Primary Amines Research Articles

Controlled Synthesis of Bioderived Poly(limonene carbonate)-Oligolysine Hybrid Macromolecules.

A straightforward and stepwise functionalization of poly(limonene carbonate) (PLC) was achieved through the use of thiol-ene click chemistry introducing primary amine groups. These amines are initiating points for N-carboxy anhydride (NCA) ring-opening polymerization (ROP) reactions, allowing us to modify the PLC backbone with oligolysine fragments, thereby creating a polymer brush type macromolecule. These newly prepared biohybrid structures show a clear hydrophilic behavior as evident from their physical behavior and contact angle measurements.

Recent Progress in the Photocatalytic Synthesis of α‐Tertiary Primary Amines

Abstractα‐Tertiary primary amines (α‐TPAs) bearing a fully substituted carbon center adjacent to the N‐unsubstituted amino group (−NH2) exhibit unique biochemical and physicochemical activities. While due to the sterically congested structure and strong nucleophilic and alkaline natures of these primary amine compounds, their facile synthesis remains an inherent challenge. Traditional methods commonly rely on tedious N‐protection/deprotection operations and highly reactive organometallic reagents, thus leading to poor atom and step‐economy and limited functional group compatibility. Modern photoredox catalysis offers a robust tool to prepare such structurally unique and synthetically valuable amine architectures via a radical pathway under extremely mild conditions. In this review, the recent progress in photocatalytic synthesis of α‐TPAs is systematically reviewed, and the reaction scope, limitations, and mechanisms for the reactions are discussed.

Organocatalytic Enantioselective Vinylogous Allylic Alkylation between β,γ‐Unsaturated Pyrazoleamides and MBH Carbonates

The direct asymmetric vinylogous allylic alkylation is an efficient method to construct chiral 1,5‐diene compounds. In this work, acyclic unsaturated amides are used as a nucleophile for enantioselective vinylogous allylic alkylation. With 10 mol% of chiral tertiary amine C11, the enantioselective vinylogous allylic alkylation between β,γ‐unsaturated pyrazoleamides and Morita‐Baylis‐Hillman carbonates is achieved, affording optically active multifunctional chiral 1,5‐dienes in moderate to excellent yields (74‐99%) with good‐to‐excellent enantioselectivities (67‐94% ee).

One‐Step Synthesis of Novel Erlotinib Analogs Catalyzed by Nano‐CuO as Potent Anticancer Agent

ABSTRACTTwenty new substituted erlotinib analogs with anticancer activity were produced with good to excellent yields through the one‐step reaction of erlotinib, aromatic aldehydes, and cyclic secondary amines such as piperidine, morpholine, pyrrolidine, N‐methylpiperazine, or imidazole using nano‐CuO in choline chloride: urea (ChCl:urea) solvent under ultrasound irradiation at 80°C. MTT protocol was applied to investigate the cytotoxicity of all produced substituted erlotinib analogs in A431 (human epidermoid carcinoma cell) and HU02 (foreskin fibroblast) cell lines. The results illustrated that at a concentration of less than 10 μM, the growth of A431 cells could be inhibited by the produced compounds. Compared to erlotinib as positive control, the highest cytotoxic activity with IC50 equal to 2.58 ± 0.57 μM belonged to compound 4c carrying 4‐fluorobenzene with piperidine substitution. All of the synthesized compounds showed significant cytotoxic activity on A431, while showing no apparent cytotoxicity to HU02. The reasons for the stronger cytotoxic activity 4c can be most probably attributed to the two phenomena of greater solubility of the fluoro derivative and the flexibility of piperidine. Based on this study, compound 4c is the most promising compound with anticancer properties.

Non-hydrolytic sol-gel synthesis of amine-functionalized silica: Template- and catalyst-free preparation of mesoporous catalysts for CO2 valorization

Carbon dioxide utilization presents an important and topical research topic. However, the performance of catalysts needed for CO2 transformations does not achieve the necessary levels for their widespread application. To this end, we decided to study non-aqueous condensations providing amine-functionalized silica catalysts, possibly active in CO2-epoxide cycloaddition reaction. While non-hydrolytic sol-gel method is well-known for its efficiency in providing highly porous Lewis and Brønsted acid metallosilicates, here we show for the first time its application for the preparation of silica-based catalysts containing basic groups. First, the reaction conditions were screened to reproducibly obtain porous materials with preserved amine moieties. These were identified as follows: silicon tetraacetate and bridging tertiary amine silanes as precursors, toluene as a solvent, and temperature between 160 and 180 °C. In such a way, materials with up to 776 m2 g−1 and 1.58 cm3 g−1 were obtained in one-step process, without any template, after conventional drying step. Next, the amine-functionalized materials were tested in CO2-epoxide coupling providing cyclic organic carbonates with high selectivity (>99 %) and moderate activity (up to 86 % epichlorohydrin conversion after 1 h at 120 °C and 10 bar CO2). The characterization of spent catalysts revealed a presence of cyclic organic carbonates at the catalyst surface as well as conversion of tertiary amine groups to quaternary ammonium moieties.

NITROGEN-CONTAINING SILANE COUPLING AGENTS: SYNTHESIS AND STRUCTURE EFFECT ON TIRE PERFORMANCE OF SILICA/SSBR/BR COMPOSITES

ABSTRACT We report synthesis of nitrogen-containing silane coupling agents (N-SCAs) and their use in a 1:1 mixture by weight with bis(triethoxysilylpropyl)tetrasulfide preparation of silica/solution SBR (SSBR)/BR composites. These N-SCAs contain in their structures, inter alia, a tertiary amine center (N1, N2), a carbamate (N3), or a urea (N4) group. In addition, N1, N3, and N4 were equipped with allyl side arms to increase the hydrophobization effect of silica particle as well as to achieve a balance between the filler–filler and filler–matrix networks being formed. By contrast, N2 consists of glycidyl side arms that contribute to the filler–filler interaction even more. The silica/SSBR/BR blends and subsequent vulcanizates were prepared and then thoroughly investigated via dynamic mechanical analysis, rubber process analysis, and tensile testing. The composite based on N1 (V/N1) exhibited exceptionally great tensile strength, abrasion resistance, and winter traction, accompanied by soft hysteresis. Therefore, N1 has potential applications in preparation of winter tire tread materials.

Photoredox-Catalyzed Alkynylation of C(sp3)-H Bonds Adjacent to a Nitrogen Atom of Tertiary Amines with Alkynyl Bromides.

A novel and robust alkynylation of C(sp3)-H bonds adjacent to a nitrogen atom of tertiary amines with alkynyl bromides as radical alkynylating reagents has been realized under visible-light irradiation. A range variety of tertiary amines including N-arylamines and N-alkylamine have been coupled with both aromatic and aliphatic alkynyl bromides to furnish 51 examples of propargylamines in moderate to excellent yields (31-80% yields). The possible mechanism was a radical addition-elimination process based on preliminary mechanistic studies.

Multicomponent Construction of Tertiary Alkylamines by Photoredox/Nickel-Catalyzed Aminoalkylation of Organohalides.

Tertiary alkylamines are privileged structural motifs widely present in natural products, pharmaceutical agents, and bioactive molecules, and their efficient synthesis has been a longstanding goal in organic chemistry. The functionalization of α-amino radicals derived from abundant precursors represents an emerging approach to accessing alkylamines, but application of this strategy to obtain tertiary alkylamines remains challenging. Here, we show that dual photoredox/nickel catalysis enables aminoalkylation of organohalides (sp2- and sp3-hybridized) in combination with secondary alkylamines and aldehydes. The multicomponent process proceeds through selective generation of α-amino radicals from the reduction of in situ-generated iminium ions by photoredox catalysis, followed by nickel-catalyzed cross-coupling to build a wide array of functionally diverse tertiary alkylamines. This strategy could also be extended to unprecedented four-component reactions and their asymmetric variants to deliver enantioenriched α-aryl-substituted γ-amino acid derivatives. Taken together, this work offers a streamlined synthetic route to aliphatic tertiary amines.

Carbon-Substituted Amines of the Cobalt Bis(dicarbollide) Ion: Stereochemistry and Acid-Base Properties.

Organic amines are found to be abundant in natural living systems. They also constitute an inestimable family of building blocks available in drug design. Considering the man-made cluster [(1,2-C2B9H11)2-3,3'-Co(III)]- ion (1-) and its application as an emerging unconventional pharmacophore, the availability of the corresponding amines has been limited and those with amino groups attached directly to carbon atoms have remained unknown. This paper describes the synthesis of compounds containing one or two primary amino groups attached to the carbon atoms of the cobaltacarborane cage that are accessible via the reduction of newly synthesized azides or via the Curtius rearrangement of the corresponding acyl azide. This substitution represents the first members of the series of azides and primary amines with functional groups bound directly to the carbon atoms of the cage. As expected, the absence of the linker along with the presence of the bulky anionic polyhedral ion leads to a significant alteration of the chemical and physicochemical properties. On a broader series of amines of the ion 1- we have thus observed significant differences in the acidity of the amino groups, depending on whether these are attached to the carbon or boron atoms of the cage, or the C-substituted amines contain an aliphatic linker of variable length. The compounds are relevant for potential use as cobalt bis(dicarbollide) structural blocks in medicinal chemistry and material science. Our study includes single-crystal X-ray diffraction (XRD) structures of both amines and a discussion of their stereochemical and structural features.

Isomerization enhanced fluorescence brightness of benzobisthiadiazole-based NIR-II fluorophores for highly efficient fluorescence imaging: A theoretical perspective

As a cutting-edge technique, fluorescence imaging in the second near-infrared window (NIR-II) is vital for both biomedical research and clinical applications. However, its intravital imaging capacity has been restricted by the extremely limited brightness of NIR-II fluorophores. To address this challenge, we elucidated the inner mechanism of constructing high-performance NIR-II chromophores based on molecular isomer engineering from detailed computational investigations. Herein, three pairs of cis–trans isomers (cis-1, 2, 3 and trans-1, 2, 3) are designed by attaching amino, methoxyl and nitro moieties to different positions on the donor–acceptor-donor molecular skeleton with benzobisthiadiazole as the acceptor and triphenylamine as the donor. All the compounds feature efficient NIR-II emission ranging in 1000–1164 nm, and the photophysical characterizations are regulated by molecular isomer manipulation. Interestingly, fluorescence quantum yields of cis-isomers are higher than those of their trans-counterparts. These enhancements can be attributed to the significant reduction in non-radiative transition, as evidenced by the non-adiabatic excitation energy, non-adiabatic electron coupling and electron-vibration coupling. Meanwhile, fluorophores with nitro terminal group exhibit superior performance facilitated by the prominently intramolecular charge transfer. As a result, cis-3 achieves an optimal brightness maxima of 196.36 M−1 cm−1 at 632 nm. Notably, the energy gap and the hole-electron related H index are respectively identified as strongly relevant to the emission wavelength and brightness, making them capable of evaluating the feasibility of fluorophores as effective NIR-II candidates. These findings highlight the correlations between molecular geometry and luminescent properties, which will inspire more insights into the development of highly efficient NIR-II fluorophores through rational isomer engineering for biomedical applications.

Co-Assembled Nanosystems Exhibiting Intrinsic Fluorescence by Complexation of Amino Terpolymer and Its Quaternized Analog with Aggregation-Induced Emission (AIE) Dye.

Aggregation-induced emission dyes (AIEs) have gained significant interest due to their unique optical properties. Upon aggregation, AIEs can exhibit remarkable fluorescence enhancement. These systems are ideal candidates for applications in bioimaging, such as image-guided drug delivery or surgery. Encapsulation of AIEs in polymeric nanocarriers can result in biocompatible and efficient nanosystems. Herein, we report the fabrication of novel nanoaggregates formulated by amino terpolymer and tetraphenylethylene (TPE) AIE in aqueous media. Poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA) hydrophilic terpolymer was utilized for the complexation of the sodium tetraphenylethylene 4,4',4″,4‴-tetrasulfonate AIE dye. Fluorescence spectroscopy, physicochemical studies, and self-assembly in aqueous and fetal bovine serum media were carried out. The finely dispersed nanoparticles exhibited enhanced fluorescence compared to the pure dye. To investigate the role of tertiary amino groups in the aggregation phenomenon, the polymer was quaternized, and quaternized polymer nanocarriers were fabricated. The increase in fluorescence intensity indicated stronger interaction between the cationic polymer analog and the dye. A stronger interaction between the nanoparticles and fetal bovine serum was observed in the case of the quaternized polymer. Thus, P(DEGMA-co-DMAEMA-co-OEGMA) formulations are better candidates for bioimaging applications than the quaternized ones, presenting both aggregation-induced emission and less interaction with fetal bovine serum.

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-naturalIonic 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.