Nature-Inspired Photocatalytic Azo Bond Cleavage with Red Light.

The emerging field of photoredox catalysis in mammalian cells enables spatiotemporal regulation of a wealth of biological processes. However, the selective cleavage of stable covalent bonds driven by low-energy visible light remains a great challenge. Herein, we report that red light excitation of a commercially available dye, abbreviated NMB+, leads to catalytic cleavage of stable azo bonds in both aqueous solutions and hypoxic cells and hence a means to photodeliver drugs or functional molecules. Detailed mechanistic studies reveal that azo bond cleavage is triggered by a previously unknown consecutive two-photon process. The first photon generates a triplet excited state, 3NMB+*, that is reductively quenched by an electron donor to generate a protonated NMBH•+. The NMBH•+ undergoes a disproportionation reaction that yields the initial NMB+ and two-electron-reduced NMBH (i.e., leuco-NMB, abbreviated as LNMB). Interestingly, LNMB forms a charge transfer complex with all four azo substrates that possess an intense absorption band in the red region. A second red photon induces electron transfer from LNMB to the azo substrate, resulting in azo bond cleavage. The charge transfer complex mediated two-photon catalytic mechanism reported herein is reminiscent of the flavin-dependent natural photoenzyme that catalyzes bond cleavage reactions with high-energy photons. The red-light-driven photocatalytic strategy offers a new approach to bioorthogonal azo bond cleavage for photodelivery of drugs or functional molecules.

Biomimetic Superstructured Interphase for Aqueous Zinc-Ion Batteries.

The practical application of aqueous zinc-ion batteries (AZIBs) is greatly challenged by rampant dendrites and pestilent side reactions resulting from an unstable Zn-electrolyte interphase. Herein, we report the construction of a reliable superstructured solid electrolyte interphase for stable Zn anodes by using mesoporous polydopamine (2D-mPDA) platelets as building blocks. The interphase shows a biomimetic nacre's "brick-and-mortar" structure and artificial transmembrane channels of hexagonally ordered mesopores in the plane, overcoming the mechanical robustness and ionic conductivity trade-off. Experimental results and simulations reveal that the -OH and -NH groups on the surface of artificial ion channels can promote rapid desolvation kinetics and serve as an ion sieve to homogenize the Zn2+ flux, thus inhibiting side reactions and ensuring uniform Zn deposition without dendrites. The 2D-mPDA@Zn electrode achieves an ultralow nucleation potential of 35 mV and maintains a Coulombic efficiency of 99.8% over 1500 cycles at 5 mA cm-2. Moreover, the symmetric battery exhibits a prolonged lifespan of over 580 h at a high current density of 20 mA cm-2. This biomimetic superstructured interphase also demonstrates the high feasibility in Zn//VO2 full cells and paves a new route for rechargeable aqueous metal-ion batteries.

Assessing r2SCAN meta-GGA functional for structural parameters, cohesive energy, mechanical modulus, and thermophysical properties of 3d, 4d, and 5d transition metals.

The recent development of accurate and efficient semilocal density functionals on the third rung of Jacob's ladder of density functional theory, such as the revised regularized strongly constrained and appropriately normed (r2SCAN) density functional, could enable rapid and highly reliable prediction of the elasticity and temperature dependence of thermophysical parameters of refractory elements and their intermetallic compounds using the quasi-harmonic approximation (QHA). Here, we present a comparative evaluation of equilibrium cell volumes, cohesive energy, mechanical moduli, and thermophysical properties (Debye temperature and thermal expansion coefficient) for 22 transition metals using semilocal density functionals, including the local density approximation (LDA), Perdew-Burke-Ernzerhof (PBE) and PBEsol generalized gradient approximations (GGAs), and the r2SCAN meta-GGA. PBEsol and r2SCAN deliver the same level of accuracies for structural, mechanical, and thermophysical properties. PBE and r2SCAN perform better than LDA and PBEsol for calculating cohesive energies of transition metals. Among the tested density functionals, r2SCAN provides an overall well-balanced performance for reliably computing cell volumes, cohesive energies, mechanical properties, and thermophysical properties of various 3d, 4d, and 5d transition metals using QHA. Therefore, we recommend that r2SCAN could be employed as a workhorse method to evaluate thermophysical properties of transition metal compounds and alloys in high throughput workflows.

Regulating Lateral Adsorbate Interaction for Efficient Electroreforming of Bio-polyols.

Tailoring the selectivity at the electrode-electrolyte interface is one of the greatest challenges for heterogeneous electrocatalysis, and complementary strategies to catalyst structural designs need to be developed. Herein, we proposed a new strategy of controlling the electrocatalytic pathways by lateral adsorbate interaction for the bio-polyol oxidation. Redox-innocent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) anion possesses the alcoholic property that facilely adsorbs on the nickel oxyhydroxide catalyst, but is resistant to oxidation due to the electron-withdrawing trifluoromethyl groups. The alien HFIP adsorbents can compete with bio-polyols and form a mixed adsorbate layer that creates lateral adsorbate interaction via hydrogen bonding, which achieved a >2-fold enhancement of the oxalate selectivity to 55 % for the representative glycerol oxidation and can be extended to various bio-polyol substrates. Through in situ spectroscopic analysis and DFT calculation on the glycerol oxidation, we reveal that the hydrogen-bonded adsorbate interaction can effectively tune the adsorption energies and tailor the oxidation capabilities toward the targeted products. This work offers an additional perspective of tuning electrocatalytic reactions via introducing redox-innocent adsorbates to create lateral adsorbate interactions.

Electrode/Electrolyte Synergy for Concerted Promotion of Electron and Proton Transfers toward Efficient Neutral Water Oxidation.

Neutral water oxidation is a crucial half-reaction for various electrochemical applications requiring pH-benign conditions. However, its sluggish kinetics with limited proton and electron transfer rates greatly impacts the overall energy efficiency. In this work, we created an electrode/electrolyte synergy strategy for simultaneously enhancing the proton and electron transfers at the interface toward highly efficient neutral water oxidation. The charge transfer was accelerated between the iridium oxide and in situ formed nickel oxyhydroxide on the electrode end. The proton transfer was expedited by the compact borate environment that originated from hierarchical fluoride/borate anions on the electrolyte end. These concerted promotions facilitated the proton-coupled electron transfer (PCET) events. Due to the electrode/electrolyte synergy, Ir-O and Ir-OO- intermediates could be directly detected by in situ Raman spectroscopy, and the rate-limiting step of Ir-O oxidation was determined. This synergy strategy can extend the scope of optimizing electrocatalytic activities toward more electrode/electrolyte combinations.

Sub-10 nm Corrugated TiO2 Nanowire Arrays by Monomicelle-Directed Assembly for Efficient Hole Extraction.

Precise synthesis of well-ordered ultrathin nanowire arrays with tunable active surface, though attractive in optoelectronics, remains challenging to date. Herein, well-aligned sub-10 nm TiO2 nanowire arrays with controllable corrugated structure have been synthesized by a unique monomicelle-directed assembly method. The nanowires with an exceptionally small diameter of ∼8 nm abreast grow with an identical adjacent distance of ∼10 nm, forming vertically aligned arrays (∼800 nm thickness) with a large surface area of ∼102 m2 g-1. The corrugated structure consists of bowl-like concave structures (∼5 nm diameter) that are closely arranged along the axis of the ultrathin nanowires. And the diameter of the concave structures can be finely manipulated from ∼2 to 5 nm by simply varying the reaction time. The arrays exhibit excellent charge dynamic properties, leading to a high applied bias photon-to-current efficiency up to 1.4% even at a very low potential of 0.41 VRHE and a superior photocurrent of 1.96 mA cm-2 at 1.23 VRHE. Notably, an underlying mechanism of the hole extraction effect for concave walls is first clarified, demonstrating the exact role of concave walls as the hole collection centers for efficient water splitting.

Smallest Stable Si/SiO_{2} Interface that Suppresses Quantum Tunneling from Machine-Learning-Based Global Search.

While the downscaling of size for field effect transistors is highly desirable for computation efficiency, quantum tunneling at the Si/SiO_{2} interface becomes the leading concern when approaching the nanometer scale. By developing a machine-learning-based global search method, we now reveal all the likely Si/SiO_{2} interface structures from thousands of candidates. Two high Miller index Si(210) and (211) interfaces, being only ∼1 nm in periodicity, are found to possess good carrier mobility, low carrier trapping, and low interfacial energy. The results provide the basis for fabricating stepped Si surfaces for next-generation transistors.

Steering the Glycerol Electro-Reforming Selectivity via Cation-Intermediate Interactions.

Electro-reforming of renewable biomass resources is an alternative technology for sustainable pure H2 production. Herein, we discovered an unconventional cation effect on the concurrent formate and H2 production via glycerol electro-reforming. In stark contrast to the cation effect via forming double layers in cathodic reactions, residual cations at the anode were discovered to interact with the glycerol oxidation intermediates to steer its product selectivity. Through a combination of product analysis, transient kinetics, crown ether trapping experiments, in situ IRRAS and DFT calculations, the aldehyde intermediates were discovered to be stabilized by the Li+ cations to favor the non-oxidative C-C cleavage for formate production. The maximal formate efficiency could reach 81.3 % under ≈60 mA cm-2 in LiOH. This work emphasizes the significance of engineering the microenvironment at the electrode-electrolyte interface for efficient electrolytic processes.

Lattice-Confined Single-Atom Fe1 Sx on Mesoporous TiO2 for Boosting Ambient Electrocatalytic N2 Reduction Reaction.

Mimicking natural nitrogenase to create highly efficient single-atom catalysts (SACs) for ambient N2 fixation is highly desired, but still challenging. Herein, S-coordinated Fe SACs on mesoporous TiO2 have been constructed by a lattice-confined strategy. The extended X-ray absorption fine structure and X-ray photoelectron spectroscopy spectra demonstrate that Fe atoms are anchored in TiO2 lattice via the FeS2 O2 coordination configuration. Theoretical calculations reveal that FeS2 O2 sites are the active centers for electrocatalytic nitrogen reduction reaction (NRR). Moreover, the finite element analysis shows that confinement of opened and ordered mesopores can facilitate the mass transport and offer an enlarged active surface area for NRR. As a result, this catalyst delivers a favorable NH3 yield rate of 18.3 µg h-1 mgcat. -1 with a high Faradaic efficiency of 17.3 % at -0.20 V versus a reversible hydrogen electrode. Most importantly, this lattice-confined strategy is universal and can also be applied to Ni1 Sx @TiO2 , Co1 Sx @TiO2 , Mo1 Sx @TiO2 , and Cu1 Sx @TiO2 SACs. Our study provides new hints for the design and biomimetic synthesis of highly efficient NRR electrocatalysts.

Electrifying Adipic Acid Production: Copper-Promoted Oxidation and C-C Cleavage of Cyclohexanol.

Adipic acid is a central platform molecule for the polymer industry. Production of adipic acid with electroreforming technology is more sustainable compared to the thermochemical synthesis route. We discovered that incorporation of Cu2+ into a Ni hydroxide lattice significantly improved the electrocatalytic oxidation of cyclohexanol into adipate with a high yield (84 %) and selectivity (87 %). This Cu promotion effect serves as a mechanistic probe that can be combined with product analysis, steady-state kinetics, and in situ spectroscopy. A two-electron oxidation into cyclohexanone first occurs, followed by consecutive hydroxylation and C-C cleavage before dione formation. The central role of Cu2+ is to weaken the interaction between the NiOOH and surface-adsorbed O-centered radical that facilitates subsequent C-C cleavage. This enables a highly efficient two-electrode system capable of electroreforming KA oil into adipate and pure H2 .

Recognition of Surface Oxygen Intermediates on NiFe Oxyhydroxide Oxygen-Evolving Catalysts by Homogeneous Oxidation Reactivity.

NiFe oxyhydroxide is one of the most promising oxygen evolution reaction (OER) catalysts for renewable hydrogen production, and deciphering the identity and reactivity of the oxygen intermediates on its surface is a key challenge but is critical to the catalyst design for improving the energy efficiency. Here, we screened and utilized in situ reactive probes that can selectively target specific oxygen intermediates with high rates to investigate the OER intermediates and pathway on NiFe oxyhydroxide. Most importantly, the oxygen atom transfer (OAT) probes (e.g., 4-(diphenylphosphino) benzoic acid) could efficiently inhibit the OER kinetics by scavenging the OER intermediates, exhibiting lower OER currents, larger Tafel slopes, and larger kinetic isotope effect (KIE) values, while probes with other reactivities demonstrated much smaller effects. Combining the OAT reactivity with electrochemical kinetic and operando Raman spectroscopic techniques, we identified a resting Fe═O intermediate in the Ni-O scaffold and a rate-limiting O-O chemical coupling step between a Fe═O moiety and a vicinal bridging O. DFT calculation further revealed a longer Fe═O bond formed on the surface and a large kinetic energy barrier of the O-O chemical coupling step, corroborating the experimental results. These results point to a new direction of liberating lattice O and expediting O-O coupling for optimizing NiFe-based OER electrocatalyst.

Values of Radial Artery Provocation Tests at Different Doses of Ergonovine in the Diagnosis of Coronary Artery Spasm.

The intracoronary drug provocation test has been the gold standard for diagnosis of coronary artery spasm (CAS); however, it has been identified with severe complications. In this study, we investigated the sensitivity, specificity, and safety of radial artery provocation test at different doses of ergonovine in the diagnosis of CAS. This study enrolled 57 patients, which were then divided into CAS group (n = 24) and control group (n = 33) after intracoronary ergonovine provocation test. All patients underwent radial artery provocation test at different doses of ergonovine. The predictive values of radial artery provocation test for the diagnosis of CAS were analyzed using receiver operator characteristic curve. In the radial artery provocation test at different doses of ergonovine, radial artery stenosis degree was all found to be significantly higher in the CAS group than in the control group (all P < 0.001). In the control group, significant differences were noted in the radial artery stenosis degree between different doses of ergonovine (all P < 0.05). In the CAS group, the radial artery stenosis degree was significantly higher in 160 µg and 100 µg of ergonovine than in 60 µg of ergonovine (all P < 0.001). The radial artery provocation test at 60 µg and 100 µg of ergonovine did not cause CAS, chest pain, and ECG ischemic changes. In the radial artery provocation test at 160 µg of ergonovine, some patients had CAS, chest pain, and ECG ischemic changes. The specificity and sensitivity of radial artery provocation test were 90.91% and 50.00% at 60 µg of ergonovine, 96.97% and 66.67% at 100 µg of ergonovine, and 90.91% and 95.83% at 160 µg of ergonovine for the diagnosis of CAS. As per our findings, we can conclude that the basic tension of radial artery increases in the CAS group. With the increase of ergonovine doses, its sensitivity and specificity improve, but its safety decreases. We will explore the most optimal dose of ergonovine in future studies.

Deciphering and Suppressing Over-Oxidized Nitrogen in Nickel-Catalyzed Urea Electrolysis.

Urea electrolysis is a prospective technology for simultaneous H2 production and nitrogen suppression in the process of water being used for energy production. Its sustainability is currently founded on innocuous N2 products; however, we discovered that prevalent nickel-based catalysts could generally over-oxidize urea into NO2 - products with ≈80 % Faradaic efficiencies, posing potential secondary hazards to the environment. Trace amounts of over-oxidized NO3 - and N2 O were also detected. Using 15 N isotopes and urea analogues, we derived a nitrogen-fate network involving a NO2 - -formation pathway via OH- -assisted C-N cleavage and two N2 -formation pathways via intra- and intermolecular coupling. DFT calculations confirmed that C-N cleavage is energetically more favorable. Inspired by the mechanism, a polyaniline-coating strategy was developed to locally enrich urea for increasing N2 production by a factor of two. These findings provide complementary insights into the nitrogen fate in water-energy nexus systems.

Jahn-Teller Disproportionation Induced Exfoliation of Unit-Cell Scale ϵ-MnO2.

Exfoliation of non-layered (structurally) bulk materials at the nanoscale is challenging because of the strong chemical bonds in the lattice, as opposed to the weak van der Waals (vdW) interactions in layered materials. We propose a top-down method to exfoliate ϵ-MnO2 nanosheets in a family of charge-ordered La1-x AEx MnO3 (AE=Ca, Sr, Ba) perovskites, taking advantage of the Jahn-Teller disproportionation effect of Mn3+ and bond-strength differences. ϵ-MnO2 crystallized into a nickel arsenide (NiAs) structure, with a thickness of 0.91 nm, displays thermal metastability and superior water oxidation activity compared to other manganese oxides. The exfoliation mechanism involves a synergistic proton-induced Mn3+ disproportionation and structural reconstruction. The synthetic method could also be potentially extended to the exfoliation of other two-dimensional nanosheet materials with non-layered structures.

A New Type of Capping Agent in Nanoscience: Metal Cations.

Capping agents are the essential factor in nanoscience and nanotechnology. However, the types of capping agents are greatly limited. Defying conventional beliefs, here is shown that metal cations can also be considered as capping agents for oxide nanoparticles, particularly in maintaining their colloidal stability and controlling their facets. Here the general stabilizing effects of multivalent cations for oxide nanoparticles, and the facet controlling role of Al3+ ions in the growth and ripening of Cu2 O octahedra, are demonstrated. This discovery broadens the view of capping agent and opens doors for nanosynthesis, surface treatment, and beyond.

Active Site Revealed for Water Oxidation on Electrochemically Induced δ-MnO2: Role of Spinel-to-Layer Phase Transition.

Seeking for active MnOx material as artificial water splitting catalyst has been a long history since the discovery of PSII system in nature. To date, the highest activity MnOx catalyst reported for oxygen evolution reaction (OER) does however not belong to common MnO2 polymorphs (α-, ß-, δ-MnO2), but rather to nascent δ-MnO2 layer produced in situ from spinel under electrochemical conditions with unknown active site structure. Here with the stochastic surface walking (SSW) pathway sampling method, we for the first time resolve the atomic-level mechanism of spinel-to-layer Mn3O4 solid phase transition in aqueous electrolyte. We show that a transient H0.5MnO2 phase is the precursor of transition that forms at high voltage (>1 V), and it undergoes the solid-to-solid phase transition to produce a δ-MnO2 layer, which is accompanied by Mn dissolution, dislocation, layer-breaking, and insertion of water/cations between layers. This leads to the generation of a variety of possible defective structures. We demonstrate using first-principles calculations that a special edge site with neighboring Mn vacancy provides the best OER activity with an overpotential of 0.59 V, 0.19 V lower than that of pristine MnO2. The high activity of such Mn sites are attributed to its special local structure: pseudocubane with one corner missing. The presence of the Mn vacancy near the active site enhances the adsorption of OH intermediate in OER. This defective cubane structure shares the common geometrical and electronic features found in the PSII system.

Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling.

BACKGROUND/AIMS: Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) exposure to myocardial cells mimics ischemia-reperfusion injuries. We studied the potential activity of ciliary neurotrophic factor (CNTF) on OGDR-treated myocardial cells. METHODS: CNTF and CNTFR expression were tested by RT-PCR assay and Western blotting assay. Cell viability and death were tested by MTT assay and LDH release assay, respectively. Akt-Nrf2 signalings were tested by Western blotting assay and qPCR assay. RESULTS: CNTF and its receptor CNTFR were functionally expressed in established H9c2 myocardial cells and primary murine myocardiocytes. Pretreatment of CNTF significantly attenuated OGDR-induced viability reduction and death in myocardial cells. Further studies show that in the myocardial cells CNTF activated NF-E2-related factor 2 (Nrf2) signaling to inhibit OGDR-induced reactive oxygen species (ROS) production and programmed necrosis, preventing adenine nucleotide translocator 1 (ANT-1)-p53-cyclophilin D (Cyp-D) mitochondrial association and mitochondrial depolarization. Nrf2 silencing or knockout almost abolished CNTF-induced H9c2 cytoprotection against OGDR. CNTF activated Akt in H9c2 cells and primary murine myocardiocytes. Conversely, Akt blockage by the pharmacological inhibitors not only blocked CNTF-induced Nrf2 Ser-40 phosphorylation and activation, but also nullified anti-OGDR actions by CNTF in myocardial cells. CONCLUSION: CNTF activates Akt-Nrf2 signaling to protect myocardial cells from OGDR.

Reaction Network of Layer-to-Tunnel Transition of MnO2.

As a model system of 2-D oxide material, layered δ-MnO2 has important applications in Li ion battery systems. δ-MnO2 is also widely utilized as a precursor to synthesize other stable structure variants in the MnO2 family, such as α-, ß-, R-, and γ-phases, which are 3-D interlinked structures with different tunnels. By utilizing the stochastic surface walking (SSW) pathway sampling method, we here for the first time resolve the atomistic mechanism and the kinetics of the layer-to-tunnel transition of MnO2, that is, from δ-MnO2 to the α-, ß-, and R-phases. The SSW sampling determines the lowest-energy pathway from thousands of likely pathways that connects different phases. The reaction barriers of layer-to-tunnel phase transitions are found to be low, being 0.2-0.3 eV per formula unit, which suggests a complex competing reaction network toward different tunnel phases. All the transitions initiate via a common shearing and buckling movement of the MnO2 layer that leads to the breaking of the Mn-O framework and the formation of Mn(3+) at the transition state. Important hints are thus gleaned from these lowest-energy pathways: (i) the large pore size product is unfavorable for the entropic reason; (ii) cations are effective dopants to control the kinetics and selectivity in layer-to-tunnel transitions, which in general lowers the phase transition barrier and facilitates the creation of larger tunnel size; (iii) the phase transition not only changes the electronic structure but also induces the macroscopic morphology changes due to the interfacial strain.

Low-concentration of perifosine surprisingly protects cardiomyocytes from oxygen glucose deprivation.

Here we found that low-concentration of perifosine, an Akt inhibitor, surprisingly protected cardiomyocytes from oxygen glucose deprivation (OGD)/re-oxygenation. In H9c2 cardiomyocytes, non-cytotoxic perifosine (0.1-0.5 µM) suppressed OGD/re-oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial translocation and cyclophilin D complexation, as well as mitochondrial membrane potential (MMP) reduction. Molecularly, perifosine activated AMP-activated kinase (AMPK) signaling to increase intracellular NADPH (nicotinamide adenine dinucleotide phosphate) content in H9c2 cells. On the other hand, AMPK inhibition by AMPKα1 shRNA-knockdown in H9c2 cells significantly reduced perifosine-induced NADPH production, and alleviated perifosine-mediated anti-oxidant and cytoprotective activities against OGD/re-oxygenation. In primary murine cardiomyocytes, perifosine similarly activated AMPK signaling, and offered significant protection against OGD/re-oxygenation, which was largely attenuated with siRNA knockdown of AMPKα1. We demonstrate an unexpected function of perifosine (low-concentration) in protecting cardiomyocytes from OGD/re-oxygenation.

Adsorption and reactions of O2 on anatase TiO2.

CONSPECTUS: The interaction of molecular oxygen with titanium dioxide (TiO2) surfaces plays a key role in many technologically important processes such as catalytic oxidation reactions, chemical sensing, and photocatalysis. While O2 interacts weakly with fully oxidized TiO2, excess electrons are often present in TiO2 samples. These excess electrons originate from intrinsic reducing defects (oxygen vacancies and titanium interstitials), doping, or photoexcitation and form polaronic Ti(3+) states in the band gap near the bottom of the conduction band. Oxygen adsorption involves the transfer of one or more of these excess electrons to an O2 molecule at the TiO2 surface. This results in an adsorbed superoxo (O2(-)) or peroxo (O2(2-)) species or in molecular dissociation and formation of two oxygen adatoms (2 × O(2-)). Oxygen adsorption is also the first step toward oxygen incorporation, a fundamental reaction that strongly affects the chemical properties and charge-carrier densities; for instance, it can transform the material from an n-type semiconductor to a poor electronic conductor. In this Account, we present an overview of recent theoretical work on O2 adsorption and reactions on the reduced anatase (101) surface. Anatase is the TiO2 polymorph that is generally considered most active in photocatalysis. Experiments on anatase powders have shown that the properties of photoexcited electrons are similar to those of excess electrons from reducing defects, and therefore, oxygen on reduced anatase is also a model system for studying the role of O2 in photocatalysis. Experimentally, the characteristic Ti(3+) defect states disappear after adsorption of molecular oxygen, which indicates that the excess electrons are indeed trapped by O2. Moreover, superoxide surface species associated with two different cation surface sites, possibly a regular cation site and a cation close to an anion vacancy, were identified by electron paramagnetic resonance spectroscopy. On the theoretical side, however, density functional theory studies have consistently found that it is energetically more favorable for O2 to adsorb in the peroxo form rather than the superoxo form. As a result, obtaining a detailed understanding of the nature of the observed superoxide species has proven difficult for many years. On reduced anatase (101), both oxygen vacancies and Ti interstitials have been shown to reside exclusively in the susbsurface. We discuss how reaction of O2 with a subsurface O vacancy heals the vacancy while leading to the formation of a surface bridging dimer defect. Similarly, the interaction of O2 with a Ti interstitial causes migration of this defect to the surface and the formation of a surface TiO2 cluster. Finally, we analyze the peroxo and superoxo states of the adsorbed molecule. On the basis of periodic hybrid functional calculations of interfacial electron transfer between reduced anatase and O2, we show that the peroxide form, while energetically more stable, is kinetically less favorable than the superoxide form. The existence of a kinetic barrier between the superoxo and peroxo states is essential for explaining a variety of experimental observations.