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A covalently bonded hexanuclear neutral complex, [Mn 6 (μ 3 -O) 2 (3-MeO-salox) 6 (OAc) 2 (H 2 O) 4 ] (1), has been synthesized and characterized by single crystal X-ray diffraction analysis along with IR and HRMS studies. Complex 1 has been found to selectively interact with human serum albumin (HSA), a model transport protein. The interaction of 1 with HSA was investigated by monitoring the change in the absorbance value of HSA at λ = 280 nm with increasing concentration of 1. Likewise, fluorescence titrations were carried out under two conditions: (i) titration of a 5 μM solution of complex 1 with the gradual addition of HSA, showing a ∼9-fold fluorescence intensity enhancement at 424 nm, upon excitation at 300 nm; and (ii) upon excitation at 295 nm, titration of 5 μM HSA solution with the incremental addition of complex 1, showing a quenching of fluorescence intensity at 334 nm, with simultaneous development of a new emission band at 424 nm. A linear form of the Stern-Volmer equation gives K SV M 4 M -1 and the Benesi-Hildebrand plot yields the binding constant as K M BH = 1.98 × 10 5 M -1 at 298 K. The thermodynamic parameters, Δ S °, Δ H °, and Δ G °, were estimated by using the van't Hoff relationship which infer the major contribution of hydrophobic interactions between HSA and 1. It was observed that quenching of HSA emission arises mainly through a dynamic quenching mechanism as indicated by the dependence of average lifetime 〈 τ 〉 on the concentration of 1. The changes in the CD (circular dichroism) spectral pattern of HSA in the presence of 1 clearly establish the variation of HSA secondary structure on interaction with 1. The most probable interaction region in HSA for 1 was determined from molecular docking studies which establish the preferential trapping of 1 in the subdomain IIA of site I in HSA and substantiated by the results of site-specific marker studies. Complex 1 was further evaluated for its antiproliferative effects in lung cancer A549 cells, which strictly inhibits the growth of the cells in both 2D and 3D mammospheres, indicating its potential application as an anticancer drug.

Here, we report the design and synthesis of a D⋯π⋯A-based fluorescent probe, ( E )-4-(4-(dibutylamine)-2-hydroxystyryl)-1-methylquinolin-1-ium (DHMQ), which is nonfluorescent in ∼100% PBS buffer medium due to a twisted intra molecular charge transfer (TICT) phenomenon and it becomes highly fluorescent (∼149 fold) in the presence of human serum albumin (HSA), owing to the restriction of its intramolecular free rotation inside the hydrophobic binding cavity of HSA. The site-selective fluorescence displacement assay and molecular docking studies clearly reveal that DHMQ selectively binds at subdomain IB of HSA. The 3 σ /slope method was adopted to determine the limit of detection (LOD) value, which was as low as 2.39 nM in ∼100% PBS medium, indicating its high sensitivity towards HSA. The low dissociation constant value [ K d = (1.066 ± 0.017) μM] suggests a strong complexation between the DHMQ and HSA. Importantly, it has been demonstrated that DHMQ is capable of detecting HSA in real human serum and urine samples and was found to be suitable for live cell imaging of HSA.

Human serum albumin (HSA) is regarded as a useful biomarker for rapid medical diagnosis of various disorders mainly related to the kidneys and liver. Hence, it is crucial to identify and monitor the HSA level in complex biofluids (urine and blood samples) using a simple approach. Herein, we have designed and synthesized an intramolecular charge transfer (ICT) based environment-sensitive fluorescent molecular probe, ( E )-2-(3-(2-(5-methoxy-1 H -indol-3-yl)vinyl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (DCI-MIN), that can selectively interact with HSA in PBS buffer solution and exhibit a ∼78-fold enhancement in fluorescence intensity with a significant Stokes shift (∼126 nm), which is important to avoid interference from the excitation light. The significant red fluorescence response can be attributed to the suppression of free intramolecular rotation of the DCI-MIN probe inside the hydrophobic binding cavity of HSA and the low polar microenvironment present within HSA. According to the 3 σ /slope method, the detection limit was found to be 1.01 nM (0.0671 mg L -1 ) in aqueous solutions, which is significantly lower than the normal level of HSA in healthy urine and blood serum, indicating its high sensitivity. DCI-MIN has the ability to exhibit useful applications, including the detection and quantification of HSA concentration in complex biofluids (human urine and blood samples) as well as the imaging of serum albumin in living cells.

Synthesis of highly functionalized spiro[4.4]nonane and spiro[4.5]decane motifs by the reaction of dimethylacetylenedicarboxylate (DMAD) with 2-(2'-ketoalkyl)-1,3-indandiones and 2-(3'-ketoalkyl)-1,3-indandiones, respectively, has been developed by utilizing a catalytic amount of DABCO. The tertiary hydroxy-containing spiro[4.4]nonane products were converted into fully conjugated pentafulvene π-systems in an acidic medium through dehydration and unprecedented C-C bond rearrangement., (© 2023 Wiley-VCH GmbH.)

Nitric oxide (NO) is a ubiquitous messenger molecule playing a key role in various physiological and pathological processes. However, producing a selective turn-on fluorescence response to NO is a challenging task due to (a) the very short half-life of NO (typically in the range of 0.1-10 s) in the biological milieu and (b) false positive responses to reactive carbonyl species (RCS) (e.g., dehydroascorbic acid and methylglyoxal etc.) and some other reactive oxygen/nitrogen species (ROS/RNS), especially with o -phenylenediamine (OPD) based fluorosensors. To avoid these limitations, NO sensors should be designed in such a way that they react spontaneously with NO to give turn-on response within the time frame of t 1/2 (typically in the range of 0.1-10 s) of NO and λ em in the visible wavelength along with good cell permeability to achieve biocompatibility. With these views in mind, a N-nitrosation based fluorescent sensor, NDAQ, has been developed that is highly selective to NO with ∼27-fold fluorescence enhancement at λ em = 542 nm with high sensitivity (LOD = 7 ± 0.4 nM) and shorter response time, eliminating the interference of other reactive species (RCS/ROS/RNS). Furthermore, all the photophysical studies with NDAQ have been performed in 98% aqueous medium at physiological pH, indicating its good stability under physiological conditions. The kinetic assay illustrates the second-order dependency with respect to NO concentration and first-order dependency with respect to NDAQ concentration. The biological studies reveal the successful application of the probe to track both endogenous and exogenous NO in living organisms.

Abnormal levels (high/low) of urinary human serum albumin (HSA) are associated with a number of diseases and thus act as an essential biomarker for quick therapeutic monitoring and biomedical diagnosis, entailing the urgent development of an effective chemosensor to quantify the albumin levels. Herein, we have rationally designed and developed a small fluorogenic molecular probe, (Z)-2-(5-((8-hydroxy-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl) methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid (HJRA) with a twisted intramolecular charge transfer (TICT) property, which can easily self-assemble into nonfluorescent nanoaggregates in aqueous solution. However, HJRA nanoaggregates can selectively bind with serum albumin proteins (HSA/BSA) in ∼100% PBS medium, thereby facilitating the disassembly of nanoaggregates into monomers, exhibiting a clear turn-on red fluorescent response toward HSA and BSA. Analysis of the specific binding mechanism between HJRA and HSA using a site-selective fluorescence displacement assay and molecular docking simulations indicates that a variety of noncovalent interactions are responsible for the disassembly of nanoaggregates with the concomitant trapping of the HJRA monomer at site I in HSA, yielding a substantial red emission caused by the inhibition of intramolecular rotation of HJRA probe inside the hydrophobic cavity of HSA. The limit of detection (LOD) determined by the 3σ/slope method was found to be 1.13 nM, which is substantially below the normal HSA concentration level in healthy urine, signifying the very high sensitivity of the probe toward HSA. The comparable results and quick response toward quantification of HSA in urine by HJRA with respect to the Bradford method clearly point toward the superiority of this method compared to the existing ones and may lead to biomedical applications for HSA quantification in urine. It may also find potential application in live-cell imaging of HSA.

Fluorescence spectroscopy is a significant bio-analytical technique for specific detection of nitric oxide (NO) and for broadcasting the in vitro and in vivo biological activities of this gasotransmitter. Herein, a benzo-coumarin embedded smart molecular probe (BCM) is employed for NO sensing through detailed fluorescence studies in purely aqueous medium. All the spectroscopic analysis and literature reports clearly validate the mechanistic insight of this sensing strategy i.e., the initial formation of 1,2,3,4-oxatriazole on treatment of the probe with NO which finally converted to its carboxylic acid derivative. This oxatriazole formation results in a drastic enhancement in fluoroscence intensity due to the photoinduced electron transfer (PET) effect. The kinetic investigation unveils the second and first-order dependency on [NO] and [BCM] respectively. The very low detection limit (16 nM), high fluorescence enhancement (123 fold) in aqueous medium and good formation constant (K f = (4.33 ± 0.48) × 10 4 M -1 ) along with pH invariability, non-cytotoxicity, biocompatibility and cell permeability make this probe a very effective one for tracking NO intracellularly.

Here, we present a detailed investigation on the interaction of 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD) embedded olanzapine derivative (OLA-NBD) with a model transport protein, human serum albumin (HSA). The thermodynamic parameters, Δ H o , Δ S o M G o , as evaluated by considering the van't Hoff relationship imply the major contribution of electrostatic/ionic interactions for the HSA-OLA-NBD association. The OLA-NBD induced quenching of HSA emission occurs through static quenching mechanism, indicating a 1:1 association, as portrayed from Benesi-Hildebrand plot, with ∼10 4 M -1 association constant value, and it is in good harmony with the value estimated from anisotropy experiment. The invariance of the time-resolved decay behavior of HSA with added OLA-NBD concentration, along with matching dependency of the binding constant ( K b ) value on temperature, also supports the occurrence of static quenching. The effect of β-cyclodextrin on HSA-OLA-NBD binding is characterized by a smaller K b value revealing that the OLA-NBD molecules are gradually removed from β-CD by HSA to achieve its medicinal outcome of drug delivery. The outcome from circular dichroism (CD) illustrates the variation of HSA secondary structure upon interaction with OLA-NBD. Concurrently, HSA-OLA-NBD association kinetics is also explored by applying the fluorescence technique. The possible interaction zone of OLA-NBD in HSA is investigated from AutoDock-based docking simulation study.

We report a novel phenazine-embedded fluorescent probe (2-[2-(pyridin-2-ylmethoxy)-phenyl]-1 H -imidazo[4,5- b ]phenazine, PIP), which upon complexation with Cu(II)-ion-forming [(PIP)Cu II (Cl)] becomes nonfluorescent but regenerates fluorescence in a selective reaction with NO and HNO over different biologically reactive oxygen and nitrogen (ROS/RNS) species under physiological conditions. The fluorescence intensity of PIP gets quenched due to the formation of the [(PIP)Cu II (Cl)] complex, which regenerates the fluorescence by 67 and 84% upon reaction either with NO or HNO, respectively, in the presence of other biological reducing species. Details of photophysical properties of PIP, [(PIP)Cu II (Cl)], and [(PIP)Cu I ] have been studied by density functional theory (DFT) calculations. The recognition efficacy of [(PIP)Cu II (Cl)] for exogenous and endogenous NO and HNO in A549 and RAW 264.7 cells with the flow cytometry application has also been demonstrated successfully.

Correction for 'A smart molecular probe for selective recognition of nitric oxide in 100% aqueous solution with cell imaging application and DFT studies' by Ananya Dutta et al., Org. Biomol. Chem., 2019, DOI: 10.1039/c9ob00177h.

Herein, a simple, least-cytotoxic as well as an efficient fluorescent sensor HqEN480 was prepared from (quinolin-8-yloxy)-acetic acid ethyl ester (L1) and N,N-dimethylethylene diamine to recognize NO in 100% aqueous solution. Its marked selectivity and sensitivity towards NO, makes it a highly suitable probe for nitric oxide under in vitro conditions with the possibility of in vivo monitoring of NO. Upon addition of 3.5 equivalents of NO, there is an approximately 7 fold enhancement in fluorescence intensity in aqueous solution with a corresponding Kf value of (1.75 ± 0.07) × 104 M-1. Quantum yields of HqEN480 and [HqEN480-NO] compounds are determined to be 0.04 and 0.22, respectively, using acidic quinine sulphate as a standard. In terms of the 3σ method, the LOD for nitric oxide was found to be 53 nM thus, making the probe suitable for tracking NO in biological systems.

We introduce herein, a novel copper complex-based fluorescent probe [CuII(DQ468)Cl]+ that exhibits a significant fluorescence turn-on response towards nitroxyl (HNO) with high selectivity over other biological reactive oxygen, nitrogen and sulfur species, including nitric oxide (NO). A smart strategy, involving HNO-induced reduction of paramagnetic [CuII(DQ468)Cl]+ to diamagnetic [CuI(DQ468)]+ with concomitant fluorescence enhancement via a PET mechanism is focused here. This reduction-based strategy was also supported by X-band EPR response and mass spectroscopy. The metal free probe (DQ468) showed high affinity towards Cu2+ to form [CuII(DQ468)Cl]+ with a 0.091 μM detection limit, which subsequently enabled the detection of HNO in an organo-aqueous medium at biological pH (7.4) in the green wavelength region (λem = 543 nm) with a LOD of 0.41 μM. The ground-state geometries of DQ468, [CuII(DQ468)Cl]+ and [CuI(DQ468)]+ were optimized by DFT calculations, which revealed that the central metal ion in [CuII(DQ468)Cl]+ is in a distorted tetrahedral geometry with the C1 point group. Additionally, the negligible cytotoxicity and good biocompatibility make the developed probe useful for the in vitro detection of HNO.

In this article, we have designed and synthesized a new, convenient and efficient phenanthroquinone-pyridoxal based fluorogenic probe PQPY, highly suitable for the selective and sensitive detection of nitric oxide in an aerated aqueous (7 : 3/H2O : MeCN) medium at pH 7.0 (10 mM HEPES buffer). Upon addition of nitric oxide, this probe exhibits emission in the green region (λem = 505 nm) which is ascribed to ICT (intramolecular charge transfer) from the phenanthroquinone moiety to the imidazole -N-N[double bond, length as m-dash]O fragment. The apparent formation constant, Kf, of the NO product of the ligand is (1.00 ± 0.2) × 105 M-1 and the LOD is 78 nM. The substantial enhancement of the life-time of the ligand (τ0 = 2.68 ns) occurs due to binding with nitric oxide (τ0 = 3.96 ns). This probe is low cytotoxicity, cell permeable and suitable for living cell imaging application.

A dual-emission pyrene-based new fluorescent probe ( N -(4-nitro-phenyl)- N '-pyren-1-ylmethyl-ene-ethane-1,2-diamine (PyDA-NP)) displays green fluorescence for nitric oxide (NO) sensing, whereas it exhibits blue emission in the aggregated state. The mechanism of nitric oxide (NO/NO + ) sensing is based on N-nitrosation of aromatic secondary amine, which was not interfered by reactive oxygen species and reactive nitrogen species. The aggregation-induced enhancement of emission (AIEE) behaviors of the PyDA-NP could be attributed to the restriction of intramolecular rotation and vibration, resulting in rigidity enhancement of the molecules. The AIEE behavior of the probe was well established from fluorescence, dynamic light scattering, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, optical fluorescence microscopy, and time-resolved photoluminescence studies. In a H 2 O/CH 3 CN binary mixture (8:2 v/v), the probe showed maximum aggregation with extensive (833-fold) increases in fluorescence intensity and high quantum yield (0.79). The aggregated state of the probe was further applied for the detection of nitroexplosives. It displayed efficient sensing of 2,4,6-trinitrophenol (TNP), corroborating mainly the charge-transfer process from pyrene to a highly electron-deficient TNP moiety. Furthermore, for the on-site practical application of the proposed analytical system, a contact-mode analysis was performed., Competing Interests: The authors declare no competing financial interest.

In this report, the interaction between a phenanthrene-pyrene-based fluorescent probe (PPI) and bovine serum albumin (BSA), a transport protein, has been explored by steady-state emission spectroscopy, fluorescence anisotropy, far-ultraviolet circular dichroism (CD), time-resolved spectral measurements, and molecular docking simulation study. The blue shift along with emission enhancement indicates the interaction between PPI and BSA. The binding of the probe causes quenching of BSA fluorescence through both static and dynamic quenching mechanisms, revealing a 1:1 interaction, as delineated from Benesi-Hildebrand plot, with a binding constant of ∼10 5 M -1 , which is in excellent agreement with the binding constant extracted from fluorescence anisotropy measurements. The thermodynamic parameters, Δ H °, Δ S °, and Δ G °, as determined from van't Hoff relationship indicate the predominance of van der Waals/extensive hydrogen-bonding interactions for the binding phenomenon. The molecular docking and site-selective binding studies reveal the predominant binding of PPI in subdomain IIA of BSA. From the fluorescence resonance energy transfer study, the average distance between tryptophan 213 of the BSA donor and the PPI acceptor is found to be 3.04 nm. CD study demonstrates the reduction of α-helical content of BSA protein on binding with PPI, clearly indicating the change of conformation of BSA., Competing Interests: The authors declare no competing financial interest.

A new sensor (L3) based on Rhodamine-B-en (2) and 2-(pyridin-2-ylmethoxy)benzaldehyde (1) has been developed for highly sensitive and selective recognition of NO in purely aqueous medium where the reaction of NO with the fluorophore leads to an unusual formation of nitrosohydroxylamine with the selective opening of the spirolactam ring over different cations, anions, amino-acids and other biological species with prominent enhancement in absorption and emission intensities. A large enhancement of fluorescence intensity for NO (11 fold) was observed upon addition of 3 equivalents of NO into the sensor in aqueous HEPES buffer (20 mM) at pH 7.20, μ = 0.05 M NaCl with naked eye detection. The corresponding Kf value was evaluated to be (7.55 ± 2.04) × 104 M-1 from the fluorescence titration plot. Quantum yields of L3 and the [L3 + NO] compound are found to be 0.07 and 0.77, respectively, using Rhodamine-6G as the standard. The LOD for NO was determined by the 3σ method and found to be 83.4 nM. The L3 sensor has low cytotoxicity, and is cell permeable and suitable for in vitro NO sensing. The in vivo compatibility of the sensor was also checked on zebrafish.

Solution-processed bovine serum albumin conjugated with ZnO nanosphere (BCZ) have been synthesized for ultra-low level mercury ion detection. Simple drop casting technique was adopted to fabricate such a mercury ion (Hg 2+ ) detection scheme. Morphological and optical characterization of the BCZ was performed by Transmission Electron Microscopy (TEM), UV-Vis and Fluorescence spectroscopic technique prior to device fabrication. The working principle of the BCZ device for Hg 2+ detection depends upon the variation of conductance with various concentration of Hg 2+ . An extensive study was carried out to investigate the effect of Hg 2+ upon transport properties of BCZ. The ultra-low level of Hg 2+ sensing was performed using this electrical detection technique. More importantly, this proposed BCZ based detection technique is found to be simple, inexpensive and very fast in responding (response time  ∼ 2.5 s) to heavy metal ion with a limit of detection (LOD) 0.03 fg/ml (S/ [Formula: see text]3).

We present a high-speed humidity sensor based on immobilization of bovine serum albumin upon multiwall carbon nanotube (IBC). A simple and versatile drop casting technique was employed to make the humidity sensor using novel material IBC at room temperature. IBC was synthesized using easy solution process technique. The working principle of the IBC humidity sensor depends upon the variation of output current or conductance with the exposure of different humidity level. Humidity sensing properties of our device is explained on the basis of charge transfer from water molecules to IBC and bovine serum albumin to multiwall carbon nanotube (MWCNT). Our sensor exhibits faster response time around 1.2 s and recovery time 1.5 s respectively.

This work demonstrates a novel label free and sensitive approach for the detection of L-histidine. This is a simple and reliable method for ultra-low level detection of L-histidine. All solution processed synthesizing technique was utilized to develop such type of detection scheme. Silicon substrate was replaced by normal transparent sheet to make it more facile and cost-effective detection technique. Fabricated device for L-histidine detection works upon the variation of current through the ZnO nanorod with L-histidine concentration. Operation principle strongly depends upon the electron charge transfer between metal cation and L-histidine inside the chelating complex. Morphological, structural and optical characterization of solution processed synthesized ZnO nanorod (ZnO NR) was carried out prior to sensor device fabrication. Our sensor device exhibits the sensitivity around 0.86 nA/fM and lower limit of detection (LOD) ∼ 0.1 fM(S/N=3).

In this paper, we demonstrate an electrical detection technique based on solution processed zinc oxide nanosphere for ultra-low level detection of bovine serum albumin (BSA). Our sensor device works on the basis of the variation of conductance of the ZnO nanosphere with different concentration of BSA. The morphological and structural characterizations of ZnO nanosphere were carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Circular dichroism (CD) spectroscopy was performed to investigate the chemical interaction between the BSA and zinc oxide nanosphere. Optical detection was performed using absorbance and Fourier transform infrared spectroscopy (FTIR) studies. Our device exhibits sensitivity 0.126 nA/pM, lower limit of detection (LOD) 10 pM and the fast response time around 5 s, confirming the highest sensitivity for BSA detection achieved so far. Sensing mechanism is governed on the basis of the charge transfer phenomenon between BSA and ZnO. All measurements were carried out at 1 V bias for low power operation.