Molecular Logic Research Articles

A Ratiometric Fluorescent Probe Dye-Functionalized MOFs Integrated with Logic Gate Operation for Efficient Detection of Acetaldehyde.

Volatile organic compounds (VOCs) are a class of hazardous gases that are widely present in the atmosphere and cause great harm to human health. In this paper, a ratiometric fluorescent probe (Dye@Eu-MOFs) based on a dye-functionalized metal-organic framework was designed to detect VOCs, which showed high sensitivity and specificity for acetaldehyde solution and vapor. A linear correlation between the integrated fluorescence intensity (I510/I616) and the concentration of acetaldehyde was investigated, enabling a quantitative analysis of acetaldehyde in the ranges of 1 × 10-4~10-5 μL/mL, with a low detection limit of 8.12 × 10-4 mg/L. The selective recognition of acetaldehyde could be clearly distinguished by the naked eye under the excitation of UV light. The potential sensing mechanism was also discussed. Significantly, a molecular logic gate was constructed based on the whole system, and finally, a molecular logic network system for acetaldehyde detection connecting basic and integrated logic operations was realized. This strategy provided an effective guiding method for constructing a molecular-level logic gate for acetaldehyde detection on a simple platform.

Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica.

Here, we introduce the Tabulae Paralytica-a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

A Schiff base functioning as a highly selective colorimetric sensor for Cu2+ ion

In this study, we employed a Schiff base ligand (L = 6,6′-((1E,1′E)-(cyclohexane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(2,4-di-tert-butylphenol)) to serve as a chemosensor exclusively for detecting Cu2+ ions over other metal ions and anions in a THF:H2O mixture (7:3, v/v). L exhibits an absorption band at 330 nm, which undergoes a bathochromic shift to 377 nm upon interaction with solely Cu2+ ions, suggesting a restricted internal charge transfer process of L. Analysis via ESI-MS and Job’s plot confirmed a 1:1 stoichiometric ratio between L and Cu2+. L demonstrated the capability to detect Cu2+ ions at a concentration as low as 0.46 μM. Furthermore, we investigated the effectiveness of L in developing molecular logic gates and its applications in analyzing Cu2+ in water samples.

The Molecular Logic of Synaptic Specificity in the Retinocollicular Pathway.

The Molecular Logic of Synaptic Specificity in the Retinocollicular Pathway.

Mango Leaves (Mangifera indica)-Derived Highly Florescent Green Graphene Quantum Dot Nanoprobes for Enhanced On-Off Dual Detection of Cholesterol and Fe2+ Ions Based on Molecular Logic Operation.

In the present study, we have engineered a molecular logic gate system employing both Fe2+ ions and cholesterol as bioanalytes for innovative detection strategies. We utilized a green-synthesis method employing the mango leaves extract to create fluorescent graphene quantum dots termed "mGQDs". Through techniques like HR-TEM, i.e., high-resolution transmission electron microscopy, Raman spectroscopy, and XPS, i.e., X-ray photoelectron spectroscopy, the successful formation of mGQDs was confirmed. The photoluminescence (PL) characteristics of mGQDs were investigated for potential applications in metal ion detection, specifically Fe2+ traces in water, by using fluorescence techniques. Under 425 nm excitation, mGQDs exhibited emission bands at 495 and 677 nm in their PL spectrum. Fe2+-induced notable quenching of mGQDs' PL intensity decreased by 97% with 2.5 μM Fe2+ ions; however, adding 20 mM cholesterol resulted in a 92% recovery. Detection limits were established through a linear Stern-Volmer (S-V) plot at room temperature, yielding values of 4.07 μM for Fe2+ ions and 1.8 mM for cholesterol. Moreover, mGQDs demonstrated biocompatibility, aqueous solubility, and nontoxicity, facilitating the creation of a rapid nonenzymatic cholesterol detection method. Selectivity and detection studies underscored mGQDs' reliability in cholesterol level monitoring. Additionally, a molecular logic gate system employing Fe2+ metal ions and cholesterol as a bioanalyte was established for detection purposes. Overall, this research introduces an ecofriendly approach to craft mGQDs and highlights their effectiveness in detecting metal ions and cholesterol, suggesting their potential as versatile nanomaterials for diverse analytical and biomedical applications.

Architecture of Molecular Logic Gates: From Design to Application as Optical Detection Devices

Three decades after A. P. de Silva’s seminal paper introduced the concept of logic gates at the molecular level, the field of molecular logic gates (MLGs) has witnessed significant advancements. MLGs are devices designed to perform logical operations, utilizing one or more physical or chemical stimulus signals (inputs) to generate an output response. Notably, MLGs have found diverse applications, with optical detection of analytes emerging as a notable evolution of traditional chemosensors. Organic synthesis methods are pivotal in crafting molecular architectures tailored as optical devices capable of analyte detection through logical functions. This review delves into the fundamental aspects and physical–chemical properties of MLGs, with a particular emphasis on synthetic strategies driving their design.

Implication of carbohydrazide chemosensors in selective sensing of Fe(III) and construction of molecular devices

Two new and two reference sensors L1-L2 and R1-R2, respectively, based on the hydrazide core were synthesized in good yields (70–86 %). A variety of analytical methods, including NMR, HRMS, and single-crystal XRD, were used to characterize these sensors. Cyclic voltammetry, UV–visible absorption, and emission spectroscopies were then used to confirm the electrochemical and photophysical characteristics of these sensors. Moreover, theoretical calculations at the level of DFT and TD-DFT were carried out to compare the experimental findings with the theoretical ones. The sensors were found to exhibit luminescence attributed to singlet ligand-centered (1LC) transitions. Based on their luminescent properties and the previous literature reports where structurally analogous sensors have been used for the detection of metal ions, these sensors were investigated as selective chemosensors for Fe(III) detection, with a "turn-off" fluorescence behaviour in a binding stoichiometry of 1:1 = sensor:M(III) [M = Fe(III)] with a limit of detection of 2.71–39 µM, or 0.15–2.81 ppm. The mechanistic details regarding the sensing of Fe(III) ion by the sensors was provided by NMR, IR, XPS and UV-visible absorption spectroscopic studies. To increase the usefulness of the sensors, L2 was also applied for the successful fabrication of the molecular logic gate and molecular lock keypad. Paper strip test and sensing of Fe(III) contaminated water by the sensors accounted for the practical applicability of the sensors in real life.

A multi-omic single-cell landscape of cellular diversification in the developing human cerebral cortex

The vast neuronal diversity in the human neocortex is vital for high-order brain functions, necessitating elucidation of the regulatory mechanisms underlying such unparalleled diversity. However, recent studies have yet to comprehensively reveal the diversity of neurons and the molecular logic of neocortical origin in humans at single-cell resolution through profiling transcriptomic or epigenomic landscapes, owing to the application of unimodal data alone to depict exceedingly heterogeneous populations of neurons. In this study, we generated a comprehensive compendium of the developing human neocortex by simultaneously profiling gene expression and open chromatin from the same cell. We computationally reconstructed the differentiation trajectories of excitatory projection neurons of cortical origin and inferred the regulatory logic governing lineage bifurcation decisions for neuronal diversification. We demonstrated that neuronal diversity arises from progenitor cell lineage specificity and postmitotic differentiation at distinct stages. Our data paves the way for understanding the primarily coordinated regulatory logic for neuronal diversification in the neocortex.

Multifunctional Antimonene-Silver Nanocomposites for Ultra-Multi-Mode and Multi-Analyte Sensing, Parallel and Batch Logic Computing, Long-Text Information Protection.

To simulate life's emergent functions, mining the multiple sensing capabilities of nanosystems, and digitizing networks of transduction signals and molecular interactions, is an ongoing endeavor. Here, multifunctional antimonene-silver nanocomposites (AM-Ag NCs) are synthesized facilely and fused for molecular sensing and digitization applications (including ultra-multi-mode and multi-analyte sensing, parallel and batch logic computing, long-text information protection). By mixing surfactant, AM, Ag+ and Sodium borohydride (NaBH4) at room temperature for 5min, the resulting NCs are comprised of Ag nanoparticles scattered within AM nanosheets and protected by the surfactant. Interestingly, AM-Ag NCs exhibit ultra-multi-mode sensing ability for multiplex metal ions (Hg2+, Fe3+, or Al3+), which significantly improved selectivity (≈2 times) and sensitivity (≈400 times) when analyzing the combined channels. Moreover, multiple sensing capabilities of AM-Ag NCs enable diverse batch and parallel molecular logic computations (including advanced cascaded logic circuits). Ultra-multi-mode selective patterns of AM-Ag NCs to 18 kinds of metal ions can be converted into a series of binary strings by setting the thresholds, and realized high-density, long-text information protection for the first time. This study provides new ideas and paradigms for the preparation and multi-purpose application of 2D nanocomposites, but also offers new directions for the fusion of molecular sensing and informatization.

A conserved molecular logic for neurogenesis to gliogenesis switch in the cerebral cortex

During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Sonic Hedgehog (Shh) signaling promotes the cortical RGC lineage switch to generate cortical oligodendrocytes and OB interneurons. During this process, cortical RGCs generate intermediate progenitor cells that express critical gliogenesis genes Ascl1, Egfr, and Olig2. The increased Ascl1 expression and appearance of Egfr+ and Olig2+ cortical progenitors are concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Furthermore, the transcriptional regulation of Olig2 and Egfr has not been explored. Here, we show that in cortical progenitor cells, multiple regulatory programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between the mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.

Dual function Schiff-base as a selective fluorescence “Turn-on” sensor for Zn2+ and a colorimetric sensor for Cu2+ and Fe3+ ions

A simple and adaptable salen-based Schiff base receptor (L = 6,6′-((1E,1′E)-(cyclohexane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenol))was employed in the current study for colorimetric detection of Cu2+, Fe3+, and fluorescence detection of Zn2+ ions in a semi-aqueous solution. L could identify the three target ions among the many different cations and anions in the solution. The turn-on fluorescence signal of L to Zn2+ ions was boosted by the restriction of the intramolecular charge transfer process, and the resulting chelation enhances the fluorescence signal. The sensing mechanisms were validated using a Job’s plot, Electrospray Ionization Mass Spectrometry (ESI-MS) analysis, Nuclear Magnetic Resonance (NMR) titration experiment, and theoretical calculation investigations. The detection limits for Zn2+ were determined to be 0.038 μM, whereas Cu2+ and Fe3+ detection limits were 0.58 μM and 0.62 μM, respectively. Next, L was used to develop solid silica gel and test strips for instantaneous colorimetric and fluorescent detection of the three target ions in real time. The trace level of Cu2+ and Fe3+ in the tap and drinking water samples could be quantitatively measured using L. Eventually, applications for keypad locks and molecular logic gates were developed utilizing the receptor L.

Coumarinyl(pyrrolyl)ethenes for the detection of Pd2+, CN− and F− ions, test strips based on them and logic gates

New coumarinyl(pyrrolyl)ethenes with a 1,3-thiazole bridge were synthesized. When irradiated at 365 nm, a hexatriene-cyclohexadiene rearrangement of the ring-opened form into a colored non-fluorescent ring-closed isomer occurs. The back reaction takes place when exposed to visible light at 540 nm. Furthermore, the compound with terminal 2,4-di-tert-butyl-6-hydroxybenzylidene receptor group represents a multifunctional sensor exhibiting selective chromogenic activity towards palladium(II) ions and CN− and F− anions. This probe interacts with Pd2+ cations with a noticeable naked eye effect - a change in the solution color from yellow to orange. The complexation stoichiometry is 1:1 and the detection limit was found to be 4.5 × 10−7 mol L−1. Similarly, CN− and F− anions cause a contrast naked eye effect with a change in the color of the solution from yellow to rose-red. For convenient detection of the above ions, test strips containing 4-(2-(2-(2,4-di-tert-butyl-6-hydroxybenzylidene)hydrazinyl)-5-(2-oxo-2H-chromen-3-yl)thiazol-4-yl)-1,5-dimethyl-1H-pyrrole-2-carbonitrile have been developed. In addition, a combinatorial molecular logic gate was designed based on multi-controllable photoswitching properties of the obtained probe.

Ferrocene-based chemosensor creates molecular logic circuit for selective detection of Hg2+ and Cu2+

A cation sensor, R, with multi-channel signaling was developed by creating a covalent connection between a ferrocene unit and pyridyl-pyrazole rings. Spectroscopic techniques and single-crystal X-ray diffraction were employed to characterize sensor R. The examination revealed a dihedral angle of 140.09° for the pyridyl-pyrazole rings. The receptor R functions as a highly selective multi-channel chemosensor, exhibiting chromogenic, fluorogenic, and electrochemical capabilities. In a CH3CN/water (9:1) solvent mixture, receptor R operates as a multi-channel signaling chemosensor, selectively detecting Hg2+ and Cu2+ ions in water. The original pale-yellow solution turned orange upon Hg2+ addition and green upon Cu2+ addition. A new low energy (LE) band at 460 nm was detected after adding one equivalent of Hg2+. In cyclic voltammetry (CV), the half-wave potential (E1/2) of 462 mV shifted to 622 mV, whereas in differential pulse voltammogram (DPV), the oxidation peak underwent an anodic shift (ΔE1/2 = 155 mV). The maximum emission at 423 nm was lowered by more than 90 % when the concentration of Hg2+ ions reached one equivalent. One equivalent addition of Cu2+ results in a new LE band at 740 nm. Cu2+ ions suppress the oxidation peak current in both the CV and DPV of R. It also demonstrates chelation-enhanced fluorescence effect (CHEF) with Cu2+. The interaction between cations and R was elucidated through 13C NMR titration. DFT calculations revealed the binding mode. Its distinctive fluorescence demonstrates a 'turn-on' response to Cu2+ and a 'turn-off' response to Hg2+ with selectivity. This concept has been applied to create a molecular combinatorial logic circuit.

A comparative study of two thienopyrimidine Schiff base probes for sequential monitoring of Ga3+ and Pd2.

Two Schiff base probes (S1 and S2) were prepared and synthesized by incorporating thienopyrimidine into salicylaldehyde or 3-ethoxysalicylaldehyde individually, with the aim of detecting Ga3+ and Pd2+ sequentially. Upon chelation with Ga3+, S1 and S2 exhibited fluorescence enhancement in DMSO/H2O buffer. Both S1-Ga3+ and S2-Ga3+ were quenched by Pd2+. The limit of detection for S1 in response to Ga3+ and Pd2+ was 2.86 × 10-7 and 4.4 × 10-9M, respectively. For S2, the limit of detection for Ga3+ and Pd2+ was 4.15 × 10-8 and 3.0 × 10-9M, respectively. Furthermore, the complexation ratios of both S1 and S2 with Ga3+ and Pd2+ were determined to be 1:2 through Job's plots, ESI-MS analysis, and theoretical calculations. Two molecular logic gates were constructed, leveraging the response behaviors of S1 and S2. Moreover, the potential utility of S1 and S2 for monitoring Ga3+ and Pd2+ in domestic water was verified.

Synthesis and Application of Salicylhydrazone Probes with High Selectivity for Rapid Detection of Cu2.

Using the aldehyde amine condensation procedure and the triphenylamine group as the skeleton structure, the new triphenylamine-aromatic aldehyde-succinylhydrazone probe molecule DHBYMH was created. A newly created acylhydrazone probe was structurally characterized by mass spectrometry (MS), NMR, and infrared spectroscopy (FTIR). Fluorescence and UV spectroscopy were used to examine DHBYMH's sensing capabilities for metal ions. Notably, DHBYMH achieved a detection limit of 1.62 × 10-7 M by demonstrating exceptional selectivity and sensitivity towards Cu2+ ions in an optimum sample solvent system (DMSO/H2O, (v/v = 7/3); pH = 7.0; cysteine (Cys) concentration: 1 × 10-4 M). NMR titration, high-resolution mass spectrometry analysis, and DFT computation were used to clarify the response mechanism. Ultimately, predicated on DHBYMH's reversible identification of Cu2+ ions in the presence of EDTA, a molecular logic gate was successfully designed.

PH-Controllable Redox Responsive Amphiphilic Viologens for Switchable Emulsions.

A pH and redox dual responsive amphiphilic viologen is synthesized, which can be reversibly transformed among the zwitterionic (SVa), monovalent anionic (SV+), and divalent anionic (SVH2+) forms upon pH variation, exhibiting pH-controllable redox responsive properties. Switchable Pickering emulsions with different droplet size and viscosity are prepared by the mixture of hydrophilic silica nanoparticles and the viologens (SV+ or SVH2+) at acidic conditions, while such combination yielded an oil-in-dispersion emulsion at neutral pH value. Not only can rapid reversible demulsification/stabilization of the Pickering emulsions be achieved by redox reactions, but the rate of redox-demulsification can also be controlled by pH trigger. The dual-responsive amphiphilic viologens have potential applications in developing intelligent colloid materials and molecular logic systems.

A captivating approach to elevate the detection of Al3+ ions incorporates the utilization of a tripodal receptor intricately embellishing the surface of zinc oxide

The FDA (Food and Drug Administration, (USA)) lists ZnO as a material that is widely acknowledged to be safe. ZnO NPs with a range of tiny particle sizes were made using the precipitation process. ZnO nanoparticles' surface is embellished with a tripodal sensor containing naphthol units. The assembly with the same receptor decorated on ZnO NPs is contrasted with the cation detection capabilities of the purified tripodal receptor. The UV–visible spectrophotometric analysis was conducted to study the state transitions of the receptor and the decorated ZnO receptor. A positive selectivity to Al3+ cations is determined by the fluorescence study under ideal circumstances. The particle size and surface morphologies are determined by DLS and SEM analysis for the same receptor − TP1 and embellished with a tripodal receptor TP2. Using a fluorescence switch-on Photoinduced Electron Transfer (PET) mechanism, the receptor coated on ZnO detects the presence of Al3+ ions with specificity. The binding constant value was determined using the B-H plot equation. Binding stoichiometry for [TP1-Al3+, TP2-Al3+] showed a 1:1 ratio. The fluorescence switches ON-OFF process of the ZnO surface adorned − TP2 with Tripodal receptor- TP1 was used to create molecular logic gates, which can function as a module for sensors and molecular switches. The addition of Na2EDTA in the solution of the [TP1; TP2 − Al3+] complex resulted in a noticeable reduction in the emission of fluorescence. This finding offers compelling support for the reversibility of the chemosensor. To enable the practical application of this sensor, we have developed a cassette containing receptors TP1 and TP2. Successfully, it can detect Al3+ metal ions. We performed a comprehensive assessment of the dependability and appropriateness of our approach in measuring the concentration of Al3+ ions in wastewater produced by important industrial procedures.

Reimagining Cortical Connectivity by Deconstructing Its Molecular Logic into Building Blocks.

Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene-projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene-projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene-projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene-projection relationship.

Molecular Logic Gates Based on Ferrocene-Containing Compounds

Ferrocene has a unique structure, i.e., a central iron atom neatly sandwiched between two cyclopentadienyl rings, which has revolutionized the chemists’ views about how metals bind to organic π-systems. This structural arrangement leads to some fascinating chemical and photophysical properties. The last three decades, there were reports about receptor molecules that could be considered to perform simple logic operations via coupling ionic bonding or more complex molecular-recognition processes with photonic (fluorescence) signals. In these systems, chemical binding (‘input’) results in a change in fluorescence intensity (‘output’) from the receptor. It has been proven that molecules respond to changes in their environment, such as the presence of various ions, neutral species, pHs, temperatures, and viscosities. Since their first realization by de Silva, molecular logic gates have been intensively experimentally studied, with purely theoretical studies being less common. Here, we present the research that has been conducted on Molecular Logic Gates (MLGs) containing ferrocene and their applications. We categorized such systems into three families of MLGs: long-chain molecules (oligomers or polymers) that incorporate ferrocene, medium-sized molecules that incorporate ferrocene, and systems where ferrocene or its derivatives are used as external additives. Furthermore, MLGs including metal cations without the ferrocene moiety are briefly presented, while computational methodologies for an accurate theoretical study of MLG, including metal cations, are suggested. Finally, future perspectives of MLGs containing ferrocene and their applications are also presented.

Quantum ChemicalStudyof a Dihydroazulene‐SpiropyranMulti‐StateMulti‐FunctionalMolecularSwitch

Quantum chemistry methods have been enacted to characterize the second‐order nonlinear optical (NLO) properties of a multi‐state molecular switch combining dihydroazulene and spiropyran units. They have demonstrated that the first hyperpolarizabilities constitute a novel output signal from the viewpoint of molecular logic, owing to the contrasts of NLO responses between the different forms of the dyad. On the one hand, the DFT calculations demonstrate that switching either unit has only a negligible impact on the geometrical parameters of the other one, as well as on the thermodynamics of their transformations. Similarly, as determined by time‐dependent DFT calculations, the UV/vis absorption spectra are in good approximation a superposition of those from the parent units. On the other hand, this additivity trend is not consistently observed for the NLO responses. However, an interpretation of these NLO responses has been proposed by using the unit sphere representation of the first hyperpolarizability tensors to address their orientational aspects as well as by resorting to the few‐state approximation and the missing state analysis to highlight the localized or charge‐transfer nature of the dominant excited states.