Molecular Engineering Approach Research Articles

Molecular Engineering of Polymyxin B for Imaging and Treatment of Bacterial Infections.

The emergence of multi-drug resistant bacteria and the lack of novel antibiotics to combat them have led to the revival of polymyxin B, a previously abandoned antibiotic due to its potential nephrotoxicity and neurotoxicity. To facilitate its widely clinical applications, increasing effort has been devoted to molecularly engineer polymyxin B for the targeted imaging and effective treatment of bacterial infections. Herein, the molecular engineering strategies will be summarized in this mini review, with selected recent advances for illustration. Perspective of the challenges and trends in this exciting and eagerly anticipated research area will also be provided in the end. We hope this mini review will inspire researchers from diverse fields to bring forward the next wave of exploiting molecular engineering approaches to propel the “old” polymyxin B to “new” clinical significance in combating bacterial infections.

Six-electron organic redoxmers for aqueous redox flow batteries.

We have developed a novel molecular design that enables six-electron redox activity in fused phenazine-based organic scaffolds. Combined electrochemical and spectroscopic tests successfully confirm the two-step 6e- redox mechanism. This work offers an opportunity for achieving energy-dense redox flow batteries, on condition that the solubility and stability issues are addressed.

Rational Design of Covalent Heptazine Frameworks with Spatially Separated Redox Centers for High-Efficiency Photocatalytic Hydrogen Peroxide Production.

The redox reaction centers in natural organisms conducting oxygenic photosynthesis are well arranged in a physically separated manner to convert sunlight into chemical energy efficiently. Mimicking natural photosynthesis via precisely constructing oxidative and reductive reaction centers within photocatalysts is ideal for enhancing catalytic performances in artificial photosynthesis. In this study, new covalent heptazine frameworks (CHFs) with spatially separated redox centers are rationally designed for photocatalytic production of H2 O2 from water and oxygen without using any sacrificial agents. Both experimental and computational investigations indicate that the two-electron oxygen reduction reaction occurs on the heptazine moiety, whereas the two-electron water oxidation reaction occurs on the acetylene or diacetylene bond in the CHFs. This unique spatial separation feature is critical for enhancing charge separation and achieving efficient H2 O2 production. Meanwhile, the measured exciton binding energy of the diacetylene-containing polymer is merely 24 meV. Under simulated solar irradiation, the rationally designed CHFs can achieve a solar-to-chemical conversion efficiency of 0.78%, surpassing previously reported photocatalytic materials. This study establishes a molecular engineering approach to construct periodically arranged and spatially separated redox centers in single-component polymer photocatalysts, representing a hallmark to create more exciting polymer structures for photocatalysis moving forward.

Overcoming transport barriers to immunotherapy.

Immunotherapies are designed to treat disease by modulating the activity of immune cells. Here, we consider how anatomy and microphysiology create transport barriers to immunotherapeutic delivery and retention at diseased sites, and summarize recent developments to overcome these barriers by exploiting immunobiology to engineer molecular and cellular engineering approaches. Creating impactful and practical solutions across these diseases requires the integration of the collective expertise of pathologists, clinicians, immunologists, biophysicists, immunoengineers, and more.

Supramolecular Self-Assembly of Nitrogen-Deficient Ag/g-C3N4 Nanofiber Films with Enhanced Charge Transfer Dynamics for Efficient Visible-Light Photocatalytic Activity.

Molecular self-assembly of organic molecules through noncovalent interactions is a powerful strategy for designing functional materials. Herein, we fabricated a novel free-standing Ag/g-C3N4 nanofiber (Ag/CNNF) film via a water-based molecular engineering approach followed by pyrolysis using a cyanuric acid-melamine complex as the precursor. Uniform dispersion of plasmonic Ag nanoparticles and incorporation of nitrogen vacancies were synchronously introduced into the 3D highly interconnected porous CNNF framework. The resulting Ag/CNNF film with multilevel interlayer spacing distributions significantly expedited more sufficient charge transfer dynamics not only at Schottky junction sites but also throughout hierarchical CN by exciton dissociation. Benefiting from the synergistic enhancement in visible light harvesting capability and steered charge carrier transfer in a longitudinal direction, the Ag/CNNF film presented remarkably boosted photocatalytic ability both for hydrogen production and tetracycline degradation. The optimal Ag/CNNF-2 film exhibited a prominent photocatalytic hydrogen evolution rate of 1240 μmol g-1 h-1 without the Pt co-catalyst under visible light illumination, which was 10.3 times as high as that of bulk g-C3N4. Significantly, 1D Ag/g-C3N4 nanofibers self-assembled into an ordered and macroscopic film, which was more favorable in practical applications owing to good reusability and high processability. This work paved the way for the facile preparation of supramolecular self-assembled CN-based film photocatalysts.

Highly Nonlinear Optical Organic Crystals for Efficient Terahertz Wave Generation, Detection, and Applications

AbstractOrganic π‐conjugated crystals with second‐order optical nonlinearity are considerably attractive materials for diverse terahertz (THz) wave photonics. An overview of the research of organic nonlinear optical (NLO) crystals for THz wave generation, detection, and applications is provided here. First, the status of organic NLO crystals compared to other alternative THz materials is described. Second, the basic theory and requirements for organic THz generators and detectors are explained. Third, with a primary focus on the organic NLO crystals that have been developed during the last decade, various molecular engineering approaches are discussed from the perspective of THz photonics. Finally, various types of high‐power broadband coherent THz sources and their applications in THz nonlinear optics are discussed.

Advances in omics technology for improving crop yield and stress resilience

AbstractGlobal climate change has emerged as the utmost environmental threat for agriculture. To maintain a sustainable food supply, climate‐resilient high‐yielding crop plants need to be developed. Over the last decade, understanding the complexity of genotype underlying agronomic traits has prompted the integrated application of various omics tools to address specific biological questions. A multi‐parallel qualitative and quantitative differential analysis of gene transcripts, proteins and metabolites provides a comprehensive picture of the interconnected gene networks and cellular signalling cascade of regulatory and effector proteins. Genetic determinants of adaptation to environmental stress and yield enhancement traits are being determined and introgressed into elite accessions through either molecular breeding or genetic engineering approaches to obtain future crops with improved traits.

Halomonas as a chassis.

With the rapid development of systems and synthetic biology, the non-model bacteria, Halomonas spp., have been developed recently to become a cost-competitive platform for producing a variety of products including polyesters, chemicals and proteins owing to their contamination resistance and ability of high cell density growth at alkaline pH and high salt concentration. These salt-loving microbes can partially solve the challenges of current industrial biotechnology (CIB) which requires high energy-consuming sterilization to prevent contamination as CIB is based on traditional chassis, typically, Escherichia coli, Bacillus subtilis, Pseudomonas putida and Corynebacterium glutamicum. The advantages and current status of Halomonas spp. including their molecular biology and metabolic engineering approaches as well as their applications are reviewed here. Moreover, a systematic strain engineering streamline, including product-based host development, genetic parts mining, static and dynamic optimization of modularized pathways and bioprocess-inspired cell engineering are summarized. All of these developments result in the term called next-generation industrial biotechnology (NGIB). Increasing efforts are made to develop their versatile cell factories powered by synthetic biology to demonstrate a new biomanufacturing strategy under open and continuous processes with significant cost-reduction on process complexity, energy, substrates and fresh water consumption.

Giant Spin Splitting in Chiral Perovskites Based on Local Electrical Field Engineering

Chiral hybrid organic-inorganic perovskites (chiral HOIPs) present potential spintronic and spin-optoelectronic applications due to their unique spin-related properties. However, the spin physics in chiral HOIPs has rarely been explored by theoretical studies. Here, with first-principles calculations, we investigate the spin characteristics of the Pb-I based chiral HOIPs and propose an effective approach to significantly increase the spin splitting with a halogen-substituted chiral molecule. Compared to the value of 13 meV without halogen substitution, the spin splitting energy can be significantly enhanced to 73, 90, and 105 meV with F, Cl, and Br substitution, respectively. A k·p model Hamiltonian based on a symmetry argument reveals that the halogen substitution enhances the local electric field, inducing distortion of the PbI6 octahedron. Further calculation demonstrates that halogen substitution can strongly modify the electrostatic potential surface of the chiral molecules. This work presents an effective molecular engineering approach to modulate spin splitting of chiral HOIPs, shedding light on the design of spintronic materials.

ELECTRONIC AND OPTICAL MODIFICATION OF ORGANIC-HYBRID PEROVSKITES

Renewed interest has brought significant attention to tune coherently the electronic and optical properties of hybrid organic–inorganic perovskites (HOIPs) in recent years. Tailoring the intimate structure–property relationship is a primary target toward the advancement of light-harvesting technologies. These constructive progresses are expected to promote staggering endeavors within the solar cells community that needs to be revisited. Several considerations and strategies are introduced mainly to illustrate the importance of structural stability, interfacial alignment, and photo-generated carriers extraction across the perovskite heterostructures. Here, we review recent strides of such vast compelling diversity in order to shed some light on the interplay of the interfacial chemistry, photophysics, and light-emitting properties of HOIPs via molecular engineering or doping approach. In addition, we outline several fundamental knowledge processes across the role of charge transfer, charge carrier extraction, passivation agent, bandgap, and emission tunability at two-dimensional (2D) level of HOIPs/molecule heterointerfaces. An extensive range of the relevant work is illustrated to embrace new research directions for employing organic molecules as targeted active layer in perovskite-based devices. Ultimately, we address important insights related to the physical phenomena at the active molecules/perovskites interfaces that deserve careful considerations. This review specifically outlines a comprehensive overview of surface-based interactions that fundamentally challenges the delicate balance between organic materials and perovskites, which promotes bright future of desired practical applications.

Molecular Engineering Approaches to Fabricate Artificial Solid‐Electrolyte Interphases on Anodes for Li‐Ion Batteries: A Critical Review

AbstractAn intrinsic challenge of Li‐ion batteries is the instability of electrolytes against anode materials. For anodes with a favorably low operating potential, a solid‐electrolyte interphase (SEI) formed during initial cycles provides stability, traded off for capacity consumption. The SEI is mainly determined by the anode material, electrolyte composition, and formation conditions. Its properties are typically adjusted by changing the liquid electrolyte's composition. Artificial SEIs (Art‐SEIs) offer much more freedom to address and tune specific properties, such as chemical composition, impedance, thickness, and elasticity. Art‐SEIs for intercalation, alloying, conversion and Li metal anodes have to fulfil varying requirements. In all cases, sufficient transport properties for Li‐ions and (electro‐)chemical stability must be guaranteed. Several approaches for Art‐SEIs preparation have been reported: from simple casting and coating techniques to elaborated Phys‐Chem modifications and deposition processes. This review critically reports on the promising approaches for Art‐SEIs formation on different type of anode materials, focusing on methodological aspects. The specific requirements for each approach and material class, as well as the most effective strategies for Art‐SEI coating, are discussed and a roadmap for further developments towards next‐generation stable anodes are provided.

MicroRNAs: Potential Targets for Developing Stress-Tolerant Crops.

Crop yield is challenged every year worldwide by changing climatic conditions. The forecasted climatic scenario urgently demands stress-tolerant crop varieties to feed the ever-increasing global population. Molecular breeding and genetic engineering approaches have been frequently exploited for developing crops with desired agronomic traits. Recently, microRNAs (miRNAs) have emerged as powerful molecules, which potentially serve as expression markers during stress conditions. The miRNAs are small non-coding endogenous RNAs, usually 20–24 nucleotides long, which mediate post-transcriptional gene silencing and fine-tune the regulation of many abiotic- and biotic-stress responsive genes in plants. The miRNAs usually function by specifically pairing with the target mRNAs, inducing their cleavage or repressing their translation. This review focuses on the exploration of the functional role of miRNAs in regulating plant responses to abiotic and biotic stresses. Moreover, a methodology is also discussed to mine stress-responsive miRNAs from the enormous amount of transcriptome data available in the public domain generated using next-generation sequencing (NGS). Considering the functional role of miRNAs in mediating stress responses, these molecules may be explored as novel targets for engineering stress-tolerant crop varieties.

Effect of electron donor and acceptor on the photovoltaic properties of organic dyes for efficient dye-sensitized solar cells

In this work, the molecular engineering approach was applied to the organic dyes of AE, AQ, TE, and TQ having the donor-acceptor (D-A) configuration to investigate the solar cell efficiency. In these structures, dimethylaniline and triphenylamine were used as the electron donors and 1,1,4,4-tetracyanobuta-1,3-dienes (originating from TCNE) and 2-(4-(4,4-dicyanobut-3-en-2-ylidene)cyclohexa-2,5-dien-1-ylidene)malononitrile (originating from TCNQ) as the electron acceptors. The incorporation of tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) due to the strong electron-withdrawing ability enhance the performance of the dye-sensitized solar cell (DSSC). The results reveal that a change in the electron donor and acceptor moieties affects the photovoltaic processes. Also, the dyes having 2-(4-(4,4-dicyanobut-3-en-2-ylidene)cyclohexa-2,5-dien-1-ylidene)malononitrile electron acceptor (AQ and TQ) have better charge transfer indices such as longer charge transfer distance (DCT) and lower overlap of electron-hole distribution (S) in comparison with the dyes having 1,1,4,4-tetracyanobuta-1,3-dienes as an electron acceptor (AE and TE). Moreover, the properties of the absorption spectra indicate that TCNQ-adduct dyes (AQ and TQ) illustrate a red-shift compared with TCNE-adduct dyes (AE and TE) due to the higher ability of the electron-withdrawing. Finally, AQ and TQ dyes are the preferred candidates to improve the efficiency of the studied DSSCs because of higher charge transfer, electron transfer rate constant, and lower chemical hardness.

Consequences and Mitigation Strategies of Abiotic Stresses in Wheat (Triticum aestivum L.) under the Changing Climate

Wheat is one of the world’s most commonly consumed cereal grains. During abiotic stresses, the physiological and biochemical alterations in the cells reduce growth and development of plants that ultimately decrease the yield of wheat. Therefore, novel approaches are needed for sustainable wheat production under the changing climate to ensure food and nutritional security of the ever-increasing population of the world. There are two ways to alleviate the adverse effects of abiotic stresses in sustainable wheat production. These are (i) development of abiotic stress tolerant wheat cultivars by molecular breeding, speed breeding, genetic engineering, and/or gene editing approaches such as clustered regularly interspaced short palindromic repeats (CRISPR)-Cas toolkit, and (ii) application of improved agronomic, nano-based agricultural technology, and other climate-smart agricultural technologies. The development of stress-tolerant wheat cultivars by mobilizing global biodiversity and using molecular breeding, speed breeding, genetic engineering, and/or gene editing approaches such as CRISPR-Cas toolkit is considered the most promising ways for sustainable wheat production in the changing climate in major wheat-growing regions of the world. This comprehensive review updates the adverse effects of major abiotic stresses and discusses the potentials of some novel approaches such as molecular breeding, biotechnology and genetic-engineering, speed breeding, nanotechnology, and improved agronomic practices for sustainable wheat production in the changing climate.

Molecular engineering of antimicrobial peptides: microbial targets, peptide motifs and translation opportunities.

The global public health threat of antimicrobial resistance has led the scientific community to highly engage into research on alternative strategies to the traditional small molecule therapeutics. Here, we review one of the most popular alternatives amongst basic and applied research scientists, synthetic antimicrobial peptides. The ease of peptide chemical synthesis combined with emerging engineering principles and potent broad-spectrum activity, including against multidrug-resistant strains, has motivated intense scientific focus on these compounds for the past decade. This global effort has resulted in significant advances in our understanding of peptide antimicrobial activity at the molecular scale. Recent evidence of molecular targets other than the microbial lipid membrane, and efforts towards consensus antimicrobial peptide motifs, have supported the rise of molecular engineering approaches and design tools, including machine learning. Beyond molecular concepts, supramolecular chemistry has been lately added to the debate; and helped unravel the impact of peptide self-assembly on activity, including on biofilms and secondary targets, while providing new directions in pharmaceutical formulation through taking advantage of peptide self-assembled nanostructures. We argue that these basic research advances constitute a solid basis for promising industry translation of rationally designed synthetic peptide antimicrobials, not only as novel drugs against multidrug-resistant strains but also as components of emerging antimicrobial biomaterials. This perspective is supported by recent developments of innovative peptide-based and peptide-carrier nanobiomaterials that we also review.

Synthesis of Pyrano [2,3-c] Pyrazole Derivatives Using a Novel Ionic-Liquid Based Nano-Magnetic Catalyst (Fe3O4@SiO2@(CH2)3NH@CC@Imidazole@SO3H+Cl−)

The current study is a molecular engineering approach designed for synthesize an ionic-liquid-based nano-magnetic solid acid heterogeneous catalyst, namely Fe3O4@SiO2@(CH2)3NH@CC@Imidazole@SO3H. Following the synthesis of the mentioned catalyst, various techniques were used to characterize, including Infrared (IR), Field Emission Scanning Electron Microscopy (FESEM) and Transmission Electron Microscopy (TEM), Energy-dispersive X-ray spectroscopy (EDX), EDX elemental mapping, Thermal gravimetric analysis (TGA) and Differential thermal analysis (DTA), and Vibrating Sample Magnetometer (VSM). The activity of the as-synthesized catalyst was evaluated in the synthesis of pyrano [2,3-c] pyrazole derivatives. It can easily be recovered using an external magnet and used repeatedly. The FTIR proved the stability of the as-synthesized catalyst even after five recovery steps. The most exciting finding was that pyrano [2,3-c] pyrazole derivatives could be produced in a short time and high yield (56–98%). The systematic design of experiment (DOE), finally, was applied to optimize the reaction condition.

Integrating molecular design and crystal engineering approaches in non-humidified intermediate-temperature proton conductors based on a Dawson-type polyoxometalate and poly(ethylene glycol) derivatives.

Anionic metal-oxygen clusters known as polyoxometalates (POMs) have been widely researched as components of proton conductors. While proton conduction under non-humidified intermediate-temperature (100-250 °C) conditions is advantageous from the viewpoint of kinetics, few solid-state materials, not to mention POM-based crystals, show truly effective proton conduction without the aid of water vapor. In this context, non-volatile proton-conductive polymers have been confined into POM-based frameworks, while fast proton conduction was infeasible. Herein, we demonstrate a new strategy to synthesize POM-polymer composites exhibiting fast proton conduction under non-humidified intermediate-temperature conditions. Specifically, a molecular design approach utilizing poly(ethylene glycol)s (PEGs) of different terminal groups or chain lengths controls the proton carrier density, and a crystal engineering approach using a large Dawson-type POM ([α-P2W18O62]6-) with an anisotropic molecular shape and alkali metal ions as counter cations fine-tunes the mobility of the confined PEGs as proton carriers. By integrating these approaches, proton conductivity over 10-4 S cm-1 at 150 °C, comparable to the well-known highly proton-conductive solid-state materials, is achieved. The proton conduction mechanism is discussed with alternative current impedance spectroscopy jointly with specific heat capacity measurements and solid-state NMR spectroscopy.

Organic Thin-Film Transistors as Gas Sensors: A Review.

Organic thin-film transistors (OTFTs) are miniaturized devices based upon the electronic responses of organic semiconductors. In comparison to their conventional inorganic counterparts, organic semiconductors are cheaper, can undergo reversible doping processes and may have electronic properties chiefly modulated by molecular engineering approaches. More recently, OTFTs have been designed as gas sensor devices, displaying remarkable performance for the detection of important target analytes, such as ammonia, nitrogen dioxide, hydrogen sulfide and volatile organic compounds (VOCs). The present manuscript provides a comprehensive review on the working principle of OTFTs for gas sensing, with concise descriptions of devices’ architectures and parameter extraction based upon a constant charge carrier mobility model. Then, it moves on with methods of device fabrication and physicochemical descriptions of the main organic semiconductors recently applied to gas sensors (i.e., since 2015 but emphasizing even more recent results). Finally, it describes the achievements of OTFTs in the detection of important gas pollutants alongside an outlook toward the future of this exciting technology.

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

At present, much attention is paid to the use of antimicrobial peptides (AMPs) of natural and artificial origin to combat pathogens. AMPs have several points that determine their biological activity. We analyzed the structural properties of AMPs, as well as described their mechanism of action and impact on pathogenic bacteria and viruses. Recently published data on the development of new AMP drugs based on a combination of molecular design and genetic engineering approaches are presented. In this article, we have focused on information on the amyloidogenic properties of AMP. This review examines AMP development strategies from the perspective of the current high prevalence of antibiotic-resistant bacteria, and the potential prospects and challenges of using AMPs against infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Molecular and functional characterization of buffalo nasal epithelial odorant binding proteins and their structural insights by in silico and biochemical approaches

The olfactory system is capable of detecting and distinguishing thousands of environmental odorants that play a key role in reproduction, social behaviours including pheromones influenced classical events. Membrane secretary odorant binding proteins (OBPs) are soluble lipocalins, localized in the nasal membrane of mammals. They bind and carry odorants within the nasal epithelium to putative olfactory transmembrane receptors (ORs). OBP has not yet been exploited to develop a suitable technique to detect oestrus which is being reported as a difficult task in buffalo. In the present study, using molecular biology and protein engineering approaches, we have cloned six novel OBP isoforms from buffalo nasal epithelium odorant-binding proteins (bnOBPs). Furthermore, 3 D models were developed and molecular-docking, dynamics experiments were performed by in silico approaches. In particular, we found four residues (Phe104, Phe134, Phe69 and Asn118) in OBP1a, which contributed to favourable interactions towards two sex pheromones, specifically oleic acid and p-cresol. We expressed this protein in Escherichia coli from female buffalo urine and validated through fluorescence quenching studies to show similar strong binding affinities of OBP1a to oleic acid and p-cresol. By using structural data, the binding specificity was also verified by site-directed mutagenesis of the four residues followed by in vitro binding assays. Our results enable us to better understand the functions of different nasal epithelium OBP isoforms in buffaloes. They also lead to improved understanding of the interaction between olfactory proteins and odorants to develop highly selective biosensing devices for non-invasive detection of oestrus in buffaloes. Communicated by Ramaswamy H. Sarma