A Water-Soluble Wavy Coordination Polymer of Cu(II) as a Turn-On Luminescent Probe for Histidine and Histidine-Rich Proteins/Peptides.

Histidine plays an essential role in most biological systems. Changes in the homeostasis of histidine and histidine-rich proteins are connected to several diseases. Herein, we report a water-soluble Cu(II) coordination polymer, labeled CuCP, for the fluorimetric detection of histidine and histidine-rich proteins and peptides. Single-crystal structure determination of CuCP revealed a two-dimensional wavy network structure in which a carboxylate group connects the individual Cu(II) dimer unit in a syn-anti conformation. The weakly luminescent and water-soluble CuCP shows turn-on blue emission in the presence of histidine and histidine-rich peptides and proteins. The polymer can also stain histidine-rich proteins via gel electrophoresis. The limits of quantifications for histidine, glycine-histidine, serine-histidine, human serum albumin (HSA), bovine serum albumin, pepsin, trypsin, and lysozyme were found to be 300, 160, 600, 300, 600, 800, 120, and 290 nM, respectively. Utilizing the fluorescence turn-on property of CuCP, we measured HSA quantitatively in the urine samples. We also validated the present urinary HSA measurement assay with existing analytical techniques. Job's plot, 1H NMR, high-resolution mass spectrometry (HRMS), electron paramagnetic resonance (EPR), fluorescence, and UV-vis studies confirmed the ligand displacement from CuCP in the presence of histidine.

Label-Free Detection of Unbound Bilirubin and Nitrophenol Explosives in Water by a Mechanosynthesized Dual Functional Zinc Complex: Recognition of Picric Acid in Various Common Organic Media.

High levels of unconjugated bilirubin (UB) in serum lead to asymptomatic and neonatal jaundice and brain dysfunctions. Herein, we have reported the detection of UB at as low as 1 µM in an aqueous alkaline medium using a Zn(II) complex. The specificity of the complex has been validated by the HPLC in the concentration window 6-90 µM, which is rare. The sensory response of the probe at physiological pH against nitro explosives developed it as an instant-acting fluorosensor for picric acid (PA) and 2,4-dinitrophenol (2,4-DNP). Spectroscopic titration provided a binding constant of 4×105  M-1 with PA. The naked eye detection was found to be 15 µM. The solid-state photoluminescent nature of the complex enabled it for PA sensing in the solid phase. Interestingly, the probe remained fluorescent in various volatile and non-volatile organic solvents. As a result, it can also detect PA and 2,4-DNP in a wide range of common organic media. NMR studies revealed the coordination of PA, 2,4-DNP, and UB to the Zn(II) center of the probe, which is responsible for the observed quenching of the probe with the analytes.

Pentafluorobenzene: Promising Applications in Diagnostics and Therapeutics.

Pentafluorobenzene (PFB) represents a class of aromatic fluorine compounds employed exclusively across a spectrum of chemical and biological applications. PFBs are credited with developing various chemical synthesis techniques, networks and biopolymers, bioactive materials, and targeted drug delivery systems. The first part of this review delves into recent developments in PFB-derived molecules for diagnostic purposes. In the latter segment, PFB's role in the domain of theragnostic applications is discussed. The review elucidates different mechanisms and interaction strategies applied in leveraging PFBs to formulate diagnostic and theragnostic tools, substantiated by proper examples. The utilization of PFBs emerges as an enabler, facilitating manifold reactions, improving materials' properties, and even opening avenues for explorative research.

Advances in the Development of Water-Soluble Fluorogenic Probes for Bioimaging of Hypochlorite/Hypochlorous Acid in Cells and Organisms.

This mini-review summarizes the development of intracellular fluorogenic probes for biological investigations of hypochlorous acid/hypochlorite (HOCl/OCl-) in living cells and tissues. Monitoring the formation or effects of reactive oxygen species (ROS) inside living systems is critical in determining their roles in human physiology. HOCl/OCl- is considered as an important member of the nonradical ROS family for its decisive microbicidal action in the innate immune system. Even though HOCl/OCl- plays a defensive role in human health, abnormal or overexpression may have detrimental effects on the host physiology leading to many diseases, including neurodegeneration and cancer. In recent years, progress in the development of fluorescent imaging probes for observing HOCl/OCl- levels in live cells and tissues has been made. Despite considerable advancement, challenges still exist in areas like working solvent/media, pH, response time, buffer selection, emission region, and others. In addition, this account aims to discuss the design strategies and sensing mechanisms of the representative fluorogenic probes for bioimaging of HOCl/OCl-, endogenously and exogenously. Herein, we also have tried to provide the future direction to develop HOCl/OCl- specific probes for disease diagnosis with particular attention to the requirement of the recognition group, solvent, and buffer media, which will be beneficial for those working in the domain of biomedical research.

A unique water soluble probe for measuring the cardiac marker homocysteine and its clinical validation.

A series of copper(II) compounds 1-4 were synthesized and developed as fluorogenic probes to measure the cardiac marker homocysteine (Hcy) without any interference from other bioanalytes prevalent in human blood plasma including, cysteine and glutathione. UV-vis and EPR studies have provided confirmatory evidence for reduction-induced-emission-enhancement of the probe, which is responsible for the observed "off-to-on" behaviour towards Hcy. Water solubility, remarkable fluorescence enhancement (55-111 fold), and low detection ability (nearly 2.5 µM) make the probe suitable for clinical testing of cardiac samples. Investigation of 1 against a few reductive interferents testifies its specificity for Hcy. Results from clinical examination of cardiac samples by 1 when combined with the outcome of the reliability testing involving a clinically approved commercial immunoassay kit, validates the prospect of the molecular probe for direct measurement of Hcy in human plasma, which is unprecedented.

Concurrent detection and treatment of cyanide-contaminated water using mechanosynthesized receptors.

The development of receptors that can detect as well as treat cyanide ions in aqueous samples is indispensable for environmental protection. Herein, we present the bulk solvent-free and instant green synthesis of a series of turn-on fluorimetric probes that can specifically detect the deadly poison cyanide among various anions and metal ions in water. Selective recognition of cyanide by the mechanosynthesized compounds is even observable by the naked eyes, which remained unaffected in the presence of various challenging species. NMR spectroscopic investigation supports the chemodosimetric sensing of cyanide by the receptors. A remarkable 55-83 fold fluorescence enhancement by the probes enabled us to reach a limit of detection (LOD) in the range of 8-26 ppb, well below the permissible limit of cyanide in drinking water. Being minuscule soluble in water, cyanide treatment studies with the ionophores showed greater than 99% reduction in the free cyanide concentration after three consecutive cycles of operation. Furthermore, the compounds can be used as sensitive probes for the estimation of cyanide in human blood serum in physiological conditions. Overall, the results presented in this article will certainly find great use in the area of cyanide pollution with regard to simultaneous sensing and treatment of free cyanide, which is heretofore unprecedented.

Estimation of bisulfate in edible plant foods, dog urine, and drugs: picomolar level detection and bio-imaging in living organisms.

In order to explore the properties of any species in solution, the actual, i.e. equilibrium concentration of the free species should be taken into account. Researchers have not paid attention to the deprotonation equilibrium between HSO4- and SO42- while probing bisulfate ion. In this study, we have addressed this concern and developed two zwitterions, CG (coumarin-integrated glycine) and CA (coumarin-integrated alanine), for the selective detection of HSO4- at a picomolar level (50 to 325 pM) with very high binding affinity (∼108 M-1) in pure water at physiological pH. The principle of HSO4- recognition was established via UV-vis and fluorescence techniques. DFT calculations suggested that the H-bonding interactions between the probes and HSO4- are the driving force for this unforeseen selectivity. The membrane penetration ability and nontoxicity of CG/CA enable them to function as staining agents in living brine shrimps and bacteria. The use of these probes for the estimation of HSO4- in various day-to-day edible foods and drugs along with urine samples is unprecedented. The significance and novelty of this study lies in the application and development of assays for estimating bisulfate in several real-world samples that are predominantly aqueous in nature, which are the first of their kind.

A Highly Selective Turn-On Biosensor for Measuring Spermine/Spermidine in Human Urine and Blood.

Spermine and spermidine serve as the key biomarkers for early-stage cancer diagnosis. This work reports a rapid, highly selective, and noninvasive sensing platform for spermine/spermidine. The hybrid material, developed in this work, has been characterized by UV-vis, IR, powder XRD, SEM, EDX, and rheological studies. Storage modulus (G') and loss modulus (G″) measurements infer that embedding boronic acid integrated coumarin softens the agarose gel fibers at room temperature. Stress resistance measurement and subsequent imaging further confirms the softness of the hybrid hydrogel over pure agarose gel and homogeneous distribution of the dye in the hybrid matrix as well. The soft hydrogel with a limit-of-detection (LOD) value of 6 µM showed a nearly 27-fold fluorescence enhancement for spermine. The hybrid hydrogel matrix can be useful within a wide concentration window (6 µM-2.5 mM spermine). Response time (≤7 s) confirms rapid detection ability of the material. Noninterference from various metal ions, common anions, monosaccharides, nucleobases, and amino acids, particularly, histidine, arginine, lysine, ornithine, glutamine, etc.,  makes the hybrid hydrogel suitable for the real-time measurement of spermine in human urinary and blood samples. Furthermore, noninterference from other biogenic amines supports the highly selective nature of the hybrid gel. The ability to measure spermine in urinary samples by the probe offers a noninvasive nature of the sensing platform. Overall, we envisioned that the hybrid material formulation would be useful for diagnosing early-stage tumors and assessing the recovery of patients undergoing chemotherapeutic treatment.

Affinity Directed Surface Functionalization of Two Different Metal Nanoparticles by a Natural Ionophore: Probing and Removal of Hg2+ and Al3+ Ions from Aqueous Solutions.

In this work, we report affinity controlled surface modifications of two different metal nanoparticles (MNPs) using a hydrophilic natural ionophore (microbial chelator) aeruginic acid (abbreviated as H2L) that possesses two different types of binding pockets viz. O/O from carboxylic acid group and N/O from a phenol-thiazole moiety. Preferred binding of the former donor set (i.e., O/O) on to the surface of silver nanoparticles (AgNPs) has resulted in a colorimetric nanomaterial HL@AgNPs, which showed naked eye observable easy detection of Hg2+ in aqueous HEPES buffer at pH 7.4, even in the presence of other metal ions. On the other hand, excellent affinity of the phenol-thiazole moiety (i.e., N/O) for iron nanosurfaces (FeNPs) develops a fluorogenic nanomaterial HL@FeNPs. Brilliant emission behavior of this nanomaterial enabled it to be useful for highly selective recognition of Al3+ under identical experimental conditions. Remarkable fluorescence enhancement (122-folds) of HL@FeNPs upon addition of Al3+ remain unchanged even in the presence of other competing metal ions. The nanomaterials HL@AgNPs and HL@FeNPs could even detect the target analytes instantly offering lower detection limits of 2 and 80 nM, respectively. Presence of toxic metal ions as environmental pollutant demands for dual-functional materials capable of performing the task of probing cum removal. Surface functionalizations of the nanomaterials of silver and iron with H2L have also resulted two removal agents that can efficiently and easily extract Hg2+ and Al3+ ions from contaminated water, respectively. We are not aware of any work that highlights the manifold utilization of a microbial chelator (i.e., natural ionophore) in the facile construction of different metal nanoparticles for environmental applications such as detection cum removal of toxic metal ions from aqueous solutions.

Instant Detection of Hydrogen Cyanide Gas and Cyanide Salts in Solid Matrices and Water by using CuII and NiII Complexes of Intramolecularly Hydrogen Bonded Zwitterions.

A series of intramolecularly hydrogen-bonded zwitterionic compartmental ligands HL1-HL4, containing a pendent diamine arm that is monoprotonated and an aldehyde functionality at two different ortho-positions of a 4-halophenoxide, is reported herein. Single-crystal X-ray diffraction (SXRD) provides persuasive evidence for the identification of this class of proton-transferred zwitterions at room temperature. The solid-state photoluminescent nature of these zwitterions remains intact in aqueous and organic solutions. Grinding of HL1 and HL2 with Cu2+ /Ni2+ salts develop turn-on probes 1-4. Compounds 1 and 4 are dinuclear CuII and NiII species, respectively. Compound 2 is a tetranuclear CuII complex. Interestingly, compound 3 is a mononuclear NiII species in which both nitrogen atoms in the pendant diamine arm are protonated and, therefore, not coordinated to the NiII center. All these probes (1-4) display an instant response to the poison gas hydrogen cyanide (HCN) and cyanide salts present in both solid matrices and aqueous (100 % water) solution. Selective and rapid sensing of HCN gas and cyanide salts in solid/soil/water phases, without any interference, by the mechanosynthesized complexes 1-4 can be perceived easily by the naked eye under a hand-held UV lamp.

Fabrication of a Cu(II)-Selective Electrode in the Polyvinyl Chloride Matrix Utilizing Mechanochemically Synthesized Rhodamine 6g as an Ionophore.

A Cu(II)-selective electrode has been fabricated by utilizing a mechanochemically synthesized copper-specific ionophore "L" embedded in a poly(vinyl chloride) membrane. 2-Nitrophenyloctylether and sodium tetraphenylborate have been used as a plasticizer and as a solvent mediator, respectively, and found to be enhancing the sensitivity of the fabricated ion-selective electrode (ISE). A range of membranes (S1-S7) with varying compositions were casted and investigated in ISE. Results revealed an excellent Nernstian response of 29.38 ± 0.55 mV/dec for the ISE S6. The fabricated ISE operates well in the pH window 4.0-7.5, and the limit of detection was found to be 5 µM (0.3 ppm). Quick response time (15 s), long shelf-life, and selectivity (on the order of 10-4 and 10-5) over a number of interfering cations enabled S6 promising for real off laboratory sample analysis and can be employed to detect copper ion in various industrial as well as biological and environmental samples. To demonstrate the practical application of these ISE, the Cu concentration in the digested printed circuit board has been estimated using the standard calibration plot. The fabricated ISE has been regenerated through extracting copper by chelating with ethylenediaminetetraacetic acid.

Siderophore coated magnetic iron nanoparticles: Rational designing of water soluble nanobiosensor for visualizing Al3+ in live organism.

This article aims to establish the judicious use of iron-binding chemistry of microbial chelators in order to functionalize the surface of iron nanoparticles to develop non-toxic nanobiosensor. Anchoring a simple siderophore 2,3-dihydroxybenzoylglycine (H3L), which bears catechol and carboxyl functionalities in tandem, on to the surface of Fe3O4 nanoparticles has developed a unique nanobiosensor HL-FeNPs which showed highly selective and sensitive detection of Al3+ in 100% water at physiological pH. The biosensor HL-FeNPs, with 20nM limit of detection, behaves reversibly and instantly. In-vivo bio-imaging in live brine shrimp Artemia confirmed that HL-FeNPs could be used as fluorescent biomarker for Al3+ in live whole organisms. Magnetic nature of the nanosensor enabled HL-FeNPs to remove excess Al3+ by using external magnet. To our knowledge, the possibility of microbial chelator in the practical development of Al3+ selective nanobiosensor is unprecedented.

Reporting a new siderophore based Ca(2+) selective chemosensor that works as a staining agent in the live organism Artemia.

A Ca(2+)-specific chemosensor involving acyclic non-ether and non-carboxylato-type metal chelating ligands is rare. The tetradentate OONO artificial receptor, HL, possessing a sulfur-containing intermediate siderophore aeruginic acid, tethered to a rhodamine 6G based signalling unit in a single molecule has been synthesized. The fluoroionophore required excitation in the visible wavelength (510 nm) and showed highly selective and sensitive detection of Ca(2+) ions in 100% water solution in HEPES buffer at physiological pH (7.4). The probe HL, with LOD as low as 70 nM, behaves reversibly and showed nearly 17-fold enhanced selectivity for Ca(2+) over other cell abundant alkali and alkaline metal ions such as Na(+), K(+), Li(+), and Mg(2+) without any intervention. Job's plot, (1)H NMR titration and ESI-MS data provided corroborative evidence in support of 1 : 1 association between HL and Ca(2+). From a wide range of transition and heavy metal ions series, HL also binds Cu(2+). However, the use of l-cysteine removes the interference from Cu(2+) and results in highly selective detection specificity of HL for Ca(2+). As a reversible "off-on-off" fluorescent chemosensor, it is possible to detect Ca(2+) at as low as 5 µM in the midgut region of the gastrointestinal tract of the live animal Artemia, a brine shrimp.

Naked eye instant reversible sensing of Cu(2+) and its in situ imaging in live brine shrimp Artemia.

A Cu(2+)-specific colorimetric reversible fluorescent receptor was designed and synthesized which showed a naked eye observable colour change from colourless to pink on addition of an aqueous buffer (pH 7.4) solution of 30 ppb Cu(2+). Short response time (≤5 s) and low detection limit (nearly 3 ppb) make suitable as a reliable "dip-in" open eye sensor for Cu(2+). Bio-imaging application in live brine shrimp Artemia enabled to detect Cu(2+) at as low as 10 ppb exposure.