Cα Cβ Research Articles

Adsorption of C–C Linkage-Contained Lignin Model Compound Over the Metal Surface of Catalysts: Quantum Simulation

To address the mechanism of C–C bond cleavage on the metal surface of the M/SiO2 (M represents metal) catalyst is desirable and vital during the catalytic depolymerization process of lignin in solvents. Density functional theory simulation is used to determine the energy of C–C bond dissociation, adsorption geometry, adsorption energy and electronic structures of three kinds of the β-1 bond contained lignin model compounds (Mo1, Mo2 and Mo3), which were adsorbed on the (100) surface of metal (Ni, Cu, W) in the catalysts. The bond dissociation energy (BDE) of Cα–Cβ was found to be lower than those of Caryl–Cα and Cβ–Caryl bond. The Cα–Cβ in Mo2 was adsorbed via a π configuration on the Ni(100) and Cu(100) surfaces, exhibiting the weak dissociation bond energy. The –OH group was anchored as a η1(O) configuration which was instable on the (100) surface of W. The model compounds might be co-adsorbed with hydrogen on the metal surface under the reaction condition. The adsorption of Mo2 on the (100) surface of Cu was changed to the η1(O) pattern, while the Cα–Cβ BDE was declined on the (100) surface of Ni and Cu involving the coverage of hydrogen. The adsorption on W(100) had no effect on the decline of Cα–Cβ BDE. The adsorption of Mo2 on the (100) surface of metals plays different roles on weakening the Cα–Cβ BDE, giving conceptual guide for the selective depolymerization of lignin to specific chemicals.

Novel chemical degradation pathways of proteins mediated by tryptophan oxidation: tryptophan side chain fragmentation.

This minireview focuses on novel degradation pathways of proteins in solution via intermediary tryptophan (Trp) radical cations, which are generated via photo-induced electron transfer to suitable acceptors such as disulfide bonds. Gas-phase mass spectrometry studies had indicated the potential for Trp radical cations to fragment via release of 3-methylene-3H-indol-1-ium from the side chain. HPLC-MS/MS analysis demonstrates that analogous fragmentation reactions occur during the exposure of peptides and proteins to light or accelerated stability testing. The light exposure of selected peptides and monoclonal antibodies leads to the conversion of Trp to glycine (Gly) or glycine hydroperoxide (GlyOOH), where GlyOOH could be reduced to hydroxyglycine, which undergoes subsequent cleavage. Product formation is consistent with Cα -Cβ fragmentation of intermediary Trp radical cations. For the peptide octreotide and specific glycoforms of IgG1 Fc domains, Trp side chain cleavage in aqueous solution is indicated by the formation of 3-methyleneindolenine (3-MEI), which adds to nucleophilic side chains, for example to Lys residues adjacent to the original Trp residues. Trp side chain cleavage leads to novel reaction products on specific peptide and protein sequences, which may have consequences for potency and immunogenicity.

Conformer-Specific and Diastereomer-Specific Spectroscopy of αβα Synthetic Foldamers: Ac-Ala-βACHC-Ala-NHBn.

The folding propensities of a capped, cyclically constrained, mixed α/β diastereomer pair, ( SRSS) Ac-Ala-βACHC-Ala-NHBn (hereafter RS) and ( SSRS) Ac-Ala-βACHC-Ala-NHBn ( SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/β-tripeptides contain a cyclohexane ring across each Cα -Cβ bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C═O/axial NH or equatorial NH/axial C═O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C═O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/β-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.

Crystal structures of resorcin[4]arene and pyrogallol[4]arene complexes with proline: A model for proline recognition through C[sbnd]H···π interaction

Resorcin[4]arene (resorcinol cyclic tetramer, abbreviated as RCT) or pyrogallol[4]arene (pyrogallol cyclic tetramer, PCT) form host–guest 1:1 complexes with DL-proline (DL-Pro) or l-proline (L-Pro), [RCT·DL-Pro]·2MeOH·3.5H2O (1) and 2[PCT·L-Pro]·2EtOH·10H2O (2), whose crystal structures have been determined. In each complex, the proline ligand is incorporated into the bowl-shaped cavity of RCT or PCT host molecules through CH … π interactions between alkyl protons of the pyrrolidine ring of proline and π-rings of RCT or PCT, forming an [RCT/PCT·Pro] structural fragment. In the crystal lattice, two [RCT/PCT·Pro] fragments self-associate to form a ligand-mediated dimeric structure, [RCT·D-Pro·L-Pro·RCT] in 1 or [PCT·L-Pro·L-Pro·PCT] in 2. A 1H NMR solution study gave the host‒ligand binding constants of 10.0 ± 1.1 M–1 for the RCT–DL-Pro system and 17.3 ± 1.3 M–1 for the PCT–L-Pro system. These complexes provide a synthetic model for the recognition of the proline residue in proline-containing substrates or inhibitors by enzymes through CH … π interaction. The CSD survey revealed that the absolute value of the torsion angle N–Cα–CO1 (O1 is cis to N) about the carboxyl Cα–C bond of proline is significantly smaller than that of the Cβ–Cα–CO2 (O2 is cis to Cβ) torsion angle.

Iridium-catalysed primary alcohol oxidation and hydrogen shuttling for the depolymerisation of lignin

A new Ir catalysed approach for the selective cleavage of the Cα–Cβ bond in lignin β-O-4 units, allowing access to novel and tuneable monomeric product mixtures.

Structural Characterization of β-Agostic Bonds in Pd-Catalyzed Polymerization

β-agostic Pd complexes are critical intermediates in catalytic reactions, such as olefin polymerization and Heck reactions. Pd β-agostic complexes, however, have eluded structural characterization, due to the fact that these highly unstable molecules are difficult to isolate. Herein, we report the single-crystal X-ray and neutron diffraction characterization of β-agostic (α-diimine)Pd–ethyl intermediates in polymerization. Short Cα–Cβ distances and acute Pd–Cα–Cβ bond angles combined serve as unambiguous evidence for the β-agostic interaction. Characterization of the agostic structure and the kinetic barrier for β-H elimination offer important insight into the fundamental understanding of agostic bonds and the mechanism of polymerization.

Perspectives for biocatalytic lignin utilization: cleaving 4-O-5 and C\u03b1\u2013C\u03b2 bonds in dimeric lignin model compounds catalyzed by a promiscuous activity of tyrosinase

BackgroundIn the biorefinery utilizing lignocellulosic biomasses, lignin decomposition to value-added phenolic derivatives is a key issue, and recently biocatalytic delignification is emerging owing to its superior selectivity, low energy consumption, and unparalleled sustainability. However, besides heme-containing peroxidases and laccases, information about lignolytic biocatalysts is still limited till date.ResultsHerein, we report a promiscuous activity of tyrosinase which is closely associated with delignification requiring high redox potentials (>1.4 V vs. normal hydrogen electrode [NHE]). The promiscuous activity of tyrosinase not only oxidizes veratryl alcohol, a commonly used nonphenolic substrate for assaying ligninolytic activity, to veratraldehyde but also cleaves the 4-O-5 and Cα–Cβ bonds in 4-phenoxyphenol and guaiacyl glycerol-β-guaiacyl ether (GGE) that are dimeric lignin model compounds. Cyclic voltammograms additionally verified that the promiscuous activity oxidizes lignin-related high redox potential substrates.ConclusionThese results might be applicable for extending the versatility of tyrosinase toward biocatalytic delignification as well as suggesting a new perspective for sustainable lignin utilization. Furthermore, the results provide insight for exploring the previously unknown promiscuous activities of biocatalysts much more diverse than ever thought before, thereby innovatively expanding the applicable area of biocatalysis.

Backbone resonance assignments for the SET domain of human methyltransferase NSD3 in complex with its cofactor.

NSD3 is a histone H3 methyltransferase that plays an important role in chromatin biology. A construct containing the methyltransferase domain encompassing residues Q1049-K1299 of human NSD3 was obtained and biochemical activity was demonstrated using histone as a substrate. Here we report the backbone HN, N, Cα, C', and side chain Cβ assignments of the construct in complex with S-adenosyl-L-methionine (SAM). Based on these assignments, secondary structures of NSD3/SAM complex in solution were determined.

On the significant relativistic heavy atom effect on 13C NMR chemical shifts of β- and γ-carbons in seleno- and telluroketones

ABSTRACTUnexpectedly large ‘Heavy Atom on Light Atom’ (HALA) effects have been found in 13C NMR (Nuclear Magnetic Resonance) chemical shifts of β- and γ-carbons of seleno- and telluroketones established by means of the high-accuracy calculations of 13C NMR chemical shifts in three representative real-life compounds, 2,2,5,5-tetramethyl-3-cyclopentene-1-selone, selenofenchone and 1,1,3,3-tetramethyl-1,3-dihydro-2H-indene-2-tellurone. The proposed computational scheme consists of the combination of accurately correlated coupled-cluster singles and doubles model approach for the non-relativistic calculations of shielding constants taking into account the solvent, vibrational and relativistic corrections, the latter obtained within the 4-component fully relativistic gauge-including atomic orbitals KT2 approach resulting in a very good agreement of the performed calculations with the experiment. The stereochemical dependence of the ‘long-range’ γ-HALA effect on the dihedral angle has been established in the model seleno- and telluroketones providing the largest shielding effect in the orthogonal orientation of the X=Cα–Cβ–Cγ (X=Se, Te) moiety.

X-Ray snapshots of a pyridoxal enzyme: a catalytic mechanism involving concerted [1,5]-hydrogen sigmatropy in methionine \u03b3-lyase

Pyridoxal 5′-phosphate (PLP)-enzymes are essentially involved in amino acid and amine metabolism of a wide variety of organisms. Despite their extensive biochemical studies, there are little evidence and structural data to comprehensively elaborate the catalytic mechanism. We obtained X-ray snapshots of l-methionine γ-lyase from Entamoeba histolytica (EhMGL), a PLP-enzyme catalyzing the γ-elimination reaction of methionine. Here, we suggest a catalytic mechanism of EhMGL by using the X-ray snapshots covering all stages of this multistep catalysis reaction. Initial formation of a Michaelis complex is followed by the migration of double bond from the C4′=Nα–Cα moiety in an intermediate PLP-methionine imine to C4′–Nα=Cα in pyridoxamine 5′-phosphate (PMP)-α,β-dehydromethionine imine without intervention of a putative quinonoid intermediate. The enzyme can facilitate the subsequent γ-elimination of methanethiol by the possible general acid-base catalysis of Tyr108 for the E1cB mechanism, enabling to form the ene-imine C4′–Nα=Cα–Cβ=Cγ structure with the s-cis conformation, which is prerequisite for the non-enzymatic symmetry-allowed suprafacial [1,5]-hydrogen shift to complete the catalytic cycle by releasing α-ketobutyrate. The mechanism based on the X-ray snapshots is consistent with the reactivity of MGL toward methionine analogues. The generality of such a mechanism involving non-enzymatic concerted reaction in other PLP enzymes is discussed.

Low-Temperature Torrefaction of Phyllostachys heterocycla cv. pubescens: Effect of Two Torrefaction Procedures on the Composition of Bio-Oil Obtained

Low-temperature torrefaction of pubescens was studied by one-step (RT–200 °C) and two-step (RT–120 °C first, and then 120–200 °C) ways. For one-step torrefaction, the cracking of intermolecular and intramolecular hydrogen bonds in cellulose promoted the formation of oligosaccharide, anhydrosugar, and levoglucosan intermediates with monosaccharide, carboxylic acid, furans, etc. The oligomers with 4-O-5, β-O-4 linkages were mainly derived from the cleavage of C–O–C bonds between lignin and cellulose, and p-hydoxyphenyl (H), ferulate (F) intermediates were derived from the cracking of β-O-4 and Cα–Cβ in lignin. In two-step torrefaction, the first step (RT–120 °C) tended to generate the intermediates of oligosaccharide, levoglucosan and pyranose, which mainly derived from the cleavage of intermolecular hydrogen bonds or ether bonds in amorphous cellulose. The lignin-based oligomers with 4-O-5 and β-O-4 linkages were mainly derived from the cracking of β-O-4 and dehydration. For the second step (120–200 °C), t...

Theoretical evidence for bond stretch isomerism in Grubbs olefin metathesis.

A comprehensive density functional theory study on the dissociative and associative mechanisms of Grubbs first and second generation olefin metathesis catalysis reveals that ruthenacyclobutane intermediate (RuCB) observed in the Chauvin mechanism is not unique as it can change to a non-metathetic ruthenacyclobutane (RuCB') via the phenomenon of bond stretch isomerism (BSI). RuCB and RuCB' differ mainly in RuCα , RuCβ , and Cα Cβ bond lengths of the metallacycle. RuCB is metathesis active due to the agostic type bonding-assisted simultaneous activation of both Cα Cβ bonds, giving hypercoordinate character to Cβ whereas an absence of such bonding interactions in RuCB' leads to typical CC single bond distances and metathesis inactivity. RuCB and RuCB' are connected by a transition state showing moderate activation barrier. The new mechanistic insights invoking BSI explains the non-preference of associative mechanism and the requirement of bulky ligands in the Grubbs catalyst design. The present study lifts the status of BSI from a concept of largely theoretical interest to a phenomenon of intense importance to describe an eminent catalytic reaction. © 2017 Wiley Periodicals, Inc.

Effect of Benzyl Functionality on Microwave-Assisted Cleavage of Cα–Cβ Bonds in Lignin Model Compounds

The effect of benzylic alcohol (Cα—OH) pretreatments on microwave-assisted cleavage of Cα—Cβ bonds in lignin model compounds was investigated by combining experimental results with density functional theory (DFT) calculations at the M06-2X/6-311++G(d,p) level. The oxidization of Cα—OH to benzylic ketone (Cα═O) facilitated the cleavage of the Cα—Cβ bond due to a greater decomposition rate constant and a lower barrier for the decomposition-determining step. The reduction of Cα—OH to benzylic hydrogen (Cα—H) resulted in no Cα—Cβ bond being cleaved. Since the Cα—OH quickly reacted with methanol solvent, the etherification of Cα—OH to benzylic ether (Cα—OCH3) had no effect on the Cα—Cβ bond cleavage. The aromatic aldehyde would be obtained from the model compounds containing Cα—OH or Cα—OCH3, while the model compound containing Cα═O would produce aromatic ester. The research also revealed that the microwave-assisted cleavage of Cα—Cβ bonds followed a first-order kinetic and radical reaction mechanism.

Reactivity of the nitrogen-centered tryptophanyl radical in the catalysis by the radical SAM enzyme NosL.

The radical SAM tryptophan (Trp) lyase NosL involved in nosiheptide biosynthesis catalyzes two parallel reactions, converting l-Trp to 3-methyl-2-indolic acid (MIA) and to dehydroglycine and 3-methylindole, respectively. The two parallel reactions diverge from a nitrogen-centered tryptophanyl radical intermediate. Here we report an investigation on the intrinsic reactivity of the tryptophanyl radical using a chemical model study and DFT calculations. The kinetics of the formation and fragmentation of this nitrogen-centered radical in NosL catalysis were also studied in detail. Our analysis explains the intriguing catalytic promiscuity of NosL and highlights the remarkable role this enzyme plays in achieving an energetically highly unfavorable transformation.

Tryptophan lyase (NosL): mechanistic insights into amine dehydrogenation and carboxyl fragment migration by QM/MM calculations

QM/MM calculations suggest two feasible pathways for the breaking of the C–C bond of the substrate. The breaking of the Cα–Cβ bond leads to the final product, whereas the cleavage of the Cα–C bond will terminate in the EPR-trapped radical intermediate.

Disease Phenotypes in a Mouse Model of RNA Toxicity Are Independent of Protein Kinase Cα and Protein Kinase Cβ.

Myotonic dystrophy type 1(DM1) is the prototype for diseases caused by RNA toxicity. RNAs from the mutant allele contain an expanded (CUG)n tract within the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The toxic RNAs affect the function of RNA binding proteins leading to sequestration of muscleblind-like (MBNL) proteins and increased levels of CELF1 (CUGBP, Elav-like family member 1). The mechanism for increased CELF1 is not very clear. One favored proposition is hyper-phosphorylation of CELF1 by Protein Kinase C alpha (PKCα) leading to increased CELF1 stability. However, most of the evidence supporting a role for PKC-α relies on pharmacological inhibition of PKC. To further investigate the role of PKCs in the pathogenesis of RNA toxicity, we generated transgenic mice with RNA toxicity that lacked both the PKCα and PKCβ isoforms. We find that these mice show similar disease progression as mice wildtype for the PKC isoforms. Additionally, the expression of CELF1 is also not affected by deficiency of PKCα and PKCβ in these RNA toxicity mice. These data suggest that disease phenotypes of these RNA toxicity mice are independent of PKCα and PKCβ.

On the high-temperature unimolecular decomposition of ethyl levulinate

The pyrolysis of ethyl levulinate (EL) was studied behind reflected shock waves over the temperature range of 1015–1325K and pressures of 750–1650Torr. The reaction progress was followed by measuring ethylene mole fraction using CO2 gas laser absorption near 10.532μm. The rate coefficients for the unimolecular dissociation of EL were extracted from the initial slope method and further ascertained by using a complete kinetic model. Our data exhibited no discernible pressure dependence under the current experimental conditions. To rationalize our results further, high-level quantum chemical and master equation calculations were employed to calculate the pressure- and temperature-dependence of the reaction. Our calculations revealed that unimolecular dissociation of EL involves simultaneous 1,5-hydrogen shift of the β-hydrogen to the carbonyl group, rupture of the O–C ester bond and formation of the π-bond (Cα–Cβ). Our results present evidences that the C2H4 elimination from EL occurs in a concerted manner. To our knowledge, this work represents the first experimental and theoretical study of the thermal unimolecular dissociation of ethyl levulinate.

Intramolecular C–C Coupling Reactions of Alkynyl, Vinylidene, and Alkenylphosphane Ligands in Rhodium(III) Complexes

Electrophilic attack with methyl trifluoromethanesulfonate or tetrafluoroboric acid, to new alkynyl rhodium complexes containing alkenylphosphanes, leads to butenynyl coupling products or to the unprecedented rhodaphosphacycle complexes [Rh(η5-C5Me5){κ4-(P,C,C,C)-iPr2PCH2C(═CH2)C(CH2R)C═C(R)}][BF4] (R = Ph (11a), p-tol (11b)). These complexes 11a,b can be explained as a result of the coupling of three organic fragments in the molecule, the alkynyl, the vinylidene, generated in situ by reaction with HBF4 (A), and the C–C double bond from the alkenylphosphane. DFT computational studies on the formation of complex 11a suggest the [2 + 2] intramolecular cycloaddition between the double bond of the allylphosphane and the Cα–Cβ of the vinylidene A as the most plausible pathway for this reaction.

On the HALA effect in the NMR carbon shielding constants of the compounds containing heavy p‐elements

AbstractThe heavy atom (HA) effect on the NMR isotropic carbon shielding constants is computationally investigated in the series of model ethanes, ethylenes, and acetylenes, CβH3CαH2XHn, CβH2CαHXHn, CβHCαXHn (n = 0, 1, 2, or 3 depending on X), where X covers p‐elements in the 13–17 groups of the 3–6 periods in as many as 60 compounds. Compounds under study provide diverse bonding situations for the α‐ and β‐carbons, which are characterized by the consecutive increase of the s‐character of the CβCα and CαX bonds, being one of the factors influencing spin‐orbit part of the HA on light atom effect (SO‐HALA). The “chalcogen dependence,” “pnictogen dependence,” “tetrel dependence,” and “triel dependence” are established for the 16th, 15th, 14th, and 13th groups, respectively. A well‐known “normal halogen dependence” for the 13C NMR chemical shifts, established much earlier for the compounds containing 17th group elements, also revealed itself in all three series under investigation. The dependence of the spin‐orbit effects size depending on the number of the lone electron pairs (LEPs) on HA X has also been investigated. The comparison of theoretical 13C NMR chemical shifts with experiment is performed for three representative tellurides. The HALA effect in this series has been shown to be strongly dependent on the number of tellurium LEPs.

Enhanced degradation of lignin by the strain fusion of Pseudomonas putida and Gordonia sp

The protoplast fusion technique was applied to construct a more efficient engineering microbial strain to degrade lignin by fusing two strains, Pseudomonas putida and Gordonia sp. At an initial lignin concentration of 900 mg/L, COD, BOD, TOC removal efficiencies increased from 69–76%, 69–72%, and 70–72% by the parent stains to 83%, 83%, and 83% of the fused strain, respectively. IR and HPLC analyses of the treated solution suggested that the fused strains were more capable of breaking the Cα–Cβ bonds of the benzene ring in lignin compared to its parent strains, yielding syringyls as the main product. GC–MS analysis was used to identify the release of three-types of lower molecular intermediates: ring-opening, monomer, and dipolymer products. The phenolic hydroxyl group in lignin was oxidized to carbonyls, followed by further degradation to acids and esters. The carboxyl group on the ether linkage that maintains the macromolecular structure of lignin was oxidized to acyls, which further led to depolymerization and the opening of benzene ring.