Chemical Exchange Saturation Transfer (CEST) Agents: Quantum Chemistry and MRI

Diamagnetic chemical exchange saturation transfer (CEST) contrast agents offer an alternative to Gd³⁺‐based contrast agents for MRI. They are characterized by containing protons that can rapidly exchange with water and it is advantageous to have these protons resonate in a spectral window that is far removed from water. Herein, we report the first results of DFT calculations of the ¹H nuclear magnetic shieldings in 41 CEST agents, finding that the experimental shifts can be well predicted (R²=0.882). We tested a subset of compounds with the best MRI properties for toxicity and for activity as uncouplers, then obtained mice kidney CEST MRI images for three of the most promising leads finding 16 (2,4‐dihydroxybenzoic acid) to be one of the most promising CEST MRI contrast agents to date. Overall, the results are of interest since they show that ¹H NMR shifts for CEST agents—charged species—can be well predicted, and that several leads have low toxicity and yield good in vivo MR images.     

Triple-period partial misfit dislocations at the InN/GaN (0001) interface: A new dislocation core structure for III-N materials

The lattice-misfit InN/GaN (0001) interface supports a triangular network of α-core 90° partial misfit dislocations. These misfit dislocations provide excellent strain relief. However, in their unreconstructed form the dislocation contains numerous high-energy N dangling bonds, which must be eliminated by reconstructing the dislocation core. Existing single-period (SP) and double-period (DP) dislocation reconstruction models eliminate these dangling bonds via a like-atom dimerization, such as N-N dimers. However, we show that these N–N dimers are unstable for the III-N materials, so an entirely new reconstruction mechanism is needed. A “triple-period” (TP) structural model is developed which eliminates N dangling bonds via the formation of N vacancies instead of N-N dimers. The model contains no N–N (or III–III) bonds, fully bonds all N atoms to four group-III neighboring atoms, and satisfies the “electron counting rule” by transferring charge from In dangling bonds to Ga dangling bonds.     

On-line monitoring of cyclotron target-gas output by means of tunable lead salt diode laser absorption spectroscopy

We demonstrate what is, to our knowledge, the first use of mid-infrared laser absorption spectroscopy for trace-gas measurements of cyclotron target outputs used for the generation of radioactive carbon-11 in positron emission tomography (PET). The spectrometer was based upon a liquid-nitrogen-cooled lead salt diode laser generating single-mode radiation in the wavenumber range of 2230–2240 cm^?1. The sample flowed to a multiple-pass optical cell with a total path length of 15.23 m and the laser radiation was detected by two liquid-nitrogen-cooled InSb photodetectors. We present the results of CO, N₂O and CO₂ measurements on PET trace cyclotron output and discuss future work on ¹¹CO and ¹¹CO₂ detection.     

Palladium‐Catalyzed Heck‐Type Cross‐Couplings of Unactivated Alkyl Iodides

A palladium‐catalyzed, intermolecular Heck‐type coupling of alkyl iodides and alkenes is described. This process is successful with a variety of primary and secondary unactivated alkyl iodides as reaction partners, including those with hydrogen atoms in the β position. The mild catalytic conditions enable intermolecular C? C bond formations with a diverse set of alkyl iodides and alkenes, including substrates containing base‐ or nucleophile‐sensitive functionality.     

High‐Density Lipoprotein Nanoparticles Deliver RNAi to Endothelial Cells to Inhibit Angiogenesis

Systemic delivery of therapeutic nucleic acids to target cells and tissues outside of the liver remains a major challenge. A biomimetic high‐density lipoprotein nanoparticle (HDL NP) is synthesized for delivery of a cholesteryl‐modified therapeutic nucleic acid to vascular endothelial cells (ECs), a cell type naturally targeted by HDL. HDL NPs adsorb cholesteryl‐modified oligonucleotides and protect them from nuclease degradation. As proof of principle, we deliver RNAi targeting vascular endothelial growth factor receptor 2 (VEGFR2) to ECs to effectively silence target mRNA and protein expression in vitro. In addition, data show that treatment strongly attenuates in vivo neovascularization measured using a standard angiogenesis assay and in hypervascular tumor allografts where a striking reduction in tumor growth is observed. For effective delivery, HDL NPs require the expression of the cell surface protein scavenger receptor type‐B1 (SR‐B1). No toxicity of HDL NPs is measured in vitro or after in vivo administration. Thus, by using a biomimetic approach to nucleic acid delivery, data demonstrate that systemically administered RNAi–HDL NPs target SR‐B1 expressing ECs to deliver functional anti‐angiogenic RNAi as a potential treatment of cancer and other neovascular diseases.     

Experimental comparison of Jψ production by π±, K±, p and p̄ beams at 39.5 GeV/c

Measurements have been made of relative production cross sections of the $\text{J}\text{ψ}$ by π^±, K^±, p and p? at 39.5 GeV/c incident on copper. $\text{J}\text{ψ}$ production rates from π^?, K^? and p? are similar. The $\text{J}\text{ψ}$ relative particle/anti-particle production cross sections for x>0 are $\text{σ(π}{}^{\mathrm{+}}\text{)}\text{σ(π}{}^{\mathrm{?}}\text{)=(0.87±0.14)}$, σ(K⁺)/σ(K^?)=(0.85±0.5) and $\text{σ(}\text{p}\text{)}\text{σ(}\text{p}\text{?}\text{)=(0.15 ±0.08)}$. The small p/p? cross section ratio disagrees with models of J/ψ production by gluon amalgamation.     

A search for charmed particles originating from the interactions of 300 GeV/c protons in emulsion nuclei

The associated production of charmed particles by the interactions of 300 GeV/c protons with complex nuclei has been sought using nuclear emulsions. The failure to observe any candidates for this process among some 60,000 interactions investigated implies, provided charmed particles lifetimes are in the range 10^?12 to 10^?14 s, a cross section for their associated production by the interactions of 300 GeV/c protons with nucleons of less than 1.5 microbarns at a 90% confidence level.