Isotope Effects in Organic Chemistry and Biochemistry

The present article shows the extent to which isotope effects are likely to be encountered in the use of isotope techniques and what problems are studied with primary and secondary isotope effects. By way of example, the results of studies on E2 reactions, particularly in the Hofmann degradation, are discussed, followed by a discussion of some “analytical isotope effects”. Finally, the problems encountered and the information that can be obtained from isotope effects studies on enzyme reactions, and the advantages and disadvantages of competitive and non-competitive techniques are described. In addition to a survey of isotope effects in dehydrogenase reactions, new isotope effects encountered in the dehydrogenation of T-labeled alcohols are reported.     

Ionic Fluids Containing Both Strongly and Weakly Interacting Ions of the Same Charge Have Unique Ionic and Chemical Environments as a Function of Ion Concentration

Liquid multi‐ion systems made by combining two or more salts can exhibit charge ordering and interactions not found in the parent salts, leading to new sets of properties. This is investigated herein by examining a liquid comprised of a single cation, 1‐ethyl‐3‐methylimidazolium ([C₂mim]⁺), and two anions with different properties, acetate ([OAc]^?) and bis(trifluoromethylsulfonyl)imide ([NTf₂]^?). NMR and IR spectroscopy indicate that the electrostatic interactions are quite different from those in either [C₂mim][OAc] or [C₂mim][NTf₂]. This is attributed to the ability of [OAc]^? to form complexes with the [C₂mim]⁺ ions at greater than 1:1 stoichiometries by drawing [C₂mim]⁺ ions away from the less basic [NTf₂]^? ions. Solubility studies with molecular solvents (ethyl acetate, water) and pharmaceuticals (ibuprofen, diphenhydramine) show nonlinear trends as a function of ion content, which suggests that solubility can be tuned through changes in the ionic compositions.     

Unexpected Molecular Weight Dependence to the Physical Aging of Thin Polystyrene Films Present at Ultra‐High Molecular Weights

The physical aging behavior, time‐dependent densification, of thin polystyrene (PS) films supported on silicon are investigated using ellipsometry for a large range of molecular weights (MWs) from M_w = 97 to 10,100 kg mol^?1. We report an unexpected MW dependence to the physical aging rate of h < 80‐nm thick films not present in bulk films, where samples made from ultra‐high MWs ≥ 6500 kg mol^?1 exhibit on average a 45% faster aging response at an aging temperature of 40 °C compared with equivalent films made from (merely) high MWs ≤ 3500 kg mol^?1. This MW‐dependent difference in physical aging response indicates that the breadth of the gradient in dynamics originating from the free surface in these thin films is diminished for films of ultra‐high MW PS. In contrast, measures of the film‐average glass transition temperature T _g(h) and effective average film density (molecular packing) show no corresponding change for the same range of film thicknesses, suggesting physical aging may be more sensitive to differences in dynamical gradients. These results contribute to growing literature reports signaling that chain connectivity and entropy play a subtle, but important role in how glassy dynamics are propagated from interfaces. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 1224–1238     

Polar Effects in Organic Reactions

Attempts to gauge the effect of polar substituents on organic reaction rates by means of “inductive substituent constants” are based on the assumption that these effects are independent of the type of reaction observed. The measured rate constants of nucleophilic substitution reactions show, however, that this assumption is only partly justified even for saturated molecules. It is invalid if the substituent and the reaction center are an electron donor and an electron acceptor, respectively, which are hyperconjugated by way of σ-bonds. In extreme cases the resulting polarization can lead to heterolytic fragmentation.     

In-vitro assays for determination of oestrogenic activity

At present, in-vitro bioassays are predominantly being seen as tools to identify, through screening programs, whether or not individual chemical compounds have an effect on the endocrine system. However, as the techniques mature, they are likely to find use in the future in monitoring of discharges to the environment for any biological effect and will compliment the range of chemical and biological techniques also available for monitoring environmental quality. Such an approach has already been utilised by a number of workers to fractionate mixtures (e.g. final effluents from STW), to isolate the oestrogenically active components and subsequently identify the compounds which are active. This paper reviews the present state of in-vitro techniques for determination of oestrogenic activity and discusses present approaches to their use in environmental monitoring in conjunction with chemical analyses in toxicity identification and evaluation.     

Electrostatic calculation of the substituent effect: an efficient test on isolated molecules

The energy of a disubstituted molecule has often been approximated by simple electrostatic formulas that represent the substituents as poles or dipoles. Herein, we test this approach on a new model system that is more direct and more efficient than testing on acid-base properties. The energies of 27 1,4-derivatives of bicyclo[2.2.2]octane were calculated within the framework of the density functional theory at the B3LYP/6-311+G(d,p) level; interaction of the two substituents was evaluated in terms of isodesmic homodesmotic reactions. This interaction energy, checked previously on some experimental gas-phase acidities, was considered to be accurate and served as reference to test the electrostatic approximation. This approximation works well in the qualitative sense as far as the sign and the order of magnitude are concerned: beginning with the strongest interaction between two poles, a weaker interaction between pole and dipole, and the weakest between two dipoles. However, all the electrostatic calculations yield energies that are too small, particularly for weak interaction, and this fundamental defect is not remedied by some possible improvements. In particular, variation of the effective permittivity would require a physically impossible value less than unity. The explanation must lie in a more complex distribution of electron density than anticipated in the electrostatic model. It also follows that possible conclusions about the transmission of substituent effects "through space" have little validity.     

Effects of drawing on creep parameters of polyoxymethylene-drawn fibers

The effects of drawing on creep parameters (modulus, viscosity, and retardation time) of polyoxymethylenedrawn fibers were examined on the basis of a series-parallel, four-element, mechanical model. These parameters increased with the draw ratio. The change in the modulus was the same between the series and parallel components. This was true also for the viscosity, although the change in the viscosity was much greater than that in the modulus. This means that the series and parallel components are deformed in the same mode by drawing. The parallel viscosity increased with elapsed loading times according to an experimental power function; this was also derived from the usual rate equation for viscosity change in the amorphous component. In contrast, the series viscosity remained unchanged over the short creep range due to an extremely larger value than that of the parallel. © 1995 John Wiley & Sons, Inc.     

Ligand and substrate effects in gas-phase reactions of NiX(+)/RH couples (X=F, Cl, Br, I; R=CH3, C2H5, nC3H7, nC4H9)

The reactions of small saturated hydrocarbons by gaseous nickel cations NiX+ (X=F, Cl, Br, I) are investigated by means of electrospray ionization mass spectrometry. The halide cations are obtained from solutions of the corresponding Ni(II) salts in water or methanol as solvents. NiF+ is the only Ni(II) halide complex that brings about thermal activation of methane. The branching ratios of the observed reactions with C2H6, C3H8, and nC4H10 are shifted systematically by changing the nature of both the ligand X and the substrate RH. In the elimination of HX (X=F, Cl, Br, I), the formal oxidation state of the metal ion appears to be conserved, and the importance of this reaction channel decreases in going from NiF+ to NiI+. A reversed trend is observed in the losses of small closed-shell neutral molecules, that is, H2, CH4 and C2H6, which dominate the gas-phase ion chemistry of NiI+/RH couples. Additionally, inner-sphere electron-transfer reactions take place for a few systems, that is, the delivery of hydride or methanide ions from the hydrocarbon to NiX+ in the course of which the hydrocarbon is converted to a carbenium ion and the cationic metal complex gives rise to a neutral RNiX molecule (R=H, CH3). This process gains importance with decreasing atomic number of the halides and with increasing the size of the alkane. Thus, it constitutes the major pathway in the reactions of NiF+ with propane and n-butane, whereas it is not observed for any of the NiI+/RH couples investigated. Concerning the regioselectivity of the reactions with propane and n-butane, heterolytic cleavage of secondary carbon--hydrogen bonds is clearly preferred compared to that of primary ones, as revealed by deuterium labeling studies. For the NiF+/C3H8 couple, the selectivity of the hydride transfer is as large as 360 in favor of the secondary positions. Though smaller, large preferences for the activation of secondary C--H bonds are also operative in homolytic bond activation of RH (R=nC3H7, nC4H9).     

Additivity rules using similarity models for chemical reactivity: calculation and interpretation of electrofugality and nucleofugality

A recently proposed, multi-parameter correlation: log k (25 degrees C)=s(f) (Ef + Nf), where Ef is electrofugality and Nf is nucleofugality, for the substituent and solvent effects on the rate constants for solvolyses of benzhydryl and substituted benzhydryl substrates, is re-evaluated. A new formula (Ef=log k (RCl/EtOH/25 degrees C) -1.87), where RCl/EtOH refers to ethanolysis of chlorides, reproduces published values of Ef satisfactorily, avoids multi-parameter optimisations and provides additional values of Ef. From the formula for Ef, it is shown that the term (sfxEf) is compatible with the Hammett-Brown (rho+sigma+) equation for substituent effects. However, the previously published values of N(f) do not accurately account for solvent and leaving group effects (e.g. nucleofuge Cl or X), even for benzhydryl solvolyses; alternatively, if the more exact, two-parameter term, (sfxNf) is used, calculated effects are less accurate. A new formula (Nf=6.14 + log k(BX/any solvent/25 degrees C)), where BX refers to solvolysis of the parent benzhydryl as electrofuge, defines improved Nf values for benzhydryl substrates. The new formulae for Ef and Nf are consistent with an assumption that sf=1.00(,) and so improved correlations for benzhydryl substrates can be obtained from the additive formula: log k(RX/any solvent/25 degrees C)=(Ef + Nf). Possible extensions of this approach are also discussed.     

On the Size Evolution of Monolayer‐Protected Gold Clusters during Ligand Place‐Exchange Reactions: The Effect of Solvents

Ligand place‐exchange (LPE) reactions are extensively applied for the post‐functionalization of monolayer‐protected gold clusters (MPCs) by using excessive incoming ligands to displace initial ones. However, the modified MPCs are often enlarged or degraded; this results in ill‐defined size‐dependent properties. The growth of MPCs essentially involves an unprotected surface that is subsequently has gold atoms added or is fused with other gold cores owing to collision. Reported herein is a guideline for the selection of solvents to suppress unwanted MPC growth. Favorable solvents are those with significant affinity to gold or with low solubility for desorbed ligands because these properties retard LPE reactions and minimize the time available for unprotected gold cores. This finding provides a general and convenient approach to regulate the size of functionalized MPCs.     

Ensemble‐Averaged QM/MM Kinetic Isotope Effects for the SN2 Reaction of Cyanide Anions with Chloroethane in DMSO Solution

The existence of solvent fluctuations leads to populations of reactant‐state (RS) and transition‐state (TS) configurations and implies that property calculations must include appropriate averaging over distributions of values for individual configurations. Average kinetic isotope effects 〈KIE〉 for NC^?+EtCl→NCEt+Cl^? in DMSO solution at 30 °C are best obtained as the ratio 〈f_RS〉/〈f_TS〉 of isotopic partition function ratios separately averaged over all RS and TS configurations. In this way the hybrid AM1/OPLS‐AA potential yields 〈KIE〉 values for all six isotopic substitutions (2° α‐²H₂, 2° β‐²H₃, α‐¹¹C/¹⁴C, leaving group ³⁷Cl, and nucleophile ¹³C and ¹⁵N) for this reaction in the correct direction as measured experimentally. These thermally‐averaged calculated KIEs may be compared meaningfully with experiment, and only one of them differs in magnitude from the experimental value by more than one standard deviation from the mean. This success contrasts with previous KIE calculations based upon traditional methods without averaging. The isotopic partition function ratios are best evaluated using all (internal) vibrational and (external) librational frequencies obtained from Hessians determined for subsets of atoms, relaxed to local minima or saddle points, within frozen solvent environments of structures sampled along molecular dynamics trajectories for RS and TS. The current method may perfectly well be implemented with other QM or QM/MM methods, and thus provides a useful tool for investigating KIEs in relation to studies of chemical reaction mechanisms in solution or catalyzed by enzymes.     

A comparative study of high-spin manganese and iron complexes

Different metal complexes of the general form M(OH) _n (H₂O)_{6– n} have been studied for manganese and iron. Oxidation states considered for manganese are Mn(III), Mn(IV) and Mn(V) and for iron Fe(II), Fe(III) and Fe(IV). Oxygen containing ligands are used throughout with varying numbers of hydroxyl and water ligands. Some metal-oxo and some charged complexes were also studied. Large Jahn-Teller distortions were found for the Mn(III) and Fe(IV) complexes. Consequences of these distortions are that water ligands have to be placed along the weak JT-axis and that five-coordination by a loss of one of these water ligands is quite competitive with six-coordination in particular for manganese. For Fe(II) and Fe(III) lower coordinations than six are preferred due to the presence of two repulsive e _g electrons. For the metal-oxo complexes five-coordination is also preferred due to the strong trans effect from the oxo ligand. All complexes studied have high-spin ground states. An interesting effect is that the spin is much more delocalized on the ligands for the iron complexes than for the manganese complexes. This effect, which is chemically important for certain iron enzymes, is rationalized by the large number of 3d electrons on iron. For manganese with only five 3d electrons no spin delocalization is needed to obtain the proper high-spin states. Received: 4 February 1997 / Accepted: 24 February 1997     

A comprehensive theoretical study on the hydrolysis of carbonyl sulfide in the neutral water

The detailed hydration mechanism of carbonyl sulfide (COS) in the presence of up to five water molecules has been investigated at the level of HF and MP2 with the basis set of 6-311++G(d, p). The nucleophilic addition of water molecule occurs in a concerted way across the C==S bond of COS rather than across the C==O bond. This preferential reaction mechanism could be rationalized in terms of Fukui functions for the both nucleophilic and electrophilic attacks. The activation barriers, DeltaH( not equal) (298), for the rate-determining steps of one up to five-water hydrolyses of COS across the C==S bond are 199.4, 144.4, 123.0, 115.5, and 107.9 kJ/mol in the gas phase, respectively. The most favorable hydrolysis path of COS involves a sort of eight-membered ring transition structure and other two water molecules near to the nonreactive oxygen atom but not involved in the proton transfer, suggesting that the hydrolysis of COS can be significantly mediated by the water molecule(s) and the cooperative effects of the water molecule(s) in the nonreactive region. The catalytic effect of water molecule(s) due to the alleviation of ring strain in the proton transfer process may result from the synergistic effects of rehybridization and charge reorganization from the precoordination complex to the rate-determining transition state structure induced by water molecule. The studies on the effect of temperature on the hydrolysis of COS show that the higher temperature is unfavorable for the hydrolysis of COS. PCM solvation models almost do not modify the calculated energy barriers in a significant way.     

锂离子电池纳微结构电极材料系列研究

纳米储锂电极材料由于奇特的纳米效应与动力学优势,为锂离子电池的发展提供了新的机遇.本文介绍了锂离子电池电极材料的尺寸效应、形貌效应以及电极材料碳包覆的作用;并以作者的近期研究为主,着重讨论了几种"动力学稳定"的纳微结构电极材料和具有"三维混合导电网络"结构的高倍率电极材料.     

Observation of curling effects in tubular and planar graphene-like structures by pyrolysis of ferrocene/dichlorobenzene mixtures

In this work, we investigate the morphological and structural properties of carbon nanostructures fabricated by means of chemical vapor deposition (CVD) methods in the presence of controlled quantities of Cl-containing precursor and ferrocene. We report the observation of a structural transition from tubular-like carbon nanotube (CNT) morphology into planar few-layers graphite in experiments involving the pyrolysis of ferrocene and dichlorobenzene mixtures. An unusual intermediate curling-like mechanism in the walls of the as-grown CNTs is found when intermediate quantities of dichlorobenzene are used. This unusual phenomenon vanishes for high quantities of dichlorobenzene, where the nucleation of planar few-layers graphene-like structures directly connected to micrometer-scale Fe₃C particles is found. Such morphological variation is investigated by means of both scanning electron microscopy (SEM) and transmission electron microscopy (TEM), whereas the structural variation of the obtained structures is analyzed through X-ray diffraction and Raman spectroscopy techniques.     

Matrix Effects in a Fluid Catalytic Cracking Catalyst Particle: Influence on Structure,Acidity, and Accessibility

Matrix effects in a fluid catalytic cracking (FCC) catalyst have been studied in terms of structure, accessibility, and acidity. An extensive characterization study into the structural and acidic properties of a FCC catalyst, its individual components (i.e., zeolite H-Y, binder (boehmite/silica) and kaolin clay), and two model FCC catalyst samples containing only two components (i.e., zeolite-binder and binder-clay) was performed at relevant conditions. This allowed the drawing of conclusions about the role of each individual component, describing their mutual physicochemical interactions, establishing structure-acidity relationships, and determining matrix effects in FCC catalyst materials. This has been made possible by using a wide variety of characterization techniques, including temperature-programmed desorption of ammonia, infrared spectroscopy in combination with CO as probe molecule, transmission electron microscopy, X-ray diffraction, Ar physisorption, and advanced nuclear magnetic resonance. By doing so it was, for example, revealed that a freshly prepared spray-dried FCC catalyst appears as a physical mixture of its individual components, but under typical riser reactor conditions, the interaction between zeolite H-Y and binder material is significant and mobile aluminum migrates and inserts from the binder into the defects of the zeolite framework, thereby creating additional Brønsted acid sites and restoring the framework structure.     

A new access to quinazolines from simple anilines

A new synthetic pathway to quinazolines is described. This new method uses hexamethylenetetramine in TFA and potassium ferricyanide in aqueous ethanolic KOH, starting from simple N-protected anilines. The method affords substituted quinazolines with high selectivities and good yields, reducing reaction-time and work-up operations.     

Non-specific adhesion on biomaterial surfaces driven by small amounts of protein adsorption

This work explores how long-range non-specific interactions, resulting from small amounts of adsorbed fibrinogen, potentially influence bioadhesion. Such non-specific interactions between protein adsorbed on a biomaterial and approaching cells or bacteria may complement or even dominate ligand–receptor mating. This work considers situations where the biomaterial surface and the approaching model cells (micron-scale silica particles) exhibit strong electrostatic repulsion, as may be the case in diagnostics and lab-on-chip applications. We report that adsorbed fibrinogen levels near 0.5 mg/m² produce non-specific fouling. For underlying surfaces that are less fundamentally repulsive, smaller amounts of adsorbed fibrinogen would have a similar effect. Additionally, it was observed that particle adhesion engages sharply and only above a threshold loading of fibrinogen on the collector. Also, in the range of ionic strength, I, below about 0.05 M, increases in I reduce the fibrinogen needed for microparticle capture, due to screening of electrostatic repulsions. Surprisingly, however, ionic strengths of 0.15 M reduce fibrinogen adsorption altogether. This observation opposes expectations based on DLVO arguments, pointing to localized electrostatic attractions and hydration effects to drive silica–fibrinogen adhesion. These behaviors are benchmarked against microparticle binding on silica surfaces carrying small amounts of a polycation, to provide insight into the role of electrostatics in fibrinogen-driven non-specific adhesion.     

Ligustri Lucidi Fructus as a traditional Chinese medicine: a review of its phytochemistry and pharmacology

Ligustri Lucidi Fructus (LLF) is the fruits of Ligustrum lucidum Ait. (Oleaceae). This review based on nearly 80 literary sources discusses the knowledge of chemistry and biological effects of this species. Several types of chemical constituents considered as the characteristic and active constituents from LLF were isolated including 40 triterpenoids, 48 iridoids, 10 flavones, 10 phenylethanoid glycosides and others. Various extracts and individual compounds derived from this species have been found to possess a variety of pharmacological effects, e.g. anti-tumour, hepatoprotective, immune regulating, antioxidative and anti-ageing effects, anti-inflammation and reducing hypercholesterolaemia effects and so on. The results of data analysis on the chemical, pharmacological characteristics of LLF support the view that this species has many therapeutic properties and indicate its potential as an effective herbal remedy. Finally, some suggestions for further research on chemical and pharmacological properties are given in this review. Theoretical basis was given for further exploiting and utilising LLF.