Rational Design Strategy Research Articles

Rational design of Zeocin binding protein variants for antibiotic resistance studies

Antibiotic resistance marker was used in this investigation because they are selected;e markers and effective in different hosts. This study used Zeocin binding protein (ZBP) due to its known 3D structure and applicability in prokaryotic and eukaryotic hosts. A library of 22 mutations was developed through a rational design strategy. Subsequently, a selection strategy was used to identify destabilizing mutations in the ZBP. ZBP variants were expressed in E.coli using a leaky expression approach, and minimum inhibitory concentration (MIC) was calculated by cultivating different variants at various Zeocin concentrations. Zeocin resistance was drastically decreased in some ZBP variants. Positive controls (wild-type ZBP) exhibited high resistance, while negative controls (pET vector without ZBP) showed susceptibility. Two variants (ZBP P9E and ZBP R26F) displayed drastic resistance loss. The variants reported in this study may identify molecular chaperones and folding modulators affecting proteostasis. These variants can potentially discover chemical chaperones that improve the stability and solubility of destabilized ZBP variants.

Integrated design of multifunctional lightweight magnetic cellulose-based aerogel with 1D/2D/3D hierarchical network for efficient microwave absorption

Developing electromagnetic wave absorption materials that are both multifunctional and high-performance, while using rational dimensional design and component strategies, remains extremely challenging. Herein, multidimensional, gradient porous, electrically, and magnetically conductive carbon nanocellulose aerogels composed of nanocellulose and highly oriented Ni chains are prepared through freeze-drying and subsequent low-temperature annealing. Interestingly, the Ni/CNCA composite achieves exceptional microwave absorption with a minimum reflection loss (RLmin) value of −62.0 dB and a maximum effective absorption bandwidth (EAB) of 6 GHz, covering the entire Ku-band. The superior electromagnetic wave absorption stems from 1D/2D/3D double-supported interpenetrating network with satisfactory impedance matching, dielectric/magnetic losses, interface/dipole polarization, and multiple/reflection scattering. Furthermore, the Ni/CNCA exhibits a low density, excellent mechanical adaptability, hydrophobicity, and corrosion resistance. This work introduces innovative approaches for developing lightweight, multifunctional microwave absorbers for practical applications.

Physics-based discrete models for magneto-mechanical metamaterials

Magneto-mechanical metamaterials are emerging smart materials whose mechanical responses can be tailored through structure architecture and magnetic interactions. The latter provides additional freedom in the material design space and leads to novel behaviors due to its nonlocal nature. The enriched functionalities open new possibilities in various applications, such as actuators, energy absorbers, and soft robots. However, the nonlinear and nonlocal coupling between elastic and magnetic forces poses a great challenge in the modeling and simulation of these systems, further hindering theory-based rational design strategies. Here, we focus on a class of magneto-mechanical metamaterials comprising elastic solids embedded with rigid permanent magnets. The clear separation between elastic and magnetic forces simplifies the design and fabrication process, yet their nonlocal interplay still allows for complex behaviors. We present a simulation framework for such magneto-mechanical metamaterials by combining a lattice spring model for the elastic solid with the dipole model for the magnetic interactions and implementing it in the LAMMPS molecular dynamics software. We demonstrate the capabilities of our framework by simulating a few representative structures, including shape-locking lattice metamaterials, a soft cellular solid with controllable buckling, and a metamaterial chain with phase-transforming behavior. For the shape-locking lattice metamaterials, we successfully capture the magnetic-actuation-driven reconfiguration and the nonlinear mechanical response of the curved lattices. For the soft cellular solid, we identify its buckling patterns under external non-uniform magnetic fields and simulate a buckling evolution process consistent with experiments. For the metamaterial chain, we include the strong long-range interactions among the embedded magnets and reproduce the controllable phase transitions in the experiments. Our work provides a simple yet versatile simulation methodology to investigate the nonlinear mechanical behaviors in the presence of strong external and internal magnetic forces, which will facilitate the design and analysis of magneto-mechanical materials. It can also be applied to other magnetically-driven smart structures, such as soft robots.

A Rational Design Strategy for Metal Exchanged Zeolites in the Conversion of Methane to Methanol – A Pathway Towards Commercial Viability

Methane is a potent greenhouse gas, and reducing methane released to the atmosphere is crucial in limiting global warming. A promising strategy is to convert methane to higher valuable chemicals right after emission. One class of materials active for this chemistry are metal exchanged zeolites. In this concept paper, we describe how it is possible to rationalize the performance of metal exchanged zeolites for the selective conversion of methane to methanol. We explore how phase diagrams can be used to identify condition dependent active site structures, how synthesis can be used to stir site distribution, and how the performance of single metal sites can be calculated. Combining these three aspects then allows to understand and predict experimentally measured quantities such as methane conversion and spectroscopic signals. In the end, we outline the most promising strategies to bring this technology to industrial feasibility.

A Review on Indole-triazole Molecular Hybrids as a Leading Edge in Drug Discovery: Current Landscape and Future Perspectives.

Molecular hybridization is a rational design strategy used to create new ligands or prototypes by identifying and combining specific pharmacophoric subunits from the molecular structures of two or more known bioactive derivatives. Molecular hybridization is a valuable technique in drug discovery, enabling the modulation of unwanted side effects and the creation of potential dual-acting drugs that combine the effects of multiple therapeutic agents. Indole-triazole conjugates have emerged as promising candidates for new drug development. The indole and triazole moieties can be linked through various synthetic strategies, such as click chemistry or other coupling reactions, to generate a library of diverse compounds for biological screening. The achievable structural diversity with indole-triazole conjugates offers avenues to optimize their pharmacokinetic and pharmacodynamic attributes, amplifying their therapeutic efficacy. Researchers have extensively tailored both indole and triazole frameworks with diverse modifications to comprehend their impact on the drug's pharmacokinetic and pharmacodynamic characteristics. The current review article endeavours to explore and discuss various research strategies to design indoletriazole hybrids and elucidate their significance in a variety of pathological conditions. The insights provided herein are anticipated to be beneficial for the researchers and will likely encourage further exploration in this field.

Ring-shaped cavity anchor Pt to derive Pt/WO3-x heterointerfaces for efficient hydrogen evolution in acidic water and seawater

Developing novelplatinum (Pt)-based hydrogen evolution reaction (HER) catalysts with high activity and stability is significant for the ever-broader applications of hydrogen energy. However, achieving precise modulation of the ultrafine Pt nanoparticles coordination environment in conventional catalysts is challenging. In this work, we developed a unique “ring-shaped cavity induced” strategy to anchor the Ptx through the ring-shaped cavity of polyoxometalates (POMs) Na33H7P8W48O184 (denoted as P8W48). The NayPtx[P8W48O184] (PtxP8W48) was in-situ converted into abundant Pt/WO3-x heterostructure with Pt (∼2 nm) and highly depressed Pt-O-W heterointerfaces. Pt/WO3-x nanoparticles supported on highly conductive rGO exhibit superior HER activity. The overpotentials of the catalyst are only 2.8 mV and 4.7 mV at 10 mA·cm−2 in acidic water and seawater, far superior to commercial 20 % Pt/C catalyst. Additionally, the catalyst can be stabilized at a current density of 30 mA·cm−2 for 180 h. This study provides a feasible strategy for rational design of Pt-based catalysts for renewable energy applications.

Engineering Versatile Bacteria-Derived Outer Membrane Vesicles: An Adaptable Platform for Advancing Cancer Immunotherapy.

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

Rational Design Strategy for High-Valence Metal-Driven Electronically Modulated High-Entropy Co-Ni-Fe-Cu-Mo (Oxy)Hydroxide as Superior Multifunctional Electrocatalysts.

Creating durable and efficient multifunctional electrocatalysts capable of high current densities at low applied potentials is crucial for widespread industrial use in hydrogen production. Herein, a Co-Ni-Fe-Cu-Mo (oxy)hydroxide electrocatalyst with abundant grain boundaries on nickel foam using a scalable coating method followed by chemical precipitation is synthesized. This technique efficiently organizes hierarchical Co-Ni-Fe-Cu-Mo (oxy)hydroxide nanoparticles within ultrafine crystalline regions (<4nm), enriched with numerous grain boundaries, enhancing catalytic site density and facilitating charge and mass transfer. The resulting catalyst, structured into nanosheets enriched with grain boundaries, exhibits superior electrocatalytic activity. It achieves a reduced overpotential of 199mV at 10mAcm2 current density with a Tafel slope of 48.8mVdec1 in a 1m KOH solution, maintaining stability over 72h. Advanced analytical techniques reveal that incorporating high-valency copper and molybdenum elements significantly enhances lattice oxygen activation, attributed to weakened metal-oxygen bonds facilitating the lattice oxygen mechanism (LOM). Synchrotron radiation studies confirm a synergistic interaction among constituent elements. Furthermore, the developed high-entropy electrode demonstrates exceptional long-term stability under high current density in alkaline environments, showcasing the effectiveness of high-entropy strategies in advancing electrocatalytic materials for energy-related applications.

Emerging Nanotechnology in Preclinical Pancreatic Cancer Immunotherapy: Driving Towards Clinical Applications.

The high malignant degree and poor prognosis of pancreatic cancer (PC) pose severe challenges to the basic research and clinical translation of next-generation therapies. The rise of immunotherapy has improved the treatment of a variety of solid tumors, while the application in PC is highly restricted by the challenge of immunosuppressive tumor microenvironment. The latest progress of nanotechnology as drug delivery platform and immune adjuvant has improved drug delivery in a variety of disease backgrounds and enhanced tumor therapy based on immunotherapy. Based on the immune loop of PC and the status quo of clinical immunotherapy of tumors, this article discussed and critically analyzed the key transformation difficulties of immunotherapy adaptation to the treatment of PC, and then proposed the rational design strategies of new nanocarriers for drug delivery and immune regulation, especially the design of combined immunotherapy. This review also put forward prospective views on future research directions, so as to provide information for the new means of clinical treatment of PC combined with the next generation of nanotechnology and immunotherapy.

Binding Affinity Determination in Drug Design: Insights from Lock and Key, Induced Fit, Conformational Selection, and Inhibitor Trapping Models.

Binding affinity is a fundamental parameter in drug design, describing the strength of the interaction between a molecule and its target protein. Accurately predicting binding affinity is crucial for the rapid development of novel therapeutics, the prioritization of promising candidates, and the optimization of their properties through rational design strategies. Binding affinity is determined by the mechanism of recognition between proteins and ligands. Various models, including the lock and key, induced fit, and conformational selection, have been proposed to explain this recognition process. However, current computational strategies to predict binding affinity, which are based on these models, have yet to produce satisfactory results. This article explores the connection between binding affinity and these protein-ligand interaction models, highlighting that they offer an incomplete picture of the mechanism governing binding affinity. Specifically, current models primarily center on the binding of the ligand and do not address its dissociation. In this context, the concept of ligand trapping is introduced, which models the mechanisms of dissociation. When combined with the current models, this concept can provide a unified theoretical framework that may allow for the accurate determination of the ligands' binding affinity.

Modulation of Li+ microenvironment in liquid electrolyte for interface design of Li‐metal anodes

AbstractWhile lithium metal anodes (LMAs) offer the highest energy density, positioning them as a promising material for graphite, they suffer from uneven electroplating morphology and the formation of Li dendrites. Given the pivotal role of the solid‐electrolyte interphase (SEI), which is formed by electrolyte decomposition, in mitigating dendritic growth, extensive research has been conducted on liquid electrolytes in Li metal batteries (LMBs). This mini‐review presents the historical advancements in LMB electrolytes, focusing on modulating the Li+ microenvironment and LMA interface chemistry to inhibit Li dendrite formation. We traced the evolution of LMB electrolytes from traditional formulations to advanced designs. In particular, the reinforcement of the SEI and the compact morphology of the deposited Li are deeply discussed at each advancement in liquid electrolytes. We subsequently identify common characteristics among these advanced electrolytes and conclude by discussing future directions and strategies for rational design.

Exploring the Pt → ligand back‐donation through the rotational barrier of an acyclic diaminocarbene

The importance of the Dewar‐Chatt‐Duncanson model for inorganic chemists cannot be overstated. It provides a simple yet robust framework for understanding metal‐ligand bonding in terms of σ‐donation and π‐back‐donation. Some years ago, a publication (Chem. Eur. J. 2015, 21, 2467) introduced a method to effectively correlate experimental NMR data with back‐donation, using [LAu(ADC)]+/0 complexes (ADC = acyclic diaminocarbene) as case study. Here, we theoretically expand the same method to [L(PH3)(ADC)PtCl]+/0 complexes, to verify whether the method is general and to gain deeper insights into the influence of L on Pt‐ADC bonding, especially in the trans position. Such insights hold potential for guiding rational catalyst design strategies.

Efficient and stable dehydrogenation of methylcyclohexane over Pt supported on mesoporous alumina with excellent textural properties

Mesoporous alumina (MA) materials with outstanding textural properties have been synthesized by a facile approach, and were evaluated as supports of Pt-based catalyst for methylcyclohexane dehydrogenation. At 300 °C, the resultant catalyst demonstrates a much higher activity with a maximum hydrogen evolution rate of 2081 mmol/gPt/min in comparison with the state-of-the-art alumina supported Pt catalysts. Interestingly, even after a long-time reaction of 100 h or regeneration, more than 80% of original activity was still maintained. The superior catalytic performance of the obtained catalyst is associated with the high specific surface area and large mesoporous size of support MA, thus benefiting the increase in the number of Pt active sites and efficiently inhibiting the formation of coke deposition during the reaction. Our contribution has provided a rational design strategy for highly efficient and stable dehydrogenation catalysts, which is a key for the utilization of methylcyclohexane-toluene system in hydrogen storage technology.

From Structure to Application: The Evolutionary Trajectory of Spherical Nucleic Acids.

Since the proposal of the concept of spherical nucleic acids (SNAs) in 1996, numerous studies have focused on this topic and have achieved great advances. As a new delivery system for nucleic acids, SNAs have advantages over conventional deoxyribonucleic acid (DNA) nanostructures, including independence from transfection reagents, tolerance to nucleases, and lower immune reactions. The flexible structure of SNAs proves that various inorganic or organic materials can be used as the core, and different types of nucleic acids can be conjugated to realize diverse functions and achieve surprising and exciting outcomes. The special DNA nanostructures have been employed for immunomodulation, gene regulation, drug delivery, biosensing, and bioimaging. Despite the lack of rational design strategies, potential cytotoxicity, and structural defects of this technology, various successful examples demonstrate the bright and convincing future of SNAs in fields such as new materials, clinical practice, and pharmacy.

Engineering Single Cu Atoms Anchored via N‐Heterocyclic Carbene in COF Mesopores for Modulating Electron Kinetics of CO2 Photoconversion

AbstractCharge transfer and carbon dioxide (CO2) adsorption/activation are critical factors for the electron kinetics during CO2 photoconversion. Herein, high‐loading and robust single Cu atoms (7.8 wt.%) are anchored via N‐heterocyclic carbene ligands derived from imidazolium ionic liquid motifs, precisely bonding to the acceptors of mesoporous donor‐acceptor pyridine‐covalent organic framework (pCOF) nanosheets. By engineering the valance and coordination structure, atomic Cu(I)‐CO2 sites, superior to Cu(II)‐CN2OCl ones, enable a 22‐fold increase of CO2 conversion rate compared to pCOF in pure water, ≈100% selectivity toward CO, and an apparent quantum yield of 1.7% (420 nm). The photoactivity outperforms analogous COF‐based photocatalysts under similar conditions. Experimental results prove single Cu(I) atoms possess more improved electron capture and CO2 adsorption/activation capacities than single Cu(II) ones. Combining fs‐ and µs‐transient absorption spectroscopy, the electron kinetics mechanism is investigated on the single‐atom pCOF photocatalyst model. The fs‐transient absorption spectra confirm single Cu(I) atoms can rapidly and precisely extract electrons from the electron‐rich region of pCOF along N‐heterocyclic carbene, exhibiting an electron transfer rate of 3 × 109 s−1. Using in situ µs‐transient absorption spectroscopy, the electron transfer efficiency is quantified to reach 60.4% under photocatalytic reaction conditions. This work provides a rational design strategy for advanced single‐atom photocatalysts.

Theory-Driven Tailoring of the Microenvironment of Quaternary Ammonium Binding Sites on Electrospun Nanofibers for Efficient Bilirubin Removal in Hemoperfusion.

Efficient adsorbents for excess bilirubin removal are extremely important for the treatment of hyperbilirubinemia. However, traditional adsorbents, such as activated carbons and ion-exchange resins, still suffer from dissatisfactory adsorption performance and poor blood compatibility. Herein, we adopted a rational design strategy guided by density functional theory (DFT) calculations to prepare blood-compatible quaternary ammonium group grafted electrospun polyacrylonitrile nanofiber adsorbents. The calculation analysis and adsorption experiments were used to investigate the structure-function relationship between group types and bilirubin adsorption, both indicating that quaternary ammonium groups with suitable configurations played a crucial role in bilirubin binding. The obtained nanofiber adsorbents showed the bilirubin removal efficiency above 90% even at a coexisting BSA concentration of 50 g L-1. The maximum adsorption capacities were 818.9 mg g-1 in free bilirubin solution and 163.7 mg g-1 in albumin bound bilirubin solution. The nanofiber adsorbents also showed considerable bilirubin removal in dynamic adsorption to reduce the bilirubin concentration to a normal level, which was better than commercial activated carbons. Our study demonstrates the high feasibility of a theory-driven design method for the development of grafted electrospun nanofibers, which have good potential as bilirubin adsorbents in hemoperfusion applications.

Multicolour stretchable perovskite electroluminescent devices for user-interactive displays

Wearable displays require mechanical deformability to conform to the skin, as well as long-term stability, multicolour emission and sufficient brightness to enable practically useful applications. However, endowing a single device with all the features remains a challenge. Here we present a rational material design strategy and simple device-manufacturing process for skin-conformable perovskite-based alternating-current electroluminescent (PeACEL) devices. These devices exhibit a narrow emission bandwidth (full-width at half-maximum, <37 nm), continuously tuneable emission wavelength (468–694 nm), high stretchability (400%) and adequate luminance (>200 cd m−2). The approach leverages a new class of perovskite zinc sulfide (PeZS) phosphors, consisting of ZnS phosphors coated with perovskite nanoparticles for electrical excitation via total intraparticle energy transfer. This strategy results in pure red and green emissions and expands the colour gamut of powder-based ACEL devices by 250%. Moreover, our processing technique facilitates the integration of PeACEL displays with wearable electronics, enabling applications in dynamic interactive displays and visual real-time temperature monitoring. These PeACEL displays offer new routes in flexible electronics and hold potential for the development of efficient artificial skins, robotics and biomedical monitoring devices.

Protective Efficacy of the Epitope-Conjugated Antigen N-Tc52/TSkb20 in Mitigating Trypanosoma cruzi Infection through CD8+ T-Cells and IFNγ Responses.

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health challenge affecting millions in Latin America and worldwide. Although significant progress has been made in vector control, no vaccine exists to prevent infection or mitigate disease pathogenesis. We developed a rationally designed chimeric protein vaccine, N-Tc52/TSkb20, incorporating immunodominant epitopes from two T. cruzi antigens, the amino-terminal portion of Tc52 and the TSkb20 epitope derived from trans-sialidase. The objectives of this study were to construct and characterize the antigen and evaluate its protective potential in an immunoprophylactic murine model of T. cruzi infection. The N-Tc52/TSkb20 protein was recombinantly expressed in E. coli and its identity was confirmed using mass spectrometry and Western blotting. Immunization with the chimeric protein significantly controlled parasitemia and reduced the heart, colon, and skeletal muscle parasite burdens compared to non-vaccinated mice. Protection was superior to vaccination with the individual parental antigen components. Mechanistically, the vaccine induced potent CD8+ T-cell and IFNγ responses against the incorporated epitopes and a protective IgG antibody profile. A relatively low IL-10 response favored early parasite control. These results validate the promising multi-epitope approach and support the continued development of this type of rational vaccine design strategy against Chagas disease.

Synergistic Bulk and Surface Engineering for Expeditious and Durable Reversible Protonic Ceramic Electrochemical Cells Air Electrode.

Reversible protonic ceramic electrochemical cells (R-PCECs) offer the potential for high-efficiency power generation and green hydrogen production at intermediate temperatures. However, the commercial viability of R-PCECs is hampered by the sluggish kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) within conventional air electrodes operating at reduced temperatures. To address this challenge, this work introduces a novel approach based on the simultaneous optimization of bulk-phase metal-oxygen bonds and in-situ formation of a metal oxide nano-catalyst surface modification. This strategy is designed to expedite the ORR/OER electrocatalytic activity of air electrodes exhibiting triple (O2-, H+, e-) conductivity. Specifically, this engineered air electrode nanocomposite-Ba(Co0.4Fe0.4Zr0.1Y0.1)0.95Ni0.05F0.1O2.9-δ demonstrates remarkable ORR/OER catalytic activity and exceptional durability in R-PCECs. This is evidenced by significantly improved peak power density from 626 to 996mW cm-2 and highly stable reversibility over a 100-h cycling period. This research offers a rational design strategy to achieve high-performance R-PCEC air electrodes with superior operational activity and stability for efficient and sustainable energy conversion and storage.

Rational Design of Lipid-Based Vectors for Advanced Therapeutic Vaccines.

Recent advancements in vaccine delivery systems have seen the utilization of various materials, including lipids, polymers, peptides, metals, and inorganic substances, for constructing non-viral vectors. Among these, lipid-based nanoparticles, composed of natural, synthetic, or physiological lipid/phospholipid materials, offer significant advantages such as biocompatibility, biodegradability, and safety, making them ideal for vaccine delivery. These lipid-based vectors can protect encapsulated antigens and/or mRNA from degradation, precisely tune chemical and physical properties to mimic viruses, facilitate targeted delivery to specific immune cells, and enable efficient endosomal escape for robust immune activation. Notably, lipid-based vaccines, exemplified by those developed by BioNTech/Pfizer and Moderna against COVID-19, have gained approval for human use. This review highlights rational design strategies for vaccine delivery, emphasizing lymphoid organ targeting and effective endosomal escape. It also discusses the importance of rational formulation design and structure-activity relationships, along with reviewing components and potential applications of lipid-based vectors. Additionally, it addresses current challenges and future prospects in translating lipid-based vaccine therapies for cancer and infectious diseases into clinical practice.