Non-applicability of band-model to β-hydrogen phthalocyanine

The mechanism of charge carrier transport in β-hydrogen phthalocyanine has been studied with the aid of the recent Munn and Siebrand theory. It is shown that the band-model is not applicable to metal-free phthalocyanine except for electron transport along the crystallographic b-axis.     

How to exploit different endocytosis pathways to allow selective delivery of anticancer drugs to cancer cells over healthy cells

It was recently shown that it is possible to exploit the nanoparticle shape to selectively target endocytosis pathways found in cancer and not healthy cells. It is important to understand and compare the endocytosis pathways of nanoparticles in both cancer and healthy cells to restrict the healthy cells from taking up anticancer drugs to help reduce the side effects for patients. Here, the clathrin-mediated endocytosis inhibitor, hydroxychloroquine, and the anticancer drug, doxorubicin, are loaded into the same mesoporous silica nanorods. The use of nanorods was found to restrict the uptake by healthy cells but allowed cancer cells to take up the nanorods via the macropinocytosis pathway. Furthermore, it is shown that the nanorods can selectively deliver doxorubicin to the nucleus of breast cancer cells and to the cytoplasm of pancreatic cancer cells. The dual-drug-loaded nanorods were able to selectively kill the breast cancer cells in the presence of healthy breast cells. This study opens exciting possibilities of targeting cancer cells based on the material shape rather than targeting antibodies.

It was recently shown that it is possible to exploit the nanoparticle shape to selectively target endocytosis pathways found in cancer and not healthy cells.     

On the Mechanism of the Thermal and Photolytic Cyclization of Diphenylamines to Carbazoles

The product of photolysis of di-p-tolyamine in petroleum ether is 3,6-dimethylcarbazole. The primary product of gas-phase thermolysis of di-p-tolylamine at 850–1000°/0.01–0.05 Torr is also 3,6-dimethylcarbazole. In the higher temperature range monomethylcarbazole and carbazole are also formed. Thermolysis of tetra-p-tolylhydrazine at 800–1000° gives only di-p-tolylamine, the latter decomposing further in the higher temperature range. It is concluded that carbazole formation involves in both cases an electrocyclization of the ortho-positions, and not a rearrangement, and that diphenylaminyl is not an intermediate.     

Probabilistic assessment for a sample to be radioactive or not: application to radioxenon analysis

When a net count value is below the type 1 error critical limit it is customary to declare that the activity is “below the detection limit”. The content of this declaration is particularly impoverished, incapable for example of discriminating between a net measurement just below the critical limit, but positive, and a negative net measurement, two types of information that it is legitimate and intuitive to think do not have the same weight of information. In the case of a spectral measurement of ^131mXe and ^133mXe certain information is available according to the various X and gamma emissions, which might all be below their respective critical limits. We shall see that a Bayesian probabilistic approach can be used, without considering the critical limits, to obtain anti-correlated maximum likelihood values taking all the information into account jointly and to obtain powerful and pertinent information in the form of the absolute probability that the sample contains ^131mXe and/or ^133mXe, all possible activity values combined. Conversely, of course, this is used immediately to deduce the probability that the sample does not contain ^131mXe and/or ^133mXe. This information enables the customary critical limit to be ignored.     

Locating conical intersections relevant to photochemical reactions

A new computerized method for locating conical intersections of interest in photochemistry is presented. The search is based on the Longuet-Higgins phase change theorem (Berry phase) which provides the subspace required for the initial search. The subspace is approximated as a plane containing three stable structures lying on a Longuet-Higgins loop. The search is conducted for a minimum of ΔE, the energy difference between two electronic states. It is started using up to three points within the circle defined by the three structures; symmetry, if relevant, is helpful but not essential. Since a two-dimensional subspace of the large 3N − 6 space is used, the search that uses either Cartesian or internal coordinates is efficient and yields a degeneracy after a few iterations. Given that not all degrees of freedom are included in the search, usually a high lying part of the conical intersection is initially located. The system is subsequently optimized along all coordinates keeping ΔE as close to zero as desired. The method is demonstrated for the symmetric H₃ system and also for the butadiene–cyclobutene–bicyclobutane system in which the three stable structures are not equivalent. The method is general and can be extended to any photochemical system.     

Strong π-π stacking interactions led to the mis-assignment of dimer emissions to the monomers of 1-acetylpyrene

Both experimental and computational studies showed owing to strong π-π stacking interactions, 1-acetylpyrene mainly exists in dimers and molecular aggregates even at low concentrations, which led to the mis-assignment of its monomer emission peaks.     

Rearrangement of allyl thienyl sulfides to allylthiophenethiols

It is shown that the rearrangement of allyl 2-thienyl and allyl 3-thienyl sulfides in various solvents at 89–136°C gives the corresponding allylthiophenethiols, which can subsequently undergo transallylation with the starting sulfide and cyclization to thienodihydrothiopyrans and methyldihydrothienothiophenes. The energy of activation of the rearrangement of both isomeric sulfides is 19 kcal/mole. The pK_a values of thiophenyl and some thiols of the thiophene series were determined, and it was established that the acidities of the allylthiophenethiols do not have a decisive effect on their ability to undergo cyclization.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 186–189, February, 1978.     

Borazine: to be or not to be aromatic

Aromaticity of borazine, which has been subject of controversial discussions, is addressed. Beside a short review on aromaticity of borazine we report a detailed analysis of two molecular fields, the induced magnetic field (B ^ind) and the electron localization function (ELF). The induced magnetic field of borazine shows a long-range shielding cone perpendicular to the molecular plane, as in benzene, but lower in magnitude. Contrary to benzene, borazine shows two weakly paratropic regions, one of them inside the ring, and the second one enveloping the boron atoms. It is necessary to separate σ and π contributions to identify whether borazine exhibits π-aromatic character comparable to benzene. Nucleus-independent chemical shift (NICS) isolines show that the σ electrons are much stronger localized than π electrons, their local paramagnetic contributions generate a short-range response and a paratropic (deshielding) region in the ring center (similar to an anti-aromatic response). Three regions can be identified as chemically meaningful domains exhibiting an internally strong electron delocalization (ELF = 0.823). Borazine may be described as a π aromatic compound, but it is not a globally aromatic species, as the electronic system is not as delocalized as in benzene. Dedicated to the 70th birthday of Prof. Tadeusz Marek Krygowski.     

Kinetic approach to heavy metal mobilization assessment in sediments: choose of kinetic equations and models to achieve maximum information

Studies of trace metal mobilization in sediments are generally performed using sequential extraction schemes at equilibrium. In the present work, a kinetic fractionation of trace metals in sediments has been developed to assess that information. The extraction rate data have been obtained using a single extraction scheme with EDTA and following a protocol previously optimized. Two kinetic equations and two kinetic models were used to fit the experimental data. The two constants equation fits well the extraction rate data used in this work but does not present any physico-chemical meaning. The diffusion model and the two first-order reactions model allow determining which parameter (the reaction between the metal M and the EDTA or the diffusion of the complex M/EDTA) is rate limiting in the trace metal extraction by EDTA. It appears that the two first-order reactions model is more efficient than the diffusion model to fit the present extraction rate data so it can be deduced that the diffusion of the complex M/EDTA is not the limiting step of the trace metal extraction by EDTA in estuarine sediments. In a second part, relationships between the fraction of metals determined with the two first-order reactions model and the sediments composition were established.     

Polymer science applied to biological problems: Prediction of cytotoxic drug interactions with DNA

It is taken for granted in the polymer world that the fundamental thermodynamic insights of Hansen solubility parameters (HSP) can be used to predict solvent/chemical interactions with polymers. The same principles should apply equally to bio-molecules interacting with that key polymer, DNA. A necessary (but not sufficient) condition for a drug to be cytotoxic is that it penetrates cell walls and be (thermodynamically) compatible with the core of the DNA polymer. The HSP of 9 cytotoxic drugs conform well to the basic HSP principle that “like (cell walls, DNA) attracts like (all 9 drugs)”. A correlation is not proof. But at the very least, HSP offer a fecund methodology for making predictions not only of how single molecules might interact with biological polymers, but how mixtures of chemicals could be more potent than the individual components. It is predicted, for example, that alcohols would provide synergism with many chemicals with their mixtures having higher affinity for the DNA bases than the individual components.     

Head to head polymers. XVII: Head to head polypropylene

Head to head polypropylene was prepared by catalytic hydrogenation of eithercis-1,4-poly(2,3-dimethylbutadiene) ortrans-1,4-poly(2,3-dimethylbutadiene) with cobalt 2-ethylhexanoate/triethylaluminium as the hydrogenation catalyst in decahydronaphthalene solution. The hydrogenation occurred predominantly bycis hydrogen addition, but was not stereospecific. The samples of head to head polypropylene were characterized by IR and NMR, particularly by¹³C-NMR spectroscopy. The polymers were amorphous and exhibited glass transition temperatures about 20°C lower than that of head to tail poly-propylene; the glass transition temperatures were measured by DSC and varied somewhat from sample to sample (sufficiently high molecular weight) according to their stereochemistry. TheT _gvalues were confirmed by Rheovibron measurements. The thermal stability of head to head polypropylene is not significantly different from that of either atactic or isotactic head to tail polypropylene.Part XVI:Grossman S., Yamada A., Vogl O., J. Macromol. Sci.-Chem.A 16, 897 (1981).     

Response mechanism of platinum electrode to uncoupled ions(I)

The transient response mechanism of the platinum electrode to the uncoupled ions may be interpreted with the mixed phase formation (MPF) model of the transient response of precipitate-based ion-selective electrodes to interfering ions for K_xy ≪ 1. It is discovered that the peak height of the transient signal is related to the solubility of M(OH)₂ and hydration heat of M²⁺. The relation between the positive peak height of transient signal of pb²⁺ or cd²⁺ and lga_m obey the Nernst equation, while that of Ca²⁺ or Mg²⁺ does not. The equilibrium potential is not of Nernst response for all ions. Project supported by the National Natural Science Foundation of China.     

Rigorous Conformational Analysis of Pyrrolidine Enamines with Relevance to Organocatalysis

It has been suggested that the origin of regio‐ and stereoselectivity in Michael additions of pyrrolidine enamines is achieved by thermodynamic rather than kinetic control through distinct conformational preferences of the enamines. We assess this proposal by elaboration of a computational protocol that warrants sufficient accuracy. The small energy differences between the conformers necessitate a high accuracy of the electronic structure method which, in addition, must allow for computationally feasible calculations of a large number of conformers. Our protocol is based on density functional theory which we validated against explicitly correlated coupled cluster theory. The results are in agreement with the available experimental data, but illustrate that conformational preferences determined for one enamine are not readily transferable to other types of enamines. We found that an appropriate conformational sampling is inevitable to arrive at meaningful conclusions. Most prominently, s‐cis and s‐trans conformers are similarly stable for aldehyde‐ and ketone‐derived enamines. The regio‐ and stereoselectivity in Michael additions of pyrrolidine‐derived enamines can not be explained by pronounced stability differences of the enamine isomers and conformers in general, disproving the thermodynamic‐control hypothesis. The elucidation of the origin of regio‐ and stereoselectivity requires further theoretical investigations of the elementary steps of Michael additions.     

First correction to surface tension for the curvature of an interface

Tolman parameter δ_T, which determines the first correction to surface tension for the interface curvature, is calculated in molecular-dynamic experiments performed for Lennard-Jones fluid within the temperature range from the critical to the triple point (and slightly below). It is shown that parameter δ_T is positive and slightly depends on temperature; its absolute magnitude is no larger than 0.1–0.2 molecular diameters and does not coincide with the distance between the equimolecular dividing surface and the surface of tension in a flat interfacial layer, as calculated through the first moment of the pressure tensor. The results of the moleculardynamic experiments are compared with the δ_T values calculated in terms of the extended version of the van der Waals theory of capillarity. It is established that taking into account terms of higher orders than the squared density gradient in the expansion of the free energy of an inhomogeneous system does not reverse the negative sign at δ_T and slightly affects its value.     

Loss of Sirt6 in adipocytes impairs the ability of adipose tissue to adapt to intermittent fasting

Intermittent fasting (IF) is gaining popularity for its effectiveness in improving overall health, including its effectiveness in achieving weight loss and euglycemia. The molecular mechanisms of IF, however, are not well understood. This study investigated the relationship between adipocyte sirtuin 6 (Sirt6) and the metabolic benefits of IF. Adipocyte-specific Sirt6-knockout (aS6KO) mice and wild-type littermates were fed a high-fat diet (HFD) ad libitum for four weeks and then subjected to 12 weeks on a 2:1 IF regimen consisting of two days of feeding followed by one day of fasting. Compared with wild-type mice, aS6KO mice subjected to HFD + IF exhibited a diminished response, as reflected by their glucose and insulin intolerance, reduced energy expenditure and adipose tissue browning, and increased inflammation of white adipose tissue. Sirt6 deficiency in hepatocytes or in myeloid cells did not impair adaptation to IF. Finally, the results indicated that the impaired adipose tissue browning and reduced expression of UCP1 in aS6KO mice were accompanied by downregulation of p38 MAPK/ATF2 signaling. Our findings indicate that Sirt6 in adipocytes is critical to obtaining the improved glucose metabolism and metabolic profiles conferred by IF and that maintaining high levels of Sirt6 in adipocytes may mimic the health benefits of IF.Subject terms: Obesity, Fat metabolism     

Deamination of protonated amines to yield protonated imines

Primary and secondary amines, when examined in atmospheric pressure chemical ionization, electrospray ionization, or chemical ionization, display protonated imines in their mass spectra. These products arise formally by nucleophilic substitution at the α-carbon with loss of both ammonia and molecular hydrogen. Collision-induced dissociation (CID) is used to characterize the product ions by comparison with authentic protonated imines. Gas-phase ion/molecule reactions of protonated amines with neutral amines also yield products that correspond to protonated imines (deamination and dehydrogenation), as well as providing simple deamination products. The reaction mechanism was investigated further by reacting the deamination product, the alkyl cation, with a neutral amine. The observed dehydrogenation of the nascent protonated secondary amine indicates that the reaction sequence is loss of ammonia followed by dehydrogenation even though the isolated protonated secondary amines did not undergo dehydrogenation upon CID. Formation of the deamination products in the protonated amine/amine reaction is competitive with proton-bound dimer formation. The proton-bound dimers do not yield deamination products under CID conditions in the ion trap or in experiments performed using a pentaquadrupole instrument. This demonstrates that the geometry of the proton-bound dimer, in which the α-carbons of the alkylamines are well separated [C _a -N-H-N-C _a ], is an unsuitable entry point on the potential energy hypersurface for formation of the imine [C _a -N-C _a ]. Isolation of the proton-bound dimers in the quadrupole ion trap is achieved with low efficiency and this characteristic can be used to distinguish them from their covalently bound isomers.     

A caveat concerning the application of the jack-knife to designed data

The jack-knife is a resampling method that is increasingly used for assessing the uncertainty in regression coefficient estimates, even when the predictor variables (X) are designed. Application of the jack-knife to designed data, however, violates a basic assumption underlying all resampling methods, namely that the resampled units should constitute a random sample from some distribution; the idea is to ‘resample the sample.’ This paper advances the view that the jack-knife should not be applied to estimate the uncertainty in regression coefficient estimates obtained from designed data, since a sound alternative is available. A literature data set is re-analyzed to lend support to this view.     

Thermal analysis of binding of iodinated contrast agents to TiO2

Iodinated contrast agents such as iohexol and diatrizoate are pharmaceutical compounds of emerging concern in sewage and drinking water. These are resistant to removal through conventional water treatment processes. Photocatalytic degradation (PD) of these compounds over titanium dioxide has been suggested as a possible technique for the removal of iohexol and diatrizoate from sewage water. Several studies have evaluated these compounds, finding that the two do not respond in the same way to the presence of photocatalyst, which could imply that direct oxidation by surface electron holes is a major route for one compound but not the other. It is necessary that analytes adsorb to the photocatalyst for this oxidation to occur. We employ thermogravimetric analysis to characterize desorption of these analytes from two different forms of titanium dioxide. Compared to pure analyte and pure photocatalyst, additional peaks are seen near 700 °C when the contrast agents are adsorbed to titanium dioxide. This implies that direct oxidation by electron holes is not a primary factor in the PD of iodinated contrast agents. We evaluate the effects of analyte concentration and titanium dioxide crystal structure on these results to address the general applicability of our approach.     

Application of a multifunctional microelectrode to the in vivo analysis of the K+ response to CO2 stress

The K⁺ concentration in the vacuole in leaf cells of Tradescantia virginiana L. decreased abruptly in response to CO₂ stress. This K⁺ response was analysed with a multifunctional microelectrode system. When valinomycin was introduced into the vacuole before exposure to CO₂, the K⁺ concentration increased from 60 to 68 mM. After reaching a steady state, CO₂ was applied again to the leaf. The abrupt decrease in K⁺ concentration observed before did not occur. When valinomycin was introduced during CO₂ exposure, the K⁺ concentration sharply increased reaching 67 mM. Therefore, the K⁺ response was caused by the K⁺ transport from the vacuole to the exterior against its concentration gradient. This phenomenon, however, preceded the H⁺ movement. This does not support the direct involvement of the H⁺ pump system. The blocking of the H⁺ pump system in the vacuolar membrane, however, caused the K⁺ response to disappear. Therefore, it is essential for the K⁺ response that the H⁺ pump system is in the active state, although they are not directly coupled.     

Failure to verify a reported synthesis of the aconitine skeleton

Attempts to verify the first three stages of a claimed synthesis of the aconitine skeleton (Samir Chatterjee, $\text{Tetrahedron Lett.}$ 3249 (1979) have given totally different results. It is concluded that the reported products of these three stages were not in fact obtained.