Stretching the α-helix: a direct measure of the hydrogen-bond energy of a single-peptide molecule

Atomic force microscopy was used to measure the force required to stretch individual molecules of the peptide cysteine₃–lysine₃₀–cysteine from the α-helical state into a linear chain (approximately 200 pN). The measured force versus peptide elongation was used to calculate the work done in breaking the hydrogen bonds which give rise to the helical structure. The average experimental value of the hydrogen-bond energy (20.2 kJ/mol) is in good agreement with reported theoretical calculations. In addition, the stiffness of individual peptides was measured directly using a force modulation technique and found to vary from approximately 0.005–0.012 N/m during elongation.     

Effect of gold nanoparticles on the fluorescence excitation spectrum of α-fetoprotein: local environment dependent fluorescence quenching

The effect of colloid gold nanoparticles (AuNPs) on the fluorescence excitation spectrum of α-fetoprotein (AFP) has been investigated experimentally. The excitation spectral peaks of AFP with low concentration from 0.01 ng ml(-1) to 12 ng ml(-1) increase monotonically with increasing of AFP concentration. When some gold colloids were added to the AFP solution, the excitation peak at 285 nm decreases distinctly. By comparing the excitation peak intensity of AFP solution with gold colloids and without gold colloids at different AFP concentrations, the quenching effect from gold nanoparticle was more effective at lower AFP concentration. So the range of concentration from 0.01 ng ml(-1) to 0.09 ng ml(-1) will be the potential range of applications because of the higher sensitivity. The physical origin based on local field effect was investigated to illuminate this local environment dependent fluorescence quenching. The changing extent of quenching with different AFP concentrations can be attributed to the nonlinear decreasing of the local field factor of gold nanoparticles as a function of environmental dielectric constant.     

How dominant is the most efficient pathway through the potential energy landscape of a slowly diffusing disordered system?

It has been suggested that the most-efficient pathway taken by a slowly diffusing many-body system is its geodesic path through the parts of the potential energy landscape lying below a prescribed value of the potential energy. From this perspective, slow diffusion occurs just because these optimal paths become particularly long and convoluted. We test this idea here by applying it to diffusion in two kinds of well-studied low-dimensional percolation problems: the 2d overlapping Lorentz model, and square and simple-cubic bond-dilute lattices. Although the most efficient path should be at its most dominant with the high-dimensional landscapes associated with many-body problems, it is useful to examine simpler, low-dimensional, constant-potential-energy problems such as these ones, both because the simpler models lend themselves to more accurate geodesic-path-finding approaches, and because they offer a significant contrast to many of the models used in the traditional energy-landscape literature. Neither the continuum nor the lattice percolation examples are adequately described by our geodesic-path formalism in the weakly disordered (relatively-fast-diffusion) limit, but in both cases the formalism successfully predicts the existence of the percolation transition and (to a certain extent) the slow diffusion characteristic of near-percolation behavior. The numerical results for these models are not nearly accurate enough near their transitions to describe critical exponents, but the models do showcase the qualitative validity of the geodesic perspective in that they allow us to see explicitly how tortuous and sparse the optimal pathways become as the diffusion constants begin to vanish.     

Franck-Condon simulation of the photoelectron spectrum of AsCl₂ and the photodetachment spectrum of AsCl ₂⁻ employing UCCSD(T)-F12a potential energy functions: IE and EA of AsCl₂

The currently most reliable theoretical estimates of the adiabatic ionization energies (AIE₀) from the X?²B₁ state of AsCl₂ to the X?¹A₁ and ã³B₁ states of AsCl, and the electron affinity (EA₀) of AsCl₂, including ΔZPE corrections, are calculated as 8.687(11), 11.320(23), and 1.845(12) eV, respectively (estimated uncertainties based on basis‐set effects at the RCCSD(T) level). State‐of‐the‐art ab initio calculations, which include RCCSD(T), CASSCF/MRCI, and explicitly correlated RHF/UCCSD(T)‐F12x (x = a or b) calculations with basis sets of up to quintuple‐zeta quality, have been carried out on the X?²B₁ state of AsCl₂, the X?¹A₁, ã³B₁, and ùB₁ states of AsCl, and the X?¹A₁ state of AsCl. Relativistic, core correlation and complete basis‐set (CBS) effects have been considered. In addition, computed UCCSD(T)‐F12a potential energy functions of relevant electronic states of AsCl₂, AsCl, and AsCl were used to calculate Franck–Condon factors, which were then used to simulate the valence photoelectron spectrum of AsCl₂ and the photodetachment spectrum of AsCl, both yet to be recorded. Lastly, we have also computed the AIE and EA values for NCl₂, PCl₂, and AsCl₂ at the G4 level and for SbCl₂ at the RCCSD(T)/CBS level. The trends in the AIE and EA values of the group V pnictogen dichlorides, PnCl₂, where Pn = N, P, As, and Sb, were examined. The AIE and EA of PCl₂ were found to be smaller than those of AsCl₂, contrary to the order expected from the IE values of P and As. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

How many dimensions are required to approximate the potential energy landscape of a model protein?

A scheme to approximate the multidimensional potential energy landscape in terms of a minimal number of degrees of freedom is proposed using a linear transformation of the original atomic Cartesian coordinates. For one particular off-lattice model protein the inherent frustration can only be reproduced satisfactorily when a relatively large number of coordinates are employed. However, when this frustration is removed in a Go-type model, the number of coordinates required is significantly lower, especially around the global potential energy minimum. To aid our interpretation of the results we consider modified disconnectivity graphs where a measure of the structural diversity and a metric relation between the stationary points are incorporated.     

Cleavage of carbon-carbon bonds through the mild release of trifluoroacetate: generation of α,α-difluoroenolates for aldol reactions

The selective cleavage of carbon-carbon bonds is a significant challenge in synthetic chemistry, yet this strategy can be a powerful way to generate reactive intermediates. We have discovered that, through the facile release of trifluoroacetate which occurs by C-C bond scission, difluoroenolates can be generated under very mild reaction conditions. Unlike existing reactions, this method is not limited to a small group of fluorinated building blocks. We have applied this process to the aldol reaction to install difluoromethylene groups.     

Communication: a chemically accurate global potential energy surface for the HO + CO → H + CO2 reaction

We report a chemically accurate global potential energy surface for the HOCO system based on high-level ab initio calculations at ~35,000 points. The potential energy surface is shown to reproduce important stationary points and minimum energy paths. Quasi-classical trajectory calculations indicated a good agreement with experimental data.     

Synthesis of α,α-disubstituted α-amino esters: nucleophilic addition to iminium salts generated from amino ketene silyl acetals

Alkoxycarbonyl iminium species are prepared easily by the oxidation of tetrasubstituted amino ketene silyl acetals, and subsequent nucleophilic addition of Grignard reagents to the iminium salts gives α,α-disubstituted α-amino ester derivatives in moderate to good yields, in which aryl and ethynyl substituents are readily introduced.     

From 2011 to 2022: The development of pyrazole derivatives through the α,β-unsaturated carbonyl compounds

The synthesis of pyrazole derivative using α,β-unsaturated carbonyl compounds has attracted increasing attention of the synthetic organic chemist community. Interestingly, the simplicity of the synthetic method, high reactivity, and ease of incorporating diversity into the desired prototype have contributed a lot toward the exploration of α,β-unsaturated carbonyl compounds by various research groups. Due to the tremendous pharmacological significance of pyrazole derivatives, their synthesis has been one of the leading research frontiers in recent years. As prime examples, sildenafil, zometapin, Celebrex, and rimonabant have been successfully commercialized in the market to treat various life-challenging diseases. Considering the great profile of α,β-unsaturated carbonyl compound in the synthesis of biologically active pyrazole derivatives, this review incorporates contemporary literature (2011–2022) on the synthesis of pyrazole and its derivatives using α,β-unsaturated carbonyl compound as a starting precursor.     

Chiral symmetry breaking via crystallization of the glycine and α-amino acid system: a mathematical model

We introduce and numerically solve a mathematical model of the experimentally established mechanisms responsible for the symmetry breaking transition observed in the chiral crystallization experiments reported by I. Weissbuch, L. Addadi, L. Leiserowitz and M. Lahav, J. Am. Chem. Soc., 1988, 110, 561-567. The mathematical model is based on five basic processes: (1) the formation of achiral glycine clusters in solution, (2) the nucleation of oriented glycine crystals at the air/water interface in the presence of hydrophobic amino acids, (3) a kinetic orienting effect which inhibits crystal growth, (4) the enantioselective occlusion of the amino acids from solution, and (5) the growth of oriented host glycine crystals at the interface. We translate these processes into differential rate equations. We first study the model with the orienting process (2) without (3) and then combine both allowing us to make detailed comparisons of both orienting effects which actually act in unison in the experiment. Numerical results indicate that the model can yield a high percentage orientation of the mixed crystals at the interface and the consequent resolution of the initially racemic mixture of amino acids in solution. The model thus leads to separation of enantiomeric territories, the generation and amplification of optical activity by enantioselective occlusion of chiral additives through chiral surfaces of glycine crystals.     

From Monomers to π Stacks, from Nonconductive to Conductive: Syntheses, Characterization, and Crystal Structures of Benzidine Radical Cations

Salts that contain radical cations of benzidine (BZ), 3,3',5,5'-tetramethylbenzidine (TMB), 2,2',6,6'-tetraisopropylbenzidine (TPB), and 4,4'-terphenyldiamine (DATP) have been isolated with weakly coordinating anions [Al(OR(F) )(4) ](-) (OR(F) =OC(CF(3) )(3) ) or SbF(6) (-) . They were prepared by reaction of the respective silver(I) salts with stoichiometric amounts of benzidine or its alkyl-substituted derivatives in CH(2) Cl(2) . The salts were characterized by UV absorption and EPR spectroscopy as well as by their single-crystal X-ray structures. Variable-temperature UV/Vis absorption spectra of BZ(.) (+) [Al(OR(F) )(4) ](-) and TMB(.) (+) [Al(OR(F) )(4) ](-) in acetonitrile indicate an equilibrium between monomeric free radical cations and a radical-cation dimer. In contrast, the absorption spectrum of TPB(.) (+) SbF(6) (-) in acetonitrile indicates that the oxidation of TPB only resulted in a monomeric radical cation. Single-crystal X-ray diffraction studies show that in the solid state BZ and its methylation derivative (TMB) form radical-cation π dimers upon oxidation, whereas that modified with isopropyl groups (TPB) becomes a monomeric free radical cation. By increasing the chain length, π stacks of π dimers are obtained for the radical cation of DATP. The single-crystal conductivity measurements show that monomerized or π-dimerized radicals (BZ(.) (+) , TMB(.) (+) , and TPB(.) (+) ) are nonconductive, whereas the π-stacked radical (DATP(.) (+) ) is conductive. A conduction mechanism between chains through π stacks is proposed.     

Evaluation of potential reaction mechanisms leading to the formation of coniferyl alcohol α-linkages in lignin: a density functional theory study

Five potential reaction mechanisms, each leading to the formation of an α-O-4-linked coniferyl alcohol dimer, and one scheme leading to the formation of a recently proposed free-radical coniferyl alcohol trimer were assessed using density functional theory (DFT) calculations. These potential reaction mechanisms were evaluated using both the calculated Gibbs free energies, to predict the spontaneity of the constituent reactions, and the electron-density mapped Fukui function, to determine the most reactive sites of each intermediate species. The results indicate that each reaction in one of the six mechanisms is thermodynamically favorable to those in the other mechanisms; what is more, the Fukui function for each free radical intermediate corroborates with the thermochemical results for this mechanism. This mechanism proceeds via the formation of two distinct free-radical intermediates, which then react to produce the four α-O-4 stereoisomers.     

Amine-catalyzed direct assembly of indanedione-fused spirobenzo[a]carbazoles from α,α-dicyanomethylidenecarbazoles

An unprecedented amine-catalyzed stereoselective reaction of α,α-dicyanomethylidenecarbazoles with indane-1,3-dione and aryl/heteroaryl aldehydes afforded a series of indanedione-fused benzo[a]carbazoles. The plausible mechanism for the formation of the final products result from the above MCR is described based on successive Knoevenagel/Michael/nucleophilic reactions. The products were obtained in moderate to good yields without the use of any chromatographic techniques. The structures of the synthesized spirocycloadducts were confirmed by elemental analysis and spectral data (FT-IR, ¹H NMR, and 13C NMR).     

An efficient and general route to the synthesis of diethyl α,α-bromofluorophosphonates

An efficient and general two-step halogenation procedure to prepare diethyl α,α-bromofluorophosphonates was described, which included bromination by PPh₃, 2,3-dichloro-5,6-dicyanobenzquinone (DDQ) and n-Bu₄NBr, and electrophilic fluorination by N-fluorobisbenzenesulfonimide (NFSI). Both aromatic and aliphatic α,α-bromofluorophosphonates could be prepared by this method.     

Addition of carbonyl fluoride to aliphatic nitriles: Formation of α,α-difluoroalkyl isocyanates

Carbonyl fluoride will add to alkane- and perfluoroalkanenitriles and alkanedinitriles in anhydrous acids to form the corresponding α,α-difluoroalkyl isocyanate, perfluoroalkyl isocyanate, or α,α,ω,ω,-tetrafluoro-α,ω-diisocyantoalkane. With acetonitrile the reaction proceeded slowly in anhydrous hydrogen fluoride or in the presence of anhydrous hydrogen chloride in benzene to yield a clear colorless liquid identified as α,α-difluoroethyl isocyanate. Increasing yields based on the lesser reactant were achieved by making the ratio of acetonitrile to carbonyl fluoride greater or less than one, having the optimum amount of anhydrous acid, the presence of an alkali metal fluoride and/or an increase in reaction time. The α,α-difluoroethyl isocyanate reacted with anhydrous ethyl alcohol to form the corresponding carbamate which slowly decomposed by splitting out hydrogen fluoride. The addition reaction proceeded more rapidly with propionitrile and less rapidly with trifluoroacetonitrile than with acetonitrile. Cyanamide yielded trifluoromethyl isocyanate and cyanuric acid. Adiponitrile produced 1,6-diisocyanato-1,1,6,6-tetrafluorohexane and 1-isocyanato-5-cyano-1,1-difluoropentane.     

One-pot synthesis of α,α-difluoroimines from alkynes through tandem catalytic diboration/fluorination/imination reaction

Tandem catalytic diboration/fluorination/imination of arylacetylenes leads to the formation of α,α-difluoroimines, where the adjacent CN and C-F₂ bonds are formed simultaneously. The convenient one-pot protocol involves a Pt(0)-catalyzed diboration of terminal or internal arylalkynes followed by electrophilic fluorination with Selectfluor in the presence of primary amines and a dehydrating agent. A plausible mechanism for the three consecutive steps (diboration/fluorination/imination) is suggested in accordance with the electronic properties of the substrates. Alkynes/catalytic diboration/alkenyl diboronate esters/Selectfluor/electrophilic fluorination/α,α-difluoroimines.     

Direct access to α,α′-diarylated ketones through N-heterocyclic carbene-catalyzed 1,6-addition of aromatic aldehydes to para-quinone methides

N-Heterocyclic carbene-catalyzed 1,6-addition of aromatic aldehydes to para-quinone methides has been developed. This method could efficiently furnish α,α′-diarylated ketones with good to high yields, which contain various functional groups.