Mn(III)-porphyrins in battle against neurodegenerative and cancer diseases.

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-PyP and Mn(III)-4-TE-PyP in modulating hyaluronan degradation, a key factor in both neuroprotection and cancer therapy. While Mn(III)-2-TE-PyP enhances oxidative degradation of high-molecular weight hyaluronan, facilitating immune recognition of cancer cells, its structural isomer Mn(III)-4-TE-PyP acts as a potent antioxidant, safeguarding neuronal integrity against oxidative stress.

Copper(II) complex with a redox-noninnocent Schiff base bearing a tetraphenyldisiloxane unit: synthesis, structure and catalytic oxidation of cyclohexane.

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)·HO with H2L7 in a mixture of organic solvents, has a tetrahedrally distorted square-planar (NO) 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-RSi-O-SiR- fragment (R = Ph and Me, respectively).

Physical properties and cytotoxicity of Cu(II) and Zn(II) complexes with a TMS-substituted indolo[2,3-]quinoline-derived Schiff base.

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, (1) and (2), were synthesized and comprehensively characterized using elemental analysis, spectroscopic techniques (IR, UV-vis, H and C NMR for HLTMS and 2), ESI mass spectrometry and single-crystal X-ray diffraction (SC-XRD) for 1 and electron diffraction (ED) for 2.

Extended Tetrathiafulvalene Multi-Redox Systems Incorporating 4,5-Dihydroazuleno[2,1,8-ija]azulene Cores.

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.

Nickel(II) complexes with 14-membered bis-thiosemicarbazide and bis-isothiosemicarbazide ligands: synthesis, characterization and catalysis of oxygen evolution reaction.

Design and development of novel, low-cost and efficient electrocatalysts for oxygen evolution reaction (OER) in alkaline media is crucial for lowering the reaction overpotential and thus decreasing the energy input during the water electrolysis process. Herein, we present the synthesis of new 14-membered bis-thiosemicarbazide and bis-isothiosemicarbazide macrocycles and their nickel(II) complexes characterized by spectroscopic techniques (H and C NMR, IR, UV-vis), electrospray ionization mass spectrometry, single crystal X-ray diffraction, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) and cyclic voltammetry. Finally, the activity of nickel(II) complexes towards OER is reported.

Are the metal identity and stoichiometry of metal complexes important for colchicine site binding and inhibition of tubulin polymerization?

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 4-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL1), 6-morpholinomethyl-2-acetylpyridine 4-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL2), and 6-morpholinomethyl-2-formylpyridine 4-phenyl-3-thiosemicarbazone (HL3), and -ligand nickel(II), zinc(II) and palladium(II) complexes with HL1, namely [Co(HL)(L)](NO) (1), [Co(HL)(L)](NO) (2), [Co(HL)(L)](NO) (3), [Fe(L)]NO (4), [Fe(HL)(L)](NO) (5), [Ni(L)]Cl (6), [Zn(L)Cl] (7) and [Pd(HL)Cl]Cl (8).

Isomerization pathway of a C-C sigma bond in a bis(octaazamacrocycle)dinickel(II) complex activated by deprotonation: a DFT study.

Unlabelled: The anti () to syn () 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 () structure, a deprotonation of one of the bridging ( hybridized) carbon atoms is suggested to allow for an to geometry twist. A 360° scan around the bridging C-C dihedral angle was performed first to find an intermediate geometry.

Extended Tetrathiafulvalenes with Fluoreno[3,2-b]fluorene and Diindeno[1,2-b : 1',2'-i]anthracene Cores.

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.

A Combined Experimental and Theoretical Study of ESR Hyperfine Coupling Constants for -Tetrasubstituted -Phenylenediamine Radical Cations.

A test set of -tetrasubstituted -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 2 value of 0.

Elucidation of Structure-Activity Relationships in Indolobenzazepine-Derived Ligands and Their Copper(II) Complexes: the Role of Key Structural Components and Insight into the Mechanism of Action.

Indolo[3,2-][1]benzazepines (paullones), indolo[3,2-][2]benzazepines, and indolo[2,3-][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2-][2]benzazepine-derived ligands - and copper(II) complexes -. All compounds were characterized by spectroscopic methods (H and C NMR, UV-vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes and , in addition, by X-ray crystallography.

Diastereomeric dinickel(II) complexes with non-innocent bis(octaazamacrocyclic) ligands: isomerization, spectroelectrochemistry, DFT calculations and use in catalytic oxidation of cyclohexane.

Diastereomeric dinickel(II) complexes with bis-octaazamacrocyclic 15-membered ligands [Ni(L1-3-L1-3)Ni] (4-6) have been prepared by oxidative dehydrogenation of nickel(II) complexes NiL1-3 (1-3) derived from 1,2- and 1,3-diketones and -methylisothiocarbohydrazide. The compounds were characterized by elemental analysis, ESI mass spectrometry, and IR, UV-vis, H NMR, and C NMR spectroscopy. Single crystal X-ray diffraction (SC-XRD) confirmed the isolation of the and isomers of bis-octaazamacrocyclic dinickel(II) complexes 4a and 4s, the -configuration of 5s and the -configuration of the dinickel(II) complex 6a.

The Ruthenium Nitrosyl Moiety in Clusters: Trinuclear Linear μ-Hydroxido Magnesium(II)-Diruthenium(II), μ-Oxido Trinuclear Diiron(III)-Ruthenium(II), and Tetranuclear μ-Oxido Trigallium(III)-Ruthenium(II) Complexes.

The ruthenium nitrosyl moiety, {RuNO}, is important as a potential releasing agent of nitric oxide and is of inherent interest in coordination chemistry. Typically, {RuNO} is found in mononuclear complexes. Herein we describe the synthesis and characterization of several multimetal cluster complexes that contain this unit.

Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions.

High levels of hyaluronic acid (HA) in tumors correlate with poor outcomes with several types of cancers due to HA-driven support of adhesion, migration and proliferation of cells. In this study we explored how to enhance the degradation of HA into low-molecular fragments, which cannot prevent the immune system to fight tumor proliferation and metastases. The physiological solution of HA was exposed to oxidative degradation by ascorbate and cupric ions in the presence of either one of three isomeric Mn(III) substituted -alkyl- and alkoxyalkylpyridylporphyrins or isomeric Mn(III) -methylpyridyl analog, commonly known as mimics of superoxide dismutase.

Ni Oxidation State and Ligand Saturation Impact on the Capability of Octaazamacrocyclic Complexes to Bind and Reduce CO.

Two 15-membered octaazamacrocyclic nickel(II) complexes are investigated by theoretical methods to shed light on their affinity forwards binding and reducing CO. In the first complex [], the octaazamacrocyclic ligand is grossly unsaturated (π-conjugated), while in the second [] one, the macrocycle is saturated with hydrogens. One and two-electron reductions are described using Mulliken population analysis, quantum theory of atoms in molecules, localized orbitals, and domain averaged fermi holes, including the characterization of the Ni-C bond and the oxidation state of the central Ni atom.

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition.

Three new thiosemicarbazones (TSCs) - as triapine analogues bearing a redox-active phenolic moiety at the terminal nitrogen atom were prepared. Reactions of - with CuCl·2HO in anoxic methanol afforded three copper(II) complexes, namely, (), [ (), and (), in good yields. Solution speciation studies revealed that the metal-free ligands are stable as - at pH 7.

Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes: Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity.

A series of thiosemicarbazone-coumarin hybrids ( and ) has been synthesised in 12 steps and used for the preparation of mono- and dinuclear copper(II) complexes, namely (), (), () and (), isolated in hydrated or solvated forms. Both the organic hybrids and their copper(II) and dicopper(II) complexes were comprehensively characterised by analytical and spectroscopic techniques, i.e.

Interfering with Metabolic Profile of Triple-Negative Breast Cancers Using Rationally Designed Metformin Prodrugs.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by an aberrant metabolic phenotype with high metastatic capacity, resulting in poor patient prognoses and low survival rates. We designed a series of novel Au cyclometalated prodrugs of energy-disrupting Type II antidiabetic drugs namely, metformin and phenformin. Prodrug activation and release of the metformin ligand was achieved by tuning the cyclometalated Au fragment.

Spectroelectrochemical Properties and Catalytic Activity in Cyclohexane Oxidation of the Hybrid Zr/Hf-Phthalocyaninate-Capped Nickel(II) and Iron(II) tris-Pyridineoximates and Their Precursors.

The in situ spectroelectrochemical cyclic voltammetric studies of the antimony-monocapped nickel(II) and iron(II) tris-pyridineoximates with a labile triethylantimony cross-linking group and Zr(IV)/Hf(IV) phthalocyaninate complexes were performed in order to understand the nature of the redox events in the molecules of heterodinuclear zirconium(IV) and hafnium(IV) phthalocyaninate-capped derivatives. Electronic structures of their 1e-oxidized and 1e-electron-reduced forms were experimentally studied by electron paramagnetic resonance (EPR) spectroscopy and UV-vis-near-IR spectroelectrochemical experiments and supported by density functional theory (DFT) calculations. The investigated hybrid molecular systems that combine a transition metal (pseudo)clathrochelate and a Zr/Hf-phthalocyaninate moiety exhibit quite rich redox activity both in the cathodic and in the anodic region.

Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells.

Thiosemicarbazones continue to attract the interest of researchers as potential anticancer drugs. For example, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, or triapine, is the most well-known representative of this class of compounds that has entered multiple phase I and II clinical trials. Two new triapine derivatives and were prepared by condensation reactions of 2-pyridinamidrazone and S-methylisothiosemicarbazidium chloride with 3--(-butyloxycarbonyl) amino-pyridine-2-carboxaldehyde, followed by a Boc-deprotection procedure.

Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters.

A series of four water-soluble salicylaldehyde thiosemicarbazones with a positively charged trimethylammonium moiety ([HL]Cl, R = H, Me, Et, Ph) and four copper(II) complexes [Cu(HL)Cl]Cl (-) were synthesised with the aim to study (i) their antiproliferative activity in cancer cells and, (ii) for the first time for thiosemicarbazones, the interaction with membrane transport proteins, specifically organic cation transporters OCT1-3. The compounds were comprehensively characterised by analytical, spectroscopic and X-ray diffraction methods. The highest cytotoxic effect was observed in the neuroblastoma cell line SH-5YSY after 24 h exposure and follows the rank order: > > > > >>[HL]Cl.

Nickel(II), Copper(II) and Palladium(II) Complexes with Bis-Semicarbazide Hexaazamacrocycles: Redox-Noninnocent Behavior and Catalytic Activity in Oxidation and C-C Coupling Reactions.

Nickel(II), copper(II), and palladium(II) complexes , where M = Ni (), Cu (), Pd (), and , where M = Ni (), Cu (), Pd (), have been prepared by reactions of NiCl·6HO, Cu(OAc)·HO, and PdCl(MeCN) with 14-membered bis-semicarbazide hexaazamacrocycles and in dimethylformamide (DMF). The compounds were characterized by elemental analysis, ESI mass spectrometry, IR, UV-vis, and 1D (H, C) and 2D (H-H COSY, H-H TOCSY, H-H NOESY, H-C HSQC, H-C HMBC) NMR spectra (, , , and ), and X-ray diffraction (, -). The complexes with MN coordination environment have = 0, 1/2, 0 ground states for Ni, Cu, and Pd, respectively.

Tuning Redox Properties and Self-Assembly of Thienoacene-Extended Tetrathiafulvalenes.

Turning on and off associations between molecules by a reversible change in their redox states is a convenient way of controlling self-assembly and hence for advancing supramolecular chemistry. Here we present systematic studies on a selection of extended tetrathiafulvalenes with thienoacene spacers. By cyclic and differential pulse voltammetry and in situ EPR/UV-Vis-NIR spectroelectrochemistry, in combination with computations, we have elucidated how the number and orientations of thiophene rings in the spacer between the two dithiafulvene rings influence both the donor strength and association properties.

Nickel(II) Complexes with Redox Noninnocent Octaazamacrocycles as Catalysts in Oxidation Reactions.

Nickel(II) complexes with 15-membered (-) and 14-membered () octaazamacrocyclic ligands derived from 1,2- and 1,3-diketones and -methylisothiocarbohydrazide were prepared by template synthesis. The compounds were characterized by elemental analysis, electrospray ionization mass spectrometry, IR, UV-vis, H NMR spectroscopies, and X-ray diffraction. The complexes contain a low-spin nickel(II) ion in a square-planar coordination environment.

Novel latonduine derived proligands and their copper(ii) complexes show cytotoxicity in the nanomolar range in human colon adenocarcinoma cells and in vitro cancer selectivity.

Four Schiff bases derived from 7-hydrazin-yl-5,8-dihydroindolo[2,3-d][2]benzazepin-(6H)-one and its bromo-substituted analogue (HL1-HL4) and four copper(ii) complexes 1-4 have been synthesised and fully characterised by standard spectroscopic methods (1H and 13C NMR, UV-vis), ESI mass spectrometry, single crystal X-ray diffraction and spectroelectrochemistry. In addition, two previously reported complexes with paullone ligands 5 and 6 were prepared and studied for comparison reasons. The CuII ion in 1-4 is five-coordinate and adopts a square-pyramidal or slightly distorted square-pyramidal coordination geometry.