Adjacent Side Chains Research Articles

A mechanism study on the viscosity evolution of heavy oil upon peroxide oxidation and pyrolysis

In the present work, we investigate the viscosity evolution of heavy oil by peroxide oxidation and successive thermal pyrolysis. Our results show that, the oxidation majorly occurs in the aromatic hydrocarbon (AH), which may debranch the side chains of aromatic derivatives forming isolated long-chain carboxylic acids, or introduce carboxyl to the tail of the branch chains in aromatic structures. The elevated interactions between adjacent debranched side chains in AH as well as condensation of the AH fragments will occur, which will transfer the AH components to resins and result in a quasi-linear correlation between the viscosity and total acid number (TAN) of heavy oil. Upon pyrolysis, resins in original heavy oil will be fragmented accompanied with decarboxylation; while the prior oxidation to heavy oil, although increases the viscosity, will benefit the fragmentation and decarboxylation, leading to approximate viscosity reduction behavior. Our work reveals that the oxygen content should be an important factor that contributes to the high viscosity of heavy oil, which could render reliable reference for developing new strategies to efficiently recover heavy oil reservoirs.

Influence of peripheral alkyl chain length on the mesomorphic behaviours of hexasubstituted triphenylene 2,3-dicarboxylic esters

ABSTRACTA comparative study of our established synthetic approaches to hexasubsituted triphenylenes 2,3-dicarboxylic esters containing four identical β-alkoxy and two adjacent β-alkoxycarbonyl side chains shows that the phase behaviours of small-sized discotic liquid crystals can be tailored over a wide range by simply varying the length of the peripheral alkyl chains. All the prepared esters in two series were observed to form a single hexagonal columnar phase, except for Tp4-1 having four β-butyloxy and two adjacent β-methoxycarbonyl chains which displays two columnar mesophase behaviours with a transition from the columnar plastic phase to hexagonal columnar phase. A significant difference between the two mesophase was observed in the variable temperature X-ray diffraction studies, and the mesophase assignment was also confirmed by polarising optical microscopy and differential scanning calorimetry. Moreover, the prepared esters in each series display the general trend of decreasing clearing temperature upon increasing alkoxy or alkoxycarbonyl chains length. The intermediate triphenylene 2,3-dicarboxylic acids were also found not only to exhibit columnar hexagonal mesophase over a narrower temperature range by maintaining high melting and clearing points but also to form organogel on mixing with toluene or dichloromethane with the assistance of hydrogen bonding.

Three-dimensional structures of two heavily N-glycosylated Aspergillus sp. family GH3 β-D-glucosidases.

The industrial conversion of cellulosic plant biomass into useful products such as biofuels is a major societal goal. These technologies harness diverse plant degrading enzymes, classical exo- and endo-acting cellulases and, increasingly, cellulose-active lytic polysaccharide monooxygenases, to deconstruct the recalcitrant β-D-linked polysaccharide. A major drawback with this process is that the exo-acting cellobiohydrolases suffer from severe inhibition from their cellobiose product. β-D-Glucosidases are therefore important for liberating glucose from cellobiose and thereby relieving limiting product inhibition. Here, the three-dimensional structures of two industrially important family GH3 β-D-glucosidases from Aspergillus fumigatus and A. oryzae, solved by molecular replacement and refined at 1.95 Å resolution, are reported. Both enzymes, which share 78% sequence identity, display a three-domain structure with the catalytic domain at the interface, as originally shown for barley β-D-glucan exohydrolase, the first three-dimensional structure solved from glycoside hydrolase family GH3. Both enzymes show extensive N-glycosylation, with only a few external sites being truncated to a single GlcNAc molecule. Those glycans N-linked to the core of the structure are identified purely as high-mannose trees, and establish multiple hydrogen bonds between their sugar components and adjacent protein side chains. The extensive glycans pose special problems for crystallographic refinement, and new techniques and protocols were developed especially for this work. These protocols ensured that all of the D-pyranosides in the glycosylation trees were modelled in the preferred minimum-energy (4)C1 chair conformation and should be of general application to refinements of other crystal structures containing O- or N-glycosylation. The Aspergillus GH3 structures, in light of other recent three-dimensional structures, provide insight into fungal β-D-glucosidases and provide a platform on which to inform and inspire new generations of variant enzymes for industrial application.

Residue-Specific Force Field (RSFF2) Improves the Modeling of Conformational Behavior of Peptides and Proteins.

A recent report of (3)J(HNHα) scalar coupling constants for hundreds of two-residue peptides has provided an important opportunity to test simulation force fields for proteins. Here, we compare the abilities of three derivatives of the Amber ff99SB force field to reproduce these data. We report molecular dynamics (MD) simulations of 256 two-residue peptides and show that the recently developed residue-specific force field (RSFF2) produces a dramatic improvement in the agreement with experimental (3)J(HNHα) coupling constants. We further show that RSFF2 also appears to produce a modest improvement in reproducing the (3)J(HNHα) coupling constants of five model proteins. Perhaps surprisingly, an analysis of neighboring residue effects (NREs) on the (3)J(HNHα) coupling constants of the two-residue peptides indicates little difference between the force fields' abilities to reproduce experimental NREs. We speculate that this might indicate limitations in the force fields' descriptions of nonbonded interactions between adjacent side chains or with terminal capping groups.

Large-Scale Examination of Factors Influencing Phosphopeptide Neutral Loss during Collision Induced Dissociation.

Collision-induced dissociation (CID) remains the predominant mass spectrometry-based method for identifying phosphorylation sites in complex mixtures. Unfortunately, the gas-phase reactivity of phosphoester bonds results in MS/MS spectra dominated by phosphoric acid (H3PO4) neutral loss events, suppressing informative peptide backbone cleavages. To understand the major drivers of H3PO4 neutral loss, we performed robust nonparametric statistical analysis of local and distal sequence effects on the magnitude and variability of neutral loss, using a collection of over 35,000 unique phosphopeptide MS/MS spectra. In contrast to peptide amide dissociation pathways, which are strongly influenced by adjacent amino acid side chains, we find that neutral loss of H3PO4 is affected by both proximal and distal sites, most notably basic residues and the peptide N-terminal primary amine. Previous studies have suggested that protonated basic residues catalyze neutral loss through direct interactions with the phosphate. In contrast, we find that nearby basic groups decrease neutral loss regardless of mobility class, an effect only seen by stratifying spectra by charge-mobility. The most inhibitory bases are those immediately N-terminal to the phosphate, presumably because of steric hindrances in catalyzing neutral loss. Further evidence of steric effects is shown by the presence of proline, which can dramatically reduce the presence of neutral loss when between the phosphate and a possible charge donor. In mobile proton spectra, the N-terminus is the strongest predictor of high neutral loss, with proximity to the N-terminus essential for peptides to exhibit the highest levels of neutral loss.

Binding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors

One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong positive cooperativity between an H-bond accepting carbonyl functionality and the adjacent P3 hydrophobic side chain. Adding an H-bond donating amine adjacent to the P3 hydrophobic side chain further increases this positive cooperativity thereby improving the Ki by as much as 546-fold. In contrast, adding an amidine multiple H-bond/salt bridge group in the distal S1 pocket does not affect this cooperativity. An analysis of the crystallographic B-factors of the ligand groups inside the binding site indicates that the strong cooperativity is mainly due to a significant mutual reduction in the residual mobility of the hydrophobic side chain and the H-bonding functionalities that is absent when the separation distance is large. This type of cooperativity is important to encode in binding affinity prediction software, and to consider in SAR studies.

The effect of intercalated behavior in polymer/fullerene blend on the performance of organic bulk heterojunction solar cells

The morphology of active layer in organic bulk heterojunction solar cells has important influence on device performance. The intercalated behavior can exist when polymer/small molecular blend system meets the two criteria: the size of the small molecules is smaller than the distance between adjacent side-chains of polymer, and the small molecules should form a ground-state charge-transfer complex with polymer. The intercalated behavior affects the film morphology and is not beneficial to energy conversion process. In this paper, the forming process of intercalation in blend system was introduced. Then we concluded the influence of intercalation on film morphology including crystallization, phase separation and device performance including exciton diffusion, exciton dissociation, and carrier transport. The chemical and physical methods to inhibit intercalated behavior were also recommended at the same time. Furthermore, we posed the critical problems to be resolved in this field and prospect its developing foreground.

Synthesis of novel helical poly(N-propargylamides) containing azobenzene pendant groups and effects of substitution groups on azobenzene on the stability of helix

A series of novel N-propargylamides bearing substituted azobenzene pendant groups (RC6H4NNC6H4CONHCH(CH3)CONHCH2CCH, R=CH3CH2N(CH2)2OOC(CH2)3CH3 (V1), R=CH3CH2N(CH2)2OOCCH2NHCOCH3 (V2), R=H (V3)) were synthesized and polymerized with [Rh(nbd)Cl]2 as a catalyst to obtain the corresponding polymers (Poly(V1–3)). The azobenzene chromophores in the side chains of Poly(V1,2) contained bulky electron-donating substituents, while the azobenzene in Poly(V3) did not bear this kind of substituent. The introduction of substituted azobenzene chromophores into the side chains of poly(N-propargylamides) was found to increase the hydrogen bond strength, steric repulsion and electrostatic interactions between the neighboring side chains. These factors worked together to improve the helical stability of poly(N-propargylamides). The solubility of these poly(N-propargylamides) was increased by introducing substituents into the azobenzene chromophores. CD and UV–vis spectra showed that all the poly(N-propargylamides) took the helical structures with predominantly one-handed screw sense, which were tight helices. Furthermore, the unsubstituted azobenzene groups in the side chains of Poly(V3) also arranged to form the helical conformation. The helical structures of Poly(V1–3) remained stable at various temperatures (5–60°C). Poly(V1,2) exhibited good helicity in polar solvent, which indicated that the bulky substituents, electrostatic and steric repulsion between the adjacent side chains lessened the effect of polar solvent on the hydrogen bonding. The main chains of Poly(V1,3) still kept helical sense after the isomerization of trans-azobenzene to the cis form upon UV irradiation. The helical array of azobenzene side chains in Poly(V3) experienced reversible arrangement–disarrangement upon photoirradiation.

Peptide backbone cleavage by α-amidation is enhanced at methionine residues.

Cleavage reactions at backbone loci are one of the consequences of oxidation of proteins and peptides. During α-amidation, the Cα -N bond in the backbone is cleaved under formation of an N-terminal peptide amide and a C-terminal keto acyl peptide. On the basis of earlier works, a facilitation of α-amidation by the thioether group of adjacent methionine side chains was proposed. This reaction was characterized by using benzoyl methionine and benzoyl alanyl methionine as peptide models. The decomposition of benzoylated amino acids (benzoyl-methionine, benzoyl-alanine, and benzoyl-methionine sulfoxide) to benzamide in the presence of different carbohydrate compounds (reducing sugars, Amadori products, and reductones) was studied during incubation for up to 48 h at 80 °C in acetate-buffered solution (pH 6.0). Small amounts of benzamide (0.3-1.5 mol%) were formed in the presence of all sugars and from all benzoylated species. However, benzamide formation was strongly enhanced, when benzoyl methionine was incubated in the presence of reductones and Amadori compounds (3.5-4.2 mol%). The reaction was found to be intramolecular, because α-amidation of a similar 4-methylbenzoylated amino acid was not enhanced in the presence of benzoyl-methionine and carbohydrate compounds. In the peptide benzoyl-alanyl-methionine, α-amidation at the methionine residue is preferred over α-amidation at the benzoyl peptide bond. We propose here a mechanism for the enhancement of α-amidation at methionine residues.

4-Methoxy-N-(pyridin-4-ylmethyl)-3-(trifluoromethyl)benzamide monohydrate

In the title compound, C15H13F3N2O2·H2O, the dihedral angle between the benzene and pyridine rings is 74.97 (1)°. The –CF3 group attached to the benzene ring is syn to the C=O bond in the adjacent side chain. In the crystal, mol­ecules are linked to one another through the water mol­ecules by strong N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds, forming a ladder-type network. The benzamide mol­ecules are also linked to one another through C—H⋯F inter­actions, forming C(6) chains parallel to the b-axis direction. Aromatic π–π stacking inter­actions [centroid–centroid separations = 3.7150 (1) and 3.7857 (1) Å] between adjacent pairs of pyridine and benzene rings are also observed, resulting in a three-dimensional architecture are also observed.

Comparative study of interactions between thiophene\\pyridine\\benzene\\heptane and 1-butyl-3-methylimidazolium trifluoromethanesulfonate by density functional theory

Density functional theory has been employed to investigate the interactions between thiophene, pyridine, benzene, heptane and 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][OTf]). The GGA/PW91 functionals and DNP basis set were used to optimize their geometries. The interactions between [BMIM][OTf] and thiophene, pyridine, benzene, and heptane have been ascribed to the formation of hydrogen bonds by NBO and AIM methods. The most stable gas-phase structure of [BMIM][OTf] ion pair indicates that hydrogen bonding interactions between the oxygen atoms on [OTf] anions and the C2-hydrogen on the imidazolium ring play a dominating role in the formation of the ion pair. Additional interactions are observed between [OTf] anion and the hydrogen atoms on the adjacent alkyl side chains of [BMIM] cation. The [OTf] anion tends to be located near a ring C2-proton, suggesting that the adsorption of thiophene, pyridine, benzene, and heptane on [BMIM][OTf] did not change the dominant interactions of [BMIM]–[OTf] pair. The predicted geometries, interaction energies and frontier orbitals implied the preferential adsorption of thiophene and pyridine on the [BMIM][OTf].

Rearrangements of Nascent Peptide Inside the Ribosomal Exit Tunnel

All proteins, from bacteria to man, are made in the ribosome and are elongated, one residue at a time, at the peptidyl transferase center (PTC). This growing peptide chain wends its way through the ribosomal tunnel to the exit port, ∼ 100 angstroms from the PTC. Regulation of the movement of the peptide within the tunnel and allosteric communication along the tunnel during translation are not well understood. Previously, we demonstrated that solvent-accessible volume surrounding a modifiable cysteine increases monotonically with increase in the van der Waal's volume of the adjacent side chain (Lu et al., J.Mol.Biol. 411: 499-510, 2011) and that the magnitude of this effect depends on location within the ribosomal tunnel. using a photocrosslinking approach, we confirm these results. We extend these studies to investigate whether mutations in the nascent peptide deep in the tunnel affect the accessibility of a modifiable reporter cysteine at the exit port and whether specific regions of the tunnel instigate these effects. Tryptophan vis-a-vis alanine, engineered into the nascent peptide at a distance of 17-19 residues from the PTC, alters the accessibility of residues at the exit port, a distance of 33 residues from the PTC, roughly 50 angstroms from the introduced point mutations. These findings are consistent with long-range rearrangements and may contribute to mechanisms governing sequence-specific signaling from different regions of the tunnel during translation. Supported by NIH grant R01GM52302.

Strong contributions from vertical triads to helix-partner preferences in parallel coiled coils.

Pairing preferences in heterodimeric coiled coils are determined by complementarities among side chains that pack against one another at the helix-helix interface. However, relationships between dimer stability and interfacial residue identity are not fully understood. In the context of the "knobs-into-holes" (KIH) packing pattern, one can identify two classes of interactions between side chains from different helices: "lateral", in which a line connecting the adjacent side chains is perpendicular to the helix axes, and "vertical", in which the connecting line is parallel to the helix axes. We have previously analyzed vertical interactions in antiparallel coiled coils and found that one type of triad constellation (a'-a-a') exerts a strong effect on pairing preferences, while the other type of triad (d'-d-d') has relatively little impact on pairing tendencies. Here, we ask whether vertical interactions (d'-a-d') influence pairing in parallel coiled-coil dimers. Our results indicate that vertical interactions can exert a substantial impact on pairing specificity, and that the influence of the d'-a-d' triad depends on the lateral a' contact within the local KIH motif. Structure-informed bioinformatic analyses of protein sequences reveal trends consistent with the thermodynamic data derived from our experimental model system in suggesting that heterotriads involving Leu and Ile are preferred over homotriads involving Leu and Ile.

The Physiological Functions of Mammalian Endoplasmic Oxidoreductin 1: On Disulfides and More

The oxidative process of disulfide-bond formation is essential for the folding of most secretory and membrane proteins in the endoplasmic reticulum (ER). It is driven by electron relay pathways that transfer two electrons derived from the fusion of two adjacent cysteinyl side chains onto various types of chemical oxidants. The conserved, ER-resident endoplasmic oxidoreductin 1 (Ero1) sulfhydryl oxidases that reduce molecular oxygen to generate an active-site disulfide represent one of these pathways. In mammals, two family members exist, Ero1α and Ero1β. The two mammalian Ero1 enzymes differ in transcriptional and post-translational regulation, tissue distribution, and catalytic turnover. A specific protein-protein interaction between either isoform and protein disulfide isomerase (PDI) facilitates the propagation of disulfides from Ero1 via PDI to nascent polypeptides, and inbuilt oxidative shutdown mechanisms in Ero1α and Ero1β prevent excessive oxidation of PDI. Besides disulfide-bond generation, Ero1α also regulates calcium release from the ER and the secretion of disulfide-linked oligomers through its reversible association with the chaperone ERp44. This review explores the functional repertoire and possible redundancy of mammalian Ero1 enzymes. Systematic analyses of different knockout mouse models will be the most promising strategy to shed new light on unique and tissue-specific roles of Ero1α and Ero1β. Moreover, in-depth characterization of the known physical interactions of Ero1 with peroxidases and PDI family members will help broaden our functional and mechanistic understanding of Ero1 enzymes.

Molecular Insights into DNA Polymerase Deterrents for Ribonucleotide Insertion

DNA polymerases can misinsert ribonucleotides that lead to genomic instability. DNA polymerase β discourages ribonucleotide insertion with the backbone carbonyl of Tyr-271; alanine substitution of Tyr-271, but not Phe-272, resulted in a >10-fold loss in discrimination. The Y271A mutant also inserted ribonucleotides more efficiently than wild type on a variety of ribonucleoside (rNMP)-containing DNA substrates. Substituting Mn(2+) for Mg(2+) decreased sugar discrimination for both wild-type and mutant enzymes primarily by increasing the affinity for rCTP. This facilitated crystallization of ternary substrate complexes of both the wild-type and Y271A mutant enzymes. Crystallographic structures of Y271A- and wild type-substrate complexes indicated that rCTP is well accommodated in the active site but that O2' of rCTP and the carbonyl oxygen of Tyr-271 or Ala-271 are unusually close (∼2.5 and 2.6 Å, respectively). Structure-based modeling indicates that the local energetic cost of positioning these closely spaced oxygens is ∼2.2 kcal/mol for the wild-type enzyme. Because the side chain of Tyr-271 also hydrogen bonds with the primer terminus, loss of this interaction affects its catalytic positioning. Our results support a model where DNA polymerase β utilizes two strategies, steric and geometric, with a single protein residue to deter ribonucleotide insertion.

Proton Transfer in Proton Exchange Membrane Based on RDF

PEM fuel cell is the most promising application as an automotive power. Proton transfer in PEM is one of important factors to understand the performance of PEM fuel cell. In this paper, the proton transfer mechanisms are analyzed by the molecular simulation based on the basic principle of molecular dynamics. Effects of water content in the proton exchange membrane and cell temperature on the proton transfer in the membrane are studied by the radial distribution function (RDF). Results show that proton transfers in the Nafion polymer by water bridges between two sulfonic groups of adjacent side chains. There are more water bridges supporting proton transfer with the increase of water content in membrane. The increase of cell temperature speeds up the form and break of O-H bond, which promotes the proton transfer. The research results are very helpful to understanding the proton transfer mechanism in proton exchange membrane and promoting the applications of PEM fuel cell.

Effects of β-glucosidase hydrolyzed products of harpagide and harpagoside on cyclooxygenase-2 (COX-2) in vitro

Harpagide (1) and harpagoside (2) are two iridoid glycosides existing in many medicinal plants. Although they are believed to be the main bioactive compounds related to the anti-inflammatory efficacy of these plants, the mechanisms of their anti-inflammatory activities remain unclear. The results of our present study showed that 1 and 2 had no effects on inhibitions of cyclooxygenase (COX)-1/2 enzyme activity, tumor necrosis factor-α (TNF-α) release, and nitric oxide (NO) production in vitro. However, the hydrolyzed products of 1 and 2 with β-glucosidase treatment showed a significant inhibitory effect on COX-2 activity at 2.5–100μM in a concentration-dependent manner. Our further study revealed that the hydrolyzed 2 product was structurally the same as the hydrolyzed 1 product (H-harpagide (3)). The structure of 3 was 2-(formylmethyl)-2,3,5-trihydroxy-5-methylcyclopentane carbaldehyde, with a backbone similar to prostaglandins and COX-2 inhibitors such as celecoxib. All of them have a pentatomic ring with two adjacent side chains. The result of molecular modeling and docking study showed that 3 could bind to the COX-2 active domain well through hydrophobic and hydrogen-bonding interactions, whereas 1 and 2 could not, implying that the hydrolysis of the glycosidic bond of 1 and 2 is a pre-requisite step for their COX-2 inhibitory activity.

Anchored clathrate waters bind antifreeze proteins to ice.

The mechanism by which antifreeze proteins (AFPs) irreversibly bind to ice has not yet been resolved. The ice-binding site of an AFP is relatively hydrophobic, but also contains many potential hydrogen bond donors/acceptors. The extent to which hydrogen bonding and the hydrophobic effect contribute to ice binding has been debated for over 30 years. Here we have elucidated the ice-binding mechanism through solving the first crystal structure of an Antarctic bacterial AFP. This 34-kDa domain, the largest AFP structure determined to date, folds as a Ca(2+)-bound parallel beta-helix with an extensive array of ice-like surface waters that are anchored via hydrogen bonds directly to the polypeptide backbone and adjacent side chains. These bound waters make an excellent three-dimensional match to both the primary prism and basal planes of ice and in effect provide an extensive X-ray crystallographic picture of the AFPice interaction. This unobstructed view, free from crystal-packing artefacts, shows the contributions of both the hydrophobic effect and hydrogen bonding during AFP adsorption to ice. We term this mode of binding the "anchored clathrate" mechanism of AFP action.

Effect of pathogenic mutations on the structure and dynamics of Alzheimer’s Aβ42-amyloid oligomers

Converging lines of evidence suggest that soluble A beta-amyloid oligomers play a pivotal role in the pathogenesis of Alzheimer's disease, and present direct effectors of synaptic and cognitive dysfunction. Three pathological E22-A beta-amyloid point mutants (E22G, E22K, E22Q) and the deletion mutant E22 Delta exhibit an enhanced tendency to form prefibrillar aggregates. The present study assessed the effect of these four mutations using molecular dynamics simulations and subsequent structural and energetic analyses. Our data shows that E22 plays a unique role in wild type A beta, since it has a destabilising effect on the oligomer structure due to electrostatic repulsion between adjacent E22 side chains. Mutations in which E22 is replaced by an uncharged residue result in higher oligomer stability. This effect is also observed to a lesser extent for the E22K mutation and is consistent with its lower pathogenicity compared to other mutants. Interestingly, deletion of E22 does not destroy the amyloid fold but is compensated by local changes in the backbone geometry that allow the preservation of a structurally important salt bridge. The finding that all mutant oligomers investigated exhibit higher internal stability than the wild type offers an explanation for the experimentally observed enhanced oligomer formation and stability.

Peculiar Stability of Amino Acids and Peptides from a Radical Perspective

Photochemical reactions of free and N-acetyl alpha-amino acids with chlorine and deuterium labeled hydrogen peroxide have been used to determine both the relative rates of reaction of molecules of these classes and the relative reactivity of their different types of hydrogen toward abstraction by chlorine and oxygen centered radicals. The relative rates of reaction of these species range over more than 3 orders of magnitude; however, where data are available from more than one amino acid for a particular type of group at a specific position on the side chain, the values are remarkably similar. The predictive utility of these results has been demonstrated for the regioselective chlorination of tripeptides. More generally this analysis shows that the backbone and adjacent side chain positions of amino acids and peptides are peculiarly resistant to hydrogen atom transfer, and a similar pattern of reactivity has been noted from earlier studies of reactions of modified substrates catalyzed by isopenicillin-N-synthetase. Such resistance stands out in contrast to the common occurrence of free radical reactions of alpha-amino acids, peptides, and proteins and their importance in biology. Nevertheless, it provides a reason for the ability of amino acids and their derivatives to avoid degradation in Nature where they are constantly exposed to radicals, and it accounts, at least in part, for the anomalous ability of enzymes to catalyze free radical reactions without being broken down by the radical intermediates.