Search Results (110)

Background/Objectives: Discriminating bacterial from mammalian membranes remains a central challenge in antibiotic design. Bacterial membranes are enriched in phosphatidylethanolamine (PE), a lipid normally absent from the outer leaflet of mammalian cells, providing a signature for selective molecular engagement. We report a compact covalent ligand, 6-dimethylamino-4-ketohexanoic acid (DMAX), which targets PE via Schiff base formation, leveraging its tertiary amine to facilitate the reaction and strengthen ionic binding with the phosphate group. Methods: The reactivity of DMAX and PE was evaluated by computational simulations, and their interaction was examined by spectroscopic analyses (NMR and FT-IR) and an artificial membrane assay. The targeting ability of DMAX for live bacteria was determined by microscopy study, and its applicability to therapeutic system was tested in vitro under washed conditions that mimic rapid in vivo clearance. Results: Spectrometric analyses revealed the selective covalent interaction of DMAX and PE, consistent with the simulated results. Fluorescently labeled DMAX selectively binds PE-enriched model membranes and efficiently recognizes Gram-negative bacteria while sparing mammalian cells. Conjugation of DMAX to Gemifloxacin (Gem) significantly enhanced antibiotic efficacy by 10-fold compared with free Gem, even after rapid drug clearance, while maintaining safety in mammalian cells. Conclusions: These results identify DMAX as an efficient and versatile PE-targeting platform, enabling selective membrane anchoring to advance precision antibiotic strategies. Full article

Three Schiff base fluorescent probes 3a–3c with N-heterocyclic structure were designed and synthesized by using the reaction of 4-diethylaminosalicylaldehyde with different N-heterocyclic amines, such as 2-aminobenzimidazole, 2-aminobenzothiazole, and 2-amino-6-methylpyridine. Compound 3a exhibited excellent selectivity towards Hg²⁺, with a detection limit of 3.21 × 10⁻⁷ M and a response time of only 30 s. It could be used as a fluorescent probe for detecting Hg²⁺. Meanwhile, compounds 3b and 3c exhibited excellent selectivity towards Zn²⁺, with detection limits of 1.61 × 10⁻⁷ M and 2.03 × 10⁻⁷ M, respectively, and response times of only 30 s. They could serve as fluorescent probes for detecting Zn²⁺. Using probe 3a for Hg²⁺ as an example, the detecting mechanism was further elucidated through ¹H NMR, ESI-MS testing, and DFT calculation analysis. For compound 3a, the coordination stoichiometry between compound 3a and Hg²⁺ was verified to be 1:1 through a Job’s plot. After coordination with Hg²⁺, the molecular rigidity of compound 3a was enhanced, which inhibited the non-radiative decay process and led to the closure of the excited-state intramolecular proton transfer (ESIPT) effect. At the same time, the fluorescence intensity was significantly increased through the chelation-enhanced fluorescence (CHEF) mechanism, which was confirmed by density functional theory (DFT) calculations. In addition, compounds 3a–3c were successfully applied in practical water samples and test strips for the detection of Hg²⁺/Zn²⁺. Full article

Schiff bases are widely studied for their biological activities, yet structure–activity relationships governing their anticancer potential remain insufficiently understood. In this work, eight structurally diverse imine derivatives (A–H) were evaluated for their cytotoxic, biochemical, and biomolecular interactions in human cancer cells. Their antiproliferative effects were assessed in HeLa, A549, and LS174T cell lines, with MRC-5 fibroblasts used as a non-malignant control. Cytotoxicity screening identified three compounds (A, B, and F) with the highest potency, prompting further mechanistic investigation. Cell cycle analysis revealed G1 arrest and accumulation of sub-G1 populations for all three derivatives, with compound B additionally increasing S-phase content and compound F inducing G2/M arrest. All compounds reduced intracellular ROS levels and caused significant DNA damage at subtoxic concentrations. Western blot analysis demonstrated downregulation of HIF-1α and PDK3, suggesting disruption of hypoxia-associated metabolic signaling. Fluorescence quenching experiments showed strong binding of the active compounds to bovine serum albumin (K_a ≈ 10⁶ M⁻¹), and molecular docking supported stable interactions near tryptophan-adjacent binding regions. Collectively, these findings indicate that selected Schiff bases exert multi-target anticancer activity by modulating oxidative stress, DNA integrity, cell-cycle progression, and metabolic adaptation pathways, warranting further investigation of their therapeutic potential. Full article

Development of new biologically active materials based on natural products has, over the years, attracted considerable attention due to their effectiveness in human health and disease. Polyphenolic compounds, particularly flavonoids, provide a wide range of health benefits, including antioxidant, anti-inflammatory, anticancer, and antibacterial properties. A series of novel Schiff base derivatives of flavonoids with amino-containing linkers was successfully designed and synthesized through condensation reactions. Naringin and naringenin derivatives with diamines, including ethylenediamine (EDA), 1,3-diamino-2-propanol (DA-2-PrOH), tetramethylenediamine (TMEDA), pentamethylenediamine (PMEDA), as well as polyamines spermidine (SPD) and spermine (SPM), were synthesized and well-characterized through FT-IR, UV–Visible, ESI–MS, ¹H and ¹³C NMR spectroscopy, and elemental analysis. The so confirmed and well-characterized derivatives were subjected to photoluminescence studies, exhibiting enhanced activity, especially for naringin-based derivatives, and quenching in some others, thus verifying the significance of chemically modifying the conjugated systems of these molecules. Their biological activity was examined in the case of their antimicrobial efficacy against two Gram (+) (Staphylococcus aureus and Bacillus cereus) and two Gram (−) (Escherichia coli and Xanthomonas campestris) bacterial strains. Antibacterial screening projected selectivity of modified flavonoids against E. coli, proposing new “dense” flavonoid-(poly)amine materials as multifunctional antimicrobial agents and fluorescent probes. Full article

A novel series of Schiff bases (3a–3k), incorporating tranexamic acid (TXA) and phenol-derived aldehydes via imine linkers, was synthesized and structurally characterized. The antimicrobial activity of the compounds was evaluated against a range of clinically and environmentally relevant bacterial and fungal strains. Among them, derivatives 3i and 3k, bearing bromine and chlorine substituents on the phenol ring, exhibited the most potent antimicrobial effects, particularly against Penicillium italicum and Proteus mirabilis (MIC as low as 0.014 mg/mL). To elucidate the underlying mechanism of action, in silico molecular docking studies were conducted, revealing strong binding affinities of 3i and 3k toward fungal sterol 14α-demethylase (CYP51B), with predicted binding energies surpassing those of the reference antifungal ketoconazole. Additionally, UV-Vis and fluorescence spectroscopy assays demonstrated good stability of compound 3k in PBS and its effective binding to human serum albumin (HSA), respectively. ADMET and ProTox-II predictions further supported the drug-likeness, low toxicity (Class 4), and favorable pharmacokinetic profile of compound 3k. Collectively, these findings highlight TXA–phenol imine derivatives as promising scaffolds for the development of next-generation antimicrobial agents, particularly targeting resistant fungal pathogens. Full article

The long-time absorption spectroscopic development of the genetically encoded microbial rhodopsin fluorescent voltage indicator QuasAr1 at room temperature in the dark was reinvestigated, mainly theoretically. The data analysis indicates protein aggregation within one day to some ten-nanometer sized Mie scattering particles. The absorption coefficient spectra can be deduced from measured attenuation coefficient spectra by scattering contribution subtraction. The initially present protonated retinal Schiff base (PRSB) Ret_580 isomerized and then deprotonated to neutral retinal Schiff base (RSB). One part of Ret_580, Ret_580_I, (fraction 43%), isomerized moderately fast to Ret_500 which then deprotonated to neutral retinal Schiff base Ret_405 (time constant ≈ 1000 h). The other part of Ret_580, Ret_580_II, (fraction 57%), isomerized slowly to Ret_460 which deprotonated to Ret_340 (time constant ≈ 400 h). The dynamics are described by a differential equation system which is solved numerically. Reaction parameters are determined by fitting the simulations to the experimental results. Full article

A novel fluorescent probe (PYB) for selective and sensitive detection of Cu²⁺ ions was rationally designed and synthesized via a multi-step organic reaction using pyrene as the fluorophore and salicylaldehyde-diethylenetriamine Schiff base as the recognition moiety. The structural characterization of PYB was confirmed by ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry (HRMS). Photophysical properties investigation revealed that the probe exhibited strong fluorescence emission at 362 nm in DMF/HEPES-NaOH buffer solution (v:v = 1:1, pH 7.4), which underwent a significant fluorescence quenching response (quenching efficiency up to 77%) upon the addition of Cu²⁺, attributed to the formation of a 1:1 PYB-Cu²⁺ complex (binding constant K = 799.65 M⁻¹). The probe showed excellent selectivity for Cu²⁺ over other common metal ions (Ba²⁺, Na⁺, Mg²⁺, Zn²⁺, Cd²⁺, Ca²⁺, Mn²⁺, Pb²⁺, Hg²⁺, Fe³⁺, Co²⁺), with a low detection limit of 8.35 × 10⁻⁷ M, which is well below the maximum allowable concentration of Cu²⁺ in drinking water specified by the World Health Organization (WHO). Furthermore, a portable fluorescent test strip based on PYB was successfully fabricated, enabling rapid and visual detection of Cu²⁺ under UV light. Fluorescence imaging experiments in living HepG2 cells demonstrated that PYB could penetrate cell membranes efficiently and realize the intracellular detection of exogenous Cu²⁺. These results collectively indicate that PYB holds great potential as a practical tool for Cu²⁺ detection in environmental monitoring, food safety, and biological systems. Full article

Copper is an important environmental pollutant that poses a significant threat to human health and environmental safety. Therefore, the development of methods for detecting Cu²⁺ is of great significance. A novel fluorometric/colorimetric dual-mode sensor for detecting Cu²⁺ was synthesized by Schiff base reaction using fluorescein hydrazide and 8-hydroxyjulonidine-9-carboxaldehyde as raw materials. Cu²⁺ could form a complex with the probe in a stoichiometric ratio of 1:1. Within 1 min, the fluorescence of the probe rapidly quenched at 540 nm, and the absorbance reached a stable state at 452 nm. The color of the solution changed from light yellow to yellow, achieving real-time and visual detection of Cu²⁺. This probe exhibited exceptional selectivity for Cu²⁺. Within the range of 0–12 μM, the fluorescence intensity of the probe demonstrated a strong linear correlation with the concentration of Cu²⁺ (R² = 0.994), with a detection limit of 0.22 µM. In the ultraviolet colorimetric method, when the Cu²⁺ concentration reached 14 μM, the absorbance stabilized (R² = 0.996), and the detection limit for Cu²⁺ was determined to be 0.38 µM. Furthermore, this probe enabled reversible detection of Cu²⁺, and its performance in real water sample analysis and cellular bioimaging was proven to be highly satisfactory. Full article

Aluminum (Al) and zinc (Zn) are two of the most widely used metals in industry, and their excessive accumulation in the body has been linked to serious diseases like Alzheimer’s, Parkinson’s, and cancer. This highlights the need for effective ways to detect and measure them. In this study, we synthesized the fluorescent chemosensor 1, which contains a Schiff base and a 1,3,4-thiadiazole ring in its structure, and evaluated its fluorescent response in the presence of various metal ions. The chemosensor enabled the selective quantification of Al³⁺ and Zn²⁺ ions through excitations at different wavelengths, yielding differentiated fluorescent emissions. For Al³⁺, excitation at 370 nm generated a strong emission at 480 nm, whereas for Zn²⁺, excitation at 320 nm led to a new small broad emission at 560 nm. We established detection limits of 2.22 × 10⁻⁶ M for Al³⁺ and 1.62 × 10⁻⁵ M for Zn²⁺; their binding stoichiometry was found to be 1:1 for Al³⁺ and 2:1 for Zn²⁺, based on Job’s plot analysis. These results show that chemosensor 1 is a promising tool for detecting Al³⁺ and Zn²⁺. Full article

Given the outstanding magnetic characteristics of lanthanide ions, the development of mononuclear or multinuclear lanthanide complexes becomes imperative. Previous research showed that a series of mononuclear Dy(III) complexes of rhodamine benzoyl hydrazone Schiff base ligands exhibit remarkable single-molecule magnetic properties and fluorescence. In this study, we used analogous ligands to synthesize lanthanide complexes [Dy(HL¹-o)(NO₃)₂(CH₃OH)₂]NO₃·CH₃OH (complex 1·MeOH) and tetranuclear complexes [Ln₄(L¹-c)₂(L²)₂(μ₃-OH)₂(NO₃)₂(CH₃OH)₄](NO₃)₂·2CH₃CN·5CH₃OH·2H₂O (Ln = Dy, complex 2; Ln = Gd, complex 3). Magnetic susceptibility measurements show that 1·2H₂O is a single-molecule magnet, 2 shows slow magnetic relaxation and 3 is a magnetic cooling material with the magnetic entropy change of 9.81 J kg⁻¹ K⁻¹ at 2 K and 5 T. The theoretical calculations on 1·MeOH indicate that it shows good magnetic anisotropy with the calculated energy barrier of 194.6 cm⁻¹. Full article

Background: Chitosan (CS) crosslinked with genipin (GNP) provides a mild, non-toxic route to generate nanogels (NGs) with enhanced integrity and colloidal stability. Objectives: To develop and characterise CS-GNP NG as a novel platform for targeted cellular delivery, optimising design through physicochemical characterisation and biocompatibility evaluation. Methods: NGs were synthesised under optimised conditions by adjusting the pH of the CS solution, followed by high-intensity ultrasound (HIUS) to achieve disaggregation. Physicochemical characterisation was carried out using UV-Vis spectroscopy, FTIR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). Rheological studies and SAXS analysis assessed structural properties. Biocompatibility was evaluated via MTT assay, and internalisation was monitored by fluorescence microscopy on mammalian cell lines. Results: NG formation was highly pH-dependent, with optimal configuration at pH 4.5, yielding stable, uniformly sized particles (~200 nm, ζ-potential +29 mV). Kinetic modelling showed a sigmoidal formation pattern, suggesting nucleation, growth, and stabilisation. FTIR confirmed covalent bonding between CS and GNP via primary amide bonds and Schiff bases. Rheology indicated pseudoplastic behaviour, and SAXS revealed a compact network formation. Biocompatibility assays confirmed non-cytotoxicity below 100 µg/mL and efficient cellular uptake. Conclusions: This study presents a rapid, reproducible protocol for generating colloidally stable, biocompatible NGs suitable for drug delivery. Full article

Their demonstrable bioactive characteristics, coupled with their wide structural diversity and coordination versatility, render Schiff bases and their coordination complexes biologically active compounds demonstrating outstanding properties. This research describes the synthesis and characterization of new Cu(II) and Ni(II) complexes with an NNO-donor hydrazone ligand (HL). The crystal structure of the HL ligand was determined through single-crystal X-ray diffraction studies. The in vitro antibacterial activities of the HL ligand and its metal(II) complexes against Gram-positive and Gram-negative bacteria demonstrated that the metal(II) complexes displayed greater antimicrobial activities compared to the free Schiff base ligand. Furthermore, the interaction of the ligand and the complexes with calf thymus DNA (CT-DNA) was explored through electronic absorption and viscosity measurements, suggesting intercalation as the most likely mode of binding. The compounds promoted oxidative DNA cleavage, as demonstrated by the strand breaks of the pmChery plasmid under oxidative stress conditions. Finally, fluorescence spectroscopy also revealed the strong binding affinity of these compounds for bovine serum albumin (BSA). Full article

We report the synthesis and characterization of five novel metal complexes. Three of them are vanadium complexes with the general formula [VO(Lⁿ)₂], where Lⁿ are Schiff bases derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with either 4-(2-aminoethyl)morpholine (L¹), 3-morpholinopropylamine (L²) or 1-(2-aminoethyl)piperidine (L³). The two other metal complexes are [Ni(L¹)₂] and [Fe(L¹)₂]Cl. They were characterized by analytical, spectroscopic (Fourier transform infrared, UV-visible absorption), and mass spectrometric techniques as well as by single-crystal X-ray diffraction (for all [VO(Lⁿ)₂] complexes and [Ni(L¹)₂]). While, in the crystal structure, the V(IV)O complexes show distorted square–pyramidal geometry with the ligands bound as bidentate through quinolate NO donors, the Ni(II) complex shows octahedral geometry with two ligand molecules coordinated through NNO donors. Stability studies in aqueous media revealed that the vanadium complexes are not stable, undergoing oxidation to VO₂(L), which was corroborated by ⁵¹V NMR and MS. This behavior is also observed in organic media, though at a significantly slower rate. The Ni complex exhibited small spectral changes over time in aqueous media. Nonetheless, all compounds show enhanced stability in the presence of bovine serum albumin (BSA). Fluorescence studies carried out for the Ni(II) and Fe(III) complexes indicate reversible binding to albumin. The cytotoxicity of the L¹ metal complexes was assessed on melanoma (B16F10 and A375) and colon cancer (CT-26 and HCT-116) cell lines, with 5-fluorouracil (5-FU) as a reference drug. The V- and Ni complexes showed the lowest IC₅₀ values (<10 μM) in either A375 or HCT-116 cells after 48 h of incubation, while the Fe(III) complex presented minimal antiproliferative effects. The complexes were generally more cytotoxic to human than murine cancer cells. Synergistic in vitro studies with 5-FU revealed antagonism in most cases, except in A375 cells, where an additive effect was observed for the combination with the V-complex. Overall, these compounds show promising potential for cancer treatment, mostly for melanoma. Full article

Using 5-methyl salicylaldehyde (2) as a reactant to react with different amines, 2-aminobenzimidazole (1a), 2-aminobenzothiazole (1b), and 2-aminopyridine (1c), respectively, three types of Schiff base fluorescent probes 3a–3c were designed and synthesized for selective detection of Al³⁺ in aqueous media. The structure of the compounds was acquired by ¹H NMR, ¹³C NMR, and X-ray single-crystal diffraction. Furthermore, their photochromic and fluorescent behaviors have been investigated systematically by fluorescence spectra. Compounds 3a–3c can exhibit high selectivity, sensitivity, and anti-interference properties towards Al³⁺ in aqueous media. Among them, the limit of detection (LOD) of probe 3b for Al³⁺ is 2.81 × 10⁻⁷ M. Notably, the response times of probes 3a–3c for Al³⁺ are 90 s, 80 s, and 80 s, respectively, which are much faster than most previously reported probes. The coordination stoichiometry between compounds 3a–3c and Al³⁺ has been verified to be 1:1 through the Job’s plot. After coordination with Al³⁺, the C=N isomerization of compounds 3a–3c is inhibited, leading to the closure of the excited state intramolecular proton transfer (ESIPT) effect. At the same time, the fluorescence intensity is significantly increased through chelation-enhanced fluorescence mechanism (CHEF), which is confirmed by density functional theory (DFT) calculations. In addition, probes 3a–3c can be potentially applied in the selective and high-precision detection of Al³⁺ in environmental systems. Full article

Biomarker detection is imperative in the realms of modern medicine, biology, and environmental science, owing to the numerous avenues for its application. The recent scientific upsurge in the development of molecules, materials, and mechanisms for such scientific development has garnered considerable attention among scientists. In this connection, excited-state intramolecular proton transfer (ESIPT) properties of photoluminescent compounds provide considerable insights into the designing, development, and detection of biomarkers. ESIPT molecules significantly show a Stokes-shifted emission due to their sensitive nature and unique photophysical properties. Leveraging this photophysical property and tunable nature, several fluorescent probes of this genre can be designed and synthesized for a plethora of application spheres. Schiff bases encompass one such category of functional molecules displaying ESIPT properties, which can be mitigated by adding several other functionalities and desired optical characteristics. The current review article spans the basics of ESIPT properties of certain photoluminescent molecules and also envisages biosensing applications of recently developed imine–functionalized Schiff base molecules with such properties as the prima-foci, along with other applications. Full article