Modeling competitive reaction mechanisms of peroxynitrite oxidation of guanine

5-Guanidino-4-nitroimidazole is a stable product from the peroxynitrite induced one-electron oxidation of guanine. Reaction mechanisms to form the 5-guanidino-4-nitroimidazole as well as 8-nitroguanine, through the combination of the guanine radical cation and nitrogen dioxide radical and through the combination of the deprotonated neutral guanine radical and nitrogen dioxide radical, have been investigated by the use of the B3LYP method of density functional theory. Our calculations suggest that the guanine radical cation mechanism is preferred over the neutral guanine radical mechanism and that a water molecule is involved in the reaction as a catalyst or as a reactant.     

Remote control of diastereoselectivity in intramolecular reactions of chiral allylsilanes

During investigations of cyclization reactions between chiral allylsilanes and N-acyliminium ions, it was discovered that a suitably positioned benzyloxy group on the allylsilane component caused a reversal in the diastereoselectivity of these reactions relative to that normally observed with alkyl-substituted allylsilanes. This effect was subsequently observed in two other reaction types. Investigations into this effect led to the proposal of product formation through thermodynamic control facilitated by neighboring group interactions with a transient cationic species. This hypothesis was experimentally supported by the isolation of an intermediate in the proposed mechanistic pathway.     

Synthesis of mono- and symmetrical di-N-hydroxy- and N-aminoguanidines

Novel mono- and symmetrical di-N-hydroxy- and N-aminoguanidines were readily prepared from the reaction of diverse hydroxylamines or hydrazines with reagent classes di(benzotriazol-1-yl)methanimine 6, (bis-benzotriazol-1-yl-methylene)amines 8a,b, benzotriazole-1-carboxamidines 10a-i, benzotriazole-1-carboximidamides 11a,b, and N'-hydroxy-1H-1,2,3-benzotriazole-1-carboximidamide 18. The preparation is described for a variety of N-hydroxy- and N-aminoguanidines with different substitution patterns in good yields.     

Phonon and electron-hole plasma effects on binding energies of excitons in wurtzite GaN/In<Subscript>x</Subscript>Ga<Subscript>1−x</Subscript>N quantum wells

The binding energy of an exciton screened by the electron-hole plasma in a wurtzite GaN/In _x Ga_1−x N quantum well (in the case of 0.1 < x < 1 within which the interface phonon modes play a dominant role) is calculated including the exciton-phonon interaction by a variational method combined with a self-consistent procedure. The coupling between the exciton and various longitudinal-like optical phonon modes is considered to demonstrate the polaronic effect which strongly depends on the exciton wave function. All of the built-in electric field, the exciton-phonon interaction and the electron-hole plasma weaken the Coulomb coupling between an electron and a hole to reduce the binding energy since the former separates the wave functions of the electron and hole in the z direction and the later two enlarge the exciton Bohr radius. The electron-hole plasma not only restrains the built-in electric field, but also reduces the polaronic effect to the binding energy.     

The Structural Rule Distinguishing a Superfold: A Case Study of Ferredoxin Fold and the Reverse Ferredoxin Fold

Superfolds are folds commonly observed among evolutionarily unrelated multiple superfamilies of proteins. Since discovering superfolds almost two decades ago, structural rules distinguishing superfolds from the other ordinary folds have been explored but remained elusive. Here, we analyzed a typical superfold, the ferredoxin fold, and the fold which reverses the N to C terminus direction from the ferredoxin fold as a case study to find the rule to distinguish superfolds from the other folds. Though all the known structural characteristics for superfolds apply to both the ferredoxin fold and the reverse ferredoxin fold, the reverse fold has been found only in a single superfamily. The database analyses in the present study revealed the structural preferences of αβ- and βα-units; the preferences separate two α-helices in the ferredoxin fold, preventing their collision and stabilizing the fold. In contrast, in the reverse ferredoxin fold, the preferences bring two helices near each other, inducing structural conflict. The Rosetta folding simulations suggested that the ferredoxin fold is physically much more realizable than the reverse ferredoxin fold. Therefore, we propose that minimal structural conflict or minimal frustration among secondary structures is the rule to distinguish a superfold from ordinary folds. Intriguingly, the database analyses revealed that a most stringent structural rule in proteins, the right-handedness of the βαβ-unit, is broken in a set of structures to prevent the frustration, suggesting the proposed rule of minimum frustration among secondary structural units is comparably strong as the right-handedness rule of the βαβ-unit.     

Phytophenol Dimerization Reaction: From Basic Rules to Diastereoselectivity and Beyond

Phytophenol dimerization, which is a radical-mediated coupling reaction, plays a critical role in many fields, including lignin biosynthesis. To understand the reaction, 2,2-diphenyl-1-picrylhydrazyl radical was used to initiate a series of phytophenol dimerization reactions in methanol. The products were identified using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS/MS) analysis in situ. The identified products mainly included biphenols, magnolol, honokiol, gingerol 6,6′-dimers, 3,6-dimethoxylcatechol β,β′ dimer, euphorbetin, bis-eugenol, dehydrodiisoeugenol, trans-ε-viniferin, (+) pinoresinol, and (−) pinoresinol. Structure–function relationship analysis allowed four basic rules to be defined: meta-excluded, C–C bonding domination, ortho-diOH co-activation, and exocyclic C=C involvement. The exocyclic C=C involvement, however, required conjugation with the phenolic core and the para-site of the -OH group, to yield a furan-fused dimer with two chiral centers. Computational chemistry indicated that the entire process was completed via a radical coupling reaction and an intramolecular conjugate addition reaction. Similar results were also found for the horseradish peroxidase (HRP)-catalyzed coniferyl alcohol dimerization, which produced (+) and (−) pinoresinols (but no (−) epipinoresinol), suggesting that the HRP-catalyzed process was essentially an exocyclic C=C-involved phytophenol dimerization reaction. The reaction was highly diastereoselective. This was attributed to the intramolecular reaction, which prohibited Re-attack. The four basic rules and diastereoselectivity can explain and even predict the main products in various chemical and biological events, especially oxidase-catalyzed lignin cyclization.     

Ultra-high-performance liquid chromatography-Quadrupole-Exactive-Orbitrap-tandem mass spectrometry-based putative identification for Eucommiae Folium (Duzhongye) and its quality-marker candidate for pharmacopeia

Eucommiae Folium (Duzhongye) is a traditional Chinese medicine with a long history of use in China. However, its quality-marker in Chinese Pharmacopoeia is poorly defined nowadays. The study, therefore, conducted an ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap tandem mass spectrometry analysis to obtain accurate data. The obtained data were then compared with the authentic standards library using Xcalibur 4.1 software package and TraceFinder General Quan. Through the comparison, the study has putatively identified 26 bioactive compounds, which include 17 flavonoid derivatives (catechin, quercetin 3-gentiobioside, quercetin 3-O-β-D-glucose-7-O-β-D-gentiobioside, taxifolin, myricetin 3-O-galactoside, myricitrin, hyperoside, rutin, isoquercitrin, quercetin 3-O-β-xylopyranoside, quercitrin, isorhamnetin 3-O-β-D-glucoside, quercetin, kaempferol, S-eriodictyol, S-naringenin, and phloridzin), four caffeoylquinic acids (neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C), two alkaloids (vincamine and jervine), one lignan (pinoresinol), one xanthone (cowaxanthone B), and one steroid (cholesteryl acetate). Of these, flavonoid isoquercitrin is recommended as the new and additional pharmacopeia quality-marker candidate, which can not only overcome the unreliability of old quality-marker but also recognize the possible counterfeit.