Structure-activity Correlations Research Articles

Hafnium-Doped Silica Nanotubes for the Upgrading of Glycerol into Solketal: Enhanced Performances and In-Depth Structure-Activity Correlation

Hafnium-Doped Silica Nanotubes for the Upgrading of Glycerol into Solketal: Enhanced Performances and In-Depth Structure-Activity Correlation

Phase reconfiguration of multivalent nickel sulfides in hydrogen evolution

We report a universal phase reconfiguration phenomenon and a doping strategy to enhance the activity of multivalent nickel sulfides in hydrogen evolution. Based on these, a life-time dynamic structure-activity correlation has been established.

Linking dual mode of action of host defense antimicrobial peptide thanatin: Structures, lipopolysaccharide and LptAm binding of designed analogs

At present, antibiotics options to cure infections caused by drug resistant Gram-negative pathogens are highly inadequate. LPS outer membrane, proteins involved in LPS transport and biosynthesis pathways are vital targets. Thanatin, an insect derived 21-residue long antimicrobial peptide may be exploited for the development of effective antibiotics against Gram-negative bacteria. As a mode of bacterial cell killing, thanatin disrupts LPS outer membrane and inhibits LPS transport by binding to the periplasmic protein LptAm. Here, we report structure-activity correlation of thanatin and analogs for the purpose of rational design. These analogs of thanatin are investigated, by NMR, ITC and fluorescence, to correlate structure, antibacterial activity and binding with LPS and LptAm, a truncated monomeric variant. Our results demonstrate that an analog thanatin M21F exhibits superior antibacterial activity. In LPS interaction analyses, thanatin M21F demonstrate high affinity binding to outer membrane LPS. The atomic resolution structure of thanatin M21F in LPS micelle reveals four stranded β-sheet structure in a dimeric topology whereby the sidechain of aromatic residues Y10, F21 sustained mutual packing at the interface. Strikingly, LptAm binding affinity of thanatin M21F has been significantly increased with an estimated Kd ~ 0.73 nM vs 13 nM for thanatin. Further, atomic resolution structures and interactions of Ala based thanatin analogs define plausible correlations with antibacterial activity and LPS, LptAm interactions. Taken together, the current work provides a frame-work for the designing of thanatin based potent antimicrobial peptides for the treatment of drug resistance Gram-negative bacteria.

Spirornatas A-C from brown alga Turbinaria ornata: Anti-hypertensive spiroketals attenuate angiotensin-I converting enzyme

Bioactive compounds with angiotensin-I converting enzyme attenuation potential are deemed as therapeutic agents for hypertension owing to their capacity to suppress the conversion of angiotensin-I into the vasoconstrictor angiotensin-II. In an aim to develop natural angiotensin-I converting enzyme (ACE-I) inhibitors from marine algae, three 6, 6-spiroketals, spirornatas A-C were isolated from the organic extract of the spiny brown marine macroalga Turbinaria ornata (Turner) (family Sargassaceae). Spirornata A exhibited comparatively greater ACE-I attenuation potential (IC50 4.5 μM) than those displayed by other studied spiroketals (IC50 4.7–4.9 μM), and its activity was comparable to the ACE inhibitory agent captopril (IC50 4.3 μM). Greater antioxidant properties of spirornata A against oxidants (IC50 1.1–1.3 mM) also substantiated its potential attenuation property against ACE-I. Structure-activity correlation studies showed that electronic properties (topological polar surface area, 71) and balanced hydrophilic-lipophilic parameters (partition coefficient of logarithmic octanol-water ∼3.2) of spirornata A appeared to play pivotal roles in the inhibition of the targeted enzyme. Predicted drug-likeness and other physicochemical parameters appeared to attribute to the acceptable oral bioavailability of spiroketal derivatives. Additionally, the least binding energy of spirornata A with ACE-I (−10.5 kcal/mol) coupled with the maximum number of hydrogen-bonding interactions with allosteric sites of the zinc-dependent dicarboxypeptidyl peptidase could recognize its potential therapeutic application against hypertensive diseases.

Rare Glutamic Acid Methyl Ester Peptaibols from Sepedonium ampullosporum Damon KSH 534 Exhibit Promising Antifungal and Anticancer Activity.

Fungal species of genus Sepedonium are rich sources of diverse secondary metabolites (e.g., alkaloids, peptaibols), which exhibit variable biological activities. Herein, two new peptaibols, named ampullosporin F (1) and ampullosporin G (2), together with five known compounds, ampullosporin A (3), peptaibolin (4), chrysosporide (5), c(Trp-Ser) (6) and c(Trp-Ala) (7), have been isolated from the culture of Sepedonium ampullosporum Damon strain KSH534. The structures of 1 and 2 were elucidated based on ESI-HRMSn experiments and intense 1D and 2D NMR analyses. The sequence of ampullosporin F (1) was determined to be Ac-Trp1-Ala2-Aib3-Aib4-Leu5-Aib6-Gln7-Aib8-Aib9-Aib10-GluOMe11-Leu12-Aib13-Gln14-Leuol15, while ampullosporin G (2) differs from 1 by exchanging the position of Gln7 with GluOMe11. Furthermore, the total synthesis of 1 and 2 was carried out on solid-phase to confirm the absolute configuration of all chiral amino acids as L. In addition, ampullosporin F (1) and G (2) showed significant antifungal activity against B. cinerea and P. infestans, but were inactive against S. tritici. Cell viability assays using human prostate (PC-3) and colorectal (HT-29) cancer cells confirmed potent anticancer activities of 1 and 2. Furthermore, a molecular docking study was performed in silico as an attempt to explain the structure-activity correlation of the characteristic ampullosporins (1–3).

Surface Electronic Structure Modulation of Cobalt Nitride Nanowire Arrays via Selenium Deposition for Efficient Hydrogen Evolution

AbstractNonmetal heteroatom incorporation into the lattice of host materials is a common way to regulate the surface electronic structure of electrocatalysts to boost their electrocatalytic performance. However, the heteroatom incorporation will inevitably trigger lattice strain and vacancy, which may lead to large changes in the structure of host materials. In this situation, the reconstruction of doped catalysts easily occurs during the catalytic process under harsh alkaline media, which hinders understanding the structure–activity correlation between catalysts and catalytic performance. Herein, taking cobalt nitride as an example, it is promulgated that a low‐temperature selenium sublimation strategy can effectively optimize the surface electronic structure in Co4N nanowire arrays with no significant change of bulk phase structure. Benefiting from surface selenium modification, the optimized SeCo4N nanowire arrays exhibit a 6.5 times enhancement of catalytic activity with structural phase stability for hydrogen evolution reaction in basic media. These findings may provide a new concept to design stable structured catalysts for energy‐related applications.

Multifunctional Dendronized Polypeptides for Controlled Adjuvanticity

Vaccination has been playing an important role in treating both infectious and cancerous diseases. Nevertheless, many diseases still lack proper vaccines due to the difficulty to generate sufficient amounts of antigen-specific antibodies or T cells. Adjuvants provide an important route to improve and direct immune responses. However, there are few adjuvants approved clinically and many of them lack the clear structure/adjuvanticity relationship. Here, we synthesized and evaluated a series of dendronized polypeptides (denpols) functionalized with varying tryptophan/histidine (W/H) molar ratios of 0/100, 25/75, 50/50, 75/25, and 100/0 as tunable synthetic adjuvants. The denpols showed structure-dependent inflammasome activation in THP1 monocytic cells and structure-related activation and antigen cross-presentation in vitro in bone marrow-derived dendritic cells. We used the denpols with bacterial pathogen Coxiella burnetii antigens in vivo, which showed both high and tunable adjuvating activities, as demonstrated by the antigen-specific antibody and T cell responses. The denpols are easy to make and scalable, biodegradable, and have highly adjustable chemical structures. Taken together, denpols show great potential as a new and versatile adjuvant platform that allows us to adjust adjuvanticity based on structure-activity correlation with the aim to fine-tune the immune response, thus advancing vaccine development.

Enzymatic Synthesis of 3'-5', 3'-5' Cyclic Dinucleotides, Their Binding Properties to the Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations.

The 3'-5', 3'-5' cyclic dinucleotides (3'3'CDNs) are bacterial second messengers that can also bind to the stimulator of interferon genes (STING) adaptor protein in vertebrates and activate the host innate immunity. Here, we profiled the substrate specificity of four bacterial dinucleotide synthases from Vibrio cholerae (DncV), Bacillus thuringiensis (btDisA), Escherichia coli (dgcZ), and Thermotoga maritima (tDGC) using a library of 33 nucleoside-5'-triphosphate analogues and then employed these enzymes to synthesize 24 3'3'CDNs. The STING affinity of CDNs was evaluated in cell-based and biochemical assays, and their ability to induce cytokines was determined by employing human peripheral blood mononuclear cells. Interestingly, the prepared heterodimeric 3'3'CDNs bound to the STING much better than their homodimeric counterparts and showed similar or better potency than bacterial 3'3'CDNs. We also rationalized the experimental findings by in-depth STING-CDN structure-activity correlations by dissecting computed interaction free energies into a set of well-defined and intuitive terms. To this aim, we employed state-of-the-art methods of computational chemistry, such as quantum mechanics/molecular mechanics (QM/MM) calculations, and complemented the computed results with the {STING:3'3'c-di-ara-AMP} X-ray crystallographic structure. QM/MM identified three outliers (mostly homodimers) for which we have no clear explanation of their impaired binding with respect to their heterodimeric counterparts, whereas the R2 = 0.7 correlation between the computed ΔG'int_rel and experimental ΔTm's for the remaining ligands has been very encouraging.

Probe-assisted NMR: Recent progress on the surface study of crystalline metal oxides with various terminated facets

The development of metal oxides with specific facet exposure for better catalytic performance in targeted applications has been well-documented. However, the understanding of surface structure-activity correlation is severely hindered by the current poor resolution of conventional surface characterization tools. In this mini-review, some of the latest research developments on the characterization of the surface structure and properties of faceted ZnO and TiO2 by probe-assisted nuclear magnetic resonance spectroscopy (NMR) are discussed.

Oxygen promoter on copper-silver coupling for electrochemical carbon dioxide reduction catalysts

The CO2-to-CO conversion catalyst is a key component in the design of an eco-friendly and energy-efficient process for the conversion of CO2 into useful chemicals. Ag and Cu are representative electrochemical catalytic materials for CO2 reduction, and coupling the two metals is an extensively used approach to increase the catalytic activity and selectivity. Through a series of first-principles calculations, we identify novel structure–activity correlations resulting from the various interfaces between the Ag surface and Cu oxide subsurface. We find that the oxygen atoms incorporated into Cu play a pivotal role in promoting Cu-Ag alloy catalysts. Our calculation results highlight that the sigma-type interaction between subsurface oxygen and surface Ag aligned perpendicular to the surface breaks the linear scaling relationship between key reaction intermediates and leads to subsequent activity enhancement for CO production. Given that Cu is susceptible to oxidation, the unraveled oxygen-induced activity promotion effect is anticipated to be taken as a practically applicable reference to ongoing efforts for the development of high-performance electrochemical CO2-to-CO conversion catalysts.

Synthesis, Chemical-Physical Characterization, and Biomedical Applications of Functional Gold Nanoparticles: A Review.

Relevant properties of gold nanoparticles, such as stability and biocompatibility, together with their peculiar optical and electronic behavior, make them excellent candidates for medical and biological applications. This review describes the different approaches to the synthesis, surface modification, and characterization of gold nanoparticles (AuNPs) related to increasing their stability and available features useful for employment as drug delivery systems or in hyperthermia and photothermal therapy. The synthetic methods reported span from the well-known Turkevich synthesis, reduction with NaBH4 with or without citrate, seeding growth, ascorbic acid-based, green synthesis, and Brust–Schiffrin methods. Furthermore, the nanosized functionalization of the AuNP surface brought about the formation of self-assembled monolayers through the employment of polymer coatings as capping agents covalently bonded to the nanoparticles. The most common chemical–physical characterization techniques to determine the size, shape and surface coverage of AuNPs are described underlining the structure–activity correlation in the frame of their applications in the biomedical and biotechnology sectors.

Dramatic Change in the Step Edges of the Cu(100) Electrocatalyst upon Exposure to CO: Operando Observations by Electrochemical STM and Explanation Using Quantum Mechanical Calculations

Systematic structure–activity correlations in the electrochemical surface science of CO2 reduction (CO2R) are typically anchored on low Miller-index (hkl) surfaces with characterization directed at the dominant well-defined basal planes. The present investigation focused on the visualization of the step edges of unreconstructed Cu(100), with and without CO dissolved in 0.1 M KOH, at the early onset-potential region of CO2R. Operando electrochemical scanning tunneling microscopy revealed that the step-edge direction changed dramatically upon the adsorption–desorption of CO at potentials of −1.0 to −0.8 V. Quantum mechanical calculations corroborated the favorable transformation of the step-edge direction from ⟨110⟩ to ⟨001⟩ as the pristine surface was decorated by CO.

Pterocarpans and their biological activities: a review

Pterocarpans, ubiquitous in Fabaceae, are protective active substances produced by the chemical defense system of plants. A total of 144 pterocarpans had been discovered before 2006. For the first time, we reported the 89 pterocarpans identified in 2006-2020. These pterocarpans not only demonstrate novel complex diversified genus-specific stereostructures but also display strong anti-microbial, anti-tumor, antioxidant, insecticidal, and anti-inflammatory activities. Through the projection of their biogenetic pathways and study of the pharmacological activities, the structure-activity correlation was further confirmed. The distribution of Leguminosae plants rich in pterocarpans has obvious regional characteristics. Therefore, the research and utilization of Leguminosae plant resources in China should be strengthened, and the popularity and application value of the geographical indicator plant resources should be improved. This paper serves as a reference for further research, development, and utilization of pterocarpans and their plant sources.

Effect of Different Chelating Agents on the Physicochemical Properties of Cu/ZnO Catalysts for Low-temperature Methanol Synthesis from Syngas Containing CO<sub>2</sub>

Nanostructured Cu/ZnO catalysts were prepared by a simple solid-state method, using cheap metal nitrates as raw materials. Special attention was paid to the influence of different chelating agents such as citric acid, formic acid and oxalic acid on the physicochemical properties of Cu/ZnO catalysts, which were characterized by detailed investigations. CuO crystallite size, oxygen vacancies and surface compositions were clearly affected by chelating agent types, leading to different CuO–ZnO interactions in the calcined catalysts as well as distinct reducibility. Different chelating agents also had significant effects on specific surface area, metallic Cu0 surface area, and Cu crystallite size, as well as ZnO (002) plane to ZnO (100) plane ratio (I(002)/I(100)) calculated based on the peak intensity of XRD patterns of the reduced samples, so influencing the catalytic activity for low-temperature methanol synthesis from syngas containing CO2. The structure-activity correlations, particularly the relationships between space time yield (STY) of methanol with Cu0 surface area and I(002)/I(100) ratio, were evaluated. Cu/ZnO catalyst prepared with oxalic acid showed the highest STY value, which was 2.3 and 5.3 times higher that of the catalysts obtained with citric acid and formic acid, respectively. The excellent catalytic performance was due to its greater Cu0 surface area, higher specific surface area and smaller Cu crystallite size. Stronger interactions between Cu and ZnO in the reduced samples were also favorable for enhancing catalytic activity for low-temperature methanol synthesis.

Vanadium-Flavonoid Complexes: A Promising Class of Molecules for Therapeutic Applications.

Several reports have revealed the superior biological activity of metal ion-flavonoid complexes when compared with the parent flavonoid. Among the different metal ions explored, vanadium and its compounds are in the forefront because of their anticancer and antidiabetic properties. However, the toxicity of vanadium-based ions and their inorganic derivatives limits their therapeutic applications. Complexation of vanadium with flavonoids not only reduces its adverse effects but also augments its biological activity. This Review discusses the nature of coordination in vanadium-flavonoid complexes, their structure-activity correlations, with special emphasis on their therapeutic activities. Several investigations suggest that the superior biological activity of vanadium complexes arise because of their ability to regulate metabolic pathways distinct from those acted upon by vanadium alone. These studies serve to decipher the underlying molecular mechanism of vanadium-flavonoid complexes that can be explored further for generating a series of novel compounds with improved pharmacological and therapeutic performance.

Manipulating the Local Coordination and Electronic Structures for Efficient Electrocatalytic Oxygen Evolution.

Non-noble-metal-based nanomaterials can exhibit extraordinary electrocatalytic performance toward the oxygen evolution reaction (OER) by harnessing the structural evolution during catalysis and the synergistic effect between elements. However, the structure of active centers in bimetallic/multimetallic catalysts is under long-time debate in the catalysis community. Here, an efficient bimetallic Ni-Fe selenide-derived OER electrocatalyst is reported and the structure-activity correlation during the OER evolution studied. By combining experiments and theoretical calculations,a conceptual advance is provided, in that the local coordination structure distortion and disordering of active sites inherited from the pre-catalyst and post-formed by a further reconstruction are responsible for boosting the OER performance. The active center is identified on Ni sites showing moderate bindings with oxygenous intermediates rather than Fe sites with strong and poisonous adsorptions. These findings provide crucial understanding in manipulating the local coordination and electronic structures toward rational design and fabrication of efficient OER electrocatalysts.

Influence of Ti Incorporation to Bimetallic Mesoporous Carbon in the Production of 2,5-Dimethylfuran from Biomass Derivatives

Monometallic and bimetallic supported catalysts were developed to produce 2,5-dimethylfuran (DMF) trough hydrogenolysis of 5-(hydroxymethyl)furfural (HMF). Detailed physicochemical characterization was done to understand structure–activity correlation. Through a series of experiments and comparatives tests, the synergistic effect among Pt, Ir, and Ti incorporated in the support was investigated. Results revealed that using the titanium contained ordered mesoporous carbon, synthesized by a novel technique, high selectivity to DMF was achieved. In the case of the best catalyst PtIr-TiC, the good activity and excellent selectivity to the desired product DMF (98% yield) was related to the high hydrogenating capacity of the bimetallic sites, the acid support characteristics and the high metal nanoparticles dispersion achieved on the mesoporous titanium modified carbon support.Graphic Abstract

In Situ Active Site for CO Activation in Fe-Catalyzed Fischer-Tropsch Synthesis from Machine Learning.

In situ-formed iron carbides (FeCx) are the key components responsible for Fischer-Tropsch synthesis (FTS, CO + H2 → long-chain hydrocarbons) on Fe-based catalysts in industry. The true active site is, however, highly controversial despite more than a century of study, which is largely due to the combined complexity in both FeCx structures and mechanism of CO hydrogenation. Herein powered by machine learning simulation, millions of structure candidates for FeCx bulk and surfaces are explored under FTS conditions, which leads to resolving the active site for CO activation. This is achieved without a priori input from experiment by first constructing the thermodynamics convex hull of bulk phases, followed by identifying the low surface energy surfaces and evaluating the adsorption ability of CO and H, and finally determining the lowest energy reaction pathway of CO activation. Rich information on FeCx structures and CO hydrogenation pathways is gleaned: (i) Fe5C2, Fe7C3, and Fe2C are the three stable bulk phases under FTS in producing olefins, where Fe7C3 and Fe2C have multiple energetically nearly degenerate bulk crystal phases; (ii) only three low surface energy surfaces of these bulk phases, namely, χ-Fe5C2(510), χ-Fe5C2(111), and η-Fe2C(111), expose the Fe sites that can adsorb H atoms exothermically, where the surface Fe:C ratio is 2, 1.75, and 2, respectively; (iii) CO activation via direct dissociation can occur at the surface C vacancies (e.g., with a barrier of 1.1 eV) that are created dynamically via hydrogenation. These atomic-level understandings facilitate the building of the structure-activity correlation and designing better FT catalysts.

Operando X-ray study of service behavior of catalytic materials based on synchrotron radiation

Considering the energy and environmental issues faced by human society, hydrogen has become increasingly important, and electrocatalytic water splitting is considered to be an ideal way to solve these energy issues. However, although most electrocatalysts will undergo a structural evolution when in service conditions, our understanding of the service behavior of catalysts is limited. To design highly active catalysts, operando characterization techniques must be used to study their dynamic structural evolution. Today, the development of synchrotron radiation devices has reached an important stage. Synchrotron-radiation-based X-ray characterization, which has high energy, large flux, and excellent collimation compared with the ordinary laboratory X-ray source, can capture the precise structure of catalytic materials. In this review, we present the development status of synchrotron radiation devices and the basic principles of operando X-ray absorption spectroscopy, X-ray diffraction spectroscopy, and X-ray photoelectron spectroscopy based on synchrotron radiation. In addition, we highlight studies related to the dynamic service behavior of water-splitting catalysts under real conditions and list a variety of operando studies of typical water-splitting catalysts, including NiFe hydroxide/(oxy)hydroxides, perovskite oxides, spinel oxides, and noble-metal-based catalysts. The use of operando X-ray techniques deepens our understanding of the catalyst reaction mechanism and provides a basis for identifying the dynamic structure–performance correlation of catalysts. We summarize the problems and challenges of operando X-ray-based techniques in complex electrochemical environments and propose the prospect of an advanced synchrotron radiation facility for operando X-ray characterization. With the development of the next-generation synchrotron radiation facility, adequately using this advanced X-ray light source to study the dynamic structure–activity correlation of catalytic materials throughout their life cycle to achieve the precise design and synthesis of complex pre-catalysts will advance the development of this field by enabling greater refinement and control.

CO and H2 adsorption on Au-Ni bimetallic surfaces: a combined experimental and DFT theoretical study

Au-Ni bimetallic thin films were grown on refractory metal substrates. CO and H2 adsorption on Au-Ni bimetallic surfaces have been studied by a combination of in situ polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), temperature-programmed desorption (TPD), and density functional theory (DFT) calculations. It is found CO desorption peak shifts from 413 K on pure Ni surfaces to 293 K on the isolated Ni atoms formed by alloying with Au atoms. The sharp decrease of CO desorption temperature on Au-Ni surfaces with increasing Au coverage is caused by the change of the favored CO adsorption sites from bridge/hollow sites on pure Ni surfaces to Ni top sites on Au-Ni bimetallic surfaces. In situ PM-IRRAS shows two CO adsorption bands on Au sites at 2119 cm−1 and 2103 cm−1 on Au-Ni surfaces at 80 K, which are due to CO bound on under-coordinated Au atoms and electron negatively charged Au sites modified with nearby Ni atoms, respectively. Even with the Au-Ni surface temperature at as low as 100 K, CO adsorption induced Ni surface segregation has been observed by in situ PM-IRRAS. Furthermore, DFT calculation results discover the adsorption energy of CO on Ni top sites continues to decrease with increasing Au coverage due to the geometric ensemble effect and the lowered d-band center after Ni alloying with Au. H2 desorption temperature decreases from 363 K on pure Ni thin films to 302 K with increasing Au coverage to 0.6 ML. A new H2 peak appears at around 170 K on the Au-Ni surfaces with Au coverages between 0.6 ML and 0.9 ML. This new H2 TPD peak is assigned to H2 desorption from the totally isolated Ni sites. With Au coverage above 1.5 ML, there is no any H2 desorption detected. The combined surface science studies and DFT calculations provide new insights into the surface structure-activity correlation of Ni-base bimetallic surface alloys.