A Prompt Study on Recent Advances in the Development Of Colorimetric and Fluorescent Chemosensors for "Nanomolar Detection" of Biologically Important Analytes.

Fluorescent and colorimetric chemosensors for selective detection of various biologically important analytes have been widely applied in different areas such as biology, physiology, pharmacology, and environmental sciences. The research area based on fluorescent chemosensors has been in existence for about 150 years with the development of large number of fluorescent chemosensors for selective detection of cations as metal ions, anions, reactive species, neutral molecules and different gases etc. Despite the progress made in this field, several problems and challenges still exist. The most important part of sensing is limit of detection (LOD) which is the lowest concentration that can be measured (detected) with statistical significance by means of a given analytical procedure. Although there are so many reports available for detection of millimolar to micromolar range but the development of chemosensors for the detection of analytes in nanomolar range is still a challenging task. Therefore, in our current review we have focused the history and a general overview of the development in the research of fluorescent sensors for selective detection of various analytes at nanomolar level only. The basic principles involved in the design of chemosensors for specific analytes, binding mode, photophysical properties and various directions are also covered here. Summary of physiochemical properties, mechanistic view and type of different chemosensors has been demonstrated concisely in the tabular forms.

Viscosity-sensitive and AIE-active bimodal fluorescent probe for the selective detection of OCl- and Cu2+: a dual sensing approach via DFT and biological studies using green gram seeds.

A novel dual-mode viscosity-sensitive and AIE-active fluorescent chemosensor based on the naphthalene coupled pyrene (NCP) moiety was designed and synthesized for the selective detection of OCl- and Cu2+. In non-viscous media, NCP exhibited weak fluorescence; however, with an increase in viscosity using various proportions of glycerol, the fluorescence intensity was enhanced to 461 nm with a 6-fold increase in fluorescence quantum yields, which could be utilized for the quantitative determination of viscosity. Interestingly, NCP exhibited novel AIE characteristics in terms of size and growth in H2O-CH3CN mixtures with high water contents and different volume percentage of water, which was investigated using fluorescence, DLS study and SEM analysis. Interestingly, this probe can also be effectively employed as a dual-mode fluorescent probe for light up fluorescent detection of OCl- and Cu2+ at different emission wavelengths of 439 nm and 457 nm via chemodosimetric and chelation pathways, respectively. The fast-sensing ability of NCP towards OCl- was shown by a low detection limit of 0.546 µM and the binding affinity of NCP with Cu2+ was proved by a low detection limit of 3.97 µM and a high binding constant of 1.66 × 103 M-1. The sensing mechanism of NCP towards OCl- and Cu2+ was verified by UV-vis spectroscopy, fluorescence analysis, 1H-NMR analysis, mass spectroscopy, DFT study and Job plot analysis. For practical applications, the binding of NCP with OCl- and Cu2+ was determined using a dipstick method and a cell imaging study in a physiological medium using green gram seeds.

A fast survey on recent developments in designing colorimetric and fluorescent sensors for the selective detection of essential amino acids.

Owing to the biological significance of various amino acids, developing accurate and cost-effective sensing techniques for the selective detection of amino acids has recently attracted growing interest. This review discusses the recent advancements of chemosensors in the selective detection of only essential amino acids out of a total of twenty amino acids, which have been applied in chemosensing research, and the mechanism of their action. The focus is directed towards the detection of the most important essential amino acids, like leucine, threonine, lysine, histidine, tryptophan and methionine, since isoleucine and valine are yet to be explored in regard to chemosensing. According to their chemical and fluorescence properties, different sensing techniques, such as the reaction-based approach, DNA-based sensors, nanoparticle formation, coordination ligand binding, host-guest chemistry, the fluorescence indicator displacement (FID) approach, electrochemical sensors, carbon dot-based sensors, MOF-based sensors and metal-based techniques, have been described.

Dual-mode chemosensor for the fluorescence detection of zinc and hypochlorite on a fluorescein backbone and its cell-imaging applications.

Fluorescein coupled with 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (FAD) was synthesized for the selective recognition of Zn2+ over other interfering metal ions in acetonitrile/aqueous buffer (1 : 1). Interestingly, there was a significant fluorescence enhancement of FAD in association with Zn2+ at 426 nm by strong chelation-induced fluorescence enhancement (CHEF) without interrupting the cyclic spirolactam ring. A binding stoichiometric ratio of 1 : 2 for the ligand FAD with metal Zn2+ was proven by a Jobs plot. However, the cyclic spirolactam ring was opened by hypochlorite (OCl-) as well as oxidative cleavage of the imine bond, which resulted in the emission enhancement of the wavelength at 520 nm. The binding constant and detection limit of FAD towards Zn2+ were determined to be 1 × 104 M-1 and 1.79 µM, respectively, and the detection limit for OCl- was determined as 2.24 µM. We introduced here a dual-mode chemosensor FAD having both the reactive functionalities for the simultaneous detection of Zn2+ and OCl- by employing a metal coordination (Zn2+) and analytes (OCl-) induced chemodosimetric approach, respectively. Furthermore, for the practical application, we studied the fluorescence imaging inside HeLa cells by using FAD, which demonstrated it can be very useful as a selective and sensitive fluorescent probe for zinc.

Colorimetric and Fluorimetric DNA Detection with a Hydroxystyryl-Quinolizinium Photoacid and Its Application for Cell Imaging.

The combination of styryl dye properties with the acidity and strong photoacidity of the 2,2'-[(1''-hydroxy-4''-methyl-(E)-2'',6''-phenylene)]-bisquinolizinium enables the detection of DNA by distinct absorption and emission color changes and the fluorimetric detection of DNA in cells with epifluorescence and confocal fluorescence microscopy.

Diphenylaminostyryl-substituted quinolizinium derivatives as fluorescent light-up probes for duplex and quadruplex DNA.

(E)-2-[1'-((Diphenylamino)styryl)quinolizinium (3a) and 2,2'-{(phenylimino)-bis[(E)-1'',1'''-styryl]}-bis[quinolizinium] (3b) were synthesized, and their interactions with duplex DNA and quadruplex DNA were investigated with a particular focus on their ability to operate as DNA-sensitive fluorescent probes. Due to the significantly different size and steric demand of these quinolizinium derivatives they exhibit different binding modes. Thus, 3a intercalates into duplex DNA and binds through π stacking to quadruplex DNA, whereas 3b favours groove binding to both DNA forms. The emission intensity of these compounds is very low in aqueous solution, but it increases drastically upon association with duplex DNA by a factor of 11 (3a) and >100 (3b) and with quadruplex DNA by a factor of >100 (3a) and 10 (3b), with emission bands between 600 and 750 nm.

A concentration dependent auto-relay-recognition by the same analyte: a dual fluorescence switch-on by hydrogen sulfide via Michael addition followed by reduction and staining for bio-activity.

H2S is shown, for the first time, to play an extraordinary dual role due to its nucleophilicity and reducing property with our single chemosensor, PND [4-(piperidin-1-yl) naphthalene-1,2-dione]. The initial nucleophilic attack via Michael addition (a lower concentration of H2S, blue fluorescence) is followed by the reduction of the 1,2-diketo functionality (a higher concentration of H2S, green fluorescence). This chemosensor, which also shows biological response, is remarkably effective in sensing the same analyte (H2S) at its different concentrations in a relay pathway via a fluorescence "off-on-on" mechanism, and this is also supported by DFT calculation and Cyclic voltammograms.

Rapid detection of hydrazine in a naphthol-fused chromenyl loop and its effectiveness in human lung cancer cells: tuning remarkable selectivity via the reaction altered pathway supported by theoretical studies.

Our designed and synthesized chemosensor naphthalene based chromenyl derivative (NAC) [1-(3-hydroxy-3 methyl-3H-benzo[f]chromen-2-yl) ethanone] has been used for fast (<30 s, DL = 0.22 ppb) and selective detection of N2H4 by a new way via the chromenyl ring opening followed by the pyrazole ring formation giving a strong blue fluorescence. The DFT study and the real application in different water samples along with the dipstick method in low cost devices have also been performed here. Human lung cancer cells (NCI-H460) have been used for hydrazinolysis of the NAC in vivo system for detection by the appearance of blue fluorescence and also for the MTT assay showing its remarkable cancer sensitivity.

Pyrophosphate selective fluorescent chemosensors: cascade recognition of nuclear stain mimicking DAPI.

A new zinc(ii) complex with a condensed hydroxynaphthyl pyridine (SPHN) as the coordinated ligand has been synthesized for the selective recognition of pyrophosphate (PPi) over other anions including phosphate in a mixed aqueous solution. The fluorescence enhancement of SPHN in association with Zn(2+) ions is quenched in the presence of intracellular pyrophosphate. This phenomenon is utilized in the construction of a logic gate. The binding of SPHN with Zn(2+) and its displacement by PPi have been established by photophysical investigation and supported by the DFT level of studies. The development of blue fluorescence in the {} complex upon binding of zinc with is shown to be useful as a nucleus marker in a cell similar to the commercially available staining compound, DAPI (diamino-2-phenylindole).

Nanomolar detection of hypochlorite by a rhodamine-based chiral hydrazide in absolute aqueous media: application in tap water analysis with live-cell imaging.

By employing the oxidation property of hypochlorite (OCl(-)), a novel rhodamine-based hydrazide of the chiral acid ((S)-(-)-2-pyrrolidone-5-carboxylic acid) (RHHP) was designed and synthesized for detection of OCl(-) absolutely in aqueous medium at nanomolar level. The structure of the chiral sensor was also proved by the X-ray crystallography. The bioactivity and the application of the probe for detection of OCl(-) in natural water system have been demonstrated. A plausible mechanism for oxidation of the sensor followed by hydrolysis is also proposed. The sensibility of the receptor toward OCl(-) was studied in absolute aqueous media, and the detection limit of hypochlorite-mediated oxidation to the receptor in nanomolar level makes this platform (RHHP) an ultrasensitive and unique system for OCl(-) oxidation.

Visual and near IR (NIR) fluorescence detection of Cr3+ in aqueous media via spirobenzopyran ring opening with application in logic gate and bio-imaging.

A new spirobenzopyran derivative (SPNH) was designed and synthesized which was applied in simultaneous colorimetric and NIR fluorescence detections for Cr(3+). This spirobenzopyran receptor is normally colorless in aqueous organic media but the formation of merocyanine occurs by Cr(3+) showing a yellow color. Here the formation of yellow color in UV-vis spectra and strong NIR fluorescence emission at 675 nm makes SPNH a good sensor for Cr(3+) ion. It is also found to be useful in cell imaging and in construction of logic gate. It shows INHIBIT gate in fluorescence and OR gate in absorption. To the best of our knowledge, this is the first report of NIR fluorescence emission of a spirobenzopyran derivative by Cr(3+) and its application to cell-biology and also in the logic gate.

A red fluorescence 'off-on' molecular switch for selective detection of Al3+, Fe3+ and Cr3+: experimental and theoretical studies along with living cell imaging.

A spirobenzopyran-quinoline (SBPQ) based sensor was synthesized which selectively detects trivalent ions viz. Al(3+), Fe(3+) and Cr(3+) through a fluorescence turn on signal in the red region (~675 nm) with the detection limit in the order of 10(-8) M. The potentiality of the probe was confirmed by employing it for fluorescence bio-imaging with Al(3+) in three different types of live-cells.

'PET' vs. 'push-pull' induced ICT: a remarkable coumarinyl-appended pyrimidine based naked eye colorimetric and fluorimetric sensor for the detection of Hg2+ ions in aqueous media with test trips.

A novel colorimetric and fluorescent chemosensor based on 7-(diethylamino)-3-(pyrimidin-4-yl)-2H-chromen-2-one (PYC) has been designed and synthesized for the detection of Hg(2+) in the presence of other competing metals in mixed aqueous media. The PYC exhibits naked eye color change from green to red, and the fluorescence color changes from yellowish green to light orange with Hg(2+). It also shows a red shift in wavelength of about 80 nm in absorption spectra. Test strips based on PYC were fabricated, which could act as convenient and efficient Hg(2+) test kits.

Selective detection and bio-imaging of Pd2+ with novel 'C-CN' bond cleavage of cyano-rhodamine, cyanation with diaminomaleonitrile.

A new rhodamine based chemosensor, cyano-rhodamine, has been designed and synthesized with a green approach which shows a specific 'C-CN' bond breaking with the action of the Pd(2+) ion to produce the specific color and fluorescence of rhodamine 6G itself in solution and in HeLa cells.

Ratiometric and absolute water-soluble fluorescent tripodal zinc sensor and its application in killing human lung cancer cells.

A new "naked-eye" and ratiometric fluorescent zinc sensor (TAQ) of carboxamidoquinoline with 2-chloro-N-(quinol-8-yl)-acetamide as a receptor was designed and synthesized. The sensor shows good water solubility and high selectivity for sensing; about a 15-fold increase in fluorescence quantum yield and a 100 nm red-shift of fluorescence emission upon binding Zn²âº in aqueous HEPES buffer solution are observed. The human lung cancer cell line (A549) activity is also demonstrated.

A highly selective and sensitive probe for colorimetric and fluorogenic detection of Cd2+ in aqueous media.

A new rhodamine-quinoline based dyad has been synthesized. It shows a highly selective response to Cd(2+) in the presence of other competing metal ions in aqueous media (pH = 7.1). The detection limit of the sensor is in the 10(-7) M level.