃ 1 M HNO3). Record high SFEu(III)/Am(III) of 162 and 264 were observed for Phen-2DIC2OH and Phen-2DIC4OH in 1.25 M HNO3 which represents the best Eu(III)/Am(III) separation performance at this acidity. UV–vis absorption, NMR and TRLFS titrations were conducted to elucidate the predominant of 1:1 ligand/metal species under extraction conditions. X-ray data of both the ligand and Eu(III) complex together with DFT calculations revealed the superior extraction performances and selectivities. The current reported hydrophilic ligands were easy to prepare and readily to scale-up, acid tolerant and highly efficient, together with their CHON-compatible nature make them promising candidates in the development of advanced separation processes.

Formation of an Unusual Pseudo-Square Planar-Induced Mercury(II) Dimeric Complex

Due to the different crystallization methods, two Hg(II) complexes of a 19-membered NO2S2-macrocycle (L) and its oxidized ligand (HLox), exhibiting different stoichiometries, were prepared. First, mercury(II) iodide reacts with L to afford a dinuclear metallacycle complex [Hg2(L)2I4] (1) in which the mercury(II) exists outside the macrocyclic cavity. Meanwhile, the slow diffusion reaction gave an unusual pseudo-square planar-induced mercury(II) complex, which shows three separated parts with the formula [Hg2(HLox)I5]2[HgI2] (2). There are two complex cation units that are exo-coordinated, along with one unit consisting of a metal cluster anion. Surprisingly, L was oxidized in the disulfoxidized form (HLox) in this condition. NMR titration was used to monitor both the structural and binding characteristics of the complex formed between L and mercury(II) iodide in a solution.

A coumarin based ratiometric fluorescent probe for the detection of Cu2+ and mechanochromism as well as application in living cells and vegetables

In this paper, a novel coumarin-derived fluorescent probe NY was designed and synthesized. NY displayed a significant ratiometric fluorescence response towards Cu2+ in PBS buffer (10 mM, pH = 7.4), with the emission wavelength blue-shifted from 580 to 495 nm, and a fluorescence change from orange to green was evident under a 365 nm UV light. Meanwhile, NY had the advantages of high selectivity, short response time (5 min), low detection limit (1.3 × 10-8 M) and large binding constant (1.45 × 105 M-1) towards Cu2+. The binding mechanism between NY and Cu2+ was elucidated by FT-IR, 1H NMR titration, TOF-MS and Job's plot analysis. In addition, NY was successfully employed in the detection of Cu2+ within environmental water and vegetable samples with satisfactory results. Laser confocal microscopy imaging results showed that NY could easily penetrate HeLa cells membrane to target mitochondria and image Cu2+ in living cells. Furthermore, NY demonstrated mechanochromic properties by exhibiting orange-red fluorescence when subjected to mechanical grinding.

Phenothiazine-derived fluorescent chemosensor: A versatile platform enabling swift cyanide ion detection and its multifaceted utility in paper strips, environmental water, food samples and living cells

A phenothiazine-linked pyridine acetonitrile with a cyanoethylene bond PZ-PY has been synthesized by Knoevenagel condensation reaction and characterized by spectroscopic and analytical techniques. The structure of PZ-PY was confirmed through single-crystal X-ray diffraction studies; revealing its monoclinic crystal system with a P21/c space group. The absorption maximum and emission spectrum of the PZ-PY receptor were observed at 431 and 608 nm respectively. Cyanide anion is one of the most prevalent chemicals in the environment, its toxic nature poses a constant threat to human daily life. The PZ-PY receptor’s recognition of cyanide ions is associated with remarkable photophysical properties. The binding stoichiometry of PZ-PY-CN- was confirmed by Job’s plot, B-H studies, 1H NMR titration, TD-DFT, and ESI-mass spectroscopy. The relatively low limit of detection was determined to be 8.79 × 10 -8 M in a linear range between 0 and 120 µL. PZ-PY receptor exhibits an aggregation-caused quenching (ACQ) nature with the increase in water fraction; it is stable between pH 2 to 11. Moreover, the practical applicability of PZ-PY was investigated through the test strip, solid-state, bioimaging (A547 cell line), detection of cyanide in diverse water samples (tap water, distilled water, and lake water), and food samples (sprouted potatoes, bitter almonds, and cassava).

Mutual induced‐fit controlled signal amplification of hydrogen‐bonded capsule formation

AbstractMutual induced‐fit is well known process in biological system and playing crucial role in enzymatic catalysis, peptide‐bond synthesis, protein synthesis, etc…, proceeds by mutual interactions of two or more than two components. However, in an artificial system, to mimic such process is challenging, especially by purely organic components. In this report, we have shown importance of mutual induced‐fit in signal amplification of hydrogen‐bonded capsule formation. Two different types of highly flexible ligands (one N‐bridged and another triazine‐bridged) are used. N‐bridged tripodal ligand acting as clip over the adduct obtained from triazine‐bridged ligand, bringing the resultant adduct in the cone‐shape conformation. The resulting cone‐shape conformation undergo solvent polarity dependent hydrogen‐bonded capsule formation as a sole product. In absence of N‐bridged tripodal ligand, only 50% capsule formation is observed through 1H NMR at 100 mM concentration. However, in the presence of N‐bridged tripodal ligand, organic components undergo mutual interactions to opt the cone‐shape conformation and 100% capsule is formed (independent of concentration). The complete process is characterized by IR‐spectra, 1H and 13C NMR spectra, concentration dependent 1H NMR titration spectra, 1H‐1H COSY, 1H‐1H NOESY, DOSY NMR, high resolution ESI mass spectra, and also by energy‐minimized structure.

Biomass-Derived Core-Shell Carbon Dots with Embedded Tripodal Receptors for the Selective Recognition of Mefenamic Acid in Pharmaceutical Formulations and Urine.

A tripodal amine (TPA) with -OH, N, and S donors is synthesized to functionalize a core-shell carbon dot composite (FCDs@SiO2-TPA) for sensing application. The TPA is characterized by spectroscopic and spectrometric techniques, and the composite is characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectra (EDS) techniques. The composite has the ability to recognize mefenamic acid (MFA) selectively even in the presence of other drugs like ibuprofen sodium, acetylsalicylic acid, naproxen sodium, diclofenac sodium, and ketoprofen. It can also be used for the quantification of MFA by recording the emission quenching response of the sample at λexc. = 350 nm and λems. = 460 nm (linear range = 1-8 μM and LOD = 197 nM). The density functional theory calculations and 1H NMR titration suggest quenching of the emission signal due to photoinduced electron transfer via hydrogen bonding between the probe and MFA. The composite FCDs@SiO2-TPA has been demonstrated as a reliable and cost-effective sensing probe for the detection of MFA in pharmaceutical formulations, water samples, and cow urine samples.

The studies on a fluorescent probe of Schiff base modified by 1,2,3-triazole to detecting Al3+ and living cell imaging

A new compound, 5-methyl-2-phenyl-1,2,3-triazole-5-hydrazid (PT) was designed and synthesized based on “click chemistry”. The fluorescence probe 5-methyl-2-phenyl-1,2,3-triazole-5-hydrazid Schiff base (PTSB) was further constructed by a chemical reaction between PT and 4-(diethylamino) salicylaldehyde. PTSB could be used to determine Al3+ in EtOH with high sensitivity and strong anti-interference performance by fluorescence and UV–vis spectroscopic methods. The limit of detection to Al3+ is 5.84 nM and it showed an obvious solvatochromic effect under ultraviolet light. Furthermore, the sensing mechanism of PTSB detecting Al3+ was confirmed in the form of planar structure and 1:1 complexation ratio based on MS, Job's plot, 1H NMR titration, DFT calculation, and the single-crystal structure of PTSB, respectively. PTSB showed less low cytotoxicity to HeLa cells and was successfully used for chromatic bioimaging Al3+ in HeLa cells. It is expected to be developed and utilized as a fluorescence probe for detecting Al3+ in vivo.

Imidazole derived PET based reversible dual fluorescent chemosensor: Sensing of zinc and carbonate ions and their usage on real samples and live cells

Three imidazole based chemosensors, HNBI, 1-NBI, and 2-NBI, were designed, synthesized and confirmed using 1H, 13C, and mass spectroscopy methods. All three receptors were tested in the presence of different cations and anions in DMSOH2O (1:1 v/v, HEPES = 50 mM, pH-7.4) solution, while HNBI, which benefits from the -OH moiety, shown fluorescence increase for Zn2+ and CO32− ions. Through the use of a jobs plot and Benesi-Hildebrand experiments, a 1:1 binding stoichiometry was discovered. The simultaneous LOD and LOQ for the detection of Zn2+ and CO32− were determined to be 1.07 × 10−9 M, 3.57 × 10−9 M, and 9.72 × 10−8 M, 3.24 × 10−9 M, respectively. By using 1H NMR titration, the binding ratio between the host and guest were further verified. Restriction of CC free rotation and blocking of the Photoinduced Electron Transfer (PET) are the two effects that follow receptor HNBI's interaction with Zn2+/CO32− ions. Additionally, HNBI was successfully examined for the detection of Zn2+/CO32− ions in water, food, soil and bacterial cell lines.

Interactions of the N- and C-Terminal SH3 Domains of Drosophila Drk with the Proline-Rich Peptides from Sos and Dos.

Drk, a homologue of human GRB2 in Drosophila, receives signals from outside the cells through the interaction of its SH2 domain with the phospho-tyrosine residues in the intracellular regions of receptor tyrosine kinases (RTKs) such as Sevenless, and transduces the signals downstream through the association of its N- and C-terminal SH3 domains (Drk-NSH3 and Drk-CSH3, respectively) with proline-rich motifs (PRMs) in Son of Sevenless (Sos) or Daughter of Sevenless (Dos). Isolated Drk-NSH3 exhibits a conformational equilibrium between the folded and unfolded states, while Drk-CSH3 adopts only a folded confirmation. Drk interacts with PRMs of the PxxPxR motif in Sos and the PxxxRxxKP motif in Dos. Our previous study has shown that Drk-CSH3 can bind to Sos, but the interaction between Drk-NSH3 and Dos has not been investigated. To assess the affinities of both SH3 domains towards Sos and Dos, we conducted NMR titration experiments using peptides derived from Sos and Dos. Sos-S1 binds to Drk-NSH3 with the highest affinity, strongly suggesting that the Drk-Sos multivalent interaction is initiated by the binding of Sos-S1 and NSH3. Our results also revealed that the two Sos-derived PRMs clearly favour NSH3 for binding, whereas the two Dos-derived PRMs show almost similar affinity for NSH3 and CSH3. We have also performed docking simulations based on the chemical shift perturbations caused by the addition of Sos- and Dos-derived peptides. Finally, we discussed the various modes in the interactions of Drk with Sos/Dos.

A novel Salamo-Salen-Salamo hybrid Mg(II) complex fluorescent chemosensor for highly effective monitoring H2PO4ˉ in Zebrafish and plants

A novel Salamo-Salen-Salamo hybrid Mg(II) complex (sensor MT) was well-designed and synthesized for selective sensing of H2PO4ˉ ions through ICT and CHEF effects and via displacement pathways in DMSO/H2O (9:1, v/v) medium. The sensor MT exhibited a bright blue fluorescence signal (470 nm) that is quenched upon encountering H2PO4ˉ ions in a short time. The simplicity and specificity of the recognition process make it an ideal fluorescent probe for detecting H2PO4ˉ in test strip, Zebrafish, and bean sprout. Theoretical studies using UV–vis spectroscopy, HR-MS, 1H NMR titration, and theory calculations (DFT & TD-DFT) provided a better understanding of the sensing mechanisms and binding modes of the sensor MT and H2PO4ˉ. This new recognition strategy may open up new avenues for further applications in vitro, in vivo, and in plants.

Anthraquinone Based Sensors for the Selective Detection of Cyanide Ion with Turn on Fluorescence with Logic Gate & Real Sample Applications.

In recent years, there is an increasing interest in finding better and more efficient ways to detect CN- ions. Most of the anthraquinone-based probes show less fluorescenceThis paper presents the design and synthesis of a new anthraquinone based imine probe with good colorimetric sensing property and fluorescent turn on behavior towardCN- ion. Herein, we report a receptor with both colorimetric and fluorescent enhancement of cyanide ion in DMSO medium is synthesized. The synthesized receptor shows an immediate color change from orange to pink when cyanide is added; and it can be readily observed visually due to the presence of diverse p-conjugated systems in the receptor. These studies wereconfirmed by UV-Visible, PL studies, DFT, HRMS and 1H NMR titration. Moreover, this receptor shows 1:1 stoichiometry and micromolar detection limit. Further the receptor wasapplied to areal sample in finger millet (Eleusine Coracana) to detect the presence of cyanide ion. Moreover, the receptor is applicable towardINHIBITION, IMPLICATION logic gates with two input systems.

Multi-channel sensing of trivalent metal ions using a simple ferrocenyl Schiff base probe with AIE property

A simple ferrocene-based Schiff base (probe L) exhibiting aggregation-induced emission (AIE) effect has been synthesized and investigated. The probe L showed selective detection for trivalent metal ions (Al3+, Cr3+and Fe3+) over a range of monovalent and divalent metal ions in methanol via multi-channel of detection using colorimetry, fluorescence and electrochemistry. Upon binding with trivalent metal ions, color change from faint yellow to pink for Al3+, Cr3+and Fe3+ was observed by the naked-eye, which was consistent with the change of UV–Vis absorption spectra. In addition, probe L showed a dramatic off-on fluorescence emission along with a large Stocks-shift of about 33 nm in the emission wavelength. The fluorescence enhancement with a blue shift may be attributed to the combined effect of rotation inhibition and an extended intramolecular charge transfer (ICT) mechanism. Moreover, electrochemical detection demonstrated that the oxidation potential difference between probe L and probe l-metal complexes was 0.028 V (Al3+), 0.044 V (Cr3+) and 0.015 V (Fe3+), respectively, indicating that trivalent metal ions induced charge transfer from the ligand to the metal (LMCT) and reduced the electron density of ferrocene moiety. Therefore, Al3+, Cr3+and Fe3+ can be selectively detected using multi-channel of detection techniques. Finally, 1H NMR titration study confirmed that two molecules of probe L bind with one metal ion through the nitrogen atom and oxygen atom of the probe L.

Influence of metal on coordination geometry and solution dynamics in complexes of cis-ethylenebis(diphenylphosphine oxide) and Ln(OTf)3 (Ln = La, Sm, Lu) X-ray crystal structures and NMR titration studies

This paper describes the synthesis and characterization of complexes containing the relatively rigid bisphosphine oxide ligand cis-ethylenebis(diphenylphosphine oxide) with three lanthanide (Ln) triflate salts (Ln = La3+, Sm3+, Lu3+). The complexes were characterized in the solid state by IR and X-Ray crystallography and show bidentate binding of the ligand to each metal center. The complexes were also studied at various Ln-ligand stoichiometries in solutions of CDCl3 using 1H and 31P NMR. These studies revealed that for the complexes where Ln = La3+ and Sm3+ ligand exchange is fast on the 1H and 31P NMR time scales when there are less than four equivalents of ligand in solution but slows when more than four equivalents are present. For the solution studies of complexes with Lu3+, ligand exchange is fast on the 1H NMR but slow on the 31P NMR time scale for all Lu-ligand stoichiometries.

Selective separation of radioactive thorium and uranium from scandium using N-heterocyclic carboxamide ligands

Scandium is a valuable strategic resource widely dispersed in nature and frequently coexists with other minerals, some of which contain radionuclides, particularly uranium and thorium. It is of great importance to remove these radioactive elements in a green and efficient manner to manufacture superior scandium products. The present study synthesized a range of N-heterocyclic carboxamide ligands and undertook a full investigation of their efficacy in extracting and separating uranium and thorium from scandium. Of these, two demonstrated preferential extraction of radioactive elements in HNO3, while the extraction of scandium was observed in HClO4. Under optimum conditions, 95.3% of uranium and 70.7% of thorium were extracted with only a 3.6% loss of scandium after a single-stage extraction, and the other rare earth elements were scarcely extracted. In addition, almost all the uranium and thorium in a simulated solution were depleted following a five-stage extraction process when treated with the phenanthroline-derived carboxamide ligand, resulting in a scandium oxide product with a 99.99% purity. The coordination mechanism of the extraction was identified using slope analysis, NMR titration, and UV–vis titration. All the evidence indicates that U(VI) and Th(IV) complexes with the phenanthroline-derived carboxamide ligand have a stoichiometry ratio of 1:1, whereas, in the case of scandium, there are both 1:1 and 1:2 species. This work enables the preparation of high-purity scandium with an ultra-low level of radioactivity and provides a new idea for the efficient processing of rare earth minerals.

A novel ratiometric NIR fluorescent probe based on tanshinone IIA with double excitation for the detection of hydrazine

Hydrazine (N2H4) is a highly reactive chemical substance which is widely used in various industrial fields. Overexposure to hydrazine can bring potential risk to environmental safety and human health due to its toxicity and carcinogenicity. In this study, a near-infrared ratiometric fluorescent probe (TPE) with dual-excitation and dual-emission mode was designed and synthesized for the sensing of hydrazine. TPE displayed a highly sensitive and selective response to hydrazine with low detection limit (58 nM), short response time (3 min) and wide pH range (5–10). The sensing mechanism was investigated by 1H NMR titration, HRMS and DFT calculations. In view of the excellent properties, TPE was successfully applied for the detection of hydrazine in multiple systems including environmental water, food and gaseous samples. In addition, TPE was also successfully utilized for the real-time sensing of hydrazine in living cells and zebrafishes.

Phenolphthalein based molecule as a lighting–up fluorescent chemoprobe for the nanomolar recognition of Al3+: DFT study and its applications in test kits, food and water samples

Phenolphthalein–based compound (PHAB) was synthesized, well–characterized and studied as a lighting–up fluorescent chemosensor for Al3+. Fluorescence studies were performed at 25 °C in H2O/CH3CN (20/80, v/v) media. Free PHAB was non–fluorescent; but, it depicted a strong fluorescence toward Al3+ at 468 nm over potential competitive cations. The mechanism of C = N isomerisation and blocking PET enhanced its emission with a remarkable color alteration from colorless to blue. The LOD value was found at nano–molar level (51.5 nM), indicating high sensitivity toward Al3+. The validation study also confirmed the sensing performance of PHAB based on different analytical parameters. Job's plot, 1H NMR titration and MALDI TOF–MS studies authenticated the stoichiometry between PHAB and Al3+ (1:2). The binding of PHAB with Al3+ was further verified by the theoretical study. Furthermore, the fluorescence sensing performance of PHAB makes it perfect for practical applications in drinkable water and food samples with satisfactory recovery values (91.42%–108.8%), as well as in simple test–kit applications.