Synergistic Coordination and Hydrogen Bonding Interaction Modulate the Emission of Iridium Complex for Highly Sensitive Glutamine Imaging in Live Cells

Highly selective detection of intracellular glutamine (Gln) is very essential to understand the roles of Gln in some biological processes. Here, we report a new fluorescent method for selective imaging of Gln in live cells with an aldehyde-containing iridium complex, [Ir­(pba)₂(DMSO)₂]­PF₆ (Hpba = 4-(2-pyridiyl)­benzaldehyde) (Ir1), as the probe. Density functional theory (DFT) calculation and experimental results suggest that the coordination and hydrogen bonding interaction between Ir1 and Gln synergistically stabilize the Ir1–Gln complex, modulate charge-transfer characteristics and emission of Ir1, and as a consequence, enable Ir1 as the probe for the fluorescent sensing of Gln. The sensing strategy is well-responsive to Gln without interference from other amino acids or Gln-containing peptides and is demonstrated to be useful for in situ Gln imaging in live cells. The study provides a new method for fluorescent imaging of Gln in live cells, which is envisioned to find interesting applications in understanding the roles of Gln in some physiological processes

Zeolitic Imidazolate Framework-Based Electrochemical Biosensor for in Vivo Electrochemical Measurements

This study demonstrates the first exploitation of zeolitic imidazolate frameworks (ZIFs) as the matrix for constructing integrated dehydrogenase-based electrochemical biosensors for in vivo measurement of neurochemicals, such as glucose. In this study, we find that ZIFs are able to serve as a matrix for coimmobilizing electrocatalysts (i.e., methylene green, MG) and dehydrogenases (i.e., glucose dehydrogenase, GDH) onto the electrode surface and an integrated electrochemical biosensor is readily formed. We synthesize a series of ZIFs, including ZIF-7, ZIF-8, ZIF-67, ZIF-68, and ZIF-70 with different pore sizes, surface areas, and functional groups. The adsorption capabilities toward MG and GDH of these ZIFs are systematically studied with UV–vis spectroscopy, confocal laser scanning microscopy, and Fourier transfer-infrared spectroscopy. Among all the ZIFs demonstrated here, ZIF-70 shows excellent adsorption capacities toward both MG and GDH and is thus employed as the matrix for our glucose biosensor. To construct the biosensor, we first drop-coat a MG/ZIF-70 composite onto a glassy carbon electrode and then coat GDH onto the MG/ZIF-70 composite. In a continuous-flow system, the as-prepared ZIF-based biosensor is very sensitive to glucose with a linear range of 0.1–2 mM. Moreover, the ZIF-based biosensor is more highly selective on glucose than on other endogenous electroactive species in the cerebral system. In the end, we demonstrate that our biosensor is capable of monitoring dialysate glucose collected from the brain of guinea pigs selectively and in a near real-time pattern

Photodecomposition of Ferrocenedicarboxylic Acid in Methanol to Form an Electroactive Infinite Coordination Polymer and Its Application in Bioelectrochemistry

Accurately characterizing the product of photodecomposition of ferrocene derivatives remains a longstanding challenge due to its structural complexity and strong dependence on the solvent and the substituent. Herein, photodecomposition of ferrocenedicarboxylic acid (FcDC) in methanol is found for the first time to form an electroactive infinite coordinate polymer (ICP) with uniform size, good water stability and photostability, and excellent electrochemical activity. The possible mechanism for the ICP formation is proposed based on the fission of the Fe-ring bond and deprotonation of FcDC under light irradiation. The dissociated Fe²⁺ is first oxidized to Fe³⁺ that consequently coordinates with the deprotonated ferrocene dicarboxylate to produce ICP nanoparticles. This work not only provides a new insight into the product formation of the photodecomposition of ferrocene derivatives but also offers a mild and simple route to the synthesis of electroactive ICPs

Alkaline Post-Treatment of Cd(II)–Glutathione Coordination Polymers: Toward Green Synthesis of Water-Soluble and Cytocompatible CdS Quantum Dots with Tunable Optical Properties

In this study, we demonstrate a facile and environmentally friendly method for the synthesis of glutathione (GSH)-capped water-soluble CdS quantum dots (QDs) with a high cytocompatibility and a tunable optical property based on alkaline post-treatment of Cd–GSH coordination polymers (CPs). Cd–GSH CPs are synthesized with the coordination reaction of Cd²⁺ with GSH at different pH values, and the CdS QDs are then formed by adding NaOH to the aqueous dispersion of the Cd–GSH CPs to break the coordination interaction between Cd²⁺ and GSH with the release of sulfur. The particle size and optical property of the as-formed CdS QDs are found to be easily tailored by simply adjusting the starting pH values of GSH solutions used for the formation of Cd–GSH CPs, in which the wavelengths of trap-state emission of the QDs red-shift with an increase in the sizes of the QDs that is caused by an increase in the starting pH values of GSH solutions. In addition, the use of GSH as the capping reagent eventually endows the as-formed CdS QDs with enhanced water solubility and good cytocompatibility, as demonstrated with HeLa cells. The method demonstrated here is advantageous in that the cadmium precursor and the sulfur source are nontoxic and easily available, and the size, optical properties, water solubility, and cytocompatibilty of the as-formed CdS QDs are simply achieved and experimentally regulated. This study offers a new and green synthetic route to water-soluble and cytocompatible CdS QDs with tunable optical properties

An Electrochemical Method for Investigation of Conformational Flexibility of Active Sites of <i>Trametes versicolor</i> Laccase Based on Sensitive Determination of Copper Ion with Cysteine-Modified Electrodes

This study demonstrates a facile yet effective electrochemical method to investigate the conformational flexibility of the active sites of <i>Trametes versicolor</i> (<i>Tv</i>) laccase based on sensitive determination of copper ions (Cu²⁺) dissociated from the enzyme with the cysteine-modified Au electrodes. In the native state, the multicopper active sites are deeply buried in the polypeptide of <i>Tv</i> laccase and are thus not electrochemically detectable even at the cysteine-modified Au electrodes. Upon the unfolding of <i>Tv</i> laccase induced by guanidine hydrochloride (GdnHCl), copper ions dissociate from the peptide chain and, as a consequence, are electrochemically reduced and thus detected at the cysteine-modified Au electrodes. Such a property could be used to investigate the conformational flexibility of multicopper active sites of <i>Tv</i> laccase in a simple way. We find that both the conformation of the multicopper active sites in <i>Tv</i> laccase and the enzyme activity change with the presence of a low concentration of GdnHCl denaturant (midpoint, where 50% of the enzyme is unfolded, at 0.7 M). This concentration is lower than that required to induce the conformational changes of <i>Tv</i> laccase molecule as a whole (midpoint at 3.4 M), as investigated by the intrinsic fluorescence of <i>Tv</i> laccase. This observation suggests that the multicopper active sites are formed by relatively weak interactions and hence may be conformationally more flexible than the intact enzyme. The electrochemical method demonstrated in this study is technically simple yet effective and could be potentially useful for investigation on the thermodynamics and kinetics of the conformational changes of multicopper oxidases induced by different denaturants

Aspartic Acid-Promoted Highly Selective and Sensitive Colorimetric Sensing of Cysteine in Rat Brain

Direct selective determination of cysteine in the cerebral system is of great importance because of the crucial roles of cysteine in physiological and pathological processes. In this study, we report a sensitive and selective colorimetric assay for cysteine in the rat brain with gold nanoparticles (Au-NPs) as the signal readout. Initially, Au-NPs synthesized with citrate as the stabilizer are red in color and exhibit absorption at 520 nm. The addition of an aqueous solution (20 μL) of cysteine or aspartic acid alone to a 200 μL Au-NP dispersion causes no aggregation, while the addition of an aqueous solution of cysteine into a Au-NP dispersion containing aspartic acid (1.8 mM) causes the aggregation of Au-NPs and thus results in the color change of the colloid from wine red to blue. These changes are ascribed to the ion pair interaction between aspartic acid and cysteine on the interface between Au-NPs and solution. The concentration of cysteine can be visualized with the naked eye and determined by UV–vis spectroscopy. The signal output shows a linear relationship for cysteine within the concentration range from 0.166 to 1.67 μM with a detection limit of 100 nM. The assay demonstrated here is highly selective and is free from the interference of other natural amino acids and other thiol-containing species as well as the species commonly existing in the brain such as lactate, ascorbic acid, and glucose. The basal dialysate level of cysteine in the microdialysate from the striatum of adult male Sprague–Dawley rats is determined to be around 9.6 ± 2.1 μM. The method demonstrated here is facile but reliable and durable and is envisaged to be applicable to understanding the chemical essence involved in physiological and pathological events associated with cysteine

Water-Stable, Adaptive, and Electroactive Supramolecular Ionic Material and Its Application in Biosensing

Developing water-stable and adaptive supramolecular materials is of great importance in various research fields. Here, we demonstrate a new kind of water-stable, adaptive, and electroactive supramolecular ionic materials (SIM) that is formed from the aqueous solutions of imidazolium-based dication and dianionic dye (i.e., 2,2′-azino-bis­(3-ethylbenzothiazoline-6-sulfonic acid), ABTS) through ionic self-assembly. The formed SIM not only shows good thermostability and unique optical and electrochemical properties that are raised from precursors of the SIM, but also exhibits good water-stability, salt-stability, and adaptive encapsulation properties toward some heterocyclic cationic dye molecules. UV–vis and FT-IR results demonstrate that this encapsulation property is essentially based on the electrostatic interactions between the guest dye molecules and ABTS in the SIM. The application of the SIM prepared here is illustrated by the development of a new electrochemical sensor for NADH sensing at a low potential. This study not only opens a new avenue to the preparation of the supramolecular materials, but also provides a versatile platform for electrochemical (bio)­sensing

Real-Time Colorimetric Assay of Inorganic Pyrophosphatase Activity Based on Reversibly Competitive Coordination of Cu²⁺ between Cysteine and Pyrophosphate Ion

In this study we demonstrate a new colorimetric method for real-time pyrophosphatase (PPase) activity assay based on reversible tuning of the dispersion/aggregation states of gold nanoparticles (Au-NPs) by controlling the coordination of Cu²⁺ between cysteine and pyrophosphate ion (PPi) with PPase. The addition of Cu²⁺ to the cysteine-stabilized Au-NP dispersion results in the aggregation of Au-NPs, while the further addition of PPi to this aggregation turns the aggregated Au-NPs into their dispersed state because of the higher coordination reactivity between Cu²⁺ and PPi than that between Cu²⁺ and cysteine. The subsequent addition of PPase to the PPi-triggered dispersed Au-NPs restores the aggregation state of Au-NPs because PPase catalyzes the hydrolysis of PPi into orthophosphate and thus consumes PPi in the reaction system. In this study, we utilize this reversibility of the change between the aggregation/dispersion states of Au-NPs for real-time colorimetric monitoring of PPase activity by continuously measuring the ratio of absorbance at the wavelength of 650 nm (<i>A</i>₆₅₀) to that at 522 nm (<i>A</i>₅₂₂) in the time-dependent UV–vis spectra of Au-NP dispersions containing different activities of PPase. To calculate the kinetics of the PPase-catalyzed hydrolysis of PPi, the <i>A</i>₆₅₀/<i>A</i>₅₂₂ values are converted into PPi concentrations to obtain the time-dependent changes of PPi concentrations in the dispersions containing different activities of PPase. The initial reaction rates (<i>v</i>₀) are thus achieved from the time-dependent logarithm of PPi concentrations with the presence of different PPase activities. Under the experimental conditions employed here, the <i>v</i>₀ values are linear with the PPase activity within a range from 0.025 to 0.4 U with a detection limit down to 0.010 U (S/N = 3). Moreover, the colorimetric method developed here is also employed for PPase inhibitor evaluation. This study offers a simple yet effective method for real-time PPase activity assay

Strong Interaction between Imidazolium-Based Polycationic Polymer and Ferricyanide: Toward Redox Potential Regulation for Selective In Vivo Electrochemical Measurements

This study effectively demonstrates a strategy to enable the ferricyanide-based second-generation biosensors for selective in vivo measurements of neurochemicals, with glucose as an example. The strategy is based on regulation of redox potential of ferricyanide mediator by carefully controlling the different adsorption ability of ferricyanide (Fe­(CN)₆^3‑) and ferrocyanide (Fe­(CN)₆^4‑) onto electrode surface. To realize the negative shift of the redox potential of Fe­(CN)₆^3‑/4‑, imidazolium-based polymer (Pim) is synthesized and used as a matrix for surface adsorption of Fe­(CN)₆^3‑/4‑ due to its stronger interaction with Fe­(CN)₆^3‑ than with Fe­(CN)₆^4‑. The different adsorption ability of Fe­(CN)₆^3‑ and Fe­(CN)₆^4‑ onto electrodes modified with a composite of Pim and multiwalled carbon nanotubes (MWNTs) eventually enables the stable surface adsorption of both species to generate integrated biosensors and, more importantly, leads to a negative shift of the redox potential of the surface-confined redox mediator. Using glucose oxidase (GOD) as the model biorecognition units, we demonstrate the validity of the ferricyanide-based second-generation biosensors for selective in vivo neurochemical measurements. We find that the biosensors developed with the strategy demonstrated in this study can be used well as the selective detector for continuous online detection of striatum glucose of guinea pigs, by integration with in vivo microdialysis. This study essentially paves a new avenue to developing electrochemical biosensors effectively for in vivo neurochemical measurements, which is envisaged to be of great importance in understanding the molecular basis of physiological and pathological events

Data_Sheet_1_Attention-deficit/hyperactive disorder updates.doc

BackgroundAttention-deficit/hyperactive disorder (ADHD) is a neurodevelopmental disorder that commonly occurs in children with a prevalence ranging from 3.4 to 7.2%. It profoundly affects academic achievement, well-being, and social interactions. As a result, this disorder is of high cost to both individuals and society. Despite the availability of knowledge regarding the mechanisms of ADHD, the pathogenesis is not clear, hence, the existence of many challenges especially in making correct early diagnosis and provision of accurate management.ObjectivesWe aimed to review the pathogenic pathways of ADHD in children. The major focus was to provide an update on the reported etiologies in humans, animal models, modulators, therapies, mechanisms, epigenetic changes, and the interaction between genetic and environmental factors.MethodsReferences for this review were identified through a systematic search in PubMed by using special keywords for all years until January 2022.ResultsSeveral genes have been reported to associate with ADHD: DRD1, DRD2, DRD4, DAT1, TPH2, HTR1A, HTR1B, SLC6A4, HTR2A, DBH, NET1, ADRA2A, ADRA2C, CHRNA4, CHRNA7, GAD1, GRM1, GRM5, GRM7, GRM8, TARBP1, ADGRL3, FGF1, MAOA, BDNF, SNAP25, STX1A, ATXN7, and SORCS2. Some of these genes have evidence both from human beings and animal models, while others have evidence in either humans or animal models only. Notably, most of these animal models are knockout and do not generate the genetic alteration of the patients. Besides, some of the gene polymorphisms reported differ according to the ethnic groups. The majority of the available animal models are related to the dopaminergic pathway. Epigenetic changes including SUMOylation, methylation, and acetylation have been reported in genes related to the dopaminergic pathway.ConclusionThe dopaminergic pathway remains to be crucial in the pathogenesis of ADHD. It can be affected by environmental factors and other pathways. Nevertheless, it is still unclear how environmental factors relate to all neurotransmitter pathways; thus, more studies are needed. Although several genes have been related to ADHD, there are few animal model studies on the majority of the genes, and they do not generate the genetic alteration of the patients. More animal models and epigenetic studies are required.</p