We report on the synthesis and characterization of four novel Ru(II) polypyridyl complexes incorporating bipyridine or phenanthroline ancillary ligands. Substituted 1,2,4-oxadiazoles are introduced here for the first time as chelating ligands for Ru(II), and the structure of a representative complex unequivocally established by single-crystal X-ray diffraction. The antiproliferative activity of the metal complexes in human colorectal (HCT116 and oxaliplatin- and BOLD-100-resistant derivatives) and ovarian (A2780 and A2780cis) cancer cell lines was evaluated. The presence of phenanthroline ancillary ligands induced the highest cytotoxicity, with platinum-resistant cells displaying enhanced sensitivity compared to parental lines. Cellular uptake of the metal complexes was quantified by ICP-MS. Finally, in vivo tests were conducted in BALB/c mice using the most promising compound, to evaluate its toxicity profile and its ability to inhibit CT-26 tumor growth. Interestingly, both duplex and G-quadruplex DNA can be excluded as potential molecular targets, as assessed by FRET-melting assays, UV-Vis spectroscopy, and circular dichroism.

Camalexin, a primary indole-analogous phytoalexin from Arabidopsis thaliana and other crucifers, inhibits the proliferation of various cancer cells. In this contribution, the synthesis and characterization of camalexin-derived Ru­(II) half-sandwich complexes are described. Formation and sufficient purity of the complexes were confirmed by 1H-, 13C- and 2D-NMR techniques, X-ray or 3D electron diffractometry, high-resolution-mass-spectrometry (HRMS) and elemental analysis. Additionally, the stability in aqueous solution was studied under pseudophysiological conditions, revealing sufficient stability for further biological studies. Investigating the in vitro anticancer potency by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and resazurin assays in four human cancer cell lines revealed IC50 values in the (mostly low) micromolar range. Tests for the capacity of generating reactive oxygen species (ROS) in the leukemic HL60 cell line identified one derivative with exceptionally high ROS induction via a 2′,7′-dichlorofluorescin diacetate (DCFH-DA)-based approach. While increased ROS levels were not decisive for cell death induction, cytotoxic activity of the complexes was associated with mitochondrial membrane depolarization and functional perturbation. Lastly, the ability of the complexes to induce apoptosis was investigated, with the complexes showing remarkable effects, while the free ligands exhibited hardly any signs of apoptosis induction.

The selective recognition of G-quadruplex (G4) DNA structures by metal complexes holds considerable promise for anticancer drug development, particularly for targeting oncogene promoters and telomeric regions. Herein, we report the synthesis, structural characterization, and DNA-binding strength evaluation of a new series of transition metal complexes derived from a N4 tetradentate naphthalene-bridged Schiff base ligand (Naphthim). The zinc(II), copper(II) and nickel(II) complexes were obtained via in situ or transmetallation protocols and characterized by NMR, HR-ESI-MS, and elemental analysis. Among them, the copper(II) complex, 2, [CuNaphthim]2+, exhibited the highest DNA-binding affinity and G4-stabilizing ability, as assessed by FRET-based DNA melting assays, UV-Vis absorption, and circular dichroism (CD) spectroscopy. Despite lacking cationic side chain substituents, 2 showed moderate stabilization of several G4 structures, with a preferential effect on the cMyc quadruplex. Comparative studies with the benchmark [CuPhenim]2+ complex revealed that π-extension of the ligand framework substantially enhances DNA-binding affinity and modulates selectivity. UV-Vis and CD spectroscopy revealed clear differences in DNA-binding behavior between 2 and [CuPhenim]2+, with compound 2 exhibiting stronger and more defined interactions across both G4 and duplex targets. These trends found support by molecular docking, which uncovered distinct binding modes depending on G4 topology and echoed the observed affinity profiles. These findings highlight the Naphthim scaffold as a promising modular platform for the design of G4-targeting metal complexes.

In recent years, the invasive Atlantic blue crab (Callinectes sapidus) has increased its spread throughout the Mediterranean Sea, threatening native biodiversity and local economies. This study aimed to valorize C. sapidus sampled in Sicily by utilizing its exoskeleton as a source of chitosan, astaxanthin, and bio-phenolic compounds. These biomolecules were evaluated for their reducing, radical scavenging, and antitumor activity. The ferric ion reducing antioxidant power (FRAP) and the free radical scavenging activity against radical 2,2-Diphenyl-1-picrylhydrazyl (DPPH) were significantly higher for chitosan (3.16 ± 0.10 mg AAE/g and 8.1 ± 0.10 µmol TE/g). No significant differences were observed among the tested biomolecules in their activity in scavenging the radical 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Both bio-phenolic compounds and astaxanthin exhibited dose-dependent cytotoxicity on CaCo-2 (IC50 = 12.47 and 18 µg/mL) and HepG2 (IC50 = 10.25 and 1.26 µg/mL) cell lines, while only bio-phenols showed no cytotoxic effect on differentiated CaCo-2 cells up to 20 µg/mL. These findings highlight the value of blue crab by-products in supporting a circular economy, offering a sustainable approach to managing this invasive species while providing bioactive compounds with promising medical and nutraceutical applications.

Based on our recent research experience, this review highlights the DNA binding of salen, salphen and salnaphen metal complexes, with a focus on G-quadruplex (G4) DNA, which is crucial in peculiar genomic regions and in cancer regulation. Such metal complexes have in fact shown significant ability to bind and stabilize G4 structures. We will point out the role of the metal center and of the ligand substituents affecting their binding and selectivity toward G4s, supported by experimental and computational studies.

Ten organometallic complexes of the general formula [M(p-cymene)thiCΛNMeIm]NO3 (M = Ru, Os; MeIm = 1-methylimidazole, thi = 4-phenylthiazole) differing in their substituents on the 4-phenylthiazole scaffold were prepared and characterized by standard analytical methods. The antiproliferative activity of the compounds was investigated in human lung adenocarcinoma (A549), colon adenocarcinoma (SW480), and human ovarian teratocarcinoma (CH1/PA-1) cell lines. IC50 values were in the low micromolar range with two exceptions. Additionally, the cytotoxicity of selected compounds was determined in the HCT116 colon carcinoma cell line in both 2D (monolayer) and 3D (multicellular spheroid) cultures. For selected compounds, the capacity of ROS induction was investigated in SW480 cells. Cellular accumulation experiments, as well as studies regarding stability and reactivity in aqueous solution, were performed, providing conclusive explanations for the observed differences in cytotoxicity. Furthermore, amino acid and DNA interaction studies were performed to elucidate aspects of the mechanism of action. The obtained insight into the antiproliferative activity in multicellular spheroids compelled us to perform in vivo studies, revealing the unexpected therapeutic efficacy of an in vitro inactive complex.

This study evaluates, for the first time, the reducing capacity, radical scavenger activity, and in vitro antitumor and anti-inflammatory effects of chitosan, astaxanthin, and bio-phenols extracted from the exoskeleton of Sicilian Procambarus clarkii, the most widespread species of invasive crayfish in the Mediterranean region. Among the extracted compounds, astaxanthin exhibited the highest antioxidant activity in all assays. Chitosan and polyphenols demonstrated reducing and radical scavenging activity; chitosan showed significant ferric ion reducing capacity in the FRAP test, while bio-phenolic compounds displayed notable radical scavenging activity in the DPPH and ABTS assays. Both astaxanthin and polyphenols showed dose-dependent cytotoxicity on two different cancer cell lines, with IC50 values of 1.45 µg/mL (phenolic extract) and 4.28 µg/mL (astaxanthin extract) for HepG2 cells and 2.45 µg/mL (phenolic extract) and 4.57 µg/mL (astaxanthin extract) for CaCo-2 cells. The bio-phenolic extract also showed potential anti-inflammatory effects in vitro by inhibiting nitric oxide production in inflamed RAW 264.7 macrophages, reducing the treated/control NO ratio to 77% and 74% at concentrations of 1.25 and 1.5 μg/mL, respectively. These results suggest that P. clarkii exoskeletons could be a valuable source of bioactive molecules for biomedical, pharmaceutical, and nutraceutical application while contributing to the sustainable management of this invasive species.

In recent decades, researchers have focused on developing less toxic and more precise cancer therapies. Carbon nanodots (CDs) are among the most promising technologies due to their high biocompatibility, tunable fluorescence, and ability to facilitate photothermal and photodynamic therapy. This study explores the synthesis and characterization of two CDs conjugated with Salphen metal complexes, namely, CDs-PEG-M1 and CDs-PEG-M2, through Sonogashira coupling. Their interaction with G-quadruplex DNA structures (G4s), motifs largely involved in cancer development, was evaluated using various spectroscopic techniques. The results indicate that CDs-PEG-M1 exhibits greater effectiveness in stabilizing G4 structures compared to the metal complex alone or nonfunctionalized CDs. This enhanced stabilization suggests that CDs-PEG-M1 could reduce the concentration of the metal complex needed for potential antitumor applications, thereby minimizing side effects on nontarget tissues. When tested on breast cancer models (MDA-MB-231 as a triple-negative model and MCF-7 as a HER-2 positive model) and on a healthy cell line (HDFa), the CDs-PEG-M1 conjugate reduced cell viability in a concentration- and time-dependent manner, showing greater potency and selectivity against cancer cells compared to virgin CDs and the free M1 complex. This synergistic anticancer effect, driven by the interaction with G4 structures and reactive oxygen species production, underscores the potential of CDs-PEG-M1 as a targeted nanotheranostic tool.

4-Phenylthiazole-based metalacycles were synthesized, characterized and examined for their anticancer potential. Preliminary mode of action studies to reveal the cellular target of these complexes were performed.

Flavin-like ligands (L-1 and L-2) with extended π-conjugation were synthesized using microwave-assisted techniques. An N,N-chelating fragment was integrated into alloxazine units, providing binding sites for metal ions while retaining redox activity. The complexation capability of L-1 and L-2 with two prototypical Ru-scaffolds was examined to design Ru(II) complexes (M-1 and M-2), whose electronic properties were studied and compared with their corresponding ligands via absorption and emission spectroscopy, computational analysis (DFT and TD-DFT), and cyclic voltammetry (CV). The ability of L-1 and M-1 to undergo alloxazine/isoalloxazine tautomerization was demonstrated to play a crucial role in the photocatalytic oxidation of NADH, including under green and red wavelengths. Moreover, the interaction of M-1 and M-2 with B-DNA and G-quadruplex structures was investigated. M-2 showed high stabilization of Kit1 and h-Telo oligonucleotides. Meanwhile, M-1 demonstrated switchable emissive properties with B-DNA and induced conformational changes in the h-Telo G-quadruplex structure.

Computer aided procedures to design and optimize forming processes have become crucial research topics as the industrial interest in cost and time reduction has been increasing. A standalone numerical simulation approach could make the design too time consuming while meta-modeling techniques enables faster approximation of the investigated phenomena, reducing the simulation time. Many researchers are, nowadays, facing such research challenge by using various approaches. Response surface method (RSM) is probably the most known one, since its effectiveness was demonstrated in the past years. The effectiveness of RSM depends both on the definition of the Design of Experiments (DoE) and the accuracy of the function approximation. The number of numerical simulations can be strongly reduced if a proper optimization approach is implemented: one of the main issues about optimization techniques is related to the design necessity of performing either global or local approximation. This paper aims to test the efficacy of some meta-modeling techniques in the optimization of a T-shaped hydroforming process. In this paper three optimization approaches based on different meta-modeling techniques are implemented. In particular, classical Polynomial Regression approach (PR), Moving Least Squares approximation (MLS) and Kriging method are applied. The results showed that, thanks to the peculiarities of MLS and Kriging methods, it is possible to strongly reduce the computational effort in sheet metal forming optimization, particularly in comparison with a classical PR approach. Differences were highlighted and quantified.

Lightweight materials have become an important strategy in the automotive industry to enable vehicle weight reduction and reduce fuel consumption. However, when developing specific strategies, the overall benefits of any material should be analyzed throughout its life cycle to comprehend energy/environmental differences that arise during its processing and its final use. A key example is aluminum which despite having great potential in the use phase requires large amounts of energy to process. This paper provides a comparison between aluminum and steel utilizing a life-cycle approach. This approach reveals the importance of incorporating a recycling strategy to leverage aluminum’s low-weight attributes.

A crucial issue in sheet stamping optimization problems is related to the process robustness improvement: critical scattering in the investigated performances arises due to some noise variables influence, often evolving up design failure itself. In fact, strong variations in the final stamped part or fluctuations of strain distribution may lead to an uncontrolled process design. Such variability cannot be controlled but anyway it is possible to develop proper design tools able to identify robust process calibrations above which the noises variations effects are admissible. In this paper, a multi-objective optimization problem was analyzed, with the aim to minimize both excessive thinning and springback occurrences in a sheet stamping process of an aluminum alloy. In fact, major stamping operations are characterized by conflicting goals to be accomplished, introducing a further difficulty in the process variability control. Two kinds of robust design approaches were compared, a hybrid deterministic-stochastic framework and a dual response based approach, with the aim to analyze how each kind of approach may address the final design choices. Actually, the variability investigation may be considered as final robustness evaluation, otherwise the process may be calibrated under the stochastic effects of the noise variables.

The aim of this paper is to develop a design tool for stamping processes, which is able to deal with the scattering of the final part quality due to the inner variability of such operations. Such variability is one of the main drawbacks for a robust process design. It results in a scattering of the most significant process results and depends on several parameters. The so called noise factors greatly influence final result variability, which often means rejecting parts and anyway achieving final properties different from the specified ones.

A very critical issue for stamping operations is the improvement of process robustness. The reliability of final results, in fact, strongly depends on the intrinsic variability due to stochastic behavior of many parameters, namely, operative ones and material properties. A given process performance may undergo a variation around the value which would be obtained neglecting stochastic behaviors of the operative or material parameters (i.e., considering a deterministic parameters behavior). Such variation introduces a significant source of uncertainty within the process design: a possible consequence may be the rejection of some stamped parts. In this paper, reliability analyses aimed to evidence and quantify the effects of material coil-to-coil variations on springback and thinning phenomena is proposed. In particular, an aluminum alloy typical of automotive applications was considered and an S-shaped U-channel process was investigated. The stochastic analysis was performed within several operative windows at the varying of restraining forces. Formerly, a sensitivity analysis was carried out in order to evaluate the single effect of each selected material parameter and to screen the most influent ones. Subsequently, a finite element method-response surface methodology-Monte Carlo simulation-integrated approach was implemented to quantify such effects. The proposed methodology provides the possibility to powerfully analyze material variability effect on the final process quality, assisting the designer in a subsequent process optimization.

In sheet metal forming most of the problems are multi objective problems, generally characterized by conflicting objectives. The definition of proper parameters aimed to prevent both wrinkles and fracture is a typical example of an optimization problem in sheet metal forming characterized by conflicting goals. What is more, nowadays, a great interest would be focused on the availability of a cluster of possible optimal solutions instead of a single one, particularly in an industrial environment. Thus, the design parameters calibration, accomplishing all the objectives, is difficult and sometimes unsuccessful. In order to overcome this drawback a multi-objectives optimization procedure based on Pareto optimal solution search techniques seems a very attractive approach to deal with sheet metal forming processes design. In this paper, an integration between numerical simulations, response surface methodology and Pareto optimal solution search techniques was applied in order to design a rectangular deep drawing process. In particular, the initial blank shape and the blank holder force history were optimized as design variables in order to accomplish two different objectives: reduce excessive thinning and avoid wrinkling occurrence. The steps of the optimization procedure include: 1) application of Central Composite Design (CCD) for the identification of the necessary data over the domain of variation of the design variables; 2) numerical simulations of the samples identified by CCD; 3) development of a response surface model to interpret the final objectives as functions of the design variables; 4) Pareto optimal solution analysis to reach the most performing design variables. The final aim is to develop a predictive tool able to identify a sort of process window for the analyzed process also minimizing the computational effort in particular with respect to mono-objective optimization techniques or traditional trial and error methods. Many possible technological scenarios were investigated by the implemented procedure and a set of reliable solutions, i.e. able to satisfy different design requirements, were obtained.