Rational Design Principles Research Articles

Rationally Designed Mo/Ru-Based Multi-Site Heterogeneous Electrocatalyst for Accelerated Alkaline Hydrogen Evolution Reaction.

The rational design of multi-site electrocatalysts with three different functions for facile H2O dissociation, H-H coupling, and rapid H2 release is desirable but difficult to achieve. This strategy can accelerate the sluggish kinetics of the hydrogen evolution reaction (HER) under alkaline conditions. To resolve this issue, a Mo/Ru-based catalyst with three different active sites (Ru/Mo2C/MoO2) is rationally designed and its performance in alkaline HER is evaluated. The experimental results and density functional theory calculations revealed that, at the heterogeneous Mo2C/MoO2 interface, the higher valence state of Mo (MoO2) and the lower valence state of Mo (Mo2C) exhibited strong OH- and H-binding energies, respectively, which accelerated H2O dissociation. Moreover, the interfacial Ru possessed an appropriate hydrogen binding energy for H-H coupling and subsequent H2 evolution. Thus, this catalyst significantly accelerated the Volmer step and the Tafel step and, consequently, HER kinetics. This catalyst also demonstrated low overpotentials of 19 and 160mV at current densities of 10 and 1000mA cm-2, respectively, in alkaline media and long-term stability superior to that of most state-of-the-art alkaline HER electrocatalysts. This work provides a rational design principle for advanced multi-site catalytic systems, which can realize multi-electron electrocatalytic reactions.

Fluorine Doping Modulating Pore Structure and Adsorption Capability of Carbon Matrix Boosting Potassium Storage Performance of Red Phosphorus Anode

AbstractThe application of alloying‐typed red phosphorus (red P) anode in potassium‐ion batteries (KIBs) with ultra‐high theoretical capacity is hindered by the limited capacity and fast capacity decay due to poor electronic conductivity and huge volume change. Herein, a facile and efficient strategy of fluorine (F) doping is innovatively developed to modulate the pore structure of carbon matrix (F‐CNS) to encapsulate red P with enhanced potassium storage capability. Theoretical calculations reveal that F doping induces additional defects within the carbon layer, which facilitates P4 molecules embedding into the F‐doping‐induced micropores, enhances the adsorption ability toward K atoms and P4 molecules, and improves electrochemical kinetics assisted with more charge transfer obtained from the electron density difference, thus enabling robust potassium storage capability for such unique Red P@F‐CNS anode. Accordingly, the Red P@F‐CNS anode demonstrates outstanding cycling stability (90% capacity retention after 800 cycles at 2A g−1), and the potassium‐ion full cell (Red P@F‐CNS//KFeHCF) exhibits exceptional long‐term cycling performance (129 mAh g−1 after 2500 cycles at 5 A g−1 with only 0.014% decay per cycle). In situ characterizations confirm the superior structural integrity of the carbon‐based matrix. This study offers a rational design principle for engineering high‐performance carbon‐supported alloying‐typed anodes for KIBs.

Mussel-Inspired, Self-Healing, Highly Effective Fully Polymeric Fire-Retardant Coatings Enabled by Group Synergy.

Fire-retardant coatings represent a universal cost-effective approach to providing fire protection for various substrates without compromising substrates' bulk properties. However, it has been attractive yet highly challenging to create waterborne polymeric fire-retardant coatings combining high-efficiency, generally strong adhesion, and self-repairability due to a lack of rational design principles. Inspired by mussel's unique adhesive, self-healing, and char-forming mechanisms, herein, a "group synergy" design strategy is proposed to realize the combination of self-healing, strong adhesion, and high efficiency in a fully polymeric fire-retardant coating via multiple synergies between catechol, phosphonic, and hydroxyethyl groups. As-created fire-retardant coating exhibits a rapid room-temperature self-healing ability and strong adhesion to (non)polar substrates due to multiple dynamic non-covalent interactions enabled by these groups. Because these functional groups enable the formation of a robust structurally intact yet slightly expanded char layer upon exposure to flame, a 200µm-thick such coating can make extremely flammable polystyrene foam very difficult to ignite and self-extinguishing, which far outperforms previous strategies. Moreover, this coating can provide universal exceptional fire protection for a variety of substrates from polymer foams, and timber, to fabric and steel. This work presents a promising material design principle to create next-generation sustainable high-performance fire-retardant coatings for general fire protection.

Theoretical Investigation of the Adsorbate and Potential-Induced Stability of Cu Facets during Electrochemical CO2 and CO Reduction

The activity and product selectivity of electrocatalysts for reactions like the carbon dioxide and carbon monoxide reduction reactions (CO2RR and CORR) are intimately dependent on the catalyst’s structure and composition. While engineering catalytic surfaces can improve performance, discovering the key sets of rational design principles remains challenging due to limitations in modeling catalyst stability under operating conditions. Herein, we perform first-principles density functional calculations adopting implicit solvation methods with potential control to study the influence of adsorbates and applied potential on the stability of different facets of model Cu electrocatalysts. Using coverage dependencies extracted from microkinetic models, we describe an approach for calculating potential and adsorbate-dependent contributions to surface energies under reaction conditions, where Wulff constructions are used to understand the morphological evolution of Cu electrocatalysts under CO2RR and CORR conditions. We identify that CO*, a key reaction intermediate, exhibits higher kinetically and thermodynamically accessible coverages on (100) relative to (111) facets, which can translate into an increased relative stabilization of the (100) facet during CO2RR. Our results support the known tendency for increased (111) faceting of Cu nanoparticles under more reducing conditions and that the relative increase in (100) faceting observed under CO2RR conditions is likely attributed to differences in CO* coverage between these facets.This work was partially performed under the auspices of the U.S. DOE by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344 and partially supported by the U.S. DOE, Office of Energy Efficiency and Renewable Energy, Advanced Materials & Manufacturing Office.

Cation/anion-doping induced electronic structure modulation of CoMoO4 for enhanced hydrogen evolution

The design and fabrication of high-performance, inexpensive and durable electrocatalyst toward hydrogen evolution reaction (HER) is supremely significant for alleviating energy crisis and environmental concerns, but still remaining challenging. Herein, we develop an experimental work based on etching and reduction strategy to reveal the remarkable effect of cation/anion co-doping in CoMoO4 on its intrinsic HER activity. The CoMoO4 with Fe and B incorporation (Fe/B-CoMoO4) exhibits a current density of 10 mA cm−2 with strikingly low potential of 38 mV coupling with Tafel slope of 51 mV dec-1, and manifesting a robust durability for 100 h with no attenuation, which is comparable to the state-of-the-art commercial Pt/C catalyst. The collective experimental and theoretical findings concomitantly illustrate that the enhanced performances are due to the strong synergistic effect resulting from the co-doping of Fe and B, which plays a pivotal role in finely tuning the electronic structure of CoMoO4, further optimizing the adsorption free energy of H intermediates and shifting the center of the d-band of Fe/B-CoMoO4 away from the Fermi level. This fantastic work highlights the critical role of foreign element incorporating for optimizing electronic structure of transition metal oxides toward HER, and offers valuable guiding principles for rational design of more efficient energy conversion devices.

Carbon Dots in the Pathological Microenvironment: ROS Producers or Scavengers?

Reactive oxygen species (ROS), as metabolic byproducts, play pivotal role in physiological and pathological processes. Recently, studies on the regulation of ROS levels for disease treatments have attracted extensive attention, mainly involving the ROS-induced toxicity therapy mediated by ROS producers and antioxidant therapy by ROS scavengers. Nanotechnology advancements have led to the development of numerous nanomaterials with ROS-modulating capabilities, among which carbon dots (CDs) standing out as noteworthy ROS-modulating nanomedicines own their distinctive physicochemical properties, high stability, and excellent biocompatibility. Despite progress in treating ROS-related diseases based on CDs, critical issues such as rational design principles for their regulation remain underexplored. The primary cause of these issues may stem from the intricate amalgamation of core structure, defects, and surface states, inherent to CDs, which poses challenges in establishing a consistent generalization. This review succinctly summarizes the recently progress of ROS-modulated approaches using CDs in disease treatment. Specifically, it investigates established therapeutic strategies based on CDs-regulated ROS, emphasizing the interplay between intrinsic structure and ROS generation or scavenging ability. The conclusion raises several unresolved key scientific issues and prominent technological bottlenecks, and explores future perspectives for the comprehensive development of CDs-based ROS-modulating therapy.

Assembly-Induced Membrane Selectivity of Artificial Model Peptides through Entropy-Enthalpy Competition.

Peptide design and drug development offer a promising solution for combating serious diseases or infections. In this study, using an AI-human negotiation approach, we have designed a class of minimal model peptides against tuberculosis (TB), among which K7W6 exhibits potent efficacy attributed to its assembly-induced function. Comprising lysine and tryptophan with an amphiphilic α-helical structure, the K7W6 sequence exhibits robust activity against various infectious bacteria causing TB (including clinically isolated and drug-resistant strains) both in vitro and in vivo. Moreover, it synergistically enhances the effectiveness of the first-line antibiotic rifampicin while displaying low potential for inducing drug resistance and minimal toxicity toward mammalian cells. Biophysical experiments and simulations elucidate that K7W6's exceptional performance can be ascribed to its highly selective and efficient membrane permeabilization activity induced by its distinctive self-assembly behavior. Additionally, these assemblies regulate the interplay between enthalpy and entropy during K7W6-membrane interaction, leading to the peptide's two-step mechanism of membrane interaction. These findings provide valuable insights into rational design principles for developing advanced peptide-based drugs while uncovering the functional role played by assembly.

Molecular modeling and cytotoxic activity of newly synthesized benzothiazole-thiazole conjugates

In the dynamic area of drug development, researchers have been urged to uncover and test novel compounds with better effectiveness and fewer side effects in order to find more effective cancer treatments. In this comprehensive study, the synthesis and anticancer efficacy of new benzothiazole-thiazole have been displayed. Initially, a series of benzothiazole-thiazole conjugates 5a-c, 7a-b, and 8 were carefully designed and synthesized from the versatile 6-acetyl-2-phenylsulfonamidobenzothiazole (2), following the guidelines of rational design principles. The DFT/B3LYP approach showed that the synthesized hybrids had a non-planar configuration, where the benzene-sulfonamide group was oriented almost perpendicularly. The tested derivatives exhibited close HOMO-LUMO energies leading to small energy gaps (ΔEH-L = 1.54–2.97 eV). Additionally, the inhibitory effects of the newly synthesized conjugates were tested on four cancer cell lines, including HepG2, HCT-116, MCF-7, and WI38. Conjugates 5a and 8 had strong inhibitory effects on the HCT-116 and MCF-7 cell lines. Additionally, the synthesized conjugates showed inhibitory action against CAIX and CAXII, where conjugate 8 also effectively inhibited both isoforms, as well as, conjugate 5a. Molecular docking analysis was performed to study the binding affinities and interactions of the newly synthesized benzothiazole-thiazole conjugates with the target PDB: 5fl4 protein. Moreover, the ADME outlines of the inspected conjugates were displayed, and conjugates 2 and 6 showed suitable characteristics for GI absorption and minor violations of Lipinski’s rules; thus, they are promising lead compounds.

Nanotechnology in Ankylosing Spondylitis: Advancements in Drug Delivery and Targeted Therapy

Ankylosing spondylitis is a chronic inflammatory disorder primarily affecting the spine and the sacroiliac joints, although it is now considered for new drug target possibilities. It is an area in which nanotechnology has shown significant potential. This report offers an extensive review of the formulation design, clinical utility, and current development in the use of nanotechnology for treating AS. The rational design principles of nanotherapeutics, created to modify the myriad processes implicated in AS pathophysiology, were examined. It comprises drug delivery systems, targeting approaches, and release processes. Clinical and preclinical evidence of nanomedicines’ tolerability and effectiveness in AS therapy is reported. In conclusion, this document reflects the recent state of these nanotechnology-based treatments for AS and discusses the author’s future goals in developing novel, powerful treatment strategies that generate strong patient outcomes.

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport

AbstractPerhalogenated closo‐borates represent a new class of membrane carriers. They owe this activity to their chaotropicity, which enables the transport of hydrophilic molecules across model membranes and into living cells. The transport efficiency of this new class of cluster carriers depends on a careful balance between their affinity to membranes and cargo, which varies with chaotropicity. However, the structure–activity parameters that define chaotropic transport remain to be elucidated. Here, we have studied the modulation of chaotropic transport by decoupling the halogen composition from the boron core size. The binding affinity between perhalogenated decaborate and dodecaborate clusters carriers was quantified with different hydrophilic model cargos, namely a neutral and a cationic peptide, phalloidin and (KLAKLAK)2. The transport efficiency, membrane‐lytic properties, and cellular toxicity, as obtained from different vesicle and cell assays, increased with the size and polarizability of the clusters. These results validate the chaotropic effect as the driving force behind the membrane transport propensity of boron clusters. This work advances our understanding of the structural features of boron cluster carriers and establishes the first set of rational design principles for chaotropic membrane transporters.

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport.

Perhalogenated closo-borates represent a new class of membrane carriers. They owe this activity to their chaotropicity, which enables the transport of hydrophilic molecules across model membranes and into living cells. The transport efficiency of this new class of cluster carriers depends on a careful balance between their affinity to membranes and cargo, which varies with chaotropicity. However, the structure-activity parameters that define chaotropic transport remain to be elucidated. Here, we have studied the modulation of chaotropic transport by decoupling the halogen composition from the boron core size. The binding affinity between perhalogenated decaborate and dodecaborate clusters carriers was quantified with different hydrophilic model cargos, namely a neutral and a cationic peptide, phalloidin and (KLAKLAK)2. The transport efficiency, membrane-lytic properties, and cellular toxicity, as obtained from different vesicle and cell assays, increased with the size and polarizability of the clusters. These results validate the chaotropic effect as the driving force behind the membrane transport propensity of boron clusters. This work advances our understanding of the structural features of boron cluster carriers and establishes the first set of rational design principles for chaotropic membrane transporters.

Design Principles Guided by DFT Calculations and High-Throughput Frameworks for the Discovery of New Diamond-like Chalcogenide Thermoelectric Materials.

Rational design principles are one pathway to discovering new materials. However, technological breakthroughs rarely occur in this way because these design principles are usually based on incremental advances that seldom lead to disruptive applications. The emergence of machine-learning (ML) and high-throughput (HT) techniques has changed the paradigm, opening up new possibilities for efficiently screening large chemical spaces and creating on-the-fly design principles for the discovery of novel materials with desired properties. In this work, the approach is used to discover novel thermoelectric (TE) materials based on quaternary diamond-like chalcogenides. A HT framework that integrates density functional theory calculations, ML, and the solution of the Boltzmann transport equation is used to efficiently rationalize the transport properties of these compounds and identify those with potential as TE materials, achieving ZT values above 2.

A General Molecular Structural Design for Highly Efficient Photopyroptosis that can be Activated within 10 s Irradiation.

Photopyroptosis is an emerging research branch of photodynamic therapy (PDT), whereas there remains a lack of molecular structural principles to fabricate photosensitizers for triggering a highly efficient pyroptosis. Herein, a general and rational structural design principle to implement this hypothesis, is proposed. The principle relies on the clamping of cationic moieties (e.g., pyridinium, imidazolium) onto one photosensitive core to facilitate a considerable mitochondrial targeting (both of the inner and the outer membranes) of the molecules, thus maximizing the photogenerated reactive oxygen species (ROS) at the specific site to trigger the gasdermin E-mediated pyroptosis. Through this design, the pyroptotic trigger can be achieved in a minimum of 10 s of irradiation with a substantially low light dosage (0.4 Jcm⁻2), compared to relevant work reported (up to 60 Jcm⁻2). Moreover, immunotherapy with high tumor inhibition efficiency is realized by applying the synthetic molecules alone. This structural paradigm is valuable for deepening the understanding of PDT (especially the mitochondrial-targeted PDT) from the perspective of pyroptosis, toward the future development of the state-of-the-art form of PDT.

Design of functionally gradient metastructure with ultra-broadband and strong absorption

Rational design principles for ultra-broadband lattice-based metastructure absorbers (MMAs) remain scarcely explored, including elucidation of the governing absorption phenomena. This work presents Octet truss lattices gradient-tailored to achieve highly efficient wide-spectrum electromagnetic (EM) wave mitigation. The optimized 15 mm thick three-dimensional printed architectures comprise three stacked sub-layers with graduated densities spanning a reflective backing. Analysis of unit cell EM responses as a function of geometric parameters facilitates concurrent broadband absorption and minimal mass. Consequently, ultra-wideband absorption below −10 dB persists from 2.84 to 40.0 GHz under normal incidence, with strongly enhanced attenuation below −15 dB between 8.51 and 40.0 GHz. Additionally, consistent absorption capacity endures up to 60° for both transverse electric (TE) and transverse magnetic (TM) polarizations, empowered by the intricate conductive networks established through wave interactions. The unique combination of additive manufacturing, hierarchical metamaterial engineering, and physical insights provides a versatile strategy for customized broadband absorption systems across application domains.

Combining anodic alcohol oxidative coupling for C-C bond formation with cathodic ammonia production.

Electrocatalytic oxidation of alcohols using heterogeneous catalysts is a promising aqueous, energy-efficient and environmentally friendly approach, especially for coupling different alcohols to prolong the carbon chain via co-oxidation. Precisely regulating critical steps to tailor electrode materials and electrolyte composition is key to selectively coupling alcohols for targeted synthesis. However, selectively coupling different alcohols remains challenging due to the lack of effective catalyst and electrolyte design promoting specific pathways. Herein, we demonstrate a paired electrolysis strategy for combining anodic oxidative coupling of ethanol (EtOH) and benzyl alcohol (PhCH2OH) to synthesize cinnamaldehyde (CAL) and cathodic ammonia production. The strategies involve: (i) utilizing the salt-out effect to balance selective oxidation and coupling rates; (ii) developing platinum-loaded nickel hydroxide electrocatalysts to accelerate intermediate coupling kinetics; (iii) introducing thermodynamically favorable nitrate reduction at the cathode to improve coupling selectivity by avoiding hydrogenation of products while generating valuable ammonia instead of hydrogen. We achieved 85% coupling selectivity and 278 μmol/h NH3 productive rate at 100mA/cm2 with a low energy input (∼1.63V). The membrane-free, low energy, scalable approach with a wide substrate scope highlights promising applications of this methodology. This work advances heterogeneous electrocatalytic synthesis through rational design principles that integrate anodic oxidative coupling with cathodic nitrate reduction reactions, having synergistic effects on efficiency and selectivity.

SuFEx-based chemical diversification for the systematic discovery of CRBN molecular glues

Molecular glues are small molecules that stabilize protein–protein interactions, enabling new molecular pharmacologies, such as targeted protein degradation. They offer advantages over proteolysis targeting chimeras (PROTACs), which present challenges associated with the size and properties of heterobifunctional constructions, but glues lack the rational design principles analogous to PROTACs. One notable exception is the ability to alter the structure of Cereblon (CRBN)-based molecular glues and redirect their activity toward new neo-substrate proteins. We took a focused approach toward modifying the CRBN ligand, 5′-amino lenalidomide, to alter its neo-substrate specificity using high-throughput chemical diversification by parallelized sulfur(VI)-fluoride exchange (SuFEx) transformations. We synthesized over 3,000 analogs of 5′-amino lenalidomide using this approach and screened the crude products using a phenotypic screen for cell viability, identifying dozens of analogs with differentiated activity. We characterized four compounds that degrade G-to-S phase transition 1 (GSPT1) protein, providing a proof-of-concept model for SuFEx-based discovery of CRBN molecular glues.

Advancements in Regenerative Hydrogels in Skin Wound Treatment: A Comprehensive Review.

This state-of-the-art review explores the emerging field of regenerative hydrogels and their profound impact on the treatment of skin wounds. Regenerative hydrogels, composed mainly of water-absorbing polymers, have garnered attention in wound healing, particularly for skin wounds. Their unique properties make them well suited for tissue regeneration. Notable benefits include excellent water retention, creating a crucially moist wound environment for optimal healing, and facilitating cell migration, and proliferation. Biocompatibility is a key feature, minimizing adverse reactions and promoting the natural healing process. Acting as a supportive scaffold for cell growth, hydrogels mimic the extracellular matrix, aiding the attachment and proliferation of cells like fibroblasts and keratinocytes. Engineered for controlled drug release, hydrogels enhance wound healing by promoting angiogenesis, reducing inflammation, and preventing infection. The demonstrated acceleration of the wound healing process, particularly beneficial for chronic or impaired healing wounds, adds to their appeal. Easy application and conformity to various wound shapes make hydrogels practical, including in irregular or challenging areas. Scar minimization through tissue regeneration is crucial, especially in cosmetic and functional regions. Hydrogels contribute to pain management by creating a protective barrier, reducing friction, and fostering a soothing environment. Some hydrogels, with inherent antimicrobial properties, aid in infection prevention, which is a crucial aspect of successful wound healing. Their flexibility and ability to conform to wound contours ensure optimal tissue contact, enhancing overall treatment effectiveness. In summary, regenerative hydrogels present a promising approach for improving skin wound healing outcomes across diverse clinical scenarios. This review provides a comprehensive analysis of the benefits, mechanisms, and challenges associated with the use of regenerative hydrogels in the treatment of skin wounds. In this review, the authors likely delve into the application of rational design principles to enhance the efficacy and performance of hydrogels in promoting wound healing. Through an exploration of various methodologies and approaches, this paper is poised to highlight how these principles have been instrumental in refining the design of hydrogels, potentially revolutionizing their therapeutic potential in addressing skin wounds. By synthesizing current knowledge and highlighting potential avenues for future research, this review aims to contribute to the advancement of regenerative medicine and ultimately improve clinical outcomes for patients with skin wounds.

Theoretical Investigation of the Adsorbate and Potential-Induced Stability of Cu Facets During Electrochemical CO2 and CO Reduction.

The activity and product selectivity of electrocatalysts for reactions like the carbon dioxide reduction reaction (CO2RR) are intimately dependent on the catalyst's structure and composition. While engineering catalytic surfaces can improve performance, discovering the key sets of rational design principles remains challenging due to limitations in modeling catalyst stability under operating conditions. Herein, we perform first-principles density functional calculations adopting implicit solvation methods with potential control to study the influence of adsorbates and applied potential on the stability of different facets of model Cu electrocatalysts. Using coverage dependencies extracted from microkinetic models, we describe an approach for calculating potential and adsorbate-dependent contributions to surface energies under reaction conditions, where Wulff constructions are used to understand the morphological evolution of Cu electrocatalysts under CO2RR conditions. We identify that CO*, a key reaction intermediate, exhibits higher kinetically and thermodynamically accessible coverages on (100) relative to (111) facets, which can translate into an increased relative stabilization of the (100) facet during CO2RR. Our results support the known tendency for increased (111) faceting of Cu nanoparticles under more reducing conditions and that the relative increase in (100) faceting observed under CO2RR conditions is likely attributed to differences in CO* coverage between these facets.

Orientation and Membrane Partition Free Energy of PeT-Based Voltage-Sensitive Dyes from Molecular Simulations.

Voltage measurement via small-molecule fluorescent indicators is a valuable approach in deciphering complex dynamics in electrically excitable cells. However, our understanding of various physicochemical properties governing the performance of fluorescent voltage sensors based on the photoinduced electron transfer (PeT) mechanism remains incomplete. Here, through extensive molecular dynamics and free energy calculations, we systematically examine the orientation and membrane partition of three PeT-based voltage-sensing VoltageFluor (VF) dyes in different lipid environment. We show that the symmetry of the molecular scaffold and the net charge of the hydrophilic headgroup of a given VF dye dominate its orientation and membrane partition, respectively. Our work provides a mechanistic understanding of the physical properties contributing to the voltage sensitivity, signal-to-noise ratio, as well as membrane distribution of VF dyes and sheds light onto rational design principles of PeT-based fluorescent probes in general.

Membrane Transport, Molecular Machines, and Maxwell's Demon

AbstractThe spontaneous generation of transmembrane gradients is an important fundamental research goal for artificial nanotechnology. The active transport processes that give rise to such gradients directly mirror the famous Maxwell's Demon thought experiment, where a Demon partitions particles between two chambers to generate a nonequilibrium state. Despite these similarities, discussion of Maxwell's Demon is absent in the literature on artificial membrane transport. By contrast, the emergence of rational design principles for nonequilibrium artificial molecular motors can trace its intellectual roots directly to this famous thought experiment. This perspective highlights the links between Maxwell's Demon and nonequilibrium machines, and argues that understanding the implications of this 19th century thought experiment is crucial to the future development of transmembrane active transport processes.