Vitamin B6 Cofactor Pyridoxal 5'-phosphate Conjugated Papain-Stabilized Fluorescent Gold Nanoclusters for Switch-on Detection of Zinc(II).

In this study, fluorescent gold nanoclusters (AuNCs) conjugated with pyridoxal-5-phosphate (PLP) were synthesized, characterized, and used for Zn2+ fluorescence turn-on sensing. PLP was conjugated over the surface of papain-stabilized fluorescent gold nanoclusters (pap-AuNCs; λex = 380 nm, λem = 670 nm) by forming imine linkage. Due to this modification, the red color emitting pap-AuNCs changed to orange color emitting nanoclusters PLP_pap-AuNCs. The nano-assembly PLP_pap-AuNCs detect Zn2+ selectively by showing a notable fluorescence enhancement at 477 nm. Zn2+ detection with PLP_pap-AuNCs was quick and easy, with an estimated detection limit of 0.14 µM. Further, paper strips and cotton buds coated with PLP_pap-AuNCs were developed for affordable on-site visual detection of Zn2+. Finally, the detection of Zn2+ in actual environmental water samples served as validation of the usefulness of PLP_pap-AuNCs.

Copper(II) Driven Fluorescence switch-on Detection of Ovalbumin and GSH Using a Pyridoxal 5'-phosphate Derived Tetradentate Schiff Base and its Applications.

The facile detection of glutathione (GSH) and ovalbumin (OVA) is of great importance in biological research. Herein, a tetradentate Schiff base N, N'-bis(pyridoxal-5-phosphate)-o-phenylenediamine (L) obtained by condensing two moles of pyridoxal 5'-phosphate (PLP) with one mole of 1,2-phenylenediamine was employed for the fluorescence switch-on detection of GSH and OVA. When excited at 389 nm, receptor L showed a weak emission at 454 nm in an aqueous medium. The addition of GSH to the solution of L caused a significant fluorescence enhancement at 454 nm. Amino acids (leucine, glycine, serine, tryptophan, homocysteine, alanine, methionine, arginine and proline) and albumins (bovine serum albumin and OVA) failed to alter the fluorescence profile of L. Receptor L can be applied to detect GSH down to 1.16 µM. However, the fluorescence emission of L was quenched upon the formation of the L-Cu2+ complex. The addition of GSH and OVA to the in-situ formed L-Cu2+ complex restored not only the fluorescence emission of L but also a noticeable fluorescence enhancement observed at 454 nm. The decomplexation of L-Cu2+, along with the interaction of L with GSH and OVA is expected to suppress the conformational flexibility of L that enhanced the fluorescent intensity at 454 nm. Using L-Cu2+ complex, the concentration of OVA and GSH can be detected down to 0.31 µM and 0.20 µM, respectively. Molecular docking and dynamics simulation were performed to analyze the binding mode, conformational flexibility and dynamic stability of the L-Cu2+-OVA complex. Finally, the analytical novelty of L-Cu2+ was examined by detecting GSH/OVA in real biological samples, such as human blood serum, urine, and egg white.

Aggregation-induced Emission Active Naphthalimide Derived Schiff Base for Detecting Cu2+ and Its Applications.

Herein, an aggregation-induced emission (AIE) active Schiff base (NHS) was synthesized by condensing naphthalimide hydrazide with salicylaldehyde. The non-fluorescent solution of NHS in DMSO turned to emissive NHS upon increasing the HEPES fraction in DMSO from 70 to 95%. The UV-Vis absorption and DLS studies supported the self-aggregation of NHS that restricted the intramolecular rotation and activated the ESIPT process. The blue fluorescence of AIE luminogen NHS in DMSO:HEPES (5:95, v/v, pH = 7.4) was examined by adding different metal ions (Al3+, Ca2+, Cd2+, Co2+, Cu2+, Cr2+, Fe2+, Fe3+, Hg2+, Mg2+, Mn2+, Ni2+, Pb2+ and Zn2+). NHS showed a selective fluorescence switch-off response for Cu2+ due to the chelation enhancement quenching effect (CHEQ). The quenching of NHS by Cu2+ was explored by using density functional theory (DFT) and Stern-Volmer plot. The practical utility of NHS was examined by quantitative and qualitative analysis of Cu2+ in real water samples.

Detecting Moisture in Building Materials and Commercial Food adducts by 2-Hydroxy-naphthaldehyde Derived Chromo-Fluorogenic Chemosensor.

A great deal of effort has been put into developing a novel and cost-effective molecular probe for selective and sensitive recognition of trace amounts of water in organic solvents due to their tremendous advantages in industrial, pharmaceutical, and laboratory-scale chemistry. Herein, a cost-effective chemosensor L has been designed and studied for the detection of trace amounts of water. The addition of water to the DMSO solution of L exhibited an enhancement of fluorescence emission at 460 nm along with a color change from green to colorless. The spectral and color changes occurred due to the self-aggregation of L. The interaction between water and L was performed by dynamic light scattering (DLS), scanning electron microscope (SEM) and finally complemented by quantum mechanical calculation. The detection limit was found to be 0.0093 wt% in DMSO. The L also exhibits a fast visual response and is effectively applied to detect trace amounts of moisture in various food materials (salt, sugar, wheat and honey) and building materials (cement, fly ash, limestone and sand).

Triazole-linked amidopyrene-tagged fluorometric probe for Au3+ ions and pH control aggregation-induced emission.

In this paper, an amidopyrene-tagged reversible fluorescence probe 1 has been constructed for the detection of Au(III) ions in H2O/CH3CN (4/1, v/v). It is used to identify the Au(III) ions over several metal ions with excellent sensitivity (LOD: 0.061 µM). The fluorescence quenching of 1 with Au(III) ions might be attributed to the reverse PET process. Probe 1 recognized Au(III) by forming tetravalent geometry with the amide -NH, triazole moiety, free water, and Cl- ion in 1:1 binding mode, which is evidenced by the DFT calculations, FT-IR spectroscopy, and HRMS value of the complex. The application utility of probe 1 was ascertained from the recovery of Au(III) ions from different sources of natural water samples. Interestingly, molecule 1 also showed aggregation-induced emission behavior at basic pH (>10) in H2O/CH3CN medium with high water content. The AIE might be attributed to the formation of self-associates of 1 upon the intermolecular H-bonding interactions between water and donor atom(s) of 1 or the increased polarity of the solvent medium.

Pyrene-based fluorescent chemosensor for rapid detection of water and its applications.

This manuscript introduces a pyrene-based Schiff base L by reacting pyrenecarboxaldehyde with 2-aminothiazole in equimolar ratio. The ligand L was characterized by various spectral data and single crystal. The water sensing ability of L was examined in different organic solvents. The weakly emissive L in DMSO showed a fluorescence enhancement upon the addition of water. The water-induced fluorescence enhancement of L was occurred due to the combined effect of aggregation-induced emission (AIE) phenomenon and suppression of photo-induced electron transfer (PET) process. Using L, the water in DMSO can be detected down to 0.50 wt% with a quantification limit of 1.52 wt%. The analytical novelty of the developed sensor L was validated by detecting moisture in a variety of raw food products.

Indole clubbed 2,4-thiazolidinedione linked 1,2,3-triazole as a potent antimalarial and antibacterial agent against drug-resistant strain and molecular modeling studies.

In the face of escalating challenges of microbial resistance strains, this study describes the design and synthesis of 5-({1-[(1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl}methylene)thiazolidine-2,4-dione derivatives, which have demonstrated significant antimicrobial properties. Compared with the minimum inhibitory concentrations (MIC) values of ciprofloxacin on the respective strains, compounds 5a, 5d, 5g, 5l, and 5m exhibited potent antibacterial activity with MIC values ranging from 16 to 25 µM. Almost all the synthesized compounds showed lower MIC compared to standards against vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus strains. Additionally, the majority of the synthesized compounds demonstrated remarkable antifungal activity, against Candida albicans and Aspergillus niger, as compared to nystatin, griseofulvin, and fluconazole. Furthermore, the majority of compounds exhibited notable inhibitory effects against the Plasmodium falciparum strain, having IC50 values ranging from 1.31 to 2.79 µM as compared to standard quinine (2.71 µM). Cytotoxicity evaluation of compounds 5a-q on SHSY-5Y cells at up to 100 µg/mL showed no adverse effects. Comparison with control groups highlights their noncytotoxic characteristics. Molecular docking confirmed compound binding to target active sites, with stable protein-ligand complexes displaying drug-like molecules. Molecular dynamics simulations revealed dynamic stability and interactions. Rigorous tests and molecular modeling unveil the effectiveness of the compounds against drug-resistant microbes, providing hope for new antimicrobial compounds with potential safety.

Structural Distortion of ß-Cyclodextrin Plays a Key Role in the pH-dependent Host-Guest Chemistry with Doxorubicin, Evident by the Electrochemical and Molecular Dynamics Approach.

ß-Cyclodextrin (ß-CD) is the potential drug carrier to deliver antitumor drugs like doxorubicin (DOX). However, the mechanism for the inclusion complex formation is still unclear and needs to be explored. This study investigated the effect of pH on the inclusion of DOX into thiolated ß-CD (ß-CD-SH) by electrochemical and molecular dynamics (MD) simulation. The electrochemical study shows a clear difference at different pH values. The redox peak due to the DOX is strongly influenced by pH. At neutral pH, the peak intensity decreases with time, while slight variation is observed at acidic and basic pH, depicting the association of DOX to the ß-CD-SH cavity at neutral pH. Also, due to the association, the charge transfer resistance variation increased with time at neutral pH and decreased at basic and acidic pH. The electrochemical study was further supported by MD simulation, suggesting that the cyclodextrin (CD) ring gets slightly elongated due to the flipping of glucose units, specifically at neutral pH leading to a strong association. Also, another significant result observed that the DOX forms an inclusion complex with ß-CD-SH in quinol conformation, not in quinone. Briefly, the study provides the necessary molecular binding information for designing an effective ß-CD-based targeted drug delivery system.

Fluorescence Turn-on Detection of Alkaline Phosphatase Activity and Al3+ Using Vitamin B6 Cofactor Conjugated GSH Capped Mn-doped ZnS Quantum Dots.

The glutathione (GSH) functionalized Mn-doped ZnS quantum dots (GSH_Mn_ZnS QDs) was conjugated with pyridoxal 5'-phosphate (PLP). The -CHO group of vitamin B6 cofactor PLP interacted with the -NH2 group of GSH functionalized Mn_ZnS QDs. The conjugation of PLP quenched the fluorescence emission of GSH_Mn_ZnS QDs at 601 nm. Addition of alkaline phosphatase (ALP) catalytically dephosphorylated the PLP into pyridoxal that restored the fluorescence emission of GSH_Mn_ZnS QDs. With a sensitivity of 0.035 U/L, the PLP conjugated GSH_Mn_ZnS QDs was applied to quantify ALP activity in human serum and plasma. Further, the developed nanoprobe PLP conjugated GSH_Mn_ZnS QDs was also applied to detect Al3+. The complexation-induced fluorescence enhancement was observed at 492 nm upon the interaction of Al3+ with the PLP conjugated GSH_Mn_ZnS QDs. Without any interference from other tested metal ions, this nanoprobe can be employed to detect Al3+ down to 2.30 µM.

Fluorescent Switch-on Detection of Cadmium(II) Using Salicylaldehyde-Decorated Gold Nanoclusters.

In this study, salicylaldehyde (SA) conjugated gold nanoclusters were synthesized, characterized, and applied for the fluorescent turn-on sensing of Cd2+. The trypsin-stabilized fluorescent gold nanocluster (Tryp-AuNCs, λem = 680 nm) was modified with SA to form the spherical-shaped SA_Tryp-AuNCs. After modification, the red-emitting Tryp-AuNCs turned to green-emitting SA_Tryp-AuNCs because of the formation of imine linkage between the -CHO group of SA with the -NH2 group of functionalized trypsin. The modified SA_Tryp-AuNCs selectively interacted with Cd2+ and exhibited a fluorescence enhancement at 660 nm. The Cd2+ detection with SA_Tryp-AuNCs is simple and rapid with an estimated nanomolar detection limit of 98.1 nM. The practical utility of SA_Tryp-AuNCs was validated by quantifying Cd2+ in real environmental water samples.

'AIE + ESIPT' Active 2-hydroxy-naphthalene Hydrazone for the Fluorescence Turn-on Sensing of Al3.

The aggregation-induced emission (AIE) behaviour of an easy-to-prepare Schiff base 2-hydroxy-naphthalene hydrazone (L) was explored in mixed DMSO/HEPES medium by selecting DMSO as a good solvent, whereas HEPES buffer (H2O, 10 mM, pH 7.4) as a poor solvent. The weakly fluorescent L in pure DMSO showed a fluorescence enhancement at 532 nm upon increasing the fraction of HEPES above 70% because of the self-aggregation of L and excited state intramolecular proton transfer (ESIPT) process. The AIE luminogen (AIEgen) L was applied for the sensing of metal ions in HEPES buffer (5% DMSO, 10 mM, pH 7.4). Among the fourteen different metal ions (Cu2+, Co2+, Ni2+, Mn2+, Mg2+, Fe3+, Fe2+, Zn2+, Cd2+, Hg2+, Pb2+, Al3+, Cr3+), AIEgen L showed a selective fluorescence enhancement at 435 nm in the presence of Al3+ without disturbing the fluorescence intensity at 532 nm due to the chelation-enhanced fluorescence effect (CHEF). The detection limit of 20 nM was estimated by performing the fluorescence titration of AIEgen L with Al3+. The reversibility of the Al3+ selective AIEgen L was demonstrated by adding a strong chelating agent EDTA. Finally, the practical utility of AIEgen L was validated by quantifying Al3+ in river and tap water samples.

Improving Copper(II) Sensitivity by Combined use of AIEE Active and Inactive Schiff Bases.

An aggregation-induced emission enhancement (AIEE) active Schiff base PNN was synthesized by condensing benzidine with 2-hydroxynaphthaldehyde. The green-fluorescent PNN (λem = 510 nm) in DMF turned to yellow-fluorescent PNN (λem = 557 nm) upon increasing the fractions of HEPES buffer (10 mM, pH 7.4) above 40%. The DLS study supports the self-aggregation of PNN that restricts the intramolecular rotation and activates the excited-state intramolecular proton transfer (ESIPT) process. The fluorescence emission of AIEE active PNN was quenched by Cu2+ with an estimated detection limit of 2.1 µM. Interestingly, the detection limit of PNN towards Cu2+ was improved in the presence of an AIEE inactive Schiff base PBPM obtained by reacting 1,4-diaminobenzene with pyridine-4-carbaldehyde. The mixed PNN-PBPM showed a detection limit of 0.49 µM. The practical utility of PNN-PBPM was validated by quantifying Cu2+ ions in real environmental water samples and green tea.

Aggregation-Induced Emission Active Benzidine-Pyridoxal Derived Scaffold for Detecting Fe3+ and pH.

Present work introduces an aggregation-induced emission (AIE) active Schiff base 4,4'-((1E,1'E)-([1,1'-biphenyl]-4,4'-diylbis(azaneylylidene))bis(methaneylylidene))bis(5-(hydroxymethyl)-2-methylpyridin-3-ol) (BNPY). Schiff base BNPY was synthesized by reacting benzidine with pyridoxal. The non-fluorescent BNPY in freely soluble DMSO medium showed a significant fluorescence enhancement at 563 nm (λex = 400 nm) upon increasing the water fraction (fw) in DMSO above 60% due to the restriction of intramolecular rotation upon the aggregation of BNPY. The AIE active BNPY was employed for the detection of metal ions in DMSO:H2O (fw = 70%). Upon the addition of Fe3+, the fluorescence emission of BNPY at 563 nm was quenched due to the chelation-enhanced fluorescence quenching (CHEQ). The Job's plot experiment supported the formation of a complex between BNPY and Fe3+ in 1:2 binding ratio. With an estimated detection limit of 5.6 × 10-7 M, BNPY was employed to detect and quantify Fe3+ ion in real water samples with satisfactory recovery percentages. Moreover, the pH studies of BNPY aggregates revealed three different fluorescence windows: non-fluorescent in acidic pH 2.02 to 3.16, yellow fluorescent between pH 3.60 to 9.33, and green fluorescent in basic pH 9.96 to 12.86.

Fluorescence Sensing of pH and p-Nitrophenol Using an AIEE Active Pyridoxal Derived Schiff Base.

An easy-to-prepare aggregation-induced emission enhancement (AIEE) active Schiff base NPY was synthesized by condensing vitamin B6 cofactor pyridoxal with 3-hydroxy-2-naphthoic hydrazide, and employed for the fluorescent sensing of pH and p-nitrophenol (p-NP). The AIEE phenomenon of NPY was investigated in mixed DMSO/H2O medium. The weakly yellow-fluorescent NPY (λem = 535 nm) in pure DMSO turned to a bright cyan-fluorescent NPY (λem = 490 nm) upon addition of poor solvent water. The DLS and SEM analyses supported the self-aggregation of NPY that restricted the intramolecular rotation and activated the excited state intramolecular proton transfer (ESIPT) process. The AIEE luminogen (AIEEgen) NPY containing 90% of water fraction (fwater) was employed for the fluorescent sensing of pH. AIEEgen NPY displays three distinct fluorescent pH windows: non-fluorescent below pH 3.0 and above pH 10.0, cyan fluorescent between pH 3.0 to 8.0, and yellow fluorescent between pH 8.0 to 10.0. AIEEgen NPY was also applied for the detection of nitroaromatics in HEPES buffer (10% DMSO, 10 mM, pH 7.0). The addition of p-NP selectively quenched the fluorescent intensity of AIEEgen NPY with an estimated detection limit of 1.73 µM. The analytical utility of AIEEgen NPY was examined by quantifying p-NP in different real water samples.

Pyridoxal Derived AIEgen for Fluorescence Turn-off Sensing of Cu2+ and Fe2+ Ions and Fluorescence Imaging of Latent Fingerprints.

Schiff base 4-((E)-((E)-(2-hydroxybenzylidene)hydrazono)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (HSP) was synthesized by condensing vitamin B6 cofactor pyridoxal with salicylaldehyde hydrazone, and characterized by standard spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and ESI-MS). The solution of HSP in DMSO/HEPES (10 mM, pH = 7.4) mixed solvents with varying HEPES fractions (fw) from 0 to 95% showed aggregation-induced emission (AIE). The AIE active HSP in 95% HEPES gave intense fluorescent emission at 570 nm was employed for the detection of metal ions. The fluorescence of HSP was quenched upon adding Cu2+ and Fe2+ ions. The association constant (Ka) of the Schiff base HSP with Cu2+ and Fe2+ ions was estimated as 4.08 × 105 M-1 and 1.23 × 105 M-1, respectively by using the online analysis tool BindFit v0.5. The HSP showed the detection limit down to 1.75 µM and 1.89 µM for Cu2+ and Fe2+ ions, respectively. Further, the aggregates of HSP were applied to visualize latent fingerprints (LFPs) over a non-porous glass slide.

Fluorescent Turn-On Sensing of Zinc(II) and Alkaline Phosphatase Activity Using a Pyridoxal-5'-Phosphate Derived Schiff Base.

A novel Zn2+ ion and alkaline phosphatase (ALP) selective fluorescence turn-on sensor L was developed by reacting pyridoxal 5'-phosphate (PLP) with hydrazine. Sensor L shows significant flurescence enhancement at 476 nm due to the formation of a L-Zn2+ complex in 1:1 binding stoichiometry with the association constant of 3.1⋅104 M- 1. Using L, the concentration of Zn2+ can be detected down to 2.34 µM, and the practical utility of L was validated by quantifying Zn2+ in real water samples. Additionally, the receptor L was applied to mimic the dephosphorylation reaction catalysed by the enzyme ALP and the resulted fluorescence change was monitored to detect the ALP activity.

A Formyl Chromone Based Schiff Base Derivative: An Efficient Colorimetric and Fluorescence Chemosensor for the Selective Detection of Hg2+ Ions.

A novel chromone-based Schiff base L was designed and synthesized by condensing an equimolar amount of 3-formyl chromone and 2,4-dinitro phenyl hydrazine. Schiff base L was developed as a potent colorimetric and fluorescent molecular probe to recognize Hg2+ ions over other competitive metal ions. In the presence of Hg2+, Schiff base L displays a naked-eye detectable color change under day and UV365 nm light. Various UV-Vis and fluorescence studies of L were performed in the absence and presence of Hg2+ to determine the sensitivity and the sensing mechanism. With high selectivity and specificity, the detection limit and association constant of L for Hg2+ were estimated at 1.87 µM and 1.234 × 107 M-1, respectively. The developed sensor L was applied to real soil samples for the detection of Hg2+.

Rapid Colorimetric and Fluorometric Discrimination of Maleic Acid vs. Fumaric Acid and Detection of Maleic Acid in Food Additives.

An anthracene thiazole based Schiff base L was synthesized and employed for fluorescence switch-on detection of maleic acid in aqueous DMSO. The non-fluorescent L (10-5 M) showed an instantaneous and selective fluorescence enhancement at 506 nm upon interaction with maleic acid (10-5 M). Other potential carboxylic acids (10-5 M), such as malic acid, citric acid, acetic acid, cinnamic acid, tartaric acid, succinic acid, fumaric acid, oxalic acid and malonic acid failed to alter the chromo-fluorogenic properties of L. Probe L can be employed to detect maleic acid down to 2.74 × 10-6 M. The probe L showed good linearity from 2.97 to 6.87 µM. Analytical utility of L was examined by detecting maleic acid in various food additives and drosophila larvae.

Fluorescent turn-on sensing of albumin proteins (BSA and ovalbumin) using vitamin B6 cofactor derived Schiff base.

The detection of albumin proteins with high accuracy by facile analytical approaches is important for the diagnosis of various diseases. This manuscript introduced an easy-to-prepare Schiff base L by condensing vitamin B6 cofactor pyridoxal 5'-phosphate (PLP) with 2-aminothiophenol for the fluorescence turn-on sensing of bovine serum albumin (BSA) and ovalbumin (OVA). The weakly emissive L showed a significant fluorescence enhancement at 485 and 490 nm in the presence of OVA and BSA with an estimated sensitivity limit of 1.7 µM and 0.3 µM, respectively. The formation of protein-ligand complex restricted the free intramolecular rotation of L is expected to show the selective fluorescence enhancement. The molecular docking and molecular dynamics simulations were performed to examine the binding affinity and modes between BSA/OVA and L. The practical utility of L as a fluorescent turn-on sensor was validated by quantifying BSA and OVA in various real biological samples of milk, serum, egg white and urine with good recovery percentages.

Computational studies on the interaction of Omicron subvariants (BA.1, BA.2, and BA.3) with ACE2 and polyphenols.

INTRODUCTION: The SARS-CoV-2 Omicron variant BA.2 is spreading widely across the globe. The World Health Organization (WHO) designated BA.2 as a variant of concern due to its high transmission rate and pathogenicity. To elucidate the structural changes caused by mutations, we conducted a comparative analysis of BA.2 with variants BA.1 and BA.3. OBJECTIVE: In the present study, we aimed to investigate the interactions of the spike glycoprotein receptor-binding domain (SGp RBD) of Omicron variants BA.1, BA.2, and BA.3 with the human receptor hACE2. Further, a library of 233 polyphenols was screened by molecular docking with the SGp RBDs of Omicron variants BA.1, BA.2, and BA.3. METHODS: Protein-protein and protein-ligand molecular docking simulations were performed with AutoDock Vina and the ClusPro 2.0 server, respectively. The protein-ligand interactions were evaluated by BIOVIA Discovery Studio and ChimeraX 1.4. The molecular dynamics simulations for 100 ns were performed using GROMACS 2021. RESULTS: Compared to other variants of concern, the structural changes in Omicron caused by mutations at key positions improved its ability to cause infection. Despite multiple mutations, many important polyphenols bind effectively at the RBDs of Omicron variants, with the required pharmacokinetic and ADME features and obeying the Lipinski rule. CONCLUSION: Even though Omicron variants have multiple mutations and their transmission rate is relatively high, the computed binding affinities of lead polyphenols like epigallocatechin-3-O-gallate (EGCG) and luteolin-7-O-glucuronide (L7G) indicate that traditional medicines and proper immunity booster diets may be useful in the long-term fight against SARS-CoV-2.