Reversing the Trend: Deciphering Self-Assembly of Unconventional Amphiphiles having both Alkyl-chain and PEG.

In the field of molecular self-assembly, the core of an assembly is always made up of hydrophobic moiety like a long alkyl chain, whereas the outer part has always been a hydrophilic moiety such as poly(ethylene glycol) (PEG), or charged species. Hence, reversing the trend to manifest self-assembled structures with a PEG core and a surface consisting of alkyl chains in aqueous system is incredibly challenging. Herein, we architected a unique class of cationic bolaamphiphiles containing low molecular weight PEG and alkyl chains of different lengths. The bolaamphiphiles spontaneously form vesicles without external stimuli. These vesicles are unprecedented because PEG makes up the vesicle core, while the alkyl chains appear on the vesicles' exterior. Hence, this is the first report on an assembly that reverses the usual trend. The vesicle size increases with the increase in alkyl chain-length. To our great surprise, we obtained large micelles for longest alkyl-chain amphiphile, which in turn act as a gemini amphiphile. The shift from a particular bolaamphiphile to gemini amphiphile with the variation of alkyl chain is also unexplored. Therefore, this specific class of self-assembled structure would compound a new paradigm in the fields of molecular self-assembly and supramolecular chemistry.

Thiol ligand-mediated exfoliation of bulk sulfur to nanosheets and nanodots: applications in antibacterial activity.

Reducing bulk materials to layers or dots results in profound alterations in their physiochemical and optoelectronic properties, leading to a wide array of applications, spanning from device manufacturing to biomedicine. In this regard, the preparation of sulfur nanomaterials has garnered significant attention due to their low toxicity. Traditional methods for sulfur nanomaterial synthesis often involve harsh reaction conditions, leaving a gap for convenient approaches to create nanomaterials, such as nanosheets (NSs) and nanodots (NDs). Herein, the mechanical exfoliation of bulk sulfur using a surfactant thiol ligand with probe sonication is reported, making a unique contribution to existing methods. In the reported method, the thiol group binds to sulfur surfaces, facilitating exfoliation and stabilization, while the hydrophilic ends provide functional groups for exfoliated nanomaterials. Exfoliation can yield either nanosheets or nanodots, depending on the thiol ligand and exfoliation time. This approach offers the opportunity to exfoliate bulk sulfur using bioactive thiol ligands. With this goal in mind, bulk sulfur was exfoliated with 4-mercaptophenylboronic acid (BA) to target Gram-positive bacteria. This innovative exfoliation strategy of bulk sulfur using thiol ligands holds immense promise for synthesizing functionalized sulfur nanomaterials with wide-ranging applications, particularly in biomedicine.

Photo-Controlled Gating of Selective Bacterial Membrane Interaction and Enhanced Antibacterial Activity for Wound Healing.

Reversible biointerfaces are essential for on-demand molecular recognition to regulate stimuli-responsive bioactivity such as specific interactions with cell membranes. The reversibility on a single platform allows the smart material to kill pathogens or attach/detach cells. Herein, we introduce a 2D-MoS2 functionalized with cationic azobenzene that interacts selectively with either Gram-positive or Gram-negative bacteria in a light-gated fashion. The trans conformation (trans-Azo-MoS2 ) selectively kills Gram-negative bacteria, whereas the cis form (cis-Azo-MoS2 ), under UV light, exhibits antibacterial activity against Gram-positive strains. The mechanistic investigation indicates that the cis-Azo-MoS2 exhibits higher affinity towards the membrane of Gram-positive bacteria compared to trans-Azo-MoS2 . In case of Gram-negative bacteria, trans-Azo-MoS2 internalizes more efficiently than cis-Azo-MoS2 and generates intracellular ROS to kill the bacteria. While the trans-Azo-MoS2 exhibits strong electrostatic interactions and internalizes faster into Gram-negative bacterial cells, cis-Azo-MoS2 primarily interacts with Gram-positive bacteria through hydrophobic and H-bonding interactions. The difference in molecular mechanism leads to photo-controlled Gram-selectivity and enhanced antibacterial activity. We found strain-specific and high bactericidal activity (minimal bactericidal concentration, 0.65 µg/ml) with low cytotoxicity, which we extended to wound healing applications. This methodology provides a single platform for efficiently switching between conformers to reversibly control the strain-selective bactericidal activity regulated by light.

Surface-Engineered Nanomaterials for Optical Array Based Sensing.

Array based sensing governed by optical methods provides fast and economic way for detection of wide variety of analytes where the ideality of detection processes depends on the sensor element's versatile mode of interaction with multiple analytes in an unbiased manner. This can be achieved by either the receptor unit having multiple recognition moiety, or their surface property should possess tuning ability upon fabrication called surface engineering. Nanomaterials have a high surface to volume ratio, making them viable candidates for molecule recognition through surface adsorption phenomena, which makes it ideal to meet the above requirements. Most crucially, by engineering a nanomaterial's surface, one may produce cross-reactive responses for a variety of analytes while focusing solely on a single nanomaterial. Depending on the nature of receptor elements, in the last decade the array-based sensing has been considering as multimodal detection platform which operates through various pathway including single channel, multichannel, binding and indicator displacement assay, sequential ON-OFF sensing, enzyme amplified and nanozyme based sensing etc. In this review we will deliver the working principle for Array-based sensing by using various nanomaterials like nanoparticles, nanosheets, nanodots and self-assembled nanomaterials and their surface functionality for suitable molecular recognition.

2D-MoS2-supported copper peroxide nanodots with enhanced nanozyme activity: application in antibacterial activity.

Peroxidase (POD)-like nanozymes are an upcoming class of new-generation antibiotics that are efficient for broad-spectrum antibacterial action. The POD-like activity employs the generation of reactive oxygen species (ROS), which have been utilized for bactericidal action. However, their intrinsic low catalytic activity and stability limit their bactericidal properties. In this study, we prepared a MoS2-based nanocomposite with copper peroxide nanodots (MoS2@CP) to achieve pH-dependent light-induced nanozyme-based antibacterial action. It has shown superior peroxidase and antibacterial activity at low pH. The mechanism behind the enhanced POD-like activity and high antibacterial activity was established. The mechanistic pathway involves estimating ROS generation, membrane depolarization, inner membrane permeabilization, metal ion release, and the effect of NIR on photothermal and photodynamic activities. Overall, our work highlighted the combinatorial approach for eradicating bacterial infections using enzyme-based antibacterial agents.

Post-functionalization of sulfur quantum dots and their aggregation-dependent antibacterial activity.

Sulfur quantum dots (SQDs) have emerged as an intriguing class of luminescent nanomaterial due to their exceptional physiochemical and optoelectronic properties. However, their biomedical application is still in its infancy due to the limited scope of their surface functionalization. Herein, we explored the surface functionalization of SQDs through different thiol ligands with tuneable functionality and tested their antibacterial efficacy. Notably, very high antibacterial activity of functionalized SQDs (10-25 ng ml-1) was noted, which is 105 times higher compared to that of nonfunctionalized SQDs. Moreover, a rare phenomenon of the reverse trend of antibacterial activity through surface modification was observed, with increasing surface hydrophobicity of various nanomaterials as the antibacterial activity increased. However, we also noted that as the surface hydrophobicity increased, the SQDs tended to exhibit a propensity for aggregation, which consequently decreased their antibacterial efficacy. This identical pattern was also evident in in vivo assessments. Overall, this study illuminates the importance of surface modifications of SQDs and the role of surface hydrophobicity in the development of antibacterial agents.

Semiconductor Quantum Dots Act as Photocatalysts for Carbon-Carbon Bond Formation: Selective Functionalization of Xanthene's 9H Position.

The potential of CdSe, CdS, MoS2, and WS2 QDs as semiconductor photocatalysts for selective functionalization of the xanthene 9H position through carbon-carbon bond formation has been investigated. Our study reveals valuable insights into the energy-transfer and electron-transfer pathways involved in these reactions, as well as the radical polar crossover (RPC) and triplet-to-triplet energy transfer (TTEnT) processes. Notably, this approach offers a range of intriguing features, including visible-light-mediated processes, inexpensive catalytic systems, mild reaction conditions, broad substrate scope, unfunctionalized starting materials, and suitability for gram-scale synthesis. This study makes a significant contribution to the newly emerging field of QD-catalyzed reactions, paving the way for future explorations.

Synthesis of biologically important tetrahydroisoquinoline (THIQ) motifs using quantum dot photocatalyst and evaluation of their anti-bacterial activity.

Our study introduces an efficient photocatalytic approach for synthesizing biologically significant C1-substituted tetrahydroisoquinoline (THIQ) motifs, employing WS2 quantum dots (QDs) as catalysts. This method enables the formation of C-C and C-P bonds at the C1 position of the THIQ motif. The resulting compounds exhibit substantial antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) bacteria, with low minimum inhibitory concentration (MIC) values. Notably, the WS2 QD catalyst demonstrates recyclability and suitability for gram-scale reactions, underscoring the sustainability and scalability of our approach. Overall, our research presents a versatile and cost-effective strategy for synthesizing C1-substituted THIQ derivatives, highlighting their potential as novel therapeutic agents in biology and medicinal chemistry.

Liposome-Based Antibacterial Delivery: An Emergent Approach to Combat Bacterial Infections.

The continued emergence and spread of drug-resistant pathogens and the decline in the approval of new antimicrobial drugs pose a major threat to managing infectious diseases, resulting in high morbidity and mortality. Even though a significant variety of antibiotics can effectively cure many bacterial infectious diseases, microbial infections remain one of the biggest global health problems, which may be due to the traditional drug delivery system's shortcomings which lead to poor therapeutic index, low drug absorption, and numerous other drawbacks. Further, the use of traditional antibiotics to treat infectious diseases has always been accompanied by the emergence of multidrug resistance and adverse side effects. Despite developing numerous new antibiotics, nanomaterials, and various techniques to combat infectious diseases, they have persisted as major global health issues. Improving the current antibiotic delivery systems is a promising approach to solving many life-threatening infections. In this context, nanoliposomal systems have recently attracted much attention. Herein, we attempt to provide a concise summary of recent studies that have used liposomal nanoparticles as delivery systems for antibacterial medicines. The minireview also highlights the enormous potential of liposomal nanoparticles as antibiotic delivery systems. The future of these promising approaches lies in developing more efficient delivery systems by precisely targeting bacterial cells with antibiotics with minimum cytotoxicity and high bacterial combating efficacy.

012 facets modulated LDH composite for neurotoxicity risk assessment through direct electrochemical profiling of dopamine.

Rising concerns of pesticide-induced neurotoxicity and neurodegenerative diseases like Parkinson's, Alzheimer's, and Multiple Sclerosis, are exacerbated by overexposure to contaminated waterbodies. Therefore, evaluating the risk accurately requires reliable monitoring of related biomarkers like dopamine (DA) through electrochemical detection. Layered double hydroxides (LDHs) have shown great potential in sensors. However, to meet the challenges of rapid detection of large patient cohorts in real-time biological media, they should be further tailored to display superior analytical readouts. Herein, a ternary LDH (Ni2CoMn0.5) was integrated with the sheets of thermally reduced graphene oxide (trGO), to expose more highly active edge planes of the LDH, as opposed to its generally observed inert basal planes. The improvement in detection performance through such a modulated structure-property is a prospect that hasn't been previously explored for any other LDH-based materials employed in sensing applications. The 2 folds superior electrochemical activity exhibited by the face-on oriented LDH with trGO as compared to the pristine LDH material was further employed for direct detection of DA in real blood plasma samples. Moreover, the designed sensor exhibited exceptional selectivity towards the detection of DA with a limit of detection of 34.6 nM for a wide dynamic range of 0.001-5 mM with exceptional stability retaining 88.56% of the initial current even after storage in ambient conditions for 30 days.

Nanomaterials in photocatalysed organic transformations: development, prospects and challenges.

Photoredox catalysis has gained widespread attention in recent years as a powerful tool to drive chemical transformations in the presence of light, particularly for molecules that are capable of showing redox activity. A typical photocatalytic pathway may involve electron or energy transfer processes. To date, photoredox catalysis has been explored mainly with Ru, Ir and other metal or small molecule based photocatalysts. Due to their homogeneous nature, they cannot be reused and are not economical. These factors have motivated researchers to look for an alternate class of photocatalysts which are more economical and reusable, thus paving the way for protocols that can be easily transferred to the industrial sectors as well. In this regard, scientists have come up with various nanomaterials as sustainable and economical alternatives. These have unique properties that arise from their structure, surface functionalization, etc. Apart from that, at the lower dimensions, they bear an increased surface to volume ratio, which can provide an enhanced number of active sites for catalysis. Nanomaterials have been used for various applications like sensing, bioimaging, drug delivery, energy generation, etc. However, their potential as photocatalysts for organic transformations has been taken up as a subject of research quite recently. This article focusses on the use of nanomaterials in photo-mediated organic transformations with a wider goal to motivate readers from materials as well as organic synthetic backgrounds to dig deeper into this area of research. Various reports have been included to cover the plethora of reactions that have been explored with nanomaterials as a photocatalyst. The scientific community has also been introduced to the challenges and prospects of the field, which will further help in its growth. In a nutshell, this writeup will help to cater to the interest of a large group of researchers to highlight the prospects of nanomaterials in photocatalysis.

Solvent Induced Conversion of a Self-Assembled Gyrobifastigium to a Barrel and Encapsulation of Zinc-Phthalocyanine within the Barrel for Enhanced Photodynamic Therapy.

A rare gyrobifastigium architecture (GB) was constructed by self-assembly of a tetradentate donor (L) with PdII acceptor in DMSO. The GB was converted to its isomeric tetragonal barrel (MB) upon treatment with water. The hydrophobic cavity of MB has been explored for the encapsulation of zinc-phthalocyanine (ZnPc), which is an excellent photosensitizer for photodynamic therapy (PDT). However, the poor water-solubility and aggregation tendency are the main reasons for the suboptimal PDT performance of free ZnPc in the aqueous medium. Effective solubilization of ZnPc in an aqueous medium was achieved by encapsulating it in the cavity of MB. The inclusion complex (ZnPc⊂MB) showed enhanced singlet oxygen generation in water. Higher cellular uptake and anticancer activity of the ZnPc⊂MB compared to free ZnPc on HeLa cells indicate that encapsulation of ZnPc in an aqueous host is a potential strategy for enhancement of its PDT activity in water.

Time-resolved fluorescence sensor array for the discrimination of phosphate anions using transition metal dichalcogenide quantum dots and Tb(III).

Phosphate detection has garnered widespread attention due to its biological and environmental impact. Among several optical techniques, time-resolved fluorescence (TRF) provides a sensitive way for the discrimination of analytes in a complex mixture as it exhibits less interference from the background, therefore providing a high signal-to-noise ratio. The sensitization of rare earth metal (REM) ions by semiconducting quantum dots (QDs) can help the former overcome the drawback of low absorption coefficient, therefore allowing exploitation of the additional advantage of the REM, namely the long-excited state lifetime. Here, we have developed a TRF-based sensor array consisting of three QDs, i.e. MoS2 , WS2 and MoSe2 as energy sensitizers for Tb3+ ions. Different QDs possess variable energy transfer abilities for Tb3+ ions. Therefore, they can be used to discriminate phosphates. It was also observed that CrO4 2- can competitively bind to Tb3+ and further enhance the efficiency of the sensor array so that it could discriminate six different phosphates at 200 µM concentration in aqueous as well as serum medium with a detection limit of 10 µM in aqueous medium. Therefore, the sensitivity of the TRF-based sensor array is rarely compromised in a complex mixture, which is advantageous over a fluorescence-based sensor array.

Ligand-Mediated Exfoliation and Antibacterial Activity of 2H Transition-Metal Dichalcogenides.

Transition-metal dichalcogenides (TMDs) exists mainly in two polymorphs, namely, 1T (metallic) and 2H (semiconducting). To tailor the characteristics and practical utility of TMDs for different applications, functionalization is essential. In our earlier studies, we have shown that functionalized 1T and 2H MoS2 exhibit exceptionally high antibacterial activity. The functionalization and related biological applications of other 1T (chemically exfoliated) TMDs were reported, but regarding other 2H TMDs, the functionalization and antibacterial activity are not explored yet. Hence, here we prepared functionalized 2H TMDs such as WS2, WSe2, and MoSe2 other than MoS2 by using a positively charged thiolate surfactant ligand. Further, functionalized 2H TMDs were utilized for antibacterial activity against Gram-positive and Gram-negative bacteria for a comparative antibacterial analysis. Interestingly, we found disparity in activity among the functionalized 2H TMDs, that is, MoS2 shows higher activity than WS2 followed by MoSe2 and WSe2. The intracellular reactive oxygen species measurement was found to be in the order MoS2 > WS2 > MoSe2 > WSe2, which is solely responsible for variation in the activity of functionalized TMDs. These results indicate that the easy functionalization of all types TMDs by using thiol ligand and importance of core material should be considered while designing functionalized material for specific applications.

Ligand Exchange on MoS2 Nanosheets: Applications in Array-Based Sensing and Drug Delivery.

Two-dimensional MoS2 nanosheets (2D-MoS2) have been widely used in many biological applications due to their distinctive physicochemical properties. Further, the development of surface modification using thiolated ligands allows us to use them for many specific applications. But the effect of possible ligand exchange on 2D-MoS2 has never been explored, which can play an important role in diverse biological applications. In this study, we have observed the ligand-exchange phenomenon on 2D-MoS2 in the presence of different thiolated ligands. The initial study proceeded with boron-dipyrromethene (BODIPY) functionalized MoS2 with different concentrations of glutathione (GSH), which is the most abundant thiol species in the cytoplasm of various cancer cells. It was found that in the presence of GSH the fluorescence of BODIPY can be regenerated, which is time and concentration dependent. We have also examined this phenomenon with different thiol ligands and transition-metal dichalcogenides (TMDs). We observed a variable rate of ligand exchange in different solvents, surface functionality, and receptor environments that helped us to construct sensor arrays. Interestingly, a ligand-exchange process was not observed in the presence of dithiols. Further, this concept was applied to a cancerous cell line for in vitro delivery. We found that BODIPY-functionalized 2D-MoS2 undergoes thiol exchange by intracellular GSH and subsequently enhanced the fluorescence in the cytoplasm of cancer cells. This strategy can be applied to the development of 2D-TMD-based materials for various biological applications related to ligand exchange.

Shifting the Triangle-Square Equilibrium of Self-Assembled Metallocycles by Guest Binding with Enhanced Photosensitization.

Shifting a triangle-square equilibrium in one direction is an important problem in supramolecular self-assembly. Reaction of a benzothiadiazole-based diimidazole donor with a cis-Pt(II) acceptor yielded an equilibrium mixture of a triangle ([C18H24N10O6S1Pt1]3≡ PtMCT) and a square ([C18H24N10O6S1Pt1]4≡ PtMCS). We report here the shifting of such equilibrium toward a triangle using a guest (pyrene aldehyde, G1). While both benzothiadiazole and pyrene aldehyde can form reactive oxygen species (ROS) in organic solvents, their therapeutic use in water is restricted due to aqueous insolubility. The enhanced water solubility of the benzothiadiazole unit and G1 by macrocycle formation and host-guest complexation, respectively, enabled enhanced ROS generation by the host-guest complex (G1' ⊂ PtMCT) in water (G1' = hydrated form of G1). The guest-encapsulated metallacycle (G1' ⊂ PtMCT) has shown synergistic antibacterial activity compared to the mixture of macrocycles upon white-light irradiation due to enhanced ROS generation. The mechanism for such enhanced activity was established by measuring the oxidative stress and relative internalization of PtMCs and G1' ⊂ PtMCT.

Fe-Doped MoS2 Nanozyme for Antibacterial Activity and Detoxification of Mustard Gas Simulant.

The peroxidase-like catalytic activity of various nanozymes was extensively applied in various fields. In this study, we have demonstrated the preparation of Fe-doped MoS2 (Fe@MoS2) nanomaterials with enhanced peroxidase-like activity of MoS2 in a co-catalytic pathway. In view of Fenton reaction, the peroxidase-like Fe@MoS2 nanozyme prompted the decomposition of hydrogen peroxide (H2O2) to a reactive hydroxyl radical (·OH). The efficient decomposition of H2O2 in the presence of Fe@MoS2 has been employed toward the antibacterial activity and detoxification of mustard gas simulant. The combined effect of Fe@MoS2 and H2O2 showed remarkable antibacterial activity against the drug-resistant bacterial strain methicillin-resistant Staphylococcus aureus and Escherichia coli with the use of minimal concentration of H2O2. Fe@MoS2 was further applied for the detoxification of the chemical warfare agent sulfur mustard simulant, 2-chloroethyl ethyl sulfide, by selective conversion to the nontoxic sulfoxide. This work demonstrates the development of a hybrid nanozyme and its environmental remediation from harmful chemicals to microbes.

Rapid Discrimination of Bacterial Drug Resistivity by Array-Based Cross-Validation Using 2D MoS2.

The precise discrimination of microbes based on family, class and drug resistivity is essential for the early diagnosis of infectious diseases. Information about the type and strength of drug resistivity can help the analyst to prescribe a suitable antibiotic at the proper dosage to completely eradicate microbes without giving them a chance to gain further resistance. Herein, we propose a sensor array based on the use of cationic two-dimensional MoS2 units and green fluorescence protein as building blocks. Cationic surfaces of receptors with various functionality were suitable for tunable interaction with anionic surfaces of microbes. The array successfully discriminates six different bacterial strains. The versatile ability of the receptors to bind with the wild-type as well as the corresponding ampicillin-resistant strain contributed significantly to rapid detection with high sensitivity. The optimized array was able to classify five different types and three different extents of drug-resistant variants of Escherichia coli by using bacteria cells and lysates. Finally, we have introduced the cross identification method using both bacteria cells and lysates and we found a great enhancement of detection in sensitivity and accuracy. This is the first report of this approach, which can be extended to many other methods for better accuracy in array-based detection.

Superparamagnetic Nickel Nanocluster-Embedded MoS2 Nanosheets for Gram-Selective Bacterial Adhesion and Antibacterial Activity.

Ever increasing infectious diseases caused by pathogenic bacteria are creating one of the greatest health problems. The extensive use of numerous antibiotics and antimicrobial agents has prompted the growth of multidrug-resistant bacterial strains. The ancient biomedical application of metals and the recent advancement in the field of nanotechnology have encouraged us to explore the antimicrobial activity of nanomaterials. Herein, we have synthesized a magnetically separable superparamagnetic nickel nanocluster-loaded two-dimensional molybdenum disulfide nanocomposite (Ni@2D-MoS2). It can selectively bind with Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis over Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. After the functionalization of Ni@2D-MoS2 with a positively charged ligand, it showed an excellent Gram-selective antibacterial activity toward MRSA and E. faecalis. Furthermore, the superparamagnetic property of the synthesized material can be used for the simultaneous removal and killing of the microbes and recycled for further use. This study demonstrates strategies to develop hybrid antimicrobial nanomaterial systems for selective antibacterial activity with recyclability.

Gram-selective antibacterial activity of mixed-charge 2D-MoS2.

The development of nanomaterial-based antibiotics can be the most potent alternative due to the increasing resistance against conventional antibiotics. However, one of the important parameters in the development of antibacterial agents is their Gram selectivity, which has been seldomly explored in the case of nano-antibiotics. The multimodal action of surface-functionalized nanomaterials can exhibit strain selectivity and enhanced antibacterial activity. Herein, we designed a Gram-selective antibacterial system based on two-dimensional molybdenum disulphide (2D-MoS2) functionalized with different proportions of positively and negatively charged ligands. Two representative ESKAPE pathogenic strains, i.e., Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) were considered to evaluate the selective antibacterial activity. The mechanistic insight behind selectivity was established by evaluating the degree of membrane depolarization together with oxidative stress. The selective generation of intracellular reactive oxygen species (ROS) together with membrane depolarization contributed to the selective killing of the pathogenic bacteria. Gram selectivity was achieved by simply controlling the surface functionality based on the different cell wall compositions and structures of bacterial strains. The interplay between polyvalent electrostatic and non-covalent interactions was mainly responsible for damaging the cell membrane. Furthermore, to establish the antibacterial mechanism, we performed extracellular and intracellular reactive oxidative stress, membrane depolarization and permeabilization assays. In summary, we prepared simple and efficient Gram-selective 2D-MoS2-based antibacterial agents, which can be extended to other nano-antibiotic systems.