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Involvement of high-valent manganese-oxo intermediates in oxidation reactions: realisation in nature, nano and molecular systems


Manganese plays multiple role in many biological redox reactions in which it exists in different oxidation states from Mn(II) to Mn(IV). Among them the high-valent manganese-oxo intermediate plays important role in the activity of certain enzymes and lessons from the natural system provide inspiration for new developments of artificial systems for a sustainable energy supply and various organic conversions. This review describes recent advances and key lessons learned from the nature on high-valent Mn-oxo intermediates. Also we focus on the elemental science developed from the natural system, how the novel strategies are realised in nano particles and molecular sites at heterogeneous and homogeneous reaction conditions respectively. Finally, perspectives on the utilisation of the high-valent manganese-oxo species towards other organic reactions are proposed.


Manganese plays an essential role in many biological processes and undergoes changes in redox state during catalysis and exists in different oxidation states from Mn(II) to Mn(IV). Among many different manganese proteins/enzymes, we are interested in the oxygen evolving complex and ribonucleotide reductases as it involved in generating high-valent intermediates for the catalytic activity. During the past year, significant advances has been made in understanding the biological chemistry of oxygen evolving complex and ribonucleotide reductase (RNR) class Ib and Ic and the unique redox properties of high-valent manganese species involved in the catalytic cycle of these enzymes are essential in the reactivity of these enzymes (Table 1) [1,2,3,4,5,6]. The oxygen evolving complex containing Mn4CaO5 cluster, catalyses one of the most important biological reactions occurring in the plants such as light driven oxidation of water to oxygen and protons. Significant progress has been made in understanding the structure and function of the OEC, however, the mechanism of O–O bond formation still remains elusive to experimentalists [7,8,9,10,11,12,13,14]. In many organisms, the manganese containing class Ib and Ic Ribonucleotide reductases (RNRs) are involved in catalysing the conversion of ribonucleotides to deoxyribonucleotides, which is the precursor for DNA replication and repair. RNR class I can be divided into subclasses Ia-Ic is based on differences in structure and metal cofactor. Class Ia RNR is expressed in all mammals and contains FeFe cofactor, whereas class Ib and Ic RNR has only been found in pathogenic bacteria and a dimanganese(III) cofactor in Ib and Mn–Fe cofactor in Ic were identified (Table 1) [15,16,17,18,19,20,21,22,23,24,25,26,27,28]. In addition, mononuclear Mn(III)-oxygen intermediates and Mn(II) ions as Lewis acid catalysts are used by various manganese enzymes of metabolic importance [4,5,6]. Many issues remain to be answered about the redox properties of enzyme-bound manganese center and the nature of the high-valent intermediate species involved in the catalytic mechanism. So these enzymes have served as inspiration for making model complexes capable of mimicking biological functions or performing synthetically useful organic and other transformations applicable to industrial level. Recent developments in bioinspired manganese chemistry has led to highly active models of the oxygen-evolving complex (OEC), oxygen activating complexes and catalysts for efficient and selective epoxidation, C–H bond oxidation and other organic conversions. Notably, central role of high-valent Mn-oxygen species in reactivity of Mn-dependent enzymes and model systems were investigated towards these reactions. In this review, the key lessons about high-valent manganese-oxo intermediates involved in catalytic cycles of manganese based enzymes are discussed. Based on the fundamental science developed from the natural system, how the novel strategies are realised in molecular sites and nano particles at homogeneous and heterogeneous condition for many different oxidations reactions are presented with previously demonstrated examples.

Table 1 High-valent Mn-oxo intermediates involved in OEC and RNR

Structure and function of oxygen evolving complex (OEC)

Water splitting is one of the most important biochemical reactions on earth in which the light energy is converted into biologically useful chemical energy and molecular oxygen catalysed by oxygen evolving complex in PSII. The water oxidation cycle is catalysed by OEC involves a series of five intermediate states that are known as S states (Kok cycle). The structural and mechanistic information of the OEC, consisting of a Mn4CaO5 cluster and the structure of PSII has been studied extensively by X-ray crystallography and significant progress has been made in understanding the inorganic and physical chemistry of five different states S0–S4 [10, 29,30,31,32,33,34,35,36,37,38]. Nonetheless the identity of the substrate water molecules and the mechanism of the coupling of O–O bond are still elusive. Because most of the collected X-ray crystal structures of PSII using conventional synchrotron radiation have suffered from radiation-induced Mn reduction [39]. Even though, in the 1.9-Å resolution PSII structure the electron densities were clearly separated for all the metal ions and bridging oxygen atoms allowing the clear cut prediction of all the atoms [34, 36]. The oxygen-evolving complex containing an inorganic Mn4CaO5 cluster in which the four Mn ions and one Ca ion are connected by µ-oxo bridges (Fig. 1) [7,8,9,10,11,12,13,14, 29,30,31,32,33,34,35,36,37,38]. The Mn4CaO5 cluster contains a distorted cuboidal Mn3O4Ca unit formed by three Mn ion and one Ca ion and four bridging oxo groups. The fourth Mn ion is located outside the cuboidal unit and linked through two oxo–bridges provided by O4 to one of its corners and O5 to the other corner. The Mn4O5Ca cluster is also surrounded and stabilised by six carboxylate ligands from two aspartate (D1-Asp170, D1-Asp342), three glutamate (D1-Glu189, D1-Glu333, CP43-Glu354) and one alanine ligands (D1-Ala344) and one nitrogen ligand from histidine (D1-His332) residues (Fig. 1b) [34, 36]. Also two water molecules are coordinated to both the terminal Mn ion and Ca ion at the active sites. The Mn4CaO5 cluster structure is in highly distorted configuration, which enables the cluster to easily undergo structural rearrangements during the catalytic cycle and considered as a salient feature of the cluster. The distorted configuration of the Mn4CaO5 cluster is originated mainly from the incorporation of calcium ion in cuboidal unit because it alters the Ca–O and Mn–O distances. Among the five oxygen atoms, the bond distances of O1–O4 to their nearby Mn ions in the range of 1.8–2.2 Å and the distance between O5 and its nearby Mn ions is in the range of 2.4–2.6 Å revealing that the O5 is coordinated very weekly with all the nearby Mn ions mainly due to the presence of Ca(II) ion. The incorporation of the Ca(II) ion in the metal cluster for high level distortion in the cuboidal structure and the unique coordination pattern of the μ-oxo-bridged oxygen atoms and their H-bonding interaction with either amino acid residues or water molecules are the important factors contributing to the flexibility and catalytic activity of the OEC [11, 12, 14, 34, 36, 37].

Fig. 1

(Copyright 2014, AAAS the science society publications. c Distances (in Å) between metal atoms and oxo bridges or water molecules [34]. Adapted with permission from [34]. Copyright 2011, Nature publishing group)

a Active site structure of the oxygen evolving complex, a Mn4O5Ca cofactor with bond lengths [35]. b The five intermediate “S” states of the reaction cycle, showing the sequence of electron- and proton-removal steps and the likely oxidation states of the Mn ions in each metastable state. Adapted with permission from [35]

During the reaction initially light energy is absorbed by chlorophyll-a (P680) and becomes excited and donates one electron to the initial electron acceptor pheophytin moiety, which consequently transfers the electron to the primary and secondary plastoquinone acceptors. The oxidized P680+ is reduced by a nearby redox active tyrosine residue, which in turn oxidizes a Mn4CaO5 cluster for water splitting, proceeds through five different states S0–S4 (Kok cycle). After the four sequential oxidation events the OEC advances stepwise through the S0, S1, S2, and S3 states. When the S3 state is advanced to the transient S4 state, O2 is spontaneously released and the S0 state is reformed [10, 11, 14, 29,30,31,32,33,34,35,36,37,38].

Spectroscopic study and DFT calculations strongly suggesting that the S0 state is the most reduced state in OEC, containing three Mn(III) and a Mn(IV) ion in the Mn4CaO5 cluster and has a ground spin state of ½ [40,41,42]. Initially, after the electron transfer cycle the nearby tyrosine radical oxidise one of the Mn(III) to Mn(IV) in the Mn4CaO5 cluster with concomitant proton transfer and the S1 state contains the Mn oxidation state pattern III, IV, IV, III with spin state of 0 and is diamagnetic [43]. During the second oxidation of the OEC it was observed that no proton is released from the cluster and positive charge is accumulated in the OEC during the transition of S1 → S2+ [44, 45]. The S2 state is paramagnetic and has been extensively studied using EPR spectroscopy and two different EPR signal at approximately g = 4.1 is observed and dramatic multiline EPR signal at g = 2 is observed based on the conditions used for the EPR measurement [46,47,48,49,50,51]. The g = 4.1 and g = 2 EPR signals represents two spin isomers of the S2 state with a ground state of S = 5/2 and S = 1/2 respectively. The Mn oxidation state pattern is IV, IV, IV, III for S = 5/2 state in which the dangler fourth Mn ion is five-coordinated with Mn(III) center and is weakly electronically coupled to the other three Mn(IV) ions in the closed cubane motif. On the other hand, the Mn oxidation state pattern for S = 1/2 state is III, IV, IV, IV in which the Mn1 is a five-coordinated Mn(III) center and all Mn ions are connected by di-µ-oxo bridges resulting in short Mn–Mn distances and promotes antiferromagnetic coupling of the Mn center leading to a low spin state [45, 47, 48, 51]. During the third oxidation of the OEC by the nearby tyrosine radical, the Mn oxidation is coupled with the proton transfer and followed by water coordination and the resulting S3 state’s contain four Mn(IV) centers with six-coordination [35, 52, 53]. Based on the coordination of second water molecule on the cluster many different mechanisms have been suggested and formation of S3 from S2 is still debated. The first mechanism considered the closed cubane S = 5/2 spin isomer and during the oxidation of the Mn4 from Mn(III) to Mn(IV), a water molecule (W3) is transferred from Ca to Mn4 and the water from the hydrogen-bonded network surrounding the OEC occupy the site previously occupied by W3 to Ca [35, 52, 53]. In another mechanism, the open cubane S = 1/2 spin isomer is considered in which a new water molecule added to Mn1 when it is oxidized from Mn(III) to Mn(IV) followed by deprotonation to form a terminal hydroxo ligand on it (Fig. 2).

Fig. 2

(Adapted with permission from [35]. Copyright 2014, AAAS the science society publications)

Theoretically calculated structures for the S2 and S3 states and the proposed mechanism of O–O bond formation

Inspired from the ammonia binding studies to the S2 state another mechanism is suggested [52, 54,55,56,57,58]. During the oxidation of Mn4 from Mn(III) to Mn(IV) a water molecules from Mn4 is inserted between Mn4 and Mn3 and the water molecule (W1) coordinated to Mn4 center replace the site previously occupied by W2 and a water molecule hydrogen bonded with O4 around is coordinated to Mn4 in the site occupied by W1 [35, 52, 56, 59]. Experimental data for the S4 and the transition of S3 → S0 states are limited, however, computational studies are supporting the mechanism of O–O bond formation and this transition consist of O2 formation and release along with two protons and binding of a water molecule to the Mn4O5Ca cluster. Two different isoelectronic intermediates species such as MnIV–O· radical or a MnV=O species are suggested to be involved in the S4 state and their involvement is still debated. An oxo–oxyl radical coupling mechanism for O–O bond formation has been supported by extensive computational studies in which the MnIV–O· radical species couple to a µ-oxo bridge [35, 60,61,62,63,64]. Based on the studies from inorganic water oxidation catalysts, the water-nucleophile attack mechanism for O–O bond formation has been suggested in which the highly electrophilic MnV=O species attack the oxygen on the water [8, 65,66,67]. However, to date, no experimental evidence has been collected to support either the oxo–oxyl radical mechanism or the water-nucleophile attack mechanism in OEC. Even though most of our understanding of O–O bond formation arrived from computational studies the chemistry of OEC is supportive in the design of synthetic catalysts for efficient water oxidation reaction. More study on OEC is crucial to understand the mechanism and how OEC stabilised in the protein pocket and utilise the high-valent Mn-oxo intermediates towards hydrogen abstraction and electron transfer reactions in a classy manner to effect the oxygen evolving reaction.

Ribonucleotide reductases (RNRs)

In all organisms, Ribonucleotide reductases (RNRs) are the key enzymes involved in catalysing the conversion of ribonucleotides to deoxyribonucleotides, the precursor for DNA replication and repair. In class-Ib RNR from Corynebacterium ammoniagenes contain a MnMn cofactor and class-Ic RNR from Chlamydia trachomatis (Ct), contain a MnFe cofactor in subunit R2, instead of an FeFe cofactor plus a redox-active tyrosine in class-Ia RNRs [15,16,17,18,19,20,21,22,23,24,25,26,27,28, 66, 67]. The 1.65 Å resolution crystal structure of \({\text{Mn}}_{2}^{\text{II}}\)-NrdF contains one monomer per asymmetric unit with the presence of two MnII sites (Fig. 3) with a Mn–Mn distance of 3.7 Å [23]. Mn1 is coordinated by His101, Asp67 and a terminal water molecule and Mn2 is coordinated by His195 and a terminal water molecule. Three glutamate residues (Glu98, Glu158, and Glu192) bridge the two metals in a manner previously not observed in RNRs and related carboxylate-bridged diiron enzymes [23, 68]. The location of the two interacting solvent molecules at Mn2 could easily accommodate by molecular oxygen [22]. These waters may dissociate, allowing the oxidant to initially bind terminally to Mn2 in this position, by analogy to the proposal for H2O2 binding to the structurally related Mn catalases [69].

Fig. 3

(Adapted with permission from ref [82]. Copyright 2013, ACS publications. c Adapted with permission from ref [87]. Copyright 2018, ACS publications)

Ribonucleotide reductase class Ib, Ic and may be Id. a X-ray crystallographic structure of \({\text{Mn}}_{2}^{\text{II}}\)-NrdF cofactor. Adapted with permission from ref [23]. Copyright 2014, AAAS the science society publications. b X-ray crystallographic structure MnIIFeII cofactor

Class Ib with dimanganese cluster participate in the generation of tyrosyl radical in R2 unit and the reduction of the catalytic site in R1 [70]. However the di-manganese cluster adopts a somewhat similar coordination environment to that of methane monooxygenase hydroxylase unit (MMOH) [23, 25, 70]. Unlike class Ia and Ib, in class Ic the tyrosyl radical site is replaced by a phenylalanine residue and all the carboxyl ligands to the metal ions are substituted by glutamate residues. By use of Mössbauer, EPR and extended X-ray absorption fine structure (EXAFS), it has been shown that in class Ic R2 proteins, a mixed metal center MnIV/FeIII is the metal cofactor [19,20,21,22, 71, 72] acting as source of the oxidation catalyst, capable of generating the thiyl radical in R1.

The mechanism of oxygen activation in the class Ib RNR is derived from EPR spectroscopy along with X-ray crystallography of the protein. RNR utilise oxygen activation mechanism and attain high-valent states and producing tyrosine radical. Two different mechanistic pathways for dimanganese and radical cofactor assembly have been proposed [23,24,25, 73]. But in both mechanisms the first step involves oxidation of the MnII/MnII to MnIII/MnIII by H2O2 is considered. In the second step, the oxo bridged MnIII/MnIII dimer converted into diamond core MnIV/MnIV intermediate and it is having sufficient oxidizing power to extract one electron and one proton from the tyrosine residue [23,24,25, 73]. However different coordination mode of the peroxide ligand is proposed. Cox and co-workers suggested that the HO2 or H2O2 coordinates to both the manganese atoms through only one oxygen atom along with the shift of the bridging carboxylate ligand to produces an oxo-bridged MnIII/MnIII complex [25]. After that the second H2O2 replace a water ligand at Mna closest to the tyrosyl radical (Fig. 4) and produce a bridging hydroperoxide species of MnIII-O-MnIII. The protonation of the bridging hydroperoxide and release a water molecule leading to a second two-electron oxidation process to produce the highly unstable MnIV/MnIV transient species followed by formation of a more stable MnIII/MnIV state by oxidizing a nearby tyrosine residue. Both MnIV/MnIV and MnIII/MnIV have the oxidizing power to extract an electron from the tyrosine cofactor [25]. But Cotruvo and Stubbe proposed that HO2 or H2O2 replaces a water ligand on Mnb, which is slightly away from the tyrosine radical site and forms a bridging hydroperoxide between the two Mn(II) ions with concomitant rearrangements of carboxylate oxygen (E202). After that the oxidation of the MnIII/MnIII cluster by the bound hydroperoxide leads to release of a water molecule to produce the diamond core MnIII/MnIV intermediate rather than a MnIV/MnIV intermediate. Also from the crystal structure of the R2F subunit with NrdI cofactor from class Ib E. coli., Cortuvo and Stubbe proposed that the flavodoxin like protein NrdI (NrdIhq) is an essential component for the making the HO2 required in the reaction cycle with di-manganese [23, 24, 69, 72]. Class Ic RNRs also utilise the dimetal cluster but instead of dimanganese in class Ib it is utilising MnFe cluster and producing cysteine radical rather than a tyrosine radical [19,20,21, 74,75,76,77,78,79,80,81,82,83,84,85,86]. In Chlamydia trachomatis (Ct) enzyme the MnII/FeII complex reacts with O2 to form a MnIV/FeIV intermediate followed by one electron reduction to produce MnIV/FeIII cofactor, in which the MnIV is the oxidant in the active state. The MnII/FeII cofactor can also react with H2O2 and converted to the to the active MnIV/FeIII state in two steps through MnIII/FeIII and MnIV/FeIV intermediates [77]. At the position of the tyrosine radical center in Ia/b proteins instead the Ic subunits have phenylalanine; and obviously it is considered as the characteristic of this subclass [19,20,21, 74,75,76,77,78,79,80,81,82]. Interestingly, a ribonucleotide reductase (RNR) from Flavobacterium johnsoniae (Fj) differs fundamentally from all the class Ia–c RNRs and it is assigned to a new subclass Id. Even though, its active site is similar to class Ib counterparts it does not require the oxidant supplying flavoprotein (NrdI) needed in Ib systems for superoxide (O2) activation and it can scavenging the oxidant from solution itself [87]. Interestingly, in all the manganese containing RNR subunits nature utilise the high-valent Mn(IV) species to initiate the hydrogen abstraction from their counter radical-harbouring domain for the further reaction, in making the biologically important conversion such as deoxyribonucleotide from ribonucleotide. Also based on having with or without the flavoprotein counter part, the Mn2 cofactor activate the active oxygen species or molecular oxygen to carry out the hydrogen atom transfer reaction (HAT).

Fig. 4

 The proposed reaction cycles for the generation of the tyrosyl radical in a class Ib and b Ic RNR suggested by Stubbe. Redrawn from ref [73]

High-valent manganese-oxo intermediates at nano sites

Natural systems successfully utilise the high-valent manganese-oxo species for robust catalytic oxidation, inspired the scientific community. Several attempts have been made to understand and utilise, the novel strategies employed by the natural system. Numerous reports are available for many different oxidation reactions utilising manganese oxide nano particles in the literature, however, studies which involves the characterisation and mechanism of high-valent Mn-oxo intermediates in the catalytic cycle are scarce. Notably, various kinds of manganese oxide nanoparticles are studied for water oxidation reaction and the importance of the distortion in the mixed valent manganese centers in the Mn4CaO5 cluster for the oxygen evolution reaction is realised on the surface of the manganese oxide nano particle [88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103].

Kurtz et al. studied the biomimetic oxidation of water and shown that the photocatalytic activity of the calcium manganese(III) oxide hydrates (CaMn2O4·xH2O) is superior than the manganese(III) oxide particles (α-Mn2O3) and related the importance of elemental composition of the Mn4OxCa core of the OEC in the activity [86]. The Jaramillo group proposed that the higher OER activity of mixed-valence MnOx film is depends on the high-valent manganese distribution on the oxide material [89, 90]. Also, the effect of hetero atom on the catalytic surface are studied in the MnOx/Au-GC composite, synthesized by adding Au to MnOx, displayed a surprisingly high enhancement in catalytic performance compared to pure MnOx catalysts [91]. He and Suib group used a similar approach in a photochemical water oxidation of the gold-nanoparticle modified MnO2, evidenced from XANES, addition of a small amount of gold to the MnO2 surface partially reduces the Mn species to create a mixed valence state thereby enhance the catalytic activity compared to pristine MnO2 [92]. Dau group observed the formation of disordered MnIVO2 motif for high catalytic activity at neutral pH [93]. Navrotsky group theoretically verified the effect of mixed valence state on OER performance. Also they experimentally demonstrated that among the four different manganese compounds, CaMnO, Mn2O3, MnO2, and Mn3O4, the mixed-valence CaMnO (Mn3+ and Mn4+) exhibited the highest catalytic activity [94]. Nocera and co-workers reported the oxygen evolution activity of electrodeposited MnOx films and explains how the original birnessite-like MnOx (δ-MnO2) undergoes disordered phase change during OER cycling to exhibit high activity [95]. The Driess group synthesised an amorphous MnOx compound using chemical oxidant ceric ammonium nitrate (CAN) and proposed that the change in oxidation state of the amorphous MnOx compared to the initial crystalline MnO is the key for high reactivity and using EXAFS analysis they insisted that the active site of amorphorized MnOx resembles that of the Mn4Ca cluster [96, 97]. They also synthesised amorphous MnOx layered Mn3N2 particles by molecular approach, in which the layer generated by stepwise oxidation of Mn2+ to Mn4+ and documented as the real active sites. Importantly, they argue that the Jahn–Teller distorted Mn-O bonds generated by Mn3+ assisted Mn4+ for binding O–O with appropriate strength is facilitating the OER [98]. Our group reported many different manganese oxide materials for OER [99,100,101,102,103,104,105,106], among them the nanosized Mn oxide catalysts display outstanding catalytic activity under neutral conditions [102, 105]. The sub-10 nm-sized monodispersed MnO nanoparticles showed unexpectedly high OER performance compared to the well-known catalysts Co-Pi and MnOx. The stability of Mn3+ intermediates on the nanosized oxide surface was also significantly improved during catalysis. Very interestingly, we successfully demonstrated that the 10 nm size MnO stably generate the Mn(III) species via proton-coupled electron transfer pathway. Furthermore, we spectroscopically characterised the reaction intermediate MnIV=O species using in situ UV–Visible and resonance raman analysis during the catalysis (Fig. 5) [105]. Raman spectra of the MnO NPs during electrolysis at constant potentials showing the characteristic Mn(II)–O stretching vibration (Ag) and Mn(III)–O stretching (Eg) modes as broad shoulder bands around 640 and 575 cm−1 respectively. Upon increasing the applied potential to 1.05 V vs NHE, new Raman peaks appeared at approximately 555 and 480 cm−1, with corresponding decrease in intensity of the Mn(III)-related bands. The shift in the Raman values and relative intensities of the generated peaks were assigned to the stretching vibration of Mn(IV)–O species. We also identified the generated reaction intermediates using in situ diffuse transmission UV–vis analysis. Initially, the MnO NPs exhibited two bands in the UV regions at approximately 350 and 380 nm, corresponding to O2− → MnII and O2− → MnIII ligand-to-metal charge transfer along with several weak peaks originating from d–d transitions in the visible region. Upon increasing the applied potentials at 0.1 V intervals, two distinct absorption bands in the regions of 400 nm and 600 nm were identified. The origins of the peaks were assigned to Mn(IV) species, by matching with broad peak in the region of 400 nm and shoulder peaks at approximately 575 and 700 nm of Mn(IV) in MnO2 [105]. In most of the water oxidising manganese oxide catalysts the generation of the distorted structure on the surface by generating the mixed valency by various thermal, chemical and electrochemical methods are realised with respect to the OEC in which the incorporation of Ca ion and mixed valency plays a crucial role in distorting the structure and function the OEC.

Fig. 5

(Adapted with permission from ref [105]. Copyright 2017, ACS publications)

a In-situ UV–Vis difference spectra of the MnO NPs based on the applied potential. b In-situ Raman spectra of the MnO NPs at various potential collected during bulk electrolysis [105]

High-valent MnIV-oxo Intermediates at Molecular Sites

Although manganese is the Nature’s choice for the catalytic oxidation of water in photosystem II, there are only a few reports of synthetic manganese compounds which are able to catalyze this reaction. However, various manganese complexes are reported for the oxygen atom transfer (OAT) and hydrogen atom transfer (HAT) reactions and realised the involvement of high-valent Mn(IV)-oxo species in the catalytic cycle. The first characterized mononuclear manganese(IV)-oxo complexes with porphyrinic ligands were reported by Groves and co-workers. The reaction of manganese(III) complex [(TMP)MnIIICl] with peroxy acid produced a stable [(TMP)MnIVO] and [(TMP)MnIVO(OH)] species, capable of transferring their oxo group to olefins to produce epoxides [107,108,109]. The manganese salen complexes (Jacobsen catalysts) have been extensively studied as catalysts for the oxidation of olefins to the corresponding epoxides, in which they identified the formation of [(Salen)MnIV(O)] species using EPR and NMR upon interaction of [(Salen)MnIII] with m-CPBA or PhIO and proposed as the reactive intermediate involved in the catalytic cycle [110, 111]. Later, Yin and co-workers isolated a non-heme monomeric Mn(IV)-complex [(Me2EBC)MnIV(OH)2]2+ (where Me2EBC = 4,11-dimethyl-1,4,8,11-tetrabicyclo[6.2.2]-hexadecane) with two hydroxo ligands and employed as catalysts for epoxidation reaction with and without peroxides [112, 113]. A novel manganese(IV) peroxide intermediate, [MnIV(Me2EBC)(O)(OOH)]+, was captured as the third kind of active intermediate responsible for epoxidation and the tert-butyl peroxide adduct of this manganese(IV) complex was also detected by mass spectroscopy under catalytic oxidation conditions [114]. Also they studied the pH dependence HAT reaction rates of the organic substrates (xanthene, fluorene, 1,4-cyclohexadiene, 9,10-dihydroanthracene) using MnIV(OH) 2+2 (BDEOH = 83.0 kcal/mol) and MnIV(O)OH+ (BDEOH = 84.3 kcal/mol) species and presented a different hydrogen atom abstraction rates [115]. Interestingly, Nam and co-workers reported the first example of reversible O–O bond cleavage and formation between the in situ generated Mn(IV)-peroxo and Mn(V)-oxo corroles supported by various spectroscopic methods such as UV–vis, EPR, ESI–MS and XAS/EXAFS analysis [116]. Later they studied the reactivity of various Mn(IV) species [MnIV(BQCN)(O)(H2O)]2+ (BQCN=N,N′-dimethyl-N,N′-bis(8-quinolyl)cyclohexanediamine), [MnIV(OH)2(H,MePytacn)] and [MnIV(O)(OH)(H,MePytacn)]+ (Pytacn=N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)-cyclohexane-trans-1,2-diamine) towards activation of C-H bonds of alkyl-functionalized aromatic molecules and the oxidation of aromatic substrates, alkenes and benzyl alcohol [117,118,119,120]. The dimerisation of the highly reactive oxo-manganese(IV) complex has been observed in the case of [(Bn-TPEN)MnIVO]2+ (Bn-TPEN=N-benzyl-N,N′,N′-tris(2-pyridylmethyl)-1,2-diaminoethane) and the HAT reaction of anthracene and anthraquinone also studied [121,122,123,124]. Also the effect of non-redox active Sc3+ ion on the stability of the Mn(IV)=O species such as [(Bn-TPEN)MnIV(O)]2+ and [(N4Py)MnIV(O)]2+ (N4Py=N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) are studied and found that the formation of MnIV(O)–(ScIII) complexes and observed that these scandium bound high-valent species catalyse the sulfoxidation of thioanisoles by direct oxygen atom transfer from MnIV(O) complexes whereas without Sc3+ ion involved in electron-transfer reaction rather than OAT [124, 125]. Talsi and coworkers studied the epoxidation of olefins with various oxidants (CH3CO3H vs. m-CPBA, t-BuOOH vs. cumyl hydroperoxide, PhIO vs. iodosylmesitylene) using non heme aminopyridinylmanganese(II) complexes [LMnII(OTf)2] as catalysts and high-valent intermediate species [LMnIVO]2+ and [LMnIV(µ-O)2MnIIIL]3+ were detected upon the interaction of complex with oxidants by EPR techniques [126]. Feringa et al. studied the mechanism of cis-dihydroxylation and epoxidation of alkenes catalysed dinuclear manganese complex [\({\text{Mn}}_{2}^{\text{IV}}\)(μ-O)3(tmtacn)2]2+ with triazacyclononane ligand framework using H2O2 as mild oxidant [127]. Interestingly, high turnover enantioselective alkene cis-dihydroxylation is achieved with H2O2 based on the chiral carboxylate ligands on the manganese complexes and the reactivity and selectivity is readily tunable by variation of the carboxylic acid employed. The preference of the [\({\text{Mn}}_{2}^{\text{III}}\)(µ-O)(µ-RCO2)2(tmtacn)2]2+ catalyst systems towards electron-rich cis-alkenes with high turnover numbers and efficiency demonstrated that this could be a sustainable and synthetically useful method with H2O2 as the terminal oxidant [128, 129]. Similarly the Mn(IV) complex [\({\text{Mn}}_{2}^{\text{IV}}\)(μ-O)3(Me3tacn)2]2+ with substituted ligands can greatly promote the alkene epoxidation efficiency under mild conditions with H2O2 and identified the active intermediate species HO-MnIII-(μ-O)-MnIV=O or O=MnIV-(μ-O)-MnIV=O spectroscopically [130]. Choe et al. explored the catalytic reactivity of di-μ-oxo-bridged diamond core complexes MnIII-(μ-O)2-MnIV by adding non-redox metal ions to dissociate those dimeric cores and provided clues to understand the mechanism of methane monooxygenase which has a similar diiron diamond core as the intermediate [131]. Kwong et al. detected manganese(IV)-oxo porphyrin upon the reaction of the manganese(III) porphyrin with PhI(OAc)2 and excellent catalytic efficiency with up to 10,000 TON was achieved for epoxidation of olefins and proposed the involvement of manganese(V)-oxo intermediate as the premier active oxidant in the catalytic cycle [132]. Recently, Dai et al., demonstrated that manganese complex with a porphyrin-like ligand catalyzes the highly chemoselective and enantioselective oxidation of heteroaromatic sulphides with hydrogen peroxide in good to excellent yields with very high enantioselectivities (up to 90% yield and up to > 99% ee) and proposed high-valent MnIV-O· radical as the reactive oxidant in the catalytic cycle [133]. Shulpin and coworkers reported the efficient oxygenation of alkanes with H2O2 catalysed by a binuclear manganese(IV) complex [Mn2L2O3]2+ (L = 1,4,7-trimethyl-1,4,7-triazacyclo-nonane) with carboxylic acid as a co-catalyst. The transformation of alkane into the corresponding alkyl hydroperoxide proceeds via generation of alkyl radicals which is rapidly react with atmospheric molecular oxygen [134]. Also the catechol oxidase activity involves HAT by the high-valent bis(oxo)-bridged manganese(IV) complex reported by Mondal group [135]. High-valent Mn(IV)-oxo intermediates mediated oxidation reactions such as epoxidation and cis-dihydroxylation of olefins, alkane oxidation, sulphoxidation and hydrogen abstraction are realised in many molecular systems and in some cases it is promising, however the issues such as stability and selectivity and use of strong oxidant are to be solved for the real industrial application of these molecular systems.

High-valent MnV-oxo Intermediates at Molecular Sites

The MnV=O species are considered to be involved in many HAT and OAT reactions during the reaction with manganese(III) complexes with dioxygen or oxidants such as hydrogen peroxide (H2O2) or tert-butylhydrogenperoxide (t-BuOOH) or m-chloroperbenzoic acid (m-CPBA) and substrate (Table 2). Initially, Kochi group studied the catalytic activity of the various substituted MnIII(salen) complexes with iodosylbenzene (PhIO) towards alkenes and studied the interaction by uv–visible spectroscopy [136]. Even though they proposed the involvement of MnV=O species in the catalytic activity there were no solid evidence has been collected. Collins group generated and characterised the first stable oxomanganese(V) complex by utilising a tetra-anioic ligands with two amido nitrogens and two alkoxide oxygen donors and upon reaction of the Mn(III) complex with t-BuOOH and found that the high-valent species are not stable in water [137]. Followed by these study the same group generated another Mn(V)=O species with tetraamido ligands which is stable in water and characterised by XRD and IR and Raman studies. However, the MnV=O species is stable at room temperature and do not undergo oxygen-atom-transfer reactions possessing diamagnetic (low-spin d2 configuration) configuration [138]. Later on, Jacobsen group reported the manganese salen-type catalysts for the asymmetric epoxidation of unfunctionalized olefins with PhIO as oxidant with moderate enantioselectivities for a few substrates (e.g. trans-alkenes, terminal alkenes) and proposed the involvement of Mn(V)=O species [139]. In 1992 Collins group again characterised the Mn(V)=O species by using isotopic labelling and Raman spectroscopic studies [140]. ƠHalloran group generated the high-valent Mn(V)=O species along with hydroxylated solvent molecules upon reaction of the tetraanionic Mn(III) complex with molecular oxygen and they also characterised the species using UV–visible spectroscopy [141]. In the year of 1997, Groves and co workers reported the successful characterisation of Mn(V)=O species using substituted porphyrin ligands and m-CPBA and observed a characteristic signal in UV–visible spectroscopy [142]. Plattner et al. first time observed the direct evidence for the involvement of high-valent Mn(V)=O species towards OAT of olefins and sulphides by reaction of Mn(salen) complexes with m-CPBA and confirmed by electrospray tandem mass spectrometry [143]. In 1998, Collins again reported the reactivity of the Mn(V)=O complexes of tetraamido ligands in which they activated the sluggish complexes by adding alkali and alkaline earth secondary metal ions and observed OAT towards olefins [144]. However, Groves observed that addition of sodium nitrite to the low-spin, d2 oxo-Mn(V) species leads to the formation of high-spin Mn(IV) and Mn(III) states in which an electron is promoted from dxy to d(xz, yz) because of the vibronic effect due to the elongation of the very short Mn-oxo bond upon reduction [145]. Also they observed the rapid and reversible oxygen atom transfer from the Mn(V)-oxo species to bromide ion [146]. Talsi et al. extensively studied and characterised the Mn(IV/V)=O species of Mn(salen) complexes generated with various oxidants using NMR and EPR techniques [110]. Nam et al. isolated oxomanganese(v) porphyrin intermediate with H2O2, in buffered aqueous solution and demonstrated as active epoxidizing intermediate in the catalytic epoxidation of olefins. Interestingly they observed the pH dependence of the O–O bond cleavage in the mechanism with various hydroperoxides [147]. The intermediate MnV=O species generated from the corresponding Mn(III) complex with H2O2 has been identified with Me3TACN ligands using ESI–MS and studied their role in HAT reactions of phenols as one-electron reductants by Oakes group [148]. After that Collman group studied the stereoselectivity of olefin epoxidation catalyzed by MnIII(salen) complexes in the presence of neutral donor ligands, employing various iodosylarenes (ArIO: PhIO, C6F5IO, and MesIO) as the oxygen atom source and single MnV(salen)-oxo species is considered to be involved as the sole oxygenating intermediate [149]. Goldberg and co-workers successfully generated the high-valent MnV=O species upon reaction of the Mn(III) Triazacorrole complex with PhIO and utilised first time for the sulphoxidation of thiols [150]. In 2007, Nam group generated the MnV=O generated with Mn(III)-porphyrin and PhIO and characterized with various spectroscopic techniques such as UV–vis, EPR, 1H and 19F NMR, resonance Raman, and X-ray absorption spectroscopy and found that it is not active towards olefins but involved in OAT of thioanisole and triphenylphosphine [151]. The same group again generated both MnV– and MnIV–oxo porphyrins in basic aqueous solution and investigated their reactivities in C–H bond activation of hydrocarbons. Also they found that the C–H bond breaking ability of MnV–oxo complex is 150 times faster than that of a MnIV–oxo complex in the oxidation of xanthenes [152]. Chang group synthesised the MnV=O species of highly bulky bis-pocket corrole 5,10,15-tris(2,4,6-triphenylphenyl)corrole (H3TTPPC) with PhIO and characterised the triply bonded Mn≡O moiety by Resonance Raman spectroscopy in manganese(V)–oxo complex and performed the direct oxygen atom transfer from (TTPPC)Mn≡O to styrene confirmed by an 18O-labeling experiment. The (TTPPC)MnIII complex also exhibits significant shape selectivity in the catalytic epoxidation of nonconjugated dienes [153]. Later for the first time trans-dioxomanganese(V) porphyrin complexes have been synthesized by Nam group and employed successfully for hydride transfer from dihydronicotinamide adenine dinucleotide (NADH) analogues proceeds via proton-coupled electron transfer, followed by rapid electron transfer [154]. Goldberg isolated the high-valent metal-oxo and metal–imido complexes manganese corrolazines (TBP8Cz)MnV(O) and (TBP8Cz)MnV(NMes) and employed as catalysts for epoxidation of alkenes with ArIO oxidants In which the metal-imido complex is a rare example of oxygen atom transfer catalyst and these reactions likely proceed via an unusual ArIO–metal–oxo/imido intermediate [155]. Interestingly, Fukuzumi et al. generated the MnV=O species by using [Ru(bpy)3]3+ as electron transfer agent and water as oxidant and catalyses alkenes and alkanes and produced epoxides and diols and aldehydes [156]. For the first time Borovik group generated the high-spin oxomanganese(V) species in a trigonal geometry unlike the other low-spin species in tetragonal geometry and characterised by EPR spectroscopy. The high-spin oxomanganese(V) complex formulation and oxidation reaction with [FeCp2]+ were monitored using optical and EPR spectroscopies [67]. Goldberg studied the effect of lewis acid Addition of anionic donors to the manganese(V)–oxo corrolazine complex MnV(O)(TBP8Cz) has a dramatic influence on oxygen-atom transfer (OAT) reactivity with thioether substrates provides new, fundamental insights regarding the influence of axial donors on high-valent MnV(O) porphyrinoid complexes. Lei et al. generated the iodosylarene metalloporphyrin adducts and manganese(V)-oxo porphyrin species as a cytochrome P450 analogue and studied the mechanism of OAT with cis-stibene using UV-visble and ESI–MS analysis [157]. Interestingly, Goldberg activated the high-valent MnV=O species of corrolazine using non-metallic lewis acid and axial coordination of the anions for the high reactivity towards thioether substrates [158, 159]. Interestingly, Neumann observed the formation of O2 in water catalysed by a polyfluorooxometallate with Mn(IV)-OH and Mn(V)-OH center confirmed by EXAFS measurement [160]. Recently, Nam group successfully generated the mononuclear non-heme manganese(V)–oxo complex [MnV(O)(TAML)] synthesized by activating dioxygen in the presence of olefins with weak allylic C–H bonds confirmed by various spectroscopic and crystallographic analysis. Also, they studied the interaction of a Mn(V)–oxo complex with Sc3+ ion and found that the binding site of the Sc3+ ion is TAML ligand not the Mn–O moiety [161]. Hayashi group studied the myoglobin reconstituted with a manganese porphycene and found that the engineered myoglobin serves as an artificial metalloenzyme for inert C–H bond activation such as oxidation of ethyl benzene via a high-valent MnV=O species similar to the species employed by native monooxygenases such as cytochrome P450A [162]. Very recently, Goldberg reported the hydrogen atom transfer reactivity of the MnV=O species with phenol and also they identified the generation of MnIV-OH species in the pathway of formation of the final Mn(III)-OH2 complex by abstraction of stepwise abstraction of two hydrogen atoms [163].

Table 2 List of MnV = O species generated and characterised with different ligands

Conclusion and perspectives

In this review, recent developments in natural systems operating high-valent Mn-oxygen intermediates for the catalytic reactions are focussed and how their inspiration are realised in nano and molecular levels are discussed. In OEC and ribonucleotide reductases high-valent Mn-oxo intermediate catalyse the O–O bond formation or radical generation respectively. In both the natural catalysts the active sites are stabilised by ligands from protein side chains which dictate the overall mechanism and stabilise the high-valent Mn-oxo intermediates to achieve the high activity and selectivity of the reaction. Inspired from these processes, as presented in the review several artificial systems have been synthesised and utilised for different oxidation reactions in which the oxygen atom transfer (OAT) or hydrogen atom transfer (HAT) mechanism is suggested. However, the stability and selectivity of the synthetic complexes are necessarily to be improved to overcome the stability issues and its catalytic function to the level of industrial production of energy and other organic materials. Inspired from the natural system, the heterobimetallic approach should be considered to induce high-level distortion in the active site to mimicking the function of the OEC and should be extended to various oxidation reactions. Only MnIV=O species are realised in nano particles however OEC complex using either MnIV-O· or MnV=O species for the O–O bond formation. So the realisation of these species and use of MnIV=O or MnV=O species for various OAT and HAT reactions on the manganese oxide nano particles should be considered, so that the strategies learned from the natural systems to be successfully applied for the real application of the mankind.


  1. 1.

    V.L. Pecoraro, M.J. Baldwin, A. Gelasco, Interaction of manganese with dioxygen and its reduced derivatives. Chem. Rev. 94, 807–826 (1994)

    Article  CAS  Google Scholar 

  2. 2.

    R. Manchanda, G.W. Brudvig, R.H. Crabtreee, High-valentoxomanganese clusters: structural and mechanistic work relevant to the oxygen-evolving center in photosystem II. Coord. Chem. Rev. 144, 1–38 (1995)

    Article  CAS  Google Scholar 

  3. 3.

    G.C. Dismukes, Manganese enzymes with binuclear active sites. Chem. Rev. 96, 2909–2926 (1996)

    Article  CAS  Google Scholar 

  4. 4.

    C.F. Yocum, V.L. Pecoraro, Recent advances in the understanding of the biological chemistry of manganese. Curr. Opin. Chem. Biol. 3, 182–187 (1999)

    Article  CAS  Google Scholar 

  5. 5.

    W. Zhu, N.G.J. Richards, Biological functions controlled by manganese redox changes in mononuclear Mn-dependent enzyme. Essays Biochem. 61, 259–270 (2017)

    Article  Google Scholar 

  6. 6.

    D.F. Leto, T.A. Jackson, Peroxomanganese complexes as an aid to understanding redox-active manganese enzymes. J. Biol. Inorg. Chem. 19, 1–15 (2014)

    Article  CAS  Google Scholar 

  7. 7.

    V.K. Yachandra, S.K. Klein, Manganese cluster in photosynthesis: where plants oxidize water to dioxygen. Chem. Rev. 96, 2927–2950 (1996)

    Article  CAS  Google Scholar 

  8. 8.

    J.P. McEvoy, G.W. Brudvig, Water-splitting chemistry of photosystem II. Chem. Rev. 106, 4455–4483 (2006)

    Article  CAS  Google Scholar 

  9. 9.

    N. Cox, J. Messinger, Reflections on substrate water and dioxygen formation. Biochim. Biophys. Acta 1827, 1020–1030 (2013)

    Article  CAS  Google Scholar 

  10. 10.

    N. Cox, D.A. Pantazis, F. Neese, W. Lubitz, Biological water oxidation. Acc. Chem. Res. 46, 1588–1596 (2013)

    Article  CAS  Google Scholar 

  11. 11.

    J. Yano, V. Yachandra, Mn4Ca cluster in photosynthesis: where and how water is oxidized to dioxygen. Chem. Rev. 114, 4175–4205 (2014)

    Article  CAS  Google Scholar 

  12. 12.

    J.R. Shen, The structure of photosystem II and the mechanism of water oxidation in photosynthesis. Annu. Rev. Plant Biol. 66, 23–48 (2015)

    Article  CAS  Google Scholar 

  13. 13.

    M. Perez-Navarro, N.F. Lubitz, D.A. Pantazis, N. Cox, Recent developments in biological water oxidation. Curr. Opin. Chem. Biol. 31, 113–119 (2016)

    Article  CAS  Google Scholar 

  14. 14.

    D.J. Vinyard, Brudvig progress toward a molecular mechanism of water oxidation in photosystem II. Annu. Rev. Phys. Chem. 68, 101–116 (2017)

    Article  CAS  Google Scholar 

  15. 15.

    A. Jordan, P. Reichard, Ribonucleotide reductases. Annu. Rev. Biochem. 67, 71–98 (1998)

    Article  CAS  Google Scholar 

  16. 16.

    A. Willing, H. Follmann, G. Auling, Ribonucleotide reductase of brevibacterium-ammoniagenes is a manganese enzyme. Eur. J. Biochem. 170, 603–611 (1996)

    Article  Google Scholar 

  17. 17.

    Y. Huque, F. Fieschi, E. Torrents, I. Gibert, R. Eliasson, The active form of the R2F protein of class Ib ribonucleotide reductase from Corynebacterium ammoniagenes is a diferric protein. J. Biol. Chem. 275, 25365–25371 (2000)

    Article  CAS  Google Scholar 

  18. 18.

    P. Nordlund, P. Reichard, Ribonucleotide reductases. Annu. Rev. Biochem. 75, 681–706 (2006)

    Article  CAS  Google Scholar 

  19. 19.

    W. Jiang, L.M. Hoffart, C. Krebs, J.M. Bollinger, Amanganese(IV)/iron(IV) intermediate in assembly of the manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase. Biochemistry 46, 8709–8716 (2007)

    Article  CAS  Google Scholar 

  20. 20.

    W. Jiang, D. Yun, L. Saleh, E.W. Barr, G. Xing, L.M. Hoffart, M.A. Maslak, C. Krebs, J.M. Bollinger, A manganese(IV)/iron(III) cofactor in chlamydia trachomatis ribonucleotide reductase. Science 316, 1188–1191 (2007)

    Article  CAS  Google Scholar 

  21. 21.

    W. Jiang, J.M. Bollinger, C. Krebs, The active form of chlamydia trachomatis ribonucleotide reductase R2 protein contains a heterodinuclear Mn(IV)/Fe(III) cluster with S = 1 ground state. J. Am. Chem. Soc. 129, 7504–7505 (2007)

    Article  CAS  Google Scholar 

  22. 22.

    N. Voevodskaya, F. Lendzian, A. Ehrenberg, A. Graslund, A High catalytic activity achieved with a mixed manganese-iron site in protein R2 of Chlamydia ribonucleotide reductase. FEBS Lett. 581, 3351–3355 (2007)

    Article  CAS  Google Scholar 

  23. 23.

    A.K. Boal, J.A. Cotruvo, J. Stubbe, A.C. Rosenzweig, Structural basis for activation of class Ib ribonucleotide reductase. Science 329, 1526–1530 (2010)

    Article  CAS  Google Scholar 

  24. 24.

    J.A. Cotruvo, J. Stubbe, An active dimanganese(III)-tyrosyl radical cofactor in Escherichia coli class Ib ribonucleotide reductase. Biochemistry 49, 1297–1309 (2010)

    Article  CAS  Google Scholar 

  25. 25.

    N. Cox, H. Ogata, P. Stolle, E. Reijerse, G. Auling, A tyrosyl dimanganese coupled spin system is the native metalloradical cofactor of the R2F subunit of the ribonucleotide reductase of Corynebacterium ammoniagenes. J. Am. Chem. Soc. 132, 11197–11213 (2010)

    Article  CAS  Google Scholar 

  26. 26.

    Y. Zhang, J. Stubbe, Bacillus subtilis class Ib ribonucleotide reductase is a dimanganese(III)-tyrosyl radical enzyme. Biochemistry 50, 5615–5623 (2011)

    Article  CAS  Google Scholar 

  27. 27.

    A.B. Tomter, G. Zoppellaro, C.B. Bell, A.L. Barra, N.H. Andersen, Spectroscopic studies of the iron and manganese reconstituted tyrosyl radical in Bacillus Cereus ribonucleotide reductase R2 protein. PLoS ONE 7, e33436 (2012)

    Article  CAS  Google Scholar 

  28. 28.

    O. Makhlynets, A.K. Boal, D.V. Rhodes, T. Kitten, A.C. Rosenzweig, J. Stubbe, Streptococcus sanguinis class Ib ribonucleotide reductase high activity with both iron and manganese cofactors and structural insights. J. Biol. Chem. 289, 6259–6272 (2014)

    Article  CAS  Google Scholar 

  29. 29.

    A. Zouni, H.T. Witt, J. Kern, P. Fromme, N. Krauss, W. Saenger, P. Orth, Crystal structure of photosystem II from Synechococcus elongatus at 3.8 Å resolution. Nature 409, 739–743 (2001)

    Article  CAS  Google Scholar 

  30. 30.

    K.N. Ferreira, T.M. Iverson, K. Maghlaoui, J. Barber, S. Iwata, Architecture of the photosynthetic oxygen-evolving center. Science 303, 1831–1838 (2004)

    Article  CAS  Google Scholar 

  31. 31.

    B. Loll, J. Kern, W. Saenger, A. Zouni, J. Biesiadka, Towards complete cofactor arrangement in the 3.0 Å resolution structure of photosystem II. Nature 438, 1040–1044 (2005)

    Article  CAS  Google Scholar 

  32. 32.

    A. Guskov, J. Kern, A. Gabdulkhakov, M. Broser, A. Zouni, W. Saenger, Cyanobacterial photosystem II at 2.9-Å resolution and the role of quinones, lipids, channels and chloride. Nat. Struct. Mol. Biol. 16, 334–342 (2009)

    Article  CAS  Google Scholar 

  33. 33.

    K. Kawakami, Y. Umena, N. Kamiya, J.R. Shen, Location of chloride and its possible functions in oxygen-evolving photosystem II revealed by X-ray crystallography. Proc. Natl. Acad. Sci. USA 106, 8567–8572 (2009)

    Article  Google Scholar 

  34. 34.

    Y. Umena, K. Kawakami, J.R. Shen, N. Kamiya, Crystal structure of oxygen-evolving photosystem II at a resolution of 1.9 Å. Nature 473, 55–60 (2011)

    Article  CAS  Google Scholar 

  35. 35.

    N. Cox, M. Retegan, F. Neese, D.A. Pantazis, A. Boussac, W. Lubit, Electronic structure of the oxygen-evolving complex in photosystem II prior to O–O bond formation. Science 345, 804–808 (2004)

    Article  CAS  Google Scholar 

  36. 36.

    M. Suga, F. Akita, K. Hirata, G. Ueno, H. Murakami, Y. Nakajima, T. Shimizu, K. Yamashita, M. Yamamoto, H. Ago, J.R. Shen, Native structure of photosystem II at 1.95 Å resolution viewed by femtosecond X-ray pulses. Nature 517, 99–103 (2015)

    Article  CAS  Google Scholar 

  37. 37.

    B. Kok, B. Forbush, M. McGloin, Cooperation of charges in photosynthetic O2 evolution. I. A linear four step mechanism. Photochem. Photobiol. 11, 457–475 (1970)

    Article  CAS  Google Scholar 

  38. 38.

    D.J. Vinyard, G.M. Ananyev, G.C. Dismukes, Photosystem II: the reaction center of oxygenic photosynthesis. Annu. Rev. Biochem. 82, 577–606 (2013)

    Article  CAS  Google Scholar 

  39. 39.

    J. Yano, J. Kern, K.D. Irrgang, M.J. Latimer, U. Bergmann, X-ray damage to the Mn4Ca complex in single crystals of photosystem II: a case study for metalloprotein crystallography. Proc. Natl. Acad. Sci. 102, 12047–12052 (2005)

    Article  CAS  Google Scholar 

  40. 40.

    K.A. Åhrling, S. Peterson, S. Styring, An oscillating manganese electron paramagnetic resonance signal from the S0 state of the oxygen evolving complex in photosystem II. Biochemistry 36, 13148–13152 (1997)

    Article  Google Scholar 

  41. 41.

    J. Messinge, J.H.A. Nugent, M.C.W. Evans, Detection of an EPR multiline signal for the S0 state in photosystem II. Biochemistry 36, 11055–11060 (1997)

    Article  Google Scholar 

  42. 42.

    J. Messinger, J.H. Robblee, W.O. Yu, K. Sauer, V.K. Yachandra, M.P. Klein, The S0 state of the oxygen evolving complex in photosystem II is paramagnetic detection of an EPR multiline signal. J. Am. Chem. Soc. 119, 11349–11350 (1997)

    Article  CAS  Google Scholar 

  43. 43.

    D. Koulougliotis, D.J. Hirsh, G.W. Brudvig, The oxygen-evolving center of photosystem II is diamagnetic in the S1 resting state. J. Am. Chem. Soc. 114, 8322–8323 (1992)

    Article  CAS  Google Scholar 

  44. 44.

    E. Schlodder, H.T. Witt, Stoichiometry of proton release from the catalytic center in photosynthetic water oxidation: reexamination by a glass electrode study at pH 5.5–7.2. J. Biol. Chem. 274, 30387–30392 (1999)

    Article  CAS  Google Scholar 

  45. 45.

    D.A. Pantazis, W. Ames, N. Cox, W. Lubitz, F. Neese, Two interconvertible structures that explain the spectroscopic properties of the oxygen-evolving complex of photosystem II in the S2 state. Angew. Chem. Int. Ed. 51, 9935–9940 (2012)

    Article  CAS  Google Scholar 

  46. 46.

    J.L. Zimmermann, A.W. Rutherford, Electron paramagnetic resonance properties of the S2 state of the oxygen-evolving complex of photosystem II. Biochemistry 25, 4609–4615 (1986)

    Article  CAS  Google Scholar 

  47. 47.

    A.V. Astashkin, Y. Kodera, A. Kawamori, Pulsed EPR study of manganese g = 4.1 signal in plant photosystem II. J. Magn. Reson. Ser. B 105, 113–119 (1994)

    Article  CAS  Google Scholar 

  48. 48.

    A. Haddy, K.V. Lakshmi, G.W. Brudvig, H.A. Frank, Q-band EPR of the S2 state of photosystem II confirms an S = 5/2 origin of the X-band g = 4.1 signal. Biophys. J. 87, 2885–2896 (2004)

    Article  CAS  Google Scholar 

  49. 49.

    A. Haddy, EPR spectroscopy of the manganese cluster of photosystem II. Photosynth. Res. 92, 357–368 (2004)

    Article  CAS  Google Scholar 

  50. 50.

    R. Pokhrel, G.W. Brudvig, Oxygen-evolving complex of photosystem II: correlating structure with spectroscopy. Phys. Chem. Chem. Phys. 16, 11812–11821 (2014)

    Article  CAS  Google Scholar 

  51. 51.

    D.J. Vinyard, S. Khan, M. Askerka, V.S. Batista, G.W. Brudvig, Energetics of the S2 state spin isomers of the oxygen-evolving complex of photosystem II. J. Phys. Chem. B 121, 1020–1025 (2017)

    Article  CAS  Google Scholar 

  52. 52.

    D. Bovi, D. Narzi, L. Guidoni, The S2 state of the oxygen-evolving complex of photosystem II explored by QM/MM dynamics: spin surfaces and metastable states suggest a reaction path towards the S3 state. Angew. Chem. Int. Ed. 52, 11744–11749 (2013)

    Article  CAS  Google Scholar 

  53. 53.

    M. Shoji, H. Isobe, K. Yamaguchi, QM/MM study of the S2 to S3 transition reaction in the oxygenevolving complex of photosystem II. Chem. Phys. Lett. 636, 172–179 (2015)

    Article  CAS  Google Scholar 

  54. 54.

    M. Pérez Navarro, W.M. Ames, H. Nilsson, T. Lohmiller, D.A. Pantazis, L. Rapatskiy, M. Nowaczyk, F. Neese, A. Boussac, J. Messinger, W. Lubitz, N. Cox, Ammonia binding to the oxygen-evolving complex of photosystem ii identifies the solvent exchangeable oxygen bridge (μ-oxo) of the manganese tetramer. Proc. Natl. Acad. Sci. USA 110, 15561–15566 (2013)

    Article  Google Scholar 

  55. 55.

    P.H. Oyala, T.A. Stich, R.J. Debus, R.D. Britt, Ammonia binds to the dangler manganese of the photosystem II oxygen evolving complex. J. Am. Chem. Soc. 137, 8829–8837 (2015)

    Article  CAS  Google Scholar 

  56. 56.

    M. Askerka, D.J. Vinyard, G.W. Brudvig, V.S. Batista, NH3 binding to the S2 state of the O2-evolving complex of photosystem II: analogue to H2O binding during the S2 → S3 transition. Biochemistry 54, 5783–5786 (2015)

    Article  CAS  Google Scholar 

  57. 57.

    D.J. Vinyard, M. Askerka, R.J. Debus, V.S. Batista, G.W. Brudvig, Ammonia binding in the second coordination sphere of the oxygen-evolving complex of photosystem II. Biochemistry 55, 4432 (2016)

    Article  CAS  Google Scholar 

  58. 58.

    M. Askerka, G.W. Brudvig, V.S. Batista, The O2-evolving complex of photosystem II: recent insights from quantum mechanics/molecular mechanics (QM/MM), extended X-ray absorption fine structure (EXAFS), and femtosecond X-ray crystallography data. Acc. Chem. Res. 50, 41–48 (2017)

    Article  CAS  Google Scholar 

  59. 59.

    M. Capone, D. Narzi, D. Bovi, L. Guidoni, Mechanism of water delivery to the active site of photosystem II along the S2 to S3 transition. J. Phys. Chem. Lett. 7, 592–596 (2016)

    Article  CAS  Google Scholar 

  60. 60.

    P.E.M. Siegbahn, Water oxidation mechanism in photosystem II, including oxidations, proton release pathways, O–O bond formation and O2 release. Biochim. Biophys. Acta 1827, 1003–1019 (2013)

    Article  CAS  Google Scholar 

  61. 61.

    P.E.M. Siegbahn, O–O bond formation in the S4 state of the oxygen-evolving complex in photosystem II. Chem. Eur. J. 12, 9217–9227 (2006)

    Article  CAS  Google Scholar 

  62. 62.

    P.E.M. Siegbahn, Recent theoretical studies of water oxidation in photosystem II. J. Photochem. Photobiol. B 104, 94–99 (2011)

    Article  CAS  Google Scholar 

  63. 63.

    D.C. Ashley, M.-H. Baik, The electronic structure of [Mn(V)=O]: what is the connection between oxyl radical character, physical oxidation state, and reactivity? ACS Catal. 6, 7202–7216 (2016)

    Article  CAS  Google Scholar 

  64. 64.

    J. Barber, A mechanism for water splitting and oxygen production in photosynthesis. Nat. Plants 3, 17041 (2017)

    Article  CAS  Google Scholar 

  65. 65.

    E.M. Sproviero, J.A. Gascon, J.P. McEvoy, G.W. Brudvig, V.S. Batista, Quantum mechanics/molecular mechanics study of the catalytic cycle of water splitting in photosystem II. J. Am. Chem. Soc. 130, 3428–3442 (2008)

    Article  CAS  Google Scholar 

  66. 66.

    Y. Gao, T. Åkermark, J.H. Liu, L.C. Sun, B. Åkermark, Nucleophilic attack of hydroxide on a MnVoxo complex: a model of the O–O bond formation in the oxygen evolving complex of photosystem II. J. Am. Chem. Soc. 131, 8726–8727 (2009)

    Article  CAS  Google Scholar 

  67. 67.

    T. Taguchi, Preparation and properties of a monomeric high-spin MnV oxo complex. J. Am. Chem. Soc. 134, 1996–1999 (2012)

    Article  CAS  Google Scholar 

  68. 68.

    B.M. Sjöberg, A never-ending story. Science 329, 1475–1476 (2010)

    Article  CAS  Google Scholar 

  69. 69.

    V.V. Barynin, M.M. Whittaker, S.V. Antonyuk, V.S. Lamzin, P.M. Harrison, P.J. Artymiuk, J.W. Whittaker, Crystal structure of manganese catalase from Lactobacillus plantarum. Structure 9, 725–738 (2001)

    Article  CAS  Google Scholar 

  70. 70.

    A.B. Tomter, G. Zoppellaroa, N.H. Andersena, H.-P. Hersletha, M. Hammerstada, Å.K. Røhr, G.K. Sandvika, K.R. Stranda, G.E. Nilssona, C.B. Bell III, A.-L. Barrac, E. Blasco, L.L. Pape, E.I. Solomon, K.K. Andersson, Ribonucleotide reductase class I with different radical generating clusters. Coord. Chem. Rev. 257, 3–26 (2013)

    Article  CAS  Google Scholar 

  71. 71.

    J.M. Younker, C.M. Krest, W. Jiang, C. Krebs, J.M. Bollinger, M.T. Green, Structural analysis of the Mn(IV)/Fe(III) cofactor of chlamydia trachomatis ribonucleotide reductase by extended x-ray absorption fine structure spectroscopy and density functional theory calculation. J. Am. Chem. Soc. 130, 15022–15027 (2008)

    Article  CAS  Google Scholar 

  72. 72.

    N. Voevodskaya, F. Lendzian, O. Sanganas, A. Grundmeier, A. Graslund, M. Haumann, Redox intermediates of the Mn-Fe site in Subunit R2 of Chlamydia trachomatis ribonucleotide reductase a X-ray absorption and EPR study. J. Biol. Chem. 284, 4555–4566 (2009)

    Article  CAS  Google Scholar 

  73. 73.

    J.A. Cotruvo, J. Stubbe, Class I ribonucleotide reductases: metallocofactor assembly and repair in vitro and in vivo. Annu. Rev. Biochem. 80, 733–767 (2011)

    Article  CAS  Google Scholar 

  74. 74.

    C. Roshick, E.R. Iliffe-Lee, G. McClarty, Cloning and characterization of ribonucleotide reductase from Chlamydia trachomatis. J. Biol. Chem. 275, 38111–38119 (2000)

    Article  CAS  Google Scholar 

  75. 75.

    A. Graslund, P. Nordlund, The radical site in chlamydial ribonucleotide reductase defines a new R2 subclass. Science 305, 245–248 (2004)

    Article  CAS  Google Scholar 

  76. 76.

    W. Jiang, L. Saleh, E.W. Barr, J. Xie, M.M. Gardner, C. Krebs, J.M. Bollinger, Branched activation- and catalysis specific pathways for electron relay to the manganese/iron cofactor in ribonucleotide reductase from Chlamydia trachomatis. Biochemistry 47, 8477–8484 (2008)

    Article  CAS  Google Scholar 

  77. 77.

    W. Jiang, J. Xie, H. Nørgaard, J.M. Bollinger, C. Krebs, Rapid and quantitative activation of Chlamydia trachomatis ribonucleotide reductase by hydrogen peroxide. Biochemistry 47, 4477–4483 (2008)

    Article  CAS  Google Scholar 

  78. 78.

    J.M. Bollinger, W. Jiang, M.T. Green, C. Krebs, The manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase: structure, assembly, radical initiation, and evolution. Curr. Opin. Struct. Biol. 18, 650–657 (2008)

    Article  CAS  Google Scholar 

  79. 79.

    W. Jiang, D. Yun, L. Saleh, J.M. Bollinger, C. Krebs, Formation and function of the manganese(IV)/iron(III) cofactor in Chlamydia trachomatis ribonucleotide reductase. Biochemistry 47, 13736–13744 (2008)

    Article  CAS  Google Scholar 

  80. 80.

    C.S. Andersson, M. Öhrström, A. Popovic-Bijelic, A. Gra ́slund, P. Stenmark, M. Högbom, ́The manganese ion of the heterodinuclear Mn/Fe cofactor in Chlamydia trachomatis ribonucleotide reductase R2c is located at metal position. J. Am. Chem. Soc. 134, 123–125 (2012)

    Article  CAS  Google Scholar 

  81. 81.

    L.M.K. Dassama, A.K. Boal, C. Krebs, A.C. Rosenzweig, J.M. Bollinger, Evidence that the beta subunit of Chlamydia trachomatis ribonucleotide reductase is active with the manganese ion of its manganese(IV)/iron(III) cofactor in site. J. Am. Chem. Soc. 134, 2520–2523 (2012)

    Article  CAS  Google Scholar 

  82. 82.

    L.M.K. Dassama, C. Krebs, J.M. Bollinger, A.C. Rosenzweig, A.K. Boal, Structural basis for assembly of the Mn(IV)/Fe(III) cofactor in the class Ic ribonucleotide reductase from Chlamydia trachomatis. Biochemistry 52, 6424–6436 (2013)

    Article  CAS  Google Scholar 

  83. 83.

    Y. Kwak, W. Jiang, L.M.K. Dassama, K. Park, C.B. Bell, L.V. Liu, S.D. Wong, M. Saito, Y. Kobayashi, S. Kitao, M. Seto, Y. Yoda, E. Ercan Alp, J. Zhao, J.M. Bollinger, C. Krebs, E.I. Solomon, Geometric and electronic structure of the Mn(IV)Fe(III) cofactor in class Ic ribonucleotide reductase: correlation to the class ia binuclear non-heme iron enzyme. J. Am. Chem. Soc. 135, 17573–17584 (2013)

    Article  CAS  Google Scholar 

  84. 84.

    H.S. Shafaat, J.J. Griese, D.A. Pantazis, K. Roos, C.S. Andersson, A. Povic-Bijelic, A. Graslund, P.E.M. Siegbahn, F. Neese, W. Lubitz, M. Högbom, N. Cox, ́Electronic structural flexibility of heterobimetallic Mn/Fe cofactors: R2lox and R2c proteins. J. Am. Chem. Soc. 136, 13399–13409 (2014)

    Article  CAS  Google Scholar 

  85. 85.

    J. Livada, R.J. Martinie, L.M.K. Dassama, C. Krebs, J.M. Bollinger, A. Silakov, Direct measurement of the radical translocation distance in the class I ribonucleotide reductase from Chlamydia trachomatis. J. Phys. Chem. B 119, 13777–13784 (2015)

    Article  CAS  Google Scholar 

  86. 86.

    R.J. Martinie, E.J. Blaesi, C. Krebs, J.M. Bollinger, A. Silakov, C.J. Pollock, Evidence for a di-μ-oxo diamond core in the Mn(IV)/Fe(IV) activation intermediate of ribonucleotide reductase from Chlamydia trachomatis. J. Am. Chem. Soc. 139, 1950–1957 (2017)

    Article  CAS  Google Scholar 

  87. 87.

    K.R. Rose, M.K. Ghosh, A.O. Maggiolo, C.J. Pollock, E.J. Blaesi, V. Hajj, Y. Wei, L.J. Rajakovich, W. Chang, Y. Han, M. Hajj, C. Krebs, A. Silakov, M.E. Pandelia, J.M. Bollinger, A.K. Boal, Structural basis for superoxide activation of Flavobacterium johnsoniae class I ribonucleotide reductase and for radical initiation by its dimanganese cofactor. Biochemistry. (2018).

    Article  Google Scholar 

  88. 88.

    M.M. Najafpour, T. Ehrenberg, M. Wiechen, P. Kurz, Calcium manganese(III) oxides (CaMn2O4·xH2O) as biomimetic oxygen-evolving catalysts. Angew. Chem. Int. Ed. 49, 2233–2237 (2010)

    Article  CAS  Google Scholar 

  89. 89.

    Y. Gorlin, T.F. Jaramillo, A bifunctional nonprecious metal catalyst for oxygen reduction and water oxidation. J. Am. Chem. Soc. 132, 13612–13614 (2010)

    Article  CAS  Google Scholar 

  90. 90.

    Y. Gorlin, B.L. Kaiser, J.D. Benck, S. Gul, S.M. Webb, V.K. Yachandra, J. Yano, T.F. Jaramillo, In situ X-ray absorption spectroscopy investigation of a bifunctional manganese oxide catalyst with high activity for electrochemical water oxidation and oxygen reduction. J. Am. Chem. Soc. 135, 8525–8534 (2013)

    Article  CAS  Google Scholar 

  91. 91.

    Y. Gorlin, C.J. Chung, J.D. Benck, D. Nordlund, L. Seitz, T.C. Weng, D. Sokaras, B.M. Clemens, T.F. Jaramillo, Understanding interactions between manganese oxide and gold that lead to enhanced activity for electrocatalytic water oxidation. J. Am. Chem. Soc. 136, 4920–4926 (2014)

    Article  CAS  Google Scholar 

  92. 92.

    C.H. Kuo, W. Li, L. Pahalagedara, A.M.E. Sawy, D. Kriz, N. Genz, C. Guild, T. Ressler, S.L. Suib, J. He, Understanding the role of gold nanoparticles in enhancing the catalytic activity of manganese oxides in water oxidation reactions. Angew. Chem. Int. Ed. 54, 2345–2350 (2015)

    Article  CAS  Google Scholar 

  93. 93.

    I. Zaharieva, P. Chernev, M. Risch, K. Klingan, M. Kohlhoff, A. Fischer, H. Dau, Electrosynthesis functional, and structural characterization of a water-oxidizing manganese oxide. Energy Environ. Sci. 5, 7081–7089 (2012)

    Article  CAS  Google Scholar 

  94. 94.

    N. Birkner, S. Nayeri, B. Pashaei, M.M. Najafpour, W.H. Casey, A. Navrotsky, Energetic basis of catalytic activity of layered nanophase calcium manganese oxides for water oxidation. Proc. Natl. Acad. Sci. USA. 110, 8801–8806 (2013)

    Article  Google Scholar 

  95. 95.

    M. Huynh, C. Shi, S.J. Billinge, D.G. Nocera, Nature of activated manganese oxide for oxygen evolution. J. Am. Chem. Soc. 137, 14887–14904 (2015)

    Article  CAS  Google Scholar 

  96. 96.

    A. Indra, P.W. Menezes, I. Zaharieva, E. Baktash, J.P. Frommer, M. Schwarze, H. Dau, M. Driess, Active mixed-valent MnOx water oxidation catalysts through partial oxidation (corrosion) of nanostructured MnO particles. Angew. Chem. Int. Ed. 52, 13206–13210 (2013)

    Article  CAS  Google Scholar 

  97. 97.

    P.W. Menezes, A. Indra, P. Littlewood, M. Schwarze, C. Göbel, R. Schomäcker, M. Driess, Nanostructured manganese oxides as highly active water oxidation catalysts: a boost from manganese precursor chemistry. Chem. Sus. Chem. 7, 2202–2211 (2014)

    Article  CAS  Google Scholar 

  98. 98.

    C. Walter, P.W. Menezes, S. Orthmann, J. Schuch, P. Connor, B. Kaiser, M. Lerch, M. Driess, A molecular approach to manganese nitride acting as a high performance electrocatalyst in the oxygen evolution reaction. Angew. Chem. Int. Ed. 57, 698–702 (2018)

    Article  CAS  Google Scholar 

  99. 99.

    Y. Kim, J.H. Lee, H. Ha, S.W. Im, K.T. Nam, Material science lesson from the biological photosystem. Nano Convergence 3, 19 (2016)

    Article  CAS  Google Scholar 

  100. 100.

    J. Park, H. Kim, K. Jin, B.J. Lee, Y.S. Park, H. Kim, I. Park, K.D. Yang, H.Y. Jeong, J. Kim, K.T. Hong, H.W. Jang, K. Kang, K.T. Nam, A New water oxidation catalyst: lithium manganese pyrophosphate with tunable Mn valency. J. Am. Chem. Soc. 136, 4201–4211 (2014)

    Article  CAS  Google Scholar 

  101. 101.

    K. Jin, J. Park, J. Lee, K.D. Yang, G.K. Pradhan, U. Sim, D. Jeong, H. Jang, S. Park, D. Kim, N. Sung, S.H. Kim, S. Han, K.T. Nam, Hydrated manganese (II) phosphate (Mn3(PO4)2·3H2O) as a water oxidation catalyst. J. Am. Chem. Soc. 136, 7435–7443 (2014)

    Article  CAS  Google Scholar 

  102. 102.

    K. Jin, A. Chu, J. Park, D. Jeong, S.E. Jerng, U. Sim, H.-Y. Jeong, C.W. Lee, Y.-S. Park, K.D. Yang, G.K. Pradhan, D. Kim, N. Sung, S.H. Kim, K.T. Nam, Partially oxidized sub-10 nm MnO nanocrystals with high activity for water oxidation catalysis. Sci. Rep. 5, 10279 (2015)

    Article  Google Scholar 

  103. 103.

    D. Jeong, K. Jin, S.E. Jerng, H. Seo, D. Kim, S.H. Nahm, S.H. Kim, K.T. Nam, Mn5O8 nanoparticles as efficient water oxidation catalysts at neutral pH. ACS Catal. 5, 4624–4628 (2015)

    Article  CAS  Google Scholar 

  104. 104.

    K. Jin, H. Seo, H. Ha, Y. Kim, K.H. Cho, J.S. Hong, K.T. Nam, Recent advances in heterogeneous Mn-based electrocatalysts toward biological photosynthetic Mn4Ca cluster. Catal. Today (2016).

    Article  Google Scholar 

  105. 105.

    K. Jin, H. Seo, T. Hayashi, M. Balamurugan, D. Jeong, Y.K. Go, J.S. Hong, K.H. Cho, H. Kakizaki, N. Bonnet-Mercier, M.G. Kim, S.H. Kim, R. Nakamura, K.T. Nam, Mechanistic investigation of water oxidation catalyzed by uniform, assembled MnO nanoparticles. J. Am. Chem. Soc. 139, 2277–2285 (2016)

    Article  CAS  Google Scholar 

  106. 106.

    H. Seo, S. Park, J.S. Hong, K.H. Cho, H. Ha, K. Jin, K.T. Nam, Water oxidation mechanism for 3d transition metal oxide catalysts under neutral condition. J. Korean Ceram. Soc. 54, 1–8 (2017)

    Article  CAS  Google Scholar 

  107. 107.

    J.T. Groves, M.K. Stern, Synthesis, characterization, and reactivity of oxomanganese(IV) porphyrin complexes. J. Am. Chem. Soc. 110, 8628–8638 (1988)

    Article  CAS  Google Scholar 

  108. 108.

    R.S. Czernuszewicz, Y.O. Su, M.K. Stern, K.A. Macor, D. Kim, J.T. Groves, T.G. Spiro, Oxomanganese(IV) porphyrins identified by resonance Raman and infrared spectroscopy. Weak bonds and the stability of the half-filled t2g subshell. J. Am. Chem. Soc. 110, 4158–4165 (1988)

    Article  CAS  Google Scholar 

  109. 109.

    R.D. Arasasingham, G.X. He, T.C. Bruice, Mechanism of manganese porphyrin-catalyzed oxidation of alkenes. Role of manganese(IV)-oxo species. J. Am. Chem. Soc. 115, 7985–7991 (1993)

    Article  CAS  Google Scholar 

  110. 110.

    K.P. Bryliakov, D.E. Babushkin, E.P. Talsi, 1H NMR and EPR spectroscopic monitoring of the reactive intermediates of (Salen)MnIII catalyzed olefin epoxidation. J. Mol. Cat. A Chem. 158, 19–35 (2000)

    Article  CAS  Google Scholar 

  111. 111.

    K.P. Bryliakov, O.A. Kholdeeva, M.P. Vanina, E.P. Talsi, Role of MnIV species in Mn(salen) catalyzed enantioselective aerobic epoxidations of alkenes: an EPR study. J. Mol. Cat A Chem. 178, 47–53 (2002)

    Article  CAS  Google Scholar 

  112. 112.

    G. Yin, M. Buchalova, A.M. Danby, C.M. Perkins, D. Kitko, J.D. Carter, W.M. Scheper, D.H. Busch, Olefin oxygenation by the hydroperoxide adduct of a nonheme manganese(IV) complex: epoxidations by a metallo–peracid produces gentle selective oxidations. J. Am. Chem. Soc. 127, 17170–17171 (2005)

    Article  CAS  Google Scholar 

  113. 113.

    G. Yin, A.M. Danby, D. Kitko, J.D. Carter, W.M. Scheper, D.H. Busch, Olefin epoxidation by alkyl hydroperoxide with a novel cross-bridged cyclam manganese complex: demonstration of oxygenation by two distinct reactive intermediates. Inorg. Chem. 46, 2173–2180 (2007)

    Article  CAS  Google Scholar 

  114. 114.

    G. Yin, A.M. Danby, D. Kitko, J.D. Carter, W.M. Scheper, D.H. Busch, Understanding the selectivity of a moderate oxidation catalyst: hydrogen abstraction by a fully characterized, activated catalyst, the robust dihydroxo manganese(IV) complex of a bridged cyclam. J. Am. Chem. Soc. 129, 1512–1513 (2007)

    Article  CAS  Google Scholar 

  115. 115.

    G. Yin, A.M. Danby, D. Kitko, J.D. Carter, W.M. Scheper, D.H. Busch, Oxidative reactivity difference among the metal oxo and metal hydroxo moieties: pH dependent hydrogen abstraction by a manganese(IV) complex having two hydroxide ligands. J. Am. Chem. Soc. 130, 16245–16253 (2008)

    Article  CAS  Google Scholar 

  116. 116.

    S.H. Kim, H. Park, M.S. Seo, M. Kubo, T. Ogura, J. Klajn, D.T. Gryko, J.S. Valentine, W. Nam, Reversible O–O bond cleavage and formation between Mn(IV)-peroxo and Mn(V)-oxo corroles. J. Am. Chem. Soc. 132, 14030–14032 (2010)

    Article  CAS  Google Scholar 

  117. 117.

    S.C. Sawant, X. Wu, J. Cho, K.-B. Cho, S.H. Kim, M.S. Seo, Y.-M. Lee, M. Kubo, T. Ogura, S. Shaik, W. Nam, Water as an oxygen source: synthesis, characterization, and reactivity studies of a mononuclear nonheme manganese(IV) oxo complex. Angew. Chem. Int. Ed. 49, 8190–8194 (2010)

    Article  CAS  Google Scholar 

  118. 118.

    I. Garcia-Bosch, A. Company, C.W. Cady, S. Styring, W.R. Browne, X. Ribas, M. Costas, Evidence for a precursor complex in C–H hydrogen atom transfer reactions mediated by a manganese(IV) oxo complex. Angew. Chem. Int. Ed. 50, 5648–5653 (2011)

    Article  CAS  Google Scholar 

  119. 119.

    I. Garcia-Bosch, A. Company, X. Fontrodona, X. Ribas, M. Costas, Efficient and selective peracetic acid epoxidation catalyzed by a robust manganese catalyst. Org. Lett. 10, 2095–2098 (2008)

    Article  CAS  Google Scholar 

  120. 120.

    X. Wu, M.S. Seo, K.M. Davis, Y.-M. Lee, J. Chen, K.-B. Cho, Y.N. Pushkar, W. Nam, A highly reactive mononuclear non-heme manganese(IV)–Oxo complex that can activate the strong C–H bonds of alkanes. J. Am. Chem. Soc. 133, 20088–20091 (2011)

    Article  CAS  Google Scholar 

  121. 121.

    S. Kim, K.-B. Cho, Y.-M. Lee, J. Chen, S. Fukuzumi, W. Nam, Factors controlling the chemoselectivity in the oxidation of olefins by nonheme manganese(IV)-oxo complexes. J. Am. Chem. Soc. 138, 10654–10663 (2016)

    Article  CAS  Google Scholar 

  122. 122.

    N. Sharma, J. Jung, Y.-M. Lee, M.S. Seo, W. Nam, S. Fukuzumi, Multi-electron oxidation of anthracene derivatives by nonheme manganese(IV)-oxo complexes. Chem. Eur. J. 23, 7125–7131 (2017)

    Article  CAS  Google Scholar 

  123. 123.

    H. Yoon, Y. Morimoto, Y.-M. Lee, W. Nam, S. Fukuzumi, Electron-transfer properties of a nonheme manganese(iv)–oxo complex acting as a stronger one-electron oxidant than the iron(iv)–oxo analogue. Chem. Commun. 48, 11187 (2012)

    Article  CAS  Google Scholar 

  124. 124.

    J. Chen, Y.-M. Lee, K.M. Davis, X. Wu, M.S. Seo, K.-B. Cho, H. Yoon, Y.J. Park, S. Fukuzumi, Y.N. Pushkar, W. Nam, A mononuclear non-heme manganese(IV)-oxo complex binding redox-inactive metal ions. J. Am. Chem. Soc. 135, 6388–6391 (2013)

    Article  CAS  Google Scholar 

  125. 125.

    H. Yoon, Y.-M. Lee, X. Wu, K.-B. Cho, R. Sarangi, W. Nam, S. Fukuzumi, Enhanced electron-transfer reactivity of nonheme manganese(IV)-oxo complexes by binding scandium ions. J. Am. Chem. Soc. 135, 9186–9194 (2013)

    Article  CAS  Google Scholar 

  126. 126.

    R.V. Ottenbacher, K.P. Bryliakov, E.P. Talsi, Nonheme manganese-catalyzed asymmetric oxidation. A Lewis acid activation versus oxygen rebound mechanism: evidence for the “Third Oxidant”. Inorg. Chem. 49, 8620–8628 (2010)

    Article  CAS  Google Scholar 

  127. 127.

    J.W. de Boer, W.R. Browne, J. Brinksma, P.L. Alsters, R. Hage, B.L. Feringa, Mechanism of Cis-dihydroxylation and epoxidation of alkenes by highly H2O2 efficient dinuclear manganese catalysts. Inorg. Chem. 46, 6353–6372 (2007)

    Article  CAS  Google Scholar 

  128. 128.

    J.W. de Boer, W.R. Browne, S.R. Harutyunyan, L. Bini, T.D. Tiemersma-Wegman, P.L. Alsters, R. Hage, B.L. Feringa, Manganese catalysed asymmetric cis-dihydroxylation with H2O2. Chem. Commun. 32, 3747–3749 (2008)

    Article  CAS  Google Scholar 

  129. 129.

    Z. Lv, C. Choe, Y. Wu, H. Wang, Z. Chen, G. Li, G. Yin, Non-redox metal ions accelerated oxygen atom transfer by Mn-Me3tacn complex with H2O2 as oxygen resource. Mol. Catal. 448, 46–52 (2018)

    Article  CAS  Google Scholar 

  130. 130.

    S.H. Lee, L. Xu, B.K. Park, Y.V. Mironov, S.H. Kim, Y.J. Song, C. Kim, Y. Kim, S.-J. Kim, Efficient olefin epoxidation by robust Re 4 cluster-supported MnIII complexes with per acids: evidence of simultaneous operation of multiple active oxidant species, MnV=O, MnIV=O, and MnIII-OOC(O)R. Chem. Eur. J. 16, 4678–4685 (2010)

    Article  CAS  Google Scholar 

  131. 131.

    C. Choe, L. Yang, Z. Lv, W. Mo, Z. Chen, G. Li, G. Yin, Redox-inactive metal ions promoted the catalytic reactivity of non-heme manganese complexes towards oxygen atom transfer. Dalton Trans. 44, 9182–9192 (2015)

    Article  CAS  Google Scholar 

  132. 132.

    K.W. Kwong, T.-H. Chen, W. Luo, H. Jeddi, R. Zhang, A biomimetic oxidation catalyzed by manganese(III) porphyrins and iodobenzene diacetate: synthetic and mechanistic investigations. Inorg. Chim. Acta 430, 176–183 (2015)

    Article  CAS  Google Scholar 

  133. 133.

    W. Dai, S. Shang, Y. Lv, G. Li, C. Li, S. Gao, Highly chemoselective and enantioselective catalytic oxidation of heteroaromatic sulfides via high-valent manganese(IV)-oxo cation radical oxidizing intermediates. ACS Catal. 7, 4890–4895 (2017)

    Article  CAS  Google Scholar 

  134. 134.

    G.B. Shul’pin, D.S. Nesterov, L.S. Shul’pina, A.J.L. Pombeiro, A hydroperoxo-rebound mechanism of alkane oxidation with hydrogen peroxide catalyzed by binuclear manganese(IV) complex in the presence of an acid with involvement of atmospheric dioxygen. Inorg. Chim. Acta. 455, 666–676 (2017)

    Article  CAS  Google Scholar 

  135. 135.

    D. Mondal, M.C. Majee, Synthesis and structural characterization of a new high-valentbis(oxo)-bridged manganese(IV) complex and its catechol oxidase activity. Inorg. Chim. Acta 465, 70–77 (2017)

    Article  CAS  Google Scholar 

  136. 136.

    K. Srinivasan, P. Michaud, J.K. Kochi, Epoxidation of olefins with cationic (salen)manganese(III) complexes. The modulation of catalytic activity by substituents. J. Am. Chem. Soc. 108, 2309–2320 (1986)

    Article  CAS  Google Scholar 

  137. 137.

    T.J. Collins, S.W. Gordon-Wylie, A manganese(V)-oxo complex. J. Am. Chem. Soc. 111, 4511–4513 (1989)

    Article  CAS  Google Scholar 

  138. 138.

    T.J. Collins, R.D. Powell, C. Slebodnick, E.S. Uffelman, A water-stable manganese(V)-oxo complex: definitive assignment of a nu.Mnv.tplbond.O infrared vibration. J. Am. Chem. Soc. 112, 899–901 (1990)

    Article  CAS  Google Scholar 

  139. 139.

    W. Zhang, J.L. Loebach, S.R. Wilson, E.N. Jacobsen, Enantioselective epoxidation of unfunctionalized olefins catalyzed by salen manganese complexes. J. Am. Chem. Soc. 112, 2801–2803 (1990)

    Article  CAS  Google Scholar 

  140. 140.

    J.M. Workman, R.D. Powell, A.D. Procyk, T.J. Collins, D.F. Bocian, Vibrational and electrochemical properties of a series of stable manganese(V)-oxo complexes. Inorg. Chem. 31, 1548–1550 (1992)

    Article  CAS  Google Scholar 

  141. 141.

    F.M. MacDonnell, N.L.P. Fackler, C. Stern, T.V. O'Halloran, Air oxidation of a five-coordinate Mn(III) dimer to a high-valent oxomanganese(V) complex. J. Am. Chem. Soc. 116, 7431–7432 (1994)

    Article  CAS  Google Scholar 

  142. 142.

    J.T. Groves, J. Lee, S.S. Marla, Detection and characterization of an oxomanganese(V) porphyrin complex by rapid-mixing stopped-flow spectrophotometry. J. Am. Chem. Soc. 119, 6269–6273 (1997)

    Article  CAS  Google Scholar 

  143. 143.

    D. Feichtinger, D.A. Plattner, Direct proof for O=MnV(salen) complexes. Angew. Chem. Int. Ed. 36, 1718–1719 (1997)

    Article  CAS  Google Scholar 

  144. 144.

    C.G. Miller, S.W. Gordon-Wylie, C.P. Horwitz, S.A. Strazisar, D.K. Peraino, G.R. Clark, S.T. Weintraub, T.J. Collins, A method for driving O-atom transfer: secondary ion binding to a tetraamide macrocyclic ligand. J. Am. Chem. Soc. 120, 11540–11541 (1998)

    Article  CAS  Google Scholar 

  145. 145.

    N. Jin, J.T. Groves, Unusual kinetic stability of a ground-state singlet oxomanganese(V) porphyrin. Evidence for a spin state crossing effect. J. Am. Chem. Soc. 121, 2923–2924 (1999)

    Article  CAS  Google Scholar 

  146. 146.

    N. Jin, J.L. Bourassa, S.C. Tizio, J.T. Groves, Reversible oxygen atom transfer between an oxomanganese(v) porphyrin and bromide: a haloperoxidase mimic with enzymatic rates. Angew. Chem. Int. Ed. 39, 3849–3851 (2000)

    Article  CAS  Google Scholar 

  147. 147.

    W. Nam, I. Kim, M.H. Lim, H.J. Choi, J.S. Lee, H.G. Jang, Isolation of an oxomanganese(V) porphyrin intermediate in the reaction of a manganese(III) porphyrin complex and H2O2 in aqueous solution. Chem. Eur. J. 8, 2067–2071 (2002)

    Article  CAS  Google Scholar 

  148. 148.

    B.C. Gilbert, J.R.L. Smith, A.M.I. Payeras, J. Oakes, Formation and reaction of O=MnV species in the oxidation of phenolic substrates with H2O2 catalysed by the dinuclearmanganese(IV) 1,4,7-trimethyl-1,4,7-triazacyclononane complex [\({\text{Mn}}_{2}^{\text{IV}}\)(μ-O)3(TMTACN)2](PF6)2. Org. Biomol. Chem. 2, 1176–1180 (2004)

    Article  CAS  Google Scholar 

  149. 149.

    J.P. Collman, L. Zeng, J.I. Brauman, Donor ligand effect on the nature of the oxygenating species in MnIII (salen)-catalyzed epoxidation of olefins: experimental evidence for multiple active oxidants. Inorg. Chem. 43, 2672–2679 (2004)

    Article  CAS  Google Scholar 

  150. 150.

    S.H. Wang, B.S. Mandimutsira, R. Todd, B. Ramdhanie, J.P. Fox, D.P. Goldberg, Catalytic sulfoxidation and epoxidation with a Mn(III) triazacorrole: evidence for a “Third Oxidant” in high-valent porphyrinoid oxidations. J. Am. Chem. Soc. 126, 18–19 (2004)

    Article  CAS  Google Scholar 

  151. 151.

    W.J. Song, M.S. Seo, S. DeBeer George, T. Ohta, R. Song, M.-J. Kang, T. Tosha, T. Kitagawa, E.I. Solomon, W. Nam, Synthesis, characterization, and reactivities of manganese(V)-oxo porphyrin complexes. J. Am. Chem. Soc. 129, 1268–1277 (2007)

    Article  CAS  Google Scholar 

  152. 152.

    C. Arunkumar, Y.-M. Lee, J.Y. Lee, S. Fukuzumi, W. Nam, Hydrogen-atom abstraction reactions by manganese(V)- and manganese(IV)-oxo porphyrin complexes in aqueous solution. Chem. Eur. J. 15, 11482–11489 (2009)

    Article  CAS  Google Scholar 

  153. 153.

    H.-Y. Liu, F. Yam, Y.-T. Xie, X.-Y. Li, C.K. Chang, A bulky bis-pocket manganese(V)-oxo corrole complex: observation of oxygen atom transfer between triply bonded MnV≡O and alkene. J. Am. Chem. Soc. 131, 12890–12891 (2009)

    Article  CAS  Google Scholar 

  154. 154.

    J.Y. Lee, Y.-M. Lee, H. Kotani, W. Nam, S. Fukuzumi, High-valent manganese(V)-oxo porphyrin complexes in hydride transfer reactions. Chem. Commun. 6, 704–706 (2009)

    Article  Google Scholar 

  155. 155.

    P. Leeladee, D.P. Goldberg, Epoxidations catalyzed by manganese(V) oxo and imido complexes: role of the oxidant-Mn-oxo(imido) intermediate. Inorg. Chem. 49, 3083–3085 (2010)

    Article  CAS  Google Scholar 

  156. 156.

    S. Fukuzumi, T. Mizuno, T. Ojiri, Catalytic electron-transfer oxygenation of substrates with water as an oxygen source using manganese porphyrins. Chem. Eur. J. 18, 15794–15804 (2012)

    Article  CAS  Google Scholar 

  157. 157.

    M. Guo, H. Dong, J. Li, B. Cheng, Y. Huang, Y. Feng, A. Lei, Spectroscopic observation of iodosylarenemetalloporphyrin adducts and manganese(V)-oxo porphyrin species in a cytochrome P450 analogue. Nat. Commun. (2012).

    Article  Google Scholar 

  158. 158.

    R.A. Baglia, M. Dürr, I. Ivanović-Burmazović, D.P. Goldberg, Activation of a high-valent manganese-oxo complex by a nonmetallic Lewis acid. Inorg. Chem. 53, 5893–5895 (2014)

    Article  CAS  Google Scholar 

  159. 159.

    H.M. Neu, T. Yang, R.A. Baglia, T.H. Yosca, M.T. Green, M.G. Quesne, S.P. de Visser, D.P. Goldberg, Oxygen-atom transfer reactivity of axially ligated Mn(V)-oxo complexes: evidence for enhanced electrophilic and nucleophilic pathways. J. Am. Chem. Soc. 136, 13845–13852 (2014)

    Article  CAS  Google Scholar 

  160. 160.

    R.E. Schreiber, H. Cohen, G. Leitus, S.G. Wolf, A. Zhou, L. Que, R. Neumann, Reactivity and O2 formation by Mn(IV)- and Mn(V)-hydroxo species stabilized within a polyfluoroxometalate framework. J. Am. Chem. Soc. 137, 8738–8748 (2015)

    Article  CAS  Google Scholar 

  161. 161.

    S. Hong, Y.-M. Lee, M. Sankaralingam, A.K. Vardhaman, Y.J. Park, K.-B. Cho, T. Ogura, R. Sarangi, S. Fukuzumi, W. Nam, A manganese(V)-oxo complex: synthesis by dioxygen activation and enhancement of its oxidizing power by binding scandium ion. J. Am. Chem. Soc. 138, 8523–8532 (2016)

    Article  CAS  Google Scholar 

  162. 162.

    K. Oohora, H. Meichin, Y. Kihira, H. Sugimoto, Y. Shiro, T. Hayashi, Manganese(V) porphycene complex responsible for inert C–H bond hydroxylation in a myoglobin matrix. J. Am. Chem. Soc. 139, 18460–18463 (2017)

    Article  CAS  Google Scholar 

  163. 163.

    J.P.T. Zaragoza, M.A. Siegler, D.P. Goldberg, A reactive manganese(IV)-hydroxide complex: a missing intermediate in hydrogen atom transfer by high-valent metal-oxo porphyrinoid compounds. J. Am. Chem. Soc. 140, 4380–4390 (2018)

    Article  CAS  Google Scholar 

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Authors’ contributions

MB: Written 1. Introduction part, 3.3. High-valent MnIV-oxo Intermediates at Molecular Sites and compilation of the whole manuscript. NS: Written the 3.2. High-valent MnIV-oxo Intermediates at Molecular Sites part. HH: Written the 3.1. High-valent Mn-oxo Intermediates at nano sites part. YHL: Written the 3.1. High-valent Mn-oxo Intermediates at nano sites part. All authors read and approved the final manuscript.


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This review was supported by Basic Science Research Program (2017R1A2B3012003) which is funded by the National Research Foundation (NRF) under the Ministry of Science, ICT and Future Planning (MSIP), South Korea and the KIST Institutional Program (2V06170).

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Correspondence to Ki Tae Nam.

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Balamurugan, M., Saravanan, N., Ha, H. et al. Involvement of high-valent manganese-oxo intermediates in oxidation reactions: realisation in nature, nano and molecular systems. Nano Convergence 5, 18 (2018).

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  • High-valent
  • Mn-oxo
  • OEC
  • RNR
  • Biomimetic