Primary Amines Research Articles

Formation of Nitrosamines from the Heterogeneous Reaction of Nitrous Acid and Organic Amines in Indoor Environments.

Carcinogenic nitrosamines have been widely studied due to their risk to human health. However, the universality and evolutionary processes of their generation, particularly concerning their secondary sources, remain unclear at present. We demonstrated through laboratory flow tube experiments that corresponding nitrosamines were generated from heterogeneous reactions of nitrous acid (HONO) with five structurally diverse amines commonly found indoors, including diphenylamine (DPhA), dibenzylamine (DBzA), dioctylamine (DOtA), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), and N-phenyl-1-naphthylamine (PANA). The heterogeneous reaction rate constants of DBzA and DOtA with HONO (∼70 ppb) were 1.21 × 10-3 and 2.13 × 10-3 min-1 at 30% relative humidity (RH), resulting in a lifetime of 13.8 and 7.8 h. As compared to higher RH (∼80%), more nitrosamines were produced from the reaction of HONO with surface-sorbed DBzA, DOtA, 6PPD, and PANA at lower RH (30%), with product yields ranging from <0.1% to 0.5%. Furthermore, we observed the formation of nitroso-6PPDs and nitro-6PPDs during room air exposure of 6PPD in a genuine indoor environment, in addition to various other transformation products indicative of reactions of 6PPD with HONO, NOx, and ozone indoors. This study confirmed the universality of the heterogeneous reaction of surface-sorbed amine with HONO as a source of nitrosamines indoors.

Substrate and Product Selective Supramolecular Catalysis by Pillar[5]arene in the Alkylation of Primary Linear Amines with Allyl Bromide

Substrate and Product Selective Supramolecular Catalysis by Pillar[5]arene in the Alkylation of Primary Linear Amines with Allyl Bromide

Modular Design and Self-assembly of pH-Responsive Multidomain Peptides Incorporating Non-natural Ionic Amino Acids.

Stimuli-responsive peptides, particularly pH-responsive variants, hold significant promise in biomedical and technological applications by leveraging the broad pH spectrum inherent to biological environments. However, the limited number of natural pH-responsive amino acids within biologically relevant pH ranges presents challenges for designing rational pH-responsive peptide assemblies. In our study, we introduce a novel approach by incorporating a library of non-natural amino acids featuring chemically diverse tertiary amine side chains. Hydrophobic and ionic properties of these non-natural amino acids facilitate their incorporation into the assembly domain when uncharged, and electrostatic repulsion promotes disassembly under lower pH conditions. Furthermore, we observed a direct relationship between the number of substitutions and the hydrophobicity of these amino acids, influencing their pH-responsive properties and enabling rational design based on desired transitional pH ranges. The structure-activity relationship of these pH-responsive peptides was evaluated by assessing their antimicrobial properties, as their antimicrobial activity is triggered by the disassembly of peptides to release active monomers. This approach not only enhances the specificity and controllability of pH responsiveness but also broadens the scope of peptide materials in biomedical and technological applications.

Amine Exchange of Aminoalkylated Phenols as Dynamic Reaction in Benzoxazine/Amine-Based Vitrimers.

Bisfunctional benzoxazine and polyether diamine-based polymers show Arrhenius-like stress-relaxation varying with stoichiometry and polymerization temperatures proving vitrimeric behavior. Molecular structural investigations reveal the presence of different aminoalkylated phenols occurring at varying ratios depending on polymer composition and polymerization conditions. The vitrimeric mechanism is found to involve an amine exchange reaction of aminoalkylated phenols in an equilibrium reaction like a nucleophilic substitution reaction. As determined by molecular studies and dissolution experiments in reactive solvents, aliphatic and aromatic primary as well as aliphatic secondary amines in the polybenzoxazine structure can act as nucleophiles in reaction with electrophilic methylene bridges. Thus, aminoalkylated phenols proved to be a relevant structural motif resulting in a vitrimeric polybenzoxazine due to amine exchange reaction.

Cyclic carbamates based on (R)-(+)-limonene oxide for ring-opening polymerization

A novel synthetic pathway for synthesizing isocyanate-free polyurethanes is reported here. β-Amino alcohols were efficiently synthesized from the aminolysis of the epoxide ring of (R)-(+)-limonene oxide with different primary amines as nucleophiles and hot water as catalysts. The regio- and diastereoselectivities of the reactions were investigated and supported by computational studies. DFT calculations were performed to understand the experimental results more deeply. It confirmed the crucial roles of water molecules and the nature of the nucleophile in forming the products. The formation of the product is entirely driven by the free energy of activation that affects the reaction rate. Cyclic carbamates were prepared from β-amino alcohols using the dialkyl carbonate (DAC) chemistry. An oligourethane was obtained from Anionic Ring-Opening Polymerization (AROP) of a cyclic carbamate derived from (R)-(+)-limonene-oxide. All the products were characterized by employing 1H and 13C NMR spectroscopies. The assignments of the signals in 1H and 13C NMR spectra were also supported by 2D NMR spectroscopy.

Combination energetic materials consisting of strained rings combined with high heat of formation tetrazoles.

The reaction of cyanogen azide with strained-ring containing primary and secondary amines led to the isolation of energetic molecules deriving their energy content from both strained rings as well as aminotetrazoles. Azo-coupling of these materials afforded novel high-nitrogen energetic materials of very high sensitivity. All compounds were chemically characterized by IR, NMR, single-crystal X-ray crystallography, and high-resolution mass spectrometry. Their impact and friction sensitivities were experimentally determined, and their energetic performances were calculated.

Enhanced Delivery of Biomolecules into Caco2 Cells Based on the Cell-Penetrating Ability of Keratin Peptides.

Keratin, as a promising bioresource, possesses significant potential for diverse biological applications due to its favorable biocompatibility, low toxicity, biodegradability, and cell adhesion ability. However, there are few studies on the cell-penetrating ability of keratin peptides (KEPs) for biomolecule delivery. Therefore, this study explored the cell-penetrating ability of KEPs with different molecular weights (Mw) on Caco2 cells using fluorescein-labeled insulin (FITC-INS) as the target intracellular biomolecule. The potential cell-penetrating mechanism was elaborated by combining cellular investigation with the physicochemical characterization of KEPs. The result shows that the KEPs <3 kDa (KEP1) exhibited the highest cell-penetrating ability at 2 mg/mL, allowing efficient delivery of FITC-INS into Caco2 cells without covalent bonding. The cellular uptake mechanism was energy-dependent, mainly involving macropinocytosis. The further fractionation of KEP1 reveals that the most effective components consisted of 8-19 amino acids, including specific hydrophobic peptides (e.g., RVVIEPSPVVV and IIIQPSPVVV), PPII amphipathic peptides (e.g., PPPVVVTFP and FIQPPPVVV), and Cys-rich peptides (e.g., LCAPTPCGPTPL and CLPCRPCGPTPL). Additionally, analysis of the secondary and tertiary structure and amino acid composition illustrated that KEP1 exhibited rich hydrophobic residues and disulfide bonds, which probably contributed to its cell-penetrating ability, as opposed to its small particle size and electrostatic interactions. This study reveals the cell-penetrating ability of KEPs, thus highlighting their potential as biomaterials for noncovalently delivering biomolecules.

Unraveling the Metal–Ligand Cooperativity in a Phosphine-Free Mn(II)-Catalyzed Transfer Hydrogenation of Nitriles to Primary Amines and Dehydrogenation of Dimethylamine Borane

Unraveling the Metal–Ligand Cooperativity in a Phosphine-Free Mn(II)-Catalyzed Transfer Hydrogenation of Nitriles to Primary Amines and Dehydrogenation of Dimethylamine Borane

Mechanistic Insights into Curvature Formation in Synthetic Vesicles.

The mimicking of natural lipid bilayers with synthetic amphiphilic systems is of great interest to researchers, as insights could lead to better understanding of the complexities of cell membranes, as well as new materials and healthcare technologies. Recapitulating natural lipid asymmetry across bilayer membranes has important implications for curvature in cell, vesicle, and organelle morphologies, but has been challenging to achieve with synthetic lipid combinations or standard amphiphilic block copolymers. In a recent article, Elizebath et al. report the synthesis of a new type of synthetic amphiphile able to induce asymmetry in an artificial bilayer membrane dynamically. The molecules were designed around an extended π-conjugated hydrophobic core with tertiary amine-terminated oxyalkylene side chains. Protonation of the tertiary amines on the bilayer exterior leads to curvature induction, bilayer fission, and vesicle formation as monitored by time-resolved spectroscopy techniques and microscopy. The results were further validated with density functional theory (DFT) calculations. The delicate balance between different molecular scale interactions in the supramolecular structures led to the dynamic transformation of the bilayer membranes. Insights described could be used to advance the assembly of hierarchical life-like materials.

Mechanistic Insights into Curvature Formation in Synthetic Vesicles

AbstractThe mimicking of natural lipid bilayers with synthetic amphiphilic systems is of great interest to researchers, as insights could lead to better understanding of the complexities of cell membranes, as well as new materials and healthcare technologies. Recapitulating natural lipid asymmetry across bilayer membranes has important implications for curvature in cell, vesicle, and organelle morphologies, but has been challenging to achieve with synthetic lipid combinations or standard amphiphilic block copolymers. In a recent article, Elizebath et al. report the synthesis of a new type of synthetic amphiphile able to induce asymmetry in an artificial bilayer membrane dynamically. The molecules were designed around an extended π‐conjugated hydrophobic core with tertiary amine‐terminated oxyalkylene side chains. Protonation of the tertiary amines on the bilayer exterior leads to curvature induction, bilayer fission, and vesicle formation as monitored by time‐resolved spectroscopy techniques and microscopy. The results were further validated with density functional theory (DFT) calculations. The delicate balance between different molecular scale interactions in the supramolecular structures led to the dynamic transformation of the bilayer membranes. Insights described could be used to advance the assembly of hierarchical life‐like materials.

Coplanar Atropochiral 5H-Cyclopenta[2,1-b:3,4-b']dipyridine Ligands: Synthesis and Applications in Asymmetric Ring-Opening Reaction.

Bipyridines represent a class of ligands renowned for their versatility and efficacy in numerous transition metal-catalyzed reactions. Chiral bipyridine ligands are noted for their distinctive reactivity and stereoselectivity. In this work, we have designed and synthesized a class of bipyridine ligands endowed with an axially chiral scaffold. These ligands feature: (a) a precisely aligned coplanar bipyridine framework that is beneficial for metal chelation; (b) a spacious environment around the metal-bipyridine complexes, capable of hosting substrates with substantial steric bulk; (c) a chiral pocket induced by the axially chiral architecture. These atropochiral planar bipyridine ligands were successfully applied in copper-catalyzed ring-opening reactions of cyclic diaryliodoniums with bulky secondary amines, achieving high efficiency and stereoselectivity that were unsuccessful in our previous efforts.

Reversible Local Protonation-Deprotonation: Tuning Stimuli-Responsive Circularly Polarized Luminescence in Chiral Hybrid Zinc Halides for Anti-Counterfeiting and Encryption.

Precise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli-responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)-C12H16N2)ZnBr4 ((R/S-LH2)ZnBr4) and monoprotonated ((R/S)-C12H15N2)2ZnBr4 ((R/S-LH1)2ZnBr4), derived from the chiral organic amine (R/S)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine ((R/S)-C12H14N2). These compounds showcase luminescent properties; the zero-dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo-layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation-deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation-deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli-responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications in information storage, anti-counterfeiting, and information encryption.

Electrochemically Gated Frustrated Lewis Pair Chemistry in Electric Double Layer.

The recent discovery of frustrated Lewis pairs (FLPs) during the activation of small molecules has inspired extensive research across the full span of chemical science. Owing to the nature of weak interactions, it is experimentally challenging to directly observe and modulate FLP at the molecular scale. Here we design a boron cluster anion building block (B10H82-) and organic amine cations ([NR4]+, R= -CH3, -C2H5) as the FLP to prove the feasibility of controlling their interaction in the electric double layer (EDL) via an electrochemical strategy. In situ single-molecule electrical measurements and Raman monitoring of B10H82--[NR4]+ FLP formed at the positively charged Au(111) electrode surface, in contrast to the free-standing B10H82- near or below the potential of zero charge (PZC). Furthermore, this FLP chemistry leads to a shift in the local density of states of boron clusters towards the EF for enhancing electron transport, providing a new prototype of a reversible single-cluster switch that digitally switches upon controlling FLP chemistry in the electric double layer.

Reversible Local Protonation‐Deprotonation: Tuning Stimuli‐Responsive Circularly Polarized Luminescence in Chiral Hybrid Zinc Halides for Anti‐Counterfeiting and Encryption

AbstractPrecise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli‐responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)‐C12H16N2)ZnBr4 ((R/S‐LH2)ZnBr4) and monoprotonated ((R/S)‐C12H15N2)2ZnBr4 ((R/S‐LH1)2ZnBr4), derived from the chiral organic amine (R/S)‐2,3,4,9‐Tetrahydro‐1H‐carbazol‐3‐amine ((R/S)‐C12H14N2). These compounds showcase luminescent properties; the zero‐dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo‐layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation‐deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation‐deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli‐responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications in information storage, anti‐counterfeiting, and information encryption.

Electrochemically Gated Frustrated Lewis Pair Chemistry in Electric Double Layer

The recent discovery of frustrated Lewis pairs (FLPs) during the activation of small molecules has inspired extensive research across the full span of chemical science. Owing to the nature of weak interactions, it is experimentally challenging to directly observe and modulate FLP at the molecular scale. Here we design a boron cluster anion building block (B10H82‐) and organic amine cations ([NR4]+, R= ‐CH3, ‐C2H5) as the FLP to prove the feasibility of controlling their interaction in the electric double layer (EDL) via an electrochemical strategy. In situ single‐molecule electrical measurements and Raman monitoring of B10H82‐–[NR4]+ FLP formed at the positively charged Au(111) electrode surface, in contrast to the free‐standing B10H82‐ near or below the potential of zero charge (PZC). Furthermore, this FLP chemistry leads to a shift in the local density of states of boron clusters towards the EF for enhancing electron transport, providing a new prototype of a reversible single‐cluster switch that digitally switches upon controlling FLP chemistry in the electric double layer.

Piperazine-Based Mixed Solvents for CO2 Capture in Bubble-Column Scrubbers and Regeneration Heat

This work used piperazine (PZ) as a base solvent, blended individually with five amines, which were monoethanolamine (MEA), secondary amines (DIPAs), tertiary amines (TEAs), stereo amines (AMPs), and diethylenetriamine (DETA), to prepare mixed solvents at the desired concentrations as the test solvents. A continuous bubble-column scrubber with one stage (1 s) was first used for the test. Six parameters were selected, including the type of mixed solvent (A), the ratio of mixed solvents (B), the solvent feed rate (C), the gas flow rate (D), the concentration of the mixed solvents (E), and the liquid temperature (F), each one having five levels. Using the Taguchi experimental design, only 25 runs were required. The outcome data, such as the absorption efficiency (EF), the absorption rate (RA), the overall mass-transfer coefficient (KGa), and the absorption factor (φ), could be determined under steady-state conditions. The optimal mixed solvents were found to be A1 (PZ + MEA) and A2 (PZ + DIPA). The parameter importance and optimal conditions for EF, RA, KGa, and ϕ were determined separately; the verification of all optimal conditions was successful. This analysis found that the importance of the parameters was D &gt; C &gt; A &gt; E &gt; B &gt; F, and the gas flow rate (D) was the most important factor. Subsequently, multiple-stage scrubbers were used to capture CO2. Comparing 1 s and 3 s (three-stage scrubber), EF, RA, KGa, and φ increased by 33%, 29%, 22%, and 38%, respectively. The desorption tests for the four optimal scrubbed solutions, including multiple stages, showed that the heat of regeneration for the three scrubbers was 3.57–8.93 GJ/t, in the temperature range of 110–130 °C, while A2 was the best solvent. Finally, the heat regeneration mechanism was also discussed in this work.

Synthesis of New Heterocyclic Derivatives from 4-(3, 5-Dimethyl-1-phenyl-1H-pyrazol-4-ylazo)- benzoic acid

In this work pyrazolin derivatives were prepared from the diazonium chloride salt of 4-aminobenzoic acid. Azo compounds were prepared from the reaction of an ethanolic solution of sodium acetate and calculated amount of active methylene compound namely, acetyl acetone to obtain the corresponding hydrazono derivative (1). Cyclocondensation reaction of compounds (1) with hydrazine hydrate and phenyl hydrazine in boiling ethanol affording the corresponding pyrazoline-5-one derivatives of 4-aminobenzoic acid (2,3). Then compound (3) was reacted with thionyl chloride to give the corresponding acid chloride derivative(4), followed by conversion into the corresponding acid hydrazide derivative (5) carboxylic acid thiosemicarbazide (11), esters (14,15), thioesters (16,17) and amides (18,19), when treated hydrazine hydrate, thiosemicarbazide, alcohols, alkylthiol and secondary amines in dry refluxing benzene; respectively. Schiff's bases (6-8) were prepared by refluxing of compound (5) with different aldehydes and ketons, then two compounds from the Schiff's bases were cyclized with ?-mercapto acetic acid to give (9 and 10). Furthermore, 1,2,4-triazole derivative (12) have been also prepared by refluxing thiosemicarbazide derivative with sodium hydroxide solution (4%) followed acidification of the result using (10%)hydrolic acid. Moreover, a thiadiazole derivative (13) has been prepared by treatment of thiosemicarbazide derivative with concentrated sulfuric acid as cyclyzing agent. Finally, oxadiazole derivative (20) has prepared by condensation of its acid hydrazide derivative with carbon disulfide in basic medium.

Organophotocatalytic Selective Deuteration of Metabolically Labile Heteroatom Adjacent C-H Bonds via H/D Exchange with D2O.

We report a general approach for efficient deuteration of the metabolically labile α-C-H bonds of widespread amides and amines. Temporarily masking the secondary amine group as a carbamate allows an unprecedented photoredox hydrogen atom transfer-promoted α-carbamyl radical formation for efficient H/D exchange with D2O. The mild protocol delivers structurally diverse α-deuterated secondary amines including "privileged" piperidine and piperazine structures highly regioselectively with excellent levels of deuterium incorporation (≤100%). Furthermore, we successfully implemented the strategy for α-deuteration of amides, lactams, and ureas with high regioselectivity and high levels of D incorporation. Finally, the observed efficient deuteration of secondary alcohol moieties in late-stage modification of complex amine-containing pharmaceuticals allows for the development of a viable method for efficient α-deuteration of the important functionality.

Exploring the Mechanisms and Kinetic Modeling of Phenol Amination Using Pd and Rh‐Based Catalysts

AbstractProducing biomass‐derived chemicals to substitute their petrochemical counterparts has long been an aspiration of the green chemistry research community. However, synthesizing secondary amines from biomass precursors presents several challenges related to catalyst nature and the mechanistic understanding of reaction systems. Here, we unravel the mechanistic and kinetic implications of the reductive amination of phenol with cyclohexylamine over Pd/C and Rh/C. A competitive Langmuir‐Hinshelwood reaction model well interpreted the kinetic data, suggesting that support‐metal interfaces serve as active sites for H2, ─NH2 and ═NH activation. The apparent activation energies for imine hydrogenation were 87.6 kJ mol−1 (Pd/C) and 34.5 kJ mol−1 (Rh/C), while ΔHads and ΔSads values confirmed the physicochemical consistency of the model. Moreover, the catalysts demonstrated their high stability to operate for several catalytic cycles, with minor activity losses due to metal leaching and partial sintering of Pd nanoparticles. Despite phenol reductive amination following similar mechanisms on Rh/C and Pd/C, they show differences in selectivity because the hydrogenation of imine is more efficient on Rh0 than on Pd0. This is the first mechanism‐oriented kinetic study for phenol reductive amination; thus, it provides valuable information for process design and scale‐up.

Data mining of PubChem bioassay records reveals diverse OXPHOS inhibitory chemotypes as potential therapeutic agents against ovarian cancer

Focused screening on target-prioritized compound sets can be an efficient alternative to high throughput screening (HTS). For most biomolecular targets, compound prioritization models depend on prior screening data or a target structure. For phenotypic or multi-protein pathway targets, it may not be clear which public assay records provide relevant data. The question also arises as to whether data collected from disparate assays might be usefully consolidated. Here, we report on the development and application of a data mining pipeline to examine these issues. To illustrate, we focus on identifying inhibitors of oxidative phosphorylation, a druggable metabolic process in epithelial ovarian tumors. The pipeline compiled 8415 available OXPHOS-related bioassays in the PubChem data repository involving 312,093 unique compound records. Application of PubChem assay activity annotations, PAINS (Pan Assay Interference Compounds), and Lipinski-like bioavailability filters yields 1852 putative OXPHOS-active compounds that fall into 464 clusters. These chemotypes are diverse but have relatively high hydrophobicity and molecular weight but lower complexity and drug-likeness. These chemotypes show a high abundance of bicyclic ring systems and oxygen containing functional groups including ketones, allylic oxides (alpha/beta unsaturated carbonyls), hydroxyl groups, and ethers. In contrast, amide and primary amine functional groups have a notably lower than random prevalence. UMAP representation of the chemical space shows strong divergence in the regions occupied by OXPHOS-inactive and -active compounds. Of the six compounds selected for biological testing, 4 showed statistically significant inhibition of electron transport in bioenergetics assays. Two of these four compounds, lacidipine and esbiothrin, increased in intracellular oxygen radicals (a major hallmark of most OXPHOS inhibitors) and decreased the viability of two ovarian cancer cell lines, ID8 and OVCAR5. Finally, data from the pipeline were used to train random forest and support vector classifiers that effectively prioritized OXPHOS inhibitory compounds within a held-out test set (ROCAUC 0.962 and 0.927, respectively) and on another set containing 44 documented OXPHOS inhibitors outside of the training set (ROCAUC 0.900 and 0.823). This prototype pipeline is extensible and could be adapted for focus screening on other phenotypic targets for which sufficient public data are available.Scientific contributionHere, we describe and apply an assay data mining pipeline to compile, process, filter, and mine public bioassay data. We believe the procedure may be more broadly applied to guide compound selection in early-stage hit finding on novel multi-protein mechanistic or phenotypic targets. To demonstrate the utility of our approach, we apply a data mining strategy on a large set of public assay data to find drug-like molecules that inhibit oxidative phosphorylation (OXPHOS) as candidates for ovarian cancer therapies.Graphical