A fluorescent chemosensor for selective detection of chromium (III) ions in environmentally and biologically relevant samples.

A simple single step one pot multicomponent reaction was performed to synthesize N-(tert-butyl)-2-(furan-2-yl)imidazo[1,2-a]pyridine-3-amine (TBFIPA). The synthesized TBFIPA was subjected to library of cations to study its ability for selective and sensitive detection of specific metal ions. Selective detection of chromium ions by TBFIPA were found from the significant hypsochromic shift (335 nm â†’ 285 nm) in the UV-Visible spectra. The fluorescent TBFIPA displays complete quenching of fluorescence under UV lamp (365 nm) only in the presence of chromium without the interference of common metal ions. Binding constant (ka) obtained from Benesi-Hildebrand plot is 0.21 × 105 M-1, limit of detection (LOD) and limit of quantification (LOQ) of TBFIPA toward Cr3+ ions are 4.70 × 10-7 M and 1.56 × 10-7 M, respectively. The mechanism proposed during complex formation were supported by stoichiometric Job continuous variation plot, 1H NMR titration and ESI-MS spectroscopic data. All the experimental confirmation for complex formation were corroborated with theoretical DFT studies optimized using RB3LYP/6-31G(d) basis set. The selectivity and sensitivity of TBFIPA toward Cr3+ ions are found suitable to design a user-friendly silica based portable test kit. Alongside, TBFIPA was successfully utilized for imaging onion epidermal cells. Furthermore, the results obtained for biological, environmental, and industrial samples provided solid evidence to estimate chromium ions using TBFIPA in these real samples.

Coordination of Distal Carboxylate Anion Alters Metal Ion Specific Binding in Imidazo[1,2-a]pyridine Congeners.

Imidazo[1,2-a]pyridine derivatives have excellent potential for chelation with transition metal ions. Two new imidazo[1,2-a]pyridine-8-carboxylates were synthesized and characterized by 1H NMR, 13C NMR, HRMS, and single crystal-XRD techniques. Methyl carboxylate (probe 1) turns on fluorescence upon coordination with Zn2+, while sodium carboxylate (probe 2) turns off its fluorescence upon coordination with Co2+ or Cu2+ ions present in aqueous acetonitrile medium. 13C NMR study revealed that the change in metal ion specific binding was due to the involvement of carboxylate anion in complex formation with Co2+ or Cu2+ ions. The carboxylate anion at 8-position also enhanced the sensitivity of detection of probe 2 by an order of magnitude (detection limits: 3.804 × 10-7 M, probe 1/Zn2+; 0.420 × 10-7 M, probe 2/Co2+ and 0.304 × 10-7 M, probe 2/Cu2+). The detection limits of probes 1 and 2 comply well with the World Health Organization (WHO) and US Environmental Protection Agency (US-EPA) guidelines for detection of heavy metal ions present in drinking water and ground water. Both the probes form a 1:1 complex with Zn2+, Co2+ or Cu2+, and the stoichiometry was verified by Job plot and ESI-mass analysis. The sensing mechanism is explained using 13C NMR experiments, ESI-mass analytical data and theoretical DFT calculations. The suitability of probes 1 and 2 for on-site detection and quantitative determination of Zn2+, Co2+ and Cu2+ ions present in biological, environmental and industrial samples is demonstrated. In addition, both 1 and 2 are used for detection of intracellular contamination of Zn2+, Co2+ or Cu2+ ions in onion epidermal cells.

Significant perspectives on various viral infections targeted antiviral drugs and vaccines including COVID-19 pandemicity.

A virus enters a living organism and recruits host metabolism to reproduce its own genome and proteins. The viral infections are intricate and cannot be completely removed through existing antiviral drugs. For example, the herpes, influenza, hepatitis and human immunodeficiency viruses are a few dreadful ones amongst them. Significant studies are needed to understand the viral entry and their growth in host cells to design effective antivirals. This review emphasizes the range of therapeutical antiviral drugs, inhibitors along with vaccines to fight against viral pathogens, especially for combating COVID-19. Moreover, we have provided the basic and in depth information about viral targets, drugs availability, their mechanisms of action, method of prevention of viral diseases and highlighted the significances of anticoagulants, convalescent plasma for COVID-19 treatment, scientific details of airborne transmission, characteristics of antiviral drug delivery using nanoparticles/carriers, nanoemulsions, nanogels, metal based nanoparticles, alike the future nanosystems through nanobubbles, nanofibers, nanodiamonds, nanotraps, nanorobots and eventually, the therapeutic applications of micro- and nanoparticulates, current status for clinical development against COVID-19 together with environmental implications of antivirals, gene therapy etc., which may be useful for repurposing and designing of novel antiviral drugs against various dreadful diseases, especially the SARS-CoV-2 and other associated variants.

A comprehensive overview of vaccines developed for pandemic viral pathogens over the past two decades including those in clinical trials for the current novel SARS-CoV-2.

The unprecedented coronavirus disease 2019 (COVID-19) is triggered by a novel strain of coronavirus namely, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Researchers are working around the clock to control this pandemic and consequent waves of viral reproduction, through repurposing existing drugs as well as designing new vaccines. Several countries have hastened vaccine design and clinical trials to quickly address this outbreak. Currently, more than 250 aspirants against SARS-CoV-2 are in progress, including mRNA-replicating or non-replicating viral vectored-, DNA-, autologous dendritic cell-based-, and inactivated virus-vaccines. Vaccines work by prompting effector mechanisms such as cells/molecules, which target quickly replicating pathogens and neutralize their toxic constituents. Vaccine-stimulated immune effectors include adjuvant, affinity, avidity, affinity maturation, antibodies, antigen-presenting cells, B lymphocytes, carrier protein, CD4+ T-helper cells. In this review, we describe updated information on the various vaccines available over the last two decades, along with recent progress in the ongoing battle developing 63 diverse vaccines against SARS-CoV-2. The inspiration of our effort is to convey the current investigation focus on registered clinical trials (as of January 08, 2021) that satisfy the safety and efficacy criteria of international wide vaccine development.

Design and synthesis of a novel peptide for selective detection of cancer cells.

Using a minimalist approach, an 11-residue peptide (Peptide 1) tagged with rhodamine fluorophore was designed and synthesized for selective detection of cancer cells. Peptide 1 contains RGD and NGR motifs to bind, respectively, integrins and aminopeptidase CD13, which are over expressed in cancer cells. Surface tension measurements revealed that peptide 1 possess surface-active property owing to the overall hydrophobicity and cationic nature of the peptide. Peptide 1 displays cancer cell-selective binding at ≤5.0 µM concentrations, while peptide 2 (randomized sequence of 1) shows non-selective binding to normal and cancer cells. Fluorescence microscopy and FACS analysis demonstrated the intracellular localization of peptide 1 in three different cancer cell lines, confirming the role of RGD and NGR motifs. Cytotoxicity assay exhibited the viability of normal and cancer cells up to 100 µM concentrations of peptide 1. Steady-state fluorescence measurements disclosed the preferential interactions of the peptide 1 with anionic POPC/POPG bilayers rather than with zwitterionic POPC lipid bilayers. Circular dichroism studies showed minimal changes in the secondary structure of peptide 1 upon binding with the anionic lipid bilayers. Peptide 1 is largely unordered, non-toxic, and useful for identification of cancer cells. Peptide 1 provides a template for designing drug-loaded peptides for targeted delivery into cancer cells.

Chelation of specific metal ions imparts coplanarity and fluorescence in two imidazo[1,2-a]pyridine derivatives: Potential chemosensors for detection of metal ions in aqueous and biosamples.

Synthesis and chelation induced fluorescence emission from two imidazo[1,2-a]pyridine derivatives are described. The nonfluorescent molecule 1 containing N and O donor atoms, achieves coplanarity upon interactions with trivalent cations Al3+, Fe3+ and Cr3+, that favors fluorescence emission. Molecule 2 containing two N donor atoms attains coplanarity upon interaction with the only Zn2+ and becomes fluorescent. Both molecules 1 and 2 form a 1:1 complex with interacting metal ions. Other trivalent metal ions (including Bi3+ and In3+) and common divalent metal ions (including Hg2+ and Cd2+) fail to form any complex with 1 or 2, and they do not interfere in the detection of Zn2+, Al3+, Fe3+ or Cr3+ ions. Noninterference of other metal ions renders 1 and 2 suitable for the detection of fungal cells contaminated with Zn2+, Al3+, Fe3+ or Cr3+ ions.

Crystal structure and Hirshfeld surface analysis of two imidazo[1,2-a]pyridine derivatives: N-tert-butyl-2-(4-meth-oxy-phen-yl)-5-methyl-imidazo[1,2-a]pyridin-3-amine and N-tert-butyl-2-[4-(di-methyl-amino)-phen-yl]imidazo[1,2-a]pyridin-3-amine.

In the title imidazo[1,2-a]pyridine derivatives, N-tert-butyl-2-(4-meth-oxy-phen-yl)-5-methyl-imidazo[1,2-a]pyridin-3-amine, C19H23N3O, (I), and N-tert-butyl-2-[4-(di-methyl-amino)-phen-yl]imidazo[1,2-a]pyridin-3-amine, C19H24N4, (II), the 4-meth-oxy-phenyl ring in (I) and the 4-(di-methyl-amino)-phenyl ring in (II) are inclined to the respective imidazole rings by 26.69 (9) and 31.35 (10)°. In the crystal of (I), mol-ecules are linked by N-H⋯N hydrogen bonds, forming chains propagating along the [001] direction. The chains are linked by C-H⋯π inter-actions, forming layers parallel to the (010) plane. In (II), the crystal packing also features N-H⋯N hydrogen bonds, which together with C-H⋯N hydrogen bonds link mol-ecules to form chains propagating along the c-axis direction. The chains are linked by C-H⋯π inter-actions to form layers parallel to the (100) plane. Inversion-related layers are linked by offset π-π inter-actions [inter-centroid distance = 3.577 (1) Å]. The inter-molecular inter-actions of both compounds were analyzed using Hirshfeld surface analysis and two-dimensional fingerprint plots.

Development of antiviral inhibitor against dengue 2 targeting Ns3 protein: In vitro and in silico significant studies.

Dengue fever is a severe, widespread disease with more than 2 million diagnosed infections per year. The Dengue virus protease represents a cardinal target for prudent drug design. Among the four serotypes Dengue 2 is known for the occurrence of its frequent epidemics. The new compound inhibited the Dengue-2 in the low-micromolar range in cells. At the moment, protease inhibitors are not actively tried against dengue virus as therapeutic option. We have identified thiosemicarbazones derived phenyl-acetyl ketones as candidate for a novel class of protease inhibitors. Here, we report the selective and non-competitive inhibition of the Dengue virus serotype 2 in vitro and in silico. Molecular docking suggests binding at a specific active site. In addition to the docking assays, few techniques were developed to interpret these molecules's antiviral profile in vitro.

Diastereoselective tandem oxidation/Michael/aldol reaction: unprecedented formation of dispirocyclopentanebisoxindoles and dispiro[acenaphthylene-1,1'-cyclopentane-3',1''-acenaphthylene]-2,2''diones.

An unprecedented tandem oxidation/Michael/aldol reaction is reported. The diastereoselective formation of only a single isomer of dispirocyclopentanebisoxindole and dispiro[acenaphthylene-1,1'-cyclopentane-3',1''-acenaphthylene]-2,2''dione is presented. The reaction generates two new C-C bonds and two all-carbon quaternary chiral stereocenters in a single step.

Antiviral activity of Thiosemicarbazones derived from α-amino acids against Dengue virus.

The endemicity and seasonal outbreaks of Dengue disease in most tropical and subtropical countries underscores an urgent need to develop effective prevention and control measures. Development of a Dengue vaccine, which is complicated by the Antibody Dependent Enhancement effect (ADE), a viral inhibitor, seems prudent as it would inhibit the spread of the virus. In vitro methods such as MTT assay and plaque formation unit reduction assays were employed for screening the viral inhibitory property of α-amino acid based Thiosemicarbazides. The results elicits that at concentrations not exceeding the maximum non cytotoxic concentration (MNCC), these compounds completely prevented Dengue virus infection in vero cells as indicated by the absence of cytopathic effects in a dose-dependent manner. The high potency of Bz-Trp-TSC against all four types of Dengue virus infection elevates Thiosemicarbazide as a lead antiviral agent for Dengue disease. Screening small molecules for antiviral activity against the most rapidly spreading mosquito-borne viral disease is being explored by several research groups. Our findings would help to augment the efforts to identify the lead compounds for antiviral therapy to combat the Dengue disease. J. Med. Virol. 89:546-552, 2017. © 2016 Wiley Periodicals, Inc.

Selective interactions of trivalent cations Fe³âº, Al³âº and Cr³âº turn on fluorescence in a naphthalimide based single molecular probe.

Synthesis and fluorescence turn-on behavior of a naphthalimide based probe is described. Selective interactions of trivalent cations Fe(3+), Al(3+) or Cr(3+) with probe 1 inhibit the PET operating in the probe, and thereby, permit the detection of these trivalent cations present in aqueous samples and live cells. Failure of other trivalent cations (Eu(3+), Gd(3+) and Nb(3+)) to inhibit the PET process in 1 demonstrates the role of chelating ring size vis-à-vis ionic radius in the selective recognition of specific metal ions.

Lewis acid catalyzed unprecedented [3 + 2] cycloaddition yields 3,3'-pyrrolidinyldispirooxindoles containing four contiguous chiral stereocenters with two contiguous quaternary spirostereocenters.

A Lewis acid catalyzed domino reaction cascades through azide-alkene cycloaddition, rearrangement, aziridine ring opening, and azomethine cycloaddition with a parent dipolarophile, resulting in 3,3'-pyrrolidinyldispirooxindoles containing four contiguous chiral stereocenters with two contiguous quaternary spirostereocenters.

Resveratrol stabilized gold nanoparticles enable surface loading of doxorubicin and anticancer activity.

The green synthesis of gold nanoparticles was achieved by exploiting the antioxidant property of resveratrol (R). The formation of resveratrol stabilized gold nanoparticles (R-GNPs) was confirmed by the observation of the surface plasmon resonance band at 537 nm. The average size of R-GNPs produced in resveratrol medium was ~35nm. The geometrical shape and zeta potential of the gold nanoparticles were spherical and -21.2 mV, respectively. R-GNPs showed excellent stability in saline and other buffers mimicking the physiological pH. The MTT assay using fibroblast cells from explants tissue revealed the biocompatibility of R-GNPs. The cytotoxic activity of doxorubicin loaded R-GNPs against glioma carcinoma cell line (LN 229), showed the suitability of R-GNPs as a carrier for anticancer drugs.

Ethyl 8''-chloro-1'-methyl-2,12''-dioxo-12''H-di-spiro-[indoline-3,2'-pyrrolidine- 3',6''-indolo[2,1-b]quinazoline]-4'-carboxyl-ate.

In the title compound, C29H23ClN4O4, the quinazoline-indole system and the indolin-2-one system are each essentially planar, with maximum deviations from their mean planes of 0.150 (2) and 0.072 (2) Å, respectively. The central pyrrolidine ring adopts a twisted conformation on the C-C bond involving the spiro C atoms. Its mean plane forms dihedral angles of 83.37 (9) and 86.56 (8)°, respectively, with the indole rings of the indolin-2-one and quinazoline-indole systems. In the crystal, mol-ecules are linked via pairs of N-H⋯O hydrogen bonds, forming inversion dimers. The dimers are linked via C-H⋯O hydrogen bonds, forming chains propagating along [001].

Tuning copper(II) ion selectivity: the role of basicity, size of the chelating ring and orientation of coordinating atoms.

Incorporation of the triazolyl moiety modulates the basicity and effective size of the chelating ring, changes the stoichiometry in complex formation and thereby imparts Cu(2+) ion selectivity.

Ethyl 1''-benzyl-1'-methyl-2''-oxodi-spiro-[indeno-[1,2-b]quinoxaline-11,3'-pyrrolidine-2',3''-indoline]-4'-carboxyl-ate.

In the title compound, C36H30N4O3, the quinoxaline-indene system is roughly planar, with a maximum deviation from the mean plane of 0.218 Šfor the C atom shared with the central pyrrolidine ring. This latter ring forms dihedral angles of 84.54 (7) and 83.91 (8)° with the quinoxaline-indene system and the indole ring, respectively. The central pyrrolidine ring has an envelope conformation with the N atom as the flap, while the pyrrolidine and five-membered rings of the indole group adopt twisted conformation and envelope (with the C atom bearing the quinoxaline-indene system as the flap) conformations, respectively. In the crystal, mol-ecules are linked via weak C-H⋯N hydrogen bonds, forming a chain running along [100].

Ethyl 1''-benzyl-2''-oxo-2',3',5',6',7',7a'-hexa-hydro-1'H-di-spiro-[indeno-[1,2-b]quinoxaline-11,2'-pyrrolizine-3',3''-indoline]-1'-carboxyl-ate monohydrate.

In the title compound, C38H32N4O3·H2O, the quinoxaline-indene and pyrrolizine systems are essentially planar, with maximum deviations from their mean planes of 0.162 and 0.563 Å, respectively. The pyrrolizine ring forms dihedral angles of 88.53 (5) and 89.95 (8)° with the quinoxaline-indene system and the indoline ring, respectively. The central pyrrolidine ring has an envelope conformation with the C atom bearing the quinoxaline-indene system as the flap. The pyrrolidine ring of the indole system adopts an envelope conformation with the C atom bonded to the pyrrolizine ring N atom as the flap. The five-membered ring attached to the central pyrolidine ring adopts a twisted conformation. In the crystal, O-H⋯N and O-H⋯O hydrogen bonds between water mol-ecules and pyrrolizine N and carbonyl O atoms together with C-H⋯O inter-actions result in chains along [100].

N-tert-Butyl-2-(2,6-di-chloro-phen-yl)imidazo[1,2-a]pyrazin-3-amine.

In the title compound, C16H16Cl2N4, the imidazole ring mean plane makes a dihedral angle of 70.01 (1)° with the phenyl ring. The Cl atoms deviate by -0.0472 (6) and 0.0245 (8) Šfrom the plane of their attached benzene ring. In the crystal, mol-ecules are linked via pairs of C-H⋯N hydrogen bonds, forming inversion dimers.

N-tert-Butyl-2-[4-(dimethyl-amino)-phen-yl]imidazo[1,2-a]pyrazin-3-amine.

In the title compound, C18H23N5, the imidazole ring makes a dihedral angles of 3.96 (8) and 19.02 (8)°, respectively, with the pyrazine and benzene rings while the dihedral angle between the pyrazine and benzene rings is 16.96 (7)°. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming chains along [010]. These chains are linked by C-H⋯N hydrogen bonds, forming two-dimensional networks lying parallel to (001).

A highly selective and efficient single molecular FRET based sensor for ratiometric detection of Fe3+ ions.

A highly selective and efficient single molecular FRET based sensor has been developed for the ratiometric detection of Fe(3+) in aqueous samples and live cells.