Aziridines in one step from hydantoins via Red-Al mediated ring-contraction

We have developed a new method to synthesize aziridines from their corresponding hydantoins in one step using an excess of Red-Al overnight in refluxing toluene. This allows direct access to N-H aziridines without the need for protecting group strategies.     

Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy

We review drug conjugates combining a tumor-selective moiety with a cytotoxic agent as cancer treatments. Currently, antibody-drug conjugates (ADCs) are the most common drug conjugates used clinically as cancer treatments. While providing both efficacy and favorable tolerability, ADCs have limitations due to their size and complexity. Peptides as tumor-targeting carriers in peptide-drug conjugates (PDCs) offer a number of benefits. Melphalan flufenamide (melflufen) is a highly lipophilic PDC that takes a novel approach by utilizing increased aminopeptidase activity to selectively increase the release and concentration of cytotoxic alkylating agents inside tumor cells. The only other PDC approved currently for clinical use is ¹⁷⁷Lu-dotatate, a targeted form of radiotherapy combining a somatostatin analog with a radionuclide. It is approved as a treatment for gastroenteropancreatic neuroendocrine tumors. Results with other PDCs combining synthetic analogs of natural peptide ligands with cytotoxic agents have been mixed. The field of drug conjugates as drug delivery systems for the treatment of cancer continues to advance with the application of new technologies. Melflufen provides a paradigm for rational PDC design, with a targeted mechanism of action and the potential for deepening responses to treatment, maintaining remissions, and eradicating therapy-resistant stem cells.     

Entrained Flow Gasification of Polypropylene Pyrolysis Oil

Petrochemical products could be produced from circular feedstock, such as waste plastics. Most plants that utilize syngas in their production are today equipped with entrained flow gasifiers, as this type of gasifier generates the highest syngas quality. However, feeding of circular feedstocks to an entrained flow gasifier can be problematic. Therefore, in this work, a two-step process was studied, in which polypropylene was pre-treated by pyrolysis to produce a liquid intermediate that was easily fed to the gasifier. The products from both pyrolysis and gasification were thoroughly characterized. Moreover, the product yields from the individual steps, as well as from the entire process chain, are reported. It was estimated that the yields of CO and H₂ from the two-step process were at least 0.95 and 0.06 kg per kg of polypropylene, respectively, assuming that the pyrolysis liquid and wax can be combined as feedstock to an entrained flow gasifier. On an energy basis, the energy content of CO and H₂ in the produced syngas corresponded to approximately 40% of the energy content of the polypropylene raw material. This is, however, expected to be significantly improved on a larger scale where losses are proportionally smaller.     

Multielement analysis of whole blood by high resolution inductively coupled plasma mass spectrometry

An analytical method using double focusing sector field inductively coupled plasma mass spectrometry (ICP-SMS) for rapid simultaneous determination of 50 elements in digested human blood is described. Sample preparation consisted of microwave digestion with nitric acid followed by dilution with ultrapure water. The importance of controlling possible contamination sources at different sample preparation and analysis stages in order to achieve adequate method detection limits (MDL) is emphasised. Correction for matrix effects was made using scandium, indium and lutecium as internal standards. Accuracy of the data for elements suffering from spectral interferences was improved by applying either a high resolution capability of the ICP-SMS or mathematical corrections. Different approaches for accuracy assessment in blood analysis are evaluated. Additional information on trace elements concentration in selected blood reference materials is given. The between-batch precision was assessed from replicate analysis (including sample preparation) of reference materials and was better than 10% RSD for 21 elements and better than 30% RSD for 36 elements under consideration. A statistical summary for results obtained for 31 blood samples from non-exposed subjects is presented. The majority of elements tested was found in the samples at concentrations higher than MDL. Received: 23 November 1998 / Revised: 6 January 1999 / Accepted: 12 January 1999     

Credit risk optimization with Conditional Value-at-Risk criterion

This paper examines a new approach for credit risk optimization. The model is based on the Conditional Value-at-Risk (CVaR) risk measure, the expected loss exceeding Value-at-Risk. CVaR is also known as Mean Excess, Mean Shortfall, or Tail VaR. This model can simultaneously adjust all positions in a portfolio of financial instruments in order to minimize CVaR subject to trading and return constraints. The credit risk distribution is generated by Monte Carlo simulations and the optimization problem is solved effectively by linear programming. The algorithm is very efficient; it can handle hundreds of instruments and thousands of scenarios in reasonable computer time. The approach is demonstrated with a portfolio of emerging market bonds. Received: November 1, 1999 / Accepted: October 1, 2000?Published online December 15, 2000     

Electron transfer in bis(hydrazines), a critical test for application of the Marcus model

Electron transfer in the cations of bis(hydrazines), bridged by six different π‐systems (compounds 1–6) is studied using ab initio and density functional theory (DFT) methods. Due to ionization from an antibonding combination of the lone‐pair orbitals of the nitrogens in one of the hydrazine units, conjugation is introduced in the N? N bond of that unit. This leads to a shortening of the N? N bond distance and an increase of the planarity around the nitrogens. Due to steric hindrance, this causes an increase of the angle, called φ, between the lone‐pair orbital on the nitrogen attached to the bridge and the p‐orbital on the adjacent bridge carbon for the ionized unit in the charge localized, relaxed state of the molecule. This angle controls the magnitude of the electronic coupling. In the fully delocalized symmetric transition state of the ion, however, this angle is low for both units, due to the fact that the conjugation introduced at the ionized hydrazine unit is now shared between both units. An extended π‐system is formed including the orbitals of the hydrazine units and the bridge, which leads to a large electronic coupling. The electronic coupling derived by optical methods, corresponding to the structure of the relaxed, asymmetric cation with a large φ for the ionized unit, appears to be much smaller. We believe this is due to an approximate cosine dependence on φ of the coupling. The calculations carried out support these conclusions. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 655–664, 2001     

Molecular rotational conformation controls the rate of singlet fission and triplet decay in pentacene dimers

Three pentacene dimers have been synthesized to investigate the effect of molecular rotation and rotational conformations on singlet fission (SF). In all three dimers, the pentacene units are linked by a 1,4-diethynylphenylene spacer that provides almost unimpeded rotational freedom between the pentacene- and phenylene-subunits in the parent dimer. Substituents on the phenylene spacer add varying degrees of steric hindrance that restricts both the rotation and the equilibrium distribution of different conformers; the less restricted conformers exhibit faster SF and more rapid subsequent triplet-pair recombination. Furthermore, the rotational conformers have small shifts in their absorption spectra and this feature has been used to selectively excite different conformers and study the resulting SF. Femtosecond transient absorption studies at 100 K reveal that the same dimer can have orders of magnitude faster SF in a strongly coupled conformer compared to a more weakly coupled one. Measurements in polystyrene further show that the SF rate is nearly independent of viscosity whereas the triplet pair lifetime is considerably longer in a high viscosity medium. The results provide insight into design criteria for maintaining high initial SF rate while suppressing triplet recombination in intramolecular singlet fission.

In this study we show that one molecule can have vastly different singlet fission and triplet recombination rates depending on its rotational freedom and the relative orientation of the pentacene moieties.     

Surface state on the SiC(0001)-(√3 × √3) surface

An angle resolved photoemission study of a surface state on the SiC(0001)-(√3 × √3) surface is reported. Experiments carried out on the 6H and 4H polytypes give essentially identical results. A surface state band with semiconducting occupation is observed, centered around 1.0 eV above the valence band maximum (VBM) and with a width of about 0.2 eV. Recently calculated results for a Si-adatom-induced √3 × √3 reconstruction give a metallic surface state band centered about 1.2 eV above the VBM and with a width of 0.35 eV. The dispersion determined experimentally is smaller than calculated but exhibits the same trend, the surface state disperses downwards towards the VBM with increasing parallel wavevector component along both the qG--- and qG--- directions of the √3 × √3 surface Brillouin zone. The VBM is determined to be located at about 2.3(±0.2) eV below the Fermi level. The results indicate that Si adatoms on top of an outermost Si---C bilayer may be an inadequate structural model for explaining recent experimental findings for the SiC(0001)-(√3 × √3) surface.     

A photoemission study of 4H---SiC(0001)

A photoemission study using synchrotron radiation of the (0001) surface of 4H-SiC is reported. The investigations were concentrated on the (√3 × √3)-R30° and (6√3 × 6√3)-R30° reconstructed surfaces, prepared by resistive heating at a temperature of about 1000°C and 1250°C, respectively. Results from surfaces heated at intermediate temperatures, exhibiting a mixture of these reconstructions, and after heating at a higher temperature, when graphitisation is clearly observed, are also presented. The √3 and 6√3 reconstructed surfaces exhibit characteristic core level and valence band spectra. High resolution core level spectra show unambiguously the presence of surface shifted components in both the Si 2p and C 1s core levels. For the √3 reconstruction, two surface shifted components are observed both in the Si 2p and C 1s level. For the 6√3 reconstruction, the surface region is found to contain a considerably larger amount of carbon. This carbon is found not to be graphitic since surface C 1s components with binding energies different from a graphitic C 1s peak are observed. Graphitisation, as revealed by the appearance of a graphitic C 1s peak, is observed only after heating to a higher temperature than that required for obtaining a well developed 6√3 diffraction pattern.