Α-carbon Atom Research Articles

Hydroalumination of dialkynylgermanes—synthesis of alkenyl–alkynylgermanes with intramolecular aluminium–carbon interactions

Reactions of dialkylaluminium hydrides, R2AlH [R = CH2CMe3, CMe3, CH(SiMe3)2], with di(phenylethynyl)germanes, R2Ge(CC–C6H5)2 [R = CH3 (1), C6H5 (2)], afforded mixed alkenyl–alkynylgermanes, R2Ge(CC–C6H5)[C(AlR2)C(H)–C6H5] (3 to 7), by hydroalumination of one of the CC triple bonds. In all cases the cis-arrangement of the Al and H atoms across the resulting CC double bond was observed. Crystal structure determinations revealed relatively strong intramolecular bonding interactions between the coordinatively-unsaturated aluminium atoms and the α-carbon atoms of the intact triple bonds bearing a partial negative charge. This interaction is only prevented by application of the very bulky bis(trimethylsilyl)methyl substituent.

Calcium Binds to LipL32, a Lipoprotein from Pathogenic Leptospira, and Modulates Fibronectin Binding

Tubulointerstitial nephritis is a cardinal renal manifestation of leptospirosis. LipL32, a major lipoprotein and a virulence factor, locates on the outer membrane of the pathogen Leptospira. It evades immune response by recognizing and adhering to extracellular matrix components of the host cell. The crystal structure of Ca(2+)-bound LipL32 was determined at 2.3 A resolution. LipL32 has a novel polyD sequence of seven aspartates that forms a continuous acidic surface patch for Ca(2+) binding. A significant conformational change was observed for the Ca(2+)-bound form of LipL32. Calcium binding to LipL32 was determined by isothermal titration calorimetry. The binding of fibronectin to LipL32 was observed by Stains-all CD and enzyme-linked immunosorbent assay experiments. The interaction between LipL32 and fibronectin might be associated with Ca(2+) binding. Based on the crystal structure of Ca(2+)-bound LipL32 and the Stains-all results, fibronectin probably binds near the polyD region on LipL32. Ca(2+) binding to LipL32 might be important for Leptospira to interact with the extracellular matrix of the host cell.

Synthesis of functionalized α-CF 3-α-aminophosphonates via Cu(I)-catalyzed 1,3-dipolar cycloaddition

A convenient method for the preparation of α-CF 3-α-aminophosphonates bearing alkynyl group at the α-carbon atom has been described. New alkynylphosphonates have been further utilized in the synthesis of functionalized triazole-containing α-CF 3-α-aminophosphonates via copper-catalyzed (3+2)-cycloaddition to different organic azides.

Toward Total Spontaneous Resolution ofsec-Butylzinc Complexes

Di-sec-butylzinc has been used to synthesize [Zn(s-Bu)2L2] complexes, where L denotes amine ligands: e.g., pyridine (py), 2-picoline (2-pic), and 3-picoline (3-pic). The crystal structures of [Zn(s-Bu)2(py)2] (1), [Zn(s-Bu)2(2-pic)2] (2), and [Zn(s-Bu)2(3-pic)2] (3) were determined. Reaction of di-sec-butylzinc with the bidentate amine ligands N,N,N′,N’-tetramethylethylenediamine (TMEDA) and N,N,N′,N’-tetraethylethylenediamine (TEEDA) afforded the chiral complexes [Zn(s-Bu)2(tmeda)] (4) and [Zn(s-Bu)2(teeda)] (5); their crystal structures were determined. Since they coordinate two s-Bu groups each, complexes 1−5 may exist both as chiral and meso molecules in solution, but the crystalline complexes were found to be exclusively chiral. The enantiomerization rate of 1−5 in benzene was found to be slow on the NMR time scale. Chiral crystalline complexes containing the Zn(s-Bu)2 moiety are of particular interest, since they display reactive chirogenic α-carbon atoms. The identification of a Zn(s-Bu)2 complex s...

Experiment study of model compound oxidation on spontaneous combustion of coal

Spontaneous combustion is one of the severest accidents in the process of coal production and transportation. Therefore it is significant to study the mechanism of coal spontaneous combustion. Based on theoretical analysis, 7 kinds of model compounds have been chosen in this paper, which are hyacinthin, anisole, diphenylmethane, phenetole, benzyl alcohol, benzhydrol, and aphenylpropanol. And they contain respectively active groups such as aldehyde group, methoxyl group, hypomethyl bond, hypomethylether bond, hypomethyl bond of a-carbon atom with hydroxyl, hypoalkyl bond of a-carbon atom with hydroxyl, and so on. According to the theory of free radical reactions, taking the model compound of coal above as research object, chemical reaction kinetic parameters, thermodynamic parameters, and products from normal temperature to 150°C have been quantitatively studied by oxidation device and analytical instrument, then the oxidation course can be deduced. The results show that all the model compounds consumed oxygen and produced CO and CO2 at different degrees after temperature programmed to 150°C. The oxidation characteristic of the active groups in coal and the effect of them on spontaneous combustion can be recognized, and spontaneous combustion mechanism can be exposited systematically in chemistry by means of studying the oxidation of model compound.

Chiraloptical properties of adducts derived from cyclic nitrones and 2( 5H)-furanones. Combined experimental and theoretical studies

The validity of the Bucourt–Legrand empirical rule, which relates the configuration at the α-carbon atom in the lactone unit with the sign of the lactone n→π ∗ transition observed in the electronic circular dichroism (ECD) spectrum of 5-5-5 and 5-5-6 fused heterocyclic systems, was investigated. For this purpose, a combination of ECD spectroscopy, time-dependent density functional theory (TD-DFT) and molecular modelling calculations supported additionally by X-ray diffraction analysis, was applied. Model compounds were obtained via the 1,3-dipolar cycloaddition of 2( 5H)-furanones and five- and six-membered cyclic nitrones. In addition, cycloadducts either with or without an additional interfering chromophore were selected. A comparison of the recorded ECD spectra with those simulated by the TD-DFT calculations gave a reasonable interpretation of the excitations observed in the 210–230 nm spectroscopic range. Generally, calculations confirmed the validity of the Bucourt–Legrand rule and demonstrated that ECD may be used as a highly sensitive probe for the three-dimensional molecular structure of the systems studied herein. Notable behaviour, however, was observed in the case of some 5-5-6 fused systems substituted with BnO group. In these cases, the conformational liability and coupling of molecular lactone excitation with other chromophores cause a change of orientation of the transition dipole moments resulting in a breakdown of the rule.

Enzymatic resolution of α-hydroxyphosphinates with two stereogenic centres and determination of absolute configuration of stereoisomers obtained

The use of quinine as a chiral solvating agent allows us to determine a tentative absolute configuration at the phosphorus atom of hydroxyphosphinates with two stereogenic centres (at the phosphorus and α-carbon atoms). Two ethyl butyryloxyalkane( P-phenyl)phosphinates were hydrolysed using various lipases. In all cases isomers possessing α-carbon atom with an ( S)-configuration were hydrolysed preferentially. The absolute configuration of both chiral centres of obtained α-hydroxyphosphinates was determined by using ( S)-(+)-MTPA-Cl and quinine. The mode of chiral discrimination of α-hydroxyphosphinates by quinine was studied by means of computational chemistry, which confirmed the experimental findings that the signals in 31P NMR spectra of compounds with an ( R P)-configuration are situated upfield when compared with the respective ( S P) isomers.

The normal modes of a protein: Native bovine pancreatic trypsin inhibitor

A completely general treatment of normal mode analysis is developed that can be used with any potential energy function and any set of generalized coordinates. The method is applied to the calculation of the normal modes of the small protein bovine pancreatic trypsin inhibitor that has been the subject of many previous theoretical studies. The potential energy function used comprises a torsion angle potential, a van der Waals potential between nonbonded pairs of atoms, and a hydrogen bond potential. Therefore, the generalized coordinates used are the 208 Φ, ϕ, and χ torsion angles about single bonds. This eliminates the difficulties inherent in using internal or Cartesian coordinates for a large molecule. Many dynamic properties of the protein may now be calculated in the normal mode description. In particular, the rms magnitudes and pair correlations of the fluctuations in positions and velocities of the α-carbon atoms and various classes of torsion angles, such as backbone, side chain, β-sheet, and α-helix, are calculated and analyzed to identify the most correlated modes. In addition, the ir intensities are calculated.

α-Substituent effects on 13C NMR chemical shifts in some aliphatic compounds: Application of principal component analysis (PCA)

The principal component analyses (PCA) were applied in investigations of α-substituent effects on 13C NMR chemical shifts of the total of 169 aliphatic compounds represented by 13 organic classes: (a) carbonyl: acetones, acetophenones, camphors and cyclohexanones; (b) carboxyl: acetic acids, methyl-, ethyl- and phenyl-acetates, ethyl thioacetates, and N, N-diethylacetamides; and (c) unsaturated compounds: cyanides, oximes, and propenes. The effects of twelve α-substituents: F, Cl, Br, I, OMe, OEt, SMe, SEt, NMe 2, NEt 2, Me and Et were considered. In PCA matrix construction the experimentally 13C NMR data for functional carbon and α-carbon atoms, and theoretically ( ab initio) obtained data were used, and two type of PCA results were generated and discussed. In the first PCA score analysis, the division in three compound groups (a–c) was obtained principally because of variations in the lowest unoccupied molecular orbital (LUMO) energies and partial charges on functional carbon atoms. The second PCA results showed division of analyzed compounds in groups of substituents according to heteroatom present (O, N, S, C or H) principally due to the differences in partial charges on α-carbon atoms as detected in the first principal component (PC), as well as, in molecular orbital coefficient of α-carbon atoms according to the second PC loading values. The halogen derivatives were treated as outliers in this PCA. Thus, knowing the structure of the Y–CH 2–X compound and calculating few theoretical ( ab initio) parameters, four in our case, one could be able to predict the functional and α-carbon NMR chemical shifts with high accuracy based on PCA scores considering two principal component models and PC1 versus PC2 plots.

Novel formation of isoxazoline N-oxide in addition to Michael adduct from the reaction of β-nitrostyrenes with 2-methoxyfuran — Experimental and theoretical studies

2-Methoxyfuran reacts with β-nitrostyrenes to give Michael adducts. Interestingly, isoxazoline N-oxides were obtained in the reactions with β-nitrostyrenes possessing additional electron-withdrawing groups [COPh (2f) and CO2Et (2g)]. (Z)-Nitrostyrene (2g) gives trans-isoxazoline (4g) and (E)-nitrostyrene (2f) leads to the cis-form product 4f. We have used theoretical methods to investigate the mechanism and to probe the regio- and stereo-selectivity observed in the rearrangement and the Michael reactions. To account for the selectivity observed in these reactions, we examined the Fukui functions and located the transition states (TS) using density functional theory (DFT) calculations at the B3LYP/6–31G* level. The first step involves a nucleophilic attack by the α-carbon atom (C4) of the furan ring on the vinyl C-atom (C5) of the nitrostyrene part to give a zwitterionic intermediate (IN1). Fission of the C–O bond of the furan ring in the intermediate and ring closure via the oxygen atom (endo-O atom) of the nitro group gives the isoxazoline N-oxide. Alternatively, the intermediate (IN1) may be transformed into the Michael adduct by an intramolecular proton transfer mediated by the formation of a four-membered transition-state structure. The potential-energy barriers for these reactions had the following values: 5.1 kcal/mol for 2f and 17.0 kcal/mol for 2g′ (CO2Me) at the rearrangement step, and 41–49 kcal/mol for the proton-transfer step. The solvent effect in CHCl3 stabilized the electrophilic attack by 1–14 kcal/mol. DFT analysis of these reactions is in good agreement with the experimental results.

Mannich-type three component condensation of α-substituted caran-4-one oximes with formaldehyde and secondary amines

Under the conditions of the Mannich reaction, 3-substituted oximes of caran-4-one undergo aminomethylation at the α-carbon atom to oxime. The reaction takes place successfully only in a mixture of methanol and acetic acid to produce α-aminomethyl derivatives in 25–83% yields. The secondary or tertiary amino group at the α’-position is eliminated under the reaction conditions to form derivatives of α,β-unsaturated oxime, while sulfur-containing substituents remain unchanged.

Thermodynamics of the Clusterization Process of Cis Isomers of Unsaturated Fatty Acids at the Air/Water Interface

In the framework of the semiempirical PM3 method, the thermodynamic parameters of cis isomers of unsaturated carboxylic acids at the air/water interface are studied. The model systems used are unsaturated cis fatty acid of the composition Delta = 12-15 and omega = 6-11, where Delta and omega refer to the number of carbon atoms between the functional group and double bond, and that between the double bond and methyl group, respectively. For dimers, trimers, and tetramers of the four acid series, the thermodynamic parameters of clusterization are calculated. It is shown that the position of the double bond does not significantly affect the values of thermodynamic parameters of formation and clusterization of carboxylic acids for equal chain lengths (n = Delta + omega). The calculated results show that for cis unsaturated fatty acid with odd Delta values the spontaneous clusterization threshold corresponds to n = 17-18 carbon atoms in the alkyl chain, while for monounsaturated acids with even Delta values this threshold corresponds to n = 18-19 carbon atoms in the alkyl chain. These differences in the clusterization threshold between the acids with even and odd Delta values are attributed to the formation of additional intermolecular hydrogen bonds between the ketonic oxygen atom of one monomer and the hydrogen atom linked to the alpha-carbon atom of the second monomer for the acids with odd Delta values or between the hydroxyl oxygen atom of one monomer and hydrogen atom linked to the alpha-carbon atom of the second monomer for the acids with even Delta values. The results obtained in the study agree satisfactorily with our experimental data for cis unsaturated nervonic (Delta15, omega9) and erucic acids (Delta13, omega9), and published data for some fatty acids, namely cis-16-heptadecenoic (Delta16, omega1), cis-9-hexadecenoic (Delta7, omega9), cis-11-eicosenoic (Delta11, omega9) and cis-9-octadecenoic acid (Delta9, omega9).

Enantioselective Direct Aldol-Type Reaction of Azlactone via Protonation of Vinyl Ethers by a Chiral Brønsted Acid Catalyst

Highly enantio- and diastereoselective direct aldol-type reaction of azlactones with oxocarbenium ions generated by protonation of vinyl ethers using a chiral phosphoric acid catalyst is presented. The method provides efficient access to biologically and pharmaceutically intriguing beta-hydroxy-alpha-amino acid derivatives having a quaternary stereogenic center at the alpha-carbon atom.

Effect of the structure of alkoxy radicals on the mass-spectral fragmentation of dialkyl alkylphosphonates

Basic fragmentation reaction of dialkyl alkylphosphinates under the conditions of electron ionization proceeds in two steps. In the first step occurs cleavage of C-O bond and splitting the olefin radical off. The intermediate ion formed therewith exerts further fragmentation by the similar way. Peaks of the intermediate ions occurs in the spectra of all dialkyl alkylphosphonates except O-methyl derivatives. In the case of branching at α-carbon atoms of alkoxy radicals cleavage of the first carbon-carbon bond of the alkoxy radical unlike the case of alkyl fluorophosphonates, in the intermediate ion rather than in molecular ion and accompanied by the elimination of alkane. These found regularities allow to explain principal fragmentation pathways of a wide series of phosphoric acids esters of general formula (RO) n P(O)X n−3 (where X is R, Hal, or OMe) with both linear and branched in α-position alkoxy radicals.

Enantioseparation with Capillary Electrophoresis (CE) as Evidence of Chirality Retention during Kolbe Electrolysis of Amino Acids

The radical Kolbe electrolysis can be applied to synthesize non-proteinogenic amino acids starting from ʟ-glutamic acid (or L-aspartic acid, respectively). Using suitable protecting groups for both amino and carboxy functionalities, the retention of chirality at the α-carbon atom can be expected.

Novel formation of phenylcyclopropanes from the reaction of β-cyanostyrenes and related compounds with 2-methoxyfuran: experimental and theoretical studies

As a diene, 2-methoxyfuran fails to generate a Diels–Alder adduct when it reacts with β-cyanostyrenes (cinnamonitriles). However, in the reaction with β-cyanostyrenes possessing additional electron-withdrawing groups (CN, CO2Et and SO2Ph), it yielded two new phenylcyclopropanes. We have used computational methods to investigate the mechanism and to probe the regioselectivity observed in the rearrangement reactions. We used a B3LYP/6-31G* level density functional calculation to locate the transition states (TS), and to account for the selectivity observed in these reactions, we examined the global electronic index involved. An analysis of the results for the reaction pathways of two adducts (the endo and exo isomers) shows that the reaction takes place via a polar stepwise mechanism. The first step involves a side-on nucleophilic attack by the α-carbon atom of the furan ring on the vinyl carbon of the cyanostyrene to give a zwitterionic intermediate. An intramolecular substitution within the intermediate (IN) gives the cyclopropane ring, together with fission of the furan ring. The potential energy barriers for these reactions had the following values: at the nucleophilic addition step, 14.6 and 13.7 kcal mol−1 for 2b, and 18.4 and 17.8 kcal mol−1 for 2c; at the rearrangement step, 22.3 and 22.8 kcal mol−1 for 2b, and 25.1 and 23.1 kcal mol−1 for 2c. Solvent effects in chloroform stabilized the rearrangement steps by 5–6 kcal mol−1, but the nucleophilic addition step appeared to be slightly affected. From the theoretical results, in the case of 2b, the energy of TS2-endo is lower than that of TS2-exo, so more trans-cyclopropane product from the endo form is formed under kinetic conditions. Conversely, in the case of 2c, the energy of TS2-exo is lower and more of the cis-product is formed. Density functional theory analysis of these reactions is in complete agreement with the experimental results.

Effect of conformational degrees of freedom on the charge transfer in model tripeptide

An extensive conformational dependence of the intramolecular charge transfer (both hole and electron) between intermediate residues of the model tripeptide in gas phase has been studied. The charge transfer integral, spatial overlap integral and site-energy for both hole and electron transfer between the intermediate residues in the tripeptides were calculated using the fragment orbital method. The site-energies and the charge transfer integrals have been calculated for different conformation of the glycine tripeptide by varying the dihedral angles ( ϕ and ψ) along the α-carbon atom of amino acid subgroups. Electronic structure calculations show that the charge transfer integral between intermediate residues is strongly depending on the nature of the conformation of the peptide. The calculations indicate that the charge transfer is maximum at the particular conformation of the intermediate amino acid residues.

An Ion Selectivity Filter in the Extracellular Domain of Cys-loop Receptors Reveals Determinants for Ion Conductance

Neurotransmitter binding to Cys-loop receptors promotes a prodigious transmembrane flux of several million ions/s, but to date, structural determinants of ion flux have been identified flanking the membrane-spanning region. Using x-ray crystallography, sequence analysis, and single-channel recording, we identified a novel determinant of ion conductance near the point of entry of permeant ions. Co-crystallization of acetylcholine-binding protein with sulfate anions revealed coordination of SO4(2-) with a ring of lysines at a position equivalent to 24 A above the lipid membrane in homologous Cys-loop receptors. Analysis of multiple sequence alignments revealed that residues equivalent to the ring of lysines are negatively charged in cation-selective receptors but are positively charged in anion-selective receptors. Charge reversal of side chains at homologous positions in the nicotinic receptor from the motor end plate decreases unitary conductance up to 80%. Selectivity filters stemming from transmembrane alpha-helices have similar pore diameters and compositions of amino acids. These findings establish that when the channel opens under a physiological electrochemical gradient, permeant ions are initially stabilized within the extracellular vestibule of Cys-loop receptors, and this stabilization is a major determinant of ion conductance.

Crystal Structure of Diaminopimelate Epimerase from Arabidopsis thaliana, an Amino Acid Racemase Critical for l-Lysine Biosynthesis

Diaminopimelate (DAP) epimerase is a key enzyme for the biosynthesis of lysine in plants. Lysine is an essential dietary nutrient for mammals. In both plants and bacteria, DAP epimerase catalyzes the interconversion of ll-DAP and dl( meso)-DAP. The absence of a mammalian homolog makes DAP epimerase a promising target for the design of novel herbicides and antibacterials. This enzyme requires no cofactors and it functions through an unusual mechanism involving two cysteine residues acting in concert and alternating as a base (thiolate) and as an acid (thiol). The present study reports the crystal structures of two enzyme–inhibitor complexes of DAP epimerase from Arabidopsis thaliana with different isomers of the irreversible inhibitor and substrate mimic, 2-(4-amino-4-carboxybutyl)-aziridine-2-carboxylate, at 1.95 and 2.3 Å resolution. These structures provide the first atomic details of a plant amino acid racemase. Structural analysis reveals that ligand binding to a cleft between the two domains of the enzyme is accompanied by domain closure with two strictly conserved cysteine residues, Cys99 and Cys254, optimally positioned to perform acid/base catalysis via a carbanion stabilization mechanism on the stereogenic α-carbon atom of the amino acid. Stereochemical control in catalysis is achieved by means of a highly symmetric catalytic site that can accommodate both the l and d stereogenic centers of DAP at the proximal site, whereas specific interactions at the distal site require only the l configuration. Structural comparisons of the plant enzyme with its bacterial counterpart from Haemophilus influenzae reveal significant conservation of amino acid residues around the active site that extends to their three-dimensional structures and catalytic mechanism.

Systematic Multiscale Parameterization of Heterogeneous Elastic Network Models of Proteins

We present a method to parameterize heterogeneous elastic network models (heteroENMs) of proteins to reproduce the fluctuations observed in atomistic simulations. Because it is based on atomistic simulation, our method allows the development of elastic coarse-grained models of proteins under different conditions or in different environments. The method is simple and applicable to models at any level of coarse-graining. We validated the method in three systems. First, we computed the persistence length of ADP-bound F-actin, using a heteroENM model. The value of 6.1 ± 1.6 μm is consistent with the experimentally measured value of 9.0 ± 0.5 μm. We then compared our method to a uniform elastic network model and a realistic extension algorithm via covariance Hessian (REACH) model of carboxy myoglobin, and found that the heteroENM method more accurately predicted mean-square fluctuations of α-carbon atoms. Finally, we showed that the method captures critical differences in effective harmonic interactions for coarse-grained models of the N-terminal Bin/amphiphysin/Rvs (N-BAR) domain of amphiphysin, by building models of N-BAR both bound to a membrane and free in solution.