Solvophobic and steric effects of side groups on polymer folding: molecular modeling studies of amine-functionalized m-poly(phenyleneethynylene) foldamers in aqueous solution

The folding behavior of five different amine-functionalized m-poly(phenyleneethynylene) (m-PPE) oligomers containing 24 phenyl rings (12 residues, where a residue includes 2 phenyl rings) in water was examined by using a combination of molecular dynamics (MD) and replica exchange molecular dynamics (REMD) simulation techniques. The REMD method employed the highly parallelized GROMACS MD software and a modified OPLS-AA force field to simulate 44 replicas of each solvated system in parallel, with temperatures ranging from 300 to 577 K. Our results showed that the REMD method was more effective in predicting the helical conformation of the m-PPE in water, from an extended structure, than canonical MD methods in the same simulation time. Furthermore, we observed from canonical MD simulations of the explicitly solvated helical m-PPEs at 300 K that the radius of gyration, average helix inner diameter, and average helix pitch of the helical structure all pass through a minima when the side group is R = OC(2)H(5) as R is changed from R = H through OC(4)H(9).     

Anion radical [2 + 2] cycloaddition as a mechanistic probe: stoichiometry- and concentration-dependent partitioning of electron-transfer and alkylation pathways in the reaction of the Gilman reagent Me2CuLi.LiI with bis(enones)

Exposure of easily reduced aromatic bis(enones) 1a-1e to the methyl Gilman reagent Me(2)CuLi.LiI at 0 degrees C in tetrahydrofuran solvent provides the products of tandem conjugate addition-Michael cyclization, 2a-2e, along with the products of [2 + 2] cycloaddition, 3a-3e. Complete partitioning of the Gilman alkylation and [2 + 2] cycloaddition pathways may be achieved by adjusting the loading of the Gilman reagent, the rate of addition of the Gilman reagent, and the concentration of the reaction mixture. The Gilman alkylation manifold is favored by the rapid addition of excess Gilman reagent at higher substrate concentrations, while the [2 + 2] cycloaddition manifold is favored by slow addition of the same Gilman reagent at lower concentrations and loadings. Notably, [2 + 2] cycloaddition to form 3a-3e is catalytic in Gilman reagent. Kinetic data reveal that the ratio of 2a and 3a changes such that the cycloaddition pathway becomes dominant upon increased consumption of Gilman reagent. These data suggest a concentration-dependent speciation of the Gilman reagent and differential reactivity of the aggregates present at higher and lower concentrations. While the species present at higher concentration induce Gilman alkylation en route to products 2a-2e, the species present at lower concentration provide products of catalytic [2 + 2] cycloaddition, 3a-3e. Moreover, upon electrochemical reduction of the bis(enones) 1a-1e, or chemically induced single-electron transfer from arene anion radicals, the very same [2 + 2] cycloadducts 3a-3e are formed. The collective data suggest that [2 + 2] cycloadducts 3a-3e arising under Gilman conditions may be products of anion radical chain cyclobutanation that derive via electron transfer (ET) from the Me(2)CuLi.LiI aggregate(s) present at low concentration. These observations provide a link between the Gilman alkylation reaction and related ET chemistry and suggest these reaction paths are mechanistically distinct. This analysis is made possible by the recent observation that easily reduced bis(enones) are subject to intramolecular [2 + 2] cycloaddition upon cathodic reduction or chemically induced ET from arene anion radicals, and is herewith showcased as a novel method of testing for the intermediacy of enone anion radicals.     

Validation of the CALUX bioassay for the screening of PCDD/Fs and dioxin-like PCBs in retail fish

The chemical-activated luciferase expression (CALUX) assay is a reporter gene assay that detects dioxin-like compounds based on their ability to activate the aryl hydrocarbon receptor (AhR) and thus expression of the reporter gene. In this paper, the CALUX assay was examined for its application in the screening of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dioxin-like PCBs) in retail fish. The sample extracts were cleaned up on a sulfuric acid-silica gel column followed by an activated carbon column, and the AhR activity of the separated PCDD/F and dioxin-like PCB fractions was determined using the assay. The quantitative limit for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) was 0.98 pg ml(-1) (0.19 pg assay(-1) in the standard curve, corresponding to 0.16 pg g(-1) of CALUX-based toxic equivalency (2,3,7,8-TCDD equivalents) in the tested sample. Recovery tests in which dioxins were added to fish samples resulted in acceptable recoveries (77-117%). The CALUX assay performed well in the analysis of dioxins in fish samples and a comparative study revealed a strong correlation between the CALUX assay and high-resolution gas chromatography-high-resolution mass spectrometry analysis for the determination of PCDD/Fs (r = 0.89) and dioxin-like PCBs (r = 0.91) in retail fish (n = 22). These data revealed that the CALUX assay would be a useful screening method for PCDD/Fs and dioxin-like PCBs in retail fish.     

Influence of the 4,6-O-benzylidene, 4,6-O-phenylboronate, and 4,6-O-polystyrylboronate protecting groups on the stereochemical outcome of thioglycoside-based glycosylations mediated by 1-benzenesulfinyl piperidine/triflic anhydride and N-iodosuccinimide/trimethylsilyl triflate

The effect of 4,6-O-benzylidene acetals, 4,6-O-phenylboronate esters, and 4,6-O-polystyrylboronate esters on the stereoselectivity of couplings to galacto-, gluco-, and mannopyranosyl thioglycosides, otherwise protected with benzyl ethers, has been investigated by the benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride (BSP), diphenyl sulfoxide/trifluoromethanesulfonic anhydride (Ph(2)SO), and N-iodosuccinimide/trimethylsilyl trifluoromethanesulfonate (NIS/TMSOTf) methods. The BSP and Ph(2)SO methods give comparable results in all three systems whereas the NIS method affords significantly different stereoselectivities in both the gluco and manno, but not the galacto series. The benzylidene acetal and boronate esters influence the stereochemistry in a similar manner in the beta-selective manno series and the alpha-selective galacto series but show significant differences with the glucose donors. The differences between the glucose, galactose, and mannose series reflect the established differences in reactivity and, especially for mannose, those in the anomeric effect and are best interpreted in terms of changes in the relative energetics between the alpha- and beta-covalent triflate intermediates and the various contact ion pairs with which they are necessarily in equilibrium.     

Single-molecule magnets: novel Mn(8) and Mn(9) carboxylate clusters containing an unusual pentadentate ligand derived from pyridine-2,6-dimethanol

The reactions of the Mn(III)(3) and Mn(II)Mn(III)(2) complexes [Mn(3)O(O(2)CEt)(6)(py)(3)][ClO(4)] and [Mn(3)O(O(2)CEt)(6)(py)(3)] with pyridine-2,6-dimethanol (pdmH(2)) afford the mixed-valence Mn(II)(6)Mn(III)(2) octanuclear complex [Mn(8)O(2)(py)(4)(O(2)CEt)(8)(L)(2)][ClO(4)](2) (1) and the Mn(II)(7)Mn(III)(2) enneanuclear complex [Mn(9)(O(2)CEt)(12)(pdm)(pdmH)(2)(L)(2)] (2), respectively. Both compounds contain a novel pentadentate ligand, the dianion of (6-hydroxymethylpyridin-2-yl)-(6-hydroxymethylpyridin-2-ylmethoxy)methanol (LH(2)), which is the hemiacetal formed in situ from the Mn-assisted oxidation of pdmH(2). Complex 1 crystallizes in the monoclinic space group P2(1)/n with the following cell parameters at -160 degrees C: a = 16.6942(5) A, b = 13.8473(4) A, c = 20.0766(6) A, beta = 99.880(1) degrees, V = 4572.27 A(3), and Z = 2, R (R(w)) = 4.78 (5.25). Complex 2.0.2MeCN crystallizes in the triclinic space group Ponemacr; with the following cell parameters at -157 degrees C: a = 12.1312(4) A, b = 18.8481(6) A, c = 23.2600(7) A, alpha = 78.6887(8) degrees, beta = 77.9596(8) degrees, gamma = 82.3176(8) degrees, V = 5076.45 A(3), and Z = 2, R (R(w)) = 4.12 (4.03). Both complexes are new structural types comprising distorted-cubane units linked together, albeit in two very different ways. In addition, complex 2 features three distinct binding modes for the chelating ligands derived from deprotonated pdmH(2). Complexes 1 and 2 were characterized by variable-temperature ac and dc magnetic susceptibility measurements and found to possess spin ground states of 0 and 11/2, respectively. Least-squares fitting of the reduced magnetization data gave S = 11/2, g = 2.0, and D = -0.11 cm(-1) for complex 2, where D is the axial zero-field splitting parameter. Direct current magnetization versus field studies on 2 at <1 K show hysteresis behavior at <0.3 K, establishing 2 as a new single-molecule magnet. Magnetization decay measurements gave an effective barrier to magnetization relaxation of U(eff) = 3.1 cm(-1) = 4.5 K.     

The search for bishomoaromatic semibullvalenes and barbaralanes: computational evidence of their identification by UV/Vis and IR spectroscopy and prediction of the existence of a blue bishomoaromatic semibullvalene

Time-dependent B3LYP/6-31G calculations have been performed at the optimized C(2) or C(2v) geometries of several substituted semibullvalenes (1(deloc)) and barbaralanes (2(deloc)), to compare the computed vertical electronic excitation energies with the temperature-dependent, long-wavelength absorptions that have been observed in the UV/vis spectra of some of these compounds by Quast and co-workers. The excellent agreement between the calculated vertical excitation energies and the observed values of lambda(max) provides strong support for the identification of the bishomoaromatic species 1(deloc) and 2(deloc) as the source of these absorptions. Furthermore, the CN stretching frequencies, computed for the C(2) geometry of 1,5-dimethyl-2,6-dicyano-4,8-diphenylsemibullvalene (1f(deloc)), fit the low-frequency absorptions seen in the IR spectrum of 1f, thus furnishing independent evidence that bishomoaromatic geometries of semibullvalenes have, in fact, been observed spectroscopically. B3LYP/6-31G calculations predict that 2,6-dicyano-4,8-diphenylsemibullvalene 1c has a C(2) equilibrium geometry (1c(deloc)) and that the long-wavelength UV/vis absorption (lambda(max) = 585 nm) and CN stretching frequencies (2192 and 2194 cm(-1)) computed for 1c(deloc) should serve to identify this bishomoaromatic semibullvalene when it is synthesized.     

Unveiling Carbon Dioxide and Ethanol Diffusion in Carbonated Water-Ethanol Mixtures by Molecular Dynamics Simulations

The diffusion of carbon dioxide (CO2) and ethanol (EtOH) is a fundamental transport process behind the formation and growth of CO2 bubbles in sparkling beverages and the release of organoleptic compounds at the liquid free surface. In the present study, CO2 and EtOH diffusion coefficients are computed from molecular dynamics (MD) simulations and compared with experimental values derived from the Stokes-Einstein (SE) relation on the basis of viscometry experiments and hydrodynamic radii deduced from former nuclear magnetic resonance (NMR) measurements. These diffusion coefficients steadily increase with temperature and decrease as the concentration of ethanol rises. The agreement between theory and experiment is suitable for CO2. Theoretical EtOH diffusion coefficients tend to overestimate slightly experimental values, although the agreement can be improved by changing the hydrodynamic radius used to evaluate experimental diffusion coefficients. This apparent disagreement should not rely on limitations of the MD simulations nor on the approximations made to evaluate theoretical diffusion coefficients. Improvement of the molecular models, as well as additional NMR measurements on sparkling beverages at several temperatures and ethanol concentrations, would help solve this issue.     

BF3-mediated additions of organolithiums to ketimines: X-ray crystal structures of BF3-ketimine complexes

[reaction: see text] Additions of lithium acetylides and n-BuLi to N-alkyl ketimines mediated by BF(3)-Et(2)O in THF afford hindered tert-alkylamines in moderate to good yields. Stereochemical results and crystal structures of three BF(3)-imine complexes suggest that allylic strain strongly influences conformation and may be an important determinant of reactivity and selectivity.     

Computational studies of the thermal fragmentation of P-arylphosphiranes: have arylphosphinidenes been generated by this method?

CASSCF, CASPT2, CCSD(T), and (U)B3LYP electronic structure calculations have been performed in order to investigate the thermal fragmentation of P-phenylphosphirane (1) to phenylphosphinidene (PhP) and ethylene. The calculations show that generation of triplet PhP via a stepwise pathway is 21 kcal mol(-1) less endothermic and has a 12 kcal mol(-1) lower barrier height than concerted fragmentation of 1 to give singlet PhP. The formation of singlet PhP via a concerted pathway is predicted to be stereospecific, whereas formation of triplet PhP is predicted to occur with complete loss of stereochemistry. However, calculations on fragmentation of anti-cis-2,3-dimethyl-P-mesitylphosphirane (cis-1Me) to triplet mesitylphosphinidene (MesP) indicate that this reaction should be more stereospecific, in agreement with the experimental results of Li and Gaspar. Nevertheless, with a predicted free energy of activation of 42 kcal mol(-1), the formation of MesP from cis-1Me is not likely to have occurred in an uncatalyzed reaction at the temperatures at which this phosphirane has been pyrolyzed.     

Boundary conditions and mode jumping in the buckling of a rectangular plate

We show that mode jumping in the buckling of a rectangular plate may be explained by a secondary bifurcation — as suggested by Bauer et al. [1] — when clamped boundary conditions on the vertical displacement function are assumed. In our analysis we use the singularity theory of mappings in the presence of a symmetry group to analyse the bifurcation equation obtained by the Lyapunov-Schmidt reduction applied to the Von Kármán equations. Noteworthy is the fact that this explanation fails when the assumed boundary conditions are simply supported.Mode jumping in the presence of clamped boundary conditions was observed experimentally by Stein [9]; simply supported boundary conditions are frequently studied but are difficult — if not impossible — to realize physically. Thus, it is important to observe that the qualitative post-buckling behavior depends on which idealization for the boundary conditions one chooses.Research sponsored in part by the U.S. Army Contract DAAG29-75-C-0024 and the N.S.F. Grant MCS77-04148Research partially supported by the N.S.F. Grant MCS77-03685 and the Research Foundation of C.U.N.Y.