Identification of a Lead Candidate in the Search for Carbene‐Stabilised Homoaromatics

The effect of carbenes as Lewis donor groups on the homoaromaticity of mono‐ and bicyclic organic molecules is surveyed. The search for viable carbene‐stabilised homoaromatics resulted in a large amount of rejected candidates as well as nine promising candidates that are further analysed for their homoaromaticity by using a number of metrics. Of these, five appeared to show modest homoaromaticity, whereas another compound showed a level of homoaromaticity comparable with the homotropylium cation benchmark compound. Isoelectronic analogues and constitutional isomers of the lead compound were investigated, however, none of these showed comparable homoaromaticity. The implications of these calculations on the design of donor‐stabilised homoaromatics are discussed.     

Facile and practical synthesis of a cannabinoid-1 antagonist via regio- and stereoselective ring-opening of an aziridinium ion

A scalable synthetic strategy of a chiral, trisubstituted imidazolidinone (1), a novel cannabinoid-1 antagonist, starting from a commercially available mandelic acid (5) is described. The key step involves a regio- and stereoselective ring-opening of an aziridinium ion by an aniline nucleophile (3). A mechanistic study revealed the insight into rate amplification at a lower temperature for vicinal diamine 12 formation via a aziridinium ion 14. Although most intermediates are not isolable by crystallization due to their intrinsic physical properties (oil or foamy solid), the reported synthesis furnished pure 1 without any chromatography purification throughout the entire synthesis. Employing green chemistry principles, this novel synthesis appears to be highly efficient for the manufacturing of multi-kilogram quantities of an optically-pure active pharmaceutical ingredient.     

Continental and Antarctic Lichens: isolation,identification and molecular modeling of the depside tenuiorin from the Antarctic lichen Umbilicaria antarctica as tau protein inhibitor

Abstract

Alzheimer´s disease (AD) is the most common form of dementia involving Aβ and tau protein. So far, AD cure remains elusive, but considering that AD progresses throughout tau pathology, which turns tau protein an appropriate target, besides tau is also included in other neurodegenerative disorders named as tauopathies. Here, we have isolated seventeen compounds belonging to six lichens species. Due to scarce of spectroscopic data of the compound 5,7-dihydroxy-6-methylphthalide, we explained their structural elucidation based on NMR data. In this study, we show that only tenuiorin from Umbilicaria antarctica inhibited 50% of tau 4R at 100?µM. Then, we shown that molecular interactions of tenuiorin with the steric zipper model of the hexapeptide ³⁰⁶VQIVYK³¹¹ were studied by docking calculations and the results suggested that tenuiorin forms both hydrogen bonds with lysine and glutamine side chains and forms several hydrophobic interactions with valine and lysine from ³⁰⁶VQIVYK³¹¹ motif.     

trans‐Selective Insertional Dihydroboration of a cis‐Diborene: Synthesis of Linear sp3‐sp2‐sp3‐Triboranes and Subsequent Cationization

The reaction of aryl‐ and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3‐trans‐dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis‐1,2‐μ‐H‐3‐hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base‐stabilized B₃H₄⁺ analogues.     

Effect of Ionic Liquid Structure on the Electrochemical Response of Dopamine at Room Temperature Ionic Liquid‐modified Carbon Paste Electrodes (IL–CPE)

In this work 12 different ionic liquids (ILs) have been used added as co‐binders in the preparation of modified carbon paste electrodes (IL–CPEs) used for the voltammetric analysis of dopamine in Britton‐Robinson buffer. The ionic liquids studied were selected based on three main criteria: (1) increasing chain length of alkyl substituents (studying 1‐ethylimidazolium and ethyl, propyl, butyl, hexyl and decylmethylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids); (2) nature of the counter ion (dicyanamide, bis(trifluoromethylsulfonyl)imide and hexafluorophosphate) in 1‐butyl‐3‐methylimidazolium ionic liquids; and (3) cation ring structures (1‐butyl‐3‐methylimidazolium, 1‐butyl‐1‐methylpiperidinium, 1‐butyl‐1‐methylpyrrolidinium and 1‐butyl‐3‐methylpyridinium) in bis(trifluoromethylsulfonyl)imide or hexafluorophosphate (1‐butyl‐3‐methylimidazolium or 1‐butyl‐3‐methylpyridinium as cations) ionic liquids. The use of IL as co‐binders in IL–CPE results in a general enhancement of both the sensitivity and the reversibility of dopamine oxidation. In square wave voltammetry experiments, the peak current increased up to a 400 % when 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide was used as co‐binder, as compared to the response found with the unmodified CPE. Experimental data provide evidence that electrostatic and steric effects are the most important ones vis‐à‐vis these electrocatalytic effects on the anodic oxidation of dopamine on IL–CPE. The relative hydrophilicity of dicyanamide anions reduced the electrocatalytic effects of the corresponding ionic liquids, while the use of 1‐ethyl‐3‐methylimidazolium hexafluorophosphate or 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide (two relatively small and highly hydrophobic ionic liquids) as co‐binders in IL–CPE resulted in the highest electrocatalytic activity among all of the IL–CPE studied.     

N‐(Tri­phenyl­methyl­sulfanyl)­phthal­imide

The title compound, C₂₇H₁₉NO₂S, contains chains of fused (19) rings formed by intermolecular C—H·O=C hydrogen bonds and running along the [011] and [01] directions. These chains are linked through short intermol­ecular C—H·π contacts, giving rise to sheets. The conformation of the title compound is dominated primarily by the nearly orthogonal lone‐pair orbitals on the N and S atoms.     

The consistency index in reciprocal matrices: Comparison of deterministic and statistical approaches

When checking the inconsistency level of a positive reciprocal matrix Saaty uses a deterministic criterion based on two parameters, a benchmark (the average), and a consistency level, usually 10%. Using results from a simulation experiment with 100,000 positive random reciprocal matrices of size varying from 3 to 15, we developed a probabilistic criterion and compare it to Saaty’s index. We found that if a positive reciprocal matrix is consistent according to the deterministic criterion is also consistent according to the probabilistic criterion only if we accept a higher than usual probability of Type I error. Reducing this error implies that the benchmark must be a small percentile of the probability distribution of the consistency index.     

Open tubular liquid chromatography: Recent advances and future trends

Nano-liquid chromatography (nanoLC) is gaining significant attention as a primary analytical technique across various scientific domains. Unlike conventional high-performance LC, nanoLC utilizes columns with inner diameters (i.ds.) usually ranging from 10 to 150 μm and operates at mobile phase flow rates between 10 and 1000 nl/min, offering improved chromatographic performance and detectability. Currently, most exploration of nanoLC has focused on particle-packed columns. Although open tubular LC (OTLC) can provide superior performance, optimized OTLC columns require very narrow i.ds. (< 10 μm) and demand challenging instrumentation. At the moment, these challenges have limited the success of OTLC. Nevertheless, remarkable progress has been made in developing and utilizing OTLC systems featuring narrow columns (< 2 μm). Additionally, significant efforts have been made to explore larger columns (10–75 μm i.d), demonstrating practical applicability in many situations. Due to their perceived advantages, interest in OTLC has resurged in the last two decades. This review provides an updated outlook on the latest developments in OTLC, focusing on instrumental challenges, achievements, and advancements in column technology. Moreover, it outlines selected applications that illustrate the potential of OTLC for performing targeted and untargeted studies.