Axial Ligation Impedes Proton-Coupled Electron-Transfer Reactivity of a Synthetic Compound-I Analogue.

The nature of the axial ligand in high-valent iron-oxo heme enzyme intermediates and related synthetic catalysts is a critical structural element for controlling proton-coupled electron-transfer (PCET) reactivity of these species. Herein, we describe the generation and characterization of three new 6-coordinate, iron(IV)-oxo porphyrinoid-π-cation-radical complexes and report their PCET reactivity together with a previously published 5-coordinate analogue, FeIV(O)(TBP8Cz+•) (TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3-) (2) (Cho, K. A high-valent iron-oxo corrolazine activates C-H bonds via hydrogen-atom transfer. J. Am. Chem. Soc. 2012, 134, 7392-7399). The new complexes FeIV(O)(TBP8Cz+•)(L) (L = 1-methyl imidazole (1-MeIm) (4a), 4-dimethylaminopyridine (DMAP) (4b), cyanide (CN-)(4c)) can be generated from either oxidation of the ferric precursors or by addition of L to the Compound-I (Cpd-I) analogue at low temperatures. These complexes were characterized by UV-vis, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies, and cryospray ionization mass spectrometry (CSI-MS). Kinetic studies using 4-OMe-TEMPOH as a test substrate indicate that coordination of a sixth axial ligand dramatically lowers the PCET reactivity of the Cpd-I analogue (rates up to 7000 times slower). Extensive density functional theory (DFT) calculations together with the experimental data show that the trend in reactivity with the axial ligands does not correlate with the thermodynamic driving force for these reactions or the calculated strengths of the O-H bonds being formed in the FeIV(O-H) products, pointing to non-Bell-Evans-Polanyi behavior. However, the PCET reactivity does follow a trend with the bracketed reduction potential of Cpd-I analogues and calculated electron affinities. The combined data suggest a concerted mechanism (a concerted proton electron transfer (CPET)) and an asynchronous movement of the electron/proton pair in the transition state.

Computational Analysis of the Superoxide Dismutase Mimicry Exhibited by a Zinc(II) Complex with a Redox-Active Organic Ligand.

Previously, we found that a Zn(II) complex with the redox-active ligand N-(2,5-dihydroxybenzyl)-N,N',N'-tris(2-pyridinylmethyl)-1,2-ethanediamine (H2qp1) was able to act as a functional mimic of superoxide dismutase, despite its lack of a redox-active transition metal. As the complex catalyzes the dismutation of superoxide to form O2 and H2O2, the quinol in the ligand is believed to cycle between three oxidation states: quinol, quinoxyl radical, and para-quinone. Although the metal is not the redox partner, it nonetheless is essential to the reactivity since the free ligand by itself is inactive as a catalyst. In the present work, we primarily use calculations to probe the mechanism. The calculations support the inner-sphere decomposition of superoxide, suggest that the quinol/quinoxyl radical couple accounts for most of the catalysis, and elucidate the many roles that proton transfer between the zinc complexes and buffer has in the reactivity. Acid/base reactions involving the nonmetal-coordinating hydroxyl group on the quinol are predicted to be key to lowering the energy of the intermediates. We prepared a Zn(II) complex with N-(2-hydroxybenzyl)-N,N',N'-tris(2-pyridinylmethyl)-1,2-ethanediamine (Hpp1) that lacks this functional group and found that it could not catalyze the dismutation of superoxide; this confirms the importance of the second, distal hydroxyl group of the quinol.

Reductive Coupling of Nitric Oxide by Cu(I): Stepwise Formation of Mono- and Dinitrosyl Species En Route to a Cupric Hyponitrite Intermediate.

Transition-metal-mediated reductive coupling of nitric oxide (NO(g)) to nitrous oxide (N2O(g)) has significance across the fields of industrial chemistry, biochemistry, medicine, and environmental health. Herein, we elucidate a density functional theory (DFT)-supplemented mechanism of NO(g) reductive coupling at a copper-ion center, [(tmpa)CuI(MeCN)]+ (1) {tmpa = tris(2-pyridylmethyl)amine}. At -110 °C in EtOH (<-90 °C in MeOH), exposing 1 to NO(g) leads to a new binuclear hyponitrite intermediate [{(tmpa)CuII}2(µ-N2O22-)]2+ (2), exhibiting temperature-dependent irreversible isomerization to the previously characterized κ2-O,O'-trans-[(tmpa)2Cu2II(µ-N2O22-)]2+ (OOXray) complex. Complementary stopped-flow kinetic analysis of the reaction in MeOH reveals an initial mononitrosyl species [(tmpa)Cu(NO)]+ (1-(NO)) that binds a second NO molecule, forming a dinitrosyl species [(tmpa)CuII(NO)2] (1-(NO)2). The decay of 1-(NO)2 requires an available starting complex 1 to form a dicopper-dinitrosyl species hypothesized to be [{(tmpa)Cu}2(µ-NO)2]2+ (D) bearing a diamond-core motif, en route to the formation of hyponitrite intermediate 2. In contrast, exposing 1 to NO(g) in 2-MeTHF/THF (v/v 4:1) at <-80 °C leads to the newly observed transient metastable dinitrosyl species [(tmpa)CuII(NO)2] (1-(NO)2) prior to its disproportionation-mediated transformation to the nitrite product [(tmpa)CuII(NO2)]+. Our study furnishes a near-complete profile of NO(g) activation at a reduced Cu site with tripodal tetradentate ligation in two distinctly different solvents, aided by detailed spectroscopic characterization of metastable intermediates, including resonance Raman characterization of the new dinitrosyl and hyponitrite species detected.

A Dibenzotetrathiafulvalene-Bridged Bis(alkenylruthenium) Complex and Its One- and Two-Electron-Oxidized Forms.

We report on the synthesis of the new bis(alkenylruthenium) complex DBTTF-(ViRu)2 with a longitudinally extended, π-conjugated dibenzotetrathiafulvalene (DBTTF) bridge, characterized by multinuclear NMR, IR, and UV/vis spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Cyclic and square-wave voltammetry revealed that DBTTF-(ViRu)2 undergoes four consecutive oxidations. IR, UV/vis/near-IR, and electron paramagnetic resonance spectroscopy indicate that the first oxidation involves the redox-noninnocent DBTTF bridge, while the second oxidation is biased toward one of the peripheral styrylruthenium entities, thereby generating an electronically coupled mixed-valent state ({Ru}-CH═CH)•+-DBTTF•+-(CH═CH-{Ru}) [{Ru} = Ru(CO)Cl(PiPr3)2]. The latter is apparently in resonance with the ({Ru}-CH═CH)•+-DBTTF-(CH═CH-{Ru})•+ and ({Ru}-CH═CH)-DBTTF2+-(CH═CH-{Ru}) forms, which are calculated to lie within 19 kJ/mol. Higher oxidized forms proved too unstable for further characterization. The reaction of DBTTF-(ViRu)2 with the strong organic acceptors 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tetracyano-p-benzoquinodimethane (TCNQ), and F4TCNQ resulted in formation of the DBTTF-(ViRu)2•+ radical cation, as shown by various spectroscopic techniques. Solid samples of these compounds were found to be highly amorphous and electrically insulating.

A Highly Water- and Air-Stable Iron-Containing MRI Contrast Agent Sensor for H2 O2.

A highly water- and air-stable Fe(II) complex with the quinol-containing macrocyclic ligand H4 qp4 reacts with H2 O2 to yield Fe(III) complexes with less highly chelating forms of the ligand that have either one or two para-quinones. The reaction increases the T1 -weighted relaxivity over four-fold, enabling the complex to detect H2 O2 using clinical MRI technology. The iron-containing sensor differs from its recently characterized manganese analog, which also detects H2 O2 , in that it is the oxidation of the metal center, rather than the ligand, that primarily enhances the relaxivity.

Reversible Multielectron Release from Redox-Active Three-Dimensional Molecular Barrels with Ruthenium-Alkenyl Moieties.

Three-dimensional molecular barrels Ru6-4 and Ru6-5 were synthesized in high yields from dinuclear ruthenium-vinyl clamps and tritopic triphenylamine-derived carboxylate linkers and characterized by multinuclear NMR spectroscopy including 1H-1H COSY and 1H DOSY measurements, high-resolution electrospray ionization mass spectrometry, and X-ray crystallography. The metal frameworks of the cages adopt the shape of twisted trigonal prisms, and they crystallize as racemic mixtures of interdigitating Δ- and Λ-enantiomers with a tight columnar packing in Ru6-4. Electrochemical studies and redox titrations revealed that the cages are able to release up to 11 electrons on the voltammetric timescale and that their cage structures persist up to the hexacation level. IR and UV-vis-near-infrared spectroelectrochemical studies confirm substituent-dependent intramolecular electronic communication within the π-conjugated 1,3-divinylphenylene backbone in the tricationic states, where all three divinylphenylene-bridged diruthenium clamps are present in mixed-valent radical cation states. The formation of 1:3 charge-transfer salts with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane as the electron acceptor is also demonstrated.

Diquinol Functionality Boosts the Superoxide Dismutase Mimicry of a Zn(II) Complex with a Redox-Active Ligand while Maintaining Catalyst Stability and Enhanced Activity in Phosphate Solution.

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.

A Macrocyclic Ligand Framework That Improves Both the Stability and T1-Weighted MRI Response of Quinol-Containing H2O2 Sensors.

Previously prepared Mn(II)- and quinol-containing magnetic resonance imaging (MRI) contrast agent sensors for H2O2 relied on linear polydentate ligands to keep the redox-activatable quinols in close proximity to the manganese. Although these provide positive T1-weighted relaxivity responses to H2O2 that result from oxidation of the quinol groups to p-quinones, these reactions weaken the binding affinity of the ligands, promoting dissociation of Mn(II) from the contrast agent in aqueous solution. Here, we report a new ligand, 1,8-bis(2,5-dihydroxybenzyl)-1,4,8,11-tetraazacyclotetradecane, that consists of two quinols covalently tethered to a cyclam macrocycle. The macrocycle provides stronger thermodynamic and kinetic barriers for metal-ion dissociation in both the reduced and oxidized forms of the ligand. The Mn(II) complex reacts with H2O2 to produce a more highly aquated Mn(II) species that exhibits a 130% greater r1, quadrupling the percentile response of our next best sensor. With a large excess of H2O2, there is a noticeable induction period before quinol oxidation and r1 enhancement occurs. Further investigation reveals that, under such conditions, catalase activity initially outcompetes ligand oxidation, with the latter occurring only after most of the H2O2 has been depleted.

A "Pretender" Croconate-Bridged Macrocyclic Tetraruthenium Complex: Sizable Redox Potential Splittings despite Electronically Insulated Divinylphenylene Diruthenium Entities.

Careful optimization of the reaction conditions provided access to the particularly small tetraruthenium macrocycle 2Ru2Ph-Croc, which is composed out of two redox-active divinylphenylene-bridged diruthenium entities {Ru}-1,4-CH=CH-C6H4-CH=CH-{Ru} (Ru2Ph; {Ru} = Ru(CO)Cl(PiPr3)2) and two likewise redox-active and potentially non-innocent croconate linkers. According to single X-ray diffraction analysis, the central cavity of 2Ru2Ph-Croc is shielded by the bulky PiPr3 ligands, which come into close contact. Cyclic voltammetry revealed two pairs of split anodic waves in the weakly ion pairing CH2Cl2/NBu4BArF24 (BArF24 = [B{C6H3(CF3)2-3,5}4]- electrolyte, while the third and fourth waves fall together in CH2Cl2/NBu4PF6. The various oxidized forms were electrogenerated and scrutinized by IR and UV/Vis/NIR spectroscopy. This allowed us to assign the individual oxidations to the metal-organic Ru2Ph entities within 2Ru2Ph-Croc, while the croconate ligands remain largely uninvolved. The lack of specific NIR bands that could be assigned to intervalence charge transfer (IVCT) in the mono- and trications indicates that these mixed-valent species are strictly charge-localized. 2Ru2Ph-Croc is hence an exemplary case, where stepwise IR band shifts and quite sizable redox splittings between consecutive one-electron oxidations would, on first sight, point to electronic coupling, but are exclusively due to electrostatic and inductive effects. This makes 2Ru2Ph-Croc a true "pretender".

Catalytic Oxygenation of Hydrocarbons by Mono-µ-oxo Dicopper(II) Species Resulting from O-O Cleavage of Tetranuclear CuI /CuII Peroxo Complexes.

One of the challenges of catalysis is the transformation of inert C-H bonds to useful products. Copper-containing monooxygenases play an important role in this regard. Here we show that low-temperature oxygenation of dinuclear copper(I) complexes leads to unusual tetranuclear, mixed-valent µ4 -peroxo [CuI /CuII ]2 complexes. These Cu4 O2 intermediates promote irreversible and thermally activated O-O bond homolysis, generating Cu2 O complexes that catalyze strongly exergonic H-atom abstraction from hydrocarbons, coupled to O-transfer. The Cu2 O species can also be produced with N2 O, demonstrating their capability for small-molecule activation. The binding and cleavage of O2 leading to the primary Cu4 O2 intermediate and the Cu2 O complexes, respectively, is elucidated with a range of solution spectroscopic methods and mass spectrometry. The unique reactivities of these species establish an unprecedented, 100 % atom-economic scenario for the catalytic, copper-mediated monooxygenation of organic substrates, employing both O-atoms of O2 .

Subcomponent Self-Assembly of Covalent Metallacycles Templated by Catalytically Active Seven-Coordinate Transition Metal Centers.

Coordination geometries of transition metals play vital roles in the self-assembly process of supramolecular coordination complexes. Herein, seven-coordinate 3d metal ions were applied as templates and catalytically active sites for subcomponent self-assembly that resulted in a new category of covalent metallacycles. Single-crystal structures showed that the sizes, configurations, and functionalization of covalent metallacycles could be tuned by the selection of rigid dihydrazide, transition metal ions, and prefunctionalized subcomponents, respectively. Moreover, metallacycles decorated with carboxylic groups could be employed as precursors to prepare aerogels through hierarchical self-assembly, which also exhibited high catalytic activity for cycloaddition of CO2 into cyclic carbonates.

Gas-Phase Transformation of Fluorinated Benzoporphyrins to Porphyrin-Embedded Conical Nanocarbons.

Geodesic nitrogen-containing graphene fragments are interesting candidates for various material applications, but the available synthetic protocols, which need to overcome intrinsic strain energy during the formation of the bowl-shaped skeletons, are often incompatible with heteroatom-embedded structures. Through this mass spectrometry-based gas-phase study, we show by means of collision-induced dissociation experiments and supported by density functional theory calculations, the first evidence for the formation of a porphyrin-embedded conical nanocarbon. The influences of metalation and functionalization of the used tetrabenzoporphyrins have been investigated, which revealed different cyclization efficiencies, different ionization possibilities, and a variation of the dissociation pathway. Our results suggest a stepwise process for HF elimination from the fjord region, which supports a selective pathway towards bent nitrogen-containing graphene fragments.

Exceptional Substrate Diversity in Oxygenation Reactions Catalyzed by a Bis(µ-oxo) Copper Complex.

The enzyme tyrosinase contains a reactive side-on peroxo dicopper(II) center as catalytically active species in C-H oxygenation reactions. The tyrosinase activity of the isomeric bis(µ-oxo) dicopper(III) form has been discussed controversially. The synthesis of bis(µ-oxo) dicopper(III) species [Cu2 (µ-O)2 (L1)2 ](X)2 ([O1](X)2 , X=PF6 - , BF4 - , OTf- , ClO4 - ), stabilized by the new hybrid guanidine ligand 2-{2-((dimethylamino)methyl)phenyl}-1,1,3,3-tetramethylguanidine (L1), and its characterization by UV/Vis, Raman, and XAS spectroscopy, as well as cryo-UHR-ESI mass spectrometry, is described. We highlight selective oxygenation of a plethora of phenolic substrates mediated by [O1](PF6 )2 , which results in mono- and bicyclic quinones and provides an attractive strategy for designing new phenazines. The selectivity is predicted by using the Fukui function, which is hereby introduced into tyrosinase model chemistry. Our bioinspired catalysis harnesses molecular dioxygen for organic transformations and achieves a substrate diversity reaching far beyond the scope of the enzyme.

Redox-Induced Hydrogen Bond Reorientation Mimicking Electronic Coupling in Mixed-Valent Diruthenium and Macrocyclic Tetraruthenium Complexes.

We present the coordination-driven self-assembly of three tetranuclear metallacycles containing intracyclic NH2, OH, or OMe functionalities through the combination of various isophthalic acid building blocks with a divinylphenylene diruthenium complex. All new complexes of this study were characterized by means of nuclear magnetic resonance spectroscopy, ultrahigh-resolution ESI mass spectrometry, cyclic and square wave voltammetry and, in two cases, X-ray diffraction. The hydroxy functionalized macrocycle 4-BOH and the corresponding half-cycle 2-OH stand out, as their intracyclic OH···O hydrogen bonds stabilize their mixed-valent one- (2-OH, 4-BOH) and three-electron-oxidized states (4-BOH). Despite sizable redox splittings between all one-electron waves, the mixed-valent monocations and trications do not exhibit any intervalence charge-transfer band, assignable to through-bond electronic coupling, but nevertheless display distinct IR band shifts of their charge-sensitive Ru(CO) tags. We ascribe these seemingly contradicting observations to a redox-induced shuffling of the OH···O hydrogen bond(s) to the remaining, more electron-rich, reduced redox site.

Catalytic H2O2 Activation by a Diiron Complex for Methanol Oxidation.

In nature, C-H bond oxidation of CH4 involves a peroxo intermediate that decays to the high-valent active species of either a "closed" {FeIV(µ-O)2FeIV} core or an "open" {FeIV(O)(µ-O)FeIV(O)} core. To mimic and to obtain more mechanistic insight in this reaction mode, we have investigated the reactivity of the bioinspired diiron complex [(susan){Fe(OH)(µ-O)Fe(OH)}]2+ [susan = 4,7-dimethyl-1,1,10,10-tetrakis(2-pyridylmethyl)-1,4,7,10-tetraazadecane], which catalyzes CH3OH oxidation with H2O2 to HCHO and HCO2H. The kinetics is faster in the presence of a proton. 18O-labeling experiments show that the active species, generated by a decay of the initially formed peroxo intermediate [(susan){FeIII(µ-O)(µ-O2)FeIII}]2+, contains one reactive oxygen atom from the µ-oxo and another from the µ-peroxo bridge of its peroxo precursor. Considering an FeIVFeIV active species, a "closed" {FeIV(µ-O)2FeIV} core explains the observed labeling results, while a scrambling of the terminal and bridging oxo ligands is required to account for an "open" {FeIV(O)(µ-O)FeIV(O)} core.

Hydrogenase Mimics in M12 L24 Nanospheres to Control Overpotential and Activity in Proton-Reduction Catalysis.

Hydrogenase enzymes are excellent proton reduction catalysts and therefore provide clear blueprints for the development of nature-inspired synthetic analogues. Mimicking their catalytic center is straightforward but mimicking the protein matrix around the active site and all its functions remains challenging. Synthetic models lack this precisely controlled second coordination sphere that provides substrate preorganization and catalyst stability and, as a result, their performances are far from those of the natural enzyme. In this contribution, we report a strategy to easily introduce a specific yet customizable second coordination sphere around synthetic hydrogenase models by encapsulation inside M12 L24 cages and, at the same time, create a proton-rich nano-environment by co-encapsulation of ammonium salts, effectively providing substrate preorganization and intermediates stabilization. We show that catalyst encapsulation in these nanocages reduces the catalytic overpotential for proton reduction by 250 mV as compared to the uncaged catalyst, while the proton-rich nano-environment created around the catalyst ensures that high catalytic rates are maintained.

Formation and Reactivity of New Isoporphyrins: Implications for Understanding the Tyr-His Cross-Link Cofactor Biogenesis in Cytochrome c Oxidase.

Cytochrome c oxidase (CcO) catalyzes the reduction of dioxygen to water utilizing a heterobinuclear active site composed of a heme moiety and a mononuclear copper center coordinated to three histidine residues, one of which is covalently cross-linked to a tyrosine residue via a post-translational modification (PTM). Although this tyrosine-histidine moiety has functional and structural importance, the pathway behind this net oxidative C-N bond coupling is still unknown. A novel route employing an iron(III) meso-substituted isoporphyrin derivative, isoelectronic with Cmpd-I ((Por•+)FeIV═O), is for the first time proposed to be a key intermediate in the Tyr-His cofactor biogenesis. Newly synthesized iron(III) meso-substituted isoporphyrins were prepared with azide, cyanide, and substituted imidazole functionalities, by adding nucleophiles to an iron(III) π-dication species formed via addition of trifluoroacetic acid to F8Cmpd-I (F8 = (tetrakis(2,6-difluorophenyl)porphyrinate)). Isoporphyrin derivatives were characterized at cryogenic temperatures via ESI-MS and UV-vis, 2H NMR, and EPR spectroscopies. Addition of 1,3,5-trimethoxybenzene or 4-methoxyphenol to the imidazole-substituted isoporphyrin led to formation of the organic product containing the imidazole coupled to aromatic substrate via a new C-N bond, as detected via cryo-ESI-MS. Experimental evidence for the formation of an imidazole-substituted isoporphyrin and its promising reactivity to form the imidazole-phenol coupled product yields viability to the herein proposed pathway behind the PTM (i.e., biogenesis) leading to the key covalent Tyr-His cross-link in CcO.

Saying NO to H2S: A Story of HNO, HSNO, and SSNO.

Interactions between small inorganic molecules are fundamental to the understanding of basic reaction mechanisms and some of the initial processes of chemical evolution that preceded organic molecules and led to the origin of life. The kinetics of these processes are suitable for the fast generation of a variety of new chemical entities and the propagation of a cascade of chemical reactions, a property that is ideal for signaling purposes even in biological systems. NO and H2S are such molecules that are nowadays recognized as biological gasotransmitters involved in the regulation of physiological functions through protein modifications such as S-nitrosothiol, disulfide, and persulfide formations. In this Viewpoint, we review the current understanding of interactions of NO (and organic and metal nitrosyl species) with H2S, in both chemical and biochemical contexts. Through the formation of HNO, (H)SNO (and its isomers), (H)SSNO, and polysulfides, these two gasotransmitters initiate reaction networks with significant roles in cell signaling. The chemical reactivities and biological effects of these nitrogen and sulfur species are still unresolved, and, thus, a cross-talk between all of them represents a challenging interdisciplinary field that awaits exciting new findings. We tackle some of the intriguing and open questions and provide perspectives for future research directions.

Solvent-Controlled Polymerization of Molecular Strontium Vanadate Monomers into 1D Strontium Vanadium Oxide Chains.

We report the polymerization of a solvent-stabilized molecular strontium vanadium oxide monomer into infinite 1D chains. Supramolecular polymerization is triggered by controlled solvent-exchange, which leads to oligomer and polymer formation. Mechanistic insights into the chain formation were obtained by solid-state, solution, and gas-phase studies. The study shows how reactivity control of molecular metal oxides can be used to assemble complex inorganic polymeric structures.

Positive Charge on Porphyrin Ligand and Nature of Metal Center Define Basic Physicochemical Properties of Cationic Manganese and Iron Porphyrins in Aqueous Solution.

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.