The dinuclear Mn-2(II,II)L-2-core (HL = 2-{[[di(2-pyridyl)methyl](methyl)amino]-methyl}phenol)has been recently reported to be the most active dual superoxide dismutase(SOD) and catalase (CAT) functional analogue, enabling cascade detoxificationof the superoxide radical anion. Here, we investigated the mechanismof catalytic O-2 (center dot-) decompositionby two stereoisomers with the Mn-2(II,II)L-2-core, Mn ( 2 ) L ( 2 ) Ac and Mn ( 2 ) L ( 2 ), in order to (i) preciselydetermine the catalytic SOD activity of the complexes, (ii) characterizethe key intermediates involved in the dismutation process, and (iii)discriminate between single- and di-Mn center catalysis in relationto the configuration of the Mn-2-core. The conclusions drawnfrom low-temperature mass spectrometry, stopped-flow kinetics, cyclicvoltammetry, water exchange O-17 nuclear magnetic resonance(NMR), and electron paramagnetic resonance (EPR) analyses were supportedby the structural characterization and quantum chemical analysis ofthe proposed reaction intermediates. This study allows us to determine k (cat) for Mn ( 2 ) L ( 2 ) Ac and Mn ( 2 ) L ( 2 ) (4.6 x 10(7) and 2.2 x 10(7) M-1 s(-1), respectively, in 3-(N-morpholino)propanesulfonic acid (MOPS) at pH = 7.4) anddetect the key intermediates involved in the catalytic cycle drivenby these Mn-2-SOD mimics, highlighting the formation ofa side-on eta(2)-Mn-2(III,II)-peroxo,as an initial intermediate. The effects of the Mn-2(II,II)-coreconfiguration on the SOD activity were discussed.

In the current work, we demonstrate ligand design concepts that significantly improve the superoxide dismutase (SOD) activity of a zinc complex; the catalysis is enhanced when two quinol groups are present in the polydentate ligand. We investigate the mechanism through which the quinols influence the catalysis and determine the impact of entirely removing a chelating group from the original hexadentate ligand. Our results suggest that SOD mimicry with these compounds requires a ligand that coordinates Zn(II) strongly in both its oxidized and reduced forms and that the activity proceeds through Zn(II)-semiquinone complexes. The complex with two quinols displays greatly enhanced catalytic ability, with the activity improving by as much as 450% over a related complex with a single quinol. In the reduced form of the diquinol complex, one quinol appears to coordinate to the zinc much more weakly than the other. We believe that superoxide can more readily displace this portion of the ligand, facilitating its coordination to the metal center and thereby hastening the SOD reactivity. Despite the presence of two redox-active groups that may communicate through intramolecular hydrogen bonding and redox tautomerism, only one quinol undergoes two-electron oxidation to a para-quinone during the catalysis. After the formation of the para-quinone, the remaining quinol deprotonates and binds tightly to the metal, ensuring that the complex remains intact in its oxidized state, thereby maintaining its catalytic ability. The Zn(II) complex with the diquinol ligand is highly unusual for a SOD mimic in that it performs more efficiently in phosphate solution.

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.

Manganese complexes with polydentate quinol-containing ligands are found to catalyze the degradation of superoxide through inner-sphere mechanisms. The redox activity of the ligand stabilizes higher-valent manganese species.

We have synthesized and characterized Co(II) ( 1 ), Zn(II) ( 2 ), Fe(III) ( 3 ) and Cu(II) ( 4 ) complexes of 2,2'‐[2,6‐pyridinediylbis(ethylidyne‐1‐hydrazinyl‐2‐ylidene)]bis[ N,N,N ‐trimethyl‐2‐oxoethanaminium] dichloride ( H 2 L Cl 2 ) by NMR, IR, and X‐Band EPR spectroscopy, respectively, as well as by single‐crystal X‐ray structural analysis. H 2 L Cl 2 belongs to the class of diacetylpyridine bis(hydrazone) ligands and bears two positively charged quaternary ammonium functionalities. The complexes 1 – 3 possess a pentagonal‐bipyramidal geometry, whereas 4 has square‐pyramidal geometry. Redox reactivity and SOD activity of the complexes was studied by means of electrochemical measurements in aqueous‐buffer and DMF or DMSO solutions, respectively, as well as by stopped‐flow measurements. Complexes 1 – 3 do not have SOD activity, whereas 4 exhibits a high catalytic rate constant for the superoxide dismutation, k cat = 1.73 × 10 7 m –1 s –1 (in MOPS buffer solution of pH = 7.4). The results were discussed in terms of complex redox potentials, electrostatic interactions and their spatial distribution, kinetic lability of metal centers, and stability of peroxo intermediates, respectively.

A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe 1[combining low line] was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, 1[combining low line] shows a distribution different from its unconjugated analogue but a similar concentration in mitochondria and a similar bioactivity.

A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic.

Recently, comprehensive studies on positively charged manganese porphyrins show that these compounds, known for their superoxide dismutase (SOD) mimetic ability, can be equally reactive toward a broad array of other redox active molecules of biological relevance present in a cellular milieu. In this context, the examination of some fundamental aspects of physicochemical behavior of metalloporphyrins behind their rich aqueous chemistry is believed to provide a valuable basis for the understanding of newly observed biological effects of these compounds in vivo and throw more light on a potential use of common SOD porphyrin mimetics for other redox active cellular targets in order to earn desirable therapeutic effects. Herein, we present versatile characteristics of highly positively charged Mn(P) and Fe(P) porphyrins (with up to +9 and +8 overall charge, respectively) with regard to their acid-base equilibria, metal coordination sphere, water-exchange dynamics, redox properties, and substitution behavior toward selected ligands. For the purpose of these comparative studies, we synthesized for the first time a 9-fold cationic manganese(III) porphyrin. The findings reported in this study enabled highlighting the most important similarities and differences characterizing the aqueous chemistry of positively charged manganese and iron porphyrins and, therefore, outlining the potential factors which can affect the intimate underlying mechanism behind the redox cycling of these metalloporphyrins.

Oxidative stress emerged as target in drug discovery due to its diverse role in various diseases, such as cardiovascular, neurodegenerative, and autoimmune diseases. During the last decades, considerable progress was made in the development of compounds with the ability to reduce reactive oxygen species (ROS) like superoxide. However, the dismutation of the latter leads to formation of another harmful ROS, hydrogen peroxide, which can be depleted through peroxidase activity. The present work describes the synthesis of a hybrid, which unifies a superoxide dismutase mimetic, Mn(II)pyane, and a glutathione peroxidase mimetic, ebselen, that are connected via an amide bond. This unique hybrid is designed in order to convert superoxide into oxygen and water, i.e. as a potential biological agent for complete ROS removal and will be used in the future as mechanistic molecular tool for further elucidation of (patho) physiological consequences of ROS removal.

In this work, four derivatives of the pentaazamacrocyclic Mn‐pyane [pyane = trans‐2,13‐dimethyl‐3,6,9,12,18‐pentaazabicyclo[12.3.1]‐octadeca‐1(18),14,16‐triene] complex were synthesized and characterized, carrying small substituents at the pyridine ring that allow fine‐tuning of the manganese centered redox potential, without significant change to the overall complex arrangement that is crucial for a correct comparison regarding their superoxide dismutase mimetic (SODm) capabilities. The crystal structure of the seven‐coordinate OMe‐substituted Mn‐pyane complex was obtained. The synthesized complexes will serve for future investigations related to an effect of complex redox potentials on their mechanistic behavior within SOD catalysis.

Reactive oxygen species are integral to many physiological processes. Although their roles are still being elucidated, they seem to be linked to a variety of disorders and may represent promising drug targets. Mimics of superoxide dismutases, which catalyse the decomposition of O 2 •− to H 2 O 2 and O 2 , have traditionally used redox-active metals, which are toxic outside of a tightly coordinating ligand. Purely organic antioxidants have also been investigated but generally require stoichiometric, rather than catalytic, doses. Here, we show that a complex of the redox-inactive metal zinc( ii ) with a hexadentate ligand containing a redox-active quinol can catalytically degrade superoxide, as demonstrated by both reactivity assays and stopped-flow kinetics studies of direct reactions with O 2 • − and the zinc( ii ) complex. The observed superoxide dismutase catalysis has an important advantage over previously reported work in that it is hastened, rather than impeded, by the presence of phosphate, the concentration of which is high under physiological conditions.