Intramolecular Interactions Research Articles

Eliminating the Deadwood: A Machine Learning Model for CCS Knowledge-Based Conformational Focusing for Lipids.

Accurate elucidation of gas-phase chemical structures using collision cross section (CCS) values obtained from ion-mobility mass spectrometry benefits from a synergism between experimental and in silico results. We have shown in recent work that for a molecule of modest size with a proscribed conformational space we can successfully capture a conformation(s) that can match experimental CCS values. However, for flexible systems such as fatty acids that have many rotatable bonds and multiple intramolecular London dispersion interactions, it becomes necessary to sample a much greater conformational space. Sampling more conformers, however, accrues significant computational cost downstream in optimization steps involving quantum mechanics. To reduce this computational expense for lipids, we have developed a novel machine learning (ML) model to facilitate conformer filtering according to the estimated gas-phase CCS values. Herein we report that the implementation of our CCS knowledge-based approach for conformational sampling resulted in improved structure prediction agreement with experiment by achieving favorable average CCS prediction errors of ∼2% for lipid systems in both the validation set and the test set. Moreover, most of the gas-phase candidate conformations obtained by using CCS focusing achieved lower energy-minimum geometries than the candidate conformations without focusing. Altogether, the implementation of this ML model into our modeling workflow has proven to be beneficial for both the quality of the results and the turnaround time. Finally, while our approach is limited to lipids, it can be readily extended to other molecules of interest.

QProtein: Exploring Physical Features of Protein Thermostability Based on Structural Proteomics.

Thermostability, which is essential for the functional performance of enzymes, is largely determined by intramolecular physical interactions. Although many tools have been developed, existing computational methods have struggled to find the universal principles of protein thermostability. Recent advancements in structural proteomics have been driven by the introduction of deep neural networks such as AlphaFold2 and ESMFold. These innovations have enabled the characterization of protein structures with unprecedented speed and accuracy. Here, we introduce qProtein, a Python-implemented workflow designed for the quantitative analysis of physical interactions on the scale of structural proteomics. This platform accepts protein sequences as input and produces four structural features, including hydrophobic clusters, hydrogen bonds, electrostatic interactions, and disulfide bonds. To demonstrate the use of qProtein, we investigate the structural features related to protein thermostability in six glycoside hydrolase (GH) families, comprising a total of 3,811 protein structures. Our results indicate that in five enzyme families (GH11, GH12, GH5_2, GH10, and GH48), the thermophilic enzymes have a larger average area of hydrophobic clusters compared to the nonthermophilic enzymes within each family. Furthermore, our analysis of the local-structure regions reveals that the hydrophobic clusters are predominantly distributed in the distal regions of the GH11 enzymes. In addition, the average hydrophobic cluster area of the thermophilic enzymes is significantly higher than that of the nonthermophilic enzymes in the distal regions of the GH11 enzymes. Therefore, qProtein is a well-suited platform for analyzing the structural features of thermal stability at the level of structural proteomics. We provide the source code for qProtein at https://github.com/bj600800/qProtein, and the web server is available at http://qProtein.sdu.edu.cn:8888.

Superior proton conductivity of amino acid-modified UiO-66-(COOH)2 embedded in chitosan: Mechanistic insights into the acid-base interactions

We focus on optimizing acid-base interactions and hydrogen bonding networks to achieve enhanced proton conductivity under low relative humidity (RH) and high temperature. By functionalizing UiO-66-(COOH)2 with glutamic acid (Glu) and lysine (Lys), we generate Glu-UiO-66-(COOH)2 and Lys-UiO-66-(COOH)2. These modified materials are subsequently incorporated into chitosan (CS) to produce the composites Glu-UiO-66-(COOH)2@CS and Lys-UiO-66-(COOH)2@CS. The successful incorporation of amino acids and cross-linking between -COOH and -NH2 groups in the composites, confirmed by FTIR and PXRD analyses, significantly enhances the structural integrity and durability by strengthening the network, and reducing polymer chain mobility. Proton conductivity assessments reveal that Lys-UiO-66-(COOH)2@CS-7 exhibits a remarkable conductivity of 0.022 S/cm at 100 % RH and 363 K, outperforming Glu-UiO-66-(COOH)2@CS-7. The lower activation energy (Ea) of 0.28 eV for Lys-UiO-66-(COOH)2@CS-7, compared to 0.336 eV for Glu-UiO-66-(COOH)2@CS-7, highlights the significant improvement in intramolecular acid-base interactions and hydrogen bonding. Furthermore, Lys-UiO-66-(COOH)2@CS-7 maintains notable proton conductivity at 43 % RH, with an Ea of 0.216 eV, demonstrating its efficacy in low-humidity conditions. These findings underscore the profound impact of amino acid modifications and cross-linking on proton conductivity by reinforcing acid-base interactions, hydrogen bonding networks, and proton transfer efficiency.

Unveiling the Complexity of cis-Regulation Mechanisms in Kinases: A Comprehensive Analysis.

Protein cis-regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis. To accomplish this, we curated an extensive dataset of kinases featuring annotated CREs, organized into homolog families through multiple sequence alignments. Key molecular attributes, including disorder and secondary structure content, active and ATP-binding sites, post-translational modifications, and disease-associated mutations, were systematically mapped onto all sequences. Additionally, we explored the potential for conformational changes between active and inactive states. Finally, we explored the presence of these kinases within membraneless organelles and elucidated their functional roles therein. CREs display a continuum of structures, ranging from short disordered stretches to fully folded domains. The adaptability demonstrated by CREs in achieving the common goal of kinase inhibition spans from direct autoinhibitory interaction with the active site within the kinase domain, to CREs binding to an alternative site, inducing allosteric regulation revealing distinct types of inhibitory mechanisms, which we exemplify by archetypical representative systems. While this study provides a systematic approach to comprehend kinase CREs, further experimental investigations are imperative to unravel the complexity within distinct kinase families. The insights gleaned from this research lay the foundation for future studies aiming to decipher the molecular basis of kinase dysregulation, and explore potential therapeutic interventions.

Enhancing Photothermal Energy Transduction through Inter- and Intramolecular Interactions of Multiple Two-Photon Dyes Appended onto Calix[4]arene.

Organic dyes-based photothermal agents (OPTAs) have received increasing attention as alternative to inorganic materials due to their higher biocompatibility and extensive diversification. Maximizing nonradiative deexcitation channels is crucial to improve the photothermal conversion efficiency (PCE) of OPTAs. This is typically achieved through individual molecular design or collective enhancement using supramolecular strategies. Furthermore, photothermal therapy (PTT) generally relies on linear one-photon absorption of the light source by the OPTA, with less consideration given to nonlinear two-photon absorption (2PA) strategies, despite their potential benefits. Here, a synergistic strategy, which combines intramolecular and intermolecular quenching, is employed to maximize the photothermal efficiency of diphenylamino-substituted distyryl dicyanobenzene (DSB), an outstanding two-photon-absorbing chromophore. One to three DSB units have been introduced on the conic p-tert-butyl-calix[4]arene (CX), serving as a preorganizing platform to allow aggregate formation and promote intramolecular quenching within the multichromophoric systems. Importantly, the multichromophoric molecules had very high two-photon absorption capabilities with cross sections (δ2PA) reaching maximal values of 3290 GM at 810 nm. Experimental data accompanied by large-scale molecular dynamics simulations and time-dependent density functional theory calculations shed light onto the interaction mechanism in those multiple DSB-appended CX compounds to rationalize their optical properties. Then, the formulation with Pluronic F127 amphiphile yields water-dispersible nanoprecipitates (Nps), in which the PCE is further maximized and the photobleaching is reduced due to the combination of intra- and intermolecular quenching. The high two-photon absorption in the near-infrared (NIR) window associated with the high PCE of these nanosized OPTAs could serve as a basis to future in vivo 2P-PTT applications.

An experimental and computational investigation of the cyclopentene-containing peptide-derived compounds: focus on pseudo-cyclic motifs via intramolecular interactions.

Conformational flexibility is one of the main disadvantages of peptide-based compounds. We focus on their molecular 'chameleonicity' related to forming pseudo-cyclic motifs via modulation of weak intramolecular interactions. It is an appealing strategy for controlling equilibrium between the polar open and the nonpolar closed conformations. Within this context, we report here the crystal structure of the (R)-(2-tert-butoxycarbonyl)amino-1-oxo-3-phenyl)propyl)-1-cyclopentene (1), synthesis of which in high yield was achieved by a facile multi-step protocol. Our Cambridge Structural Database (CSD) overview for the peptide-based crystals revealed the exclusivity of this compound from the viewpoint of the unusual pseudo-bicyclic system via C-H…O and C-O…π interactions, in which cyclopentene shields the amide bond. Notably, cyclopentene as a bioisostere of proline is an appealing scaffold in medicinal chemistry. An extensive combined experimental and computational study provided more profound insight into the supramolecular landscape of 1 with respect to similar derivatives deposited in the CSD, including the tendency of cyclopentene for the generation of pseudo-cyclic motifs through weak H-bonding and π-based intramolecular interactions. These weak interactions have been examined by either the quantum theory of 'atoms-in-molecules' (QTAIM) or complex Hirshfeld surface methodology, including enrichment ratios, molecular electrostatic potential surfaces and energy frameworks. In all analysed crystals, all types of H-bonded motifs involving cyclopentene are formed at all levels of supramolecular architecture. A library of cyclopentene-based H-bonding synthons is provided. A molecular docking study depicted vital interactions of cyclopentene with key amino acid residues inside the active sites of two prominent protein kinases, uncovering the therapeutic potential of 1 against breast cancer. To a large extent, dispersion forces have significance in stabilizing the supramolecular structure of both ligand and bio-complex ligand-protein. Finally, the satisfactory in silico bio-pharmacokinetic profile of 1 related to drug-likeness and blood-brain barrier permeation was also revealed.

Molecular dynamics simulations of hydrogen-bonded network structures of polybenzoxazines in the gas phase and aqueous solution

The crucial role of the amine functional group at the Mannich bridge of polybenzoxazines (PBZs) has been reported to be responsible for their hydrogen-bonded network structures. However, they have not been thoroughly studied in an aqueous solution and at the atomistic level. In this study, molecular dynamics simulations were applied to investigate the formation of hydrogen bond interactions of PBZs prepared from bisphenol A/methylamine (m-PBZ), bisphenol A/aniline-based (a-PBZ), and bisphenol A/2-(methylamino)ethylamine (e-PBZ). Based on the simulation results, the hydrogen-bonded network structures of the PBZs interfered with water molecules, leading to less compaction of the PBZ structure in the aqueous solution. The hydrogen bonding species of the m-PBZ and a-PBZ structures consisted of the –OH...N(Mannich) and –OH...O intramolecular interactions. However, for e-PBZ, the –OH...O species was not present, but the 2-(ethylamino)ethylamine substituent formed more hydrogen bonding species than those of m-PBZ and a-PBZ. Additionally, the intermolecular hydrogen bond interactions of the PBZs and water molecules were not detected in any of the aqueous solution simulations.

Synthesis, spectroscopy, solvation effect, topology and molecular docking studies on 2,2′-((1,2 phenylenebis (azaneylylidene)) bis (methaneylylidene)) bis(4-bromophenol)

The 2,2′-((1,2 phenylenebis (azaneylylidene)) bis (methaneylylidene)) bis(4-bromophenol) (5BSOP) Schiff base was synthesized, characterized using different spectroscopic techniques, and the data are compared with predictions from DFT computations. The calculated energy values are -8.65 eV (HOMO) and -6.66 eV (LUMO), and the energy gap was found to be 1.99 eV. The reactive atom sites in the chemical are identified by MEP analysis. The locations of localized and delocalized orbitals are revealed through ELF and LOL surface maps. The sites of non-covalent interactions are exposed by RDG and NCI analysis. The possible inter and intra-molecular interactions were determined by NBO analysis and the highest stabilization energy observed was 40.07 kcal/mol. Biological performance as a HMGCS2 expression enhancer was predicted by Pass online studies. Molecular docking simulation with protein 706I having HMGCS2 expression inhibition characteristics revealed a stable receptor-ligand interaction pose at a binding energy of -4.74 kcal/mol. The interaction of the Phe61 amino acid chain of 706I with 5BSOP through conventional H-bond expressed a bond distance of 3.24 A°.

Surface functionalization of XC18 steel using a new transition metal complex for remarkable corrosion performance: Empirical and theoretical studies

Synthesis of transition metal complexes (TMC) having specific characteristics is advantageous for combining their organic and inorganic properties, to help prevent metals from corrosion. In this study, the corrosion inhibition behavior of [N, N’-bis(salicylidene)-2,2-dimethyl-1,3-propanediaminato] copper (II) (CuL) on the surface of XC18 steel surface immersed in 1.0 M HCl was investigated. The thermodynamic and kinetic corrosion parameters were determined using the mass loss (ML) and electrochemical measurement methods. CuL exhibited a good corrosion inhibition efficiency of 96.72 %. The adsorption behavior of CuL followed the Langmuir isotherm model, indicating both physical and chemical interactions. Morphological structural analysis demonstrated that CuL formed a protective film between the surface of XC18 steel and the corrosives elements, thus confirming its adsorption onto XC18 steel surface. Theoretical calculations were consistent with the experimental findings, thereby confirming that the adsorption of CuL onto the steel surface comprises both physisorption and chemisorption processes. These calculations elucidate the specific bonding nature and emphasize the significant inter- and intra-molecular interactions that enhance the stability and adsorption capability of the CuL inhibitor. The successful formation of a protective layer on the surface of XC18 steel using a TMC signifies exciting prospects for the development of advanced materials with diverse applications.

Simple synthesis of monocyclic pyrimidine-based energetic molecule with “amino–nitro–hydrazino” arrangement

With the constant development of energetic materials, numerous explosive molecules have been synthesized, some of which feature competitive performances. However, energetic materials are directly oriented to application requirements. Therefore, more emphasis is gradually placed on route simplification and cost reduction while designing novel energetic molecules. In this work, monocyclic energetic compound 2,4-diamino-6-hydrazineyl-5-nitropyrimidine (3) was successfully obtained. This compound exhibits an alternating “amino–nitro–hydrazino” arrangement, featuring strong intramolecular hydrogen-bonding interaction. With cheap raw material, the whole reaction comprised only two steps, and exhibited simple post processing, only filtration. This novel energetic molecule possesses excellent mechanical security (IS > 40 J, FS > 360 N), acceptable thermal stability (Td = 225°C), and good detonation parameters (Dv = 8470 m·s‒1, P = 24.9 GPa), indicating that compound 3 may act as a candidate of insensitive explosives.

Sumoylation of thymine DNA glycosylase impairs productive binding to substrate sites in DNA

The base excision repair enzyme thymine DNA glycosylase (TDG) protects against mutations by removing thymine or uracil from guanine mispairs and functions in active DNA demethylation by excising 5-formylcytosine (fC) and 5-carboxylcytosine (caC). Post-translational modification of TDG by SUMO (small ubiquitin-like modifier) reduces its glycosylase activity but the mechanism remains unclear. We investigated this problem using biochemical and biophysical approaches and a TDG construct comprising residues 82-340 (of 410) that includes the SUMOylation site and the motif for non-covalent SUMO binding. Single turnover kinetics experiments were collected at multiple enzyme concentrations ([E]) and the hyperbolic dependence of activity (kobs) on [E] yielded the maximal glycosylase activity (kmax), the enzyme concentration giving half-maximal activity (K0.5), and the catalytic efficiency (kmax/K0.5). Sumoylation of TDG (or TDG82-340) causes large reductions in catalytic efficiency for G·T, G·U, G·fC, and G·caC DNA substrates, due largely to weakened substrate affinity (increased K0.5). 19F NMR experiments show that sumoylation of TDG82-340 reduces productive binding to G·U mispairs and dramatically impairs binding to G·T mispairs. A mutation in the TDG SUMO-interacting motif (SIM), E310Q, shown previously to perturb noncovalent binding of SUMO to unmodified TDG, rescues the glycosylase activity of sumoylated TDG82-340. Similarly, NMR studies show the mutation restores productive binding of sumoylated TDG82-340 to G·U and G·T pairs. Together, the results indicate that intramolecular SUMO-SIM interactions mediate the adverse effect of sumoylation on TDG activity and suggest a model whereby the disruption of SUMO-SIM interactions enables productive binding of sumoylated TDG to substrate sites in DNA.

Evaluating interaction energy versus electron density relationships to estimate inter and intramolecular H-bonding

We investigate the computational effects on the relationships between interaction energy (ΔE) and electron density (ρ), at the critical point obtained from 19 intermolecular H-bonded dimers, to estimate inter and intramolecular interactions of larger H-bonded systems. Our analysis examines basis set superposition error (BSSE) effects, dispersion energy corrections, and the exchange-correlation energy model on the ΔE vs. ρ linear regressions. The calculations were carried out within density functional theory (DFT) combined with the 6-31+G(d,p) and def2-TZVPP basis sets. This procedure quantifies the average effects of BSSE for different levels of approximation, and underscore the sensitivity of the ΔE estimation together with dispersion corrections. This is valuable for the development of DFT-based estimators of multiple interaction energies of large H-bonded systems with low computational cost. We have applied this procedure by analyzing H-bonded biological molecules, such as DNA base pairs, an asparagine side chain, and an AZT molecule. Our estimated H-bond interaction energies are in agreement with previous studies, and emphasize the importance of methodological considerations for accurately predicting interaction energies using DFT combined with topological parameters.

The Role of the Nitro Group on the Formation of Intramolecular Hydrogen Bond in the Methyl Esters of 1-Vinyl-Nitro-Pyrazolecarboxylic Acids

All reactions involving the nitrogen atom in 3(5)-substituted pyrazoles inevitably lead to a mixture of N-substituted 3- and 5- isomers due to tautomerism. The position of substituent can affect the behavior of N-vinyl isomers, in particular, the ability of some functional groups to form =C-H...O or =C-H...N weak hydrogen bonding type interaction with α-hydrogen of vinyl group due to steric reasons. Moreover, the additional substituents in the pyrazole ring can further influence the possibility and nature of specific intramolecular interactions. Here we have shown the effect of the nitro group on the formation of hydrogen bonds in methyl esters of 1-vinyl-4-nitro-3(5)- and 1-vinyl-5-nitro-3(5)-pyrazole carboxylic acids. A comprehensive study, including synthesis, quantum chemical calculations, NMR and XRD analysis, allowed to conclude that, contrary to expected, in the methyl ester of 1-vinyl-4-nitro-5-pyrazolecarboxylic acid, the formation of a planar conformation is unfavorable, preventing formation of a classical hydrogen bond. On the other hand, there is a hydrogen bond between the nitro group and vinyl group in 1-vinyl-5-nitro-pyrazolecarboxylic acids.

Design, Synthesis, and Quantum Chemical Calculations of Triazole-Based Aroylhydrazone Molecules: Dual Assessment of Antioxidant Properties via in vitro and in silico Approaches

In this study, five novel Triazole-Based Aroylhydrazone compounds (6a-e) were synthesized in high yields (87-79%), starting from deferasirox which has known iron chelator, and characterized with NMR, FTIR, Mass, and UV-vis spectroscopic methods. Quantum chemical calculations of all synthesized molecules were performed at the DFT/B3LYP/6,311G(d,p) level. It was observed that both theoretical and experimental spectral values were compatible. Optimized molecular geometries were acquired from DFT calculations and used in molecular docking studies. Tyrosinase (PDB ID: 3NM8) protein, which is a related antioxidant, was utilized in molecular docking studies. 6d-3NM8 complex had the highest docking score with the -10.1 kcal/mol. Stabilization of the 6d-3NM8 complex during 100 ns was determined via molecular dynamics simulations. Intramolecular interactions of all molecules were also analyzed by NCI-RDG analysis. The frequently used cupric ion reducing antioxidant capacity method (CUPRAC) was used to determine the antioxidant activity of synthesized compounds and Trolox which is unknown in the literature on its activity in DMSO. The highest TEAC value was 1.76 (6d) while the lowest one was 1.34 (6e). It is possible to say that the synthesized substance 6d has the potential to be an antioxidant reagent based on the results of in vitro and in silico antioxidant activity. An explanation of the reason for using the CUPRAC method was added to the manuscript.

Boron-bridged bis(tetrathiafulvalene) zwitterionic neutral radical conductors: substituent effects on intramolecular and intermolecular electronic interactions and physical properties

Abstract We have recently proposed a new molecular design for neutral radical molecular conductors, based on the chemical composition of D2X-type charge-transfer salts (D = π-electron donor molecule, X = monovalent anion). Namely, we connected two tetrathiafulvalene (TTF)-based π-electron skeletons having a charge of +0.5 via a boron anion B–, to obtain a purely organic zwitterionic neutral radical {[(PDT-TTF-Cat)2]+B–}• that shows unique electronic states and properties in the crystal due to the intramolecular and intermolecular interactions of the +0.5-charged π-skeletons. In order to further explore the structural and electronic features of this kind of zwitterionic neutral radical conductor, in this study, we have examined chemical modifications to {[(PDT-TTF-Cat)2]+B–}•. As a result, an analog molecule {[(BMT-TTF-Cat)2]+B–}•, in which propylenedithio (PDT) groups on the TTF terminals in {[(PDT-TTF-Cat)2]+B–}• are replaced by bis(methylthio) ones, was successfully synthesized as air-stable single crystals. Interestingly, this chemical modification causes intramolecular charge disproportionation between the two TTF-based π-skeletons (i.e. the monovalent cation radical TTF+• and the neutral TTF0) coupled to the modulation of the intermolecular distances and interactions between these π-skeletons, leading to electrical and magnetic properties significantly different from those of the crystal of {[(PDT-TTF-Cat)2]+B–}•.

Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning.

Throughout evolution, protein families undergo substantial sequence divergence while preserving structure and function. Although most mutations are deleterious, evolution can explore sequence space via epistatic networks of intramolecular interactions that alleviate the harmful mutations. However, comprehensive analysis of such epistatic networks across protein families remains limited. Thus, we conduct a family wide analysis of the B1 metallo-β-lactamases, combining experiments (deep mutational scanning, DMS) on two distant homologs (NDM-1 and VIM-2) and computational analyses (in silico DMS based on Direct Coupling Analysis, DCA) of 100 homologs. The methods jointly reveal and quantify prevalent epistasis, as ~1/3rd of equivalent mutations are epistatic in DMS. From DCA, half of the positions have a >6.5 fold difference in effective number of tolerated mutations across the entire family. Notably, both methods locate residues with the strongest epistasis in regions of intermediate residue burial, suggesting a balance of residue packing and mutational freedom in forming epistatic networks. We identify entrenched WT residues between NDM-1 and VIM-2 in DMS, which display statistically distinct behaviors in DCA from non-entrenched residues. Entrenched residues are not easily compensated by changes in single nearby interactions, reinforcing existing findings where a complex epistatic network compounds smaller effects from many interacting residues.

Mapping the Interaction Landscape of Adenosine and Minoxidil Sulfate Using an Independent Gradient Model Based on Hirshfeld Partition and Interaction Region Indicator.

Using theoretical techniques, the interactions between adenosine (AD) and minoxidil sulfate (MS) were studied using the DFT/M06-2X/aug-cc-pVDZ level of theory. The formation of the complex was thermodynamically favorable, so we carried out further studies. Frontier molecular orbital analysis shows that the HOMO-LUMO- gap is high (6.81 eV), which means that the complex is kinetically stable. The global reactivity parameters were also calculated to get insight about the chemical reactivity of the complex. Molecular electrostatic potential and charge analyses were carried out for the optimized complex. To study the charge transfer and inter- and intramolecular interactions present in the complex molecule, we employed natural bond orbital analysis. Noncovalent interaction (NCI) analysis along with IGMH and IRI analyses further helped us find the weak interactions. The presence of hydrogen bonds between the N atom (N27) of MS and H atom (H66) of AD and O atom (O32) of MS and H atom (H46) of AD was the main finding of these analyses. QTAIM investigation also supports this finding. EDA analysis was carried out to further study the intermolecular interactions present within the complex. Thus, the present investigation unveils the existence of weak NCIs in the complex.

The essential synergy of MD simulation and NMR in understanding amorphous drug forms.

Molecular dynamics (MD) simulations and chemical shifts from machine learning are used to predict 15N, 13C and 1H chemical shifts for the amorphous form of the drug irbesartan. The local environments are observed to be highly dynamic well below the glass transition, and averaging over the dynamics is essential to understanding the observed NMR shifts. Predicted linewidths are about 2 ppm narrower than observed experimentally, which is hypothesised to largely result from susceptibility effects. Previously observed differences in the 13C shifts associated with the two tetrazole tautomers can be rationalised in terms of differing conformational dynamics associated with the presence of an intramolecular interaction in one tautomer. 1H shifts associated with hydrogen bonding can also be rationalised in terms of differing average frequencies of transient hydrogen bonding interactions.

Constructing Donor–Acceptor-Linked COFs Electrolytes to Regulate Electron Density and Accelerate the Li+ Migration in Quasi-Solid-State Battery

HighlightsDonor–acceptor-linked covalent organic framework (COF)-based electrolyte can not only fulfill highly-selective Li+ conduction, but also offer a crucial opportunity to understand the role of electronic density in quasi-solid-state Li metal batteries.Donor–acceptor-linked COF electrolyte results in Li+ transference number 0.83, high ionic conductivity 6.7 × 10–4 S cm−1 and excellent cyclic ability in Li metal batteries.In situ characterizations, density functional theory calculation and time-of-flight secondary ion mass spectrometry are adopted to expound the mechanism of the rapid migration of Li+ in the “donor–acceptor” electrolyte system.

A Novel Bioluminescent Biosensor Quantifying Intramolecular Interaction and Levels of Pyroptosis Effector GSDMD.

Gasdermin D (GSDMD) is a key executor of pyroptosis, a form of inflammation-induced programmed cell death. Recently, GSDMD has been shown to play important roles in the development of various inflammatory-related human diseases including heart failure and cancer, suggesting that it is a promising therapeutic target for these diseases. While extensive studies on GSDMD's role in pyroptosis have been reported, it is challenging to study its function due to the lack of enzymatic activity of GSDMD. In this study, we used the NanoBiT technology to develop a novel GSDMD bioluminescent biosensor (GSDMD-BS) that detects the amount of non-cleaved GSDMD. This sensor allows us to quantify GSDMD's intramolecular interactions, the amounts of uncleaved GSDMD after caspase-1 cleavage, and expression levels in living cells. In vitro experiments using purified GSDMD-BS also confirmed the sensor's accuracy in reporting GSDMD levels and cleavage. Moreover, the potential for in vivo application was demonstrated in a xenograft mouse model. In conclusion, we have developed a GSDMD biosensor that is a valuable tool for real-time monitoring of GSDMD dynamics and pyroptosis. This biosensor will significantly expedite pyroptosis research and can be used for high-throughput screening for drugs targeting GSDMD for the therapy of many inflammation-related diseases.