Mn K‑Edge X‑ray Absorption Studies of Oxo- and Hydroxo-manganese(IV) Complexes: Experimental and Theoretical Insights into Pre-Edge Properties

Mn K-edge X-ray absorption spectroscopy (XAS) was used to gain insights into the geometric and electronic structures of [Mn^II(Cl)₂­(Me₂EBC)], [Mn^IV(OH)₂­(Me₂EBC)]²⁺, and [Mn^IV(O)­(OH)­(Me₂EBC)]⁺, which are all supported by the tetradentate, macrocyclic Me₂EBC ligand (Me₂EBC = 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]­hexadecane). Analysis of extended X-ray absorption fine structure (EXAFS) data for [Mn^IV(O)­(OH)­(Me₂EBC)]⁺ revealed Mn–O scatterers at 1.71 and 1.84 Å and Mn–N scatterers at 2.11 Å, providing the first unambiguous support for the formulation of this species as an oxohydroxomanganese­(IV) adduct. EXAFS-determined structural parameters for [Mn^II(Cl)₂­(Me₂EBC)] and [Mn^IV(OH)₂­(Me₂EBC)]²⁺ are consistent with previously reported crystal structures. The Mn pre-edge energies and intensities of these complexes were examined within the context of data for other oxo- and hydroxomanganese­(IV) adducts, and time-dependent density functional theory (TD-DFT) computations were used to predict pre-edge properties for all compounds considered. This combined experimental and computational analysis revealed a correlation between the Mn–O­(H) distances and pre-edge peak areas of Mn^IVO and Mn^IV–OH complexes, but this trend was strongly modulated by the Mn^IV coordination geometry. Mn 3d-4p mixing, which primarily accounts for the pre-edge intensities, is not solely a function of the Mn–O­(H) bond length; the coordination geometry also has a large effect on the distribution of pre-edge intensity. For tetragonal Mn^IVO centers, more than 90% of the pre-edge intensity comes from excitations to the MnO σ* MO. Trigonal bipyramidal oxomanganese­(IV) centers likewise feature excitations to the MnO σ* molecular orbital (MO) but also show intense transitions to 3d_<i>x</i>²_{–<i>y</i>²} and 3d_<i>xy</i> MOs because of enhanced 3d-4p_x,y mixing. This gives rise to a broader pre-edge feature for trigonal Mn^IVO adducts. These results underscore the importance of reporting experimental pre-edge areas rather than peak heights. Finally, the TD-DFT method was applied to understand the pre-edge properties of a recently reported <i>S</i> = 1 Mn^VO adduct; these findings are discussed within the context of previous examinations of oxomanganese­(V) complexes

Formation, Characterization, and O–O Bond Activation of a Peroxomanganese(III) Complex Supported by a Cross-Clamped Cyclam Ligand

Although there have been reports describing the nucleophilic reactivity of peroxomanganese­(III) intermediates, as well as their conversion to high-valent oxo-bridged dimers, it remains a challenge to activate peroxomanganese­(III) species for conversion to high-valent, mononuclear manganese complexes. Herein, we report the generation, characterization, and activation of a peroxomanganese­(III) adduct supported by the cross-clamped, macrocyclic Me₂EBC ligand (4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]­hexadecane). This ligand is known to support high-valent, mononuclear Mn^IV species with well-defined spectroscopic properties, which provides an opportunity to identify mononuclear Mn^IV products from O–O bond activation of the corresponding Mn^III–peroxo adduct. The peroxomanganese­(III) intermediate, [Mn^III(O₂)­(Me₂EBC)]⁺, was prepared at low-temperature by the addition of KO₂ to [Mn^II(Cl)₂(Me₂EBC)] in CH₂Cl₂, and this complex was characterized by electronic absorption, electron paramagnetic resonance (EPR), and Mn K-edge X-ray absorption (XAS) spectroscopies. The electronic structure of the [Mn^III(O₂)­(Me₂EBC)]⁺ intermediate was examined by density functional theory (DFT) and time-dependent (TD) DFT calculations. Detailed spectroscopic investigations of the decay products of [Mn^III(O₂)­(Me₂EBC)]⁺ revealed the presence of mononuclear Mn^III–hydroxo species or a mixture of mononuclear Mn^IV and Mn^III–hydroxo species. The nature of the observed decay products depended on the amount of KO₂ used to generate [Mn^III(O₂)­(Me₂EBC)]⁺. The Mn^III–hydroxo product was characterized by Mn K-edge XAS, and shifts in the pre-edge transition energies and intensities relative to [Mn^III(O₂)­(Me₂EBC)]⁺ provide a marker for differences in covalency between peroxo and nonperoxo ligands. To the best of our knowledge, this work represents the first observation of a mononuclear Mn^IV center upon decay of a nonporphyrinoid Mn^III–peroxo center

Ligand Effects on the Regioselectivity of Rhodium-Catalyzed Hydroformylation: Density Functional Calculations Illuminate the Role of Long-Range Noncovalent Interactions

Density functional theory calculations have been performed to gain insight into the origin of ligand effects in rhodium (Rh)-catalyzed hydroformylation of olefins. In particular, the olefin insertion step of the Wilkinson catalytic cycle, which is commonly invoked as the regioselectivity-determining step, has been examined by considering a large variety of density functionals (e.g., B3LYP, M06-L); a range of substrates, including simple terminal (e.g., hexene, octene), heteroatom-containing (e.g., vinyl acetate), and aromatic-substituted (e.g., styrene) alkenes, and different ligand structures (e.g., monodentate PPh₃ ligands and bidentate ligands such as DIOP, DIPHOS). The calculations indicate that the M06-L functional reproduces the experimental regioselectivities with a reasonable degree of accuracy, while the commonly employed B3LYP functional fails to do so when the equatorial–equatorial arrangement of phosphine ligands around the Rh center is considered. The different behavior of the two functionals is attributed to the fact that the transition states leading to the Rh–alkyl intermediates along the pathways to isomeric aldehydes are stabilized by the medium-range correlation containing π–π (ligand–ligand) and π–CH (ligand–substrate) interactions that cannot be handled properly by the B3LYP functional due to its inability to describe nonlocal interactions. This conclusion is further validated using the B3LYP functional with Grimme’s empirical dispersion correction term: i.e., B3LYP-D3. The calculations also suggest that transition states leading to the linear Rh–alkyl intermediates are selectively stabilized by these noncovalent interactions, which gives rise to the high regioselectivities. In the cases of heteroatom- or aromatic-substituted olefins, substrate electronic effects determine the regioselectivity; however, these calculations suggest that the π–π and π–CH interactions also make an appreciable contribution. Overall, these computations show that the steric crowding-induced ligand–ligand and ligand–substrate interactions, but not intraligand interactions, influence the regioselectivity in Rh-catalyzed hydroformylation when the phosphine ligands are present in an equatorial–equatorial configuration in the Rh catalyst

Importance of Long-Range Noncovalent Interactions in the Regioselectivity of Rhodium-Xantphos-Catalyzed Hydroformylation

M06-L-based quantum chemical calculations were performed to examine two key elementary steps in rhodium (Rh)-xantphos-catalyzed hydroformylation: carbonyl ligand (CO) dissociation and the olefin insertion into the Rh–H bond. For the resting state of the Rh-xantphos catalyst, HRh­(xantphos)­(CO)₂, our M06-L calculations were able to qualitatively reproduce the correct ordering of the equatorial–equatorial (<i>ee</i>) and equatorial–axial (<i>ea</i>) conformers of the phosphorus ligands for 16 derivatives of the xantphos ligand, implying that the method is sufficiently accurate for capturing the subtle energy differences associated with various conformers involved in Rh-catalyzed hydroformylation. The calculated CO dissociation energy from the <i>ea</i> conformer (Δ<i>E</i> = 21–25 kcal/mol) was 10–12 kcal/mol lower than that from the <i>ee</i> conformer (Δ<i>E</i> = 31–34 kcal/mol), which is consistent with prior experimental and theoretical studies. The calculated regioselectivities for propene insertion into the Rh–H bond of the <i>ee</i>-HRh­(xantphos)­(propene)­(CO) complexes were in good agreement with the experimental l:b ratios. The comparative analysis of the regioselectivities for the pathways originating from the <i>ee</i>-HRh­(xantphos)­(propene)­(CO) complexes with and without diphenyl substituents yielded useful mechanistic insight into the interactions that play a key role in regioselectivity. Complementary computations featuring xantphos ligands lacking diphenyl substituents implied that the long-range noncovalent ligand–ligand and ligand–substrate interactions, but not the bite angles per se, control the regioselectivity of Rh-diphosphine-catalyzed hydroformylation of simple terminal olefins for the <i>ee</i> isomer. Additional calculations with longer chain olefins and the simplified structural models, in which the phenyl rings of the xantphos ligands were selectively removed to eliminate either substrate–ligand or ligand–ligand noncovalent interactions, suggested that ligand–substrate π-HC interactions play a more dominant role in the regioselectivity of Rh-catalyzed hydroformylation than ligand–ligand π–π interactions. The present calculations may provide foundational knowledge for the rational design of ligands aimed at optimizing hydroformylation regioselectivity

X‑Band Electron Paramagnetic Resonance Comparison of Mononuclear Mn^IV-oxo and Mn^IV-hydroxo Complexes and Quantum Chemical Investigation of Mn^IV Zero-Field Splitting

X-band electron paramagnetic resonance (EPR) spectroscopy was used to probe the ground-state electronic structures of mononuclear Mn^IV complexes [Mn^IV(OH)₂­(Me₂EBC)]²⁺ and [Mn^IV(O)­(OH)­(Me₂EBC)]⁺. These compounds are known to effect C–H bond oxidation reactions by a hydrogen-atom transfer mechanism. They provide an ideal system for comparing Mn^IV-hydroxo versus Mn^IV-oxo motifs, as they differ by only a proton. Simulations of 5 K EPR data, along with analysis of variable-temperature EPR signal intensities, allowed for the estimation of ground-state zero-field splitting (ZFS) and ⁵⁵Mn hyperfine parameters for both complexes. From this analysis, it was concluded that the Mn^IV-oxo complex [Mn^IV(O)­(OH)­(Me₂EBC)]⁺ has an axial ZFS parameter <i>D</i> (<i>D</i> = +1.2(0.4) cm^–1) and rhombicity (<i>E</i>/<i>D</i> = 0.22(1)) perturbed relative to the Mn^IV-hydroxo analogue [Mn^IV(OH)₂(Me₂EBC)]²⁺ (|<i>D</i>| = 0.75(0.25) cm^–1; <i>E</i>/<i>D</i> = 0.15(2)), although the complexes have similar ⁵⁵Mn values (<i>a</i> = 7.7 and 7.5 mT, respectively). The ZFS parameters for [Mn^IV(OH)₂(Me₂EBC)]²⁺ were compared with values obtained previously through variable-temperature, variable-field magnetic circular dichroism (VTVH MCD) experiments. While the VTVH MCD analysis can provide a reasonable estimate of the magnitude of <i>D</i>, the <i>E</i>/<i>D</i> values were poorly defined. Using the ZFS parameters reported for these complexes and five other mononuclear Mn^IV complexes, we employed coupled-perturbed density functional theory (CP-DFT) and complete active space self-consistent field (CASSCF) calculations with second-order <i>n</i>-electron valence-state perturbation theory (NEVPT2) correction, to compare the ability of these two quantum chemical methods for reproducing experimental ZFS parameters for Mn^IV centers. The CP-DFT approach was found to provide reasonably acceptable values for <i>D</i>, whereas the CASSCF/NEVPT2 method fared worse, considerably overestimating the magnitude of <i>D</i> in several cases. Both methods were poor in reproducing experimental <i>E</i>/<i>D</i> values. Overall, this work adds to the limited investigations of Mn^IV ground-state properties and provides an initial assessment for calculating Mn^IV ZFS parameters with quantum chemical methods

Saturation Kinetics in Phenolic O–H Bond Oxidation by a Mononuclear Mn(III)–OH Complex Derived from Dioxygen

The mononuclear hydroxomanganese­(III) complex, [Mn^III(OH)­(dpaq)]⁺, which is supported by the amide-containing N₅ ligand dpaq (dpaq = 2-[bis­(pyridin-2-ylmethyl)]­amino-<i>N</i>-quinolin-8-yl-acetamidate) was generated by treatment of the manganese­(II) species, [Mn^II(dpaq)]­(OTf), with dioxygen in acetonitrile solution at 25 °C. This oxygenation reaction proceeds with essentially quantitative yield (greater than 98% isolated yield) and represents a rare example of an O₂-mediated oxidation of a manganese­(II) complex to generate a single product. The X-ray diffraction structure of [Mn^III(OH)­(dpaq)]⁺ reveals a short Mn–OH distance of 1.806(13) Å, with the hydroxo moiety <i>trans</i> to the amide function of the dpaq ligand. No shielding of the hydroxo group is observed in the solid-state structure. Nonetheless, [Mn^III(OH)­(dpaq)]⁺ is remarkably stable, decreasing in concentration by only 10% when stored in MeCN at 25 °C for 1 week. The [Mn^III(OH)­(dpaq)]⁺ complex participates in proton-coupled electron transfer reactions with substrates with relatively weak O–H and C–H bonds. For example, [Mn^III(OH)­(dpaq)]⁺ oxidizes TEMPOH (TEMPOH = 2,2′-6,6′-tetramethylpiperidine-1-ol), which has a bond dissociation free energy (BDFE) of 66.5 kcal/mol, in MeCN at 25 °C. The hydrogen/deuterium kinetic isotope effect of 1.8 observed for this reaction implies a concerted proton–electron transfer pathway. The [Mn^III(OH)­(dpaq)]⁺ complex also oxidizes xanthene (C–H BDFE of 73.3 kcal/mol in dimethylsulfoxide) and phenols, such as 2,4,6-tri-<i>t</i>-butylphenol, with BDFEs of less than 79 kcal/mol. Saturation kinetics were observed for phenol oxidation, implying an initial equilibrium prior to the rate-determining step. On the basis of a collective body of evidence, the equilibrium step is attributed to the formation of a hydrogen-bonding complex between [Mn^III(OH)­(dpaq)]⁺ and the phenol substrates

Spectroscopic and Computational Investigations of a Mononuclear Manganese(IV)-Oxo Complex Reveal Electronic Structure Contributions to Reactivity

The mononuclear Mn­(IV)-oxo complex [Mn^IV(O)­(N4py)]²⁺, where N4py is the pentadentate ligand <i>N</i>,<i>N</i>-bis­(2-pyridylmethyl)-<i>N</i>-bis­(2-pyridyl)­methylamine, has been proposed to attack C–H bonds by an excited-state reactivity pattern [Cho, K.-B.; Shaik, S.; Nam, W. J. Phys. Chem. Lett. 2012, 3, 2851−2856 (DOI: 10.1021/jz301241z)]. In this model, a ⁴E excited state is utilized to provide a lower-energy barrier for hydrogen-atom transfer. This proposal is intriguing, as it offers both a rationale for the relatively high hydrogen-atom-transfer reactivity of [Mn^IV(O)­(N4py)]²⁺ and a guideline for creating more reactive complexes through ligand modification. Here we employ a combination of electronic absorption and variable-temperature magnetic circular dichroism (MCD) spectroscopy to experimentally evaluate this excited-state reactivity model. Using these spectroscopic methods, in conjunction with time-dependent density functional theory (TD-DFT) and complete-active space self-consistent-field calculations (CASSCF), we define the ligand-field and charge-transfer excited states of [Mn^IV(O)­(N4py)]²⁺. Through a graphical analysis of the signs of the experimental <i>C</i>-term MCD signals, we unambiguously assign a low-energy MCD feature of [Mn^IV(O)­(N4py)]²⁺ as the ⁴E excited state predicted to be involved in hydrogen-atom-transfer reactivity. The CASSCF calculations predict enhanced Mn^III-oxyl character on the excited-state ⁴E surface, consistent with previous DFT calculations. Potential-energy surfaces, developed using the CASSCF methods, are used to determine how the energies and wave functions of the ground and excited states evolved as a function of MnO distance. The unique insights into ground- and excited-state electronic structure offered by these spectroscopic and computational studies are harmonized with a thermodynamic model of hydrogen-atom-transfer reactivity, which predicts a correlation between transition-state barriers and driving force

Spectroscopic and Structural Characterization of Mn(III)-Alkylperoxo Complexes Supported by Pentadentate Amide-Containing Ligands

Manganese-alkylperoxo species have been proposed as important intermediates in certain enzymatic pathways and are presumed to play a key role in catalytic substrate oxidation cycles involving manganese catalysts and peroxide oxidants. However, structural and spectroscopic understanding of these intermediates is very limited, with only one series of synthetic Mn^III-alkylperoxo complexes having been reported. In the present study, we describe the formation and properties of two new Mn^III-alkylperoxo complexes, namely, [Mn^III(OO^<i>t</i>Bu)­(dpaq)]⁺ and [Mn^III(OO^<i>t</i>Bu)­(dpaq^2Me)]⁺, which utilize the anionic, amide-containing pentadentate dpaq ligand platform. These complexes were generated by reacting the corresponding Mn^II precursors with a large excess of ^<i>t</i>BuOOH at −15 °C in MeCN. In both cases, the corresponding mononuclear Mn^III-hydroxo complexes [Mn^III(OH)­(dpaq)]⁺ and [Mn^III(OH)­(dpaq^2Me)]⁺ are observed as intermediates en route to the Mn^III-alkylperoxo adducts. These new Mn^III-alkylperoxo complexes were characterized by electronic absorption, infrared, and Mn K-edge X-ray absorption spectroscopies. Complementary density functional theory calculations were also performed to gain insight into their bonding and structural properties. Compared to previously reported Mn^III-alkylperoxo adducts, the Mn^III centers in these complexes exhibit significantly altered primary coordination spheres, with a strongly donating anionic amide nitrogen located trans to the alkylperoxo moiety. This results in Mn^III-alkylperoxo bonding that is dominated by σ-interactions between the alkylperoxo π_ip*­(O–O) orbital and the Mn d_<i>z</i>² orbital

Near-UV and Visible Light Degradation of Iron (III)-Containing Citrate Buffer: Formation of Carbon Dioxide Radical Anion via Fragmentation of a Sterically Hindered Alkoxyl Radical

Citrate is a commonly used buffer in pharmaceutical formulations which forms complexes with adventitious metals such as Fe3+. Fe3+-citrate complexes can act as potent photosensitizers under near-UV and visible light exposure, and recent studies reported evidence for the photo-production of a powerful reductant, carbon dioxide radical anion (•CO2–), from Fe3+-citrate complexes (Subelzu, N.; Schöneich, N., Mol. Pharm.2020, 17, 4163−4179). The mechanisms of •CO2– formation are currently unknown but must be established to devise strategies against •CO2– formation in pharmaceutical formulations which rely on the use of citrate buffer. In this study, we first established complementary evidence for the photolytic generation of •CO2– from Fe3+-citrate through spin trapping and electron paramagnetic resonance (EPR) spectroscopy, and subsequently used spin trapping in conjunction with tandem mass spectrometry (MS/MS) for mechanistic studies on the pathways of •CO2– formation. Experiments with stable isotope-labeled citrate suggest that the central carboxylate group of citrate is the major source of •CO2–. Competition studies with various inhibitors (alcohols and dimethyl sulfoxide) reveal two mechanisms of •CO2– formation, where one pathway involves β-cleavage of a sterically hindered alkoxyl radical generated from the hydroxyl group of citrate

Relationship between Hydrogen-Atom Transfer Driving Force and Reaction Rates for an Oxomanganese(IV) Adduct

Hydrogen atom transfer (HAT) reactions by high-valent metal-oxo intermediates are important in both biological and synthetic systems. While the HAT reactivity of Fe^IV-oxo adducts has been extensively investigated, studies of analogous Mn^IV-oxo systems are less common. There are several recent reports of Mn^IV-oxo complexes, supported by neutral pentadentate ligands, capable of cleaving strong C–H bonds at rates approaching those of analogous Fe^IV-oxo species. In this study, we provide a thorough analysis of the HAT reactivity of one of these Mn^IV-oxo complexes, [Mn^IV(O)­(2pyN2Q)]²⁺, which is supported by an N5 ligand with equatorial pyridine and quinoline donors. This complex is able to oxidize the strong C–H bonds of cyclohexane with rates exceeding those of Fe^IV-oxo complexes with similar ligands. In the presence of excess oxidant (iodosobenzene), cyclohexane oxidation by [Mn^IV(O)­(2pyN2Q)]²⁺ is catalytic, albeit with modest turnover numbers. Because the rate of cyclohexane oxidation by [Mn^IV(O)­(2pyN2Q)]²⁺ was faster than that predicted by a previously published Bells–Evans–Polanyi correlation, we expanded the scope of this relationship by determining HAT reaction rates for substrates with bond dissociation energies spanning 20 kcal/mol. This extensive analysis showed the expected correlation between reaction rate and the strength of the substrate C–H bond, albeit with a shallow slope. The implications of this result with regard to Mn^IV-oxo and Fe^IV-oxo reactivity are discussed