Electrophilic aromatic prenylation via cascade cyclization

To gain access to prenylated hexahydroxanthenes, tandem cascade cyclization–electrophilic aromatic substitution reactions have been studied on substrates bearing allylic and propargylic substituents. Both BF₃·OEt₂ and TMSOTf can be used to initiate this reaction sequence, resulting in different ratios of the C-2 and C-6 substitution products. Even though allylic transposition is observed in some cases, the results of a crossover experiment are consistent with an intramolecular reaction sequence. Taken together, these studies now allow preparation of either the C-2 or C-6 prenylated hexahydroxanthene products.     

Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model

Purpose: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. Experimental design: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. Results: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. Conclusions: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.     

Cellulose nanofibril (CNF) reinforced starch insulating foams

In this study, biodegradable foams were produced using cellulose nanofibrils (CNFs) and starch (S). The availability of high volumes of CNFs at lower costs is rapidly progressing with advances in pilot-scale and commercial facilities. The foams were produced using a freeze-drying process with CNF/S water suspensions ranging from 1 to 7.5 wt% solids content. Microscopic evaluation showed that the foams have a microcellular structure and that the foam walls are covered with CNF’s. The CNF’s had diameters ranging from 30 to 100 nm. Pore sizes within the foam walls ranged from 20 to 100 nm. The materials’ densities ranging from 0.012 to 0.082 g/cm³ with corresponding porosities between 93.46 and 99.10 %. Thermal conductivity ranged from 0.041 to 0.054 W/m-K. The mechanical performance of the foams produced from the starch control was extremely low and the material was very friable. The addition of CNF’s to starch was required to produce foams, which exhibited structural integrity. The mechanical properties of materials were positively correlated with solids content and CNF/S ratios. The mechanical and thermal properties for the foams produced in this study appear promising for applications such as insulation and packaging.     

A high statistics measurement of the Lambda(+)(c) lifetime

A high statistics measurement of the Lambda(+)(c) lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat) +/- 2.5 (syst) fs from 8034 +/- 122 Lambda(+)(c)-->pK(-)pi(+) decays represents a significant improvement over the present world average.     

Solid-Phase Synthesis of a Monofunctional trans-a(2)Pt(II) Complex Tethered to a Single-Stranded Oligonucleotide

Cross-linking ability is possible with the oligonucleotide-tethered, monofunctional trans-Pt(II) complex shown. It was synthesized by a novel solid-phase approach comprising conjugation of immobilized tetrathymidylic acid with a trans-a(2)Pt(II) building unit, ammonolysis, and transformation of the resulting complex (R=1-N-cyclohexylmethylthyminate) into the chloro derivative (R=Cl). a=NH(2)CH(3), T=thymine.     

Solvent-dependent stabilization of the E configuration of propargylic secondary amides

Secondary amides typically exist 98-99% in the Z rotamer to avoid steric repulsion between the substituent on the carbonyl carbon and the nitrogen. In contrast, secondary amide 3a displays 24% E rotamer at room temperature in aqueous solution. The analogous ester displays 6% E rotamer in chloroform, which suggests that the relatively high E conformer population observed for 3a in water results in part from the low steric bulk of the sp-hybridized carbons and in part from the hydrophobic effect.     

Solution conformational preferences of glutaric, 3‐hydroxyglutaric, 3‐methylglutaric acid,and their mono‐ and dianions

Conformational preferences of glutaric, 3‐hydroxyglutaric and 3‐methylglutaric acid, and their mono‐ and dianions have been investigated with the aid of NMR spectroscopy. In contrast to succinic acid, glutaric acid displays essentially statistical conformational equilibria in polar and non‐polar solutions of high and low hydrogen‐bonding ability with no clear evidence for intramolecular hydrogen‐bonding interactions. The acid ionization constant ratios, K ₁/K₂, in D₂O and DMSO of glutaric, 3‐hydroxyglutaric, and 3‐methylglutaric acids also indicate that intramolecular interactions are much less important than, or indeed insignificant, for shorter‐chain acids. FTIR studies on 3‐methylglutaric acid indicate some preference for either association with solvent or dimerization, depending on the solvent, rather than intramolecular hydrogen bonding. Copyright © 2008 John Wiley & Sons, Ltd.     

A high temperature Mössbauer effect study of iron-doped YBa2Cu3O7 superconductor

Superconducting YBa₂Cu_2.955Fe_0.045O₇ has been studied at temperatures between 300 and 1000 K. Spectra were recorded on a sample which was sealed as a pellet pressed with boron nitride. An atmosphere of oxygen was maintained in the sample region at all times. At temperatures up to 900 K, we observed the four iron sites A, (Cu(1) chain-site; square planar oxygen coordination with O(5) vacancy on thea-axis), B, (Cu(2) plane-site; square pyramidal oxygen coordination), C, (Cu(1) chain-site; square pyramidal oxygen coordination with O(5) site occupied) and D, (Cu(1) chain-site; quasi-tetrahedral oxygen coordination with O(4) vacancy along theb-axis). At temperatures up to 700 K, the relative area of the B and C sites remained nearly constant as the temperature was increased. However, the area of the A site decreased while, the D site area increased with increasing temperature. At all times, the total area of sites A and D remained constant, thereby indicating the possibility of oxygen atom hopping in thea-b plane. The quadrupole splitting of each site, except the B site, decreased linearly with increasing temperature.Research supported in part by the Old Dominion University Undergraduate Research Program.