N4 Ligand Research Articles

Synthesis, molecular docking, antibacterial and antifungal studies of Fe (II) and Ni (II) complexes of N1, N2-bis((1,3-diphenyl-1H-pyrazol-4-yl) methylene) ethane-1,2-diamine

1,3-Diphenyl pyrazole terminated ligand N1,N2- bis((1,3-diphenyl-1H-pyrazol-4-yl)methylene)ethane- 1,2-diamine and its iron and nickel complexes were synthesized. The structural environment of synthesis of ligand and its metal complexes was confirmed by elemental analysis, UV-Vis, FT-IR 1HNMR and 13NMR spectroscopic techniques. These compounds were further screened in vitro antimicrobial activities against some bacterial and some fungal strains and compared with the standard drugs. The result showed that the metal complexes are good candidates as antimicrobial agents than the ligands at the same concentration. The biological activity of the synthesized analogues was predicted in molecular docking experiments with specific target proteins. The molecular docking studies were carried out using the online software Arguslab 4.0.1 and revealed that both the ligand and its complexes are exhibiting a possible interaction with the proteins murD ligase and c-met Kinase.

Reactions of copper(II) bromide with 2,6-diacetylpyridine bis(phenyl-hydrazone) (L)-molecular and crystal structure of L and its mixed-valence complex [CuIIL2][CuI2Br4

Utilizing X-ray crystallography, the crystal and molecular structures of 2,6-diacetylpyridine bis(phenylhydrazone) (L) were determined. The energetics of the intermolecular interactions in the crystal structure were assessed with computational methods, revealing that dispersion interactions are dominant. The basic structural unit of the crystal packing was revealed to be the herring- bone type arrangement of L molecules. Assignation of the IR spectrum of L with the aid of DFT calculations was performed. Furthermore, new reactions of L with CuBr2 in different solvents are described, which led to the synthesis of the mixed Cu(II)?Cu(I) complex with the formula [CuIIL2][CuI 2Br4] (1), and its structural characterization. In the complex cation, two molecules of tridentate N3 ligand are meridionally arranged in a very distorted octahedral environment of a Cu(II) ion. In [Cu2Br4]2-, the bromide ions are arranged in a trigonal- -planar geometry around each copper(I) atom. Finally, for ligand, 1, and the previously synthesized complex [CuL2]Br2, the thermal properties were examined. The thermal stability of the complexes were lower than that of the ligand and decrease in the order: L (250?C) > [CuL2]Br2 (221?C) > [CuIIL2][CuI 2Br4] (212?C). The differences in thermal stability of the complexes are due to differences in the packing efficacy of the constitutional ions.

Exploring different equatorial donors in a series of five-coordinate Cu(II) complexes supported by rigid tetradentate ligands

A series of tetradentate mixed-donor ligands has been synthesized containing an amine, thioether, or phosphine donor at the 8-position of a 2-(1,1-di(pyridin-2-yl)ethyl)quinoline backbone. Upon metalation with CuCl2, the preorganized N4, N3P, and N3S donor ligands enforce distorted trigonal bipyramidal coordination environments around the copper metal center, in which a chlorido donor occupies the remaining axial coordination site. The complexes were characterized by elemental analysis, high-resolution mass spectrometry, and X-ray crystallography. The non-pyridyl equatorial donor was the sole difference from among the tetradentate ligands, and is responsible for the structural and electronic variations across the series. Indeed, more intermediate geometries between the ideal trigonal bipyramidal and square pyramidal extremes are observed with the larger phosphorus and sulfur donors. Relative to the N4 derivative, the N3P and N3S systems have greater chemical stability upon redox cycling as observed in spectroelectrochemical experiments and lower inner-sphere reorganization energies for the CuII/I redox couples based on density functional theory calculations.

Electron-Rich Pincer Ligand-Coupled Cobalt Porphyrin Polymer with Single-Atom Sites for Efficient (Photo)Electrocatalytic CO2 Reduction at Ultralow Overpotential.

Porphyrin and phthalocyanine complexes bearing single-atom catalytic sites (M-N4 ) have been explored as promising electrocatalysts for CO2 reduction reaction (CO2 RR), whose activity can be improved by regulating the ligands and/or the metal centers. Moreover, their photosensitive features also provide the possibility for highly efficient photoelectrocatalytic CO2 RR. Herein, a novel N'NN'-pincer-ligand (N3 )-coupled cobalt porphyrin (CoPor-N3 ) polymer is developed for realizing efficient (photo)electrocatalytic CO2 RR. The unraveled electronic structure and (photo)electrocatalytic features suggest that a synergistic effect between the electron-rich N3 ligands and the Co-N4 single-atom sites in the CoPor-N3 polymer results in the Co centers attaining more electrons, which is beneficial to facilitating the electron transfer to CO2 for the activation and reduction processes. As expected, the resultant CoPor-N3 polymer delivers a good long-term durability and high CO faradaic efficiency (96%) at an ultralow overpotential (0.39V), which outperforms the CoPor alone and most porphyrin-/phthalocyanine-based electrocatalysts reported so far. Moreover, the photosensitivity of CoPor units can further reduce the overpotential to 0.34V with a CO faradaic efficiency over 90% under light illumination. The present findings offer a new approach to constructing porphyrin-based photosensitive electrocatalysts with high-efficiency photoelectrocatalytic CO2 RR.

Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease.

The SARS-CoV-2 main protease (Mpro) is one of the molecular targets for drug design. Effective vaccines have been identified as a long-term solution but the rate at which they are being administered is slow in several countries, and mutations of SARS-CoV-2 could render them less effective. Moreover, remdesivir seems to work only with some types of COVID-19 patients. Hence, the continuous investigation of new treatments for this disease is pivotal. This study investigated the inhibitory role of natural products against SARS-CoV-2 Mpro as repurposable agents in the treatment of coronavirus disease 2019 (COVID-19). Through in silico approach, selected flavonoids were docked into the active site of Mpro. The free energies of the ligands complexed with Mpro were computationally estimated using the molecular mechanics-generalized Born surface area (MM/GBSA) method. In addition, the inhibition process of SARS-CoV-2 Mpro with these ligands was simulated at 100 ns in order to uncover the dynamic behavior and complex stability. The docking results showed that the selected flavonoids exhibited good poses in the binding domain of Mpro. The amino acid residues involved in the binding of the selected ligands correlated well with the residues involved with the mechanism-based inhibitor (N3) and the docking score of Quercetin-3-O-Neohesperidoside (−16.8 Kcal/mol) ranked efficiently with this inhibitor (−16.5 Kcal/mol). In addition, single-structure MM/GBSA rescoring method showed that Quercetin-3-O-Neohesperidoside (−87.60 Kcal/mol) is more energetically favored than N3 (−80.88 Kcal/mol) and other ligands (Myricetin 3-Rutinoside (−87.50 Kcal/mol), Quercetin 3-Rhamnoside (−80.17 Kcal/mol), Rutin (−58.98 Kcal/mol), and Myricitrin (−49.22 Kcal/mol). The molecular dynamics simulation (MDs) pinpointed the stability of these complexes over the course of 100 ns with reduced RMSD and RMSF. Based on the docking results and energy calculation, together with the RMSD of 1.98 ± 0.19 Å and RMSF of 1.00 ± 0.51 Å, Quercetin-3-O-Neohesperidoside is a better inhibitor of Mpro compared to N3 and other selected ligands and can be repurposed as a drug candidate for the treatment of COVID-19. In addition, this study demonstrated that in silico docking, free energy calculations, and MDs, respectively, are applicable to estimating the interaction, energetics, and dynamic behavior of molecular targets by natural products and can be used to direct the development of novel target function modulators.

Synthesis, characterization and antimicrobial activity of nickel(II) complexes of tridentate N3 ligands

The desire to develop new antimicrobial agents against the rising threat of extensive antibiotic resistance led to the exploration of many natural and synthetic compounds. Herein, we report the isolation and structural characterization of nickel(II) complexes of the type [Ni(L)2]2+ (1 and 2) of tridentate N3 ligands such as bis(pyridin-2-ylmethyl)amine (L1) and 1-(1-methyl-1H-imidazol-2-yl)-N-(pyridin-2-ylmethyl)methanamine (L2). Both the complex cations of [Ni(L1)2]2+ (1) and [Ni(L2)2]2+ (2) possess a distorted octahedral coordination geometry in which Ni(II) is chelated to two equivalents of the tridentate L1 and L2 ligand in facial coordination, respectively. Complexes 1 and 2 exhibit the bands in the visible region in UV–Vis spectra and peaks in the downfield region in paramagnetic NMR spectra suggesting the octahedral coordination geometry of the complexes in solution as well. Further, complexes 1 and 2 were evaluated for their antimicrobial activity against various clinical pathogens. With in vitro studies, complex 1 displayed activity against Vibrio parahaemolyticus and V. alginolyticus, Staphylococcus aureus, Candida albicans, and Salmonella typhi, and complex 2 displayed activity against S. aureus, S. typhi, and C. albicans. In addition, with in vivo studies, complex 1 was effective in inhibiting Vibrio infection in brine shrimp larvae while having no toxicity on the larvae. We believe these results will encourage medicinal chemists to further the study on metal complexes against multi-resistant pathogens.

Air-stable nickel(II) borohydrides as prohydrides: Reactions with halocarbons and aerial carbon dioxide

Non-noble metal hydrides are highly attractive reagents owing to their involvement in the reactions of environmental and industrial interest. However, they are often cumbersome to isolate as a shelf-stable reagent. Herein, we have described the synthesis of non-noble metal hydrides by simple manual grounding of Ni(II)-chelates and NaBH4 in open air at room temperature without using organic solvents. Two nickel(II) complexes of tetradentate N4 ligands, [(LNHCy)Ni(CH3CN)(H2O)](ClO4)2 and [(tren)Ni(CH3CN)2](BPh4)2, were synthesized and their solid-state structures were confirmed by single crystal X-ray diffraction studies. Both the nickel complexes were manually ground with sodium borohydride in open air to produce corresponding nickel(II)-borohydrides that were characterized using FT-IR spectroscopy and powder X-ray diffraction techniques. Further, the borohydrides (prohydrides) activate the C-X bond in benzyl bromide, CDCl3, trityl chloride and iodobenzene to yield toluene, CHDCl2, triphenylmethane and benzene; the borohydrides reacted with trityl cation and air in acetonitrile solution to yield triphenylmethane and carbonate.

Dynamic Cooperativity of Ligand-Residue Interactions Evaluated with the Fragment Molecular Orbital Method.

By the splendid advance in computation power realized with the Fugaku supercomputer, it has become possible to perform ab initio fragment molecular orbital (FMO) calculations for thousands of dynamic structures of protein-ligand complexes in a parallel way. We thus carried out electron-correlated FMO calculations for a complex of the 3C-like (3CL) main protease (Mpro) of the new coronavirus (SARS-CoV-2) and its inhibitor N3 incorporating the structural fluctuations sampled by classical molecular dynamics (MD) simulation in hydrated conditions. Along with a statistical evaluation of the interfragment interaction energies (IFIEs) between the N3 ligand and the surrounding amino-acid residues for 1000 dynamic structure samples, in this study we applied a novel approach based on principal component analysis (PCA) and singular value decomposition (SVD) to the analysis of IFIE data in order to extract the dynamically cooperative interactions between the ligand and the residues. We found that the relative importance of each residue is modified via the structural fluctuations and that the ligand is bound in the pharmacophore in a dynamic manner through collective interactions formed by multiple residues, thus providing new insight into structure-based drug discovery.

Catecholase Activities of Copper(II) Complexes With N4 Ligands

Two new N4 ligands, 1,2‐bis(2‐((pyridine‐2‐yl)methyleneamino) phenyl)ethane (L1) and tris((2‐benzylideneamino) ethyl)amine (L2), derived from 2,2′‐ethylenedianiline and tren, respectively, were developed and their copper(II) complexes [Cu(L1)(ClO4)](ClO4)CH3OH∙H2O and [Cu(L2) (CH3COO)](ClO4) were synthesized. Crystal structures of the complexes were determined to show that both the complexes have distorted square pyramidal coordinations with very similar geometrical parameters. Catecholase activities of the complexes were investigated for the oxidation of 3,5‐di‐tert‐butylcatechol (3,5‐H2dtbc) to 3,5‐di‐tert‐butyl‐o‐quinone (3,5‐dtbq) in the presence of O2. Kinetic behaviors and spectroscopic measurements on the catalytic reactions were supportive to the proposal in which the mechanical pathway of the catecholase activities by the complexes were initiated by the anaerobic oxidation of 3,5‐H2dtbc to 3,5‐dtbq, followed by the catalytic cycles with Cu(I) active forms.

Enhancing Chemo- and Stereoselectivity in C-H Bond Oxygenation with H2O2 by Nonheme High-Spin Iron Catalysts: The Role of Lewis Acid and Multimetal Centers.

Spin states of iron often direct the selectivity in oxidation catalysis by iron complexes using hydrogen peroxide (H2O2) on an oxidant. While low-spin iron(III) hydroperoxides display stereoselective C-H bond hydroxylation, the reactions are nonstereoselective with high-spin iron(II) catalysts. The catalytic studies with a series of high-spin iron(II) complexes of N4 ligands with H2O2 and Sc3+ reported here reveal that the Lewis acid promotes catalytic C-H bond hydroxylation with high chemo- and stereoselectivity. This reactivity pattern is observed with iron(II) complexes containing two cis-labile sites. The enhanced selectivity for C-H bond hydroxylation catalyzed by the high-spin iron(II) complexes in the presence of Sc3+ parallels that of the low-spin iron catalysts. Furthermore, the introduction of multimetal centers enhances the activity and selectivity of the iron catalyst. The study provides insights into the development of peroxide-dependent bioinspired catalysts for the selective oxygenation of C-H bonds without the restriction of using iron complexes of strong-field ligands.

A molecular docking study of potential inhibitors and repurposed drugs against SARS-CoV-2 main protease enzyme

COVID-19 has affected millions of people. Although many drugs are in use to combat disease, there is not any sufficient treatment yet. Having critical role in propagation of the novel coronavirus (SARS-CoV-2) works Main Protease up into a significant drug target. We have performed a molecular docking study to define possible inhibitor candidates against SARS-CoV-2 Main Protease enzyme. Besides docking Remdesivir, Ribavirin, Chloroquine and 28 other antiviral inhibitors (totally 31 inhibitors) to Main Protease enzyme, we have also performed a molecular docking study of 2177 ligands, which are used against Main Protease for the first time by using molecular docking program Autodock4. All ligands were successfully docked into Main Protease enzyme binding site. Among all ligands, EY16 coded ligand which previously used as EBNA1-DNA binding blocker candidate showed the best score for Main Protease with a binding free energy of −10.83 ​kcal/mol which was also lower than re-docking score of N3 ligand (−10.72 ​kcal/mol) contained in crystal structure of Main Protease. After analyzing the docking modes and docking scores we have found that our ligands have better binding free energy values than the inhibitors in use of treatment. We believe that further studies such as molecular dynamics or Molecular Mechanic Poisson Boltzmann Surface Area studies can make contribution that is more exhaustive to the docking results.

Proton Switch in the Secondary Coordination Sphere to Control Catalytic Events at the Metal Center: Biomimetic Oxo Transfer Chemistry of Nickel Amidate Complex.

High-valent metal-oxo species are key intermediates for the oxygen atom transfer step in the catalytic cycles of many metalloenzymes. While the redox-active metal centers of such enzymes are typically supported by anionic amino acid side chains or porphyrin rings, peptide backbones might function as strong electron-donating ligands to stabilize high oxidation states. To test the feasibility of this idea in synthetic settings, we have prepared a nickel(II) complex of new amido multidentate ligand. The mononuclear nickel complex of this N5 ligand catalyzes epoxidation reactions of a wide range of olefins by using mCPBA as a terminal oxidant. Notably, a remarkably high catalytic efficiency and selectivity were observed for terminal olefin substrates. We found that protonation of the secondary coordination sphere serves as the entry point to the catalytic cycle, in which high-valent nickel species is subsequently formed to carry out oxo-transfer reactions. A conceptually parallel process might allow metalloenzymes to control the catalytic cycle in the primary coordination sphere by using proton switch in the secondary coordination sphere.

Rapid atmospheric carbon dioxide fixation by nickel(II) complexes: meridionally coordinated diazepane-based 3N ligands facilitate fixation.

Octahedral complexes of the type [Ni(L)(H2O)3](ClO4)2 (1 and 2), where L is the tridentate 3N ligand 4-methyl-1-(pyrid-2-ylmethyl)-1,4-diazacycloheptane (L1, 1), or 4-methyl-1-(N-methylimidazolyl)-1,4-diazacycloheptane (L2, 2), have been isolated and characterized using elemental analysis, ESI-MS and electronic absorption spectroscopy. The DFT optimized structures of 1 and 2 reveal that the tridentate 3N ligands are coordinated meridionally constituting a distorted octahedral coordination geometry around nickel(ii). In methanol solution, the complexes, upon treatment with triethylamine, generate the reactive red colored low-spin square planar Ni-OH intermediate [Ni(L1/L2)(OH)]+ (1a and 2a), as characterized by ESI-MS and electronic absorption spectroscopy, and energy minimized structures. The latter when exposed to the atmosphere rapidly absorbs atmospheric CO2 to produce the carbonate bridged dinickel(ii) complexes [Ni2(L1/L2)2(μ-CO3)(H2O)2](ClO4)2 (3 and 4), as characterized by elemental analysis and the IR spectral feature (∼1608 cm-1) characteristic of bridging carbonate. The single crystal X-ray structure of 3 reveals the presence of a dinickel(ii) core bridged by a carbonate anion in a symmetric mode. Both the Ni(ii) centers are identical to each other with each Ni(ii) possessing a distorted octahedral coordination geometry constituted by a meridionally coordinated 3N ligand, a carbonate ion and a water molecule. The decay kinetics of the red intermediates generated by 1 (kobs, 7.7 ± 0.1 × 10-5 s-1) and 2 (kobs, 5.8 ± 0.3 × 10-4 s-1) in basic methanol solution with atmospheric CO2 has been determined by absorption spectroscopy. DFT studies illustrate that meridional coordination of the 3N ligand and the electron-releasing imidazole ring as in 2 facilitate fixation of CO2. The carbonate complex 3 efficiently catalyzes the conversion of styrene oxide into cyclic carbonate by absorbing atmospheric and pure CO2 with excellent selectivity.

Электрохимический контроль электронной проводимости тонких пленок металлоорганических полимеров

The dependence of the conductivity in thin films of polymer complexes of nickel with N4 ligands with macrocyclic and chelate structure on the doping level has been studied by the electrochemical in-situ conductance method. The electrochemical conductivity window of polymers depends on the structure of the monomers and approached 1.2 V for the macrocyclic complex. Electrochemical doping changes the electrical resistance of the investigated materials by 4 orders of magnitude

Electrocatalytic water oxidation by a water-soluble copper complex with a pentadentate amine-pyridine ligand

A water-soluble copper complex bearing a pentadentate N5 ligand works as an efficient and stable electrocatalyst for the water oxidation reaction in basic aqueous solution.

Ni(II) complexes of tripodal N4 ligands as catalysts for alkane hydroxylation and O-arylation of phenol: Structural and reactivity effects induced by fluoro substitution

Nickel(II) complexes [NiII(L1-2)(OAc)(H2O)][BPh4] (1–2) and [NiII(L3)(OAc)][BPh4] (3) derived from fluorinated tripodal ligands viz. N-((6-fluoropyridin-2-yl)methyl)(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine (L1 or FTPA), N,N′-bis((6-fluoropyridin-2-yl)methyl)(pyridin-2-yl)methanamine (L2 or F2TPA) and tris((6-fluoropyridin-2-yl)methyl)amine (L3 or F3TPA) have been synthesized and characterized by spectroscopic (UV–visible, FT-IR, paramagnetic NMR), elemental analysis, electrochemistry and X-ray diffraction techniques. In structurally similar complexes 1 and 2, Ni(II) center has a distorted octahedral coordination geometry constituted by all the four N atoms of the ligands, one acetate group and a water molecule. Complex 3 has different structural aspects. It does not have the water molecule in the coordination sphere and contains one acetate group bound with metal center in a bidentate mode. All the complexes exhibit a one-electron oxidation corresponding to the NiII/NiIII redox couple, the potential of which is influenced by the donor functionalities of ligand. These complexes catalyze the oxidation of cyclohexane efficiently (turn over number: 586–698) and selectively (alcohol to ketone ratio: 7.9:1 to 8.4:1). The study also includes the catalysis of adamantane oxidation to a mixture of ketones and alcohols. Catalytic potential of all the three complexes (1–3) has also been screened for CO coupling reactions of phenol with aryl halides. Among them, complex 1 is more efficient than 2 and 3 for such reactions.

Hydrogen bonding promotes diversity in nitrite coordination modes at a single iron(II) center

A low-valent [FeN5(OTf)2] complex and its bisnitrite adduct, [FeN5(NO2)2], have been synthesized in the interest of extending the reactivity of Fe complexes featuring redox-active ligands with secondary coordination sphere hydrogen-bond donors to nitrite reduction. Crystallographic characterization of [FeN5(NO2)2] reveals that the nitrite ligands demonstrate both ɳ 1-NO2 (N-nitro) and ɳ 1-ONO (O-nitrito) coordination modes. H-bonding between nitrite ligands and the protons on secondary amine moieties in the N5 ligand play a pivotal role in positioning the nitrite ligands in multiple coordination modes. These results provide insights into the role of H-bonding in supporting disparate coordination modes of this substrate that can be translated to mechanisms of nitrite reduction in biological systems.

Improved Oxidative C-C Bond Formation Reactivity of High-Valent Pd Complexes Supported by a Pseudo-Tridentate Ligand.

There is a large interest in developing oxidative transformations catalyzed by palladium complexes that employ environmentally friendly and economical oxidizing reagents such as dioxygen. Recently, we have reported the isolation and characterization of various mononuclear PdIII and PdIV complexes supported by the tetradentate ligands N,N'-dialkyl-2,11-diaza[3.3](2,6)pyridinophane (RN4, R = tBu, iPr, Me), and the aerobically induced C-C and C-heteroatom bond formation reactivity was investigated in detail. Given that the steric and electronic properties of the multidentate ligands were shown to tune the stability and reactivity of the corresponding high-valent Pd complexes, herein we report the use of an asymmetric N4 ligand, N-mehtyl-N'-tosyl-2,11-diaza[3.3](2,6)pyridinophane (TsMeN4), in which one amine N atom contains a tosyl group. The N-Ts donor atom exhibits a markedly reduced donating ability, which led to the formation of transiently stable PdIII and PdIV complexes, and consequently the corresponding O2 oxidation reactivity and the subsequent C-C bond formation were improved significantly.

Iron-Catalyzed Highly Enantioselective cis-Dihydroxylation of Trisubstituted Alkenes with Aqueous H2 O2.

Reliable methods for enantioselective cis-dihydroxylation of trisubstituted alkenes are scarce. The iron(II) complex cis-α-[FeII (2-Me2 -BQPN)(OTf)2 ], which bears a tetradentate N4 ligand (Me2 -BQPN=(R,R)-N,N'-dimethyl-N,N'-bis(2-methylquinolin-8-yl)-1,2-diphenylethane-1,2-diamine), was prepared and characterized. With this complex as the catalyst, a broad range of trisubstituted electron-deficient alkenes were efficiently oxidized to chiral cis-diols in yields of up to 98 % and up to 99.9 % ee when using hydrogen peroxide (H2 O2 ) as oxidant under mild conditions. Experimental studies (including 18 O-labeling, ESI-MS, NMR, EPR, and UV/Vis analyses) and DFT calculations were performed to gain mechanistic insight, which suggested possible involvement of a chiral cis-FeV (O)2 reaction intermediate as an active oxidant. This cis-[FeII (chiral N4 ligand)]2+ /H2 O2 method could be a viable green alternative/complement to the existing OsO4 -based methods for asymmetric alkene dihydroxylation reactions.

Iron‐Catalyzed Highly Enantioselective cis‐Dihydroxylation of Trisubstituted Alkenes with Aqueous H2O2

AbstractReliable methods for enantioselective cis‐dihydroxylation of trisubstituted alkenes are scarce. The iron(II) complex cis‐α‐[FeII(2‐Me2‐BQPN)(OTf)2], which bears a tetradentate N4 ligand (Me2‐BQPN=(R,R)‐N,N′‐dimethyl‐N,N′‐bis(2‐methylquinolin‐8‐yl)‐1,2‐diphenylethane‐1,2‐diamine), was prepared and characterized. With this complex as the catalyst, a broad range of trisubstituted electron‐deficient alkenes were efficiently oxidized to chiral cis‐diols in yields of up to 98 % and up to 99.9 % ee when using hydrogen peroxide (H2O2) as oxidant under mild conditions. Experimental studies (including 18O‐labeling, ESI‐MS, NMR, EPR, and UV/Vis analyses) and DFT calculations were performed to gain mechanistic insight, which suggested possible involvement of a chiral cis‐FeV(O)2 reaction intermediate as an active oxidant. This cis‐[FeII(chiral N4 ligand)]2+/H2O2 method could be a viable green alternative/complement to the existing OsO4‐based methods for asymmetric alkene dihydroxylation reactions.