Aromatic Heterocycles Research Articles

Exploration of pyridine-based self-assembled complexes-An overview

Pyridine is a heterocyclic aromatic compound with a six-membered ring that is essential for the design and synthesis of self-assembled complexes because of its unique electrical characteristics and intrinsic capacity to participate in various non-covalent interactions. Pyridine-based complexes have attracted much interest and are being used in modern science. They are invaluable in various industries due to their adaptability and unique qualities. These compounds function as catalysts in catalysis, quickening chemical reactions and promoting effective procedures. Additionally, they are essential to drug delivery systems because they guarantee the precise and regulated release of medicinal substances, improving treatment outcomes and lowering adverse effects. They are also helpful in biomedical imaging and used as contrast agents to produce detailed and crisp diagnostic images. Moreover, pyridine-based compounds play a crucial role in sensing and detection applications by selectively and sensitively identifying particular molecules or ions. Their versatility and wide range of applications highlight their importance in advancing science and technology. This review provides a comprehensive overview and analysis of the synthesis methods employed in creating a diverse range of novel pyridine-based complexes.

Exploring the potential of olive pomace derived activated charcoal as an efficient adsorbent for methylene blue dye: a comprehensive investigation of isotherms, kinetics, and thermodynamics

Methylene blue (MB) is a heterocyclic aromatic chemical compound used as a dye in various dyeing processes. The accumulation of such an organic compound poses a significant threat to both the environment and human health. Therefore, numerous biological, physical, and chemical processes have been established to remove MB dye, with adsorption being the most predominant dye-based treatment technology. In this context, the aim of this work was to evaluate the adsorption properties of activated carbon derived from olive pomace against methylene blue. To this end, scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDS), and Fourier transform infrared spectroscopy (FT-IR) analyses were carried out to confirm the adsorption of MB on carbon structures. In addition, the effect of contact time, pH, initial dye concentration, adsorbent dose, and temperature on the adsorption efficiency of MB was investigated. On the other hand, kinetic and isothermal models were used to further understand the adsorption mechanism, which showed a good correlation with the pseudo-second-order kinetic model and the Langmuir isotherm. Finally, thermodynamic analysis showed favorable conditions for physisorption, with the process being both endothermic and spontaneous.

Elucidating the Crystallization‐Caused Phosphorescence Quenching Mechanism to Achieve Efficient Photoactivated Persistent Luminescence for High‐Quality Light Printing

AbstractThe development of polymer‐based luminescent materials with efficient photoactivated ultralong organic phosphorescence (UOP) is of great importance but very challenging. Herein, a new class of organic phosphorescent luminogens is constructed by attaching phenyl rings and/or ethyl benzoates to the nitrogen atoms of a planar aromatic heterocycle pyrrolodiindole (PDI). The compounds show a significant elevation in phosphorescence emission capability after incorporating the ester group(s). However, they cannot produce room‐temperature phosphorescence in the crystalline state. These observations are identified to be associated with the formation of dimers and excimers and the motions of substituents within the molecules. In this context, the PDI derivatives are doped into epoxy polymers with compact and permanent 3D covalent networks. The resulting polymer films show reversible photoactivated UOP under ambient conditions, with quantum yields and lifetimes of up to 24.4% and 2.03 s, respectively, thereby enabling high‐quality and erasable light printing and multi‐level anti‐counterfeiting applications. In addition, they also exhibit excellent water and chemical resistance. This work is conducive to understanding the generation and decay mechanisms of the triplet excitons of organic luminophores with planar aromatic heterocycles in the crystalline state and provides a direction for the development of high‐performance photoactivated UOP materials.

Studies on the Thermal Decomposition Course of Nitrogen-Rich Heterocyclic Esters as Potential Drug Candidates and Evaluation of Their Thermal Stability and Properties.

Drug candidates must undergo thermal evaluation as early as possible in the preclinical phase of drug development because undesirable changes in their structure and physicochemical properties may result in decreased pharmacological activity or enhanced toxicity. Hence, the detailed evaluation of nitrogen-rich heterocyclic esters as potential drug candidates, i.e., imidazolidinoannelated triazinylformic acid ethyl esters 1-3 (where R1 = 4-CH3 or 4-OCH3 or 4-Cl, and R2 = -COOC2H5) and imidazolidinoannelated triazinylacetic acid methyl esters 4-6 (where R1 = 4-CH3 or 4-OCH3 or 4-Cl, and R2 = -CH2COOCH3)-in terms of their melting points, melting enthalpy values, thermal stabilities, pyrolysis, and oxidative decomposition course-has been carried out, using the simultaneous thermal analysis methods (TG/DTG/DSC) coupled with spectroscopic techniques (FTIR and QMS). It was found that the melting process (documented as one sharp peak related to the solid-liquid phase transition) of the investigated esters proceeded without their thermal decomposition. It was confirmed that the melting points of the tested compounds increased in relation to R1 and R2 as follows: 2 (R1 = 4-OCH3; R2 = -COOC2H5) < 6 (R1 = 4-Cl; R2 = -CH2COOCH3) < 5 (R1 = 4-OCH3; R2 = -CH2COOCH3) < 3 (R1 = 4-Cl; R2 = -COOC2H5) < 1 (R1 = 4-CH3; R2 = -COOC2H5) < 4 (R1 = 4-CH3; R2 = -CH2COOCH3). All polynitrogenated heterocyclic esters proved to be thermally stable up to 250 °C in inert and oxidising conditions, although 1-3 were characterised by higher thermal stability compared to 4-6. The results confirmed that both the pyrolysis and the oxidative decomposition of heterocyclic ethyl formates/methyl acetates with para-substitutions at the phenyl moiety proceed according to the radical mechanism. In inert conditions, the pyrolysis process of the studied molecules occurred with the homolytic breaking of the C-C, C-N, and C-O bonds. This led to the emission of alcohol (ethanol in the case of 1-3 or methanol in the case of 4-6), NH3, HCN, HNCO, aldehydes, CO2, CH4, HCl, aromatics, and H2O. In turn, in the presence of air, cleavage of the C-C, C-N, and C-O bonds connected with some oxidation and combustion processes took place. This led to the emission of the corresponding alcohol depending on the analysed class of heterocyclic esters, NH3, HCN, HNCO, aldehydes, N2, NO/NO2, CO, CO2, HCl, aromatics, and H2O. Additionally, after some biological tests, it was proven that all nitrogen-rich heterocyclic esters-as potential drug candidates-are safe for erythrocytes, and some of them are able to protect red blood cells from oxidative stress-induced damage.

Distribution and transfer of organics in the coagulation–anaerobic hydrolysis–aerobic treatment process of cutting fluid wastewaters

ABSTRACT Two kinds of real cutting fluid wastewater samples (i.e., sample A and sample B) and two kinds of coagulants (i.e., polymerized aluminum chloride (PAC) and polymeric iron sulfate (PFS)) were studied during coagulation experiment, and the coagulation effluent of sample B with PAC was utilized for subsequent anaerobic hydrolysis–aerobic treatment, and the molecular weight (MW) distribution and ultraviolet (UV) absorption spectroscopy were used to explore the distribution and transfer of organics of each treatment unit. The results showed that sample A and sample B both mainly contained macromolecular organics with MW &amp;gt; 100 kDa and small molecule organics with MW &amp;lt; 3 kDa, and PAC had significant coagulation performance for organics with MW &amp;gt; 100 kDa in both samples, while neither PAC nor PFS achieved good coagulation performance for the small molecule organics with MW &amp;lt; 3 kDa in both samples. It could be inferred by UV spectra that the coagulation effluent of sample A and B might both contain organics with conjugated double bonds, monocyclic aromatic hydrocarbons, and the coagulation effluent of sample B might also contain polycyclic aromatic hydrocarbons and heterocyclic compounds with low MW. MW distribution analysis and the UV spectra results showed that biological treatment could further remove organics with conjugated double bonds and aromatic compounds with MW &amp;lt; 3 kDa.

Elucidation of the Pyridine Ring-Opening Mechanism of 2,2'-Bipyridine or 1,10-Phenanthroline Ligands at Re(I) Carbonyl Complexes.

The cleavage of the C-N bonds of aromatic heterocycles, such as pyridines or quinolines, is a crucial step in the hydrodenitrogenation (HDN) industrial processes of fuels in order to minimize the emission of nitrogen oxides into the atmosphere. Due to the harsh conditions under which these reactions take place (high temperature and H2 pressure), the mechanism by which they occur is only partially understood, and any study at the molecular level that reveals new mechanistic possibilities in this area is of great interest. Herein, we unravel the pyridine ring-opening mechanism of 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) ligands coordinated to the cis-{Re(CO)2(N-RIm)(PMe3)} (N-RIm= N-alkylimidazole) fragment under mild conditions. Computational calculations show that deprotonation of the pyridine ring, once dearomatized, is crucial to induce ring contraction, triggering extrusion of the nitrogen atom from the ring and cleavage of the C-N bond. It is noteworthy that different products (regioisomers) are obtained depending on whether the ligand used is bipy or phen due to the additional rigidity and stability conferred by the central ring of the phen ligand, an issue also addressed and clarified computationally. Strong support for the proposed mechanism is provided by the characterization and isolation, including three single-crystal X-ray diffraction structures, of several of the proposed reaction intermediates.

Isomorphic Fluorescent Nucleosides.

In 1960, Weber prophesied that "There are many ways in which the properties of the excited state can be utilized to study points of ignorance of the structure and function of proteins". This has been realized, illustrating that an intrinsic and highly responsive fluorophore such as tryptophan can alter the course of an entire scientific discipline. But what about RNA and DNA? Adapting Weber's protein photophysics prophecy to nucleic acids requires the development of intrinsically emissive nucleoside surrogates as, unlike Trp, the canonical nucleobases display unusually low emission quantum yields, which render nucleosides, nucleotides, and oligonucleotides practically dark for most fluorescence-based applications.Over the past decades, we have developed emissive nucleoside surrogates that facilitate the monitoring of nucleoside-, nucleotide-, and nucleic acid-based transformations at a nucleobase resolution in real time. The premise underlying our approach is the identification of minimal atomic/structural perturbations that endow the synthetic analogs with favorable photophysical features while maintaining native conformations and pairing. As illuminating probes, the photophysical parameters of such isomorphic nucleosides display sensitivity to microenvironmental factors. Responsive isomorphic analogs that function similarly to their native counterparts in biochemical contexts are defined as isofunctional.Early analogs included pyrimidines substituted with five-membered aromatic heterocycles at their 5 position and have been used to assess the polarity of the major groove in duplexes. Polarized quinazolines have proven useful in assembling FRET pairs with established fluorophores and have been used to study RNA-protein and RNA-small-molecule binding. Completing a fluorescent ribonucleoside alphabet, composed of visibly emissive purine (thA, thG) and pyrimidine (thU, thC) analogs, all derived from thieno[3,4-d]pyrimidine as the heterocyclic nucleus, was a major breakthrough. To further augment functionality, a second-generation emissive RNA alphabet based on an isothiazolo[4,3-d]pyrimidine core (thA, tzG, tzU, and tzC) was fabricated. This single-atom "mutagenesis" restored the basic/coordinating nitrogen corresponding to N7 in the purine skeleton and elevated biological recognition.The isomorphic emissive nucleosides and nucleotides, particularly the purine analogs, serve as substrates for diverse enzymes. Beyond polymerases, we have challenged the emissive analogs with metabolic and catabolic enzymes, opening optical windows into the biochemistry of nucleosides and nucleotides as metabolites as well as coenzymes and second messengers. Real-time fluorescence-based assays for adenosine deaminase, guanine deaminase, and cytidine deaminase have been fabricated and used for inhibitor discovery. Emissive cofactors (e.g., SthAM), coenzymes (e.g., NtzAD+), and second messengers (e.g., c-di-tzGMP) have been enzymatically synthesized, using xyNTPs and native enzymes. Both their biosynthesis and their transformations can be fluorescently monitored in real time.Highly isomorphic and isofunctional emissive surrogates can therefore be fabricated and judiciously implemented. Beyond their utility, side-by-side comparison to established analogs, particularly to 2-aminopurine, the workhorse of nucleic acid biophysics over 5 decades, has proven prudent as they refined the scope and limitations of both the new analogs and their predecessors. Challenges, however, remain. Associated with such small heterocycles are relatively short emission wavelengths and limited brightness. Recent advances in multiphoton spectroscopy and further structural modifications have shown promise for overcoming such barriers.

Sorption of Polycyclic Aromatic Sulfur Heterocycles (PASH) on Nylon Microplastics at Environmentally Relevant Concentrations.

Microplastics have garnered an infamous reputation as a sorbate for many concerning environmental pollutants and as a delivery vehicle for the aquatic food chain through the ingestion of these contaminated small particulates. While sorption mechanisms have been extensively studied for polycyclic aromatic hydrocarbons, polycyclic aromatic sulfur heterocycles (PASHs) have not been investigated, partly due to their low concentrations in aquatic ecosystems. Herein, an analytical methodology is presented for the analysis of dibenzothiophene, benzo[b]naphtho[1,2-b]thiophene, benzo[b]naphtho[2,1-b]thiophene, benzo[b]naphtho[2,3-b]thiophene, chryseno[4,5-bcd]thiophene and dinaphtho[1,2-b:1',2'-d]thiophene at relevant environmental concentrations based on solid phase extraction and high-performance liquid chromatography. The sorption uptake behavior and the sorption kinetics of the three benzo[b]napthothiophene isomers were then investigated on nylon microplastics to provide original information on their environmental fate and avoid human contamination through the food chain. The obtained information might also prove relevant to the development of successful remediation approaches for aquatic ecosystems.

The effects of co-existing acridine on adsorption-desorption behavior of carbazole in soils: Co-sorption and mechanism insight

Carbazole (CBZ) and acridine (ACR) are polycyclic aromatic nitrogen heterocycles (PANHs) widely found in combined contaminated soils, while investigations on organic-organic interactions have been very limited. In this study, batch experiments were carried out on five soils with different properties, taking CBZ as a representative of PANHs and ACR as a co-existing contaminant. The adsorption isotherms of CBZ (50–1000 μg/L) were nonlinear. Soil organic matter (SOM) and cation exchange capacity (CEC) showed positive correlations with CBZ adsorption-desorption coefficients. The adsorption mechanisms of CBZ involved hydrogen bonding, π-π interaction, and cation-π bonding. Different concentrations of ACR had varying effects on CBZ. The adsorption of CBZ was inhibited with 250 μg/L ACR. The cooperative adsorption was observed on three soils with increasing ACR concentration (1000 μg/L) and led to more pronounced nonlinear isotherms. The S-shaped isotherms of ACR indicated that ACR was adsorbed to the soil surface in a perpendicular configuration. New adsorption sites were created allowing for increased CBZ adsorption through π-π interaction with ACR. Therefore, variations in soil properties and potential impacts of co-existing contaminants should be well considered when assessing the combined pollution of site soil. This will contribute to a more accurate estimation of environmental and health risks.

Synthesis, crystal structure, and spectroscopic characterization of a new non-centrosymmetric compound, 1-(2-chloroquinolin-3-yl)-N-(4-fluorobenzyl)methanimine

In this work, we report the synthesis and characterization of a new condensed aromatic heterocycle (1-(2-chloroquinolin-3-yl)-N-(4-fluorobenzyl)methanimine) useful in various fields, mainly in medicinal and therapeutic chemistry, with interesting biological properties. Characterization of the title compound was carried out by 1H, 13C, 19F nuclear magnetic resonance and X-ray diffraction techniques. The crystal structure reveals that title compound crystallizes in the monoclinic system and crystal data for C17H12ClFN2: monoclinic, space group P21 (no. 4), a = 7.2253(10) Å, b = 5.7720(10) Å, c = 17.105(2) Å, β = 95.338(10)°, V = 710.26(18) Å3, Z = 2, T = 298(2) K, μ(MoKα) = 0.274 mm-1, Dcalc = 1.397 g/cm3, 5010 reflections measured (4.784° ≤ 2Θ ≤ 54.324°), 3160 unique (Rint = 0.0501, Rsigma = 0.0506) which were used in all calculations. The final R1 was 0.0339 (I &gt; 2σ(I)) and wR2 was 0.0907 (all data). The obtained molecular structure has an antiparallel arrangement of the molecular unit leading to a one-dimensional framework.

Preparation, Characterization, and Antiangiogenic Evaluation of a Novel 5-Fluorouracil Derivative Solid Lipid Nanoparticle with a Hen's Egg Chorioallantoic Membrane Assay and Wound Healing Response in HaCaT Keratinocytes.

5-Fluorouracil is a heterocyclic aromatic organic compound, and it is commonly used as a chemotherapeutic agent in many cancers. The present goal is to analyze and characterize the physicochemical and biological properties of a new therapeutic formulation of 5-FUD-Gal under simulated chronic wound and oxidative stress conditions. After synthesis of a new 5-fluorouracil derivative, preparation and characterization of the formulation were carried out. The antiangiogenic effect, wound healing, and oxidative stress responses were conducted with a HET-CAM assay and in vitro cell culture technique. The results initially demonstrated that 5-FUD-Gal synthesized by a series of reactions and the SLN formulation were prepared successfully. A strong cell protective effect above 98% cell viability was detected at 20 μM at 48 h. The wound closure of the HaCaT scratch assay was calculated to be 90.12 and 98.98% at 10 and 20 μM concentrations, respectively, at 48 h. Moreover, the strongest effect of 5-FUD-Gal-F was observed at 20 μM concentration on chicken embryos. This study provides novel insights that a new derivative of semisynthetic 5-FUD-Gal-F can be further evaluated as a therapeutic chemical compound in cancer disease.

Structure evolution characteristic of hydrochar and nitrogen transformation mechanism during co-hydrothermal carbonization process of microalgae and biomass

Co-hydrothermal carbonization (co-HTC) of microalgae and lignocellulosic biomass has high potential for producing nitrogen-rich carbon materials (hydrochar) with relatively high yield. The synergistic effect, hydrochar structure evolution and nitrogen transformation mechanism during the co-HTC process were depicted in depth. The results of the co-HTC process showed that the positive synergy between biomass and microalgae could improve the hydrochar yield and facilitate incorporation of nitrogen into the hydrochar aromatic heterocycles structures. Moderate reaction conditions were beneficial for co-HTC hydrochar nitrogen enrichment and porosity increment, and the optimal nitrogen content and specific surface area reached 3.50% and 5.91 m2/g in co-HTC hydrochars at 240 °C and 1 h. Severe reaction conditions could enhance the formation of stable heterocyclic nitrogen species (reaching 54% at 300 °C). The hydrochar structure evolution and nitrogen transformation mechanism during co-HTC process could be generally divided into two stages. The first stage took place from 180 to 260 °C, and the nitrogen-rich secondary chars could be formed by the interaction of the hydrolysis intermediates. The second stage occurred from 260 to 300 °C, and the previously formed secondary char would be gradually decomposed. This study provides theoretical guidance for regulating the co-HTC process to produce nitrogen-rich carbon materials.

Tunable molecular editing of indoles with fluoroalkyl carbenes.

Building molecular complexity from simple feedstocks through precise peripheral and skeletal modifications is central to modern organic synthesis. Nevertheless, a controllable strategy through which both the core skeleton and the periphery of an aromatic heterocycle can be modified with a common substrate remains elusive, despite its potential to maximize structural diversity and applications. Here we report a carbene-initiated chemodivergent molecular editing of indoles that allows both skeletal and peripheral editing by trapping an electrophilic fluoroalkyl carbene generated in situ from fluoroalkyl N-triftosylhydrazones. A variety of fluorine-containing N-heterocyclic scaffolds have been efficiently achieved through tunable chemoselective editing reactions at the skeleton or periphery of indoles, including one-carbon insertion, C3 gem-difluoroolefination, tandem cyclopropanation and N1 gem-difluoroolefination, and cyclopropanation. The power of this chemodivergent molecular editing strategy has been highlighted through the modification of the skeleton or periphery of natural products in a controllable and chemoselective manner. The reaction mechanism and origins of the chemo- and regioselectivity have been probed by both experimental and theoretical methods.

Pulsed Laser Manufactured Heteroatom Doped Carbon Dots via Heterocyclic Aromatic Hydrocarbons for Improved Tribology Performance.

Traditional laser-assisted method (top-down synthesis strategy) is applied in the preparation of carbon dots (CDs) by cutting larger carbon materials, which requires harsh conditions, and the size distribution of the CDs is seldom monodisperse. In this work, heteroatom-doped CDs, represented by N,S co-doped CDs (N,S-CDs), can be prepared successfully by pulsed laser irradiation of heterocyclic aromatic hydrocarbons-based small molecule compound solution. The friction coefficient (COF) of base oil PAO decreases from 0.650 to 0.093, and the wear volume reduces by 92.0% accompanied by 1 wt.% N,S-CDs addition, while the load-bearing capacity is improved from 100 to 950 N. The excellent lubrication performance is mainly attributed to the formation of a robust tribofilm via a tribochemical reaction between N,S-CDs and friction pairs, and the N,S-CDs can play a mending effect and polishing effect for worn surfaces. Furthermore, the lubricant containing heteroatom doped CDs are capable of being prepared in situ via pulsed laser irradiation of heterocyclic aromatic hydrocarbons in base oil, which can avoid the redispersed problem of nano-additive in base oil to maintain long-term dispersion, with COF of 0.103 and low wear volume ≈1.99 × 105 µm3 (76.9% reduction) even after standing for 9 months.

Organic Donor-Acceptor Complexes As Potential Semiconducting Materials.

In this review article, the synthesis, characterization and physico-chemical properties of the organic donor-acceptor complexes are highlighted and a special emphasis has been placed on developing them as semiconducting materials. The electron-rich molecules, i. e., donors have been broadly grouped in three categories, namely polycyclic aromatic hydrocarbons, nitrogen heterocycles and sulphur containing aromatic donors. The reactions of these classes of the donors with the acceptors, namely tetracyanoquinodimethane (TCNQ), tetracyanoethylene (TCNE), tetracyanobenzene (TCNB), benzoquinone, pyromellitic dianhydride and pyromellitic diimides, fullerenes, phenazine, benzothiadiazole, naphthalimide, DMAD, maleic anhydride, viologens and naphthalene diimide are described. The potential applications of the resulting DA complexes for physico-electronic purposes are also included. The theoretical investigation of many of these products with a view to rationalise their observed physico-chemical properties is also discussed.

A validated approach for analysis of heterocyclic aromatic compounds in sediment samples

The scientific literature is replete with analytical methods for the analysis of homocyclic aromatic compounds especially polycyclic aromatic hydrocarbons and their alkylated analogs. However, there is a paucity of methods for the analysis of nitrogen-, sulfur- and oxygen-containing polycyclic aromatic compounds (PACs). The lack of commercially available analytical standards, the presence of many structural derivatives and isomers and lack of certified reference materials all contribute to the inherent challenges in measuring these compounds. Gas chromatography coupled with a tandem mass spectrometer was used to develop two multiple reaction monitoring methods to detect and quantify fifty-three non-halogenated and halogenated hetero-polycyclic aromatic compounds (HPACs). Because of their greater polarity, strongly non-polar solvents typically employed to extract homocyclic PACs from sediment samples did not yield acceptable recoveries of our target analytes. By adding ethyl acetate to dichloromethane (50:50), recoveries of our target analytes using accelerated solvent extraction increased markedly. The performance characteristics of the validated method including accuracy [> than 67% for 46 (out of 53) analytes], inter- and intra-day precision [<30% for all analytes, (expressed as relative standard deviation)], limits of detection (0.1 to 2.3 ng/g) and quantitation (1.5 to 7.6 ng/g) imply that the method is fit for its intended purpose. A sediment sample from a known contaminated site in Canada was analyzed for both homo- and hetero-PACs. Measured concentrations of Σ27HPAC (7.3 μg/g, dry weight) were significantly smaller (p<0.05) than Σ16PAHs (80.9 μg/g, dry weight) and Σ30Alkylated-PAHs (14.2 μg/g, dry weight). These results suggest that the developed method is an effective and efficient approach for the targeted analysis of HPACs and their halogenated derivatives in sediment samples.

Shaping Chirality via Stereoselective, Organocatalytic [4+2] Cycloadditions involving Heterocyclic ortho-Quinodimethanes.

Polycyclic compounds bearing a complex heterocyclic core such as an aromatic heterocycle "fused" with one or more functionalized rings, are widespread leading molecules in the domain of synthetic organic chemistry and pharmaceuticals. Although many synthetic methodologies have been devised to access achiral, fused heteroaromatic scaffolds, or related chiral variants adorned with out-of-cycle stereogenic elements, equally efficient strategies to afford chiral heterocycles featuring in-cycle stereocenters, exist to a lesser extent and presently represent a growing field of investigation. The mild, organocatalytic generation of elusive ortho-quinodimethane intermediates (oQDMs), derived from suitable heteroaromatic carbonyl- or carbonyl-like pronucleophiles has recently proved successful in the synthesis of such peculiar chiral architectures via stereoselective [4+2] cycloadditions. This review provides an overview of the most important advances attained in this field over the last decade.

14N to 15N Isotopic Exchange of Nitrogen Heteroaromatics through Skeletal Editing.

The selective modification of nitrogen heteroaromatics enables the development of new chemical tools and accelerates drug discovery. While methods that focus on expanding or contracting the skeletal structures of heteroaromatics are emerging, methods for the direct exchange of single core atoms remain limited. Here, we present a method for 14N → 15N isotopic exchange for several aromatic nitrogen heterocycles. This nitrogen isotope transmutation occurs through activation of the heteroaromatic substrate by triflylation of a nitrogen atom, followed by a ring-opening/ring-closure sequence mediated by 15N-aspartate to effect the isotopic exchange of the nitrogen atom. Key to the success of this transformation is the formation of an isolable 15N-succinyl intermediate, which undergoes elimination to give the isotopically labeled heterocycle. These transformations occur under mild conditions in high chemical and isotopic yields.

The Pharmaceutical Industry in 2023: An Analysis of FDA Drug Approvals from the Perspective of Molecules.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 marks the second-best yearly FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with the most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody-drug conjugates (ADCs) have been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year's harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs after the withdrawal of peginesatide from the market in 2013. Following the trends in recent years, two bispecific drugs have been authorized in 2023. As in the preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Enhancing characterization of organic nitrogen components in aerosols and droplets using high-resolution aerosol mass spectrometry

Abstract. This study aims to enhance the understanding and application of the Aerodyne high-resolution aerosol mass spectrometer (HR-AMS) for the comprehensive characterization of organic nitrogen (ON) compounds in aerosol particles and atmospheric droplets. To achieve this goal, we analyzed 75 N-containing organic compounds, representing a diverse range of ambient non-organonitrate ON (NOON) types, including amines, amides, amino acids, N heterocycles, protein, and humic acids. Our results show that NOON compounds can produce significant levels of NHx+ and NOx+ ion fragments, which are typically recognized as ions representative of inorganic nitrogen species. We also identified the presence of CH2N+ at m/z = 28.0187, an ion fragment rarely quantified in ambient datasets due to substantial interference from N2+. As a result, the utilization of an updated calibration factor of 0.79 is necessary for accurate NOON quantification via the HR-AMS. We also assessed the relative ionization efficiencies (RIEs) for various NOON species and found that the average RIE for NOON compounds (1.52 ± 0.58) aligns with the commonly used default value of 1.40 for organic aerosol. Moreover, through a careful examination of the HR-AMS mass spectral features of various NOON types, we propose fingerprint ion series that can aid the NOON speciation analysis. For instance, the presence of CnH2n+2N+ ions is closely linked with amines, with CH4N+ indicating primary amines, C2H6N+ suggesting secondary amines, and C3H8N+ representing tertiary amines. CnH2nNO+ ions (especially for n values of 1–4) are very likely derived from amides. The co-existence of three ions, C2H4NO2+, C2H3NO+, and CH4NO+, serves as an indicator for the presence of amino acids. Additionally, the presence of CxHyN2+ ions indicates the occurrence of 2N-heterocyclic compounds. Notably, an elevated abundance of NH4+ is a distinct signature for amines and amino acids, as inorganic ammonium salts produce only negligible amounts of NH4+ in the HR-AMS. Finally, we quantified the NOON contents in submicron particles (PM1) and fog water in Fresno, California, and PM1 in New York City (NYC). Our results revealed the substantial presence of amino compounds in both Fresno and NYC aerosols, whereas concurrently collected fog water in Fresno contained a broader range of NOON species, including N-containing aromatic heterocycle (e.g., imidazoles) and amides. These findings highlight the significant potential of employing the widespread HR-AMS measurements of ambient aerosols and droplets to enhance our understanding of the sources, transformation processes, and environmental impacts associated with NOON compounds in the atmosphere.