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Lung cancer remains one of the leading causes of death worldwide. Due to the side effects of chemotherapeutic agents on normal cells and the development of resistance by cancer cells, there is an urgent need for alternative new pharmacological agents. Palladium (Pd)-conjugated Schiff base (SB) compounds represent an alternative approach with promising potential applications in cancer treatment. This study aims to identify novel therapeutic agents on A549 cells through the synthesis and characterization of Schiff base conjugated-Palladium complexes (Pd-L1 and Pd-L2). Additionally, it seeks to elucidate the mechanism of action of these compounds on both the A549 and NIH/3T3 cell lines. In the present study, two new Pd-L1 and Pd-L2 were synthesized for the first time and characterized mainly by single crystal X-ray diffraction and 1 H, 13 C, 31 P NMR techniques. The cytotoxic effect of the compounds was evaluated by MTT assay on A549 and NIH/3T3 cell lines for 24 and 48 h. Cisplatin was used as a positive control group. Based on the cytotoxicity results, the complexes were evaluated for their anticancer activities against A549 cell lines for 48 h through reactive oxygen species (ROS), cell cycle, apoptotic, and necrotic cell analyses. The most potent cytotoxic effects were determined for Pd-L1 (IC 50 : 23.33 μM), Pd-L2 (IC 50 : 3.19 μM), and cisplatin (IC 50 : 33.27 μM) on A549 cells (p < 0.05). The compounds exhibited a significant cytotoxic effect at lower concentrations on A549 cells compared to NIH/3T3 cells (p < 0.05). All compounds showed a significant increase in ROS levels in A549 cells compared to the control group (p < 0.05). While necrosis and apoptosis was observed in A549 cells treated with cisplatin, induction of apoptosis was effective in cell death for A549 cells treated with Pd-L1 and Pd-L2 (p < 0.05). Additionally, it was observed that the compounds inhibited cell proliferation in the G0/G1 and G2/M cell cycle phases (p < 0.05). All compounds induced cell cycle arrest and cell death in A549 cells by increasing ROS levels. The results obtained in the present study could advance the utilization of the compounds as anticancer agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Burcu Demirbag reports financial support was provided by Mersin University, Türkiye. Hakan Unver reports financial support was provided by Eskisehir Technical University, Türkiye. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite significant improvements in the treatment of cancerous tumors in the last decades, cancer remains one of the deadliest diseases worldwide. To overcome the shortcomings of currently applied chemotherapeutic treatments, much research efforts have been devoted towards the development of ferroptosis inducing anticancer agents. Ferroptosis is a newly described form of regulated, non-apoptotic cell death that is associated with high potential inside the clinics. Herein, the chemical synthesis and biological evaluation of a Co(III) polypyridine sulfasalazine complex as a ferroptosis inducer is reported. Upon entering the cancerous cells, the metal complex primarily accumulated in the mitochondria, triggering the production of hydroxy radicals and lipid peroxides, ultimately causing cell death by ferroptosis. The compound demonstrated to eradicate various monolayer cancer cells as well as colon carcinoma multicellular tumor spheroids. To the best of our knowledge this study reports on the first example of a Co(III) complex that is capable of inducing ferroptosis., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

New therapeutic strategies for osteosarcoma (OS) have demonstrated the potential efficacy of copper compounds as anticancer drugs and as a substitute for the often used platinum compounds. OS is a type of bone cancer, primarily affecting young adults and children.The main objective of this work is to discover the molecular targets and cellular pathways related to the antitumor properties of a Cu(II)-hydrazone toward human OS 2D and 3D systems. Cell viability study using MG-63 cells was evaluated in OS monolayer and spheroids. CuHL significantly reduced cell viability in OS models (IC 50 2D: 2.6±0.3 μM; IC 50 3D: 9.9±1.4 μM) (p<0.001). Also, CuHL inhibits cell proliferation and it induces cells to apoptosis. The main mechanism of action found for CuHL are the interaction with DNA, genotoxicity, the ROS generation and the proteasome activity inhibition. Besides, 67 differentially expressed proteins were found using proteomic approaches. Of those 67 proteins, 40 were found overexpressed and 27 underexpressed. The response to stress and to unfolded protein, as well as ATP synthesis were the most affected biological process among upregulated proteins, whilst proteins related to DNA replication and redox homeostasis were downregulated., (© 2024 Wiley-VCH GmbH.)

Cu(II) complexes with 2,2':6',2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl 2 (L n )]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes ( Cu1a and Cu1b ) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).

To effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC), we developed a high-efficiency and low-toxicity arene ruthenium (Ru) complex based on apoferritin (AFt). To achieve this, we optimized a series of Ru(II) 1,10-phenanthroline-2,9-diformaldehyde thiosemicarbazone complexes by studying their structure-activity relationships to obtain an arene binuclear Ru(II) complex (C5) with significant cytotoxicity and high accumulation in the mitochondria of tumor cells. Subsequently, a C5-AFt nanoparticle (NPs) delivery system was constructed. We found that the C5/C5-AFt NPs effectively inhibited TNBC growth and metastasis with few side effects. The C5-AFt NPs improved the anticancer and targeting abilities of C5 in vivo. Moreover, we confirmed the mechanism by which C5/C5-AFt NPs inhibit tumor growth and metastasis via mitochondrial damage-mediated ferroptosis and activation of the cGAS-STING pathway.

Developing drugs for treating glioblastoma has been a significant challenge. Herein, a series of arene ruthenium(II) complexes have been synthesized and investigated as potential candidates to suppress the proliferation and metastasis of glioblastoma. It is found that para-substituent-modified molecules, especially 6 , exhibit higher antitumor activity than ortho-substituents. Further studies show that 6 can trigger tumor cell autophagy by regulating the PI3K/AKT/mTOR pathway. Moreover, it is also found that 6 can induce DNA damage in glioblastoma cells through binding and stabilizing VEGF G-quadruplex DNA. Furthermore, it is confirmed that 6 can inhibit the proliferation and metastasis of U87-MG glioblastoma cell in situ xenograft in the zebrafish model. Hence, arene ruthenium(II) complexes can be developed as promising therapeutic agents for glioblastoma treatment in the future.

CuATSM, a copper(II) complex of a bis(thiosemicarbazone) of diacetyl, prevents oxidative cell death and acts as a neuroprotectant in vivo , prompting its evaluation to treat amyotrophic lateral sclerosis and other neurodegenerative conditions in the clinic. We recently demonstrated that CuATSM functions as a potent radical-trapping antioxidant (RTA), inhibiting lipid peroxidation and associated ferroptotic cell death by a noncanonical mechanism based on radical addition to the ligand backbone. Herein we report our investigations of the generality of this reactivity, which include studies of corresponding complexes of various other metals, including Co, Ru, Ni, Pd, Pt, and Au. Inhibited autoxidations of styrene and dioxane reveal that most of these complexes exhibit RTA activity, consistent with ligand-based reactivity, but the identity of the metal atom nevertheless plays a role. In particular, analyses of the electronic structures of the complexes of metals within the same group (i.e., the group 10 metals Ni, Pd and Pt) highlight how the metal atom can modulate the ligand-based reactivity by enabling spin delocalization to the other thiosemicarbazone moiety. The RTA activity determined in organic solution largely translates to phospholipid bilayers and mammalian cells, where most complexes inhibited lipid peroxidation and associated ferroptotic cell death. A preliminary structure-activity study revealed Pt complexes with potencies eclipsing those of archetype ferroptosis inhibitors ferrostatin-1 and liproxstatin-1, suggesting that Pt (and to a lesser extent Ni) bis(thiosemicarbazone)s may be better suited to optimization for therapeutic development than those based on Cu.

Ru(II)-complexes have been recognised as promising in treating cancer. However, targeted delivery is an important facet to augment the efficiency of drugs. Consequently, this article portrays the construction of biotinylated-MWCNTs as an SMVT-guided nano-platform for the precise delivery of our previously-developed potent Ru(II)-scaffold, making it more effective against MCF-7 cells.

Herein, we describe the synthesis and characterization of a series of thiosemicarbazone platinacycles. Their activity towards HCT116 and A2780 cancer cell lines as well as normal fibroblasts was explored and conclusions about the influence of their structures were drawn based on the results. Ligands L1-3, tetranuclear compounds [Pt( L1-3 )] 4 , [Pt( L1-3 )(PPh 3 )] , and [Pt( L1-L3 ) 2 {Ph 2 P(CH 2 ) 4 PPh 2 }] , and phosphine derivatives, were deemed unpromising owing to their lack of activity. However, mono-coordinated diphosphine complexes [Pt( L1-L3 )(Ph 2 PCH 2 PPh 2 - P )] showed high selectivity and low IC 50 values, and their antiproliferative activity was further studied. The three studied derivatives 3a, 3b and 3c showed a fast internalization of HCT116 colorectal cancer cells with similar IC 50 values, which induced a depolarization of mitochondrial membrane potential, with the subsequent triggering of apoptosis and autophagy in the case of 3c. In the case of compounds 3a and 3b, cell death mechanisms (extrinsic and intrinsic apoptosis, respectively) were triggered via the induction of reactive oxygen species (ROS). The three compounds were not toxic to a chicken embryo in vivo (after 48 h), and, importantly, showed an anti-angiogenic potential after exposure to the IC 50 of compounds 3a, 3b and 3c.

With increasing clinical applications and interest in targeted alpha therapy, there is growing interest in developing alternative chelating agents for [ 212 Pb]Pb 2+ and [ 212/213 Bi]Bi 3+ that exhibit rapid radiolabeling kinetics and kinetic inertness. Herein we report the synthesis and detailed investigation of diacetate and dipicolinate 18- and 21-membered macrocyclic chelators BADA-18, BADA-21, BADPA-18, and BADPA-21 for the complexation of Pb 2+ and Bi 3+ ions with potential use in the preparation of radiopharmaceuticals. The formation of mononuclear complexes was established by using ESI-mass spectrometry, and their stability constants were determined by potentiometric titration. A thorough study of the structure of the metal complexes was carried out by using X-ray diffraction and NMR spectroscopy. It was shown how the stability of the complex is influenced by an increase in the size of the macrocycle, the replacement of acetate arms with picolinate ones, the rigidity of the ligand, as well as the type of conformation ( syn - or anti -) of the metal complex. The new ligands were radiolabeled with [ 210 Pb]Pb 2+ and [ 207 Bi]Bi 3+ , and the in vitro stability of the resulting complexes in a competitive environment of serum and biologically significant metal ions was assessed. Rapid complex formation in 1-2 min at room temperature, as well as the high kinetic inertness of the complexes Pb(BADPA-18) and Bi(BADPA-18) in biological media, demonstrate its potential for use in targeted radionuclide therapy.

Ferroptosis plays an essential role in the pathological progression of hepatic ischemia-reperfusion injury (HIRI), which is closely related to iron-dependent lipid peroxidation. Since mitochondria are thought to be the major site of reactive oxygen species (ROS) production and iron storage, monitoring the variations of mitochondrial hypochlorous acid (HClO) (an important member of ROS) has important implications for the assessment of ferroptosis status, as well as the formulation of treatment strategies for HIRI. However, reliable imaging tools for the visualization of mitochondrial HClO and monitoring its dynamic changes in ferroptosis-mediated HIRI are still lacking. Herein, in this work, an HClO-activated near-infrared (NIR) cyclometalated iridium(III) complex-based probe, named NIR-Ir-HClO, was developed for the visual monitoring of the mitochondrial HClO fluxes in ferroptosis-mediated HIRI. The newly prepared probe showed fast response (<30 s), good sensitivity, excellent selectivity, good cell biocompatibility, and satisfactory mitochondrial-targeting performance, making it suitable for accurate monitoring of mitochondrial HClO in living cells. Moreover, visualization of the variations of mitochondrial HClO in ferroptosis-mediated HIRI and monitoring of the treatment response of ferroptosis-mediated HIRI to the ferroptosis inhibitors were achieved for the first time. All these show that probe NIR-Ir-HClO can be utilized as a reliable imaging tool for revealing the pathological mechanism of mitochondrial HClO in ferroptosis-mediated HIRI, as well as for the formulation of new treatment strategies for HIRI.

Current anticancer therapies suffer from issues such as off-target side effects and the emergence of drug resistance; therefore, the discovery of alternative therapeutic approaches is vital. These can include the development of drugs with different modes of action, and the exploration of new biomolecular targets. For the former, there has been increasing interest in drugs that are activated by an external stimulus (e. g. light irradiation) to generate cytotoxic chemicals such as reactive oxygen species (ROS). For the latter, significant efforts are being directed to explore non-canonical DNA and RNA structures (e. g. guanine-quadruplexes), as alternative biomolecular targets. Herein we report the synthesis of a library of 21 new platinum(II)-Salphen complexes (square planar platinum(II) complexes coordinated to tetradentate O,N,N,O-Schiff base ligands), and the investigation, for all complexes, of their photophysical and photochemical properties, their interactions with duplex and quadruplex DNA, and their cytotoxicity against HeLa cancer cells both in the dark and upon light irradiation. Thanks to the intrinsic phosphorescence of the platinum(II) complexes, confocal microscopy was used for six of the complexes to determine their cellular permeability and localisation in two cancer cell lines (HeLa and U2OS). Altogether, these studies have allowed us to identify two lead platinum(II) complexes with high guanine-quadruplex DNA affinity and selectivity, good cell permeability and nuclear localisation, and high cytotoxicity against HeLa cancer cells upon irradiation with no detected cytotoxicity in the dark., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Compounds that can induce oxidative stress in cancer cells while remaining nontoxic to healthy cells are extremely promising for potential anticancer drugs. 2,2':6',2''-terpyridine-metal complexes possess these properties. The high level of activity (IC 50  = 0.605 µM) of 2,2':6',2''-terpyridine-metal complexes on lung, breast, pancreatic, and glioblastoma multiforme cancer lines and their selectivity (SI > 41.32) on human normal fibroblasts were confirmed and presented in this paper. The mechanism of action of these compounds is associated with the generation of reactive oxygen species, which affects several cellular pathways and signals. The results demonstrate that 2,2':6',2''-terpyridine-metal complexes affect cell cycle inhibition in the G0/G1 phase as well as the activation of apoptosis and autophagy cell death. These results were confirmed in several independent studies, including experiments measuring the fluorescence levels of reactive oxygen species, flow cytometry, and gene and protein analysis., (© 2024. The Author(s).)

Photodynamic therapy (PDT) often faces challenges such as oxygen dependence and limited tumour specificity. We report a tumour-targeting photosensitizer (PS), RuCXB, which enhances uptake by cancer cells by targeting overexpressed cyclooxygenase-2 enzyme in tumours. RuCXB also reduces oxygen dependence via a type I PDT mechanism and achieves a strong therapeutic effect through the synergistic induction of ferroptosis and apoptosis. This work presents a reliable strategy for developing potent PSs with enhanced PDT efficacy, tumour selectivity, and diminished oxygen dependence.

We report the synthesis, characterization, anti-cancer activity and mechanism of action of a novel water-soluble Cu(II) complex with salicylidene carbohydrazide as the ligand and o -phenanthroline as the co-ligand. The synthesized complex (1) was characterized by FT-IR, EPR, and electronic spectroscopy, as well as single crystal X-ray diffraction. This compound was found to be paramagnetic from EPR spectra and X-ray crystallography revealed that the molecule crystallized in an orthorhombic crystal system. The crystal lattice was asymmetric containing two distinct binuclear copper complexes containing the Schiff base as the major ligand, o -phenanthroline as a co-ligand, two nitrate anions, and two water molecules. The Cu(II) in the first site coordinated with the enolised ligand comprising enolate O - , phenolate O - , and the imine N and N,N from o -phen. The major part of this complex exists as Cu(II) coordinated with two H 2 O molecules at the second site with nitrate acting as the counter anion. However, a smaller portion of the complex exists where Cu(II) is coordinated with NO 3 - and H 2 O, and the remaining water molecule acts as lattice water. It was tested for DNA binding and cleavage properties which revealed that it binds in an intercalative mode to CT-DNA with K b value of 1.25 × 10 4 M -1 . Furthermore, cleavage studies reveal that the complex has potential for efficient DNA cleavage under both oxidative and hydrolytic conditions. It was able to enhance the rate of cleavage by 2.8 × 10 8 times. The complex shows good cytotoxicity to breast cancer monolayer (2D) as well as spheroid (3D) systems. The IC 50 values for MDA-MB-231 and MCF-7 monolayer culture was calculated as 1.86 ± 0.17 μM and 2.22 ± 0.08 μM, respectively, and in (3D) spheroids of MDA-MB-231 cells, the IC 50 value was calculated to be 1.51 ± 0.29 μM. It was observed that the complex outperformed cisplatin in both breast cancer cell lines. The cells treated with complex 1 underwent severe DNA damage, increased oxidative stress and cell cycle arrest which finally led to programmed cell death or apoptosis in triple negative breast cancer cells through an intrinsic pathway.

A new nitro-nitrosyl complex [RuNO(Phen)(NO 2 ) 2 OH] (1) was synthesized and characterized by X-ray diffraction, where Phen = 1,10-phenanthroline. The complex was crystallized in two different modifications without (1) and with a solvent molecule of DMF (1a). The photolysis process together with the determination of the quantum yield of NO release was investigated in acetonitrile solution using a special flow-through system for the simultaneous registration of infrared (IR) and optical absorption (UV-vis) spectra under irradiation with 450 nm light. The quantum yield of photoinduced NO release was 4.0 ± 0.2%. DFT calculations showed that the main contribution to the absorption band at 450 nm is made by the HOMO/HOMO-1 → LUMO transitions, which are represented by the transfer of electron density from the -OH and -NO 2 ligands to the orbitals located on the Ru-NO bond. The dark and photoinduced cytotoxicity of the complex was studied against the human breast adenocarcinoma (MCF-7) and lung carcinoma (A549) cell lines and human non-tumor lung fibroblasts (MRC5). The complex shows a low cytotoxicity on MCF-7 cells (ICdark50 = 90.6 ± 6.2 μM and ICirr.50 = 95.3 ± 11.4 μM) and a moderate dark cytotoxicity on A549 and MRC5 cells (ICdark50 = 33.4 ± 2.6 μM and ICdark50 = 62.6 ± 3.1 μM, respectively), which slightly increases after irradiation (ICirr.50 = 21.2 ± 3.3 μM and ICirr.50 = 47.2 ± 2.3 μM, respectively).

In this work, we report the synthesis of two cobalt-based porous coordination polymers (PCPs): [Co 3 (BTC) 2 (H 2 O) 12 ] n (1) and [Co 3 (BTC) 2 (DMP) 8 ] n (2) [where BTC = 1,3,5-benzenetricarboxylate and DMP = 3,5-dimethylpyrazole]. These compounds were characterized using a range of physicochemical techniques, including UV-DRS, FT-IR, SCXRD, PXRD, TGA, and FE-SEM/EDX. The synthesized PCPs effectively catalyzed the degradation of various persistent organic pollutants (POPs) rapidly, which includes both cationic and anionic dyes such as Malachite Green (MG), Methylene Blue (MB), Indigo Carmine (IC), Methyl Orange (MO), Orange G (OG), and Eriochrome Black T (EBT). They also have excellent efficacy in degrading nitroaromatics viz. 4-nitrophenol (4-NP), 2,4-dinitrophenol (2,4-DNP), and 2,4,6-trinitrophenol (2,4,6-TNP) in the presence of NaBH 4 as a reductant. In addition, these PCPs exhibited remarkable antibacterial and antifungal properties, demonstrating strong activity against bacterial strains such as Escherichia coli , Staphylococcus aureus , and Bacillus subtilis , as well as the fungal strain Candida albicans . These results indicate that these two PCPs have considerable potential for catalyzing the rapid degradation of POPs, while also showing promising biological activities, offering substantial opportunities for future research.

Three novel complexes of deprotonated diflunisal ( dif ) with neocuproine ( neo ) were synthesized and characterized via elemental, spectral (UV-vis, FTIR, fluorescence, and mass spectrometry), and single-crystal X-ray diffraction analyses. Although the compounds shared a similar composition of [MCl( dif )( neo )], where M represents Zn(II) (1), Co(II) (2) and Cu(II) (3), only 1 and 2 were isostructural, while 3 differed in both the molecular and supramolecular structures. In all three complex molecules, the central atom is coordinated by two nitrogen atoms of neo in a bidentate chelate mode, and one chlorido ligand and dif is bonded in either a monodentate mode via one oxygen atom of the carboxylate in 1 and 2 or in a bidentate chelate mode via both carboxylate oxygen atoms in 3. All three compounds demonstrated remarkable antiproliferative activity against human prostate (PC-3), colon (HCT116) and breast (MDA-MB-468) cancer cell lines with IC 50 values in the nanomolar range, with the lowest values observed in the case of PC-3 and MDA-MB-468 with 2 (20.0 nM) and 3 (31.1 nM), respectively. Moreover, complex 2, as the most active, was further investigated for its potential to induce perturbations in the cell cycle of PC-3 cells. The results indicated an induction of caspase-independent apoptosis. The interaction of the complexes with genomic DNA isolated from the respective cancer cell lines was evaluated for the intercalative mode, with binding strength correlated with the antiproliferative activity against PC-3 and MDA-MB-468 cancer cell lines.

Quaternization of ruthenium complexes may be a promising strategy for the development of new antibiotics. In response to the increasing bacterial resistance, we integrated the quaternary amine structure into the design of ruthenium complexes and evaluated their antibacterial activity. All the ruthenium complexes showed good antibacterial activity against the tested Staphylococcus aureus (S. aureus). Ru-8 was the most effective antibacterial agent that displayed excellent antibacterial activity against S. aureus (MIC = 0.78-1.56 μg/mL). In vitro experiments showed that all nine ruthenium complexes had low hemolytic toxicity to rabbit erythrocytes. Notably, Ru-8 was found to disrupt bacterial cell membranes, alter their permeability, and induce ROS production in bacteria, all the above leading to the death of bacteria without inducing drug resistance. To further explore the antibacterial activity of Ru-8in vivo, we established a mouse skin wound infection model and a G. mellonella larvae infection model. Ru-8 exhibited significant antibacterial efficacy against S. aureus in vivo and low toxicity to mouse tissues. The Ru-8 showed low toxicity to Raw264.7 cells (mouse monocyte macrophage leukemia cells). This study indicates that the ruthenium complex ruthenium quaternary was a promising strategy for the development of new antibacterial agents., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier Masson SAS.)

Metal complexes showing dual activity against cancer and bacterial infections are currently the focus of significant interest for their potential in treating life-threatening diseases. Aiming to investigate the impact of ligand substituents on these bioactivity properties of Group 11 d 10 metal complexes, we herein present a series of mononuclear Cu(I) and Ag(I) complexes featuring the bis-NH 2 -substituted heterocyclic thioamide dap2SH (=4,6-diaminopyrimidine-2-thione), namely [AgCl(dap2SH)(PPh 3 ) 2 ] (1), [CuBr(dap2SH)(PPh 3 ) 2 ] (2), [CuBr(dap2SH)(xantphos)] (3), [Ag(dap2S)(xantphos)] (4), and [Cu(dap2S)(xantphos)] (5) (xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene). Complexes were characterized by means of different physicochemical methods (i.e., single crystal X-ray diffraction as well as FTIR, NMR, UV-Vis and fluorescence spectroscopy), and studied in-vitro for their antibacterial and anticancer activity against a variety of bacterial strains and cancer cell lines. Complexes 1-3 effectively inhibited both Gram (+) and Gram (-) bacterial growth, while cellular uptake studies for the most potent complex 1 against E. coli bacteria revealed the accumulation of Ag(I) ions in the periplasm of the bacteria. A high anti-proliferative effect was observed for 1 and 5 against A549, MCF7 and PC3 cancer cell lines, with 1 being capable of inducing apoptosis in A549 cells, as suggested by flow cytometry analysis. DNA interaction studies revealed the capacity of 1 to intercalate between base-pairs of CT DNA. All complexes had a moderate-to-high capacity to scavenge free radicals preventing oxidative stress. Molecular docking calculations, in combination with the experimentally obtained data, provided insights for potential mechanisms of the bioactivity of the complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Reaction between the polymeric [RuCl 2 (CO) 2 ] n and the N,N-bidentate ligand, 8-amino-quinoline (Quin), in methanol, afforded the photoactivated CO releasing molecule with the formula of trans-(Cl,Cl)-[RuCl 2 (CO) 2 Quin]. In the presence of biomolecules or in solvents with varying polarity and coordinating abilities, the solvatochromic characteristics and dark stability were investigated. A new board band emerged in the visible spectrum during the illumination, and its position varies according to the type of solvent used, indicating the role of the solvent in controlling the nature of the CO-depleted species. Spectral methods were used in combination with density functional theory simulations to get insight into the local minimum structure and the electronic properties of the Ru(II) complex. The results of the myoglobin assay showed that within the first two hours of illumination, one of the two CO molecules was released. The cytotoxic properties of the Ru(II)-based complex were investigated against normal mice bone marrow stromal cells and malignant human acute monocytic leukaemia cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified and can bind several substituents, including transition metals as, for instance, gold derivatives. Gold-NHC complexes possess various biological activities and were demonstrated good candidates as anticancer drugs. Besides, carbazole derivatives are characterized by various pharmacological properties, such as anticancer, antibacterial, anti-inflammatory, and anti-psychotropic. Amongst the latter, N-thioalkyl carbazoles were proved to inhibit cancer cells damaging the nuclear DNA, through the inhibition of human topoisomerases. Herein, we report the design, synthesis and biological evaluation of nine new hybrid molecules in which NHC-Au(I) complexes and N-alkylthiolated carbazoles are linked together, in order to obtain novel biological multitarget agents. We demonstrated that the lead hybrid complexes possess anticancer, anti-inflammatory and antioxidant properties, with a high potential as useful tools for treating distinct aspects of several diseases, amongst them cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In an effort to develop hypoxia-active iridium(III) complexes with long visible-light absorption, we synthesized and characterized five bis(terpyridine) Ir(III) complexes bearing oligothienyl substituents on one of the terpyridine ligands, i.e., n T-Ir ( n = 0-4). The UV-vis absorption, emission, and transient absorption spectroscopy were employed to characterize the singlet and triplet excited states of these complexes and to explore the effects of varied number of thienyl units on the photophysical parameters of the complexes. In vitro photodynamic therapeutic activities of these complexes were assessed with respect to three melanoma cell lines (SKMEL28, A375, and B16F10) and two breast cancer cell lines (MDA-MB-231 and MCF-7) under normoxia (∼18.5% oxygen tension) and hypoxia (1% oxygen tension) upon broadband visible (400-700 nm), blue (453 nm), green (523 nm), and red (633 nm) light activation. It was revealed that the increased number of thienyl units bathochromically shifted the low-energy absorption bands to the green/orange spectral regions and the emission bands to the near-infrared (NIR) regions. The lowest triplet excited-state lifetimes and the singlet oxygen generation efficiency also increased from 0T to 2T substitution but decreased in 3T and 4T substitution. All complexes exhibited low dark cytotoxicity toward all cell lines, but 2T-Ir-4T-Ir manifested high photocytotoxicity for all cell lines upon visible, blue, and green light activation under normoxia, with 2T-Ir showing the strongest photocytotoxicity toward SKMEL28, MDA-MB-231, and MCF-7 cells, and 4T-Ir being the most photocytotoxic one for B16F10 and A375 cells. Singlet oxygen, superoxide anion radicals, and peroxynitrite anions were found to likely be involved in the photocytotoxicity exhibited by the complexes. 4T-Ir also showed strong photocytotoxicity upon red-light excitation toward all cell lines under normoxia and retained its photocytotoxicity under hypoxia toward all cell lines upon visible, blue, and green light excitation. The hypoxic activity of 4T-Ir along with its green to orange light absorption, NIR emission, and low dark cytotoxicity suggest its potential as a photosensitizer for photodynamic therapy applications.

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{ cis -Pt(NH 3 ) 2 } 2 (μ-OH)(μ-azolato)]X 2 , where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y ([{ cis -Pt(NH 3 ) 2 } 2 (μ-OH)(μ-tetrazolato- N2 , N3 )](ClO 4 ) 2 ), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin ( cis -diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Y suppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

We discussed and summarized the latest data from the global literature on the action of polyphenolic antioxidants and their metal complexes. The review also includes a summary of the outcomes of theoretical computations and our many years of experimental experience. We employed various methods, including spectroscopy (FT-IR, FT-Raman, NMR, UV/Vis), X-ray diffraction, thermal analysis, quantum calculations, and biological assays (DPPH, ABTS, FRAP, cytotoxicity, and genotoxicity tests). According to our research, the number and position of hydroxyl groups in aromatic rings, as well as the delocalization of electron charge and conjugated double bonds, have a major impact on the antioxidant effectiveness of the studied compounds. Another important factor is metal complexation, whereby high ionic potential metals (e.g., Fe(III), Cr(III), Cu(II)) enhance antioxidant properties by stabilizing electron charge, while the low ionic potential metals (e.g., Ag(I), Hg(II), Pb(II)) reduce efficacy by disrupting electron distribution. However, we observed no simple correlation between ionic potential and antioxidant capacity. This paper gives insights that will aid in identifying new, effective antioxidants, which are vital for nutrition and the prevention of neurodegenerative illnesses. Our results outline the connections between biological activity and molecular structure, offering a foundation for the methodical design of antioxidants. Our review also shows in detail how we use various complementary methods to assess the impact of metals on the electronic systems of ligands. This approach moves beyond the traditional "trial and error" method, allowing for the more efficient and rational development of future antioxidants.

In this study, we introduce a novel indole-containing pyridine-based Schiff base, (E)-2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole, C 20 H 15 N 5 (2-DPHI), and its cadmium(II) complex poly[[2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole]di-μ-chlorido-cadmium(II)], [CdCl 2 (C 20 H 15 N 5 )] n (pCd2), as potential anticancer agents. The Schiff base was synthesized by reacting dipyridylmethanone hydrazone with indole-2-formaldehyde, while the cadmium complex was prepared by combining CdCl 2 and 2-DPHI in methanol at room temperature. Both compounds were evaluated for their cytotoxicity against three human cancer cell lines (A375, A549 and HeLa) and a normal cell line (HFF-1). The ligand 2-DPHI exhibited notable antitumour activity, with an IC 50 value of 12.22 µM against A375 and 15.17 µM against A549 after 48 h, while the pCd2 complex showed an even stronger inhibition of A375 cells, with an IC 50 value of 4.88 µM, outperforming both 2-DPHI and CdCl 2 . Both compounds demonstrated lower toxicity towards normal cells compared to cancer cells. The structures of 2-DPHI and pCd2 were fully characterized using single-crystal X-ray diffraction, elemental analysis, high-resolution mass spectrometry and FT-IR, 1 H NMR, 13 C NMR and UV-Vis spectroscopy.

Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L 1 ), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L 2 ): [Sm(L 1 ) 2 ][Sm(L 1 )(NO 3 ) 3 ]·CHCl 3 ·2CH 3 OH (1), [Gd(L 1 ) 2 ][Gd(L 1 )(NO 3 ) 3 ]·CHCl 3 ·2CH 3 OH (2), [Sm(L 2 )(NO 3 ) 2 ] 2 ·CH 3 OH (3), and [Eu(L 2 )(NO 3 ) 2 ] 2 ·CH 3 OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI-H460 cells in G1 phase and induced mitochondria-mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca 2+ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex 1 is a potential anticancer agent., (© 2024 Wiley Periodicals LLC.)

To inhibit the growth and metastasis of triple-negative breast cancer (TNBC), two Fe(III) thiosemicarbazone complexes (Fe1 and Fe2) were designed and synthesized. The structures of the Fe(III) complexes were characterized by single crystal X-ray diffraction. The antiproliferative activity of Fe1 and Fe2 against four cancer lines (MDA-MB-231, T98G, HepG2, 143B) and human renal proximal tubular epithelial cell line (HK-2) was evaluated by MTT assay. Among all cells, Fe2 showed significant cytotoxicity to TNBC cells (MDA-MB-231), with an IC 50 value of 12.38 μM. Furthermore, Fe2 showed less toxicity to HK-2 cells. The two Fe(III) complexes can produce excess of reactive oxygen species, decrease of mitochondrial membrane potential, and induce DNA damage, then lead to apoptosis of MDA-MB-231 cells. In addition, Fe1 and Fe2 can also inhibit migration and invasion of MDA-MB-231 cells. This study provides guidance for the development of metal complexes that inhibit the growth and metastasis of TNBC., (© 2024 Wiley Periodicals LLC.)

Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (1-4) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, l-valine) and characterized by 1 H NMR, 13 C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes 1-4 inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pancreatic cancer, is an aggressive type of cancer and the most common malignancy with a poor prognosis regarding metastatic disease (survival < 10 %). The development of Novel chemotherapeutic drugs holds significant prospects for practical applications. Here, this work focuses on the interaction between two lanthanide complexes, Yb-BZA and Er-BZA, with DNA, as well as their anticancer activity against pancreatic cancer. The relationship between complexes and DNA is revealed by fluorescence, absorption spectral titration, cyclic voltammetric (CV) experiments, indicating that the Yb-BZA and Er-BZA interact with FS-DNA by bind groove. Moreover, molecular docking technology was utilized to confirm the binding of Yb-BZA and Er-BZA with 1BNA and 4AV1. The cytotoxic effects of Yb-BZA and Er-BZA on cancer cells BxPC-3 were evaluated, Yb-BZA (IC 50  = 6.459 μg/mL) is more effective than oxaliplatin (IC 50  = 16.46 μg/mL) evaluated using cytotoxicity assay. Yb-BZA and Er-BZA has the potential to become a chemotherapy drug for pancreatic cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest regarding the publications of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The design of novel chelators for therapeutic applications has been the subject of extensive research to address various diseases. Many chelators can manipulate the levels of metal ions within cells and effectively modulate the metal excess. In some cases, chelators show significant toxicity to cells. We investigated polyimidazole ligands by potentiometry and UV-Vis spectroscopy for their ability to form copper(II) complexes. We also compared the antiproliferative activity of the polyimidazole ligands and their copper(II) complexes with polypyridine ligands in CaCo-2 (colorectal adenocarcinoma), SH-SY5Y (neuroblastoma) and K562 (chronic myelogenous leukemia) cells and normal HaCaT (keratinocyte) cells. Polyimidazole ligands are less cytotoxic than their analogous polypyridine ligands. All polyimidazole ligands, except the tetraimidazole ligand for K562 cells, did not show any significant effect on the viability of cancer and normal cells. In contrast, the cytotoxic activity of polypiridine ligands was also observed in normal cells with IC 50 values similar to those of cancer cells. Tetraimidazole ligand, the only ligand active on the leukemic K562 cell line, induced caspase-dependent apoptosis and increased intracellular reactive oxygen species production with mitochondrial damage. The low cytotoxicity of the polyimidazole ligands, even if it limits their use as anticancer agents, could make them useful in other medical applications, such as in the treatment of metal overload, microbial infections, inflammation or neurodegenerative disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Graziella Vecchio reports financial support was provided by Italian Ministry of Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The overuse of antimicrobial agents in medical and veterinary applications has led to the development of antimicrobial resistance in some microorganisms and this is now one of the major concerns in modern society. In this context, the use of transition metal complexes with photoactivatable properties, which can act as drug delivery systems triggered by light, could become a potent strategy to overcome the problem of resistance. In this work several Ru complexes with terpyridine ligands and the clotrimazole fragment, which is a potent antimycotic drug, were synthesized. The main goal was to explore the potential photoactivated activity of the complexes as antifungal agents and evaluate the effect of introducing different substituents on the terpyridine ligand. The complexes were capable of delivering the clotrimazole unit upon irradiation with visible light in a short period of time. The influence of the substituents on the photodissociation rate was explained by means of TD-DFT calculations. The complexes were tested against three different yeasts, which were selected based on their prevalence in fungal infections. The complex in which a carboxybenzene unit was attached to the terpyridine ligand showed the best activity against the three species under light, with minimal inhibitory concentration values of 0.88 μM and a phototoxicity index of 50 achieved. The activity of this complex was markedly higher than that of free clotrimazole, especially upon irradiation with visible light (141 times higher). The complexes were more active on yeast species than on cancer cell lines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The success of a classic inorganic coordination compound, Cisplatin, cis-[Pt(NH 3 ) 2 Cl 2 ], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized. They were characterized in the solid state, including a new crystal structure of [Cu 2 (3-(4-hydroxyphenyl)propanoate) 3 (phenanthroline) 2 ]Cl·H 2 O. The obtained complexes presented a variety of stoichiometries. In solution, complexes were partially dissociated in the corresponding Cu-diimine complex. The complexes bound to the DNA by partial intercalation and groove binding, as assessed by Circular Dichroism, relative viscosity change and UV-Vis titration. The cytotoxicity of the complexes was determined in vitro on MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (breast nontumoral), A549 (human lung epithelial carcinoma), and MRC-5 (human nontumoral lung epithelial cells), finding an activity higher than that of Cisplatin, although with less selectivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the chronicles of human history, infectious diseases played a pivotal role, influencing societies, steering advancements in medicine, and significantly impacting the well-being of people worldwide. Consequently, in the pursuit of identifying effective combating agents for infectious ailments, the Co(II), Ni(II), Cu(II), Zn(II) complexes of N'-(4-nitrobenzylidene)benzohydrazide were synthesized in the current investigation. Numerous spectral and physical analysis were conducted to characterize the compounds which revealed octahedral stereochemistry of complexes. The anti-tuberculosis, anti-inflammatory, antibacterial and antifungal investigations demonstrated that the compounds (1-5) have significant efficacy for these infectious ailments. The [Zn(L) 2 (H 2 O) 2 ] complex (5) has comparable TB inhibition potency to streptomycin as shown by MIC value of 0.0196±0.0003 μmol/mL. Additionally, the anti-inflammatory, antibacterial and antifungal studies also revealed the comparable inhibiting property of (5) to standard drugs with significant IC 50 (07.49±0.08 μM) and MIC (0.0098 μmol/mL) values. Furthermore, pharmacophore modeling with addition of molecular docking, DFT, MESP, ADMET were employed against compounds (1-5) to give a new insight in biological evaluations. The pharmacophore modeling suggested that (5) has a distinctive pharmacophoric features including cationic sites, hydrogen-bond donors and acceptors which provide valuable insights into rational drug design for specific pharmacological applications. Moreover, another in silico investigations authenticate the bioactivity of (5) through substantial binding affinities, binding energy, stability, hardness, electrophilicity etc. Overall, the combined computational and experimental results highlight the potential of [Zn(L) 2 (H 2 O) 2 ] as a promising candidate for tuberculosis treatment, meriting further in vivo investigations., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

In the upcoming decades, the incidence and mortality rates of cancer are expected to rise globally, with colorectal and prostate cancers among the most prevalent types. Despite advancements in molecular targeted therapy, platinum-based chemotherapies remain the cornerstone of treatment, especially for colorectal and prostate cancer, with oxaliplatin and cisplatin being extremely effective due to their DNA-targeting capabilities. In our pursuit of new platinum-based chemotherapeutics that are potentially less toxic and more effective, we have explored the combination of the Pt-binding groups of the diaminocyclohexane ring used in oxaliplatin, with the stable amino-pyrimidine hemicurcumin moiety. This new derivative exhibit improved stability in physiological conditions and increased solubility in aqueous media, demonstrating promising effects on cell proliferation of both colorectal and prostate cells. We report herein the complete synthesis and chemical characterization in solution of the new derivative [(1R,2R)-N1-(3-(4-((E)-2-(2-Amino-6-methylpyrimidin-4-yl)vinyl)-2-methoxyphenoxy) propyl) cyclohexane-1,2-diamine] (MPYD). Our analysis includes an examination of its acid-base equilibria, speciation and stability in physiological conditions. The synthesis and in situ formation of Pt(II) complexes were investigated by nuclear magnetic resonance spectroscopy, while density functional theory calculations were employed to elucidate the chemical structure in solution. Results on the biological activity were obtained through cell viability assays on different colorectal and prostate cell lines (HCT116, HT29, PC3 and LNCaP)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Six novel tri-aryl antimony(V) hydroximato complexes (3-8) with composition [SbAr 3 (O 2 NCR)] (3: Ar = Ph, R = o-(OH)Ph, 4: Ar = Ph, R = Me, 5: Ar = Ph, R = Ph; 6: Ar = Mes, R = Me, 7: Ar = Mes, R = Ph, 8: Ar = Mes, R = o-(OH)Ph (where Ph = phenyl, Me = methyl, Mes = mesityl)), were synthesised and evaluated for anti-parasitic activity towards Leishmania major (L. major) promastigotes and amastigotes. Complexes of the form [SbAr 3 (O 2 NCR)], with the dianionic hydroximato ligand binding O,O'-bidentate to the Sb(V) centre, exist in the solid-state for the mesityl-derived complexes. In contrast, the phenyl-ligated Sb(V) complexes crystallise as the hexacoordinate, hydroxamato species [SbPh 3 (O 2 NHC(OH))], with the OH ligand derived from entrained H 2 O in the crystallisation solvent. It is found that both the aryl and hydroximato ligands are found to influence the bioactivity of the Sb(V) complexes. Complexes 3-8 exhibited varied anti-promastigote activity with IC 50 values ranging from 1.53 μM for 6 to 36.0 μM for 3, also reflected in varied anti-amastigote activity with a percentage infection range of 5.50% for 6 to 29.00% for 3 at a concentration of 10 μM. The complexes were relatively non-toxic to human fibroblasts with an IC 50 value range of 59.3 μM (7) to ≥100 μM (3-6, 8), and exhibited varied toxicity towards J774.1 A macrophages (IC 50 : 3.97 (6) to ≥100 (8) μM). All complexes showed enhanced activity compared to the parent hydroxamic acids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga 3+ has been investigated by ISEH + (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl (aq) at I = 0.2 mol dm -3 and at T = 298.15 K. Further experiments were also performed adopting both the metal (with Fe 3+ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)] + , [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH) 2 ] - and [Ga(8-HQA) 2 ] - species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)] - and [Ga(EDTA)(OH)] 2- in the above conditions. Due to the relevance of Ga 3+ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga 3+ hydrolysis constants at T = 298.15 K, in different ionic media, in the ionic strength range 0 < I / mol dm -3  ≤ 1.0. The synthesis and characterization (by ElectroSpray Ionization - Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga 3+ /8-HQA complexes were also performed, identifying [Ga(8-HQA) 2 ] - as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga 3+ /8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely Actinomyces viscosus, Streptococcus mutans, Streptococcus sobrinus, Pseudomonas putida, Pseudomonas fluorescens and Escherichia coli), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga 3+ /8-HQA complex was observed on Actinomyces viscosus, while showing a potential radiosensitizing effect against Streptococcus mutans and Streptococcus sobrinus. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga 3+ /8-HQA complex. Nevertheless, Ga 3+ /8-HQA complex highlighted potential anti-inflammatory properties., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sofia Gama reports financial support was provided by National Science Centre Poland. Demetrio Milea reports financial support was provided by Italian Ministry of University and Research. Sandra Cabo Verde reports financial support was provided by Foundation for Science and Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Complexes [Cu(PI) 2 (H 2 O)](NO 3 ) 2 (1), [Cu(PBI) 2 (NO 3 )]NO 3 (2), [Cu(TBI) 2 (NO 3 )]NO 3 (3), [Cu(BBIP) 2 ](ClO 4 ) 2 (4) and [Cu(BBIP)(CH 3 OH)(ClO 4 ) 2 ] (5) were synthesized from the reactions of Cu(II) salts with 2-(2'-pyridyl)imidazole (PI), (2-(2'-pyridyl)benzimidazole (PBI), 2-(4'-thiazolyl)-benzimidazole (TBI), 2,6-bis(benzimidazol-2-yl)-pyridine (BBIP), respectively. Their compositions and crystal structures were determined. Their in-vitro antitumor activities were screened on four cancer cell lines and one normal cell line (HL-7702) using cisplatin as the positive control. Complexes 2 and 4 show higher cytotoxicity than the other three complexes. The cytotoxicity of complex 2 are comparable to those for cisplatin, and the cytotoxicity for 4 are much higher than those for cisplatin. From a viewpoint of antitumor, 2 might be a nice choice on the tumor cell line of T24 because its IC50 values on T24 and HL-7702 are 15.03 ± 1.10 and 21.34 ± 0.35, respectively. Thus, a mechanistic study for complexes 2 and 4 on T24 cells was conducted. It revealed that they can reduce mitochondrial membrane potential and increase mitochondrial membrane permeability, resulting in increased intracellular ROS levels, Ca 2+ inward flow, dysfunctional mitochondria and the eventual cell apoptosis. In conclusion, they can induce cell apoptosis through mitochondrial dysfunction. These findings could be useful in the development of new antitumor agents., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The biguanide Cu(II) complexes [Cu(L 1-4 ) 2 ](ClO 4 ) 2 were synthesized and spectroscopic/analytical techniques were used to clarify their structures. Single crystals of complex [Cu(L 4 ) 2 ](ClO 4 ) 2 was obtained and its definite structure was determined by single crystal X-ray diffraction study. The complexes [Cu(L 1-4 ) 2 ](ClO 4 ) 2 were screened for their FSds-DNA interactions by using UV-Vis absorption and fluorescence spectroscopies. The complexes [Cu(L 2 ) 2 ](ClO 4 ) 2 and [Cu(L 3 ) 2 ](ClO 4 ) 2 were shown to exhibit higher affinity for binding DNA. Examining the EB-DNA interaction, it is believed that the complexes interact with DNA through a groove binding mechanism. The interaction of complexes with BSA were observed through the quenching of the fluorescence emission. Complexes [Cu(L 2 ) 2 ](ClO 4 ) 2 and [Cu(L 3 ) 2 ](ClO 4 ) 2 show moderate binding affinity to BSA through a static mode. Additionally, the Cu(II) complexes were screened for their antibacterial activities against various bacterial strains. Complexes showed potential antimicrobial activity against Salmonella typhimurium, Bacillus cereus, Salmonella typhimurium and S. aureus., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Triphenylphosphine substitution reactions of [RuCl(PPh 3 ) 2 (tpm)]Cl, 1, featuring tris(pyrazolyl)methane (tpm) as ligand, with the chlorambucil-decorated pyridine ligand Py CA , 3-aminopyridine (Py NH2 ) and 4-pyridinemethanol (Py OH ) afforded the corresponding pyridine complexes 2-4 in high yields. Py CA was preliminarily obtained via esterification of 4-pyridinemethanol with chlorambucil. The new compounds Py CA and 2-3 were characterized by IR and multinuclear NMR spectroscopy. Additionally, the structure of 3 was ascertained by single crystal X-ray diffraction. The in vitro anti-proliferative activity of 2-4 and Py CA was determined against a panel of cancer cell lines, outlining 2 as the most performing compound. Targeted studies were subsequently undertaken using 2 to elucidate mechanistic aspects, including the assessment of ruthenium cellular uptake, cell cycle arrest, production of reactive oxygen species (ROS), western blotting and DNA damage (comet test). Overall, data highlight that the anticancer activity provided by 2 primarily affects the mitochondria pathway with a potential additional contribution from DNA damage., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mitophagy is an important target for antitumor drugs development. A series of ciclopirox (CPX) platinum(IV) hybrids targeting PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitophagy were designed and prepared as antitumor agents. The dual CPX platinum(IV) complex with cisplatin core was screened out as a candidate, which displayed promising antitumor activities both in vitro and in vivo. Mechanistically, it caused serious DNA damage in tumor cells. Then, remarkable mitochondrial damage was induced accompanied by the mitochondrial membrane depolarization and reactive oxygen species generation, which further promoted apoptosis through the Bcl-2/Bax/Caspase3 pathway. Furthermore, mitophagy was ignited via the PINK1/Parkin/P62/LC3 axis, and exhibited positive influence on promoting the apoptosis of tumor cells. The antitumor immunity was boosted by the block of immune check point programmed cell death ligand-1 (PD-L1), which further increased the density of T cells in tumors. Subsequently, the metastasis of tumor cells was inhibited by inhibiting angiogenesis in tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

New Schiff base ligand: 4-methoxy salicaldhyde-2-2-phenyl-hydrazono acetaldehíyde prepared by facile method. The molecular structures characterized by elemental analysis and proton magnetic resonance spectra ( 1 H-NMR spectra). This spectra at the chemical shifts (3.5-10.39 ppm) confirmed the types and the numbers of protons. The sharp melting point at the range 110-112 °C confirmed purity. New optically active metal (samarium, terbium and gadolinium) complexes of the Schiff base synthesized in a one pot reaction. Vibrational IR spectra confirmed functional groups. Scanning electron microscopy micrographs confirmed that the modified microstructure of the metal complexes differed in morphology than the ligand. Powder X-ray diffraction patterns confirmed good crystalline structure. The optically activity of the solid metal complexes confirmed from electronic absorption spectra. The UV absorbance band at the wavelength range 280-390 nm and the intense phosphorescence bands up to 830 nm enabled application in photo dynamic therapy for apoptosis cancer cells by conversion triplet oxygen in the tissues into reactive singlet oxygen. Low charge transfer energy: 2.59-2.61 eV, high molar extinction coefficients (ε) at the order of magnitude [Formula: see text] M - 1  cm - 1 and the intense phosphorescence bands reflected good photodynamic activity. The metal complexes are thermally stable., (© 2024. The Author(s).)

This study investigates novel zinc and indium phthalocyanines with Schiff base and sulphur moieties, focusing on their potential for cancer therapy and antimicrobial applications. It explores the effectiveness of photochemical and sono-photochemical methods to enhance singlet oxygen production, which is crucial for photodynamic therapy. The synthesized complexes in this study demonstrated high singlet oxygen quantum yields, with D3 (ZnPc) and D4 (InPc) showing Φ ΔPDT values of 0.71 and 0.75, and Φ ΔSPDT values of 0.91 and 0.94, respectively. Furthermore, the evaluation for biological properties revealed that both D3 and D4 exhibit significant antidiabetic properties, DPPH radical scavenging activity, DNA cleavage, antimicrobial activity, biofilm inhibition, and microbial cell viability impacts, both with and without photodynamic therapy. Notably, D3 and D4 achieved antimicrobial cell viability inhibition rates of 84.67 ± 4.67% and 98.32 ± 5.96%, respectively, showcasing their effectiveness in photodynamic antimicrobial therapy. Overall, the study highlights the potential of these phthalocyanine complexes as advanced photosensitizers, with strong singlet oxygen generation and promising biological activities, paving the way for future therapeutic applications.

The supramolecular palladium complex G-Pd, formed via self-assembly of the Pd-complex of guanidinium pillar[5]arene with Pd 2+ , was used to encapsulate doxorubicin to form G-Pd@DOX. The nanoparticles exhibit responsiveness to glutathione, controlled drug release, the ability to damage mitochondria, and potent anticancer activity while maintaining low toxicity towards normal cells. This work provides a good example for the application of pillararene-based palladium complexes in cancer therapy and is significant for the discovery of new medicines from supramolecular coordination complexes.

The coordination chemistry and electrochemistry of novel N -acridine thiosemicarbazones (NATs) were investigated along with their redox activity, antiproliferative efficacy, transmetalation, and dissociation properties. The ability of NAT Fe(III) complexes to inhibit detrimental oxy-myoglobin (oxy-Mb) oxidation was also examined. The NATs act as tridentate ligands with a 2:1 L/Zn(II) complex crystal structure, revealing a distorted octahedral geometry, where both ligands bind Zn(II) in a meridional conformation. The NAT Fe(III) complexes exhibited fully reversible one-electron Fe III/II couples with more positive potentials than the Fe(III) complexes of a related clinically trialed thiosemicarbazone (e.g., [Fe(DpC) 2 ] + ) due to the electron-donating capacity of acridine. Surprisingly, the NAT-Zn(II) complexes showed generally greater or similar antiproliferative activity than their ligands, Cu(II), or Fe(III) complexes. This may be explained by ( 1 ) formation of a highly lipophilic Zn(II) complex that acts as a chaperone to promote cellular uptake and ( 2 ) the capacity of the Zn(II) complex to dissociate or undergo transmetalation to the redox-active Cu(II) complex. Of the NAT-Fe(III) complexes, [Fe(AOBP) 2 ] + demonstrated a significant ( p < 0.0001) improvement in preventing oxy-Mb oxidation than the Fe(III) complex of the clinically trialed thiosemicarbazone, DpC. This article advances our understanding of NAT coordination chemistry, electrochemistry, and the intriguing biological activity of their complexes.

Photoactivated chemotherapy (PACT) is a form of target-oriented cancer therapy that exploits light of the proper wavelength to selectively activate the drug. Among the prodrugs used for this purpose, ruthenium-based complexes are particularly interesting, as when irradiated by light, they can release ligands by forming aquo-complexes able to bind DNA in both single and double strand fashions, causing its distortion. Using as model system a Ru(II) polypyridyl complex that has been demonstrated to be a promising photochemotherapeutic agent, all of the key aspects of the photoinduced solvolysis process and subsequent DNA interaction have been scrutinized using density functional theory (DFT) and time-dependent-DFT (TDDFT). Photoexcitation, intersystem crossing, internal conversion, mechanism by which photoinduced ligand release, and subsequent aquation steps occur have been examined. Pathways leading to the formation of both cis and trans biaquated photoproducts have been described, and the formation of the cis form of the biaquated photoproduct being the most favorable one, its reaction with a guanine base has also been reported in order to account for DNA binding.

Two-photon photodynamic therapy (TP-PDT) has become a major cancer treatment due to its larger tissue penetration depth, good spatial selectivity, and less damage to normal cells. In this contribution, a series of novel photosensitizer molecules ( Ir-2 , Ir-2-1 ∼ Ir-2-4 ) have been designed based on the experimentally demonstrated photosensitizer [Ir(ppy) 2 (osip)] (PF 6 ) by fine tuning the π-conjugated structure and introducing different nitrogen-heterocyclic substituents. The electronic structures, one- and two-photon absorption spectra, triplet excited state lifetime, solvation-free energy, and photosensitizing performance were evaluated by means of density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results suggested that the molecule Ir-2 , incorporating thiophene as the π-connecting group, exhibits a higher probability of triplet state formation, enhanced two-photon absorption cross-section, and prolonged triplet state lifetime. Furthermore, the four designed nitrogen-heterocyclic complexes Ir-2-1 ∼ Ir-2-4 demonstrate favorable photosensitizing properties, with two-photon absorption cross-sections reaching up to 110 GM and triplet excited state lifetimes exceeding 1000 μs for Ir-2-4 .

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.

Two new Ag(I) complexes with coumaric carboxylic acid derivatives have been synthesized. Structural studies of these noncrystalline complexes have been performed using a methodology that combines laboratory and synchrotron techniques, supported by density functional theory calculations. The arrangement of ligands around the Ag(I) cation has been refined using infrared, extended X-ray absorption fine structure, and X-ray absorption near edge structure spectroscopies. Different coordination modes of carboxylate ligands are observed for the studied compounds. Carboxylate bridges are characteristic for the Ag(I) complex with 4-oxo-4 H -1-benzopyran-2-carboxylic acid ( 1 ), while a bidentate chelating motif was found for the complex with 2-oxo-2 H -1-benzopyran-3-carboxylic acid ( 2 ). Additionally, the carbonyl oxygen atom of the coumarin ring coordinates to the silver cation in complex 2 , while it is inactive in complex 1 . Antimicrobial evaluation has been performed for both compounds. The complexes show activity against selected bacteria as well as Candida yeast. This activity is slightly lower for bacteria and the same or higher for Candida in relation to the reference substances: ciprofloxacin or fluconazole.