Two phenoxido-bridged dinuclear Ni(II) and Co(II) complexes, [M2(SAIDPPO)2(NO3)2] (M = Ni, Co), have been synthesized using a new Schiff base phosphine oxide ligand (SAIDPPO-). Single-crystal X-ray diffraction revealed closely related Ni2O2 and Co2O2 cores with distinct magnetostructural features. Magnetic studies showed that the Ni(II) complex (1) exhibits ferromagnetic coupling (J = +9.75 cm-1) associated with a near-orthogonal Ni-O-Ni angle (95.50 degrees) and pronounced easy-axis anisotropy (D =-19.44 cm-1). In contrast, the Co(II) analog (2) displays weak antiferromagnetic coupling (J approximate to-4.32 cm-1) combined with significant easy-axis anisotropy (D =-28.45 cm-1) arising from strong spin-orbit coupling. The comparison of the Ni2O2 and Co2O2 cores highlights how subtle structural variations, particularly the M-O-M angle, govern the balance between exchange interactions and magnetic anisotropy.

Background/Objectives: Gold(I) complexes are promising bioactive agents with anticancer and anti-inflammatory potential. This study evaluated cytochrome P450 (CYP) interactions and in vitro pharmacokinetic properties of two Au(I)-triphenylphosphine complexes bearing 6-alkoxy-9-deazapurine ligands. Methods: Complexes [Au(HL1,2)(PPh3)] (HL1 = 6-isopropyloxy-9-deazapurine, complex 1; HL2 = 6-benzyloxy-9-deazapurine, complex 2) were investigated. Inhibition of nine human CYP isoforms was assessed in liver microsomes, and kinetics were analyzed using Dixon and Lineweaver-Burk plots. CYP binding was evaluated by UV-Vis difference spectroscopy. ADME properties (chemical/plasma stability, microsomal stability, plasma protein binding, and PAMPA permeability) were determined. Binding thermodynamics were analyzed by ITC. Results: Both complexes weakly inhibited most CYP isoforms, with stronger effects on CYP2C9 and CYP3A4/5. A non-competitive inhibition mechanism was observed, which may be related to the binding of the complexes to the substrate channels of CYP2C9 and CYP3A4, thereby limiting the active site's accessibility to the substrate, as supported by molecular docking studies. UV-Vis spectra showed type I binding with Kd values of 9.32 µM (1) and 12.64 µM (2). Both compounds showed high chemical and plasma stability (>90%), moderate microsomal stability (~60% after 60 min), high plasma protein binding (~80%), and low passive permeability. Conclusions: Au(I)-triphenylphosphine complexes with 6-alkoxy-9-deazapurine ligands exhibit moderate CYP affinity and defined pharmacokinetic profiles, supporting further preclinical evaluation.

A family of three heterometallic molecular phosphonate clusters with {CoxDy} (x = 6, 7, 9) cores was synthesized using the Schiff-base-derived phosphonate ligand HSAA2-. The reactions of CoCl2·6H2O and DyCl3·6H2O with HSAA2- under various conditions afforded the polynuclear complexes [Co9Dy(SAA)6Cl3] (1), [Na2Co7Dy(SAA)6(SA)] (2), and [Na3Co6Dy(SAA)6] (3), which are based on a common {Co6Dy} phosphonate core further stabilized by additional cobalt or sodium cations. The complexes were found to be thermally stable up to 250 °C, soluble, and stable in polar aprotic solvents. Direct current (dc) magnetic susceptibility measurements recorded over the temperature range 2-300 K were interpreted using an effective-spin model. The analysis revealed an isotropic Co2+ contribution and a strong axial Dy3+ response consistent with Ising-type magnetic behavior. Despite the presence of strongly anisotropic Dy3+ centers, alternating current (ac) magnetic measurements revealed negligible slow relaxation of magnetization, even under an external magnetic field.

ABSTRACT Polyhedral carboranes are highly biologically stable, non‐toxic clusters. Whereas they are typically encountered in anionic or neutral forms, positively charged species have only recently been discovered. The in vitro antiproliferative effects of selected carboranes were assessed using a panel of human cancer cell lines, and off‐target toxicity was evaluated at normal cell lines. The results demonstrated significant anticancer activity and a favorable resistance factor (RF ≈ 1) for monocationic carborane o ‐2a , surpassing the effects of doxorubicin and cisplatin . In pursuit of even more efficient substrates, the first dicationic polyhedral boranes were synthesized. These water‐stable dications exhibit a reversible closo‐ / nido‐ cage opening, triggered either by a strong base (DMAP) or by a combination of triethylamine and molecular hydrogen, and reversed upon the addition of acid. The former transformation proceeds without a redox change, while the latter involves a H 2 /2H + conversion in a proton‐coupled electron process.

The novel diiron amine complexes [Fe2Cp2(CO)(NH2R')(μ-CO){μ-CN(Me)(Cy)}]CF3SO3 [R' = H, 3; Cy, 4; CH2CH2NH2, 5; CH2CH2NMe2, 6; CH2CH2(4-C6H4OMe), 7; CH2CH2(4-C6H4OH), 8; Cp = η5-C5H5, Cy = C6H11 = cyclohexyl] were synthesized in 49-92 % yields from [Fe2Cp2(CO)2(μ-CO){μ-CN(Me)(Cy)}]CF3SO3, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [Fe2Cp2(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CF3SO3 (R = Cy, 2a; Me, 2b; Xyl = 2,6-C6H3Me2, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions. The in vitro antiproliferative activity of 2a-c and 3-8 was tested on seven human cancer cell lines (A2780, A2780R, PC3, A549, MCF7, HOS and HT-29), while the selectivity was evaluated using normal MRC-5 cells. Overall, the complexes exhibited variable cytotoxicity, with IC50 values reaching the low micromolar range for 3, 7 and 8 in A2780 and A2780R cells, along with significant selectivity. Targeted experiments covered cell cycle modification, induction of cell death, mitochondrial membrane potential, ROS production and interaction with DNA and bovine serum albumin (BSA) as a model protein. The interaction of 3 with BSA was further investigated through computational studies. Results showed a negligible increase in intracellular ROS levels (except for 2b) and insignificant changes in mitochondrial membrane potential.

Monocationic [RuCl(κ3-tpm)(L)(PPh3)]Cl (L = PPh3, 1; NCMe, 2; 1,3,5-triaza-7-phosphaadamantane (PTA), 3; phosphinoferrocene, 4; 3-methyl-pyrazole, 5; NH2(CH2)2OH, 6; NH2(CH2)2(4-C6H4OH) (tyramine), 7; cyclohexylamine, 8; NH2CH2CH2NH2, 9; tpm = tris-pyrazolylmethane) and bis-cationic ruthenium complexes [RuCl(κ3-tpm)(PPh3)(LL')][NO3]2 (LL' = ethylenediamine, 10; 1,10-phenanthroline, 11; 2-picolylamine, 12; N-phenyl-1-(2-pyridinyl)methanimine, 13) and [RuCl(κ3-tpm)(PPh3)(NCMe)2][NO3]2 (14) were evaluated for their anticancer potential. Complexes 4-9 and 13-14 are novel and were obtained in 72-98% yields from thermal exchange reactions of 1. They were characterized by IR and multinuclear NMR spectroscopy, and the solid-state structures of 4, 5, 6, 7, and 14 were determined by single-crystal X-ray diffraction. Complexes 3-8 and 10-14 were further examined for solubility and stability in aqueous media, and octanol/water partition coefficients. The complexes were assessed for their in vitro cytotoxicity on a panel of six cancer and two normal cell lines. Complex 1 and the ruthenium-ferrocenyl conjugate 4 revealed significant-to-moderate activity against the cancer cells, with IC50 values ranging from 1.8 to 25.2 μM. Mechanistic studies in A2780 cells included time-dependent cytotoxicity, intracellular ruthenium uptake, cell cycle analysis, autophagy induction, production of ROS (reactive oxygen species), and mitochondrial membrane potential measurements. Moreover, a detailed study was conducted to evaluate DNA and bovine serum albumin (BSA) binding capacity. Overall, the results revealed distinct potential mechanisms of action driven by ligand diversity, specifically mitochondrial uncoupling for 1 and 4, and apoptosis- and necrosis-induced cell death for 13 and 14.

The new diiron complexes [Fe2Cp2(CO)(L)(mu-CO){mu-CN(Me)(Cy)}]CF3SO3 (L = pyridine, 3a; 4-aminopyridine, 3b; 4-dimethylaminopyridine, 3c; 4-trifluoromethylpyridine, 3d; nicotinic acid, 4; Cp = eta 5-C5H5, Cy = C6H11 = cyclohexyl) were synthesized in moderate to high yields using two distinct synthetic routes from the precursors 1 (L = CO, for 4) and 2 (L = NCMe, for 3a-d), respectively. All products were characterized by IR and multinuclear NMR spectroscopy, and the structures of 3b and 3d were ascertained by X-ray diffraction studies. The behavior of the complexes in aqueous solutions (solubility, Log Pow, stability) was assessed using NMR and UV-Vis methods. The in vitro antiproliferative activity of 3a-c and 4 was evaluated against seven human cancer cell lines (A2780, A2780R, A549, MCF-7, PC3, HOS and HT-29) and one normal cell line (MRC-5), following 24 h of incubation (MTT test). Overall, 3-4 demonstrated stronger cytotoxicity than cisplatin, with 3c emerging as the most potent compound. The activity seems primarily linked to the inhibition of metabolic processes in the cancer cells, including depletion of reactive oxygen species (ROS) levels. However, subtle differences have been observed between the complexes, with 4 exerting its cytotoxicity through a distinct multimodal mechanism.

Five mononuclear Ln(III) complexes {Ln = Gd (1), Tb (2), Dy (3), Ho (4) and Er (5)} of the general composition [Ln(L)(NO3)(H2O)]& sdot;solv (solv = H2O and/or DMF) were synthesized and thoroughly characterized. The pentadentate H2L Schiff base ligand, formed by condensation of 2,4-bishydrazino-6-amino-s-triazine with 3-ethoxysalicylaldehyde, is coordinated to the Ln(III) atoms in the N3O2 donor set in an equatorial plane. The coordination geometry of the central metal atoms is then completed by a bidentate-bonded nitrato ligand and one water molecule, thus forming a biaugmented trigonal prism environment, as follows from the X-ray structure of complex 1. A detailed magnetic evaluation (static (dc) and dynamic (ac) data) of complexes 1-5 uncovered that they behave as magnetically diluted paramagnetics with weak antiferromagnetic features originating probably in the presence of non-covalent bonding in the solid samples. Only the complexes of Dy (3) and Er (5) showed signs of slow relaxation of magnetization with the estimated energy barrier values of Ueff = 9.4 (5) K (for 3) and Ueff = 9.9 (6) K (for 5), and relaxation times of tau 0 = 0.25 (8) mu s (for 3) and tau 0 = 0.45(9) mu s (for 5).

Three copper(II) complexes with variously substituted amine-bisphenolates (H2L1, H2L2 and H2L3) have been prepared. Variation in the composition and structure of the free ligands resulted in the formation of three structurally distinct copper(II) complexes: dinuclear 1, mononuclear 2 and trinuclear 3. Various physical techniques were used to characterise the complexes, including single-crystal X-ray analysis and variable-temperature magnetic susceptibility measurements (5-297 K). The compounds were evaluated for their in vitro anti-proliferative effects against three human cancer cell lines (ovarian A2780 and A2780R, breast MCF7) and normal HaCaT cells. The results showed that both the free ligands and the complexes exhibit strong-to-moderate cytotoxicity. 2 and 3 are significantly more effective against A2780, A2780R and MCF7 cells than the metallodrug cisplatin. The cytotoxicity of complexes 1-3 is bound to the cytotoxicity of the free ligands and remains almost unchanged over 24, 48 and 72 h. The copper accumulation in A2780 cells was studied by ICP-MS over 2-72 h of co-incubation of 1-3. Complex 1 caused the highest uptake of copper into A2780 cells, reaching up to 100 times higher Cu concentration compared to untreated cells, while 2 and 3 showed only ca 5-10-fold increase of Cu uptake in A2780 cells. No apparent signs of hydrolysis of 1-3 in a MeOH/water mixture were observed in mass spectrometry experiments even after 72 h of standing at laboratory temperature. The mass spectrometry-based interaction studies of 1-3 with L-cysteine (Cys) and reduced glutathione (GSH) did not show direct evidence of the interaction product formation. Only the signals, corresponding to the free ligands were identified in mass spectra after 24 h and 72 h of incubation.

A series of eight gold(I) N-heterocyclic carbene (NHC) complexes [Au(IMes)(Ln)] based on 1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene (IMes) and 7-azaindole derivatives (HLn), where n = 1-8 for HL1 = 5-fluoro7-azaindole, HL2 = 5-bromo-7-azaindole, HL3 = 3-chloro-7-azaindole, HL4 = 3-iodo-7-azaindole, HL5 = 5bromo-3-chloro-7-azaindole, HL6 = 5-bromo-3-iodo-7-azaindole, HL7 = 4-chloro-2-methyl-7-azaindole and HL8 = 7-azaindole, was prepared, characterised and studied for their in vitro anti-cancer and anti-inflammatory effects. The complexes showed significant cytotoxicity on human ovarian cancer cell lines (A2780, IC50 approximate to 8-19 mu M and A2780R, IC50 approximate to 8-19 mu M) and lowered toxicity in normal HaCat and MRC-5 cells. Cellular effects of the selected complexes 1 and 7 were evaluated in A2780 cells using flow cytometry. Moreover, the time-dependent cellular uptake in A2780 cells, a shotgun proteomic analysis, an ESI-MS study of hydrolysis and interactions with L-cysteine and reduced glutathione (GSH) were performed. Complexes 1 and 7 revealed remarkable antiinflammatory effects via inhibition of NF-kappa B activity in human endothelial cells.

Structurally diverse zinc( ii ) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

A bis(chalcone) molecule (H2L) was synthesized via Aldol's condensation from terephthalaldehyde and 2 ' hydroxyacetophenone and it was used as bridging ligand for the preparation of five dinuclear copper(II) complexes of the composition [Cu(N-N)(mu-L)Cu(N-N)](NO3)2 & sdot;nH2O (n = 0-2) (1-5), where N-N stands for a bidentate N-donor ligand such as phen (1,10-phenanthroline, 1), bpy (2,2 '-bipyridine, 2), mebpy (5,5 '-dimethyl2,2 '-dipyridine, 3), bphen (bathophenanthroline, 4) and nphen (5-nitro-1,10-phenanthroline, 5). The compounds were characterized by different suitable techniques to confirm their purity, composition, and structure. Moreover, the products were evaluated for their in vitro cytotoxicity on a panel of human cancer cell lines: ovarian (A2780), ovarian resistant to cisplatin (A2780R), prostate (PC3), osteosarcoma (HOS), breast (MCF7) and lung (A549), and normal fibroblasts (MRC-5), showing significant cytotoxicity in most cases, with IC50 approximate to 0.35-7.8 mu M. Additionally, the time-dependent cytotoxicity and cellular uptake of copper, together with flow cytometric studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/ superoxide production in A2780 cells, were also performed. The results of biological testing on A2780 cells pointed out a possible mechanism of action characterized by the G2/M cell cycle arrest and induction of apoptosis by triggering the intrinsic signalling pathway associated with the damage of mitochondrial structure and depletion of mitochondrial membrane potential. Synopsis: Dinuclear Cu(II) complexes bearing a bridging bis(chalcone) ligand revealed high in vitro cytotoxicity, initiated A2780 cell arrest at G2/M phase and efficiently triggered intrinsic pathway of apoptosis.

A series of potassium isothiocyanato-(N-salicylidene-aminoacidato) cuprates (1-5) with the general formula of the monomeric unit K[Cu(sal-aa)(NCS)] & sdot; xH(2)O (x=0 or 2), containing a Schiff-base ligand (H(2)sal-aa) derived from natural amino acids such as glycine, DL-alpha-alanine, DL-valine, DL-phenylalanine and beta-alanine, and salicylaldehyde, was screened for in vitro antiradical and major cellular effects against selected cancerous and normal cells. The complexes exhibited strong antioxidant properties against superoxide in vitro and a protective effect on DNA under Fenton-like reaction conditions. Screening of their cellular effects revealed moderate in vitro cytotoxicity against human cancer cell lines (A2780, A2780R and MCF-7), with IC50 values of 25-35 mu M, and relatively low toxicity to normal fibroblast MRC-5 cells (with IC50 values>50 mu M). Additional experiments performed on A2780 cells revealed that the most potent complex 5 significantly increased the number of A2780 cells arrested in the G2/M phase of the cell cycle and triggered intracellular oxidative stress. The selected flow cytometry experiments (detection of apoptosis/autophagy and activation of caspases 3/7 and depletion of mitochondrial membrane potential) did not reveal the dominant mechanism underlying the cytotoxicity of the complexes but clearly differentiated their molecular effects from those of the reference drug cisplatin. All the complexes exerted anti-inflammatory effects by modulating the levels of the proinflammatory cytokines TNF-alpha and IL-1 beta in LPS-activated THP-1 macrophage-like cells. Complex 5 also slightly influenced the activity of the upstream NF-kappa B transcription factor, while no effect on PPAR gamma activation was detected.

Correction for ‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N -indolyl derivative as a prospective anticancer agent’ by Matteo Fiaschi et al. , Inorg. Chem. Front. , 2024, 11 , 2841–2862, https://doi.org/10.1039/D4QI00096J.

Copper(ii) and zinc(ii) complexes with lapachol (HLap) of the composition [M(Lap)2(N-N)] and [Cu(Lap)(H2O)(terpy)]NO3 (4), where M = Cu (1-3) or Zn (for 5-7), and N-N stands for bathophenanthroline (1 and 5), 5-methyl-1,10-phenanthroline (2 and 6), 2,2'-bipyridine (3), 2,2';6',2''-terpyridine (terpy, 4) and 1,10-phenanthroline (7), were synthesised and characterised. Complexes 1-5 revealed strong in vitro antiproliferative effects against A2780, A2780R, MCF-7, PC-3, A549 and HOS human cancer lines and MRC-5 normal cells, with IC50 values above 0.5 μM, and reasonable selectivity index (SI), with SI > 3.8 for IC50(MRC-5)/IC50(A2780). Considerable time-dependent cytotoxicity in A2780 cells was observed for complexes 6 and 7, with IC50 > 50 μM (24 h) to ca. 4 μM (48 h). Cellular effects of complexes 1, 5 and 7 in A2780 cells were investigated by flow cytometry revealing that the most cytotoxic complexes (1 and 5) significantly perturbed the mitochondrial membrane potential and the interaction with mitochondrial metabolism followed by the triggering of the intracellular pathway of apoptosis.

A series of eight N ‐heterocyclic carbenes (NHC) gold(I) complexes, involving 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene (iPr) ligand in combination with 6‐mercaptopurine derivatives (HL 1–8 ), has been prepared and thoroughly characterized, including elemental analysis, mass spectrometry, infrared and multinuclear NMR spectroscopy, and single crystal X‐ray analysis. The complexes, showing general composition of [Au (iPr)(L n )] 1 – 8 , were evaluated for their in vitro cytotoxicity against four human cancer cell lines including A2780 (ovarian) and A2780R (ovarian Cisplatin resistant), PC3 (prostate) and MCF‐7 (breast), and normal human MRC‐5 cells (lung fibroblasts). The complexes revealed significant cytotoxicity, with the best IC 50 values ≈ 3.4–6.4 μM against A2780 and reasonable selectivity. Cellular effects of the selected complexes on the A2780 cells were evaluated using various flow cytometry assays. Complexes 1 , 3 , and 4 showed a strong pro‐apoptotic effect and a strong effect on the loss of mitochondrial membrane potential. These findings indicate that their major mechanism of action is based on the collapse of the mitochondrial metabolism and activation of the intrinsic signaling pathway of apoptosis, consequently resulting in cell death. The complexes 1 – 8 revealed only negligible effect on the production of inflammatory‐related cytokine (TNF‐α), as well as the activation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) or peroxisome proliferator‐activated receptor gamma (PPARγ). Moreover, the shotgun proteomic analysis was performed, and the obtained results suggest that the mechanism of action of complexes 1 , 3 , and 4 differs somewhat from that of Auranofin .

Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC50 ≈ 2 μM) and osteosarcoma (HOS, with IC50 ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.