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.

Advances on fluorescence chemosensors for selective detection of water.

Water, although an important part of everyday life, is acts as one of the most significant contaminants in various applications such as biomedical monitoring, chemical production, petroleum-based fuel and food processing. In fact, the presence of water in other solvents is a huge concern. For the quantification of trace water content, different methods such as Karl-Fischer, electrochemical, nuclear magnetic resonance, chromatography, and thermogravimetric analysis have been used. Although every technique has its own benefit, each one suffers from several drawbacks that include high detection costs, lengthy procedures and specialized operations. Nowadays, the development of fluorescence-based chemical probes has become an exciting area of research for the quick and accurate estimation of water content in organic solvents. A variety of chemical processes such as hydrolysis reaction, metal ions promoted oxidation reaction, suppression of the -C═N isomerization, protonation and deprotonation reactions, and molecular aggregation have been well researched in the last few years for the fluorescent detection of trace water. These chemical processes eventually lead to different photophysical events such as aggregation-induced emission (AIE), aggregation-induced emission enhancement (AIEE), aggregation-caused quenching (ACQ), fluorescent resonance energy transfer (FRET), charge transfer, photo-induced electron transfer (PET), excited state intramolecular proton transfer (ESIPT) that are responsible for the detection. This review presents a summary of the fluorescence-based chemosensors reported in recent years. The design of water sensors, sensing mechanisms and their potential applications are reviewed and discussed.

Fluorescent ovalbumin-functionalized gold nanocluster as a highly sensitive and selective sensor for relay detection of salicylaldehyde, Hg(II) and folic acid.

A sensitive and selective relay-based scheme for the detection of salicylaldehyde, Hg2+, and folic acid (FA) has been demonstrated using fluorescent ovalbumin functionalized gold nanoclusters (OVA-AuNCs, λem = 655 nm) in this article. The OVA-AuNCs were conjugated to salicylaldehyde via an imine linkage to form Salic_OVA-AuNCs conjugate. The molecular docking study reveals that multiple functional groups and amino acid residues are involved in the interaction between salicylaldehyde and the OVA-AuNCs. The coupling of salicylaldehyde with OVA-AuNCs results in fluorescence quenching at 655 nm and concomitant formation of an emission band at 500 nm, which have leveraged to detect salicylaldehyde down to 2.02 µM. Following that, the Salic_OVA-AuNCs has been used for the detection of Hg2+ and FA. Several processes, such as internal charge transfer (ICT), photoinduced electron transfer (PET) and metallophilic interactions, are involved between the Salic_OVA-AuNCs nanoprobe and the analytes, which allowed to detect Hg2+ and FA down to 0.13 nM and 0.11 nM, respectively. The Salic_OVA-AuNCs nanoprobe has an additional naked-eye utility when applied to paper-strip sensing strategy for Hg2+ and FA detection.

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.

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.

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.

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.

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.

Sugar-based carboxamidoquinoline conjugate for sensing Cu2+ and Au3+ ions in water through different binding modes and real application.

A simple water-soluble carboxamidoquinoline derivative of glucofuranose 1 exhibited reversible selectivity toward Cu2+ and Au3+ ions in different binding modes. Sensor 1 is an example of a dual sensor for identifying copper and gold ions in the water medium. Sensor 1 exhibited excellent selection ability and sensitivity for Cu2+ and Au3+ ions rather than several metal ions and anions with a wide pH range (5-10). The association constants for both ions were determined to be 3.58 × 104 M-1 and 1.84 × 104 M-1, respectively. The 1:1 binding chemistry of the complexes was verified from the Job method and again validated through mass spectra. Sensor 1 can detect Cu2+ and Au3+ ions at very low concentrations, such as 0.014 µM for Cu2+ and 0.058 µM for Au3+. The different sensing strategies of sensor 1 towards Cu2+ and Au3+ were manifested from the photophysical properties of sensor 2 with metal ions, FT-IR spectra, and theoretical (DFT) observations. The useful relevance of the sensor for Cu2+ and Au3+ ions was tested in different water samples.

Computational insight of antioxidant and doxorubicin combination for effective cancer therapy.

Doxorubicin (DOX) is the most effective antineoplastic agent, destroys cancer cells by interrupting cellular function. However, the serious side effects on the heart limits its utility. To curb these unwanted side effects, nutritionist recommend antioxidants use along with DOX while chemotherapy. But it was not supported by various oncologists as it can alter the toxicity of DOX towards cancer cells. Therefore, here we explored the in silico pharmacokinetics and combination effect of DOX and antioxidants on topoisomerases-II (Top-II) and cyclophilin D (Cyp-D) therapeutic targets involved in cancer proliferation and post-myocardial infarction, respectively. The molecular docking study was conducted on target proteins and DOX including most prescribed antioxidants (melatonin, N-acetylcysteine (NAC), glutathione (GSH), ß-carotene and vitamin C). GSH showed effective binding potential for Top-II and Cyp-D active sites, but other considered antioxidants possess low binding affinity. The highest docked conformations were subjected to molecular dynamics (MD) simulations to understand conformer stability of DOX and GSH with Cyp-D and Top-II for 100 ns. The results revealed that ligands pose at Top-II active sites where DOX showed strong binding affinity to DNA binding pocket and GSH to a buried site. The computational data summarised and proposed the GSH and DOX combination as antagonist effects on Top-II. Conversely, the binding compactness of GSH improved due to surface fit at the active pocket of Cyp-D and completely blocking DOX binding affinity, suppress adverse reactions of post-myocardial infarction.Communicated by Ramaswamy H. Sarma.

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.

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.

Computational studies on searching potential phytochemicals against DNA polymerase activity of the monkeypox virus.

Objectives: The outbreak of monkeypox virus (MPXV) is an emerging epidemic of medical concern with 65353 confirmed cases of infection and a fatality of 115 worldwide. Since May 2022, MPXV has been rapidly disseminating across the globe through various modes of transmission, including direct contact, respiratory droplets, and consensual sex. Because of the limited medical countermeasures available to treat MPXV, the present study aimed to identify potential phytochemicals (limonoids, triterpenoids, and polyphenols) as antagonists to target the DNA polymerase protein of MPXV with the ultimate goal to inhibit the viral DNA replication mechanism and immune-mediated responses. Methods: The protein-DNA and protein-ligand molecular docking were performed with the help of computational programs AutoDock Vina, iGEMDOCK and HDOCK server. The BIOVIA Discovery studio and ChimeraX were used to evaluate the protein-ligand interactions. The GROMACS 2021 was used for the molecular dynamics simulations. The ADME and toxicity properties were computed by using online servers SwissADME and pKCSM. Results: Molecular docking of 609 phytochemicals and molecular dynamics simulations of lead phytochemicals glycyrrhizinic acid and apigenin-7-O-glucuronide generated useful data that supported the ability of phytochemicals to obstruct the DNA polymerase activity of the monkeypox virus. Conclusions: The computational results supported that appropriate phytochemicals can be used to formulate an adjuvant therapy for the monkeypox virus.

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.

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.

G2/M-Phase-Inhibitory Mitochondrial-Depolarizing Re(I)/Ru(II)/Ir(III)-2,2'-Bipyrimidine-Based Heterobimetallic Luminescent Complexes: An Assessment of In Vitro Antiproliferative Activity and Bioimaging for Targeted Therapy toward Human TNBC Cells.

Triple-negative breast cancer (TNBC) is an extremely vicious subtype of human breast cancer having the worst prognosis along with strong invasive and metastatic competency. Hence, it can easily invade into blood vessels, and presently, no targeted therapeutic approach is available to annihilate this type of cancer. Metal complexes have successfully stepped into the anticancer research and are now being applauded due to their anticancer potency after the discovery of cisplatin. Many of these metal complexes are also well recognized for their activity toward breast cancer. As the TNBC is a very dangerous subtype and has long been a challenging ailment to treat, we have intended to develop a few brand new mixed metallic Ru(II)/Ir(III)/Re(I)-2,2'-bipyrimidine complexes [L'Re2], [L'RuRe], and [L'IrRe] to abate the unbridled proliferation of TNBC cells. The potency of the complexes against TNBC cells has been justified using MDA-MB-468 TNBC cell lines where complex [L'IrRe] has displayed significant potency among all the three complexes with an IC50 value of 24.12 µM. The complex [L'IrRe] has been competent to cause apoptosis of TNBC cells through inhibition of the G2/M phase in the cell cycle in association with a profuse amount of ROS generation and mitochondrial depolarization.

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.

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.