Applications of Functionalized Carbon-Based Quantum Dots in Fluorescence Sensing of Iron(III).

Iron, an essential trace element exhibits detrimental effects on human health when present at higher or lower concentration than the required. Therefore, there is a pressing demand for sensitive and selective detection of Fe3+ in water, food etc. Unfortunately, in several instances, the traditional approaches suffer from a number of shortcomings like complicated procedures, limited sensitivity, poor selectivity and more expensive and time consuming. The scope of optical tuning and excellent photophysical properties of carbon- based nanomaterials like carbon dots (C-dots) and graphene dots (g-dots) have made them promising optical sensors of metal ions. Moreover, high surface area, superior stability of such materials contributes towards the fruitful development of sensors. The present review offered critical information on the fabrication and fluorimetric applications of these functional nanomaterials for sensitive and selective detection of Fe3+. An in-depth discussion on fluorescent C-dots made from naturally occurring materials and chemical techniques were presented. Effect of doping in C-dots was also highlighted in terms of improved fluorescence response and selectivity. In a similar approach g-dots were also discussed. Many of these sensors exhibited great selectivity, superior sensitivity, high quantum yield, robust chemical and photochemical stability and real-time applicability. Further improvement in these factors can be targeted to develop new sensors.

Method for highly selective, ultrasensitive fluorimetric detection of Cu2+ and Al3+ by Schiff bases containing o-phenylenediamine and o-aminophenol.

Schiff base probes (1 and 2) made from o-phenylenediamine and o-aminophenol were appeared as highly selective fluorimetric chemosensor of Cu2+ and Al3+ ions respectively. Strong fluorescence emission of probe 1 at 415 nm (excitation at 350 nm) was instantly turned off on addition of Cu2+. Very weak fluorescence of probe 2 at 506 nm (excitation at 400 nm) was immediately turned on specifically by Al3+. Job's plot and ESI-MS results suggested 1:1 molar stoichiometric ratio of metal ion and probe in their respective complexes. Probe 1 and 2 had demonstrated very low detection limit (9.9 and 2.5 nM respectively). Binding of Cu2+ with probe 1 was found chemically reversible on addition of EDTA, while complexation between Al3+ and probe 2 was not reversible. On the basis of density functional theory (DFT) and spectroscopic results, probable mode of sensing of the metal ions by the probes were proposed. Quenching of the fluorescence of probe 1 by Cu2+ was attributed to the extensive transfer of charge from the probe molecule to paramagnetic copper ion. Whereas, in the Al3+-complex of probe 2, photo-induced electron transfer (PET) process from the imine nitrogen to salicylaldehyde moiety was restricted and thereby the weak emission intensity of probe 2 was enhanced significantly. Effective pH range of sensing the metal ions by probe 1 and 2 were 4 to 8 and 6 to 10 respectively. Probe 1 was also applied in the design of a logic gate for Cu2+ detection. Moreover, probe 1 and 2 was also used in water sample analysis for quantitative estimation of Cu2+ and Al3+ respectively.

Cathodoluminescence and optical absorption spectroscopy of plasmonic modes in chromium micro-rods.

Manipulating light at the sub-wavelength level is a crucial feature of surface plasmon resonance (SPR) properties for a wide range of nanostructures. Noble metals like Au and Ag are most commonly used as SPR materials. Significant attention is being devoted to identify and develop non-noble metal plasmonic materials whose optical properties can be reconfigured for plasmonic response by structural phase changes. Chromium (Cr) which supports plasmon resonance, is a transition metal with shiny finished, highly non-corrosive, and bio-compatible alloys, making it an alternative plasmonic material. We have synthesized Cr micro-rods from a bi-layer of Cr/Au thin films, which evolves from face centered cubic to hexagonal close packed (HCP) phase by thermal activation in a forming gas ambient. We employed optical absorption spectroscopy and cathodoluminescence (CL) imaging spectroscopy to observe the plasmonic modes from the Cr micro-rod. The origin of three emission bands that spread over the UV-Vis-IR energy range is established theoretically by considering the critical points of the second-order derivative of the macroscopic dielectric function obtained from density functional theory (DFT) matches with interband/intraband transition of electrons observed in density of states versus energy graph. The experimentally observed CL emission peaks closely match thes-dandd-dband transition obtained from DFT calculations. Our findings on plasmonic modes in Cr(HCP) phase can expand the range of plasmonic material beyond noble metal with tunable plasmonic emissions for plasmonic-based optical technology.

Exploring naphthyl derivatives as SARS-CoV papain-like protease (PLpro) inhibitors and its implications in COVID-19 drug discovery.

Novel coronavirus disease 2019 (COVID-19) emerges as a serious threat to public health globally. The rapid spreading of COVID-19, caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), proclaimed the multitude of applied research needed not only to save the human health but also for the environmental safety. As per the recent World Health Organization reports, the novel corona virus may never be wiped out completely from the world. In this connection, the inhibitors already designed against different targets of previous human coronavirus (HCoV) infections will be a great starting point for further optimization. Pinpointing biochemical events censorious to the HCoV lifecycle has provided two proteases: a papain-like protease (PLpro) and a 3C-like protease (3CLpro) enzyme essential for viral replication. In this study, naphthyl derivatives inhibiting PLpro enzyme were subjected to robust molecular modelling approaches to understand different structural fingerprints important for the inhibition. Here, we cover two main aspects such as (a) exploration of naphthyl derivatives by classification QSAR analyses to find important fingerprints that module the SARS-CoV PLpro inhibition and (b) implications of naphthyl derivatives against SARS-CoV-2 PLpro enzyme through detailed ligand-receptor interaction analysis. The modelling insights will help in the speedy design of potent broad spectrum PLpro inhibitors against infectious SARS-CoV and SARS-CoV-2 in the future.

Multispectroscopic studies on the molecular interactions between bovine γ-globulin and borohydride-capped silver nanoparticles.

Interactions between bovine γ-globulin (BGG) and borohydride-capped silver nanoparticles (BAgNPs) were studied using dynamic light scattering (DLS) and spectroscopic techniques such as UV-vis spectroscopy, fluorescence, and circular dichroism. The results were compared with earlier reported interactions between γ-globulin and citrate-coated AgNPs (CAgNPs). BAgNPs were synthesized and characterized. Irrespective of the coating on AgNPs, nanoparticles had formed ground-state complexes with the protein. CAgNPs, as well as BAgNPs had caused static quenching of tryptophan (Trp) fluorescence of the protein. The change in the capping agent from citrate to borohydride weakened the binding of nanoparticles with the protein. But the same change in capping agent had increased the fluorescence quenching efficiency of AgNPs. Hydrogen bonding and van der Waals interactions were involved in BGG-BAgNPs complex similar to the CAgNPs complex with γ-globulin. Polarity of the Trp microenvironment in BGG was not altered using BAgNPs as opposed to CAgNPs, as supported using synchronous and three-dimensional fluorescence. Resonance light scattering experiments also suggested nano-bio conjugation. Far-UV and near-UV circular dichroism (CD) spectra respectively pointed towards changes in the secondary and tertiary structure of BGG by BAgNPs, which was not observed for CAgNPs.

Fabrication of N-Doped Reduced Graphite Oxide/MnCo2O4 Nanocomposites for Enhanced Microwave Absorption Performance.

The present work reports on the fabrication of a lightweight microwave absorber comprising MnCo2O4 prepared from the urea complex of manganese (Mn)/cobalt (Co) and nitrogen-doped reduced graphite oxide (NRGO) by facile hydrothermal method followed by annealing process and characterized. The phase analysis, compositional, morphological, magnetic, and conductivity measurements indicated dispersion of paramagnetic MnCo2O4 spherical particles on the surface of NRGO. Our findings also showed that Mn, Co-urea complex, and GO in the weight ratio of 1:4 (NGMC3) exhibited maximum shielding efficiency in the range of 55-38 dB with absorption as an overall dominant shielding mechanism. The reflection loss of NGMC3 was found to be in the range of -90 to -77 dB with minima at -103 dB (at 2.9 GHz). Such outstanding electromagnetic wave absorption performance of NRGO/MnCo2O4 nanocomposite compared to several other metal cobaltates could be attributed to the formation of percolated network assisted electronic polarization, interfacial polarization and associated relaxation losses, conductance loss, dipole polarization and corresponding relaxation loss, impedance matching, and magnetic resonance to some extent.

Functionalized Graphene/Nickel/Polyaniline Ternary Nanocomposites: Fabrication and Application as Electromagnetic Wave Absorbers.

The evolution of high electromagnetic absorption materials is essential in the fast growing electronic industry in overcoming electromagnetic pollution. In view of this, a series of Ni nanoparticle-decorated functionalized graphene sheets (FG/Ni) are synthesized by a solvothermal method using different ratios of FG/Ni precursors. Subsequently, FG/Ni is subjected to in situ polymerization of aniline to form FG/Ni/PANI ternary composites and characterized. The total electromagnetic interference shielding efficiency (SET) measurements on FG/Ni/PANI with an optimized FG/Ni ratio (50 mg:600 mg NiCl2·6H2O) exhibit enhanced performance, i.e., ∼47-65 dB (2-3.8 GHz) and ∼65-45 dB (3.8-8 GHz), following absorption as the dominant mechanism due to the matching of dielectric loss and magnetic loss. It is anticipated that such excellent performance of robust FG/Ni/PANI ternary composites at a very low thickness (0.5 mm) has great potential in the application of microwave-absorbing materials.

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brutally perils physical and mental health worldwide. Unavailability of effective anti-viral drug rendering global threat of COVID-19 caused by SARS-CoV-2. In this scenario, viral protease enzymes are crucial targets for drug discovery. This extensive study meticulously focused on two viral proteases such as main protease (Mpro) and papain-like protease (PLpro), those are essential for viral replication. This review provides a detail overview of the targets (Mpro and PLpro) from a structural and medicinal chemistry point of view, together with recently reported protease inhibitors. An insight into the challenges in the development of effective as well as drug like protease inhibitors is discussed. Peptidomimetic and/or covalent coronavirus protease inhibitors possessed potent and selective active site inhibition but compromised in pharmacokinetic parameters to be a drug/drug like molecule. Lead optimization of non-peptidomimetic and/or low molecular weight compounds may be a better option for oral delivery. A masterly combination of adequate pharmacokinetic properties with coronavirus protease activity as well as selectivity will provide potential drug candidates in future. This study is a part of our endeavors which surely dictates medicinal chemistry efforts to discover effective anti-viral agent for this devastating disease.

Unmasking of crucial structural fragments for coronavirus protease inhibitors and its implications in COVID-19 drug discovery.

Fragment based drug discovery (FBDD) by the aid of different modelling techniques have been emerged as a key drug discovery tool in the area of pharmaceutical science and technology. The merits of employing these methods, in place of other conventional molecular modelling techniques, endorsed clear detection of the possible structural fragments present in diverse set of investigated compounds and can create alternate possibilities of lead optimization in drug discovery. In this work, two fragment identification tools namely SARpy and Laplacian-corrected Bayesian analysis were used for previous SARS-CoV PLpro and 3CLpro inhibitors. A robust and predictive SARpy based fragments identification was performed which have been validated further by Laplacian-corrected Bayesian model. These comprehensive approaches have advantages since fragments are straight forward to interpret. Moreover, distinguishing the key molecular features (with respect to ECFP_6 fingerprint) revealed good or bad influences for the SARS-CoV protease inhibitory activities. Furthermore, the identified fragments could be implemented in the medicinal chemistry endeavors of COVID-19 drug discovery.

Chemical-informatics approach to COVID-19 drug discovery: Exploration of important fragments and data mining based prediction of some hits from natural origins as main protease (Mpro) inhibitors.

As the world struggles against current global pandemic of novel coronavirus disease (COVID-19), it is challenging to trigger drug discovery efforts to search broad-spectrum antiviral agents. Thus, there is a need of strong and sustainable global collaborative works especially in terms of new and existing data analysis and sharing which will join the dots of knowledge gap. Our present chemical-informatics based data analysis approach is an attempt of application of previous activity data of SARS-CoV main protease (Mpro) inhibitors to accelerate the search of present SARS-CoV-2 Mpro inhibitors. The study design was composed of three major aspects: (1) classification QSAR based data mining of diverse SARS-CoV Mpro inhibitors, (2) identification of favourable and/or unfavourable molecular features/fingerprints/substructures regulating the Mpro inhibitory properties, (3) data mining based prediction to validate recently reported virtual hits from natural origin against SARS-CoV-2 Mpro enzyme. Our Structural and physico-chemical interpretation (SPCI) analysis suggested that heterocyclic nucleus like diazole, furan and pyridine have clear positive contribution while, thiophen, thiazole and pyrimidine may exhibit negative contribution to the SARS-CoV Mpro inhibition. Several Monte Carlo optimization based QSAR models were developed and the best model was used for screening of some natural product hits from recent publications. The resulted active molecules were analysed further from the aspects of fragment analysis. This approach set a stage for fragment exploration and QSAR based screening of active molecules against putative SARS-CoV-2 Mpro enzyme. We believe the future in vitro and in vivo studies would provide more perspectives for anti-SARS-CoV-2 agents.

Inherent Impurities in Graphene/Polylactic Acid Filament Strongly Influence on the Capacitive Performance of 3D-Printed Electrode.

Additive manufacturing or 3D-printing have become promising fabrication techniques in the field of electrochemical energy storage applications such as supercapacitors, and batteries. Of late, a commercially available graphene/polylactic acid (PLA) filament has been commonly used for Fused Deposition Modeling (FDM) 3D-printing in the fabrication of electrodes for supercapacitors and Li-ion batteries. This graphene/PLA filament contains metal-based impurities such as titanium oxide and iron oxide. In this study, we show a strong influence of inherent impurities in the graphene/PLA filament for supercapacitor applications. A 3D-printed electrode is prepared and subsequently thermally activated for electrochemical measurement. A deep insight has been taken to look into the pseudocapacitive contribution from the metal-based impurities which significantly enhanced the overall capacitance of the 3D-printed graphene/PLA electrode. A systematic approach has been shown to remove the impurities from the printed electrodes. This has a broad implication on the interpretation of the capacitance of 3D-printed composites.

Protective role of hesperetin against posttranslational oxidation of tryptophan residue of human γD-crystallin: A molecular level study.

Crystallin proteins undergo various posttranslational modifications with aging of eye lens. Oxidation of tryptophan (Trp) residues of a major γ-crystallin namely human γD-crystallin (HGD) was found to be inhibited by a naturally occurring flavonoid hesperetin at relatively low concentration mostly due to its antioxidant activity. Further the molecular interactions between HGD and hesperetin were elucidated on the basis of the quenching of Trp fluorescence of the protein by the flavonoid. Ground state complexation between HGD and hesperetin caused static quenching of the Trp fluorescence of HGD. Binding and quenching constants were in the order of (103- 104 M-1). Energy transfer from protein to hesperetin was suggested by FRET calculations. Thermodynamic parameters reveal significant hydrophobic association between the protein and hesperetin. Synchronous fluorescence and CD spectroscopic results had ruled out conformational changes in the protein due to binding of hesperetin. Docking studies suggested the proximity of hesperetin with Trp 42, which largely corroborates our experimental findings.

Structure-activity relationship of human carbonic anhydrase-II inhibitors: Detailed insight for future development as anti-glaucoma agents.

Human carbonic anhydrase-II (hCA-II) is the most dominant physiologic isoform amongst the sixteen reported hCA isoforms. Because of its high availability in the different anatomical, and cellular sites of the eye like retina and lens, it plays a more prominent role in the regulation of intraocular pressure than the other twelve catalytically active hCA isoforms. This isoform is also located in the brain, kidney, gastric mucosa, osteoclasts, RBCs, skeletal muscle, testes, pancreas, lungs, etc. Earlier, hCA-II inhibitors were designed based on the sulfonamides e.g. acetazolamide, dichlorphenamide, methazolamide, ethoxzolamide, etc. and they were used systemically in antiglaucoma therapy. Many successful attempts have been made by the researchers in order to design more potent and effective inhibitors by incorporating various moieties in sulphonamides. Some novel scaffolds like chalcones, thiophenes, organotellurium compounds, dithiocarbamate, selenide, and 2-benzylpyrazine, etc. were also designed as hCA-II inhibitors and their inhibitory efficacy was proved in the nanomolar range. In order to obtain relevant information from the insights of their structure-activity relationship, the reported hCA-II inhibitors from the year 1989 to 2019 were critically analysed. It gave a complete insight into the relationship between their structure-activity and hCA-II inhibition. The broad spectrum of our investigation may help researchers to summarize all the crucial structural information required for the development of more potent hCA-II inhibitors for glaucoma.

2-Aryl benzazole derived new class of anti-tubercular compounds: Endowed to eradicate mycobacterium tuberculosis in replicating and non-replicating forms.

The high mortality rate and the increasing prevalence of Mtb resistance are the major concerns for the Tuberculosis (TB) treatment in this century. To counteract the prevalence of Mtb resistance, we have synthesized 2-aryl benzazole based dual targeted molecules. Compound 9m and 9n were found to be equally active against replicating and non-replicating form of Mtb (MIC(MABA) 1.98 and 1.66 µg/ml; MIC(LORA) 2.06 and 1.59 µg/ml respectively). They arrested the cell division (replicating Mtb) by inhibiting the GTPase activity of FtsZ with IC50 values 45 and 64 µM respectively. They were also capable of kill Mtb in non-replicating form by inhibiting the biosynthesis of menaquinone which was substantiated by the MenG inhibition (IC50 = 11.62 and 7.49 µM respectively) followed by the Vit-K2 rescue study and ATP production assay.

Crystallins and Their Complexes.

The crystallins (α, ß and γ), major constituent proteins of eye lens fiber cells play their critical role in maintaining the transparency and refractive index of the lens. Under different stress factors and with aging, ß- and γ-crystallins start to unfold partially leading to their aggregation. Protein aggregation in lens basically enhances light scattering and causes the vision problem, commonly known as cataract. α-crystallin as a molecular chaperone forms complexes with its substrates (ß- and γ-crystallins) to prevent such aggregation. In this chapter, the structural features of ß- and γ-crystallins have been discussed. Detailed structural information linked with the high stability of γC-, γD- and γS-crystallins have been incorporated. The nature of homologous and heterologous interactions among crystallins has been deciphered, which are involved in their molecular association and complex formation.

Identification of structural fingerprints for in vivo toxicity by using Monte Carlo based QSTR modeling of nitroaromatics.

Monte Carlo based method by using either SMILES based or combination of SMILES and Graph-based descriptors is an important strategy to build the QSAR/QSTR model for prediction of different biological endpoints. In this study, Monte Carlo based QSTR approach was applied to the dataset of 90 nitroaromatic compounds related to their in vivo toxicity, represented by 50% lethal dose concentration for rats (LD50). Both classification and regression-based QSTR models were developed to get an idea about different fingerprints for promoters and hinderers of nitroaromatics toxicity. The best classification model was obtained by using SMILES and graph-based (GAO) descriptor with 1ECK connectivity (sensitivity = 0.7143, specificity = 1.0000, accuracy = 0.8889, and MCC = 0.7774). The best regression model calculated by using SMILES and hydrogen-suppressed graph descriptors with 0ECk connectivity (R2 = 0.7386, Q2 = 0.6315, S = 0.467, and MAE = 0.340). Finally, a consensus QSTR model was generated to predict efficiently the toxicity of new compounds. The study highlighted that the comparative QSTR models by using the Monte Carlo method can also be generated and will be a useful tool for structural fingerprint analysis in case of nitroaromatics for preliminary evaluation of its toxicity to mammals.

Nanostructured ZrO2/MWCNT Hybrid Materials: Fabrication, Characterization and Applications in Shielding of Electromagnetic Pollution.

ZrO2/MWCNT nanocomposites have been prepared by simple refluxing method and characterized by X-ray diffraction (XRD). Fourier-transform infrared spectroscopy (FTIR), and Raman analysis suggests chemical interactions present between zirconia and Multiwalled carbon nanotube (MWCNT) in the as prepared nanocomposites. Electromagnetic inteference shielding efficiencies (EMI SE) for the nanocomposites were found to increase with increasing amount of MWCNT loading. Highest EMI SE value of 29.1-30.5 dB was obtained for nanocomposite containing 15 wt% loading of MWCNT in the microwave frequency range of 2-8 GHz. This optimum performance is due to several factors like highest percentage of intermolecular H-bonding, highly defective, interconnected network structure, high conductivity and dielectric permittivities of the nanocomposites.

Inhibition of copper-mediated aggregation of human γD-crystallin by Schiff bases.

Protein aggregation, due to the imbalance in the concentration of Cu2+ and Zn2+ ions is found to be allied with various physiological disorders. Copper is known to promote the oxidative damage of ß/γ-crystallins in aged eye lens and causes their aggregation leading to cataract. Therefore, synthesis of a small-molecule 'chelator' for Cu2+ with complementary antioxidant effect will find potential applications against aggregation of ß/γ-crystallins. In this paper, we have reported the synthesis of different Schiff bases and studied their Cu2+ complexation ability (using UV-Vis, FT-IR and ESI-MS) and antioxidant activity. Further based on their copper complexation efficiency, Schiff bases were used to inhibit Cu2+-mediated aggregation of recombinant human γD-crystallin (HGD) and ß/γ-crystallins (isolated from cataractous human eye lens). Among these synthesized molecules, compound 8 at a concentration of 100 µM had shown ~95% inhibition of copper (100 µM)-induced aggregation. Compound 8 also showed a positive cooperative effect at a concentration of 5-15 µM on the inhibitory activity of human αA-crystallin (HAA) during Cu2+-induced aggregation of HGD. It eventually inhibited the aggregation process by additional ~20%. However, ~50% inhibition of copper-mediated aggregation of ß/γ-crystallins (isolated from cataractous human eye lens) was recorded by compound 8 (100 µM). Although the reductive aminated products of the imines showed better antioxidant activity due to their lower copper complexing ability, they were found to be non-effective against Cu2+-mediated aggregation of HGD.

Quinone-Bodipy H-bonding interaction over π-stacking in toluene.

Quinone type compounds (o-chloranil, p-chloranil and DDQ) demonstrate excellent H-bonding interactions with a meso-phenol Bodipy dye (1) in both ground and excited state in a non-polar toluene medium. The spectroscopic detection of isosbestic absorption occurs with both quinones and fullerenes, but only quinones form isoemissive complexes with dye 1. (1)H NMR study and Monte Carlo global minima searching justified the above mentioned results with efficiency.

Interaction of different prototropic species of an anticancer drug ellipticine with HSA and IgG proteins: multispectroscopic and molecular modeling studies.

Studies on interactions between an anticancer alkaloid, ellipticine, and various carrier proteins in blood serum show tangible results to gain insight into the solubility and transport of the drug under physiological conditions. In this report, we extensively studied the interactions of different prototropic species of ellipticine with two prominent serum proteins namely human serum albumin (HSA) and immunoglobulin G (IgG) in their native and partially unfolded states using steady state and time resolved fluorescence spectroscopy, molecular docking and circular dichroism (CD). Both the fluorescence techniques and molecular modeling studies elucidate that only neutral species of ellipticine binds to HSA in the sudlow site II. Unlike HSA, IgG in the native state mostly binds to cationic species of ellipticine. However, in partially unfolded configuration, IgG binds to the neutral ellipticine molecules. Molecular docking studies indicate the prevalence of electrostatic interactions involving charged residues in the binding process of cationic species of ellipticine with native IgG in its Fab region. In native conformation, the hydrophobic residues of the Fab region are found to be buried completely by the ligand. This implies that the hydrophobic interaction will be favored by unfolding of IgG through which the hydrophobic pocket will be more accessible to neutral species of ellipticine. The circular dichroism measurements reveal that upon interaction with ellipticine, heat and acid treated HSA resumes its α-helical content. This conclusive comparative study on interactions of IgG and HSA with ellipticine yields the result that native HSA is responsible for transport of neutral species of ellipticine whereas IgG carries cationic ellipticine in its native form.