Search Results (205)

In this paper, a multifunctional polymer BT-PGA-TPE-HNPE was designed and synthesized by modifying γ-polyglutamic acid (γ-PGA) with biotin, the tetraphenylethylene derivative O-TPE-HNPE and an acid-sensitive imine bond. The polymer was used to fabricate paclitaxel (PTX)-loaded micelles. As expected, the BT-PGA-TPE-HNPE micelles demonstrated strong AIE characteristics, fluorescing yellow under normal conditions and blue in acidic settings. Moreover, the drug was specifically released under acidic conditions. In vitro and in vivo tumor suppression experiments showed that the micelles had enhanced antitumor activity with minimal systemic toxicity. The BT-PGA-TPE-HNPE micelles had wide application prospects in the fields of chemotherapy and bioimaging. Full article

Heterocyclic compounds have shown that they hold significant therapeutic activities, highlighting the importance of discovering and developing novel candidates against cancers, infections, and oxidative stress-associated disorders. In this study, we demonstrated the biological activity of our previously synthesized thiazolidinone derivatives (TZDs-1, 6, and 7). Furthermore, we synthesized and structurally characterized a new derivative (TZD-5) using IR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the presence of its key functional groups, namely, carbonyl and imine. Their antioxidant activity was assessed through the DPPH assay, with TZD-5 showing the most potent effect (IC₅₀ = 24.4 µg/mL), comparable to ascorbic acid, an effect attributed to the methoxy group introduced via N-alkylation. Cytotoxicity was evaluated using the MTS assay on normal (HFF-1) and cancerous (HepG2 and A549) cell lines at two time points: 24- and 48 h exposure. Our findings highlight clear differences in cytotoxicity and selectivity among the tested thiazolidinone derivatives. TZD-1 and TZD-6 demonstrated significant, dose-dependent cytotoxic effects on both cancerous (HepG2 and A549) and normal (HFF-1) cell lines, thus limiting their therapeutic potential due to insufficient selectivity. TZD-5 exhibited moderate selectivity with higher susceptibility for HepG2 cells compared to normal cells. Notably, TZD-7 showed the most favorable cytotoxic profile, demonstrating strong selective cytotoxicity toward cancer cell lines with minimal adverse effects on normal fibroblasts. Overall, the results highlight TZD-5 and TZD-7 as promising candidates for antioxidant and selective anticancer therapies. Full article

Gold nanoparticles (AuNPs) are a promising tool for drug delivery due to their unique chemical properties that make them biocompatible and easy to functionalize. However, when AuNPs are introduced into biological systems, they are coated by the so-called protein corona (PC), which affects their biodistribution and limits their therapeutic efficacy. The functionalization of AuNPs with endogenous carbohydrates can be a possible strategy to reduce immune recognition, thus enhancing their biocompatibility and circulation time. Suitable candidates for this approach are the ABO blood sugar antigens, di- and tri-saccharides that represent the terminal portion of some glycolipids and glycoproteins present on the surface of human red blood cells and other tissues. In this work, we illustrate the synthesis of trisaccharide antigen A derivative, whose last step is worthy of investigation. During the final hydrogenolysis reaction, intended to remove protecting groups, an unexpected side reaction occurred, the isolated product bearing an N,N-dimethyl moiety on the anomeric propyl linker. This side reaction might be ascribed to the in situ formation of formaldehyde and successive imine formation and reduction. The obtained compound can be used as a monomeric control compound in biochemical and structural biology studies involving ABO blood sugar antigens. Full article

The development of sustainable epoxy vitrimers with outstanding mechanical strength and facile self-healing capabilities are of great significance for prolonging the lifespan and enhancing the reliability of electronic devices. In this study, we present a castor oil-derived epoxy vitrimer (ASB–ECO) featuring dual dynamic networks enabled by rationally designed ester–imine bonds and an aromatic Schiff base-conjugated crosslinker architecture. This molecular design strategy effectively enhances the mechanical properties of vegetable oil-based vitrimers and endows them with controllable self-healing capabilities under photothermal conversion. The 1.0-ASB–ECO system demonstrates dynamic characteristics with an activation energy (Ea) of 37.25 kJ/mol and a topological freezing transition temperature (Tv) of 123.13 °C. The material exhibits a photothermal conversion efficiency (ηPT = 61.42%) and can achieve a self-healing rate of 100% under visible-light radiation. In addition, 1.0-ASB–ECO displays a dielectric constant (Dk) of 5.54 and a loss tangent (Df) of 0.025 at 106 Hz. This study on biomass-based epoxy vitrimers presents a novel approach to developing electronic materials, achieving a combination of high mechanical performance, sustainability, and photothermal self-healing properties. Full article

The [3+2] cycloaddition chemistry of (2S)-5-methylene-2-t-butyl-1,3-dioxolan-4-one, derived from lactic acid, has been examined, and spiro adducts have been obtained with benzonitrile oxide, acetonitrile oxide, diazomethane and diphenyldiazomethane. The structure and absolute stereochemistry of the benzonitrile oxide adduct has been confirmed by X-ray diffraction, and all the adducts have been fully characterised by ¹H and ¹³C NMR. Attempted cycloaddition with a nitrile sulfide, a nitrile imine and azides failed. Pyrolysis results in a range of novel gas-phase reactions, with the nitrile oxide adducts giving pivalaldehyde, CO₂, the nitrile and ketene, the diazomethane adduct losing only N₂ to give a cyclopropane-fused dioxolanone, and the diphenylcyclopropane derived from diphenyldiazomethane giving mainly benzophenone in a sequence involving the loss of pivalaldehyde and methyleneketene. Full article

The association of an aromatic ring with an N-H-unsubstituted imine generates families of compounds that have been little studied until now except when the ring is a phenyl group. Recently, such imines substituted by a furan or thiophene group have been synthesized. This work reports a similar study where a pyrrole or pyridine ring is directly linked to an N-unsubstituted aldimine or ketimine group in order to isolate such compounds and to open the way to the knowledge of their physicochemical properties. The lower volatility of pyrrole and pyridine derivatives compared to aryl, furan, or thiophene derivatives greatly increases the difficulty of the synthesis and isolation of these kinetically unstable compounds. Full article

Background/Objectives: Recently, there has been great interest in metallopharmaceuticals as potential anticancer agents. In this context, presented studies aim to synthesize and evaluate of two copper(II) complexes derived from phthalazine- and imidazoline-based ligands against on three human cancer cell lines: cervix epithelial cell line (HeLa), breast epithelial-like adenocarcinoma (MCF-7), and triple–negative breast epithelial cancer cell line (MDA-MB-231), as well as non-tumorigenic cell line (HDFa). Moreover their antimicrobial, and antioxidant properties were assessed. Methods: The synthetized compounds—both free ligands L1, L2, L3 and copper(II) complexes C1 and C2—were characterized by elemental analysis, infrared spectroscopy. Additionally, a single-crystal X-ray diffraction studies we performed for free ligand L3 and its copper(II) complex C2. The stability of Cu(II)-complexes C1 and C2 was evaluated by UV-Vis spectroscopy. The cytotoxic potency of free ligands and their copper(II) complexes was estimated on HeLa, MCF-7, MDA-MB-231, as well as non-cancerous HDFa by use of an MTT assay after 48 h of incubation. Moreover, the antimicrobial activity of ligands L1 and L3 and their copper(II) complexes C1 and C2 was evaluated using reference strains of the following bacteria and yeasts: Staphylococcus aureus, Escherichia coli, and Candida albicans. The free radical scavenging properties of free ligands L1, L3 and the corresponding copper(II) complexes C1, C2 was tested with two colorimetric methods—ABTS, DPPH, and reduction ability assay (FRAP). Additionally, the ADME webtool was used to assess the drug-likeness of the synthesized compounds, as well as their physicochemical and pharmacokinetic properties. Results: Copper(II) complex C2 exhibited antitumor properties towards MDA-MB-231 compared with Cisplatin (cancer cell viability rate of 23.6% vs. 22.5%). At a concentration of 200 μg/mL, complexes C1 and C2 were less cytotoxic than the reference Cisplatin against a normal, non-cancerous skin fibroblast cell line (HDFa). According to in vitro tests, C2 reduced the viability of HeLa, MCF-7, and MDA-MB-231 cells by about 57.5–81.2%. It was evident that all compounds were devoid of antibacterial or antifungal activity. In vitro assays revealed that a moderate antiradical effect was observed for free ligand L1 containing phthalazin-1(2H)-imine in the ABTS radical scavenging assay (IC₅₀ = 23.63 µg/mL). Conclusions: The anticancer studies revealed that the most potent compound was copper(II) complex C2 bearing a phthalazin-1(2H)-one scaffold. None of the tested compounds showed antimicrobial or antifungal activity. This feature seems to be beneficial in terms of their potential uses as anticancer agents in the future. In vitro antiradical assays revealed that a moderate antioxidant effect was observed only for free ligand L1 containing phthalazin-1(2H)-imine. Full article

Conventional epoxy thermosets, with irreversible crosslinking networks, cannot be reprocessed and recycled. Furthermore, the utilization of petroleum-based materials accelerates the depletion of non-renewable resources. The introduction of dynamic covalent bonds and the use of bio-based materials for thermosets can effectively address the above issues. Herein, a series of bio-based epoxy vitrimers with dynamic covalent imine bonds were synthesized via a simple solvent-free, one-pot method using vanillin-derived aldehyde monomers, 4,4-diaminodiphenylsulfone (DDS) and bisphenol F diglycidyl ether (BFDGE) as raw materials. The effect of crosslinking density, crosslinking structure and imine bond content on the resulting bio-based vitrimers was studied, demonstrating their excellent thermal properties, UV shielding and solvent resistance, as well as outstanding mechanical properties compared to those of the previously reported vitrimers. In particular, the cured neat resin of vitrimer had a maximum tensile strength of 109 MPa and Young’s modulus of 6257 MPa, which are higher than those of previously reported imine-based vitrimers. The dynamic imine bonds endow these vitrimers with good reprocessability upon heating (over 70% recovery) and degradation under acidic conditions, enabling recycling by physical routes and gentle degradation by chemical routes. This study demonstrates a simple and effective process to prepare high-performance bio-based and recycled epoxy thermosets. Full article

A novel Schiff base, (E)-4-acetyl-N-(4-hydroxy-3-methoxybenzylidene)aniline (abbreviated as ANHMA), was synthesized and characterized using infrared and ¹H- and ¹³C-NMR spectroscopies. Optical properties in different solvents were evaluated using UV-vis absorption spectroscopy. The compound is shown to exhibit both positive and negative solvatochromism with reversal occurring for solvents with E_T(30)~45 (e.g., DMSO). The solvatochromic behavior of the compound was found to be strongly dependent on the hydrogen bond abilities and polarizability of the solvent, the observed reversal in solvatochromism being explained by the change in the dominant solvent effects in non-polar and polar–aprotic solvents (H-bond acceptor ability of the solvent and polarizability) compared to polar–protic solvents (H-bond donor ability), according to the developed Catalán multiparametric solvatochromic model. In all freshly prepared solutions studied, the (E)-enol-imine tautomer of the compound was found to strongly predominate over the keto-amine tautomeric forms, the latter increasing their populations over time in the presence of H-bond donor/acceptor species. Irradiation of ANHMA with UV light (λ ≥ 311 nm) was also investigated in several solvents and shown to follow a general pattern, with the conversion of the (E)-enol-imine tautomer into the keto-amine forms in a solvent-mediated enol-imine/keto-amine tautomerism, and (Z)→(E) C=C isomerization between the keto-imine forms. The experimental results received support from an extensive series of calculations on the structure and UV-vis spectra of the relevant tautomeric/isomeric forms of the compound performed at the DFT(B3LYP)/6-311++G(d,p) level of approximation (including time-dependent DFT calculations and solvent consideration). Full article

Push-pull imines with strong electron donor group(s) display exceptional basicity in the gas phase. Most of them do not exhibit prototropic tautomerism, and gas-phase acid-base equilibria have been already well described and reviewed. Some questions remain for tautomeric systems, particularly for their uncommon forms. As shown by quantum-chemical calculations, some often-neglected tautomers display higher basicity than the thermodynamically favored forms. However, their participation in tautomeric mixtures being in equilibrium is negligible, and their basicity can be impossible to measure in the gas phase by the equilibrium method. During this work, we examined the gas-phase proton basicity for some acyclic and cyclic push-pull organic bases containing the tautomeric amidine or guanidine group. By quantum-chemical calculations, we confirmed the existence of very low amounts of rare tautomeric forms, in particular, those bearing a methylidene (=CH₂) group. We also demonstrated that the alkyl derivatives of rare tautomers, being free of prototropy, can be good candidates as very strong push-pull C bases, i.e., bases protonated on the =CH₂ group. Full article

A new approach to 1,2,5-trisubstituted 1H-indole-3-carboxylic esters has been developed and studied. The method begins with the preparation of imines from aldehyde and primary amine derivatives. Treatment of these imines with the K₂CO₃-derived anion from methyl 2-(2-fluoro-5-nitrophenyl)acetate or methyl 2-(5-cyano-2-fluorophenyl)acetate in DMF initiates a [3+2] cyclization by addition of the anion to the imine followed by ring closure of the adduct nitrogen to the activated aromatic moiety via an S_NAr process. Twenty-one examples are reported. Temperatures required for the conversion range from 90 to 95 °C for the nitro-activated substrates to 125 to 130 °C for the cyano-activated precursors. Though efficient and atom economical, limitations arise from steric hindrance in the reacting partners. The initial indoline formed is not observed but instead undergoes spontaneous air oxidation to the give the aromatic heterocycle. Imines from nonaromatic aldehydes and amines are also possible, but these give slightly lower yields of 1H-indoles and only react with the nitro-activated substrates. The results are presented with a discussion of the mechanism and the factors important to the success of the reaction. Full article

Butyl phenyl-H-phosphinate that is not available commercially was prepared from phenyl-H-phosphinic acid by three methods: by alkylating esterification (i), by microwave-assisted direct esterification (ii), and unexpectedly, by thermal esterification (iii). Considering the green aspects, selectivity and scalability, the thermal variation seemed to be optimal. However, there was need for prolonged heating. The butyl phenyl-H-phosphinate, along with the ethyl analogue, was utilized in the synthesis of alkyl (α-alkylamino-arylmethyl-)phenyl phosphinates in the aza-Pudovik reaction with imines obtained from primary amines and substituted benzaldehydes. The aminophosphinates were obtained as diastereomeric mixtures in 65–92% yields. The aza-Pudovik approach was more efficient than the Kabachnik–Fields condensation. Interestingly, one aminophosphinate, the butyl (α-butylamino-benzyl-)phenylphosphinate, was of significant cytotoxic activity on the PANC-1 pancreas cell line. Another derivative, ethyl (α-benzylamino-benzyl-)phenylphosphinate, revealed a selective toxic activity on U266 myeloma cells. Full article

Hydrogenation and dehydrogenation reactions are fundamental in chemistry and essential for all living organisms. We employ density functional theory (DFT) to understand the reaction mechanism of the oxidative dehydrogenation (ODH) of the pyridyl-amine complex [Fe^IIIL³]³⁺ (L³, 1,9-bis(2′-pyridyl)-5-[(ethoxy-2″-pyridyl)methyl]-2,5,8-triazanonane) to the mono-imine complex [Fe^IIL⁴]²⁺ (L⁴, 1,9-bis(2′-pyridyl)-5-[(ethoxy-2″-pyridyl)methyl]-2,5,8-triazanon-1-ene) in the presence of dioxygen. The nitrogen radical [Fe^IIL³_N8•]²⁺, formed by deprotonation of [Fe^IIIL³]³⁺, plays a crucial role in the reaction mechanism derived from kinetic studies. O₂ acts as an oxidant and is converted to H₂O. Experiments with the deuterated ligand L³ reveal a primary C-H kinetic isotope effect, k^CH/k^CD = 2.30, suggesting C-H bond cleavage as the rate-determining step. The DFT calculations show that (i) ³O₂ abstracts a hydrogen atom from the α-pyridine aliphatic C-H moiety, introducing a double bond regio-selectively at the C₇N₈ position, via the hydrogen atom transfer (HAT) mechanism, (ii) O₂ does not coordinate to the iron center to generate a high-valent Fe oxo species observed in enzymes and biomimetic complexes, and (iii) the experimental activation parameters (ΔH^≠ = 20.38 kcal mol⁻¹, ΔS^≠ = −0.018 kcal mol⁻¹ K⁻¹) fall within in the range of values reported for HAT reactions and align well with the computational results for the activated complex [Fe^IIL³_N8•]²⁺···³O₂. Full article

Orthopalladated derivatives from substituted phenylglycines [Pd(μ-Cl)(C₆H₃R₁C(R₂)(R₃)N(R₄)₂]₂ (1) react with halogenating reagents (PhICl₂, Br₂, I₂) (2) to give the corresponding o-halogenated amino acids C₆H₃(X)R₁C(R₂)(R₃)N(R₄)₂ (3). The reaction is general and tolerates a variety of functional groups (R₁ to R₄) at the aryl ring, the Cα, and the N atom. On the other hand, the reaction of [Pd(μ-Cl)(C₆H₃R₁C(R₂)(R₃)N(R₄)₂]₂ (1) with PhI(OAc)₂ in the presence of a variety of alcohols R₅OH (4) gives the o-alkoxylated phenylglycines C₆H₃(OR₅)R₁C(R₂)(R₃)N(R₄)₂ (5), also as a general process. A partial loss of the enantiomeric excess is observed when the starting phenylglycine is enantiomerically pure, this arising from the formation of bridging azavinylidene (6) and imine intermediate species (7), which were characterized by X-ray diffraction methods. Full article

The coupling between bis(2-oxazolines) and two equivalents of aromatic aldehydes in the presence of catalytic amounts of NiCl₂ affords an ester-imine product in synthetically useful yields. This virtually unknown, 100% atom-economic transformation involves the formal metathesis between the C=N double bond of the bis(2-oxazoline) moiety, which undergoes ring-opening, and the C=O double bond of the aldehyde. The scope of this transformation is studied, and a mechanism is proposed based on DFT calculations. Full article