A series of imidazole-based thiosemicarbazones (TSCs) was developed, and their metal complexation behavior was comprehensively investigated in solution. In addition, the structures of four ligands and four corresponding complexes were determined by single-crystal X-ray diffraction, revealing that Cu(II) and Fe(III) complexes adopt coordination through the (N,N,S) donor set. Lipophilicity, acid-base and complex formation equilibria with Cu(II), Fe(II/III), and Ni(II) were characterized using pH-potentiometry, UV-visible and electron paramagnetic resonance spectroscopy methods. Based on the solution equilibrium data, the imidazole-TSCs exist predominantly in their neutral form at physiological pH (7.4), and exhibit a stronger affinity for Cu(II) than for Fe(II), Fe(III) or Ni(II). They form mono-ligand complexes with all of these metals, and additionally tetranuclear complexes with Cu(II). The electrochemical properties of the Cu(II) complexes were characterized by cyclic voltammetry and UV-visible spectroelectrochemistry, revealing all Cu(II) complexes of imidazole-TSCs follow an electrochemical dual-pathway square scheme. The anticancer activity of imidazole-TSC derivatives was evaluated against the human cancer cell lines Colo205 and the doxorubicin-resistant Colo320. Coordination of imidazole-TSC derivatives to Cu(II) or Ni(II) markedly enhanced their anticancer activity against Colo205 and Colo320 cells. Among the compounds tested, Me2-imidazole-TSC demonstrated the greatest potency, while the benzimidazole-TSC complex also exhibited pronounced activity. Methyl substitution and aromatic conjugation were found to substantially improve the cytotoxic effect.

Indoloquinolines are potent anticancer agents, but their poor aqueous solubility prevents clinical development. Indoloquinoline-based metal complexes offer an opportunity to circumvent this drawback. A series of new indolo[2,3-c]quinoline derivatives HL1-HL8 and their copper(II) complexes were synthesized, comprehensively characterized and tested for antiproliferative activity against MDA-MB-231, MCF-7, MCF-7 KCR, A549 and DU-145 cancer cells and compared to known isomeric indolo[3,2-c]quinolines (HL11-HL14 and 11-14). The Cu(II) complexes were generally as active, or slightly more so, than the proligands. Lead compounds HL8 and 8 showed superior anticancer activity compared to isomers HL14 and 14, respectively. Complex 8 was superior to HL8 in ROS generation in A549 cells, induced mitochondrial dysfunction as evidenced by JC-1 staining, induced lactate dehydrogenase release in medium, inhibited DNA synthesis and triggered apoptosis. DNA-binding studies, supported by molecular docking calculations, showed strong affinity of the compounds for double stranded DNA, to which they bind by intercalation.

Morpholine-functionalized 8-hydroxyquinoline (HQ) derivatives with reduced Schiff base linkers, Morph-Et-HQ and Morph-Pr-HQ, were synthesized and comprehensively characterized to investigate the influence of linker length on donor-set preference, metal binding, and the behavior of RhCp* complexes. Both ligands exhibited excellent aqueous solubility due to the predominance of positively charged species at physiological pH, but showed no cytotoxicity, which is partly attributed to their reduced iron-binding ability compared to classical HQ systems. Solution speciation studies revealed unusual coordination behavior toward Fe(II), Zn(II), and Cu(II), involving tridentate and tetradentate donor sets beyond the classical (N,O) binding modes. In Zn(II) and Cu(II) systems, coordination rearrangements and the coexistence of multiple binding modes were observed. Although the RhCp* complex of Morph-Pr-HQ bearing the longer linker behaved similarly to conventional HQ-based complexes, Morph-Et-HQ exhibits markedly different coordination chemistry. Spectroscopic, pH-potentiometric, NOESY NMR, and density functional theory (DFT) results consistently supported the predominant (N,N,N) coordination of Morph-Et-HQ at pH 7.4, which was associated with moderate cytotoxic activity. Our results demonstrate that minor structural modifications of the linker can shift the preferred coordination mode of morpholine-functionalized HQs from classical (N,O) binding to unconventional nitrogen-donor coordination, strongly influencing their physicochemical and biological properties.

Manganese(III)-porphyrins - Mn(III)P-exhibit remarkable redox activity, influencing oxidative and antioxidative processes in biological systems. In this study, we explore the dual roles of Mn(III)-2-TE-PyP5+ and Mn(III)-4-TE-PyP5+ in modulating hyaluronan degradation, a key factor in both neuroprotection and cancer therapy. While Mn(III)-2-TE-PyP5+ enhances oxidative degradation of high-molecular weight hyaluronan, facilitating immune recognition of cancer cells, its structural isomer Mn(III)-4-TE-PyP5+ acts as a potent antioxidant, safeguarding neuronal integrity against oxidative stress. Employing rotational viscometry, oximetry, electron paramagnetic resonance (EPR), and gas chromatography-mass spectrometry (GC-MS), we delineate the mechanisms underlying the redox transformations of Mn(III)P-derivatives and their impact on glycocalyx integrity. Our findings provide new insights into the selective therapeutic applications of Mn(III)P-derivatives, offering promising strategies for targeted cancer treatment and neurodegenerative disease prevention.

An organic-inorganic diamine, 1,3-bis(aminopropyl)tetraphenyldisiloxane, was prepared and introduced as a flexible spacer into the structure of a salen-type Schiff base (H2L7) extending the available small library of similar compounds derived from 1,3-bis(aminopropyl)tetramethyldisiloxane and substituted 2-hydroxybenzaldehydes (H2L1-H2L6). Like the previously reported mononuclear copper(II) complexes [CuL1]-[CuL6], the new copper(II) complex [CuL7], obtained by reaction of Cu(OAc)2·H2O with H2L7 in a mixture of organic solvents, has a tetrahedrally distorted square-planar (N2O2) coordination geometry. X-ray crystallography has shown that compared to [CuL1]-[CuL6] the Si-O-Si angle in [CuL7] is even closer to linear due to stronger intramolecular interactions between Ph groups than between Me groups in the central-R2Si-O-SiR2- fragment (R = Ph and Me, respectively). [CuL7] can be electrochemically reversibly oxidised by two successive one-electron processes, generating stable phenoxyl mono- and diradicals. Both oxidations are ligand-centred, leading to the formation of coordinated phenoxyl radicals. The UV spectrum of [CuL7] consists of π → π* and LMCT σ → d transitions. The low-energy d-d absorption is well described by AILFT CAS(9,5)/NEVPT2 calculations. The one-electron oxidised compound [CuL7]+ should exist in the triplet ground state as 3[CuL7]+ with one unpaired electron located on the dx2-y2 orbital of copper(II) (d9, SCu = ½) and another electron on the molecular orbital (MO) comprising pz oxygen and carbon atoms of the phenoxyl radical (Srad = ½). The broad absorption in the vis-NIR region of the optical spectrum of the one-electron oxidised complex is due to intervalence charge transfer in the triplet species 3[CuL7]+, but not in the [CuL7]2+ one. The doubly oxidised [CuL7] species shows very close doublet and quartet states, where the doublet state has an unpaired electron located on the Cu(II) d-orbital, while the quartet state has one unpaired electron on the Cu(II) d-orbital and two unpaired electrons on π-bonding orbitals. In all state-averaged CASSCF cases, the occupation of the Cu(II) d-orbital is nearly 1.0, indicating its limited involvement in the excited states. Catalytic studies showed that [CuL7] acts as a catalyst for the oxidation of alkanes with peroxides under very unusual solvent-free conditions, converting cyclohexane into cyclohexanol and cyclohexanone (with hydrogen peroxide or tert-butyl hydroperoxide as the oxidant) or into cyclohexanol and ε-caprolactone (with m-chloroperoxybenzoic acid as the oxidant). Theoretical investigations of the catalytic reaction mechanisms disclosed the principal intermediates.

The introduction of 4,5-dihydroazuleno[2,1,8-ija]azulene as a central core between two 1,4-dithiafulvene (DTF) units provides a novel class of extended tetrathiafulvalene (TTF) electron donors. Herein we present the synthesis of such compounds with the azulenoazulene further expanded by annulation to benzene, naphthalene, or thiophene rings. Moreover, unsymmetrical donor-acceptor chromophores with one DTF and one carbonyl at the central core are presented. The effect of the odd-membered rings of the polycyclic aromatic hydrocarbon cores on the geometrical features and the extent of bond conjugation in these systems were investigated by UV/Vis absorption spectroscopy, (spectro)electrochemical studies, X-ray and electron diffraction, and computational studies. Altogether these studies reveal that, upon oxidation, the non-planar core of the bis(benzo)-fused dihydro-azulenoazulene-extended TTF generates a large 22π-aromatic system (together with two 6π-aromatic 1,3-dithiolium appendages) characterized by significant bond length equalizations. The dication formed by oxidation is EPR silent, indicating a singlet ground state. Computations reveal that the closed-shell singlet species and its open-shell singlet counterpart are nearly degenerate and of lower energy than a triplet species. According to cyclic voltammetry, the compounds can be oxidized further and present multi-redox systems.

The incorporation of electron-withdrawing 1,3,4-oxadiazole into the extended oligomeric it-electron structure can lead to highly attractive compounds in the research and development of organic light-emitting diodes, fluorescent materials, and ambipolar organic semiconductors. Herein, we describe the synthesis of parental 2,5bis(2,3,4,5,6-pentafluorophenyl)-1,3,4-oxadiazole (1) and its next three new derivatives substituted in the para position with lateral N,N-diphenylamine and p-tolyloxy moieties. The redox properties of the prepared compounds were investigated using electrochemical and in situ EPR/UV-vis-NIR spectroelectrochemical techniques in anodic and cathodic regions. Upon repetitive cycling, the formation of new dimeric and/or oligomeric products of 1 with an elongated it-conjugation was observed with considerably less negative reduction potentials compared to the initial monomer. The coupling of anion radicals from bis(pentafluorophenyl)-1,3,4-oxadiazoles is accompanied by the release of fluoride anions at different positions on the fluorinated phenyl ring. A similar electrochemical and spectroelectrochemical response was found during the cathodic reduction of 1 analogues bearing nonsymmetric N,N-diphenylamine and symmetric p-tolyloxy moieties. In the anodic part, the formation of dimer oligomer structures via coupling at N,N-diphenylamine moiety was found under formation of benzidinelike structures. The site of dimerization and further oligomerization and the mapping of the unpaired spin density for both the corresponding radical anions and the radical cations are interpreted using the quantum chemical calculations performed at the density functional theory level. The possible use of electrochemical approach as effective method of synthesis of perfluorinated oligomers is discussed.

The incorporation of non-native chemical elements, such as silicon, into drug molecules has gained significant attention as a strategy to broaden the chemical space in medicinal chemistry and develop novel drug candidates. Traditionally, research has focused on the isosteric replacement of a carbon atom with silicon ("silicon switch") in known drug structures or the attachment of a trimethylsilyl (TMS) group to biologically active scaffolds. In this study, a TMS-substituted indoloquinoline-based Schiff base (HLTMS) and its corresponding metal complexes, Cu(HLTMS)Cl2 (1) and Zn(HLTMS)Cl2 (2), were synthesized and comprehensively characterized using elemental analysis, spectroscopic techniques (IR, UV-vis, 1H and 13C NMR for HLTMS and 2), ESI mass spectrometry and single-crystal X-ray diffraction (SC-XRD) for 1 and electron diffraction (ED) for 2. The attachment of the TMS group enhanced the lipophilicity of HLTMS, while complex formation with Cu(II) substantially improved the antiproliferative activity. Exploitation of their intrinsic fluorescence to investigate cellular uptake and intracellular localization in cancer cells was impeded by limited solubility. Both HLTMS and 2 were found to generate reactive oxygen species under cell-free conditions in accord with their redox activity established by cyclic voltammetry. The photochemical activity of the indolo[2,3-c]quinoline-based proligand HLTMS and its complexes 1 and 2 has been disclosed. The compounds exhibited significant toxicity on various human cancer cells and disrupted the mitochondrial membrane potential, suggesting the contribution of mitochondrial dysfunction, triggered by HLTMS and its metal complexes, to their toxic effects. These findings highlight the potential of TMS-substituted Schiff bases as promising anticancer drug candidates.

The Ni(ii) complexes reported in this work show high performance for OER and are suggested as promising candidates for alkaline water electrolysis.

Quite recently we discovered that copper(II) complexes with isomeric morpholine-thiosemicarbazone hybrid ligands show good cytotoxicity in cancer cells and that the molecular target responsible for this activity might be tubulin. In order to obtain better lead drug candidates, we opted to exploit the power of coordination chemistry to (i) assemble structures with globular shape to better fit the colchicine pocket and (ii) vary the metal ion. We report the synthesis and full characterization of bis-ligand cobalt(III) and iron(III) complexes with 6-morpholinomethyl-2-formylpyridine 4N-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL1), 6-morpholinomethyl-2-acetylpyridine 4N-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL2), and 6-morpholinomethyl-2-formylpyridine 4N-phenyl-3-thiosemicarbazone (HL3), and mono-ligand nickel(II), zinc(II) and palladium(II) complexes with HL1, namely [CoIII(HL1)(L1)](NO3)2 (1), [CoIII(HL2)(L2)](NO3)2 (2), [CoIII(HL3)(L3)](NO3)2 (3), [FeIII(L2)2]NO3 (4), [FeIII(HL3)(L3)](NO3)2 (5), [NiII(L1)]Cl (6), [Zn(L1)Cl] (7) and [PdII(HL1)Cl]Cl (8). We discuss the effect of the metal identity and metal complex stoichiometry on in vitro cytotoxicity and antitubulin activity. The high antiproliferative activity of complex 4 correlated well with inhibition of tubulin polymerization. Insights into the mechanism of antiproliferative activity were supported by experimental results and molecular docking calculations.

The development of copper(II) thiosemicarbazone complexes as potential anticancer agents, possessing dual functionality as inhibitors of R2 ribonucleotide reductase (RNR) and tubulin polymerization by binding at the colchicine site, presents a promising avenue for enhancing therapeutic effectiveness. Herein, we describe the syntheses and physicochemical characterization of four isomeric proligands H2L3-H2L6, with the methylmorpholine substituent at pertinent positions of the pyridine ring, along with their corresponding Cu(II) complexes 3-6. Evidently, the position of the morpholine moiety and the copper(II) complex formation have marked effects on the in vitro antiproliferative activity in human uterine sarcoma MES-SA cells and the multidrug-resistant derivative MES-SA/Dx5 cells. Activity correlated strongly with quenching of the tyrosyl radical (Y-center dot) of mouse R2 RNR protein, inhibition of RNR activity in the cancer cells, and inhibition of tubulin polymerization. Insights into the mechanism of antiproliferative activity, supported by experimental results and molecular modeling calculations, are presented.

The anti (a) to syn (s) isomerization pathway of the deprotonated form of the dimer with two nickel(II) 15-membered octaazamacrocyclic units connected via a carbon–carbon (C–C) σ bond was investigated. For the initial anti (a) structure, a deprotonation of one of the bridging (sp3 hybridized) carbon atoms is suggested to allow for an a to s geometry twist. A 360° scan around the bridging C–C dihedral angle was performed first to find an intermediate geometry. Subsequently, the isomerization pathway was explored via individual steps using a series of mode redundant geometry optimizations (internal coordinates potential energy surface scans) and geometry relaxations leading to the s structure. The prominent geometries (intermediates) of the isomerization pathway are chosen and compared to the a and s structures, and geometry relaxations of the protonated forms of selected intermediates are considered.

The main aims of this work were the synthesis and characterization of iron(III) complexes with with a ditopic ligand H2L consisting of a bis(salicylidene)isothiosemicarbazide moiety with a N2O2 binding site and a crown-ether (O6) moiety. A series of high-spin iron(III) complexes, i.e. [FeIIILClBa(CH3OH)(H2O)0.5(ZnCl4)] (1), [FeIIILCl] (2), [FeIIIL(N3)] (3) and [(FeIIIL)2O] (4), were synthesized. The complexes were characterized by mass spectrometry, IR and UV-vis spectroscopy, variable temperature (VT) magnetic susceptibility measurements, M?ssbauer spectroscopy, single crystal X-ray diffraction and cyclic voltammetry.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

In one-dimensional polycyclic aromatic hydrocarbons (PAHs) containing five- and six-membered rings fused together, one key question is whether the structures possess a quinoidal or aromatic diradical character. Here, we generate such PAHs by reversible oxidation of PAH-extended tetrathiafulvalenes (TTFs). Extended TTFs were thus prepared and studied for their geometrical properties (crystallography), redox properties, and UV/Vis/NIR/EPR characteristics as a function of charge state. The EPR measurements of radical cations showed unique features for each PAH-TTF. The dications, formally composed of fluoreno[3,2-b]fluorene and diindeno[1,2-b:1',2'-i]anthracene cores, were experimentally found to exhibit singlet ground states. For the latter, calculations reveal the closed shell, quinoid singlet state to be isoenergetic with the open shell singlet diradical. Each charge state exhibited unique optical properties with radical cations absorbing strongly in the NIR region with signatures from π-dimers for the large core. The experimental results were paralleled and supported by detailed computations, including spin density distribution calculations, EPR simulations, and nucleus independent chemical shift (NICS) xy scans.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The anti (a) to syn (s) isomerization pathway of the deprotonated form of C-C σ dimer complex with two nickel(II) 15-membered octaazamacrocyclic units was investigated. For the initial anti (a) structure a deprotonation of one of the bridging (sp3 hybridized) carbon atoms is suggested to allow for an a to s geometry twist. A 360° scan around the bridging C-C dihedral angle was performed first. Subsequently, the isomerization pathway was explored via individual steps using a series of mode redundant geometry optimizations and geometry relaxations. Geometries of the isomerization pathway are compared to the a and s structures. Finally, geometry relaxations of the protonated forms of selected intermediates is considered.

A test set of N,N,N’,N’-tetrasubstituted p-phenylenediamines are experimentally explored using ESR (electron spin resonance) spectroscopy and analysed from a computational standpoint thereafter. This computational study aims to further aid structural characterisation by comparing experimental ESR hyperfine coupling constants (hfccs) with computed values calculated using ESR-optimised “J-style” basis sets (6-31G(d,p)-J, 6-31G(d,p)-J, 6-311++G(d,p)-J, pcJ-1, pcJ-2 and cc-pVTZ-J) and hybrid-DFT functionals (B3LYP, PBE0, TPSSh, ωB97XD) as well as MP2. PBE0/6-31g(d,p)-J with a polarised continuum solvation model (PCM) correlated best with the experiment, giving an R2 value of 0.8926. A total of 98% of couplings were deemed satisfactory, with five couplings observed as outlier results, thus degrading correlation values significantly. A higher-level electronic structure method, namely MP2, was sought to improve outlier couplings, but only a minority of couples showed improvement, whilst the remaining majority of couplings were negatively degraded.

Reliance of human population on quickly depleting fossil fuels stimulates a search for sustainable alternatives. Hydrogen represents one of the most promising candidates to replace the largely consumed fossil fuels. One of the crucial issues of the hydrogen cycle is the H2 gas storage under ambient conditions. Hence, a search for effective H2 storage devices is of urge importance. The H2 storage capacity of the Cr-, Mn-, and Fe-doped circumcoronenes (CCs) in the presence of N and B co-dopants is investigated at the DFT level of theory. Obtained results suggest that the presence of N co-dopants significantly enhances the affinity of the studied systems towards H2 binding, which consequently leads to improved H2 storage properties. Moreover, the presence of three N co-dopants energetically stabilizes the Cr-, Mn-, and Fe-doped CCs in their low-spin states, which are the most suitable for the H2 adsorption. In addition, the H2 adsorption performance of the Mn–3N-doped CCs can be altered by the oxidation and reduction. This finding indicates that an application of the external electric potential may control the H2 release-and-capture mechanism in Mn-doped CC storage devices. In addition, the metal-doped CC cation appears as the energetically preferred form (metal-doped CC is a strong reducing agent when compared to the ferrocene couple).

Indolo[3,2-d][1]benzazepines (paullones), indolo[3,2-d][2]benzazepines, and indolo[2,3-d][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2-d][2]benzazepine-derived ligands HL1-HL4 and copper(II) complexes 1-4. All compounds were characterized by spectroscopic methods (1H and 13C NMR, UV-vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes 2 and 3, in addition, by X-ray crystallography. Their purity was confirmed by HPLC coupled with high-resolution ESI mass spectrometry and/or elemental analysis. The stability of compounds in aqueous solutions in the presence of DMSO was confirmed by 1H NMR and UV-vis spectroscopy measurements. The compounds revealed high antiproliferative activity in vitro in the breast cancer cell line MDA-MB-231 and hepatocellular carcinoma cell line LM3 in the low micromolar to nanomolar concentration range. Important structure-activity relationships were deduced from the comparison of anticancer activities of HL1-HL4 and 1-4 with those of structurally similar paullone-derived (HL5-HL7 and 5-7) and latonduine-derived scaffolds (HL8-HL11 and 8-11). The high anticancer activity of the lead drug candidate 4 was linked to reactive oxygen species and endoplasmic reticulum stress induction, which were confirmed by fluorescent microscopy and Western blot analysis.