Advances in the application of logic gates in nanozymes.

Nanozymes are a class of nanomaterials with biocatalytic function and enzyme-like activity, whose advantages include high stability, low cost, and mass production. They can catalyze the substrates of natural enzymes based on specific nanostructures and serve as substitutes for natural enzymes. Their applied research involves a wide range of fields such as biomedicine, environmental governance, agriculture, and food. Molecular logic gates are a new cross-disciplinary discipline, which can simulate the function of silicon circuits on a molecular scale, perform single or multiple input logic operations, and generate logic outputs. A molecular logic gate is a binary operation that converts an input signal into an output signal according to the rules of Boolean logic, generating two signals, a high level, and a low level. The high and low levels represent the "true" and "false" values of the logic gates, and their outputs correspond to "l" and "0" of the molecular logic gates, respectively. The combination of nanozymes and logic gates is a novel and attractive research direction, and the cross-application of the two brings new opportunities and ideas for various fields, such as the construction of efficient biocomputers, intelligent drug delivery systems, and the precise diagnosis of diseases. This review describes the application of logic gates based on nanozymes, which is expected to provide a certain theoretical foundation for researchers' subsequent studies.

Development of gold nanoparticles-aptamer nanocomposite for multiplexed analysis of antibiotics and design of molecular logic gates.

The widespread use of antibiotics caused severe problems of antibiotic residues in foodstuffs and water, posing a serious threat to public health and thus urging the development of sensitive, selective, and rapid detection methods for antibiotics. In this study, a fluorescence resonance energy transfer (FRET)-based system is developed for the multiplexed analysis of chloramphenicol (CAP) and streptomycin (Strep) with detection limits of 2.51 and 8.69µg l-1, respectively. The FRET-based system consists of Cy3-tagged anti-CAP aptamer-conjugated gold nanoparticles (AuNPs) (referred to as AuNPs-AptCAP) and Cy5-tagged anti-Strep aptamer-conjugated AuNPs (referred to as AuNPs-AptStrep). In addition, AuNPs-AptCAP and AuNPs-AptStrep have been demonstrated to serve as signal transducers for implementing a series of logic operations such as YES, NOT, INH, OR, (2-4)-Decoder and even more complicated multi-level logic gates (OR-INH). Based on the outputs of logic operations, it could be figured out whether targeted analytes were present or not, thus enabling multiplex sensing and evaluation of pollution status. This proof of concept study might provide a new route for the enhanced sensing performance to distinguish different pollution status as well as the design of molecular mimics of logic elements to demonstrate better applicability.

Dye/metal ion-based chemosensing ensemble towards l-histidine and l-lysine determination in water via different optical responses.

In this study, a novel simple type of label-free, ultra-sensitive, and highly selective UV-Vis absorption and naked-eye detection of histidine (His) and lysine (Lys) using a dye/metal ion ensemble is developed. The outcoming high sensitivity and selectivity for histidine and lysine were attained by changing the metal ions. The indicator is released due to its displacement from the murexide (Mure)/Cu2+ complex by histidine and the change in absorbance may be due to the further complexation of lysine with the additional coordination sites present in the zinc atom of Mure/Zn2+ complex. The label-free chemosensor provided sensitive and selective detection of l-histidine and l-lysine with detection limits of 9.1 and 9.4 nmol L-1, respectively. The protocol especially offers high selectivity for the determination of His and Lys among amino acids found in human urine samples. Furthermore, INHIBIT and NAND molecular logic gates were obtained using chemical inputs and UV-Vis absorbance signal output.

A Molecular Secret Sharing Scheme.

A method for implementing a secret sharing scheme at the molecular level is presented. By creating molecular code generators that are self-assembled from several molecular components, we established a means for distributing distinct code-activating elements among several participants. In this way, an authorization code can only be generated when all the participants are present, which ensures that highly secured systems cannot be operated by unauthorized individuals or disloyal users. Additional layers of protection result from the ability to program the security code by replacing one or several molecular components and by subjecting the system to distinct chemical inputs.

Self-Assembling Molecular Logic Gates Based on DNA Crossover Tiles.

DNA-based computational hardware has attracted ever-growing attention due to its potential to be useful in the analysis of complex mixtures of biological markers. Here we report the design of self-assembling logic gates that recognize DNA inputs and assemble into crossover tiles when the output signal is high; the crossover structures disassemble to form separate DNA stands when the output is low. The output signal can be conveniently detected by fluorescence using a molecular beacon probe as a reporter. AND, NOT, and OR logic gates were designed. We demonstrate that the gates can connect to each other to produce other logic functions.

Luminescent Benzothiazole-Based Fluorophore of Anisidine Scaffoldings: a "Turn-On" Fluorescent Probe for Al3+ and Hg2+ Ions.

A new anisidine possessing benzothiaozle-based chemosensor (1) has been designed and synthesized. The chemosensor 1 was designed to provide hard base environment for ratiometric detection of comparatively less studied Al3+ ions. In CH3CN, the fluorescence spectra of chemosensor 1 red shifted from 368 to 430 nm with addition of Al3+ and Hg2+ ions; while Cu2+ ions caused quenching of emission intensity of 1. These differential changes observed with Al3+ and Cu2+ ions addition enabled chemosensor 1 to construct "NOR" and "TRANSFER" logic gates.

Spectral and DFT studies of anion bound organic receptors: Time dependent studies and logic gate applications.

New colorimetric receptors R1 and R2 with varied positional substitution of a cyano and nitro signaling unit having a hydroxy functionality as the hydrogen bond donor site have been designed, synthesized and characterized by FTIR, 1H NMR spectroscopy and mass spectrometry. The receptors R1 and R2 exhibit prominent visual response for F- and AcO- ions allowing the real time analysis of these ions in aqueous media. The formation of the receptor-anion complexes has been supported by UV-vis titration studies and confirmed through binding constant calculations. The anion binding process follows a first order rate equation and the calculated rate constants reveal a higher order of reactivity for AcO- ions. The 1H NMR titration and TDDFT studies provide full support of the binding mechanism. The Hg2+ and F- ion sensing property of receptor R1 has been utilized to arrive at "AND" and "INHIBIT" molecular logic gate applications.

Tunable Molecular Logic Gates Designed for Imaging Released Neurotransmitters.

Tunable dual-analyte fluorescent molecular logic gates (ExoSensors) were designed for the purpose of imaging select vesicular primary-amine neurotransmitters that are released from secretory vesicles upon exocytosis. ExoSensors are based on the coumarin-3-aldehyde scaffold and rely on both neurotransmitter binding and the change in environmental pH associated with exocytosis to afford a unique turn-on fluorescence output. A pH-functionality was directly integrated into the fluorophore π-system of the scaffold, thereby allowing for an enhanced fluorescence output upon the release of labeled neurotransmitters. By altering the pH-sensitive unit with various electron-donating and -withdrawing sulfonamide substituents, we identified a correlation between the pKa of the pH-sensitive group and the fluorescence output from the activated fluorophore. In doing so, we achieved a twelvefold fluorescence enhancement upon evaluating the ExoSensors under conditions that mimic exocytosis. ExoSensors are aptly suited to serve as molecular imaging tools that allow for the direct visualization of only the neurotransmitters that are released from secretory vesicles upon exocytosis.

An "AND" Molecular Logic Gate as a Super-Enhancers for De Novo Designing Activatable Probe and Its Application in Atherosclerosis Imaging.

Developing activatable fluorescent probes with superlative fluorescence enhancement factor (F/F0 ) to improve the signal-to-noise (S/N) ratio is still an urgent issue. "AND" molecular logic gates are emerging as a useful tool for enhanced probes selectivity and accuracy. Here, an "AND" logic gate is developed as super-enhancers for designing activatable probes with huge F/F0 and S/N ratio. It utilizes lipid-droplets (LDs) as controllable background input and sets the target analyte as variable input. The fluorescence is tremendously quenching due to double locking, thus an extreme F/F0 ratio of target analyte is obtained. Importantly, this probe can transfer to LDs after a response occurs. The target analyte can be directly visualized through the spatial location without a control group. Accordingly, a peroxynitrite (ONOO- ) activatable probe (CNP2-B) is de novo designed. The F/F0 of CNP2-B achieves 2600 after reacting with ONOO- . Furthermore, CNP2-B can transfer from mitochondria to lipid droplets after being activated. The higher selectivity and S/N ratio of CNP2-B are obtained than commercial probe 3'-(p-hydroxyphenyl) fluorescein (HPFin vitro and in vivo. Therefore, the atherosclerotic plaques at mouse models are delineated clearly after administration with in situ CNP2-B probe gel. Such input controllable "AND" logic gate is envisioned to execute more imaging tasks.

Tracing a new path in the field of AI and robotics: mimicking human intelligence through chemistry. Part I: molecular and supramolecular chemistry.

Chemical Artificial Intelligence (CAI) is a brand-new research line that exploits molecular, supramolecular, and systems chemistry in wetware (i.e., in fluid solutions) to imitate some performances of human intelligence and promote unconventional robotics based on molecular assemblies, which act in the microscopic world, otherwise tough to be accessed by humans. It is undoubtedly worth spreading the news that AI researchers can rely on the help of chemists and biotechnologists to reach the ambitious goals of building intelligent systems from scratch. This article reports the first attempt at building a Chemical Artificial Intelligence knowledge map and describes the basic intelligent functions that can be implemented through molecular and supramolecular chemistry. Chemical Artificial Intelligence provides new tools and concepts to mimic human intelligence because it shares, with biological intelligence, the same principles and materials. It enables peculiar dynamics, possibly not accessible in software and hardware domains. Moreover, the development of Chemical Artificial Intelligence will contribute to a deeper understanding of the strict link between intelligence and life, which are two of the most remarkable emergent properties shown by the Complex Systems we call biological organisms.

Hybrid films composed of ethyl(hydroxyethyl)cellulose and silica xerogel functionalized with a fluorogenic chemosensor for the detection of mercury in water.

Ethyl(hydroxyethyl)cellulose (EHEC) and a silica-based xerogel (SBX) were functionalized with a (18-crown-6)-styrylpyridine precursor (1) to obtain the modified polymers EHEC-1 and SBX-1, respectively. Films were obtained and the resulting materials were used as fluorogenic devices for the detection of Hg2+ in water. The films produced from EHEC-1 showed high water retention, making it difficult to apply as a reusable optical chemosensor. Since SBXs are recognized in the literature for their hydrophobicity, a hybrid film composed of EHEC and SBX-1 which did not show water retention was produced and characterized. This system showed rapid response time, outstanding selectivity compared to several other studied metal ions, and sensitivity for the detection of Hg2+ in water. The detection limit for this material using fluorescence technique was 2 ppb (∼10-8 mol L-1). The reversibility of the complex formed between EHEC-SBX-1 film and Hg2+ was demonstrated by the addition of cysteine to the medium. The result obtained also allowed the assembly of INHIBIT and IMPLICATION molecular logic gates, using Hg2+ and cysteine as inputs. The results described in this article have important significance in the development of novel reversible fluorogenic chemosensors and adsorbent materials for the effective removal of Hg2+ ions.

Fluorescent Probes as a Tool in Diagnostic and Drug Delivery Systems.

Over the last few years, the development of fluorescent probes has received considerable attention. Fluorescence signaling allows noninvasive and harmless real-time imaging with great spectral resolution in living objects, which is extremely useful for modern biomedical applications. This review presents the basic photophysical principles and strategies for the rational design of fluorescent probes as visualization agents in medical diagnosis and drug delivery systems. Common photophysical phenomena, such as Intramolecular Charge Transfer (ICT), Twisted Intramolecular Charge Transfer (TICT), Photoinduced Electron Transfer (PET), Excited-State Intramolecular Proton Transfer (ESIPT), Fluorescent Resonance Energy Transfer (FRET), and Aggregation-Induced Emission (AIE), are described as platforms for fluorescence sensing and imaging in vivo and in vitro. The presented examples are focused on the visualization of pH, biologically important cations and anions, reactive oxygen species (ROS), viscosity, biomolecules, and enzymes that find application for diagnostic purposes. The general strategies regarding fluorescence probes as molecular logic devices and fluorescence-drug conjugates for theranostic and drug delivery systems are discussed. This work could be of help for researchers working in the field of fluorescence sensing compounds, molecular logic gates, and drug delivery.

Ratio Fluorescent Detecting of Tryptophan and Its Metabolite 5-Hydroxyindole-3-acetic Acid Relevant with Depression via Tb(III) Modified HOFs Hybrids: Further Designing Recyclable Molecular Logic Gate Connected by Back Propagation Neural Network.

Exploring intelligent fluorescent materials with high reliability and precision to diagnose diseases is significant but remains a great challenge. Herein, based on coordination post-synthetic modification, a Tb3+ functionalized ME-PA (Tb@1) is prepared, which can emit brilliant green fluorescence through ligand-to-mental charge transfer-assisted energy transfer (LMCT-ET) process from ME-PA to Tb3+ ions. Tb@1 can simultaneously distinguish Tryptophan (Try) and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA), two effective indicators for depression, in ratio and colorimetric mode. And this sensor behaves the advantages of high efficiency and sensitivity, as well as excellent reusability and anti-interference. The PET process from ME to Try and 5-HIAA, and the competitive absorption between analytes and Tb@1 may be relevant to sensing mechanism. In realistic serum or urine environment, the detection limits of Tb@1 for Try and 5-HIAA are 0.0183 and 0.0149 mg L-1 respectively. Moreover, in conjunction with back propagation neural network (BPNN), two dual-output molecular logic gates that can be calculated circularly are further designed, which realizes intelligent control of the electronic component to identify the existence of two biomarkers and judge their concentrations from fluorescence images. This work offers a novel approach to modulate logic circuits based on ML-assisted HOF fluorescent sensor, with promising application for a precise and pictorial depression diagnosis.

Electrochemical label-free biomolecular logic gates regulated by distinct inputs.

In current work, with elaborate designs of G-quadruplex containing "Y" junction structures, we demonstrate the construction of several new and label-free electrochemical logic gate operations (OR, AND, NOR, and NAND) by defining two distinct biomolecules, human 8-oxo-7,8-dihydroguanine DNA glycosylase 1 (hOGG1) and microRNA-141 (miRNA-141), as the inputs. The "Y" junction structures are immobilized onto the surface of gold electrode as the signal transduction platform. The presence of the input molecules with different combinations can alter the "Y" junction structures to disrupt the formation of the complete G-quadruplexes via 8-oxoG-site specific cleavage and miRNA-141-triggered displacement of the "Y" junctions. Subsequent association of hemin with the G-quadruplex sequences thus yields significant current variation outputs upon electrochemical reduction of hemin on the electrode, leading to the successful function of different logic operations without the involvement of labeling the DNA sequences with electro-active species. Featured with the advantages of multiple logic operations with distinct inputs and the label-free electrochemical format, such molecular logic gates can potentially provide promising opportunities for the development of simple and robust biological logic gates for various applications.

Development of dual enzyme responsive molecular AND logic gate.

Molecular logic gates are information processing devices that can respond to environmental signals and produce a readable output in response through Boolean logic operations. Molecules with these properties have been used to build smart sensors and therapeutic agents. In this work, dual enzyme-responsive molecular AND logic gate is developed with the intention to discriminate various combinations of enzyme level and/or activity. A resorufin-based sensor is substituted with self-immolative tyrosinase recognition site, 3-hydroxy benzyl group. The Hydroxyl group is protected with acetyl moiety which decreases the affinity of the enzyme. When both tyrosinase and esterase are present in the solution, the acetyl group is removed by the latter enzyme, allowing the former to recognise the ligand. Oxidation of the ligand by tyrosinase triggers self-immolative cleavage of the substitution, leading to almost 70 fold enhancement in fluorescence. When single enzyme is applied, there is no significant change in the emission intensity overall, an AND logic gate is constructed. Selectivity and Michaelis-Menten kinetics of the sensor is analysed. Smart molecular probes can contribute to the research on the development of biosensors that can discriminate diseases having characteristic combinations of enzyme activities.

Preparation of Tetrabenzo[4.4.2]undecastarphene by On-Surface Synthesis.

A large dissymmetric starphene molecule, the tetrabenzo[a,c,u,w]naphtho[2,3-l]nonaphene, was obtained by first preparing a soluble precursor which was then sublimated on a Au(111) surface in an ultra-high vacuum. In a second step, controlled annealings from 200 °C to 275 °C initiated two successive cyclodehydrogenation steps with the formation of 3 new carbon-carbon bonds. A second conformer was also stable enough during the annealing step to give another compound in similar yield, the benzodibenzo[7,8,9,10]naphthaceno[2,1-h]phenanthro[9,10-p]hexaphene. The formation of this more-hindered species stresses the importance of strong molecule-surface interactions during the cyclodehydrogenations steps of these large polyaromatic hydrocarbons.

Infochemistry and the Future of Chemical Information Processing.

Nowadays, information processing is based on semiconductor (e.g., silicon) devices. Unfortunately, the performance of such devices has natural limitations owing to the physics of semiconductors. Therefore, the problem of finding new strategies for storing and processing an ever-increasing amount of diverse data is very urgent. To solve this problem, scientists have found inspiration in nature, because living organisms have developed uniquely productive and efficient mechanisms for processing and storing information. We address several biological aspects of information and artificial models mimicking corresponding bioprocesses. For instance, we review the formation of synchronization patterns and the emergence of order out of chaos in model chemical systems. We also consider molecular logic and ion fluxes as information carriers. Finally, we consider recent progress in infochemistry, a new direction at the interface of chemistry, biology, and computer science, considering unconventional methods of information processing.

Bistable (Supra)molecular Switches on 3D-Printed Responsive Interfaces with Electrical Readout.

Molecular switching memories have gained great importance in recent years because of the current sharp increase in the production of consumer electronics. Herein, 3D-printed nanocomposite carbon electrodes (3D-nCEs) have been explored as unconventional responsive interfaces to electrically readout bistable molecular switches via electrochemical impedance spectroscopy as the output system. As a proof-of-concept, two different 3D-printed responsive interfaces have been devised using surface engineering for covalently anchoring (supra)molecular components that well-define two electrical states (on/off) driven by either electrical or optical stimuli. Accordingly, this work paves the way for the functionalization of 3D-nCEs through fundamental chemistry, opening up new horizons in unprecedented tailored 3D-printed responsive interfaces which could be utilized as potential (bio)sensors, (opto)electronic devices, or molecular logic gates.

A Reconfigurable, Dual-Output INHIBIT and IMPLICATION Molecular Logic Gate.

Molecules that respond to input stimulations to produce detectable outputs can be exploited to mimic Boolean logic operators and reproduce basic arithmetic functions. We have designed a two-state fluorescent probe with tunable emission wavelength for the construction of a molecular logic gate with reconfigurable single- or dual-output capability. The system is based on a BODIPY skeleton coupled with 4-(dimethylamino)benzaldehyde. The behavior of the molecular logic gate can be easily investigated in solution with fluorescence spectroscopy, and the optical readout (fluorescence) can be monitored in one (green) or two (green and red) channels. Depending on the solvent of choice, single INHIBIT or dual INHIBIT/IMPLY logic functions can be achieved using chemical inputs (acid and base). Reconfiguration from single- to dual-output is thus made possible by operating the system in acetonitrile (single output) or toluene (dual output), respectively. The logic gate can be switched by manipulating the fluorescence emission via protonation or deprotonation, even when immobilized onto a glass substrate. At the solid state, the resulting output can be stored for extended periods of time. This feature provides two added benefits: (i) memory function and (ii) "set/reset" capability of the logic gate. Our design thus provides a proof-of-concept interface between the molecular and electronic domains.

Multilevel, Dual-Readout Logic Operations Based on pH-Responsive Holmium(III)-Doped Carbon Nanodots.

The increasing demand for large-scale integrated logic systems urges the development of multireadout molecular logic gates. Especially, it is of great significance to explore dual-readout logic devices with both fluorescence (FL) and magnetic resonance (MR) signals as measurable outputs, since the signal combination of FL/MR might render molecular logic devices better practicality in biomedical applications. In this study, holmium(III)-doped carbon nanodots (Ho-CDs), which exhibited pH-responsive behaviors in both FL and MR signals, were synthesized by a facile one-pot pyrolysis method. When triggered by H+, Fe3+, or Fe2+, the Ho-CDs served as a switch for both FL and MR signals, leading to dual-readout and multiaddressable logic gates. A series of elementary Boolean operations including YES, NOT, OR, NOR, XOR, PASS 0, and INH have been successfully demonstrated by varying the chemical inputs of H+/Fe3+/Fe2+. More importantly, multilevel integrative Boolean operations with higher functions (NOR-INH and MR (XOR + INH)-OR), which realize the concatenation of different logic gates, have also been successfully demonstrated. This study may pave an avenue to design multilevel, dual-readout molecular logic systems with better operation stability, which hold great potential for biomedical applications in the future.