Equivalent Protons Research Articles

Cytochrome P450-The Wonderful Nanomachine Revealed through Dynamic Simulations of the Catalytic Cycle.

This Account addresses the catalytic cycle of the enzyme cytochrome P450 (CYP450) as a prototypical biological machine with automatic features. CYP450 is a nanomachine that uses dioxygen and two reducing and two proton equivalents to oxidize a plethora of molecules (so-called substrates) as a means of supplying bio-organisms with essential molecules (e.g., brain neurotransmitters, sex hormones, etc.) and protecting biosystems against poisoning. An enticing property of CYP450s is that entrance of an oxidizable substrate into the active site initiates a series of events that constitute the catalytic cycle, which functions "automatically" in a regulated sequence of events culminating in the production of the oxidized substrates (e.g., hydroxylated, epoxidized, etc.), oftentimes with remarkable stereo- and regioselectivities. It is timely to demonstrate how theory uses molecular dynamics (MD) simulations and quantum-mechanical/molecular-mechanical (QM/MM) calculations to complement experiments and elucidate the choreography by which the protein regulates the catalytic cycle. CYP450 is a heme enzyme that contains a ferric ion (FeIII) coordinated by a porphyrin ligand, a water molecule, and a cysteinate ligand that is provided by a strategic residue of the encapsulating protein. While many of the individual steps are sufficiently well-understood, we shall provide here an overview of the factors that cause all of the steps to be sequentially coordinated. To this end, we use examples from three different CYP450 enzymes: the bacterial ones CYP450BM3 and CYP450CAM and the mammalian enzyme CYP4503A4. The treatment is limited to the catalytic cycle, as aspects of two-state reactivity were reviewed previously (e.g., Shaik , S. ; et al. Chem. Rev. 2005 , 105 , 2279 ). What are the principles that govern the seeming automatic feature? For example, how do substrate entrance and binding gate the enzyme? How does the reductase attachment to the enzyme affect the next steps? What triggers the attachment of the reductase? How does the electron transfer (ET) that converts FeIII to FeII occur? Is the ET coordinated with the entrance of O2 into the active site? What is the mechanism of the latter step? Since the entrance of the substrate expels the water molecules from the active site, how do water molecules re-enter to form a proton channel, which is necessary for creating the ultimate oxidant Compound I? How do mutations that disrupt the water channel nevertheless create a competent oxidant? By what means does the enzyme produce regio- and stereoselective oxidation products? What triggers the departure of the oxidized product, and how does the exit occur in a manner that generates the resting state ready for the next cycle? This Account shows that the entrance of the substrate triggers all of the ensuing events.

Directing the reactivity of metal hydrides for selective CO2 reduction

A critical challenge in electrocatalytic CO2 reduction to renewable fuels is product selectivity. Desirable products of CO2 reduction require proton equivalents, but key catalytic intermediates can also be competent for direct proton reduction to H2 Understanding how to manage divergent reaction pathways at these shared intermediates is essential to achieving high selectivity. Both proton reduction to hydrogen and CO2 reduction to formate generally proceed through a metal hydride intermediate. We apply thermodynamic relationships that describe the reactivity of metal hydrides with H+ and CO2 to generate a thermodynamic product diagram, which outlines the free energy of product formation as a function of proton activity and hydricity (∆GH-), or hydride donor strength. The diagram outlines a region of metal hydricity and proton activity in which CO2 reduction is favorable and H+ reduction is suppressed. We apply our diagram to inform our selection of [Pt(dmpe)2](PF6)2 as a potential catalyst, because the corresponding hydride [HPt(dmpe)2]+ has the correct hydricity to access the region where selective CO2 reduction is possible. We validate our choice experimentally; [Pt(dmpe)2](PF6)2 is a highly selective electrocatalyst for CO2 reduction to formate (>90% Faradaic efficiency) at an overpotential of less than 100 mV in acetonitrile with no evidence of catalyst degradation after electrolysis. Our report of a selective catalyst for CO2 reduction illustrates how our thermodynamic diagrams can guide selective and efficient catalyst discovery.

Synthesis of new potential biological active substances among 3-mercapto-4-amino-5-benzyl-1,2,4-triazol-4H derivatives

Conventional approaches to the formation of 1,2,4-triazole ring allow to introduce different substituents into the heterocyclic ring during the synthesis of key intermediates stage. In continuation of previous studies the synthesis of 3-mercapto-4-amino-5-benzyl-1,2,4-triazole-4H derivatives is described.
 The aim of investigation was synthesis of a series of new derivatives of 3-mercapto-4-amino-5-benzyl-1,2,4-triazole, proving their structure by physico-chemical methods and planning of pharmacological screening using PASS.
 Phenylacetic acid ethyl ester has been used for the synthesis as starting substance. It was subjected to hydrazinolysis to receive an appropriate hydrazide. In the next stage substance obtained was processed with hydrogen disulfide and appropriate potassium ditiokarbaminat has been received, which by reaction with an excess of hydrazine hydrate has been cyclised into a target 3-mercapto-4-amino-5-benzyl-1,2,4-triazol-4H. The first stage of chemical transformation reactions of key intermediate was its alkylation with chloroacetanilides under alkaline catalysis. By Paal–Knorr reaction the amino group in the synthesized alkylthio-4-amino-5-benzyl-1,2,4-triazole-4H was modified into pyrrole ring by the action of 2,5-dimethoxytetrahydrofuran in acetic acid medium.
 The structure of the compounds synthesized has been proved by 1H NMR spectroscopy. The successful alkylation of mercapto group indicates the disappearance of its proton signal at the spectra and appearance of the acetanilide residues protons signals. Modification of the amino derivatives into corresponding pyrrolyl substituted has been accompanied by the appearance of the triplet signals of magnet equivalent methyne protons of the pyrrole ring (protons at positions 3.4) at 6.30 ppm. The signals of the second pyrrole protons pair overlap with other aromatic protons signals.
 For the planning of pharmacological screening previous prognosis of the potential pharmacological activity spectrum has been carried out using software PASS. The prognosis showed that for all pyrrolyl substituted substances predominant in the spectrum of action was the influence on the central nervous system, and the probability of the activity of their synthetic precursors mainly limited to moderate antioxidant properties.

Heterogeneous Parahydrogen Pairwise Addition to Cyclopropane.

Hyperpolarized gases revolutionize functional pulmonary imaging. Hyperpolarized propane is a promising emerging contrast agent for pulmonary MRI. Unlike hyperpolarized noble gases, proton-hyperpolarized propane gas can be imaged using conventional MRI scanners with proton imaging capability. Moreover, it is non-toxic odorless anesthetic. Furthermore, propane hyperpolarization can be accomplished by pairwise addition of parahydrogen to propylene. Here, we demonstrate the feasibility of propane hyperpolarization via hydrogenation of cyclopropane with parahydrogen. 1 H propane polarization up to 2.4 % is demonstrated here using 82 % parahydrogen enrichment and heterogeneous Rh/TiO2 hydrogenation catalyst. This level of polarization is several times greater than that obtained with propylene as a precursor under the same conditions despite the fact that direct pairwise addition of parahydrogen to cyclopropane may also lead to formation of propane with NMR-invisible hyperpolarization due to magnetic equivalence of nascent parahydrogen protons in two CH3 groups. NMR-visible hyperpolarized propane demonstrated here can be formed only via a reaction pathway involving cleavage of at least one C-H bond in the reactant molecule. The resulting NMR signal enhancement of hyperpolarized propane was sufficient for 2D gradient echo MRI of ∼5.5 mL phantom with 1×1 mm2 spatial resolution and 64×64 imaging matrix despite relatively low chemical conversion of cyclopropane substrate.

Bio-regeneration of activated carbon: A comprehensive review

Abstract The use of microorganisms to regenerate activated carbon (AC), bio-generation, can avert costly and logistically challenging ex-situ steam regeneration of carbon normally required to recover its adsorptive capacity. Bio-regeneration employs microbial metabolism in which the microbes use the available organic substrates (contaminants) to generate energy. During this process, they generate equivalent protons and electrons, which are transferred to the substrates to finally break them down to simpler molecules or ions, such as CO2, methane and Cl−. The optimal microbial conditions depend on the temperature, available nitrogen and phosphorus levels, dissolved oxygen levels, and microbe/substrate stoichiometric ratios and the residence time of the AC particles within the reactor. In this review, the authors highlight the most recent development in bio-regeneration including the regeneration mechanism, the relationship between the reversibility of adsorption and the efficiency of bio-regeneration, the general aspects affecting bio-regeneration, the principle and target compounds for bio-regeneration, different established methods for quantifying the bio-regeneration and the efficiency of bio-regeneration. Few case studies of bio-regeneration of activated carbon loaded with different contaminants are presented. Research on microbiology regeneration has gained considerable attention in recent years, but it still needs more contribution from other disciplines including process engineering, biochemistry and material sciences for optimizing the process performance.

1H NMR Spectroscopy of [FeFe] Hydrogenase: Insight into the Electronic Structure of the Active Site.

The [FeFe] hydrogenase HydA1 from Chlamydomonas reinhardtii has been studied using 1H NMR spectroscopy identifying the paramagnetically shifted 1H resonances associated with both the [4Fe-4S]H and the [2Fe]H subclusters of the active site “H-cluster”. The signal pattern of the unmaturated HydA1 containing only [4Fe-4S]H is reminiscent of bacterial-type ferredoxins. The spectra of maturated HydA1, with a complete H-cluster in the active Hox and the CO-inhibited Hox–CO state, reveal additional upfield and downfield shifted 1H resonances originating from the four methylene protons of the azadithiolate ligand in the [2Fe]H subsite. The two axial protons are affected by positive spin density, while the two equatorial protons experience negative spin density. These protons can be used as important probes sensing the effects of ligand-binding to the catalytic site of the H-cluster.

Characteristics of energy deposition from 1-1000 MeV proton and neutron induced nuclear reactions in silicon

The characteristics of the energy deposition of the secondary particles from the proton and neutron induced elastic and nonelastic reactions in silicon over a wide energy range of 1-1000 MeV, which are of great value for the proton and neutron single event effect (SEE) study, are investigated systematically in detail with Geant4 simulations. According to our simulation results, some important issues about the proton and neutron SEEs, including the energy dependence of the SEE cross sections, the equivalence of protons and neutrons in SEEs, the effects of the critical charge on SEEs, the geometric effect of the sensitive volumes, and the role of the elastic scattering mechanism in SEEs, are discussed. And some significant conclusions are tried to be drawn. With our systematic study, a comprehensive and profound understanding about the proton and neutron SEEs is reached from the physical perspective.

Bang-bang optimal control of large spin systems: Enhancement of 13C–13C singlet-order at natural abundance

Using a bang-bang optimal control technique, we transfer polarization from a set of abundant high-γ nuclei directly to singlet order of a low-γ spin-pair. This approach is analogous to algorithmic cooling (AC) procedure used in quantum state purification. Specifically, we apply this method for enhancing the singlet order in a natural abundant 13C- 13C spin pair by exploiting nine equivalent protons of an 11-spin system. Compared to the standard method not involving polarization transfer, we find an enhancement of singlet order by about 3.4 times. In addition, since the singlet magnetization is contributed by the faster relaxing protons, the recycle delay is halved. Thus effectively we observe a reduction in the overall experimental time by a factor of 23. We also discuss a possible extension of AC, known as heat-bath algorithmic cooling (HBAC).

Entanglement and co-tunneling of two equivalent protons in hydrogen bond pairs.

A theoretical study is reported of a system of two identical symmetric hydrogen bonds, weakly coupled such that the two mobile protons can move either separately (stepwise) or together (concerted). It is modeled by two equivalent quartic potentials interacting through dipolar and quadrupolar coupling terms. The tunneling Hamiltonian has two imaginary modes (reaction coordinates) and a potential with a single maximum that may turn into a saddle-point of second order and two sets of (inequivalent) minima. Diagonalization is achieved via a modified Jacobi-Davidson algorithm. From this Hamiltonian the mechanism of proton transfer is derived. To find out whether the two protons move stepwise or concerted, a new tool is introduced, based on the distribution of the probability flux in the dividing plane of the transfer mode. While stepwise transfer dominates for very weak coupling, it is found that concerted transfer (co-tunneling) always occurs, even when the coupling vanishes since the symmetry of the Hamiltonian imposes permanent entanglement on the motions of the two protons. We quantify this entanglement and show that, for a wide range of parameters of interest, the lowest pair of states of the Hamiltonian represents a perfect example of highly entangled quantum states in continuous variables. The method is applied to the molecule porphycene for which the observed tunneling splitting is calculated in satisfactory agreement with experiment, and the mechanism of double-proton tunneling is found to be predominantly concerted. We show that, under normal conditions, when they are in the ground state, the two porphycene protons are highly entangled, which may have interesting applications. The treatment also identifies the conditions under which such a system can be handled by conventional one-instanton techniques.

Path to 1-MW at J-PARC Rapid Cycling Synchrotron

The accelerator system at Japan Proton Accelerator Research Complex (J-PARC) has been operational since May 2008 and has mainly been used to perform physics experiments. The accelerator system consists of a Linac, a Rapid Cycling Synchrotron (RCS), and a Main Ring Synchrotron. The originally designed RCS injection energy is 400MeV, but the first operation started at 181MeV. New acceleration cavities were installed in J-PARC Linac during the summer shutdown of 2013, and user operation by the Material and Life science Facility (MLF) at the injection energy of 400MeV was started from February 2014. Post beam commissioning of 400MeV injection energy, beam loss was small enough, and we established 300kW continuous operation. Subsequently, the peak current of the Linac was increased from 30mA to 50mA. This upgrade enabled us to try 1-MW beam acceleration. Finally, after some additional improvements, we successfully accelerated 1-MW equivalent protons.

Spectral, optical, thermal, Hirshfeld, antimicrobial studies and computational calculations of a new organic crystal, 1H-benzo[d]imidazol-3-ium-3,5-dinitrobenzoate

Single crystals of 1H-benzo[d]imidazol-3-ium-3,5-dinitrobenzoate (BDNB) were grown by reacting 3,5-dinitrobenzoic acid and benzimidazole by slow evaporation method. UV–Vis–NIR spectral studies of the BDNB show that the crystal is excellently transparent in entire visible region. Chemically and magnetically equivalent protons in BDNB were identified by 1H NMR technique. The carbon frame work of the molecule was established by 13C NMR spectroscopy. Proton transfer mechanism was confirmed by the presence of N+H group in BDNB by FT-IR spectroscopic technique. TG/DTA analyses confirmed that the crystal is stable up to172 °C. Single crystal XRD analysis was carried out to ascertain the molecular structure and the crystal belongs to monoclinic system with space group P21/c. Computational studies that include optimization of molecular geometry, natural bond analysis, Mulliken population analysis and HOMO-LUMO analysis were performed using B3LYP method at 6–31 g level. The low HOMO-LUMO energy gap of BDNB confirms high reactivity of BDNB. Hirshfeld analysis expose that O⋯H/H⋯O interactions are the prominent interactions. Theoretical calculations indicate that first order hyperpolarizability is 16 times greater than urea. The results show that the BDNB may be used for opto-electronic applications. The antimicrobial and antioxidant analyses shows concentration of the compound increases inhibition activity also increases.

The Mg2+-containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four Pumping Proton Equivalents in Each Catalytic Cycle

Bovine heart cytochrome c oxidase (CcO) pumps four proton equivalents per catalytic cycle through the H-pathway, a proton-conducting pathway, which includes a hydrogen bond network and a water channel operating in tandem. Protons are transferred by H3O+ through the water channel from the N-side into the hydrogen bond network, where they are pumped to the P-side by electrostatic repulsion between protons and net positive charges created at heme a as a result of electron donation to O2 bound to heme a3 To block backward proton movement, the water channel remains closed after O2 binding until the sequential four-proton pumping process is complete. Thus, the hydrogen bond network must collect four proton equivalents before O2 binding. However, a region with the capacity to accept four proton equivalents was not discernable in the x-ray structures of the hydrogen bond network. The present x-ray structures of oxidized/reduced bovine CcO are improved from 1.8/1.9 to 1.5/1.6 Å resolution, increasing the structural information by 1.7/1.6 times and revealing that a large water cluster, which includes a Mg2+ ion, is linked to the H-pathway. The cluster contains enough proton acceptor groups to retain four proton equivalents. The redox-coupled x-ray structural changes in Glu198, which bridges the Mg2+ and CuA (the initial electron acceptor from cytochrome c) sites, suggest that the CuA-Glu198-Mg2+ system drives redox-coupled transfer of protons pooled in the water cluster to the H-pathway. Thus, these x-ray structures indicate that the Mg2+-containing water cluster is the crucial structural element providing the effective proton pumping in bovine CcO.

Proton‐Coupled Reduction of an Iron Cyanide Complex to Methane and Ammonia

AbstractNitrogenase enzymes mediate the six‐electron reductive cleavage of cyanide to CH4 and NH3. Herein we demonstrate for the first time the liberation of CH4 and NH3 from a well‐defined iron cyanide coordination complex, [SiPiPr3]Fe(CN) (where [SiPiPr3] represents a tris(phosphine)silyl ligand), on exposure to proton and electron equivalents. [SiPiPr3]Fe(CN) additionally serves as a useful entry point to rare examples of terminally‐bound Fe(CNH) and Fe(CNH2) species that, in accord with preliminary mechanistic studies, are plausible intermediates of the cyanide reductive protonation to generate CH4 and NH3. Comparative studies with a related [SiPiPr3]Fe(CNMe2) complex suggests the possibility of multiple, competing mechanisms for cyanide activation and reduction.

Proton-Coupled Reduction of an Iron Cyanide Complex to Methane and Ammonia.

Nitrogenase enzymes mediate the six-electron reductive cleavage of cyanide to CH4 and NH3 . Herein we demonstrate for the first time the liberation of CH4 and NH3 from a well-defined iron cyanide coordination complex, [SiP(iPr) 3 ]Fe(CN) (where [SiP(iPr) 3 ] represents a tris(phosphine)silyl ligand), on exposure to proton and electron equivalents. [SiP(iPr) 3 ]Fe(CN) additionally serves as a useful entry point to rare examples of terminally-bound Fe(CNH) and Fe(CNH2 ) species that, in accord with preliminary mechanistic studies, are plausible intermediates of the cyanide reductive protonation to generate CH4 and NH3 . Comparative studies with a related [SiP(iPr) 3 ]Fe(CNMe2 ) complex suggests the possibility of multiple, competing mechanisms for cyanide activation and reduction.

EPR and DFT study of the ethylene reaction with O− radicals on the surface of nanocrystalline MgO

Different radical forms of oxygen (O−, O 2 − and O 3 − ) on the surface of nanocrystalline MgO are well known. It was earlier demonstrated that EPR-silent species with properties very similar to those of O− radicals exist on the surface of magnesium oxide in addition to the O− radicals observed by EPR. In this study we characterized the reactivity of these two types of O− radicals in reaction with ethylene. It was demonstrated that this reaction yields different products for observable and unobservable O− radicals. Conventional $${\text{O}}_{{3{\text{C}}}}^{ - }$$ radicals generated by MgO illumination with UV light at room temperature in the presence of oxygen initiate hydrogen atom abstraction from ethylene to form secondary radicals H2C=C− with hyperfine splitting A 1 = 59 G, A 2 = 6 G. The $${\text{O}}_{{4{\text{C}}}}^{ - }$$ radicals not observed directly by EPR were synthesized by MgO illumination in the presence of oxygen at 163 K followed by evacuation at 203 K. They were shown to react with ethylene to form an addition product with two groups of two equivalent protons with isotropic hyperfine constants A 1 = 38 G and A 2 = 23 G. Such radicals were obtained for the first time by reaction of O− radicals with ethylene on the MgO surface. Their concentration was approximately equal to the concentration of [ $${\text{O}}_{{4{\text{C}}}}^{ - }$$ ·O2] complexes observed by EPR before the oxygen desorption. The structures of both radicals were simulated by DFT, and a good match between the experimental and computational results was obtained.

The Mg2 +-containing water cluster of mammalian cytochrome c oxidase collects four pumping proton equivalents in each catalytic cycle

The Mg2 +-containing water cluster of mammalian cytochrome c oxidase collects four pumping proton equivalents in each catalytic cycle

Modulation of Proton-Coupled Electron Transfer through Molybdenum-Quinonoid Interactions.

An expanded series of π-bound molybdenum-quinonoid complexes supported by pendant phosphines has been synthesized. These compounds formally span three protonation-oxidation states of the quinonoid fragment (catechol, semiquinone, quinone) and two different oxidation states of the metal (Mo(0), Mo(II)), notably demonstrating a total of two protons and four electrons accessible in the system. Previously, the reduced Mo(0)-catechol complex 1 and its reaction with dioxygen to yield the two-proton/two-electron oxidized Mo(0)-quinone compound 4 was explored, while, herein, the expansion of the series to include the two-electron oxidized Mo(II)-catechol complex 2, the one-proton/two-electron oxidized Mo-semiquinone complex 3, and the two-proton/four-electron oxidized Mo(II)-quinone complexes 5 and 6 is reported. Transfer of multiple equivalents of protons and electrons from the Mo(0) and Mo(II) catechol complexes, 1 and 2, to H atom acceptor TEMPO suggests the presence of weak O-H bonds. Although thermochemical analyses are hindered by the irreversibility of the electrochemistry of the present compounds, the reactivity observed suggests weaker O-H bonds compared to the free catechol, indicating that proton-coupled electron transfer can be facilitated significantly by the π-bound metal center.

An Fe-N₂ Complex That Generates Hydrazine and Ammonia via Fe═NNH₂: Demonstrating a Hybrid Distal-to-Alternating Pathway for N₂ Reduction.

Biological N2 fixation to NH3 may proceed at one or more Fe sites in the active-site cofactors of nitrogenases. Modeling individual e(-)/H(+) transfer steps of iron-ligated N2 in well-defined synthetic systems is hence of much interest but remains a significant challenge. While iron complexes have been recently discovered that catalyze the formation of NH3 from N2, mechanistic details remain uncertain. Herein, we report the synthesis and isolation of a diamagnetic, 5-coordinate Fe═NNH2(+) species supported by a tris(phosphino)silyl ligand via the direct protonation of a terminally bound Fe-N2(-) complex. The Fe═NNH2(+) complex is redox-active, and low-temperature spectroscopic data and DFT calculations evidence an accumulation of significant radical character on the hydrazido ligand upon one-electron reduction to S = (1)/2 Fe═NNH2. At warmer temperatures, Fe═NNH2 rapidly converts to an iron hydrazine complex, Fe-NH2NH2(+), via the additional transfer of proton and electron equivalents in solution. Fe-NH2NH2(+) can liberate NH3, and the sequence of reactions described here hence demonstrates that an iron site can shuttle from a distal intermediate (Fe═NNH2(+)) to an alternating intermediate (Fe-NH2NH2(+)) en route to NH3 liberation from N2. It is interesting to consider the possibility that similar hybrid distal/alternating crossover mechanisms for N2 reduction may be operative in biological N2 fixation.

Quantitative Detection of PEGylated Biomacromolecules in Biological Fluids by NMR.

The accumulation, biodistribution, and clearance profiles of therapeutic agents are key factors relevant to their efficacy. Determining these properties constitutes an ongoing experimental challenge. Many such therapeutics, including small molecules, peptides, proteins, tissue scaffolds, and drug delivery vehicles, are conjugated to poly(ethylene glycol) (PEG) as this improves their bioavailability and in vivo stability. We demonstrate here that (1)H NMR spectroscopy can be used to quantify PEGylated species in complex biological fluids directly, rapidly, and with minimal sample preparation. PEG bears a large number of spectroscopically equivalent protons exhibiting a narrow NMR line width while resonating at a (1)H NMR frequency distinct from most other biochemical signals. We demonstrate that PEG provides a robust signal allowing detection of concentrations as low as 10 μg/mL in blood. This PEG detection limit is lowered by another order of magnitude when background proton signals are minimized using (13)C-enriched PEG in combination with a double quantum filter to remove (1)H signals from non-(13)C-labeled species. Quantitative detection of PEG via these methods is shown in pig blood and goat serum as examples of complex biological fluids. More practically, we quantify the blood clearance of (13)C-PEG and PEGylated-BSA (bovine serum albumin) following their intravenous injection in live rats. Given the relative insensitivity of line width to PEG size, we anticipate that the biodistribution and clearance profiles of virtually any PEGylated biomacromolecule from biological fluid samples can be routinely measured by (1)H NMR without any filtering or treatment steps.

Inward diffusion and loss of radiation belt protons

AbstractRadiation belt protons in the kinetic energy range 24 to 76 MeV are being measured by the Relativistic Electron Proton Telescope on each of the two Van Allen Probes. Data have been processed for the purpose of studying variability in the trapped proton intensity during October 2013 to August 2015. For the lower energies (≲32 MeV), equatorial proton intensity near L = 2 showed a steady increase that is consistent with inward diffusion of trapped solar protons, as shown by positive radial gradients in phase space density at fixed values of the first two adiabatic invariants. It is postulated that these protons were trapped with enhanced efficiency during the 7 March 2012 solar proton event. A model that includes radial diffusion, along with known trapped proton source and loss processes, shows that the observed average rate of increase near L = 2 is predicted by the same model diffusion coefficient that is required to form the entire proton radiation belt, down to low L, over an extended (∼103 year) interval. A slower intensity decrease for lower energies near L = 1.5 may also be caused by inward diffusion, though it is faster than predicted by the model. Higher‐energy (≳40 MeV) protons near the L = 1.5 intensity maximum are from cosmic ray albedo neutron decay. Their observed intensity is lower than expected by a factor ∼2, but the discrepancy is resolved by adding an unspecified loss process to the model with a mean lifetime ∼120 years.