Search Results (98)

The disadvantages of Cisplatin in anticancer treatment are connected to its poor selectivity, resistance developed of cancers to the drug, and its toxicity against normal organs. An important strategy in anticancer treatment is the synthesis and clinical investigation of non-platinum metal complexes with superior anticancer activity and improved selectivity compared to Cisplatin, combined with lower toxicity, fewer side effects and decreased resistance of cancer to the drug. In the current study, we aim to summarize the potential of important non-platinum metal-based organic compounds as therapeutic agents against different cancer cell types. The review covers the general principles of chemotherapy. A literature analysis shows that organic complexes of the metalloids arsenic (As), boron (B), antimony (Sb), and selenium (Se), and of metals, such as Ag, Au, Co, Cu, Fe, Mn, Mo, Ni, Zn, Ce, Ga, Gd, Ir, Os, Pd, Re, Rh, Ru, Ti, and V, have been investigated for potential applications in cancer therapy. This is due to their antiproliferative effects against different cancer types: lung [Cd(II), Co(II), Cu(II), Ni(II), Mn(II), Ru(II), Zn(II)]; breast [Ag(I), Cu(I), Cu(II), Ir(III), Ni(II), Mn(II),. Rh(III), Ru(II)]; gastric [Cu(II), Cu(II)-La(III)]; colon [Ag(I), Cu(II), Ir(III), Pd(II), Rh(III), Ru(II), vanadium(V)]; colorectal [Ag(I), Co(II), Cu(II), Zn(II)]; liver [Ag(I), Co(II), Cu(II), Gd(III), vanadium(V)]; pancreatic [vanadium(IV)]; bladder [Ag(I), Cu(II), Ru(II)]; cervical [Ag(I), Au(I), Cu(I), Cu(II), Fe(II), Ir(III), Rh(III), Ru(II)]; testicular [vanadium(IV)]; prostate [Cu(II), Pd(II), Zn(II)]; leukemia [Ag(I), Co(II), Cu(II), Pd(II), Zn(II)]; sarcoma [Co(II), Ni(II), Zn(II)]; mesothelioma [Cu(II)]; neuroblastoma [Cu(II)]; glioma [Cu(II)]; and melanoma [Au(I), Cu(II), Pd(II), Ru(II)]. The main goals for increasing anticancer metal-based complexes include increasing anticancer activity and selectivity, reducing toxicity, and avoiding cancer cell resistance. Compared to Cisplatin, organocomplexes of copper, ferrocene, and ruthenium are more active. Ruthenium and copper complexes, in particular, are also more selective. Notably, ruthenium and ferrocene derivatives are less toxic than Cisplatin. Lastly, cancers appear to exhibit less resistance against copper, gold, ruthenium, palladium, and ferrocene complexes. Full article

The precise determination of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels is critical for understanding the photophysical and photochemical properties of carbon dots (C-dots), which directly govern their performance in optoelectronic, catalytic, and sensing applications. However, the lack of distinct redox peaks in cyclic voltammetry (CV) curves of C-dots poses a major challenge to conventional energy level calculation methods. Herein, we propose a novel strategy to calculate the HOMO–LUMO energy levels of C-dots by combining electron transfer (ET) kinetics with Marcus theory. A series of quinones (electron acceptors, EAs) and ferrocene derivatives (electron donors, EDs) were employed to quench the fluorescence of C-dots, and the ET rate constants (K) were derived from fluorescence lifetime measurements. The CV curves of EAs and EDs provided their respective oxidation and reduction potentials, which were used as reference energy levels. The UV–Vis absorption spectra confirmed that the fluorescence quenching mechanism was dominated by ET rather than energy transfer. Based on Marcus theory, the free energy change (ΔG) of ET reactions was correlated with K, and the HOMO and LUMO energy levels of C-dots were calculated to be −1.84 V (vs. SCE) and +1.60 V (vs. SCE), respectively. This study not only provides a reliable method for determining the energy levels of C-dots without distinct redox peaks but also deepens the understanding of ET mechanisms between C-dots and small molecules. The proposed strategy is expected to be extended to other fluorescent nanomaterials with similar CV limitations. Full article

Ruthenocene (Rc) and its derivatives form a structurally versatile class of metallocenes with unique and multifunctional applicability. This review presents a detailed analysis of Rc chemistry including the structural comparison with ferrocene, its redox behavior, and substituent effects. We also discuss its applications in sensing, energy storage, photochemistry, and biomedicine. Rc exhibits unique conformational and adaptive electronic properties based on one and two-electron oxidation processes. Electrochemical investigations of Rc to date indicate that its redox behavior is strongly dependent on the electrolyte system, exhibiting quasi-Nernstian characteristics, the formation of stabilized dimeric species [Rc₂]²⁺, and interconversion among Ru(II), Ru(III), and Ru(IV) oxidation states. Rc-based systems exhibit superior performance as redox mediators and labels in electrochemical sensing systems in terms of electron-transfer kinetics, signal amplification, and surface immobilization. In the field of energy storage, Rc decreases the charging overpotential and increases the cycle life of Li-O₂ batteries. Rc further acts as a photoinitiator via charge-transfer-to-solvent and efficient photoinduced electron transfer in metalloporphyrin and fullerene dyads. In biomedical research, Rc derivatives as well as bioconjugates possess promising anticancer activities, displaying reactive oxygen species generation, topoisomerase inhibition, thioredoxin reductase inhibition, receptor-mediated uptake, and target peptide conjugation. Given its flexible ligand design, electrolyte driven redox behaviors, and antiproliferative properties, Rc exhibits a very adaptive molecular scaffold for next generation electrochemical technologies as well as metallodrug design. Full article

The N-ferrocenoylation of uracil was studied to evaluate regioselectivity and optimise preparation protocols. Regioselectivity was monitored under various reaction conditions, with particular attention paid to the effects of the solvent and the base. Reactions in DMF were regiospecific, yielding only the N1 product, while reactions in CH₃CN produced both N1 and N1/N3 products, with ratios depending on the reaction conditions. The highest yield of N1/N3-diferrocenoyl uracil was achieved with an extended reaction time of 90 min using uracil and triethylamine. Optimised conditions were applied to C5-uracil derivatives, producing N1 and N1/N3 products. Regioselectivity and N-substitution were confirmed by NMR, and solvent effects were supported by quantum chemical calculations. The resulting ferrocene–pyrimidine conjugates exhibited oxidative and immunomodulatory activity, highlighting their biological potential. Full article

While many [FeFe]-hydrogenase biomimetics are effective proton-reduction catalysts, few are active for H₂ oxidation, and examples containing both a pendant amine group, able to act as a proton relay, and a second redox center, both essential features of the enzymes, are rare. Here we report the preparation and oxidation chemistry of two ferrocene-functionalized amino-diphosphines (PCNCP), (CH₂PR₂)₂NCH₂Fc (R = Ph (1), Cy (2)), and their ethylenedithiolate (edt) diiron complexes, [Fe₂(CO)₄(μ-edt){κ²-(R₂PCH₂)₂NCH₂Fc}] (R = Ph (3), Cy (4)). Their crystallographic characterization shows that PCNCP occupies an apical–basal position. CV responses are slightly R-dependent, showing for 3 and 4 in three separate oxidative processes assigned to successive one-electron oxidation of the diiron core (quasireversible), appended Fc (reversible), and the amine–diiron moiety (irreversible), as confirmed by IR and UV–Vis spectroelectrochemical studies supported by Density Functional Theory (DFT) and Time-dependent Density Functional Theory (TDDFT) calculations. The first oxidation results in a structural rearrangement of the Fe(PNP)(CO) unit and the formation of a semi-bridging carbonyl. Slow protonation of 3 with HBF₄∙Et₂O affords the corresponding N-protonated cation in acetone, whilst μ-hydride products dominate for both 3 and 4 in CD₂Cl₂. A preliminary H₂ oxidation study was carried out with 3, and while there was some evidence of activity, it was much lower than reported for alkyl-functionalized PCNPC diiron derivatives. Full article

Copper-based catalysts have emerged as promising materials for electrochemical carbon dioxide reduction reactions, owing to copper’s unique ability to facilitate multi-electron transfer processes and produce valuable products such as methanol and ethanol. In this study, novel trisferrocenyltrithiophosphite–copper(I) bromide composites with Cu-to-ligand molar ratios of 1:1 and 2:1 were synthesized and evaluated for their catalytic performance. The composites were characterized by a combination of techniques, including powder X-ray diffraction (PXRD), linear sweep voltammetry (LSV), potentiostatic testing, chromatographic analysis, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Electrochemical measurements demonstrated significant current enhancements in the presence of CO₂, highlighting the composites’ catalytic activity. Potentiostatic tests revealed excellent stability, with only a 9% decline in current density over 5 h of electrolysis. Product analysis via gas chromatography indicated the formation of methanol for the 1:1 composite and ethanol for the 2:1 composite with Faradaic efficiencies of 5.79% and 9.26%, respectively. While absolute efficiencies remain modest due to competitive hydrogen evolution, these results demonstrate a tunable catalytic performance based on the Cu-to-ligand ratio. SEM and XPS studies further supported the formation of active catalytic centers and changes in the oxidation states of copper during CO₂ reduction. PXRD analysis confirmed the retention of structural integrity for both composites before and after catalytic testing. Full article

Redox mediators are central to electrochemical biosensors, enabling electron transfer between deeply buried enzymatic cofactors and electrode surfaces when direct electron transfer is kinetically inaccessible. Among all design parameters, the reversibility of mediator redox cycling remains the most decisive yet under-examined factor governing biosensor stability, drift and long-term reproducibility. This review establishes reversibility as a unifying framework grounded in inorganic and organometallic redox chemistry, with particular emphasis on coordination environments, ligand-field effects and outer-sphere electron-transfer pathways. Recent advances (2010–2025) in ruthenium and osmium polypyridyl complexes, cobalt macrocycles, hexacyanoferrates and Prussian Blue analogues are examined alongside ferrocene derivatives and other organometallic mediators, which together define the upper limits of reversible behaviour. Organic mediator families, including quinones, phenazines, indophenols, aminophenols and viologens, are discussed as mechanistic contrasts that highlight the structural and thermodynamic constraints that limit long-term cycling in aqueous media. Mechanistic indicators of reversibility, including peak separation, current ratios and heterogeneous electron-transfer rate constants, are linked to mediator architecture, coordination chemistry and immobilisation environment. By integrating molecular electrochemistry with applied sensor engineering, this review provides a mechanistically grounded basis for selecting or designing redox mediators that sustain efficient electron transfer, minimal fouling and calibration stability across diverse sensing platforms. Full article

Choline is a central metabolite that connects membrane turnover, neurotransmission, and one-carbon metabolism, and its reliable measurement across diverse biological matrices remains a significant analytical challenge. This review brings together biological context, electrochemical mechanisms, and device engineering to define realistic performance targets for choline sensors in blood, cerebrospinal fluid, extracellular space, and milk. We examine enzymatic sensor architectures ranging from peroxide-based detection to mediated electron transfer via ferrocene derivatives, quinones, and osmium redox polymers and assess how applied potential, oxygen availability, and film structure shape electron-transfer pathways. Evidence for direct electron transfer with choline oxidase is critically evaluated, with emphasis on the essential controls needed to distinguish true flavin-based communication from peroxide-related artefacts. We also examine bienzymatic formats that allow operation at low or negative bias and discuss strategies for matrix-matched validation, selectivity, drift control, and resistance to fouling. To support reliable translation, we outline reporting standards that include matrix-specific concentration ranges, reference electrode notation, mediator characteristics, selectivity panels, and access to raw electrochemical traces. By connecting biological requirements to mechanistic pathways and practical design considerations, this review provides a coherent framework for developing choline sensors that deliver stable, reproducible performance in real samples. Full article

Background/Objectives: This study focused on synthesizing novel alkenyl derivatives of azinylferrocenes and evaluating their potential as Alzheimer’s disease (AD) therapeutics. Methods: 1-Azinyl-1′-acetylferrocenes were obtained by regioselective acetylation of azinylferrocenes, followed by the Wittig reaction or reduction of 1-azinyl-1′-acetylferrocenes and subsequent dehydration of the resulting alcohols. The synthesized compounds underwent the following biological activity testing relevant to AD: inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and off-target carboxylesterase (CES); antioxidant capacity (ABTS and FRAP assays); inhibition of Aβ₄₂ self-aggregation (thioflavin method); blocking AChE-induced β-amyloid aggregation (propidium displacement); and cytotoxicity in SH-SY5Y and MSC-Neu cells (MTT assay). Results: Quinoline and bipyridine derivatives demonstrated effective cholinesterase inhibition, especially quinoline 7b (AChE IC₅₀ 3.32 μM; BChE IC₅₀ 3.68 μM), while acridine derivatives were poor inhibitors. Quantum chemical (QC) calculations predicted that acridine derivatives were especially prone to form stable dimers. Molecular docking into protein targets generated by an AlphaFold3 reproduction code showed that these dimers were too bulky to access enzyme active sites, yet they could bind to protein surfaces to inhibit Aβ₄₂ self-aggregation and displace propidium from the AChE peripheral anionic site. All compounds showed high antioxidant activity in ABTS and FRAP assays, with quinoline derivatives being 2–4 times more potent than Trolox. QC calculations supported these findings. Quinoline and bipyridine derivatives also exhibited low cytotoxicity and scant CES inhibition. Conclusions: Overall, the synthesized ferrocenes, particularly the quinoline and bipyridine derivatives, appear promising for further research as multifunctional therapeutic agents targeting AD due to their anticholinesterase, antiaggregating, and antioxidant activities combined with low toxicity. Full article

Tamoxifen is a well-established selective estrogen receptor modulator (SERM) widely used in breast cancer treatment, yet its efficacy varies across tumor types. To enhance its antitumor potential, we previously synthesized and investigated novel ferrocene-linked (T5, T15) derivatives. This publication is a close continuation of this work, introducing a new indene-based (T6) derivative. Objectives: The main aim of this study was to further broaden our knowledge of the mechanism behind the increased antitumor effect of the ferrocene-linked drugs (T5 and T15) and compare it with a new, indene-based tamoxifen derivative, T6. The indene moiety was selected as a rigid, hydrophobic aromatic unit to probe pharmacological effects independent of ferrocene’s redox activity. Methods: The compounds were tested on MCF7, MDA-MB231 and PANC1 cells. Cell viability was assessed with the AlamarBlue assay and the xCELLigence SP system. Reactive oxygen species (ROS) production was measured with the ROS Glo assay. Flow cytometry and RT-qPCR experiments were conducted to assess apoptosis and ROS regulation as well. Results: The modified compounds demonstrated an increased cell-viability-decreasing effect in breast (MCF7, MDA-MB-231) and pancreatic (PANC1) cancer cell lines, influencing both estrogen-receptor-dependent and -independent pathways. T6 led to G2/M phase arrest in PANC1 cells. Beyond cell cycle disruption, these derivatives significantly elevated ROS levels, contributing to apoptosis. Conclusions: Our findings suggest that these structural modifications retain tamoxifen’s pharmacophore properties while expanding its mechanism of action, particularly through universal interactions independent of the ER status of tumor cells. The enhanced antitumor effects highlight the potential of these derivatives as promising candidates for improved cancer therapies. Full article

Ferrocene (Fc), a redox-active organometallic scaffold, has attracted significant attention in medicinal chemistry due to its favorable physicochemical and pharmacological properties. The present study explores the therapeutic potential of novel Fc-functionalized analogues of imatinib and nilotinib, aimed at targeting BCR-ABL1+ chronic myeloid leukemia (CML) cells. A series of Fc-based derivatives (compounds 6, 9, 14, and 18) were synthesized by systematically substituting key pharmacophoric regions of the parent tyrosine kinase inhibitors with Fc units. The antiproliferative activity of these compounds was evaluated against four BCR-ABL1-positive leukemia cell lines (K-562, BV-173, AR-230, and LAMA-84), with imatinib serving as a reference drug. Biological assays revealed distinct structure–activity relationships. Compounds 6 and 9 demonstrated superior activity against the K-562 cell line, while compounds 14 and 18 exhibited enhanced potency and higher ligand efficiencies (LEs) against BV-173 and AR-230 cells compared to imatinib. Selectivity assays further indicated favorable toxicity profiles of compounds 9 and 14 toward malignant versus non-malignant cells. Molecular docking studies supported these findings, showing that Fc substitution alters binding interactions within the c-Abl kinase ATP-binding site while retaining key stabilizing contacts. Computationally predicted LEs showed strong correlation with experimental data, especially for K-562 and LAMA-84 cells, confirming the kinase as a relevant target. Full article

In this study, a series of (Z)- and (E)-2-substituted-3-ferrocene-acrylonitrile derivatives were synthesized, characterized, and evaluated in vitro for their anticancer and anti-migration properties. The compounds were synthesized via the Knoevenagel condensation of the appropriate benzyl cyanide or benzoyl acetonitrile with ferrocenecarboxaldehyde 1, producing isolated yields of 99 to 23%. The structures of the compounds were analyzed using IR, ¹H NMR, ¹³C{¹H} NMR, GC-MS, and UV/Vis spectroscopic methods. Single-crystal X-ray diffraction analysis of representative compounds 21, 27, and 29 demonstrated that the geometry of the double bond was that of the (Z)-isomer. For representative compound 33, the geometry of the double bond was that of the (E)-isomer. Additionally, the electrochemistry of the compounds was investigated using cyclic voltammetry. The cytotoxic and anti-migratory effects of these compounds were evaluated in the MCF-7 and MDA-MB-231 breast cancer cell lines, providing insight into the structure–activity relationships. Preliminary investigations of their anticancer activity revealed that several compounds exhibit moderate antiproliferative effects on cancer cell lines, with GI₅₀ values ranging from 23 to 44 μM for the MCF-7 cell line and from 9 to 41 μM for the MDA-MB-231 cell line. Moreover, compound (Z)-25 inhibited 13% of the migration activity of the metastatic MDA-MB-231 cell line. Full article

Chemically modified electrodes based on derivatives of 2-thioxothiazolidin-4-one were mentioned as possible solutions for heavy metal (HM) ions heterogeneous recognition. Such ligands form thin films with reversible responses in the ferrocene redox probe with a well-defined symmetrical peak and symmetrical values for the anodic and cathodic currents. Their selectivity in coordinating HM ions was proven. In this paper, a computer-added study was performed using density functional theory (DFT) based on two methods, B3LYP and ωB97XD, to arrive at a better inside of their structure. Properties related to their reactivity concerning experimental electrochemical behaviour and spectral results were calculated using specific molecular descriptors. DFT-calculated HOMO-LUMO energies were found in good linear correlation with experimental redox potential. The accuracy of the calculations was also proven by a good agreement between the energy calculated by the DFT method and the UV-Vis spectra for the studied ligands. Such a computational approach can be used to evaluate the properties of possible new ligands for such electrochemical applications. The strong correlation between DFT-predicted quantum parameters and experimental redox potentials underscores the relevance of these computational approaches in designing selective molecular sensors. The results obtained using the two functionals are in good agreement, although there are also situations and parameters for which the results are not identical. There is a symmetry of the values obtained by the electrochemical and spectral methods with those calculated by DFT. Full article

Ferrocene is an organometallic compound that has attracted considerable scientific interest due to its unique properties, including low toxicity, excellent stability in aqueous and aerobic media, and high lipophilicity, which enhances membrane permeability. The ferrocene moiety has been effectively used as a bioisostere of phenyl rings and heteroaromatic groups in the structures of approved tyrosine kinase inhibitors and histone deacetylase inhibitors (HDACis). HDACis exert their cytotoxic effects by blocking cyclin/CDK complexes, causing cell cycle arrest, inducing apoptosis, inhibiting angiogenesis, and through non-histone-directed mechanisms. This mini-review summarizes the synthesis and biological evaluation of small libraries of compounds in which a ferrocenyl moiety is incorporated into the structure of suberoylanilide hydroxamic acid (SAHA) and a number of analogues. The influence of the organometallic function on the antiproliferative effect is investigated. Both docking analysis and in vitro studies confirm that the ferrocenyl-modified HDACis exhibit potent cytotoxicity and strong inhibitory activity against the various enzyme isoforms. Full article

Ferrocene (Fc) has long been celebrated for its remarkable redox properties and structural versatility, making it a cornerstone of electrochemical sensor development. While extensive research has focused on cation detection using Fc-based systems, the equally critical recognition of neutral and anionic molecules remains underexplored despite their significance in biological, environmental, and industrial contexts. This review addresses this gap by exploring the latest advancements in Fc-based electrochemical sensors designed to overcome the unique challenges posed by these species—including diverse geometries, high hydration enthalpies, and the absence of formal charge. Molecular architectures such as amide-functionalised receptors, urea derivatives, Lewis acid-containing receptors, triazolium, and carboxylic acid-containing systems are examined, highlighting how these sensors achieve high selectivity and sensitivity. Furthermore, the influence of solvent environments on sensor performance is discussed, providing a critical analysis of how different receptor functionalities and solvents affect sensor behaviour. Emphasising the advantages of redox-based detection, this review aims to inspire further innovation in developing Fc-based technologies for detecting neutral and anionic species. Full article