Formation of CdTe core and CdTe@ZnTe core-shell quantum dots via hydrothermal approach using dual capping agents: deciphering the food dye sensing and protein binding applications.

Excessive use of food coloring agents in the food industry to make the food more attractive or improve the taste has caused various health and ecological problems. Therefore, it is necessary to develop a reliable, sensitive, and selective sensing probe to detect food dyes in different food products for future industrial processing and biosafety. In recent decades, surface-functionalized quantum dots (QDs), owing to their unique optical properties, have gained tremendous interest for a wide range of applications, including biomedical, bioimaging and sensing applications. Herein, we have reported the synthesis of excellent colloidal stable and highly luminescent CdTe core and CdTe@ZnTe core-shell QDs using dual functionalizing agents, polyvinyl pyrrolidone and vitamin C. The synthesized QDs were explored as excellent sensing probes for the food dyes carmoisine, Ponceau 4R and tartrazine with limit of detection (LOD) values of 0.097 ± 0.006, 0.147 ± 0.001 and 0.044 ± 0.001 µM for CdTe-PVP QDs and 0.079 ± 0.001, 0.114 ± 0.002 and 0.042 ± 0.001 µM for CdTe@ZnTe-PVP QDs, respectively. The sensitivity of the synthesized QDs for the food dyes was also investigated in real samples (soft drinks and medications). Moreover, considering the potential effects of QDs as therapeutics or nano-drug carriers, the interactions between the synthesized QDs and carrier protein human serum albumin (HSA) were investigated. The binding affinity was observed to be in the order of 104 M-1. QDs were found to quench the intrinsic fluorescence of HSA, and both types of quenching (static and dynamic) occur via electrostatic interactions in association with hydrophobic forces without any significant alteration in the protein structure.

Ruthenium(II) Complex-Based G-quadruplex DNA Selective Luminescent 'Light-up' Probe for RNase H Activity Detection.

A bis-heteroleptic ruthenium(II) complex, 1[PF6 ]2 of benzothiazole amide substituted 2,2'-bipyridine ligand (bmbbipy) has been synthesized for the selective detection of G-quadruplex (GQ) DNA and luminescence-assay-based RNase H activity monitoring. Compound 1[PF6 ]2 exhibited aggregation-caused quenching (ACQ) in water. Aggregate formation was supported by DLS, UV-vis, and 1 H NMR spectroscopy results, and the morphology of aggregated particles was witnessed by SEM and TEM. 1[PF6 ]2 acted as an efficient GQ DNA-selective luminescent light-up probe over single-stranded and double-stranded DNA. The competency of 1[PF6 ]2 for selective GQ structure detection was established by PL and CD spectroscopy. For 1[PF6 ]2 , the PL light-up is exclusively due to the rigidification of the benzothiazole amide side arm in the presence of GQ-DNA. The interaction between the probe and GQ-DNA was analyzed by molecular docking analysis. The GQ structure detection capability of 1[PF6 ]2 was further applied in the luminescent 'off-on' RNase H activity detection. The assay utilized an RNA:DNA hybrid, obtained from 22AG2-RNA and 22AG2-DNA sequences. RNase H solely hydrolyzed the RNA of the RNA:DNA duplex and released G-rich 22AG2-DNA, which was detected via the PL enhancement of 1[PF6 ]2 . The selectivity of RNase H activity detection over various other restriction enzymes was also demonstrated.

Highly Sensitive Bifunctional Probe for Colorimetric Cyanide and Fluorometric H2S Detection and Bioimaging: Spontaneous Resolution, Aggregation, and Multicolor Fluorescence of Bisulfide Adduct.

A 4-methylbenzothiazole linked maleimide-based single molecular bifunctional probe 1 has been synthesized for the colorimetric and fluorometric detection of highly competitive H2S and cyanide ion in aqueous DMSO media. The probe 1 selectively detected CN- under the UV-vis spectroscopy through the rapid appearance of deep pink color. The bright pink color developed due to ICT in the moderately stable cyano substituted enolate intermediate. The absorbance titration of 1 with CN- revealed a new band at 540 nm and the nonlinear curve fitting analysis showed good fit with 1:1 model. In fluorescence channel, 1 was found to be highly selective to H2S in 50% aqueous buffer (pH 7). It exhibited ∼16-fold fluorescence intensity enhancement at 435 nm after reaction with 1 equiv of H2S due to the inhibition of PET. The 1-SH adduct showed TICT phenomenon and behaved like molecular rotor. It further displayed aggregation behavior at higher concentration and excitation wavelength dependent multicolor emission properties. Most interestingly, the spontaneous resolution of chiral S-isomer of the 1-SH adduct occurred during crystallization. The cell imaging study revealed the staining of the cell and multicolor emission in the presence of H2S.

Ruthenium(II) Complex-Based Luminescent Bifunctional Probe for Ag+ and Phosphate Ions: Ag+-Assisted Detection and Imaging of rRNA.

A new bis-heteroleptic Ru(II) complex (1) of benzimidazole-substituted 1,2,3-triazole pyridine ligand has been designed and constructed for the photoluminescent detection of cationic and anionic analytes, Ag+ and phosphate ions. Compound, 1[PF6]2 was fully characterized by various spectroscopic techniques and the solid-state structure was determined via single-crystal X-ray diffraction. The cation and anion sensing properties in 50% aqueous buffer (pH 9.2) and pure acetonitrile were carefully examined in photoluminescence (PL) spectroscopy. The 1[PF6]2 was found to be highly selective to pyrophosphate; PPi/HP2O73- and H2PO4- ions in CH3CN. It showed ∼10-fold PL intensity enhancement at 583 nm in the presence of only 1 and 2 equiv of PPi and H2PO4- ions, respectively. The PL titrations of 1[PF6]2 with PPi and H2PO4- in CH3CN furnished the association constant (Ka = 3.3 × 103 M-1 and 6.8 × 103 M-1) and the detection limit was as low as 5.73 and 5.19 ppb, respectively. The 1[PF6]2 also selectively detected Ag+ over other competitive cations through the luminescence light up in 50% aqueous buffer (pH 9.2) media. The PL titration of 1[PF6]2 with Ag+ showed ∼8-fold luminescence enhancement at 591 nm and yielded association constant, Ka = 3.5 × 104 M-1 and the detection limit was determined to be 5.05 ppb. A new cation sensing mechanism has been established where the Ag+ ion is detected in photoluminescence spectroscopy through the unique cyclometalated Ag+-triazolide complex formation. The high selectivity of 1[PF6]2 for phosphates and Ag+ was established by PL in the presence of various competing ions. Finally, for biological application, the cytotoxicity study was performed. The probe showed low cytotoxicity and was suitable for intracellular Ag+ imaging. The cell imaging and in vitro photoluminescence study revealed that the probe stained the cell nucleoli and specifically bind with ribosomal RNA (rRNA) and, therefore, it can also serve as a luminescent probe for rRNA in the presence of Ag+.

Unleashing the binding interaction of chrysin-Cu(II) complex with the biomacromolecular targets: further studies of cell cytotoxicity and radical scavenging properties.

Flavonoids are significant dietary components and have ability to coordinate with metal ions to produce novel drug discovery leads that are superior to those of the parent flavonoids. Here, in this report, we have synthesized chrysin-Cu(II) complex (as per reported article) and characterized it further with different analytical techniques. The synthesized complex was evaluated for radical scavenging and cell cytotoxicity studies where it exhibited enhanced activity as compared to bare chrysin. The interaction studies of the complex with ct-DNA (Kb ⁓ 105 M-1), human serum albumin (HSA) and ovalbumin (Kb ⁓ 104 M-1) were evaluated using multi-spectroscopic and molecular docking studies. Groove binding mode with ct-DNA was observed as confirmed from competitive displacement studies, viscosity measurement, melting temperature estimation and docking analyses. The complex exhibited comparatively higher affinity towards ct-DNA which indicated it efficient transportation by the carrier proteins and controlled release in the target DNA.Communicated by Ramaswamy H. Sarma.

Bio-Nano Synergy in Therapeutic Applications: Drug-Graphene Oxide Nanocomposites for Modulated Acetylcholinesterase Inhibition and Radical Scavenging.

The current study explores the synergistic application of biophysical chemistry and nanotechnology in therapeutic treatments, focusing specifically on the development of advanced biomaterials to repurpose FDA-approved Alzheimer's disease (AD) drugs as potent antioxidants. By integration of AD drugs into graphene oxide (GO) nanocomposites, an attempt to enhance the acetylcholinesterase (AChE) inhibition and increase radical scavenging activity is proposed. This bionano synergy is designed to leverage the unique properties of both the nanomaterial surface and the bioactive compounds, improving treatment effectiveness. The nanocomposites also promise targeted drug delivery, as GO can traverse the blood-brain barrier to inhibit AChE more effectively in AD patients. Furthermore, the drug-GO nanocomposite exhibits enhanced radical scavenging capabilities, offering additional therapeutic benefits. This study also elucidates a molecular level understanding on how the properties of the drugs are modified when integrated into nanocomposites with GO, enabling the development of more effective materials. The interdisciplinary approach presented in this study exploits the potential of nanotechnology to enhance drug delivery systems and achieve superior therapeutic outcomes through bionano synergy.

A chitosan-α-naphthaldehyde hydrogel film containing pineapple leaf fibers for wound dressing applications.

In recent decades, polysaccharide-based hydrogels have gained significant attention due to their natural biocompatibility, biodegradability, and non-toxicity. The potential for using polysaccharides to synthesize hydrogels is due to their ability to support cell proliferation, which is important for practical applications, particularly in the biomedical field. In this study, we have synthesized a chitosan-α-naphthal hydrogel film using a cost-effective one-step synthesis approach. The prepared hydrogel film exhibited high encapsulation efficiency for antibacterial drugs such as ciprofloxacin and lomefloxacin, with the ability to release the antibiotics in a controlled manner over an extended period and prevent long-term bacterial infections. Moreover, the Korsmeyer and Peppas power law, based on Fickian diffusion, was employed to model the entire complex drug release process and predict the drug release behavior. The hydrogel film also shows pH-induced swelling ability due to the presence of an imine bond in the hydrogel network, which is degradable at acidic pH. The incorporated therapeutic agents having antibacterial activity were effective against Gram-negative (Escherichia coli DH5α) and Gram-positive (Staphylococcus aureus subsp. aureus) bacterial strains. A wound dressing material should possess mechanical strength, but the prepared hydrogel film has low mechanical strength. To increase the mechanical strength, we have infused pineapple leaf fibers (PLFs) in the film network, resulting in a mechanical strength of 1.12 ± 0.89 MPa. In addition to its mechanical strength, significant cell viability against human embryonic kidney (HEK-293) cells was observed from in vitro cell culture experiments for this PLF-hydrogel film. As a result, the prepared therapeutic agent-loaded hydrogel film under study meets the requirements to be considered for use as a wound dressing material.

Human serum albumin directed formation of cadmium telluride quantum dots: Applications in biosensing, anti-bacterial activities and cell cytotoxicity measurements.

Although cadmium-based quantum dots (QDs) are highly promising candidates for numerous biological applications, their intrinsic toxicity limits their pertinency in living systems. Surface functionalization of QDs with appropriate molecules could reduce the toxicity level. Herein, we have synthesized the smaller sized (1-5 nm) aqueous-compatible biogenic CdTe QDs using human serum albumin (HSA) as a surface passivating agent via a greener approach. HSA-functionalized CdTe QDs have been explored in multiple in vitro sensing and biological applications, namely, (1) sensing, (2) anti-bacterial and (3) anti-cancer properties. Using CdTe-HSA QDs as a fluorescence probe, a simple fluorometric method has been developed for highly sensitive and selective detection of blood marker bilirubin and hazardous Hg2+ ion with a limit of detection (LOD) of 3.38 and 0.53 ng/mL, respectively. CdTe-HSA QDs also acts as a sensor for standard antibiotics, tetracycline and rifampicin with LOD values of 41.34 and 114.99 ng/mL, respectively. Nano-sized biogenic CdTe-HSA QDs have shown promising anti-bacterial activities against both gram-negative, E. coli and gram-positive, E. faecalis strains confirming more effectiveness against E. faecalis strains. The treatment of human cervical cancer cell lines (HeLa cells) with the synthesized QDs reflected the proficient cytotoxic properties of QDs.

Elucidation of inhibitory effects of bioactive anthraquinones towards formation of DNA advanced glycation end products (DNA-AGEs).

DNA is essential in biological processes as it directs transcription and translation assisting in RNA and protein synthesis. Extended periods of elevated blood glucose levels cause non-enzymatic DNA glycation, which results in the formation of DNA-AGEs and the production of free radicals, causing structural perturbation of DNA. In this work, we have investigated the glycation of calf thymus (ct-DNA) DNA and examined its inhibition by two anthraquinone derivatives, purpurin and aloin. Ribose sugar served as the glycating agent inducing non-enzymatic glycation of DNA and subsequent DNA-AGEs formation. UV-vis and fluorescence spectroscopic methods were utilized to characterize DNA-AGE formation in vitro. Circular dichroism (CD) spectroscopy was used to observe the structural disruption of DNA caused by glycation. The changes in AGEs fluorescence intensity and melting temperature (Tm) were measured to assess the inhibition of glycation process by aloin and purpurin. These derivatives demonstrated inhibitory effects via binding to glycating sites of ct-DNA or by scavenging free radicals generated during glycation. The current study elucidates the inhibitory actions of aloin and purpurin on DNA glycation, suggesting their possible applications in mitigating the adverse consequences linked to increased ribose concentrations.

Mutations in EFHC1 cause juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.

An aggregation induced emission active bis-heteroleptic ruthenium(II) complex for luminescence light-up detection of pyrophosphate ions.

A red emissive ruthenium(II) complex 1[PF6]2 of an amino ethanol substituted 1,10-phenanthroline-based ligand (L1) has been developed and characterized by spectroscopic analysis and single-crystal X-ray diffraction. Complex 1 shows an aggregation-induced emission (AIE) enhancement and forms nano-aggregates in the poor solvent water and highly dense polyethylene glycol (PEG) media. The possible reason behind the AIE properties may be the rigidity gained through weak supramolecular interactions between neighbouring phenanthroline ligands and PF6- counterions. The AIE properties were supported by UV-vis and photoluminescence (PL) spectroscopy and dynamic light scattering (DLS) studies to substantiate the formation of nano-aggregates and to understand the morphology of the aggregated particles, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies were performed. Compound 1[PF6]2 was highly selective towards pyrophosphate ions (PPi) over other phosphates such as ATP, ADP, AMP and H2PO4- ions and other competitive anions in the PL spectroscopic channel in acetonitrile. The PL titrations of 1[PF6]2 with PPi in CH3CN furnished the association constant Ka = 1.08 × 104 M-1 and the detection limit was calculated as low as 1.54 µM. The PPi detection has been established through the unique H-bonding interaction, supported by 1H NMR titration. Finally, the cytotoxicity study and bioimaging were carried out for biological application. The complex shows very low cytotoxicity and good biocompatibility and is suitable for intracellular PPi imaging.

Complexation of turmeric and curcumin mediated silver nanoparticles with human serum albumin: Further investigation into the protein-corona formation, anti-bacterial effects and cell cytotoxicity studies.

Biosynthesized noble metal nanoparticles have been of recent interest due to their broad implications in the future biomedicinal field. We have synthesized silver nanoparticle using turmeric-extract and its major component curcumin as reducing and stabilizing agents. Further, we have investigated the protein-NPs interaction focusing the inspection of the role of biosynthesized AgNPs on any conformational changes of the protein, binding and thermodynamic parameters using spectroscopic techniques. Fluorescence quenching studies revealed that both CUR-AgNPs and TUR-AgNPs have moderate binding affinities (∼104 M-1) towards human serum albumin (HSA) and static quenching mechanism was involved in the binding. Estimated thermodynamic parameters indicate the involvement of hydrophobic forces in the binding processes. The surface charge potential of the biosynthesized AgNPs became more negative upon complexation with HSA as observed from Zeta potential measurements. Antibacterial efficacies of the biosynthesized AgNPs were evaluated against Escherichia coli (gram-negative) and Enterococcus faecalis (gram-positive) bacterial strains. The AgNPs were found to destroy the cancer (HeLa) cell lines in vitro. The overall findings of our study successfully outline the detailed insight of the protein corona formation by biocompatible AgNPs and their biological applications concerning the future scope in the biomedicinal field.

Formation of ZnS quantum dots using green tea extract: applications to protein binding, bio-sensing, anti-bacterial and cell cytotoxicity studies.

Biocompatible quantum dots (QDs) have attracted a lot of attention due to their potential biological applications (drug delivery, sensing and diagnosis). Here, we have synthesized 2-4 nm sized biocompatible zinc sulphide (ZnS) QDs using a plant leaf extract as an immobilizing and stabilizing agent via a green route. We have investigated the biological effects of ZnS QDs in a variety of applications, including (1) anti-bacterial activity, (2) cell cytotoxicity, (3) bio-sensing and (4) protein binding. Studies on the anti-bacterial activity of the as-synthesized ZnS QDs against E. coli and E. faecalis inhibited bacterial growth effectively and showed a cytotoxic effect on the HeLa cell line. The biosynthesized ZnS QDs act as a fluorescence probe to detect bilirubin and rifampicin (RFP) with a wide linear range, high sensitivity, good selectivity, and a low limit of detection (LOD), with LOD values of 22.12 ± 0.25 ng mL-1 and 122.37 ± 0.42 ng mL-1, respectively. In a biological matrix, the QDs can form a complex with biomacromolecules; therefore, we studied the interaction between a carrier protein (HSA) and the as-synthesized ZnS QDs. The surface functionalized and nano-sized ZnS-GT QDs were observed to form complexes with the human serum albumin (HSA) protein and quenched the intrinsic fluorescence of HSA through static and dynamic quenching modes. The binding affinity was observed to be of the order of 105 M-1 for the HSA-ZnS-GT QD interactions, which can be considered as a reversible mode of binding. The effect of the ZnS QDs on other ligands and protein interactions was also studied. Enhanced binding affinities for HSA-quercetin ((5.994 ± 0.139) × 105 M-1) and HSA-luteolin ((3.068 ± 0.127) × 105 M-1) interactions were also observed in the presence of ZnS-GT QDs.

Cyclometalated iridium(III) complex of a 1,2,3-triazole-based ligand for highly selective sensing of pyrophosphate ion.

A new cyclometalated Ir(III) complex of a methylene-bridged benzimidazole-substituted 1,2,3-triazole methanol ligand has been synthesized for the photoluminescent detection of pyrophosphate (H2P2O72-) anions. The solution structure of 1[PF6] was fully characterized by 1D (1H, 13C) and 2D (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC) NMR spectroscopy, and ESI-HRMS. The 1[PF6] acted as a highly selective luminescent sensor for H2P2O72- in CH3CN over other competitive ions, including H2PO4-, ATP, ADP and AMP. The PL titration of 1[PF6] with H2P2O72- in CH3CN furnished the association constant Ka = 8.6 × 107 M-1 and a low detection limit of ∼127 nM. The structure of the analyte interacting ligand renders the Ir(III) complex-based probe highly selective for H2P2O72- ions. The PL enhancement with H2P2O72- is due to the hydrogen bonding interaction of H2P2O72- with the triazole C-H, imidazole N-H, methylene hydrogen and hydroxyl groups of the ligand that has been supported by 1H NMR titration. Further, the PL enhancement of 1·H2P2O72- adducts was supported by triplet-state TDDFT calculations. In 1·H2P2O72-, the 3MLCT-3MC energy gap is increased, and the 1·H2P2O72- emits efficiently from the 3MLCT and 3ILCT excited states. Finally, a cytotoxicity study and live-cell imaging were performed. The probe showed low cytotoxicity against HeLa cells and was suitable for intracellular pyrophosphate imaging.

Biocompatible silver nanoparticles: An investigation into their protein binding efficacies, anti-bacterial effects and cell cytotoxicity studies.

Green synthesis of silver nanoparticles (AgNPs) has garnered tremendous interest as conventional methods include the use and production of toxic chemicals, products, by-products and reagents. In this regard, the synthesis of AgNPs using green tea (GT) extract and two of its components, (-)-epigallocatechin gallate (EGCG) and (+)-catechin (Ct) as capping/stabilizing agents, is reported. The synthesized AgNPs showed antibacterial activity against the bacterial strains Staphylococcus aureus and Escherichia coli, along with anticancer activity against HeLa cells. After administering nanoparticles to the body, they come in contact with proteins and results in the formation of a protein corona; hence we studied the interactions of these biocompatible AgNPs with hen egg white lysozyme (HEWL) as a carrier protein. Static quenching mechanism was accountable for the quenching of HEWL fluorescence by the AgNPs. The binding constant (K b) was found to be higher for EGCG-AgNPs ((2.309 ± 0.018) × 104 M-1) than for GT-AgNPs and Ct-AgNPs towards HEWL. EGCG-AgNPs increased the polarity near the binding site while Ct-AgNPs caused the opposite effect, but GT-AgNPs had no such observable effects. Circular dichroism studies indicated that the AgNPs had no such appreciable impact on the secondary structure of HEWL. The key findings of this research included the synthesis of AgNPs using GT extract and its constituent polyphenols, and showed significant antibacterial, anticancer and protein-binding properties. The -OH groups of the polyphenols drive the in situ capping/stabilization of the AgNPs during synthesis, which might offer new opportunities having implications for nanomedicine and nanodiagnostics.

Sulfonylurea Class of Antidiabetic Drugs Inhibit Acetylcholinesterase Activity: Unexplored Auxiliary Pharmacological Benefit toward Alzheimer's Disease.

Contemporary literature documents extensive research on common causative mechanisms, pathogenic pathways and dual effective remedies for Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM). Tolbutamide (TBM), chlorpropamide (CPM), and glyburide (GLY) are three sulfonylurea antidiabetic drugs of different generations. All these drugs were found to exhibit moderate to strong inhibitory efficiency on the neurotransmitter degrading enzyme acetylcholinesterase (AChE) with GLY (IC50 = 0.74 ± 0.02 µM) being the most potent, followed by CPM (IC50 = 5.72 ± 0.24 µM) and TBM (IC50 = 28.9 ± 1.60 µM). Notably, the inhibition efficiency of GLY is even comparable with the FDA approved AD drug, donepezil (DON). The larger size of GLY spans almost the full gorge of AChE ranging from catalytic active site (CAS) to the peripheral active site (PAS) with relatively strong binding affinity (6.0 × 105 M-1) and acts as a competitive inhibitor for AChE. On the other hand, while they show relatively weak binding ((2-6) × 104 M-1), both CPM and TBM act as noncompetitive binders. While these two drugs can bind to PAS, MD simulation results predict an alternative noncompetitive inhibition mechanism for CPM. These results open the possibility of repurposing the antidiabetic drugs, particularly GLY, in the treatment of AD. The consequential side effect of excess acetylcholine production, due to the administration of these drugs to AD-unaffected patients, can be rectified by using colloidal gold and silver nanofluids as potential AChE activity boosters.

Novel coumarin derivatives as potent acetylcholinesterase inhibitors: insight into efficacy, mode and site of inhibition.

The inhibitory efficacy of two substituted coumarin derivatives on the activity of neurodegenerative enzyme acetylcholinesterase (AChE) was assessed in aqueous buffer as well as in the presence of human serum albumin (HSA) and compared against standard cholinergic AD drug, Donepezil (DON). The experimental data revealed the inhibition to be of non-competitive type with both the systems showing substantial inhibitory activity on AChE. In fact, one of the tested compounds Chromenyl Coumarate (CC) was found to be better inhibitor (IC50 = 48.49 ± 5.6 nM) than the reference drug DON (IC50 = 74.13 ± 8.3 nM), unequivocally amplifying its importance. The structure of the compound was found to play a vital role in the inhibitory efficiency, validating previous Structure Activity Relationship (SAR) reviews for coumarin. The mechanism of inhibition remained impervious when the experimental medium was switched from aqueous buffer to HSA, albeit noticeable change in the inhibition potency of the compound 3, 3'- Methylene-bis (4-hydroxy coumarin) (MHC) (38%) and CC (35%). Both the coumarin derivatives were observed to bind to the peripheral anionic site (PAS) of AChE and also found to displace the fluorescence marker thioflavinT (ThT) from AChE binding pocket. All experimental observations were seconded by molecular docking and MD simulation results. The inferences drawn in this study form a foundation for further investigation on these compounds; magnifying the probability of their usage as AD drugs and re-emphasizes the significance of drug delivery media while considering the inhibition potencies of targeted drugs.

A cationic organoiridium(iii) complex-based AIEgen for selective light-up detection of rRNA and nucleolar staining.

A green emissive cationic organoiridium(iii) complex, 2[PF6], with a benzimidazole-substituted 1,2,3-triazole-pyridine (BiPT) ligand has been synthesized for target-specific cellular imaging and selective detection of ribosomal RNA (rRNA) over other competitive biomolecules in aqueous buffer solution at physiological pH. Complex 2 shows aggregation-induced emission enhancement (AIEE) properties and forms nano-aggregates in the presence of poor solvents. DFT and TD-DFT-based quantum mechanical calculations were performed to substantiate some photophysical features and to establish the intermolecular π-π interactions which detain the vibrational as well as rotational motions to form the aggregates, resulting in enhanced photoluminescence (PL). To corroborate the formation of nano-aggregates and to understand the morphology of the aggregated particles, dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) measurements were performed. 2[PF6] showed low cytotoxicity and good biocompatibility and was successfully employed in organelle-specific intracellular imaging. The in vivo and in vitro photoluminescence investigations affirmed that the probe stains cell nucleoli and selectively binds rRNA. It is assumed that the supramolecular π-π interactions between the benzimidazole of the BiPT ligand and the secondary structures of rRNA may facilitate aggregation and enable PL enhancement.

Aggregation-Induced Emission-Active Ruthenium(II) Complex of 4,7-Dichloro Phenanthroline for Selective Luminescent Detection and Ribosomal RNA Imaging.

The development of red emissive aggregation-induced emission (AIE) active probes for organelle-specific imaging is of great importance. Construction of metal complex-based AIE-active materials with metal-to-ligand charge transfer (MLCT), ligand-to-metal charge transfer (LMCT) emission together with the ligand-centered and intraligand (LC/ILCT) emission is a challenging task. We developed a red emissive ruthenium(II) complex, 1[PF6]2, and its perchlorate analogues of the 4,7-dichloro phenanthroline ligand. 1[PF6]2 has been characterized by spectroscopic and single-crystal X-ray diffraction. Complex 1 showed AIE enhancement in water, highly dense polyethylene glycol media, and also in the solid state. The possible reason behind the AIE property may be the weak supramolecular π···π, C-H···π, and C-Cl···H interactions between neighboring phen ligands as well as C-Cl···O halogen bonding (XB). The crystal structures of the two perchlorate analogues revealed C-Cl···O distances shorter than the sum of the van der Waals radii, which confirmed the XB interaction. The AIE property was supported by scanning electron microscopy, transmission electron microscopy, dynamic light scattering, and atomic force microscopy studies. Most importantly, the probe was found to be low cytotoxicity and to efficiently permeate the cell membrane. The cell-imaging experiments revealed rapid staining of the nucleolus in HeLa cells via the interaction with nucleolar ribosomal ribonucleic acid (rRNA). It is expected that the supramolecular interactions as well as C-Cl···O XB interaction with rRNA is the origin of aggregation and possible photoluminescence enhancement. To the best of our knowledge, this is the first report of red emissive ruthenium(II) complex-based probes with AIE characteristics for selective rRNA detection and nucleolar imaging.

Correlation of cholinergic drug induced quenching of acetylcholinesterase bound thioflavin-T fluorescence with their inhibition activity.

The development of new acetylcholinesterase inhibitors (AChEIs) and subsequent assay of their inhibition efficiency is considered to be a key step for AD treatment. The fluorescence intensity of thioflavin-T (ThT) bound in the active site of acetylcholinesterase (AChE) quenches substantially in presence of standard AChEI drugs due to the dynamic replacement of the fluorophore from the AChE active site as confirmed from steady state emission as well as time-resolved fluorescence anisotropy measurement and molecular dynamics simulation in conjunction with docking calculation. The parametrized % quenching data for individual system shows excellent correlation with enzyme inhibition activity measured independently by standard Ellman AChE assay method in a high throughput plate reader system. The results are encouraging towards design of a fluorescence intensity based AChE inhibition assay method and may provide a better toolset to rapidly evaluate as well as develop newer AChE-inhibitors for AD treatment.