Central Ring Research Articles

Compensating the Meniscus Effect in Phase Contrast Microscopy Using an LCD for Adaptive Condenser Annulus Shifting.

The meniscus effect in cell culture vessels limits the observable areas with phase contrast microscopy. For meniscus effect compensation in microtiter plates (MTPs), we present a method using an LCD to replace the fixed condenser annulus, which enables adaptive annulus shifting based on image analysis. This approach led to an increase in phase contrast area by a factor of 8.3. Utilizing a standard phase contrast microscope, we substituted the static condenser annulus with a transparent LCD that displays an adaptive annulus, which can be repositioned to counteract meniscus-induced refraction across an entire MTP-24 well. We developed image analysis using Bertrand lens images to determine the misalignment between annulus center and phase ring, enabling the calculation of the required annulus shift. Experiments demonstrate the effectiveness of this image analysis technique. The detected shift was translated into new LCD settings through a linear regression model to ensure proper alignment for the following image. We proved that an algorithm based on background brightness yields a reliable metric for assessing phase contrast conditions within well-plates. The proposed approach substantially increased the phase contrast area in 24-well MTPs at 10× magnification from 5.0% with conventional microscopy to 41.9%, thereby restoring phase contrast conditions throughout the well, except near the edges.

Stabilizing Contorted Doubly-Reduced Tetraphenylene with Heavy Alkali Metal Complexation: Crystallographic and Theoretical Evidence.

The two-fold reduction of tetrabenzo[a,c,e,g]cyclooctatetraene (TBCOT, or tetraphenylene, 1) with K, Rb, and Cs metals reveals a distinctive core transformation pathway: a newly formed C-C bond converts the central eight-membered ring into a twisted core with two fused five-membered rings. This C-C bond of 1.589(3)-1.606(6) Å falls into a single σ-bond range and generates two perpendicular π-surfaces with dihedral angles of 110.3(9)°-117.4(1)° in the 1TR 2- dianions. As a result, the highly contorted 1TR 2- ligand exhibits a "butterfly" shape and could provide different coordination sites for metal-ion binding. The K-induced reduction of 1 in THF affords a polymeric product with low solubility, namely [{K+(THF)}2(1TR 2-)] (K2-1TR 2-). The use of a secondary ligand facilitates the isolation of discrete complexes with heavy alkali metals, [Rb+(18-crown-6)]2[1TR 2-] (Rb2-1TR 2-) and [Cs+(18-crown-6)]2[1TR 2-] (Cs2-1TR 2-). Both internal and external coordination are observed in K2-1TR 2-, while the bulky 18-crown-6 ligand only allows external metal binding in Rb2-1TR 2- and Cs2-1TR 2-. The reversibility of the two-fold reduction and bond rearrangement is demonstrated by NMR spectroscopy. Computational analysis shows that the heavier alkali metals enable effective charge transfer from the 1TR 2-TBCOT dianion, however, the aromaticity of the polycyclic ligand remains largely unaffected.

High-Pressure Polymerization of Phenol toward Degree-4 Carbon Nanothread.

Saturated sp3-carbon nanothreads (CNTh) have garnered significant interest due to their predicted high Young's modulus and thermal conductivity. While the incorporation of heteroatoms into the central ring has been shown to influence the formation of CNTh and yield chemically homogeneous products, the impact of pendant groups on the polymerization process remains underexplored. In this study, we investigate the pressure-induced polymerization of phenol, revealing two phase transitions occurring below 0.5 and 4 GPa. Above 20 GPa, phenol polymerizes into degree-4 CNThs featuring hydroxyl and carbonyl groups. Hydrogen transfer of hydroxyl groups was found to hinder the formation of degree-6 nanothreads. Our findings highlight the crucial role of the hydroxyl group in halting further intracolumn polymerization and offer valuable insights for future mechanism research and nanomaterial synthesis.

Recent Achievements in the Synthesis of Carbazole Derivatives

Abstract: Carbazole derivatives possess tricyclic structure consisting of two benzene rings fused on both sides with the central pyrrole ring. These compounds diversely appear both in natural and synthetic sources. Carbazole-based compounds have a wide range of bioactivities such as antimicrobial, anticancer, antiparasitic, antihypertensive, antineuropathic, and anti-inflammatory activities. Some carbazole derivatives have been employed as drugs in the market. The synthesis of carbazole derivatives has attracted intensive interest from chemists and a huge number of studies on the synthesis of carbazole-based compounds have been published over the years. In this article, we will give a comprehensive review of studies on the synthesis of carbazoles, which date back to 2012. One hundred twenty-six studies on the synthesis of carbazoles are summarized. A huge number of novel methods have been developed to improve efficiency or employ environmentally benign procedures. In most cases, reaction mechanisms were included. The review article might be useful for chemists who work in the synthesis of heterocycles or drug chemistry.

Multifocal electroretinogram evaluation of different optical coherence tomography patterns of diabetic macular edema

Purpose To correlate macular function to morphological patterns of diabetic macular edema (DME) observed by optical coherence tomography (OCT). Patients and methods This study included 100 DME eyes and 60 control eyes. OCT patterns of DME were divided into: Type 1: diffuse retinal thickening (DRT); Type 2: cystoid macular edema (CME); Type 3: neurosensory detachment (NSD); and Type 4: the combined type that was further subdivided into: Type 4a: DRT with CME, Type 4b: DRT with NSD, and Type 4c: CME with NSD. These types were correlated with LogMAR VA and P1 wave amplitude and implicit time of multifocal electroretinogram. Results In both central ring 1 and paracentral ring 2, P1 amplitude was significantly reduced in all types of DME compared with control group. P1 amplitude was highest in Type 1, and lowest in Type 4c compared with other DME types. P1 implicit time was significantly delayed in all types, and significantly delayed in Type 4c compared with Type 1. Conclusion DRT was the best type for macular function, CME was associated with decreased P1 wave amplitude in central macular ring, NSD was associated with decreased P1 wave amplitude in the paracentral macular ring, combined CME with NSD carried the poorest visual function. From a practical point of view, combining OCT and multifocal electroretinogram testing may offer a potent method to assess the degree of retinal injury.

Crystal structure of p-xylene@silicalite-1.

The crystal structure of a highly loaded complex of silicalite-1 (SL-1) with eight mol-ecules of p-xylene per unit cell has been solved by single-crystal X-ray diffraction. In the crystal, four symmetrical Si24O48·2C8H10 subunits per unit cell are observed. The p-xylene mol-ecules sit at two different positions within the SL-1 channels. The first mol-ecule is located at the inter-section of the sinusoidal and straight channels, while the second guest mol-ecule is positioned in the center of the double ten-membered ring (10-MR) of the sinusoidal channel.

Annulated carbocyclic gallylene and bis-gallylene with two-coordinated Ga(i) atoms.

The first carbocyclic gallylene [(ADC)2Ga(GaI2)] and bis-gallylene [(ADC)Ga]2 (ADC = PhC{N(Dipp)C}2; Dipp = 2,6-iPr2C6H3) featuring a central C4Ga2 ring annulated between two 1,3-imidazole rings are prepared by KC8 reductions of [(ADC)GaI2]2. Treatment of [(ADC)Ga]2 with Fe2(CO)9 affords complex [(ADC)GaFe(CO)4]2 in which each Ga(i) atom serves as a two-electron donor. [(ADC)Ga]2 activates white phosphorus (P4) and the Csp2 -F bond of aryl fluorides (ArF) to yield compounds [(ADC)Ga(P4)]2 and cis-/trans-[(ADC)GaF(Ar)]2, respectively. [(ADC)Ga]2 undergoes oxidation with (Me2S)AuCl to give [(ADC)GaCl2]2, while with PhN[double bond, length as m-dash]NPh it forms [1 + 4]-cycloaddition product [(ADC)GaN(Ph)N[double bond, length as m-dash]C6H5]2 by the dearomatization of one of the phenyl rings.

Enhancing optoelectronic performance of organic solar cells: Alkoxy substitution of central cores and π-bridge units in fully non-fused ring electron acceptors

To systematically elucidate the impact of fluorination and alkoxy modification on the fully non-fused ring electron acceptors (NFREAs) for organic solar cells (OSCs), six fully NFREAs were engineered featuring a benzene core, a selenophene-thiophene unit as the π-bridge, and IC-2F end groups. The derivatives R-D2F and R-D2O were designed by introducing para-substituted fluorine and alkoxy groups onto the central benzene ring of R. Further modifications to the π-bridge of R-D2O, involving variations in the position and number of alkoxy groups, resulted in the derivatives R-DW4O, R-DN4O, and R-D6O. Molecular Dynamics (MD), Density Functional Theory (DFT), and Time-Dependent Density Functional Theory (TD-DFT) simulations were used to predict the optoelectronic properties of these compounds. A comprehensive analysis was conducted on aspects including intramolecular non-covalent interactions, transition density matrix (TDM), electron-hole distributions, charge density difference (CDD), and inter-fragment charge transfer (IFCT). Additionally, the electron transfer rate constants (Ke) and electron mobility (μe) of dimeric structures were calculated to better understand the electronic transmission behavior of these acceptor molecules. The results show that alkoxy substitution on the central core, rather than fluorine substitution, enhances planarity, strengthens intermolecular interactions, reduces the energy gap, induces a red shift in the absorption spectrum, and improves electron excitation efficiency and net charge transfer. The addition of alkoxy groups to the π-bridge further promotes non-covalent interactions, enhancing light absorption and increasing light harvesting efficiency (LHE). Among the derivatives, R-D6O, which features cooperative alkoxy substitution on both the thiophene and selenophene units, exhibits the highest electron mobility, making it a promising candidate for OSC applications. These findings provide valuable insights into the design of high-performance fully NFREAs for OSCs.

Structure-activity relationship expansion and microsomal stability assessment of the 2-morpholinobenzoic acid scaffold as antiproliferative phosphatidylcholine-specific phospholipase C inhibitors.

Dysregulation of choline phospholipid metabolism and overexpression of phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in various cancers. Current known enzyme inhibitors include compounds based on a 2-morpholino-5-N-benzylamino benzoic acid, or hydroxamic acid, scaffold. In this work, 81 compounds were made by modifying this core structure to explore the pharmacophore. Specifically, these novel compounds result from changes to the central ring substitution pattern, alkyl heterocycle and methylation of the N-benzyl bridge. The anti-proliferative activity of the synthesised compounds was assessed against cancer cell lines MDA-MB-231 and HCT116. PC-PLCBC enzyme inhibition was also assessed, and the development of a pharmacokinetic profile was initiated using a microsomal stability assay. The findings confirmed the optimal pharmacophore as a 2-morpholino-5-N-benzylamino benzoic acid, or acid derivative, scaffold, and that this family of molecules demonstrate a high degree of stability following treatment with rat microsomes. Additionally, benzylic N-methylated compounds were the most biologically active compounds, encouraging further investigation into this region of the pharmacophore.

Relationship Between Electronegativity of the Extra-Framework Cations and Adsorption Capacity for CO2 Gas on Mordenite Framework.

Synthetic mordenite is widely used as a molecular sieve, adsorbent, and catalyst. To enhance these functionalities, it is crucial to understand the ion-exchange properties and cation-exchange sites of the zeolite. In this study, we analyzed the structural changes in fully Cs-, Sr-, Cd-, and Pb-exchanged mordenite by using synchrotron X-ray powder diffraction under ambient conditions. Rietveld structure refinement revealed that the Cs+ cation is predominantly located near the 8-membered ring (8MR) due to its low electronegativity and hydration energy. In contrast, divalent cations such as Sr2+ and Cd2+ cations, with higher hydration energies compared to monovalent cations, are present as hydrated ions at the center of the 12-membered ring along the c-axis (12MRc). Pb2+ ions, due to their higher electronegativity than the framework atoms, exhibit a strong affinity for the electron cloud of framework oxygen atoms, which positions them close to the wall of the 12MRc. The observed differences in the locations of the extra-framework cations are attributed to electrostatic and hydration effects. Furthermore, the CO2 adsorption capacity was assessed based on the type and site of exchangeable cations. The findings indicate that an increase in the CO2 adsorption capacity correlates with the number of cations that can effectively interact with CO2.

Total Syntheses of Scabrolide B, Ineleganolide, and Related Norcembranoids.

Concise total syntheses of several 5/7/6 norcembranoids, including ineleganolide, scabrolide B, sinuscalide C, and fragilolide A have been achieved through a fragment coupling/ring closure approach. The central seven-membered ring was forged through sequential Mukaiyama-Michael/aldol reactions using norcarvone and a decorated bicyclic lactone incorporating a latent electrophile. Subsequent manipulations installed the reactive enedione motif and delivered scabrolide B in 11 steps from a chiral pool-derived enone. Finally, ineleganolide, sinuscalide C, and fragilolide A were each accessed in one additional step.

A Stable Carbon-Centered Radical Showing Six Amphoteric Redox States.

An air- and moisture-stable hydrocarbon radical with four six- and three five-membered rings alternately fused to a heptacycle was obtained by ortho fusion in a suitably ortho,ortho'-substituted diphenylfluorene and subsequent re-establishment of the conjugation. The radical was obtained in five consecutive steps from commercially available starting materials with a total yield of 34 %; key steps are Suzuki couplings and cyclizing SEAr reactions. Mesityl substituents at the five-membered rings ensure the stability of the radical. This cyclopenta-fused polyaromatic hydrocarbon (CP-PAH) was characterized by EPR and UV/Vis spectroscopy and by cyclic voltammetry. Quantum chemical calculation disclosed further properties and led to simulated spectra (spin densities, aromaticity, orbital energies, and UV/Vis/NIR). This radical is best described with the unpaired electron centered in the outer five-membered rings; these resonance formulas show the largest number of fully intact benzene rings. Its triradical character was computed to be very small and can be neglected. The five-membered rings show notable antiaromatic character, especially in the central ring. The constitution of the radical could be further substantiated by X-ray crystallographic analysis of its direct precursor.

Structural studies of (2R,3R)-(+)-bis(diphenylphosphino)butane and (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

Abstract The crystal structures of two chiral phosphanes, ((R,R)-chiraphos = (2R,3R)-(+)-2,3-bis(diphenylphosphino)butane and R-Tol-BINAP = (R)-(+)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl) are unambiguously determined by X-ray crystallography and reported for the first time. The aim is to understand the structural characteristics and their chiral arrangement of the molecules. The (R,R)-chiraphos structure was solved in the orthorhombic space group P212121 while R-Tol-BINAP was solved in the triclinic space group P1. This set of compounds demonstrates attractive intramolecular phenyl ring interactions involving two terminal phenyl rings in (R,R)-chiraphos, while a terminal tolyl ring and the central binaphthyl ring occurs in R-Tol-BINAP. The crystal structure analyses also revealed that all aromatic units have close C–H⋯arylcentroid weak contacts forming continuous networks of columns and layers in (R,R)-chiraphos and R-Tol-BINAP respectively.

Unraveling the Stereoisomer Configurations of 1,1'-bis(tert-butylphosphino)Ferrocene in the Gas Phase.

The molecular structure of a ferrocene derivative with adjacent centers of chirality, 1,1'-bis(tert-butylphosphino)ferrocene, has been examined in the gas phase using broadband microwave spectroscopy under the isolated and cold conditions of a supersonic jet. The diastereomers of 1,1'-bis(tert-butylphosphino)ferrocene can adopt homo- and hetero-chiral configurations, owing to the P-chiral substituents on the cyclopentadienyl rings. Moreover, the internal ring rotation of each diastereomer gives rise to four conformers with eclipsed ring arrangements, where the two tert-butylphosphino groups were separated by dihedral angles of approximately 72°, 144°, 216°, and 288° with respect to the two ring centers. The interconversion barriers between the conformations are below 2 kJ/mol, whereas the pyramidal inversion of the tert-butylphosphino groups is hindered by more than 140 kJ/mol, calculated at the B3LYP-D3(BJ)/def2-QZVP level of theory. In the experimental microwave spectrum, we unambiguously identified the two global-minimum diastereomers with 72° conformations. The absence of other conformers can be attributed to the relaxation dynamics in the supersonic jet, which transfers the high-energy conformers to the respective global-minimum geometries. Additionally, we discovered that London dispersion interactions between the two tert-butylphosphino groups play a crucial role in stabilizing the structures of this ferrocene complex.

Kinetic Implications of IP6 Anion Binding on the Molecular Switch of the HIV-1 Capsid Assembly.

HIV-1 capsid proteins (CA) self-assemble into a fullerene-shaped capsid, enabling cellular transport and nuclear entry of the viral genome. A structural switch comprising the Thr-Val-Gly-Gly (TVGG) motif either assumes a disordered coil or a 310 helix conformation to regulate hexamer or pentamer assembly, respectively. The cellular polyanion inositol hexakisphosphate (IP6) binds to a positively charged pore of CA capsomers rich in arginine and lysine residues mediated by electrostatic interactions. Both IP6 binding and TVGG coil-to-helix transition are essential for pentamer formation. However, the connection between IP6 binding and TVGG conformational switch remains unclear. Using extensive atomistic simulations, we show that IP6 imparts structural order at the central ring, which results in multiple kinetically controlled events leading to the coil- to-helix conformational change of the TVGG motif. IP6 facilitates the helix-to-coil transition by allowing the formation of intermediate conformations. Our results identify the key kinetic role of IP6 in HIV-1 pentamer formation.

Dynamics of Nanoparticles in Solutions of Semiflexible Ring Polymers.

We use hybrid molecular dynamics-multiparticle collision dynamics (MD-MPCD) simulations to investigate the influence of chain stiffness on the transport of nanoparticles (NPs) through solutions of semiflexible ring polymers. The NPs exhibit subdiffusive dynamics on short time scales before transitioning to normal diffusion at longer times. The terminal NP diffusivity decreases with increasing ring stiffness, similar to the behavior observed in solutions of semiflexible linear chains. The NP subdiffusive exponent is found to be strongly correlated with that of the polymer center of mass (COM) for the range of chain stiffnesses examined, which is at odds with the pronounced decoupling of the NP and polymer COM motions previously observed upon increasing the stiffness of linear chains. Our analysis indicates that these marked differences in the intermediate dynamics are rooted in distinct structural changes that emerge with increasing bending stiffness: Stiffer ring polymers adopt increasingly circular conformations and stack into transient tubes. The void space created near the ring centers is occupied by NPs and other polymers, resulting in strong dynamic coupling on short time scales.

A practical approach for the synthesis of lactate dehydrogenase A inhibitor GNE-140

GNE-140 is the first lactate dehydrogenase A (LDHA) inhibitor that demonstrates both sub-micromolar cellular potency and adequate pharmacokinetic properties, making it suitable for in vivo applications as a tool compound. However, the synthetic route reported by Genentech is complex, relying on transition metal catalysis and yielding low overall amounts. This study presents a practical, scalable method for constructing the core six-membered ring and quaternary carbon center of GNE-140 without transition metal catalysis, achieving a 48.5% racemic yield in a seven-step sequence, paving the way for future LDHA inhibitor development.

Quantum‐Classical Simulations Reveal the Photoisomerization Mechanism of a Prototypical First‐Generation Molecular Motor

Light‐driven molecular rotary motors convert the energy of absorbed light into unidirectional rotational motion and are key components in the design of molecular machines. The archetypal class of light‐driven rotary motors is chiral overcrowded alkenes, where the rotational movement is achieved through consecutive cis‐trans photoisomerization reactions and thermal helix inversion steps. While the thermal steps have been rather well understood by now, our understanding of the photoisomerization reactions of overcrowded alkene‐based motors still misses key points that would explain the striking differences in operation efficiency of the known systems. Here, we employ quantum‐chemical calculations and nonadiabatic molecular dynamics simulations to investigate the excited‐state decay and photoisomerization mechanism in a prototypical alkene‐based first‐generation rotary motor. We show that the initially excited bright state undergoes an ultrafast relaxation to multiple excited‐ state minima separated by low energy barriers and reveal a slow picosecond‐timescale decay to the ground state, which only occurs from a largely twisted dark excited‐state minimum, far from any conical‐intersection point. Additionally, we attribute the origin of the high yields of forward photoisomerization in our investigated motor to the favorable topography of the ground‐state potential energy surface, which is controlled by the conformation of the central cyclopentene rings.

4'-(2-Meth-oxy-phen-yl)-2,2':6',2''-terpyridine.

In the title compound, C22H17N3O, the N atoms of the pyridine rings exhibit a typical trans-trans arrangement: the dihedral angles between the central pyridine ring and the peripheral rings are 22.24 (4) and 2.38 (4)°. In the crystal, pairwise C-H⋯N hydrogen bonds form inversion dimers described by an R 2 2(6) graph set descriptor, which further inter-act through C-H⋯π and π-π inter-actions, creating a two-dimensional supra-molecular network propagating in the bc plane.

Relationship Between Short-Term Blood Pressure Variability and Choroidal-Retinal Thicknesses Assessed by Optical Coherence Tomography in Hypertensive Subjects.

Background/Objectives: The complications of hypertension depend not only on the mean blood pressure (BP) but also on its variability (BPV). Recent studies suggest that the choroid may serve as an indicator of systemic vascular damage. These studies have been made possible by the increased availability of optical coherence tomography (OCT). The aim of our study was to analyze the relationship between short-term BP variability (STBPV) and choroid-retinal thickness in hypertensive patients. Methods: A total of 98 patients with a mean age of 49 ± 12 years were enrolled in the study. All participants underwent 24 h blood pressure (BP) monitoring to measure 24 h mean systolic (SBP) and diastolic blood pressure (DBP), along with their respective standard deviations (SD), the weighted SD of 24 h SBP and DBP, and the average real variability (ARV) of 24 h SBP and DBP. The choroid-retinal region was assessed using Swept-Source OCT, with choroidal thickness (ChT) and retinal thickness divided into three concentric rings, and their mean choroidal thickness (ChT-or) was calculated. Results: The choroidal thickness of the concentric rings was found to be inversely correlated with all ARV values of the monitored blood pressure means. In particular, a correlation was observed between the ARV of daytime DBP and ChT-or. This correlation remained statistically significant (β = -0.34; p = 0.02) even after adjustment for various confounding factors. The ARV of daytime DBP was the only STBPV index to maintain a significant association, in the multivariate analysis, with the central ring mean thickness (β = -0.314; p = 0.001) and the inner choroidal ring mean thickness (β = -0.262; p = 0.003). Conclusions: Our study demonstrated an independent negative association between short-term BP variability (STBPV), when expressed as ARV of daytime DBP, and choroidal thickness. This finding confirms the value of choroidal thickness as a marker of cardiovascular risk.