Biological Oxidation Reactions Research Articles

Mechanism Insights into Allylic Hydroxylation versus Epoxidation of Propene Catalyzed by Model Catalyst Iron Phthalocyanine in the Presence of Hydrogen Peroxide.

High-valent metal-oxo species are key reactive intermediates in many biological and biological oxidation reactions. Herein, allylic hydroxylation (C-H) versus epoxidation (C═C) reactions of propene with a model catalyst iron phthalocyanine (FePc) in the presence of hydrogen peroxide were investigated contrastively, aiming to probe the active intermediates, structure-activity relationship, and reaction pathways. Our results showed that H2O2 as an oxygen-donor reagent can be easily decomposed on FePc to produce key active intermediates O═FePc and O═FePc═O with the energy barriers of 19.57 and 23.89 kcal/mol, respectively. In the selective oxidation of propene, O═FePc has a small preference for C═C epoxidation over C-H hydroxylation while O═FePc═O has a small preference for C-H hydroxylation. Since the electron-withdrawing O axial ligand in O═FePc═O further increases the radical character (Fe-O·) and Fe-O bond length of the iron-oxo moiety, O═FePc═O has better catalytic performance in both C═C epoxidation and C-H hydroxylation than O═FePc. Furthermore, in the whole reaction processes, the dual-hydrogen bonds between the two terminal H atoms of the alkene and allylic groups of propene and oxygen atom of the iron-oxo moiety would lead to the reaction toward C═C epoxidation while the single-hydrogen bond between the terminal H atom of the allylic group and the oxygen atom of the iron-oxo moiety would lead to the reaction toward C-H hydroxylation, implying that the weakly interacting hydrogen bonds affecting oxidation pathways also play a very important role in the regioselectivity of C═C epoxidation and C-H hydroxylation.

Enhanced Reactivities of Iron(IV)-Oxo Porphyrin Species in Oxidation Reactions Promoted by Intramolecular Hydrogen-Bonding.

High-valent iron-oxo species are one of the common intermediates in both biological and biomimetic catalytic oxidation reactions. Recently, hydrogen-bonding (H-bonding) has been proved to be critical in determining the selectivity and reactivity. However, few examples have been established for mechanistic insights into the H-bonding effect. Moreover, intramolecular H-bonding effect on both C-H activation and oxygen atom transfer (OAT) reactions in synthetic porphyrin model system has not been investigated yet. In this study, a series of heme-containing iron(IV)-oxo porphyrin species with or without intramolecular H-bonding are synthesized and characterized. Kinetic studies revealed that intramolecular H-bonding can significantly enhance the reactivity of iron(IV)-oxo species in OAT, C-H activation, and electron-transfer reactions. This unprecedented unified H-bonding effect is elucidated by theoretical calculations, which showed that intramolecular H-bonding interactions lower the energy of the anti-bonding orbital of iron(IV)-oxo porphyrin species, resulting in the enhanced reactivities in oxidation reactions irrespective of the reaction type. To the best of the knowledge, this is the first extensive investigation on the intramolecular H-bonding effect in heme system. The results show that H-bonding interactions have a unified effect with iron(IV)-oxo porphyrin species in all three investigated reactions.

Metal-Organic Framework for the Immobilization of Oxidoreductase Enzymes: Scopes and Perspectives.

Oxidoreductases are a wide class of enzymes that can catalyze biological oxidation and reduction reactions. Nowadays, oxidoreductases play a vital part in most bioenergetic metabolic pathways, which have important applications in biodegradation, bioremediation, environmental applications, as well as biosensors. However, free oxidoreductases are not stable and hard to be recycled. In addition, cofactors are needed in most oxidoreductases catalyze reactions, which are so expensive and unstable that it hinders their industrial applications. Enzyme immobilization is a feasible strategy that can overcome these problems. Recently, metal-organic frameworks (MOFs) have shown great potential as support materials for immobilizing enzymes due to their unique properties, such as high surface-area-to-volume ratio, chemical stability, functional designability, and tunable pore size. This review discussed the application of MOFs and their composites as immobilized carriers of oxidoreductase, as well as the application of MOFs as catalysts and immobilized carriers in redox reactions in the perspective of the function of MOFs materials. The paper also focuses on the potential of MOF carrier-based oxidoreductase immobilization for designing an enzyme cascade reaction system.

Enantioselective effects of chiral fragrance carvone (L- and D-carvone) on the physiology, oxidative damage, synthesis, and release of microcystin-LR in Microcystis aeruginosa

Carvone is a widely used chiral fragrance with two isomers (L-carvone and D-carvone). D-carvone smells like a caraway, whereas L-carvone smells like mint. Carvone imposes a potential burden on the aquatic ecosystem. However, the enantioselective toxic effect of carvone enantiomers on cyanobacteria remains unknown. This study aims to investigate the effects of L- and D-carvone on the physiological processes and related gene transcription (phoU, rbcL, and mcyH) in M. aeruginosa. Results showed that in the presence of L- and D-carvone, the oxidative damage and inhibitory effects on growth occurred in a concentration-dependent manner. The contents of chlorophyll a and protein and the rbcL transcription level were inhibited in M. aeruginosa. In addition, intracellular adenosine triphosphate (ATP) was heavily depleted because of various biological processes, including growth, oxidation reactions, and gene regulation. Meanwhile, L- and D-carvone stimulated the production and release of MC-LR and upregulated the expression level of the MC-LR-related gene mcyH. Intracellular MC-LR likely leaked to the water body under L-carvone exposure, posing a potential threat to the water environment. This study indicated that L- and D-carvone can regulate the physiological and metabolic activity of M. aeruginosa and show enantioselective toxic effects. The findings will also provide important insights into the influence of chiral fragrance on cyanobacterial blooms. Furthermore, this study will guide the safe application of chiral fragrance as personal care products.

The Dual Function of PhOH Included in the Coordination Sphere of the Nickel Complexes in the Processes of Oxidation with Dioxygen.

The role of ligands in the regulation of the catalytic activity of Ni-complexes (Ni(acac)2) in green process-selective ethylbenzene oxidation with O2 into α-phenyl ethyl hydroperoxide is considered in this article. The dual function of phenol (PhOH) included in the coordination sphere of the nickel complex as an antioxidant or catalyst depends on the ligand environment of the metal. The role of intermolecular H-bonds and supramolecular structures (AFM method) in the mechanisms of selective catalysis by nickel complexes in chemical and biological oxidation reactions is analyzed.

Effects of Diminished NADPH:cytochrome P450 Reductase in Human Hepatocytes on Lipid and Bile Acid Homeostasis.

NADPH:cytochrome P450 oxidoreductase (POR) is the obligate electron donor for microsomal cytochrome P450 (CYP) enzymes involved in the biosynthesis of endogenous substances like bile acids and other steroids as well as in the oxidative metabolism of xenobiotics. P450 oxidoreductase also supports other redox enzymes in fatty acid and cholesterol pathways. Recently, we have established CRISPR/Cas9-mediated POR knockdown in a human hepatic cell model, HepaRG, and demonstrated the differential effects of limited POR expression on CYP activity. The aim of the present work was to systematically investigate the impact of POR knockdown with a focus on the expression of ADME (absorption, distribution, metabolism, and excretion) genes and related regulators. Functional consequences have been assessed using quantitative mass spectrometry for targeted metabolomics covering bile acids, and cholesterol and its precursors, and for untargeted proteomics. In addition to the previously described alteration of RNA expression of CYP genes, we showed significant downregulation of transcriptional regulators of drug metabolism and transport, including NR1I3 (CAR), NR1I2 (PXR), NR1H4 (FXR), and NR1H3 (LXRα) in cells with POR gene disruption. Furthermore, POR knockdown resulted in deregulated bile acid and cholesterol biosynthesis demonstrated by low levels of cholic acid derivates and increased concentrations of chenodeoxycholic acid derivates, respectively. Systemic effects of POR knockdown on global protein expression were indicated by downregulation of several metabolic pathways including lipid metabolism and biological oxidation reactions. The deduced protein network map corroborates CYP enzymes as direct interaction partners, whereas changes in lipid metabolism and homeostasis are the result of indirect effects. In summary, our results emphasize a widespread role of POR in various metabolic pathways and provide the first human data on the effects of diminished POR expression on drug and endogenous metabolism in a genomeedited HepaRG cell model.

Hydrocarbon Oxidation by an Exposed, Multiply Bonded Iron(III) Oxo Complex.

The iron oxo unit, [Fe=O]n+ is a critical intermediate in biological oxidation reactions. While its higher oxidation states are well studied, relatively little is known about the least-oxidized form [FeIII=O]+. Here, the thermally stable complex PhB(AdIm)3Fe=O has been structurally, spectroscopically, and computationally characterized as a bona fide iron(III) oxo. An unusually short Fe–O bond length is consistent with iron–oxygen multiple bond character and is supported by electronic structure calculations. The complex is thermally stable yet is able to perform hydrocarbon oxidations, facilitating both C–O bond formation and dehydrogenation reactions.

Controlled Regulation of the Nitrile Activation of a Peroxocobalt(III) Complex with Redox-Inactive Lewis Acidic Metals.

Redox-inactive metal ions play vital roles in biological O2 activation and oxidation reactions of various substrates. Recently, we showed a distinct reactivity of a peroxocobalt(III) complex bearing a tetradentate macrocyclic ligand, [CoIII(TBDAP)(O2)]+ (1) (TBDAP = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)pyridinophane), toward nitriles that afforded a series of hydroximatocobalt(III) complexes, [CoIII(TBDAP)(R-C(═NO)O)]+ (R = Me (3), Et, and Ph). In this study, we report the effects of redox-inactive metal ions on nitrile activation of 1. In the presence of redox-inactive metal ions such as Zn2+, La3+, Lu3+, and Y3+, the reaction does not form the hydroximatocobalt(III) complex but instead gives peroxyimidatocobalt(III) complexes, [CoIII(TBDAP)(R-C(═NH)O2)]2+ (R = Me (2) and Ph (2Ph)). These new intermediates were characterized by various physicochemical methods including X-ray diffraction analysis. The rates of the formation of 2 are found to correlate with the Lewis acidity of the additive metal ions. Moreover, complex 2 was readily converted to 3 by the addition of a base. In the presence of Al3+, Sc3+, or H+, 1 is converted to [CoIII(TBDAP)(O2H)(MeCN)]2+ (4), and further reaction with nitriles did not occur. These results reveal that the reactivity of the peroxocobalt(III) complex 1 in nitrile activation can be regulated by the redox-inactive metal ions and their Lewis acidity. DFT calculations show that the redox-inactive metal ions stabilize the peroxo character of end-on Co-η1-O2 intermediate through the charge reorganization from a CoII-superoxo to a CoIII-peroxo intermediate. A complete mechanistic model explaining the role of the Lewis acid is presented.

Ligand‐Constraint‐Induced Peroxide Activation for Electrophilic Reactivity

Abstractμ‐1,2‐peroxo‐bridged diiron(III) intermediates P are proposed as reactive intermediates in various biological oxidation reactions. In sMMO, P acts as an electrophile, and performs hydrogen atom and oxygen atom transfers to electron‐rich substrates. In cyanobacterial ADO, however, P is postulated to react by nucleophilic attack on electrophilic carbon atoms. In biomimetic studies, the ability of μ‐1,2‐peroxo‐bridged dimetal complexes of Fe, Co, Ni and Cu to act as nucleophiles that effect deformylation of aldehydes is documented. By performing reactivity and theoretical studies on an end‐on μ‐1,2‐peroxodicobalt(III) complex 1 involving a non‐heme ligand system, L1, supported on a Sn6O6 stannoxane core, we now show that a peroxo‐bridged dimetal complex can also be a reactive electrophile. The observed electrophilic chemistry, which is induced by the constraints provided by the Sn6O6 core, represents a new domain for metal−peroxide reactivity.

Flavin-mediated reductive iron mobilization from frog M and Mycobacterial ferritins: impact of their size, charge and reactivities with NADH/O2.

In vitro, reductive mobilization of ferritin iron using suitable electron transfer mediators has emerged as a possible mechanism to mimic the iron release process, in vivo. Nature uses flavins as electron relay molecules for important biological oxidation and oxygenation reactions. Therefore, the current work utilizes three flavin analogues: riboflavin (RF), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which differ in size and charge but have similar redox potentials, to relay electron from nicotinamide adenine dinucleotide (NADH) to ferritin mineral core. Of these, the smallest/neutral analogue, RF, released more iron (~ threefold) in comparison to the larger and negatively charged FMN and FAD. Although iron mobilization got marred during the initial stages under aerobic conditions, but increased with a greater slope at the later stages of the reaction kinetics, which gets inhibited by superoxide dismutase, consistent with the generation of O2∙- in situ. The initial step, i.e., interaction of flavins with NADH played critical role in the iron release process. Overall, the flavin-mediated reductive iron mobilization from ferritins occurred via two competitive pathways, involving the reduced form of flavins either alone (anaerobic condition) or in combination with O2∙- intermediate (aerobic condition). Moreover, faster iron release was observed for ferritins from Mycobacterium tuberculosis than from bullfrog, indicating the importance of protein nanocage and the advantages they provide to the respective organisms. Therefore, these structure-reactivity studies of flavins with NADH/O2 holds significance in ferritin iron release, bioenergetics, O2-based cellular toxicity and may be potentially exploited in the treatment of methemoglobinemia. Smaller sized/neutral flavin analogue, riboflavin (RF) exhibits faster reactivity towards both NADH and O2 generating more amount of O2∙- and releases higher amount of iron from different ferritins, compared to its larger sized/negatively charged derivatives such as FMN and FAD.

Adsorption of HOOO. radical on pristine and doped graphene—a first-principles study

It is believed that HOOO. radicals play a key role in atmospheric and environmental chemistry as well as in biological oxidation reactions. In the present contribution, we aim to understand the ability of graphene to scavenge HOOO. radicals by studying the adsorption of HOOO. radical on the pristine and doped (B-doped, N-doped and (B,N)-codoped) graphene using density functional theory (DFT) calculations. It is found that mechanisms of adsorption of HOOO. radical on the pristine and N-doped graphene involve physisorption whereas those on the B-doped and (B,N)-codoped graphene involve chemisorption. The interaction between the pristine graphene and HOOO. radical is found to be weaker than that between doped graphene and HOOO. radical. Our calculations demonstrate that both the pristine and doped-graphene studied here can scavenge the HOOO. radicals. However, the B- and N-doped graphene can do this job more effectively.

Microbial Oxidoreductases: Biotechnological and Synthetic Applications

Enzymes are biocatalysts responsible for driving all biochemical reactions in the cells. The enzymes determine the physiology of a cell and together regulate the growth and proliferation of cells in response to various environmental signals. The ability of cells to adapt and respond to environmental conditions can be utilized for industrial applications. Hydrolases and oxidoreductases are the most common classes of enzymes used in various industries such as pharmaceutical, food and beverages, bioremediation and biofuels, among others. Oxidoreductases are the EC1 class enzymes that catalyze the biological oxidation and reduction reactions. They transfer electrons from one molecule (reductant that donates electron) to other molecules (oxidants those accept electron). Usually, the enzymes of this class are NAD+ (Nicotinamide Adenine Dinucleotide) or NADP (Nicotinamide Adenine Dinucleotide Phosphate)-dependent. The oxidoreductases are a diverse class of enzymes responsible for catalyzing highly stereo selective and regioselective reactions, because of which they are the enzymes of choice for synthesis of optically-active compounds. Alcohol dehydrogenase (ADH) is one of the most studied oxidoreductases. Generally, ADHs have narrow specificity towards their substrates. Here we are looking for ADH having high/ broad specificity towards the substrate. This review discusses the enzyme oxidoreductase, synthetic transformation with oxidoreductase and application of oxidoreductase in bioremediation.

Iron and manganese oxo complexes, oxo wall and beyond.

High-valent metal-oxo species with multiply-bonded M-O groups have been proposed as key intermediates in many biological and abiological catalytic oxidation reactions. These intermediates are implicated as active oxidants in alkane hydroxylation, olefin epoxidation and other oxidation reactions. For example, [FeivO(porphyrinato•-)]+ cofactors bearing π-radical porphyrinato•- ligands oxidize organic substrates in cytochrome P450 enzymes, which are common to many life forms. Likewise, high-valent Mn-oxo species are active for H2O oxidation in photosystem II. The chemistry of these native reactive species has inspired chemists to prepare highly oxidized transition-metal complexes as functional mimics. Although many synthetic Fe-O and Mn-O complexes now exist, the analogous oxo complexes of the late transition metals (groups 9-11) are rare. Indeed, late-transition-metal-oxo complexes of tetragonal (fourfold) symmetry should be electronically unstable, a rule commonly referred to as the 'oxo wall'. A few late metal-oxos have been prepared by targeting other symmetries or unusual spin states. These complexes have been studied using spectroscopic and theoretical methods. This Review describes mononuclear non-haem Fe-O and Mn-O species, the nature of the oxo wall and recent advances in the preparation of oxo complexes of Co, Ni and Cu beyond the oxo wall.

Cross-linked poly(4-vinylpyridine-N-oxide) as a polymer-supported oxygen atom transfer reagent

Oxygen atom transfer (OAT) reagents are common in biological and industrial oxidation reactions. While many heterogeneous catalysts have been utilized in OAT reactions, heterogeneous OAT reagents have not been explored. Here, cross-linked poly(4-vinylpyridine-N-oxide), called x-PVP-N-oxide, was tested as a heterogeneous OAT reagent and its oxidation chemistry compared to its molecular counterpart, pyridine-N-oxide. The insoluble oxidant x-PVP-N-oxide demonstrated comparable reactivity to pyridine-N-oxide in direct oxidation reactions of phosphines and phosphites in acetonitrile, but x-PVP-N-oxide did not react in other solvents. The polymer backbone of x-PVP-N-oxide, however, allowed for easy filtering and recycling in sequential oxidation reactions. In addition, x-PVP-N-oxide was tested as the stoichiometric oxidant in a copper-catalyzed OAT reaction to α-diazo-benzeneacetic acid methyl ester. The heterogeneous oxidant was much less reactive than pyridine-N-oxide, indicating that interaction with the metal catalyst was challenging. These results demonstrated a proof-of-concept that recyclable, polymer-supported OAT reagents could be a viable OAT reagents in direct oxidation reactions without metal catalysts.

The Role of Iodanyl Radicals as Critical Chain Carriers in Aerobic Hypervalent Iodine Chemistry

Summary Selective O 2 utilization remains a substantial challenge in synthetic chemistry. Biological small-molecule oxidation reactions often utilize aerobically generated high-valent catalyst intermediates to effect substrate oxidation. Available synthetic methods for aerobic oxidation catalysis are largely limited to substrate functionalization chemistry by low-valent catalyst intermediates (i.e., aerobically generated Pd(II) intermediates). Motivated by the need for new chemical platforms for aerobic oxidation catalysis, we recently developed aerobic hypervalent iodine chemistry. Here, we report that in contrast to the canonical two-electron oxidation mechanisms for the oxidation of organoiodides, the developed aerobic hypervalent iodine chemistry proceeds via a radical chain mechanism initiated by the addition of aerobically generated acetoxy radicals to aryl iodides. Despite the radical chain mechanism, aerobic hypervalent iodine chemistry displays substrate tolerance similar to that observed with traditional terminal oxidants, such as peracids. We anticipate that these insights will enable new sustainable oxidation chemistry via hypervalent iodine intermediates.

Tunneling Controls the Reaction Pathway in the Deformylation of Aldehydes by a Nonheme Iron(III)-Hydroperoxo Complex: Hydrogen Atom Abstraction versus Nucleophilic Addition.

Mononuclear nonheme iron(III)-hydroperoxo intermediates play key roles in biological oxidation reactions. In the present study, we report the highly intriguing reactivity of a nonheme iron(III)-hydroperoxo complex, [(TMC)FeIII(OOH)]2+ (1), in the deformylation of aldehydes, such as 2-phenylpropionaldehyde (2-PPA) and its derivatives; that is, the reaction pathway of the aldehyde deformylation by 1 varies depending on reaction conditions, such as temperature and substrate. At temperature above 248 K, the aldehyde deformylation occurs predominantly via a nucleophilic addition (NA) pathway. However, as the reaction temperature is lowered, the reaction pathway changes to a hydrogen atom transfer (HAT) pathway. Interestingly, the reaction rate becomes independent of temperature below 233 K with a huge kinetic isotope effect (KIE) value of 93 at 203 K, suggesting that the HAT reaction results from tunneling. In contrast, reactions with a deuterated 2-PPA at the α-position and 2-methyl-2-phenylpropionaldehyde proceed exclusively via a NA pathway irrespective of the reaction temperature. We conclude that the bifurcation pathways between NA and HAT result from the tunneling effect in the HAT reaction by 1. To the best of our knowledge, this study reports the first example showing that tunneling plays a significant role in the activation of substrate C-H bonds by a mononuclear nonheme iron(III)-hydroperoxo complex.

Cupric-superoxide complex that induces a catalytic aldol reaction-type C\u2013C bond formation

Much recent attention has been focused on the structure and reactivity of transition-metal superoxide complexes, among which mononuclear copper(II)-superoxide complexes are recognized as key reactive intermediates in many biological and abiological dioxygen-activation processes. So far, several types of copper(II)-superoxide complexes have been developed and their electrophilic reactivity has been explored in C–H and O–H bond activation reactions. Here we demonstrate that a mononuclear copper(II)-(end-on)superoxide complex supported by a N-[(2-pyridyl)methyl]-1,5-diazacyclooctane tridentate ligand can induce catalytic C–C bond formation reaction between carbonyl compounds (substrate) and the solvent molecule (acetone), giving β-hydroxy-ketones (aldol). Kinetic and spectroscopic studies at low temperature as well as DFT calculation studies support a nucleophilic reactivity of the superoxide species toward the carbonyl compounds, providing new insights into the reactivity of transition-metal superoxide species not only in biological oxidation reactions but also in synthetic organic chemistry.

Heme and Nonheme High-Valent Iron and Manganese Oxo Cores in Biological and Abiological Oxidation Reactions.

Utilization of O2 as an abundant and environmentally benign oxidant is of great interest in the design of bioinspired synthetic catalytic oxidation systems. Metalloenzymes activate O2 by employing earth-abundant metals and exhibit diverse reactivities in oxidation reactions, including epoxidation of olefins, functionalization of alkane C–H bonds, arene hydroxylation, and syn-dihydroxylation of arenes. Metal–oxo species are proposed as reactive intermediates in these reactions. A number of biomimetic metal–oxo complexes have been synthesized in recent years by activating O2 or using artificial oxidants at iron and manganese centers supported on heme or nonheme-type ligand environments. Detailed reactivity studies together with spectroscopy and theory have helped us understand how the reactivities of these metal–oxygen intermediates are controlled by the electronic and steric properties of the metal centers. These studies have provided important insights into biological reactions, which have contributed to the design of biologically inspired oxidation catalysts containing earth-abundant metals like iron and manganese. In this Outlook article, we survey a few examples of these advances with particular emphasis in each case on the interplay of catalyst design and our understanding of metalloenzyme structure and function.

Biological anodic oxidation and cathodic reduction reactions for improved bioelectrochemical treatment of petroleum refinery wastewater

Abstract Bioelectrochemical systems (BESs) were evaluated for the bioelectrochemical treatment (BET) of petroleum refinery wastewater (PRW) by applying mild electrochemical potential in the range of 400–1000 mV on a single chamber membrane-less BES configured with anodic and cathodic biofilms. After four days of cycle operation in batch mode, BES achieved a maximum current density of 278 mA/m2 and a power density of 222 mW/m2 using applied potential of 800 mV. This system also achieved COD degradation rate of 0.364 kg COD/m3-day. Diesel range organics (DROs) exhibited more than 90% degradation, which is 15 times higher than the abiotic control. Electrochemically active bioanode and biocathode contributed to the degradation of PRW through both oxidation and reduction reactions with mild applied potentials. This also resulted in a 30% improvement in COD removal compared to MFC with biocatalyst only on the anode. The function of improved bioelectrochemical treatment was also exhibited by redox current values of cyclic voltammograms.

A theoretical characterization of reactions of HOOO radical with guanine: formation of 8-oxoguanine

Hydrogen trioxide (HOOO) radical and other polyoxides of general formula, ROnR (where R stands for hydrogen, other atoms or groups and n ≥ 3), are believed to be key intermediates in atmospheric chemistry and biological oxidation reactions. In this contribution, DFT calculations using M06-2X density functional and the 6-31G(d,p) and 6-311+G(d,p) basis sets have been carried out to study different reactions of HOOO radical with guanine such as addition of HOOO radical at the C2, C4, C5, and C8 sites of guanine, abstraction of hydrogen atoms (H1, H2a, and H8) of guanine, and the mechanisms of oxidation of guanine with HOOO radical yielding 8-oxoguanine(a highly mutagenic derivative of guanine) and its radical in gas phase and aqueous media. The polarizable continuum model (PCM) has been used for solvation calculations in aqueous media. Our calculations reveal that the C8 site of guanine is the most reactive site for addition of HOOO radical, and adduct formed at this site would be appreciably stable. The rate constant ( $$ =\frac{K_bT}{h}{e}^{-\frac{\Delta {E}^b}{RT}} $$ ) at the C8 site is found to be 6.07 × 107 (2.89 × 107) s−1 at the M06-2X/6-311+G(d,p) level of theory in gas phase (aqueous media). The calculated barrier energy and heat of formation of hydrogen abstraction reactions show that HOOO radical would not abstract hydrogen atoms of guanine. Oxidation of guanine with HOOO radical can occur following two schemes (Scheme 1 and Scheme 2). It is found that formation of 8-oxoguanine radical via Scheme 1 would predominate over formation of 8-oxoguanine via Scheme 2, in a reaction of HOOO radical and guanine. Thus, HOOO radical can be treated as a member of reactive oxygen species (ROS) which play key roles in biological oxidation reactions, in agreement with previous literature reports.