Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease

The accumulation of the amyloid-β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ self-associates into a series of complex assemblies with different structural and biophysical properties. It is the interaction of these oligomeric, protofibril and fibrillar assemblies with lipid membranes, or with membrane receptors, that results in membrane permeability and loss of cellular homeostasis, a key event in Alzheimer's disease pathology. Aβ can have an array of impacts on lipid membranes, reports have included: a carpeting effect; a detergent effect; and Aβ ion-channel pore formation. Recent advances imaging these interactions are providing a clearer picture of Aβ induced membrane disruption. Understanding the relationship between different Aβ structures and membrane permeability will inform therapeutics targeting Aβ cytotoxicity.     

Role of quaternary ammonium salts as new additives in the enantioselective organocatalytic β-benzylation of enals

We report herein the efficiency of quaternary ammonium salts as co-catalysts in organocatalytic Michael reactions involving iminium activation of α,β-unsaturated aldehydes. The enantioselective formal benzylation of these substrates has been optimized and used to rationalize the role of the ammonium salts in these processes.     

Insights into the Role of Glucose and Glycerol as a Mixed Carbon Source in the Improvement of ε-Poly-l-Lysine Productivity

Using glucose–glycerol mixed carbon source has proved to be an effective strategy for ε-poly-l-lysine (ε-PL) production with rapid cell growth and much higher ε-PL productivity. In this study, we attempt to focus on key enzymes and intracellular energy cofactors to reveal the underlying mechanisms involved in such significant improvements. The activities of key enzymes involved in the pentose phosphate pathway, TCA cycle, anaplerotic pathway and the aspartate family amino acid biosynthesis pathway as well as ε-PL synthetase showed overall enhancement with the mixed carbon source, especially in the late stages of fermentation, compared with those in either glucose or glycerol single carbon sources. Moreover, the intracellular cofactors in terms of NADH and ATP kept higher formation and consumption rates in the mixed carbon source, respectively, throughout batch fermentation. As a result, Streptomyces sp. M-Z18 could be accelerated in cell growth and precursor l-lysine biosynthesis in the mixed carbon source, thus finally shortening fermentation time and enhancing ε-PL productivity. Understanding this process will provide information for the rational regulation of the metabolism network of the quantative production of ε-PL by metabolic engineering.     

Origin of the Aggregation-Induced Phosphorescence of Platinum(II) Complexes: The Role of Metal–Metal Interactions on Emission Decay in the Crystalline State

Discerning the origins of the phosphorescent aggregation-induced emission (AIE) from Pt(II) complexes is crucial for developing the broader range of photo-functional materials. Over the past few decades, several mechanisms of phosphorescent AIE have been proposed, however, not have been directly elucidated. Herein, we describe phosphorescence and deactivation processes of four class of AIE active Pt(II) complexes in the crystalline state based on experimental and theoretical investigation. These complexes show metal-to-ligand and/or metal−metal-to-ligand charge transfer emission in crystalline state with different heat resistance against thermal emission quenching. The calculated energy profiles including the minimum energy crossing point between S₀ and T₁ states were consistent with the heat resistant properties, which provided the mechanism for AIE expression. Furthermore, we have clarified the role of metal-metal interaction in AIE by comparing two computational models.     

The Role of Acetylcholine in the Cognitive Function of Frontal Neurons in Monkeys

To study the role of acetylcholine(ACh) in the cognitive function of frontal lobes, ACh and atropine were applied iontophoretically to the task-related neurons recorded from an area around the superior ramus of arcuate sulcus in the frontal cortex of 4 rhesus monkeys during the performance of two tasks. The spontaneous discharges and taskrelated responses of most of the neurons which increased their discharge rate in the delay and differentiation periods of the discrimination response go/no-go task and in the cue and delay periods of the delayed discrimination go/no-go task, were further increased during the application of ACh and suppressed during atropine. These results suggest that ACh may be involved in the excitatory process of the activity of the neurons in the above-mentioned area of frontal cortex to play an important role in the cognitive functions of attention, discrimination and short-term memory.     

The predicted unfolding order of the β-strands in the starch binding domain from Aspergillus niger glucoamylase

The unfolding of the β-strands in the starch binding domain from Aspergillus niger glucoamylase was predicted to follow the order of β3→β2→β6→β5→β4→β1→β7 by 600 ps molecular dynamics simulations at 300, 400, and 600 K. The interior region around β-strands 2 and 3 acts as the initiation site for unfolding. β-Strands 1 and 7 are probably stabilized by the disulfide bond formed between Cys509 and Cys604. β-Strand 4 is stabilized by forming an antiparallel β-sheet with β-strand 1. Hydrophobic and electrostatic interactions between side chains instead of the hydrogen bonds are important in stabilizing these β-strands, thus the entire starch binding domain.     

Recent Advances in One-Electron-Oxidized CuII–Diphenoxide Complexes as Models of Galactose Oxidase: Importance of the Structural Flexibility in the Active Site

The phenoxyl radical plays important roles in biological systems as cofactors in some metalloenzymes, such as galactose oxidase (GO) catalyzing oxidation of primary alcohols to give the corresponding aldehydes. Many metal(II)–phenoxyl radical complexes have hitherto been studied for understanding the detailed properties and reactivities of GO, and thus the nature of GO has gradually become clearer. However, the effects of the subtle geometric and electronic structural changes at the active site of GO, especially the structural change in the catalytic cycle and the effect of the second coordination sphere, have not been fully discussed yet. In this Review, we focus on further details of the model studies of GO and discuss the importance of the structural change at the active site of GO.     

The Role of Guest Molecules in the Self-assembly of Metal—ligand Clusters

Abstract

Understanding the self-assembly of nanoscale metal—ligand clusters is an important research area in supramolecular chemistry, especially, if one wishes to develop a truly predictive design strategy for synthesizing these nanoscale clusters. As the building blocks for forming these clusters have become larger and more complex, spacious clusters have been synthesized which often contain large cavities. These assemblies can house guest molecules which play a previously uncharacterized role in the self-assembly processes. We seek to analyze this role: do these guest molecules act as templates? Are the guest molecules necessary for cluster formation? Does the guest drive cluster assemble by forming a stable host—guest complex with the cluster? Must a truly rational design strategy for forming metal—ligand clusters incorporate the use of templates? The role of guest molecules in the self-assembly of nanoscale coordination clusters is reviewed in this article.     

Anion–π Interactions in Light-Induced Reactions: Role in the Amidation of (Hetero)aromatic Systems with Activated N-Aryloxyamides

The importance of anion–π interactions as a driving force for chemical and biological processes is increasingly being recognized. In this communication, we describe for the first time its key participation in light-induced reactions. We show, in particular, how transient complexes formed through noncovalent anion–π interactions between electron-poor N-aryloxyamides and multiply-charged anions (such as carbonate or phosphate) can undergo facile light-promoted N−O cleavage, affording amidyl radicals that can subsequently be trapped by (hetero)aromatics.     

Insights into the Role of Graphitic Carbon Nitride as a Photobase in Proton-Coupled Electron Transfer in (sp3)C−H Oxygenation of Oxazolidinones

Graphitic carbon nitride (g-CN) is a transition metal free semiconductor that mediates a variety of photocatalytic reactions. Although photoinduced electron transfer is often postulated in the mechanism, proton-coupled electron transfer (PCET) is a more favorable pathway for substrates possessing X−H bonds. Upon excitation of an (sp²)N-rich structure of g-CN with visible light, it behaves as a photobase—it undergoes reductive quenching accompanied by abstraction of a proton from a substrate. The results of modeling allowed us to identify active sites for PCET—the ‘triangular pockets’ on the edge facets of g-CN. We employ excited state PCET from the substrate to g-CN to selectively cleavethe endo-(sp³)C−H bond in oxazolidine-2-ones followed by trapping the radical with O₂. This reaction affords 1,3-oxazolidine-2,4-diones. Measurement of the apparent pK_a value and modeling suggest that g-CN excited state can cleave X−H bonds that are characterized by bond dissociation free energy (BDFE) ≈100 kcal mol⁻¹.     

The Role of Sulphonamides and N-Sulphonyl Ketimines/Aldimines as Directing Groups in the Field of C−H Activation

Sulphonamides and N-sulphonyl ketimines/aldimines have turned out to be versatile motifs in the field of synthetic and medicinal chemistry. The field of C−H activation/functionalization flourished remarkably due to their synthetic applicability and directing group plays a remarkable role to achieve regioselectivity in these reactions. The current review summarizes recent tactics by utilizing sulphonamides and N-sulphonyl ketimines/aldimines as directing groups for C−H activation or functionalization. As a directing group, they also facilitate site selectivity and late-stage functionalization of drug molecules in order to construct complex scaffolds of therapeutic importance by C−H activation.     

The Importance of Nutraceuticals in COVID-19: What’s the Role of Resveratrol?

Since COVID-19 has affected global public health, there has been an urgency to find a solution to limit both the number of infections, and the aggressiveness of the disease once infected. The main characteristic of this infection is represented by a strong alteration of the immune system which, day by day, increases the risk of mortality, and can lead to a multiorgan dysfunction. Because nutritional profile can influence patient’s immunity, we focus our interest on resveratrol, a polyphenolic compound known for its immunomodulating and anti-inflammatory properties. We reviewed all the information concerning the different roles of resveratrol in COVID-19 pathophysiology using PubMed and Scopus as the main databases. Interestingly, we find out that resveratrol may exert its role through different mechanisms. In fact, it has antiviral activity inhibiting virus entrance in cells and viral replication. Resveratrol also improves autophagy and decreases pro-inflammatory agents expression acting as an anti-inflammatory agent. It regulates immune cell response and pro-inflammatory cytokines and prevents the onset of thrombotic events that usually occur in COVID-19 patients. Since resveratrol acts through different mechanisms, the effect could be enhanced, making a totally natural agent particularly effective as an adjuvant in anti COVID-19 therapy.     

Effect of Notoginsenoside-Rg1 on the Expression of Several Proteins in the Striatum of Rat Models with Parkinson＇s Disease

After establishing hemi-Parkinsonian rat models, the relationships between neuron death and the expression of several proteins, such as c-Fos, GFAP, GDNF, NF-κB and some cytokines were determined. Therapeutics experiments with notoginsenoside-Rg1 were carried out. The research results show that the expressions of GFAP, NF-Kκ and c-Fos will obviously increase in the lesion side of the striatum and the expression of GDNF will decrease, which implies that the signal transduction pathway may participate in the apoptosis in neurons. The levels of some cytokines such as TNF-α, IL-1β in the striatum of PD rat models increased compared to those of normal rats. The results of the therapeutics experiments show that notoginsenoside-Rg1 may repress the immune inflammation response and regulate the immune function through the neuro-immune molecular network. Therefore, notoginsenoside-Rg1 can be used as an effective drug for anti-oxidation and anti-inflammation, and can be used in the therapy of Parkinson＇s disease（PD）.     

Effect of Notoginsenoside-Rg_1 on the Expression of Several Proteins in the Striatum of Rat Models with Parkinson′s Disease

Introduction Parkinson′sdisease(PD),alsocalledshaking palsy,isaneurodegenerativedisorderandfrequently occursinthepeopleabovetheageof65[1].PDisa relativelycommonneurodegenerativedisorder,which hasclinicalsymptomsincludingbradykinesia,rest tremor,rigidity,…     

Syntheses and evaluation of fluorinated benzothiazole anilines as potential tracers for β-amyloid plaques in Alzheimer's disease

[¹¹C]2-(4′-(Methylamino)phenyl)-6-hydroxybenzothiazole ([¹¹C]PIB) is a most potential PET tracer for detecting the β-amyloid plaques in Alzheimer's disease. Here the syntheses of three fluorinated PIB, namely 2-(4′-(methylamino)phenyl)-6-fluoroethoxybenzothiazole (O-FEt-PIB), 2-(4′-(methylamino)phenyl)-6-fluoro-benzothiazole (F-N-Me) and 2-(4′-(dimethylamino)phenyl)-6-fluorobenzo-thiazole (F-N,N-Me), and the radiosynthesis of one corresponding ¹⁸F-labeled PIB compound, [¹⁸F]O-FEt-PIB, as well as their in vitro/in vivo biological characters were reported. The structures of the products were confirmed by IR, ¹H NMR, EI/ESI-MS, elemental analysis and HRMS techniques. The radiolabeled product was characterized by radio-TLC and radio-HPLC and purified by semi-preparative radio-HPLC. The suitable biological characters showed these tracers were potential to be developed as probes for detecting β-amyloid plaques in Alzheimer's disease.     

The Mechanism of the Palladium Hydride β-Elimination Step in the Heck Reaction

The kinetics of competitive phenylation of alkenes with iodobenzene over palladium complexes (the Heck reaction) was studied. The effect of one alkene on the arylation rate of another alkene conflicts with the conventional mechanism of the Heck reaction in which the arylated alkene is formed through the unimolecular step of palladium hydride -elimination. Based on experimental data obtained, another mechanism is proposed in which a reaction product is formed through the transfer of palladium hydride to the initial alkene molecule.     

Role of the 3(ππ*) state in photolysis of lumisantonin: insight from ab initio studies

The CASSCF and CASPT2 methodologies have been used to explore the potential energy surfaces of lumisantonin in the ground and low-lying triplet states along the photoisomerization pathways. Calculations indicate that the (1)(nπ*) state is the accessible low-lying singlet state with a notable oscillator strength under an excitation wavelength of 320 nm and that it can effectively decay to the (3)(ππ*) state through intersystem crossing in the region of minimum surface crossings with a notable spin-orbital coupling constant. The (3)(ππ*) state, derived from the promotion of an electron from the π-type orbital mixed with the σ orbital localized on the C-C bond in the three-membered alkyl ring to the π* orbital of conjugation carbon atoms, plays a critical role in C-C bond cleavage. Based on the different C-C bond rupture patterns, the reaction pathways can be divided into paths A and B. Photolysis along path A arising from C1-C5 bond rupture is favorable because of the dynamic and thermodynamic preferences on the triplet excited-state PES. Path B is derived from the cleavage of the C5-C6 bond, leading first to a relatively stable species, compared to intermediate A-INT formed on the ground state PES. Accordingly, path B is relatively facile for the pyrolytic reaction. The present results provide a basis to interpret the experimental observations.