A series of novel 2-phenylbenzothiazole-appended acylthiourea (AcTU) ligands and their Ru(II) half-sandwich complexes was synthesized and fully characterized using 1H and 13C NMR, IR spectroscopy, elemental analysis and single-crystal X-ray diffraction. Crystal structures were determined for [dichloro(p-cymene)ruthenium (II) complexes 4gRu, 5eRu, and 5fRu, that adopt "piano-stool" geometry, with the eta 6-arene ligand as a seat, AcTU and two chlorides as the three legs in the pseudo-octahedral crystal field. The synthesized compounds were evaluated against lung (H460), colorectal (SW620), hepatocellular (HepG2), and breast (MCF-7) cancer cell lines, as well as non-tumorigenic HEK293 cells, and compared to cisplatin, a platinum-based chemotherapy drug. The 4-fluorobenzoyl-substituted ligand 5c and the Ru(II) complexes 4cRu and 5cRu demonstrated the highest potency and selectivity, particularly in MCF-7 cells, outperforming anti-proliferative activity of cisplatin in MCF7 cells while maintaining low toxicity toward normal HEK293T cells. Molecular docking and end-point binding free energy calculation studies suggested that 4c and 5c may target the STAT3 SH2 domain, with 4c showing stronger binding stability and 5c offering a broader interaction network, indicating potential advantages in selectivity. In silico ADMET predictions confirmed favorable drug-like properties for the ligands, whereas Ru(II) complexes exhibited reduced bioavailability due to increased size and lipophilicity. Overall, the results demonstrate that the 4-fluorobenzoyl-substituted ligand 5c emerges as the most promising candidate, with superior selectivity and efficacy in breast cancer cells compared with cisplatin, while displaying low cytotoxicity in normal cells, favorable drug-like properties, and a low predicted risk of acute toxicity, thereby identifying it as a potential novel anti-breast cancer agent.

Two tridentate ligands, bis(2-picolyl)amine (bpa) with a preference for formation of cis-fac isomers and iminodiacetamide (imda) with a trans-fac preference, showed a variety of different coordination behavior across a series of late transition metal complexes (Co, Ni, Cu, Zn), such as easy oxidation of Co(II) to Co(III), solution mediated disassembly and reassembly of crystals, and concentration dependent polymorphism of a weakly soluble ML complex. Nine crystal structures of ML2 complexes were determined and the stereochemistry and energetics of the complexes were further studied by DFT calculations.

Chirality on C4-atoms of non-bridging monodentate oxazolines direct stereoselective formation of helical chirality in [M(1)2X2] tetrahedral metal complexes of zinc(II), cadmium(II) and cobalt(II) halides, as revealed by their crystal structures. This feature was used to prepare a set of helically chiral derivatives with various structural motifs. In particular, bulkiness, non-covalent interactions and choice of point chirality combinations were found to strongly affect induction of chirality on the metal atom. The substituent influence on complexation and chiral induction was analyzed using XRD-diffraction studies, NMR, UV-Vis and CD spectroscopies, as well as DFT calculations.

Novel 6-substituted 2-(trifluoromethyl)quinoline 5a-5e and coumarin 6a-6d ligands with aldoxime ether linked pyridine moiety were synthesized by O-alkylation of quinoline and coumarin with (E)-picolinaldehyde oxime and subsequently with [Re(CO)5Cl] gave rhenium(I) tricarbonyl complexes 5aRe-5eRe and 6aRe-6dRe that were fully characterized by NMR, single-crystal X-ray diffraction, IR and UV-Vis spectroscopy. The results of antiproliferative evaluation of quinoline and coumarin ligands and their rhenium(I) tricarbonyl complexes on various human tumor cell lines, including acute lymphoblastic leukemia (CCRF-CEM), acute monocytic leukemia (THP1), cervical adenocarcinoma (HeLa), colon adenocarcinoma (CaCo-2), T-cell lymphoma (HuT78), and non-tumor human fibroblasts (BJ) showed that the quinoline complexes 5aRe-5eRe had higher inhibitory activity than coumarin complexes 6aRe-6dRe, particularly against T-cell lymphoma (HuT78) cells. 6-Methoxy-2-(trifluoromethyl)quinoline 5e and 6-methylcoumarin 6d, and their rhenium(I) tricarbonyl complexes 5eRe and 6dRe were found to arrest the cell cycle of HuT78 cells by causing a significant accumulation of cells in the G0/G1 phase and a marked decrease in the number of cells in the G2/M phase. These rhenium(I) tricarbonyl complexes also slightly increased ROS production and significantly decreased the mitochondrial membrane potential by 50 % (5eRe) and 45 % (6dRe) compared to untreated cells and cells treated with 5e and 6d. These results suggest that the cytotoxic effects of these compounds are mediated by their effects on mitochondrial membrane potential and the subsequent increase in ROS production.

Oxazoline amino acid bioconjugates were synthesized; the relative stability of a supramolecular dimer of a tris-derivative was investigated using mean absolute error values (MAE), derived from 1H NMR experiments and DFT calculations.

Bis(2‐picolyl)amine (bpa), iminodiacetamide (imda), and bis‐1,2,3‐triazole (bta) ferrocene ligands (L) with and without an aliphatic linker were prepared by multi‐step synthesis. The cis‐fac, trans‐fac, or mer stereochemistry of their ML2 complexes with Ni(II), Cu(II), Cd(II), and Zn(II) was studied in the solid state (infrared [IR] and single‐crystal X‐ray diffraction [SC‐XRD]), in solution (nuclear magnetic resonance [NMR] and cyclic voltammetry [CV]) and by density functional theory (DFT) calculations. Crystal structures were determined for bpa ligand 7, and complexes [Ni(1)2](NO3)2 (1Ni), [Cu(8)2]OTf2 (8Cu), [Ni(10b)2](NO3)2 (10bNi), and [Cu(10b)2]OTf2 (10bCu). The bond strength of the central metal ion to the ligand amine nitrogen atom was studied by NMR, electrochemistry, and DFT. The information on redox‐active centers, electron transfer properties of ferrocene ligands (L), and their in situ complexation with zinc(II) and nickel(II) ions were obtained by voltammetric analysis. In addition, DFT calculations showed that the electron ionization in ML2 complexes occurs from one of the ferrocene units, leaving the electronic structure of the other ligand intact, while some of the expelled electron density is recovered by the adjacent amine through resonance. This effect is more pronounced in the free ligands, because the eventual amine resonance in ML2 needs to balance its Zn(II) coordination participation, which justifies why they show higher ionization energies over free ligands. Moreover, due to lower steric hindrance, the N(amino)–Zn(II) coordination is additionally stronger in 1:1 ML complexes, which makes their electron depletion further more demanding. If compared with the clinical drug cisplatin, complexes of bpa 1Ni and imda 2Ni showed a better effect on the viability of different tumor cell lines and better selectivity towards normal cells. Treatment with 1Ni and 2Ni causes an increase of cells in the S phase of the cell cycle and leads to the accumulation of cells in G0/G1. A decrease in the expression level of anti‐apoptotic marker Bcl‐2 upon treatment with both compounds together with increased amount of Annexin V‐FITC positive cells implied apoptosis as the mode of cell death.

This publication describes monodentate phosphine and oxazoline ligands attached to an amino acid ester and the application of their supramolecularly assembled rhodium(i) or iridium(i) complexes in asymmetric catalysis. The major feature of these complexes is the transmission of chirality from distant hydrogen bonded amino acids to the prochiral catalytic metal center ("backdoor induction"). The in situ generated homoleptic and heteroleptic rhodium(i) or iridium(i) precatalysts were studied by NMR, UV-VIS and CD spectroscopy as well as X-ray single crystal diffraction. In asymmetric hydrogenation of methyl alpha-acetamidocinnamate, rhodium(i) and iridium(i) complexes afforded complete conversions with enantioselectivities up to 85%, while iridium complexes proved to be more sensitive to the variation of reaction conditions, including catalyst loading, metal to ligand ratio and temperature. The hydrogenation of four other dehydroamino acid substrates resulted in similar conversion and selectivity as obtained with methyl alpha-acetamidocinnamate. The influence of the phosphine/oxazoline heteroleptic mixtures in catalysis was studied using both rhodium(i) and iridium(i) complexes. Finally, a homoleptic phosphine rhodium(i) complex was successfully applied in asymmetric hydroformylation of styrene and 1-octene with complete conversions and selectivity up to 40% ee for the branched styrene product.

Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium-based anticancer drugs and the cytostatic activity of organometallic complexes with triazole- and coumarin-derived ligands, we set out to synthesize Ru(II) complexes of coumarin-1,2,3,-triazole hybrids (L) with the general formula [Ru(L)(p-cymene)(Cl)]ClO4. The molecular structure of the complex [Ru(2a)(p-cymene)(Cl)]ClO4 (2aRu) was determined by single-crystal X-ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC-1 pancreatic cancer cells. Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.

With the aim of achieving bioorthogonal intracellular catalysis, a library of platinum(II) complexes was synthesized. Their non-toxicity to living cells was demonstrated and their catalytic activity was evaluated on a cyclization reaction leading to a highly fluorescent coumarin. None of the platinum complexes showed any catalytic activity for coumarin synthesis. Still, we demonstrated that the silver salt AgSbF6 commonly used to 'activate' metal catalysts by removing a chloride is a very efficient catalyst for the studied intramolecular cyclization reaction.

Bioorganometallic complexes have attracted considerable interest and have shown promise for potential application in the treatment and diagnosis of cancer, as well as bioimaging agents, some acting as theranostic agents. The series of novel ferrocene, benzimidazo[1,2-a]quinoline and fluorescein derivatives with bidentate pyridyl-1,2,3-triazole and 2,2'-dipyridylamine and their tricarbonylrhenium(I) complexes was prepared and fully characterised by NMR, single-crystal X-ray diffraction, UV-Vis and fluorescence spectroscopy in biorelevant conditions. The fluorescein and benzimidazo[1,2-a]quinoline ligands and their complexes with Re(I) showed interactions with ds-DNA/RNA and HSA, characterised by thermal denaturation measurements, fluorimetric and circular dichroism titrations. The binding constants revealed that addition of Re(I) increases the affinity of fluorescein but decreases the affinity of benzimidazo[1,2-a]quinoline. The complexation of Re(I) had the opposite effect on fluorescein and benzimidazo[1,2-a]quinoline ligands' fluorimetric sensitivity upon biomacromolecule binding, Re(I) fluorescein complex emission being strongly quenched by DNA/RNA or HSA, while emission of Re(I) benzimidazo[1,2-a]quinolone complex was enhanced, particularly for HSA, making it a promising fluorescent probe. Some mono- and heterobimetallic complexes showed considerable antiproliferative activity on colon cancer cells (CT26 and HT29), with ferrocene dipyridylamine complexes exhibiting the best inhibitory activity, comparable to cisplatin. The correlation of the cytotoxicity data with the linker type between the ferrocene and the 1,2,3-triazole ring suggests that direct binding of the metallocene to the 1,2,3-triazole is favourable for antitumor activity. The Re(I) benzimidazo[1,2-a]quinolone complex showed moderate antiproliferative activity, in contrast to the Re(I) fluorescein complex, which exhibited weak activity on CT26 cells and no activity on HT29 cells. The accumulation of the Re(I) benzimidazo[1,2-a]quinolone complex in the lysosomes of CT26 cells indicates the site of its bioactivity, thus making this complex a potential theranostic agent.

The isomerism of zinc complex [Zn(L)2]2+ with tridentate ligand L having acetamide and pyridine groups on each side of the central amino- nitrogen atom has been investigated by DFT calculations, liquid state NMR and single-crystal X-ray diffraction. DFT was used for obtaining the ensembles of low-energy conformers of L and [Zn(L)2]2+ and for the calculation of NMR parameters for all conformers. For all generated conformers of L and [Zn(L)2]2+, the Mean Absolute Error [MAE(conf)] was tested as a structural quality parameter and compared with MAE(Bolz) for Boltzmann weighted ensembles. The most populated conformers had MAE(conf) values below 0.1 and 1 ppm for 1H shifts and 13C shifts, respectively. For the [Zn(L)2]2+ complex, the mer- C2 symmetric isomer was the most stable, in accordance with the X-ray structure of [Zn(L)2]2[SiF6][BF4]2. The cancellation of the magnetic equivalence of some nuclei valid for free L, when coordinated to the Zn2+ cation, was theoretically explained by the correct averaging of NMR parameters in the calculation procedure.

Seven bis(2-picolyl)amine (bpa) and five iminodiacetamide (imda) ligands were prepared with different modifications in their side chain structure. The coordination properties of the ligands (L) were influenced by changes in the aliphatic linker length (C1, C2, or C3), amide group isomers and type of chiral terminal group. Complexation with Cu(II) afforded two polymorphs of a ML complex which features tetradentate coordination of a ligand with C2 linkers, while crystal structures of three trans-fac ML2 complexes with Cu(II) and Ni(II) show tridentate coordination of ligands with a C3 linker. The stoichiometry and stereochemistry of Zn(II) and Cu(II) complexes was further studied in solution by NMR and UV-Vis spectroscopy. DFT calculations gave an insight into the relative stability of isomers, as well as potential hydrogen bonding between two ligands in a ML2 complex. Furthermore, ML complexes of Cu(II) exhibited DNA cleavage activity.

An unexpected tandem reaction consisting of amide coupling and hydroamination occurring with common triazole coupling reagents.

Ferrocene derivatives with mono- (8a-c) and bis-1,2,3-triazolyl (9 and 10a-13c) chelating groups were synthesized by regioselective copper(I)-catalysed 1,3-dipolar cycloaddition of terminal alkynes with ferrocene azides. Metal complexes of the ligands were prepared with Cu(II) and Zn(II) salts. Crystal structures of ligands 9 and 11a were determined, as well as the structures of complexes [Cu(8a)(2)](CF3SO3)(2) (8a(Cu)) and [Cu(8c)(2)(CH3OH)(2)](BF4)(2) (8c(Cu)). In addition to NMR and UV-Vis spectroscopy, the metal complexes were characterized by cyclic voltammetry. The cytotoxic effect of ferrocene conjugates and their Zn(II) and Cu(II) complexes was explored, and cell cycle analysis was performed. The complex [Cu(8c)(2)](CF3SO3)(2) showed the most prominent and selective cytotoxicity on cervical carcinoma (HeLa), ovarian cancer (MES-OV), non-small cell lung cancer (A549) and breast carcinoma (MDA-MB-231) cells. This complex increased cell population in the S and G(2)/M phase of the cell cycle, which was accompanied by an increase of the cells present in the sub-G(0)/G(1) fraction.

An ultrasound-assisted synthesis has been used for the preparation of novel benzothiazole Schiff bases (1-3) as ligands for Zn(II) and Cu(II) metal complexes. In this class of Schiff base ligands, the isolated complexes 1a and 2a appear to be the only ones that have structures which include both the Schiff base ligand and the hydrolysis product 2- aminobenzothiazole in the same complex molecule. The aldehydes formed by Schiff base hydrolysis formed a rare example of a trans-isomer in pentacoordinated 2,4-disubstituted benzaldehyde complexes.

The crystal structure of tris[dimethyl 5-({1-[(pyridin-2-yl-κ N )carbamoyl-κ O ]ethyl}carbamoyl)benzene-1,3-dicarboxylate]zinc(II) dinitrate acetonitrile trisolvate, [Zn(C 19 H 19 N 3 O 6 ) 3 ](NO 3 ) 2 ·3CH 3 CN or [Zn( L ) 3 ](NO 3 ) 2 ·3CH 3 CN, ( 1 ), has been determined by single-crystal X-ray diffraction. The neutral ligand L coordinates to the Zn 2+ cation in a bidentate fashion via the pyridine N atom and an amide O atom, forming a six-membered chelate ring. The Λ-helical chirality of the Zn 2+ coordination sphere is induced by pendant l -alanine residues through stacking interactions between the arene groups of two coordinated ligands, assisted by a hydrogen bond between amide groups bonded to the stacked arene rings. The third ligand is coordinated to the Zn 2+ cation by the same six-membered chelate ring, but in the opposite direction with respect to the analogous chelate rings of the first two coordinated ligands. Besides ionic interactions between [Zn L 3 ] 2+ complexes and NO 3 − anions, several types of hydrogen bonds and intermolecular stacking interactions contribute to the stability of the solid-state phase.

p-Disubstituted phenyldiketopiperazines 1 (R = H), 2 (R = NO2) and 3 (R = -N(CH3)(2)) were synthesized and characterized by NMR in solution and IR spectroscopy. The identity of the compounds was confirmed and their fragmentation analyzed by ESI-MS and HRMS spectrometry. X-ray single crystal structures revealed that the three compounds crystallize in space groups P2(1) (1), Pbca (2) and P2(1)/c (3), respectively. The solid-state structures of 1-3 were further analyzed by a combination of solid-state NMR spectroscopy and GIPAW calculations. The NMR crystallography approach was used to analyze symmetry breaking of nearly centrosymmetric molecules in 1, and disorder of piperazine groups in crystal structure of 3. (C) 2021 Elsevier B.V. All rights reserved.

The crystal structure of tris[dimethyl 5-({1-[(pyridin-2-yl-κN)carbamoyl-κO]ethyl}carbamoyl)benzene-1,3-dicarboxylate]zinc(II) dinitrate acetonitrile trisolvate, [Zn(C19H19N3O6)3](NO3)2·3CH3CN or [Zn(L)3](NO3)2·3CH3CN, (1), has been determined by single-crystal X-ray diffraction. The neutral ligand L coordinates to the Zn2+ cation in a bidentate fashion via the pyridine N atom and an amide O atom, forming a six-membered chelate ring. The Λ-helical chirality of the Zn2+ coordination sphere is induced by pendant L-alanine residues through stacking interactions between the arene groups of two coordinated ligands, assisted by a hydrogen bond between amide groups bonded to the stacked arene rings. The third ligand is coordinated to the Zn2+ cation by the same six-membered chelate ring, but in the opposite direction with respect to the analogous chelate rings of the first two coordinated ligands. Besides ionic interactions between [ZnL3]2+ complexes and NO3- anions, several types of hydrogen bonds and intermolecular stacking interactions contribute to the stability of the solid-state phase.

We present a double-stranded ferrocene pseudopeptide 2b which exhibits stimuli responsive chirality inversion triggered by solvent exchange or acid addition. Compound 2b exists as a mixture of self-assembled fast exchanging oligomers which macroscopically behave as a chiroptical switch with two stable states. The ferrocene group inversion results in a distinct CD signal in the visible part of the spectrum. The inversion is accomplished through a conformational change due to a rearrangement of hydrogen bonding forcing the rotation of ferrocene rings.