Search Results (378)

Type 2 diabetes mellitus (T2DM) demands safer and more effective therapies to control postprandial hyperglycemia. Here, we report the synthesis and in vitro evaluation of ten salicylic acid-derived Schiff base derivatives (4a–4j) as α-glucosidase inhibitors. Compounds 4e, 4g, 4i, and 4j exhibited potent enzyme inhibition, with IC₅₀ values ranging from 14.86 to 18.05 µM—substantially better than acarbose (IC₅₀ = 45.78 µM). Molecular docking and 500 ns molecular dynamics simulations revealed stable enzyme–ligand complexes driven by π–π stacking, halogen bonding, and hydrophobic interactions. Density Functional Theory (DFT) calculations and molecular electrostatic potential (MEP) maps highlighted key electronic factors, while ADMET analysis confirmed favorable drug-like properties and reduced nephrotoxicity. Structure–activity relationship (SAR) analysis emphasized the importance of halogenation and aromaticity in enhancing bioactivity. Full article

Two hydrazone Schiff base-bridging ligands with different heterocycles {2-[(E)-(5-chloro-2-hydroxyphenyl)methylidene]diazanyl}(pyrazine-2-yl)methanone (H₂L_Schiff-1) and (E)-N′-(2-hydroxy-3-methoxybenzylidene)nicotinohydrazide (H₂L_Schiff-2) together with 1,3-di(2-pyridyl)-1,3-propanedione (Hdpp) were chosen to construct two new Dy₂ complexes, [Dy₂(L_Schiff-1)₂(DMF)₂(dpp)₂]·0.5DMF (1) and [Dy₂(L_Schiff-2)₂(DMF)₂(dpp)₂]·2DMF (2). Although the [N₂O₆] coordination spheres are observed for the Dy³⁺ ions in 1 and 2, their coordination configurations have some differences (both the biaugmented trigonal prism and the Snub diphenoid J84 in 1 and only the biaugmented trigonal prism in 2). Magnetic research revealed that both 1 and 2 possess ferromagnetic interactions between two Dy³⁺ ions and perform as zero-field single-molecule magnets, with U_eff/k values of 49.7 K at 0 Oe for 1 and 151.8 K at 0 Oe for 2. This work suggests that the heterocycle groups (pyrazine vs. pyridine) on the hydrazone Schiff base-bridging ligands have effects on the SMM properties of 1 and 2. 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

The alarming increase in antimicrobial resistance has intensified the search for novel therapeutic agents capable of combating resistant microbial strains. Copper complexes have emerged as promising antimicrobial agents due to their intrinsic redox activity, ability to disrupt microbial membranes, and interactions with vital biomolecules such as DNA and proteins. This review critically evaluates the antimicrobial potential of copper complexes reported between 2018 and 2025, emphasizing their structural diversity, mechanisms of action, and biological performance against a wide range of bacterial and fungal pathogens. Key findings reveal that Schiff base copper complexes, amino acid derivatives, heterocyclic ligands, and mixed-ligand systems exhibit potent antimicrobial activities, often surpassing standard antibiotics. Mechanistically, copper complexes induce reactive oxygen species (ROS) generation, inhibit enzyme function, cause DNA cleavage, and compromise cell membrane integrity. Furthermore, structure–activity relationship (SAR) analyses indicate that ligand type, coordination geometry, and lipophilicity significantly influence antimicrobial efficacy. Overall, the reviewed studies support the development of copper-based compounds as viable candidates for antimicrobial drug development. This review also identifies current challenges and gaps in knowledge, such as limited in vivo studies and toxicity assessments, which must be addressed to advance these compounds toward clinical application. Full article

Two iron(III) spin crossover complexes [Fe(⁵Cl-L)(NCS)] (1) and [Fe(⁵Cl-L)(NCSe)] (2) were synthesized with the pentadentate Schiff base ligand ⁵Cl-L and thiocyanato and selenocyanato as coligands. ⁵Cl-L, as an asymmetric {N₃O₂} donor Schiff base, was synthesized by a condensation reaction of 5-chlorosalicyladehyde using the asymmetric N-(2-aminoethyl)-1,3-propanediamine. The complexes exhibited a spin crossover at 280 (1) and 293 K (2), respectively, and were subjected to electron spin resonance (ESR) and Mössbauer spectroscopy at 77, 295 and 325 K. Ab initio CASSCF calculations followed by the NEVPT2 method were applied for predicting the g-tensor components as well as Mössbauer parameters. 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

Two phenoxy-ketimines ligands, 2-(1-(benzylimino)ethyl)phenol (HL^BSMe) and 2-((benzylimino)(phenyl)methyl)phenol (HL^BSPh), were synthesized and used as supporting ligands of new copper(II), copper(I), and silver(I) complexes. In order to confer different solubility properties to the metal complexes and to stabilize Cu and Ag in their +1 oxidation state, the lipophilic triphenylphosphine (PPh₃) and the hydrophilic 1,3,5-triaza-7-phosphaadamantane (PTA) were selected as co-ligands in the syntheses of the Cu(I) and Ag(I) complexes. All compounds were characterized by CHN analysis, NMR, FT-IR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS); the molecular structure of the copper(II) complex [Cu(L^BSPh)₂] was also determined by single-crystal X-ray diffraction. Finally, the antibacterial activity of the metal complexes, the Schiff base ligands and phosphane co-ligands, were assessed by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Full article

Current breast cancer therapies are unable to positively impact the lives of a significant proportion of diagnosed patients (24% based on 10-year survival rate). Breast cancer relapse and metastasis, the leading cause of breast cancer-associated deaths, is linked to the existence of breast cancer stem cells (CSCs). Redox-modulating metal complexes have been used to perturb the redox balance in breast CSCs and effect cell death. Here, we sought to expand this promising class of anti-breast CSC agents. Specifically, we report the synthesis, and anti-breast CSC properties of a series of copper(II) complexes bearing regioisomeric vanillin Schiff base ligands (1–4). X-ray crystallography studies show that the copper(II) complexes 1–4 adopt square planar geometries with the copper(II) centre coordinated to two vanillin Schiff base ligands. The most effective copper(II) complex within the series 4 displays low micromolar potency towards breast CSCs, up to 4.6-fold higher than salinomycin and cisplatin. Mechanistic studies indicate that copper(II) complex 4 elevates reactive oxygen species levels in breast CSCs, leading to activation of the JNK/p38 pathway and caspase-dependent apoptosis. Overall, this work expands the library of anti-breast CSC copper(II) complexes and provides insight into their mode of action. Full article

Due to the lack of UV-protective properties for cotton textiles and the potential of cotton textiles to cause microbes to their users, we synthesized benzimidazole Schiff base derivative (BZI) namely N-((1H-benzo[d]imidazol-2-yl)methyl)-1-(4-fluorophenyl)methanimine and their V(III), Fe(III), Co(II), Ni(II), and Cu(II) complexes as UV protection and antimicrobial agents for cotton textile. Several techniques investigated these compounds: ¹H, ¹³C NMR, IR, UV–Vis, elemental analysis, DTA, and TGA. The Schiff base ligand behaved as a bidentate ligand. The prepared ligand and its complexes are used to treat the cotton fabrics (CFs) by immersing the fabric in the solution of the samples under ultrasonic. The treated cotton fabrics were investigated using IR and SEM-EDX analysis. The UPF values of the treated cotton fabric were obtained. The results showed that the cotton fabric treated with Fe(III) and Cu(II) complexes had excellent UV protection with UPF values of 50+. The disc diffusion method evaluated the treated cotton fabric’s antimicrobial activity. The antifungal activities of the treated CFs demonstrated that the Co(II)-BZI-CF was active on C. albicans with an inhibition zone of 12 mm, while the other samples were inactive on C. albicans and A. flavus. The V(III)-BZI-CF and Fe(III)-BZI-CF had no activity against S. aureus and E. coli bacteria while the other samples gave an inhibition zone of between 10 to 17 mm. Unlike previous studies that primarily focused on either UV protection or antimicrobial properties of metal complexes separately, this research integrates both functionalities by synthesizing benzimidazole Schiff base metal complexes and applying them to cotton textiles, demonstrating enhanced UV protection and selective antimicrobial activity. Full article

The copper(II) complexes of general formula [Cu(^GL2^H,H)(Cl)] (A4–A6, G = NO₂, H and OMe, respectively), bearing NNO tridentate Schiff base ligands (^GL2^H,H)⁻ derived from the mono-condensation of 1,3-diaminopropane and G-substituted salicylaldehydes, are here reported. The elongation of the diamine with one additional carbon atom with respect to the triad derived from ethylenediamine [Cu(^GL1^H,H)(Cl)] (A1–A3, G = NO₂, H and OMe, respectively) led to different synthetic procedures, with the difficult isolation of A6 that could be obtained only in few crystals suitable for X-ray diffractions. Operating in acidic conditions to promote the coordination of chloride and expulsion of pyridine from the complex [Cu(^GL2^H,H)(py)](ClO₄) (G = NO₂) allows for obtaining A4. On the other hand, structural rearrangement occurs when G = H, yielding the dinuclear species [Cu₂(μ-saltn)(^HL2^H,H)](ClO₄)⋅0.5MeOH (D5⋅0.5MeOH) instead of the desired A5, which can be obtained by avoiding the use of HCl and operating in the excess of LiCl. Finally, A4 and A5 were investigated as cytotoxic agents against malignant (MDA-MB-231 and 22-Rv1) and healthy (HaCaT) cell lines, and the ability of the most promising A5 to be internalized and interact with cellular targets was studied. Full article

This review provides an overview of the synthesis, characterization and application of coordination polymers based on N,O-donor Schiff base ligands. The coordination polymers (CPs) represent a novel class of inorganic–organic hybrid materials with tunable compositions and fascinating structures. They are composed of metal ions and organic ligands. Therefore, the nature of the metal ion and type of organic ligand is the most significant factor in constructing targeted coordination polymers with the desired properties. Due to the versatile coordination modes, N,O-donor Schiff base ligands are also used to construct various CPs. Full article

A series of mononuclear complexes, [Fe(L5)(bylim)](BPh₄), where L5 represents a pentadentate Schiff base ligand, bylim is 1-benzyl-1-imidazole, and BPh₄⁻ is the tetraphenylborate anion, was synthesized. The determined crystal structures indicate the absence of significant cooperative interactions, which influence the properties of the eventual spin transition. Changes in magnetic behavior induced by substitution of the pentadentate ligand were investigated through magnetic susceptibility measurements. It was found that only complexes containing a non-substituted secondary amino group exhibit some form of spin crossover, whereas the majority of those with a methyl substituent remain in the high-spin state across the entire measured temperature range (2–300 K). The changes induced by the substitution of the secondary amine group were further explored through theoretical calculations at DFT and CASSCF/NEVPT2 levels of theory. The topology and energetics of electron density and atomic charges were investigated through QT-AIM calculations. Full article

Vibrational circular dichroism (VCD) enhancement by low-lying electronic states (LLESs) is a fascinating phenomenon, but accounting for it theoretically remains a challenge despite significant research efforts over the past 20 years. In this article, we synthesized two transition metal complexes using the tetradentate Schiff base ligands (R,R)- and (S,S)-N,N′-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine with Co(II) and Mn(III), referred to as Co(II)-salen-chxn and Mn(III)-Cl-salen-chxn, respectively. Their stereochemical properties were explored through a combined experimental chiroptical spectroscopic and theoretical approach, with a focus on Co(II)-salen-chxn. Extensive conformational searches in CDCl₃ for both high- and low-spin states were carried out and the associated infrared (IR), VCD, ultraviolet-visible (UV-Vis) absorption, and electronic circular dichroism (ECD) spectra were simulated. A good agreement between experimental and simulated data was achieved for IR, VCD, UV-Vis, and ECD, except in the case of VCD of Co(II)-salen-chxn which exhibits significant intensity enhancement and monosignate VCD bands, attributed to the LLESs. Interestingly, detailed comparisons with Mn(III)-Cl-salen-chxn and previously reported Ni(II)-salen-chxn and Cu(II)-salen-chxn complexes suggest that the enhancement factor is predicted by the current density functional theory simulations. However, the monosignate signatures observed in the experimental Co(II) VCD spectrum were not captured theoretically. Based on the experiment and theoretical VCD and ECD comparison, it is tentatively suggested that Co(II)-salen-chxn exists in both low- and high-spin states, with the former being dominant, while Mn(III)-Cl-salen-chxn in the high-spin state. The study indicates that VCD enhancement by LLESs is at least partially captured by the existing theoretical simulation, while the symmetry consideration in vibronic coupling provides further insight into the mechanisms behind the VCD sign-flip. Full article

In recent years, metallodrugs have emerged as captivating and promising compounds in the fields of cancer therapy and antimicrobial agents. While noble metals have shown remarkable biological activity, increasing interest lies in utilizing more abundant and cost-effective metals in medicinal chemistry. This is primarily due to their pivotal role in biological processes and their lower cost compared to precious metals. Among these, copper(II) complexes have emerged with promising applications in medicine. Notably, copper compounds bearing Schiff bases stand out as innovative metallodrugs. They exhibit intriguing cytotoxic properties against a wide range of cancer cell lines, while also demonstrating inhibitory effects on prevalent bacterial and fungal strains. Nevertheless, research into Cu(II) complexes with Schiff bases remains of paramount interest. One strategic avenue to bolster their biological activity involves the introduction of fluorine groups into the ligands. This approach has demonstrated a significant augmentation in efficacy and selectivity, particularly in targeting cancer cells and microbial pathogens, because fluorine incorporation can improve metabolic stability and cellular uptake. This further reinforces the therapeutic potential of these metallodrugs. Thanks to these promising outcomes, research into the development of Cu(II) complexes with fluorinated Schiff bases is advancing significantly. This holds immense potential for progressing the field of medicinal chemistry, with the aim of addressing unmet clinical needs in both cancer therapy and antimicrobial treatment. This review comprehensively explores the latest advancements in Cu(II) complexes bearing fluorinated Schiff bases, encompassing diverse coordination modes. It delves into their scope and applications in cytotoxic evaluations, as well as their efficacy as antimicrobial and antifungal agents. Full article

Glioblastoma, an aggressive cancer, is difficult to treat due to its location, late detection, drug resistance, and poor absorption of chemotherapeutics. Intratumoral drug administration offers a promising potential treatment alternative with localized delivery and minimal systemic toxicity. Vanadium(V) coordination complexes, incorporating Schiff base and catecholate ligands, have shown effects as antiproliferative agents with tunable efficacy and reactivity, stability, steric bulk, hydrophobicity, uptake, and toxicity optimized for the intratumoral administration vehicle. A new series of oxovanadium(V) Schiff base–catecholate complexes were synthesized and characterized using nuclear magnetic resonance (NMR), UV-Vis, and infrared spectroscopy and mass spectrometry. Stability under physiological conditions was assessed via UV-Vis spectroscopy, and the antiproliferative activity was evaluated in T98G glioblastoma and SVG p12 normal glial cells using viability assays. The newly synthesized [VO(3-tBuHSHED)(TIPCAT)] complex was more stable (t_1/2 ~4.5 h) and had strong antiproliferative activity (IC₅₀ ~1.5 µM), comparing favorably with the current lead compound, [VO(HSHED)(DTB)]. The structural modifications enhanced stability, hydrophobicity, and steric bulk through substitution with iso-propyl and tert-butyl groups. The improved properties were attributed to steric hindrance associated with the new Schiff base and catecholato ligands, as well as the formation of non-toxic byproducts upon degradation. The [VO(3-tBuHSHED)(TIPCAT)] complex emerges as a promising candidate for glioblastoma therapy by demonstrating enhanced stability and a greater selectivity, which highlights the role of strategic ligand design in developing localized therapies for the treatment of resistant cancers. In reporting the new class of compounds effective against T98G glioblastoma cells, we describe the generally desirable properties that potential drugs being developed for intratumoral administration should have. Full article