NMR Studies Research Articles

Investigation of the Dyeing Ability of Some Reactive Triazine Azo Dyes Containing Pyrazole Fragment.

The IR, 1H NMR, and DFT studies indicated that the prepared reactive disperse dyes predominately exist as hydrazone tautomers. The electronic absorption spectra in methanol were observed and compared to those computed using B3LYP/6-311G(d,p). The dyeing efficiency of the produced dispersed reactive dyes was examined on polyester, cotton, and polyester/cotton blended fabrics. The degree of exhaustion and the quick properties of the dyed samples in terms of perspiration, washing, scorch and light fastness were assessed. It was found that reactive disperse dyes under investigation have a higher affinity for dyeing polyester textiles than cotton textiles. Moreover, the reflectance and color strength of the synthesized dyes were measured and discussed.

Stereochemical Behavior of Pyrrolo-Pyrazole Peptidomimetics Promoting Phase-Selective Supramolecular Organogels

Supramolecular gels were developed by taking advantage of an assembly of small dipeptides containing pyrrolo-pyrazole scaffolds. The dipeptides were prepared through a robust and ecofriendly synthetic approach from the commercially available starting materials of diazoalkanes and maleimides. By playing with the functionalization of the scaffold, the choice of the natural amino acid, and the stereochemistry, we were able to obtain phase-selective gels. In particular, one peptidomimetic showed gelation ability and thermoreversibility in aromatic solvents at very low concentrations. Rheology tests showed a typical viscoelastic solid profile, indicating the formation of strong gels that were stable under high mechanical deformation. NMR studies were performed, allowing us to determine the conformational and stereochemical features at the base of the supramolecular interactions.

Synthesis of α,α-Difluoro-β-amino Ketones from N-Boc-α-Amidosulfones and Pentafluoro-gem-diols.

To circumvent the synthesis and isolation of imines, a method was devised to construct α,α-difluoro-β-amino ketones from N-Boc-α-amidosulfones. The reactive nucleophiles, difluoroenolates, are generated in situ from the pentafluoro-gem-diols using cesium fluoride in pyridine. NMR studies confirm the role of the α-amidosulfones in this process. Incubation of the α,α-difluoro-β-amino ketones in rat serum demonstrates the relative stability of this structure as well as its value as a chemical probe or lead.

Improving the Stability and Kinetic Inertness of Mn(II) Complexes by Increasing the Bridge Length in Bicyclic CDTA-like Ligands.

Kinetic inertness of Mn(II)-based MRIcontrast agents can be improved by increasing the rigidity of the polydentate ligand that tightly coordinate the metal ion. Taking inspiration from the remarkable increase in kinetic inertness of [Mn(CDTA)]2-compared to [Mn(EDTA)]2-due to the cyclohexyl backbone rigidity, we devised that bicyclic ligandswould further improve the kinetic inertness of the Mn(II) complexes. The length of the alkyl bridge on the cyclohexane ring was varied from methylene (BCH-DTA), ethylene (BCO-DTA) to propylene (BCN-DTA) to evaluate the influence of the differenttrans-diaminotetraacetate ligands onrelaxometric, thermodynamic and kinetic properties of the Mn(II)-complexes.1H and17O NMR relaxometricstudies showed a slight increase in relaxivity and a faster water exchange rate in these Mn(II)-complexes with respect to [Mn(CDTA)]2-. Solution studies revealed that the conditional stability (pMn) and dissociation half-life (t1/2) at pH 7.4 follow the order [Mn(BCH-DTA)]2-< [Mn(BCO-DTA)]2-< [Mn(BCN-DTA)]2- by highlighting the effect of the bridge length on the overall stability of the Mn(II)-complexes. Remarkably, [Mn(BCN-DTA)]2- shows an improved pMn value and a 7-times higher kinetic inertness than [Mn(CDTA)]2-. NMR studies on the Zn(II) analogues confirm the rigidity of the bicyclic complexes with an isomerization process at >313Kfor the smaller bridged complex [Zn(BCH-DTA)]2.

Iron catalyzed oxidative Csp3-Csp3 radical coupling reaction between thiohydantoins and O-acetyl oximes for the synthesis of 1,3-dibenzyl-3,4-dihydropyrrolo[2,3-d]imidazole-2(1H)-thione derivatives

A unified heteroannelation method to achieve the synthesis of 1,3-dibenzyl-3,4-dihydropyrrolo[2,3-d]imidazole-2(1H)-thione derivatives with an iron catalyst is proposed. The annelation reaction is followed by Csp3-Csp3 radical coupling between thiohydantoins and O-acetyl oximes. The synthetic approach enables access to several alkynylated thiohydantoins and O-acetyl oximes with controlled selectivity for Csp3-Csp3 coupling rather than Csp3-O coupling in moderate to higher yield. The optimization study has been carried out by changing catalyst loading, oxidants, solvents, and varying temperatures. Synthesized compounds were characterized through 1H NMR, 13C NMR, and mass spectral studies.

Do Electrostatics Control the Diffusive Dynamics of Solitary Water? NMR and MD Studies of Water Translation and Rotation in Dipolar and Ionic Solvents.

NMR-based measurements of the diffusion coefficients and rotation times of solitary water and benzene at 300 K are reported in a diverse collection of 13 conventional organic solvents and 10 imidazolium ionic liquids. Proton chemical shifts of water are found to be correlated to water OH-stretching frequencies, confirming the importance of electrostatic interactions in these shifts. However, the influence of magnetic interactions in aromatic solvents renders chemical shifts a less reliable indicator of electrostatics. Diffusion coefficients (DB) and rotational correlation times (τB) of benzene in the solvents examined are accurately described as functions of viscosity (η) by DB ∝ η-0.81 and τB ∝ η0.64. Literature values of DB and τB in alkane and normal alcohols, which were not included among the solvents studied here, are systematically faster than predicted by these correlations, indicating that factors beyond solvent viscosity play a role in determining the friction on benzene. In contrast to benzene, water diffusion and rotation are poorly described in terms of viscosity alone, even in the dipolar and ionic solvents measured here. The present data and the substantial literature data already available on dilute water diffusion show a systematic dependence of DW on solvent polarity among isoviscous solvents. The aspect of solvent polarity most relevant to water dynamics is the ability of a solvent to accept hydrogen bonds from water, as conveniently quantified by the frequency of water's OH stretching band, ΔνOH. The friction on translation, ζtr = kBT/DW, and rotation, ζrot = kBTτW, are both well correlated by functions of the form ζ(η, ΔνOH) = a1ηa2 exp (a3ΔνOH), where the ai are adjustable parameters. Molecular dynamics simulations reveal a strong coupling between electrostatic and nonelectrostatic water-solvent interactions, which makes it impossible to dissect the friction on water into additive dielectric and hydrodynamic components. Simulations also provide a tentative explanation for the unusual form of the correlating function ζ(η, ΔνOH), at least in the case of ζrot.

Ferroelectric Smectic Liquid Crystals

Since the discovery of the first ferroelectric liquid crystal (FLC) in the chiral smectic C (SmC*) phase, ferroelectricity in liquid crystals has attracted much attention due to not only the fundamental interest but also the applications. This review focuses on the evolution of the design concept for ferroelectric smectic liquid crystals. It progresses from considering macroscopic phase symmetry to designing intermolecular interactions. For the purpose of understanding the molecular organization in smectic phases, we propose a dynamic model of constituent molecules in the smectic A (SmA) and SmC* phases based on 13C NMR studies. Then, we follow the structure–property relationship in ferroelectric SmC* liquid crystals for FLC displays. We reconsider de Vries-like materials that can provide defect-free alignment. We pay attention to the electro-optical switching in the chiral de Vries smectic A phase. Finally, we show several liquid crystals exhibiting polar smectic A phases and discuss how the polar order occurs in the highest symmetric smectic A phase.

Electrochemical Reduction of Perfluorooctanoic Acid (PFOA): An Experimental and Theoretical Approach.

Perfluorooctanoic acid (PFOA) is an artificial chemical of global concern due to its high environmental persistence and potential human health risk. Electrochemical methods are promising technologies for water treatment because they are efficient, cheap, and scalable. The electrochemical reduction of PFOA is one of the current methodologies. This process leads to defluorination of the carbon chain to hydrogenated products. Here, we describe a mechanistic study of the electrochemical reduction of PFOA in gold electrodes. By using linear sweep voltammetry (LSV), an E0' of -1.80 V vs Ag/AgCl was estimated. Using a scan rate diagnosis, we determined an electron-transfer coefficient (αexp) of 0.37, corresponding to a concerted mechanism. The strong adsorption of PFOA into the gold surface is confirmed by the Langmuir-like isotherm in the absence (KA = 1.89 × 1012 cm3 mol-1) and presence of a negative potential (KA = 3.94 × 107 cm3 mol-1, at -1.40 V vs Ag/AgCl). Based on Marcus-Hush's theory, calculations show a solvent reorganization energy (λ0) of 0.9 eV, suggesting a large electrostatic repulsion between the perfluorinated chain and water. The estimated free energy of the transition state of the electron transfer (ΔG‡ = 2.42 eV) suggests that it is thermodynamically the reaction-limiting step. 19F - 1H NMR, UV-vis, and mass spectrometry studies confirm the displacement of fluorine atoms by hydrogen. Density functional theory (DFT) calculations also support the concerted mechanism for the reductive defluorination of PFOA, in agreement with the experimental values.

Abstract ND07: BBO-8520, a first-in-class, direct inhibitor of KRASG12C (ON), locks GTP-bound KRASG12C in the state 1 conformation resulting in rapid and complete blockade of effector binding

Abstract The glycine to cysteine mutation on codon 12 of KRAS (KRASG12C) is found in ~15% of non-small cell lung cancers and in a low percentage of colorectal and pancreatic adenocarcinomas. This activating mutation pushes the balance of cellular KRAS towards its active, GTP-bound (ON) state that signals downstream and drives cellular proliferation. Recently approved inhibitors of KRASG12C that bind and sequester the oncogenic protein in its inactive GDP-bound (OFF) state, have demonstrated clinical efficacy; however, median duration of response has been &amp;lt; 9 months. Rapid tumor cell adaptation to KRASG12C (OFF)-only inhibitors like sotorasib and adagrasib has been attributed to reactivation of MAPK signaling through increased RTK flux and KRASG12C gene amplification that result in increased KRASG12C (ON) presence and activity. To block rapid KRASG12C (ON)-driven adaptation to KRASG12C (OFF) inhibitors, we have developed a first-in-class, direct, small molecule covalent inhibitor of both KRASG12C (ON) and (OFF) states. BBO-8520 binds in the switch II pocket and covalently modifies both the (ON) and (OFF) forms of KRASG12C independently of any other partner proteins. Mass spectrometry analysis of KRASG12C covalent engagement by BBO-8520 shows complete modification of both KRASG12C states within 15 minutes, while sotorasib and adagrasib, only modify the (OFF) state. 31P NMR studies demonstrate that BBO-8520 inhibits KRASG12C (ON) by locking the GTP-bound protein in state 1, a conformation where it is unable to bind effectors. The ability to directly bind KRASG12C (ON) leads to potent (~30 nM) inhibition in an effector (Raf1) binding assay where inactive (OFF) inhibitors demonstrate no measurable potency. BBO-8520 displays highly significant binding to KRASG12C in a global cysteine proteome analysis and is 100x more selective for KRASG12C than for WT KRAS and other mutant isoforms, with no measurable activity against N- or H-RAS. Cellular signaling and viability assays show that BBO-8520 has sub-nanomolar potency against KRASG12C mutant cell lines. In effector binding assays, BBO-8520 rapidly and completely blocks the RAS-RAF1 interaction, clearly differentiating it from inactive (OFF) inhibitors that require longer times to allow for cycling to the inactive (OFF) state. Additionally, long-term clonogenic assays that detect the emergence of resistance in the presence of inhibitors show that BBO-8520 is at least 30x more potent than sotorasib and adagrasib at preventing outgrowth. Importantly, the presence of growth factors (e.g., EGF) that push KRASG12C into its (ON) state, and significantly lower the potency of inactive (OFF) inhibitors (&amp;gt;20x), have only minor effects on BBO-8520’s potency. Drug-like pharmacokinetic properties allow BBO-8520 to achieve strong dose- and time-dependent pharmacodynamic effects (&amp;gt;80% inhibition of pERK) following a single, oral dose in KRASG12C mutant tumor bearing mice. In vivo target engagement and pERK inhibition in the MIAPaCa-2 and H358 KRASG12C mutant tumor models resulted in durable tumor regressions at 10 mg/kg. Similarly, daily dosing of 10 mg/kg of BBO-8520 in the KrasG12C-p53 driven GEMM model for 6 weeks resulted in better than 50% lung tumor volume regression. BBO-8520’s potent activity against KRASG12C (ON) presents, for the first time, the potential opportunity to directly target all mutant KRASG12C in cells, including the active form of KRASG12C, enabling efficacy following complete or near-complete target inhibition. Citation Format: Anna E. Maciag, James Stice, Bin Wang, Alok Sharma, Albert Chan, Ken Lin, Devansh Singh, Marcin Dyba, Yue Yang, Saman Setoodeh, Brian P. Smith, Dana Rabara, Zuhui Zhang, Erik K. Larsen, Dom Esposito, John Paul Denson, Michela Ranieri, Mary Meynardie, Sadaf Mehdizadeh, Patrick Alexander, Maria Abreu Blanco, David Turner, Rui Xu, Felice C. Lightstone, Kwok Kin Wong, Dhirendra Simanshu, Keshi Wang, Andrew G. Stephen, Kerstin Sinkevicius, Dwight V. Nissley, Eli Wallace, Frank McCormick, Pedro J. Beltran. BBO-8520, a first-in-class, direct inhibitor of KRASG12C (ON), locks GTP-bound KRASG12C in the state 1 conformation resulting in rapid and complete blockade of effector binding [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr ND07.

Revealing the mechanism of combining best properties of homogeneous and heterogeneous catalysis in hybrid Pd/NHC systems

The formation of transient hybrid nanoscale metal species from homogeneous molecular precatalysts has been demonstrated by in situ NMR studies of catalytic reactions involving transition metals with N‐heterocyclic carbene ligands (M/NHC). These hybrid structures provide benefits of both molecular complexes and nanoparticles, enhancing the activity, selectivity, flexibility, and regulation of active species. However, they are challenging to identify experimentally due to the unsuitability of standard methods used for homogeneous or heterogeneous catalysis. Utilizing a sophisticated solid‐state NMR technique, we provide evidence for the formation of NHC‐ligated catalytically active Pd nanoparticles (PdNPs) from Pd/NHC complexes during catalysis. The coordination of NHCs via C(NHC)‐Pd bonding to the metal surface was first confirmed by observing the Knight shift in the 13C NMR spectrum of the frozen reaction mixture. Computational modeling revealed that as little as few NHC ligands are sufficient for complete ligation of the surface of the formed PdNPs. Catalytic experiments combined with in situ NMR studies confirmed the significant effect of surface covalently bound NHC ligands on the catalytic properties of the PdNPs formed by decomposition of the Pd/NHC complexes. This observation shows the crucial influence of NHC ligands on the activity and stability of nanoparticulate catalytic systems.

Revealing the mechanism of combining best properties of homogeneous and heterogeneous catalysis in hybrid Pd/NHC systems.

The formation of transient hybrid nanoscale metal species from homogeneous molecular precatalysts has been demonstrated by in situ NMR studies of catalytic reactions involving transition metals with N-heterocyclic carbene ligands (M/NHC). These hybrid structures provide benefits of both molecular complexes and nanoparticles, enhancing the activity, selectivity, flexibility, and regulation of active species. However, they are challenging to identify experimentally due to the unsuitability of standard methods used for homogeneous or heterogeneous catalysis. Utilizing a sophisticated solid-state NMR technique, we provide evidence for the formation of NHC-ligated catalytically active Pd nanoparticles (PdNPs) from Pd/NHC complexes during catalysis. The coordination of NHCs via C(NHC)-Pd bonding to the metal surface was first confirmed by observing the Knight shift in the 13C NMR spectrum of the frozen reaction mixture. Computational modeling revealed that as little as few NHC ligands are sufficient for complete ligation of the surface of the formed PdNPs. Catalytic experiments combined with in situ NMR studies confirmed the significant effect of surface covalently bound NHC ligands on the catalytic properties of the PdNPs formed by decomposition of the Pd/NHC complexes. This observation shows the crucial influence of NHC ligands on the activity and stability of nanoparticulate catalytic systems.

Ni2+ removal by ion exchange resins and activated carbon: a benchtop NMR study

AbstractHeavy metal pollution in water is a critical environmental concern, demanding effective remediation techniques. Traditional methods, including ion exchange and adsorption, often rely on inductively coupled plasma (ICP) atomic emission spectroscopy/mass spectrometry (AES/MS) for the indirect and time-consuming measurement of residual metal concentrations. In contrast, this study employs innovative direct monitoring of nickel removal by benchtop NMR relaxometry using the paramagnetic properties of Ni2+. To prove the feasibility of the NMR follow-up of Ni2+ uptake, batch experiments were performed with Amberlite IR120, Amberlite IRC748, Dowex Marathon MSC, and activated carbon (AC), which were previously characterized by various techniques. The effect of contact time, pH, and Ni2+ concentration on removal efficiency were studied. Pseudo-first and pseudo-second order kinetic models were used. The Langmuir model effectively described the equilibrium isotherms. The longitudinal and transverse relaxation curves of the loaded resins were biexponential. For sulfonic resins, a strong correlation was observed between the relaxation rates of the fast-relaxing fraction and the Ni2+ content determined by ICP-AES/MS. For IRC748, the effect of Ni2+ loading on the relaxation rates was weaker because of Ni2+ complexation. The relaxation curves of loaded AC revealed multiple fractions. Centrifugation was employed to eliminate the contribution of intergranular water. The remaining intragranular water contribution was biexponential. For high Ni2+ loadings, the relaxation rates of the slow relaxing fraction increased with the AC Ni2+ content. These results mark the initial stage in developing a column experiment to monitor, in real-time, adsorbent loading by NMR relaxometry.

Exploring the chemical physics in tetraphenylporphyrin-N-methylfulleropyrrolidine supramolecular complex by spectroscopic investigations and quantum chemical calculations

The interaction between N-methylfulleropyrrolidine (A) and 5,10,15,20-tetraphenylporphyrin, i.e., D, is studied in solution. Absorption spectrophotometric study reveals formation of charge transfer (CT) absorption band for the DA complex from which CT transition energy (hνCT) is estimated to be 1.673 eV. Quenching of fluorescence of D in presence of A is utilized for determination of the binding constant of the DA complex as 13780 dm3⋅mol−1. DFT calculations generate both geometry optimized and electronic structures of the DA complex and the estimated HOMO-LUMO energy gap, i.e., 1.683 eV, correlates excellently well with the experimentally obtained value of hνCT. Proton NMR studies provide substantial support in favour of strong binding between D and A and provide a clear picture regarding orientation of bound guest (here A) with host (here D). The DA system reported in present work would certainly provide very good perspective for the construction of fulleropyrrolidine based photochromic devices in near future.

17O Solid-State NMR Spectroscopy of Lipid Membranes.

Despite the limitations posed by poor sensitivity, studies have reported the unique advantages of 17O based NMR spectroscopy to study systems existing in liquid, solid, or semisolid states. 17O NMR studies have exploited the remarkable sensitivity of quadrupole coupling and chemical shift anisotropy tensors to the local environment in the characterization of a variety of intra- and intermolecular interactions and motion. Recent studies have considerably expanded the use of 17O NMR to study dynamic intermolecular interactions associated with some of the challenging biological systems under magic angle spinning (MAS) and aligned conditions. The very fast relaxing nature of 17O has been well utilized in cellular and in vivo MRS (magnetic resonance spectroscopy) and MRI (magnetic resonance imaging) applications. The main focus of this Review is to highlight the new developments in the biological solids with a detailed discussion for a few selected examples including membrane proteins and nanodiscs. In addition to the unique benefits and limitations, the remaining challenges to overcome, and the impacts of higher magnetic fields and sensitivity enhancement techniques are discussed.

Aromatic-Carbonyl Interactions as an Emerging Type of Non-Covalent Interactions.

Aromatic-carbonyl (Ar···C═O) interactions, attractive interactions between the arene plane and the carbon atom of carbonyl, are in the infancy as one type of new supramolecular bonding forces. Here the study and functionalization of aromatic-carbonyl interactions in solution is reported. A combination of aromatic-carbonyl interactions and dynamic covalent chemistry provided a versatile avenue. The stabilizing role and mechanism of arene-aldehyde/imine interactions are elucidated through crystal structures, NMR studies, and computational evidence. The movement of imine exchange equilibria further allowed the quantification of the interplay between arene-aldehyde/imine interactions and dynamic imine chemistry, with solvent effects offering another handle and matching the electrostatic feature of the interactions. Moreover, arene-aldehyde/imine interactions enabled the reversal of kinetic and thermodynamic selectivity and sorting of dynamic covalent libraries. To show the functional utility diverse modulation of fluorescence signals is realized with arene-aldehyde/imine interactions. The results should find applications in many aspects, including molecular recognition, assemblies, catalysis, and intelligent materials.

Rationally designed dual channel reversible probe for cyanide recognition in aqueous medium with solid-state sensing abilities

A novel chromogenic azo-azomethine chemosensor, namely 2-((E)-(2-(benzo[d]thiazol-2-yl) hydrazineylidene)methyl)-4-((E)-phenyldiazenyl)phenol (referred to as L), was rationally designed and synthesized. The molecular structure of L was established using various spectroscopic and spectrometry techniques including NMR, FT-IR and mass. The spectral profile including absorption and fluorescence were recorded in solvents of varying polarity. The sensor responsiveness towards different anions was evaluated visually and established using UV–vis spectroscopy and NMR studies. A binary solution of DMSO/H2O (6:4, v:v) was used for anion recognition studies. A color change from colorless to yellow was noticed upon addition of CN– ion to the probe (L) solution. The developed probe was found to be very sensitive towards CN– ion with a detection limit of 21 nM. Benesi-Hildebrand plot revealed a binding constant of 1.2*103 and the binding stoichiometry of 1:2 was confirmed using Job’s plot. 1H NMR studies were utilised to ascertain the recognition mechanism which revealed the CN– ion assisted deprotonation of N-H and O-H group of L. The recognition mechanism established using NMR technique has been supported theoretically by DFT based studies. Additionally, cost-effective paper strips coated with L has been proved to be a convenient tool for detecting CN– ion in aqueous solutions. The reversibility and reusability of the developed probe was also investigated in both solution as well as solid state using trifluoroacetic acid (TFA) without any loss of the sensitivity of the developed probe. Moreover, the developed probe recognises cyanide ion in environmental samples with around 100 % recovery. The practical application of the Logic gate response of L was confirmed by paper strip experiment.

Study of Structural Elucidation, Degradation Kinetics and Antimicrobial Analysis of Copper (II) Sesame-Soap Complexes with Urea and Thiourea Ligand in Non-aqueous Solvents

Abstract: Surfactants have great importance in biological and drug industries and the complexes of metallic soaps with various ligands are used in approximately every region of national economy. Therefore, our keen interest to study of degradation kinetics and biological importance of Cu (II) surfactants in non-aqueous and non-polar solvent benzene. Present research work has been initiated with synthesis, systematic study of structural elucidation, thermal degradation, kinetics and biocidal activities of copper (II) sesame-soap complexes with macrocyclic nitrogen and sulphur containing donar ligands like urea and thiourea. The thermal degradation of copper (II) sesame-soap complexes were carried out for analysis of degradation kinetics and estimation of kinetic and thermodynamic parameters using different methods at heating rate 10oC min-1. Copper (II) sesame-soap complexes of such ligands have also been analysed against Staphylococus aureus. This research work consolidates the synthesis of copper (II) sesame soap-urea and thiourea complexes by conventional methods and the structure of these complexes were assigned according to elemental analysis and molecular weight determinations. IR, NMR and ESR spectral studies have also been done to understand structural aspects. The anti-microbial activities of copper (II) sesame-soap urea and thiourea complexes have been evaluated by testing against Staphylococus aureus. The present research work includes information of thermal analysis using TGA technique to find out their kinetic and thermodynamic parameters by using diverse equations such as Coats-Redfern equation, Horowitz-Metzger equation, Broido equation, Piloyan–Novikova equation. Moreover, the results obtained from anti-microbial screening have been used to analyze the anti-microbial activities of copper (II) sesame-soap urea and thiourea complexes against gram-positive bacteria Staphylococus aureus. These results show that complexes of copper ion co-ordinated with different nitrogen, oxygen and sulphur containing ligands, are very important in the field of pharmaceutical chemistry due to its significant role in the inhibition activity. The study of these complexes concludes that the synthesized complexes were found to possess appreciable bactericidal properties at different concentrations because chelation increases the anti-microbial potency.

DNA binding reveals hidden interdomain allostery of a MazE antitoxin from Mycobacterium tuberculosis

Type II toxin−antitoxin (TA) systems are ubiquitously distributed genetic elements in prokaryotes and are crucial for cell maintenance and survival under environmental stresses. The antitoxin is a modular protein consisting of the disordered C-terminal region that physically contacts and neutralizes the cognate toxin and the well-folded N-terminal DNA binding domain responsible for autorepression of TA transcription. However, how the two functional domains communicate is largely unknown. Herein, we determined the crystal structure of the N-terminal domain of the type II antitoxin MazE-mt10 from Mycobacterium tuberculosis, revealing a homodimer of the ribbon-helix-helix (RHH) fold with distinct DNA binding specificity. NMR studies demonstrated that full-length MazE-mt10 forms the helical and coiled states in equilibrium within the C-terminal region, and that helical propensity is allosterically enhanced by the N-terminal binding to the cognate operator DNA. This coil-to-helix transition may promote toxin binding/neutralization of MazE-mt10 and further stabilize the TA–DNA transcription repressor. This is supported by many crystal structures of type II TA complexes in which antitoxins form an α-helical structure at the TA interface. The hidden helical state of free MazE-mt10 in solution, favored by DNA binding, adds a new dimension to the regulatory mechanism of type II TA systems. Furthermore, complementary approaches using X-ray crystallography and NMR allow us to study the allosteric interdomain interplay of many other full-length antitoxins of type II TA systems.

Study on characterization of Bupleurum chinense polysaccharides with antioxidant mechanisms focus on ROS relative signaling pathways and anti-aging evaluation in vivo model

This study explored the structures of three polysaccharides from Bupleurum chinense DC. (BCPRs), and evaluated their antioxidant and anti-aging properties. The HPGPC and ion chromatography analyses revealed that the molecular weights of the BCPRs ranged from 12.05 to 21.20 kDa, and were primarily composed of rhamnose, arabinose, xylose, galactose, glucose and galacturonic acid. Methylation and NMR studies identified 10 PMAAs, establishing the various backbones of BCPRs 1–3. BCPR-3 demonstrated potent antioxidant activities, including DPPH, ABTS, hydroxy, and superoxide radicals scavenging in vitro. At concentrations between 125 and 500 μg/mL, BCPR-3 increased T-AOC, SOD and GSH-Px activities, while decreasing MDA levels in H2O2-induced SH-SY5Y cells. In addition, RNA-seq results indicated that BCPR-3 considerably downregulated the expression of 49 genes and upregulated five genes compared with the control group. KEGG analysis suggested that these differentially expressed genes (DEGs) were predominantly involved in the TNF and PI3K/Akt signaling pathways. Furthermore, in vivo experiment with Drosophila melanogaster showed that BCPR-3 could extend the average lifespan of flies. In conclusion, polysaccharides from B. chinense exhibited potential antioxidant and anti-aging activities, which could be developed as new ingredients to combat oxidative stress damage and slow the aging process.

Inclusion complex of ionic liquid 1-dodecylpyridinium tetrafluoroborate with sulfobutyl ether-β-cyclodextrin: Preparation and characterization

In this article an inclusion complex of hydrophobic ionic liquid 1-dodecylpyridinium tetrafluoroborate (PyrC12-BF4) and sodium salt of sulfobutyl ether β-cyclodextrin (SB-β-CD) has been synthesized and studied using NMR spectroscopy, UV–Vis spectroscopy, FT-IR, TGA, DSC and XRD. The results of 1H NMR study revealed physicochemical interactions between the hydrophobic alkyl chain of PyrC12-BF4 and protons of the inner cavity of SB-β-CD, as well as between the CH protons of pyridinium cation and the polar SB-β-CD groups. The formation of an inclusion complex has also been revealed by Wilhelmy plate method. The binding constant of the SB-β-CD/PyrC12-BF4 complex determined by the method of Higuchi and Connors was found to be 1210 M–1. According to DSC analysis data, only one endothermic peak is observed in the thermogram of the SB-β-CD/PyrC12-BF4 inclusion complex, thus confirming the formation of a new supramolecular system. Additional characterization methods such as thermal mass spectroscopy and TEM were also applied for characterization of the synthesized complex. Complexation of long-chain pyridinium salt with SB-β-CD can be an efficient approach for the preparation of new antimicrobial formulations with reduced toxicity.