Factors influencing the formation of silver-rich solid solutions in rare-earth-silver alloy systems

The solid solubilities of all of the naturally occurring rare-earth metals in silver have been determined by using the X-ray parametric method. The solubilities range from 0.01 to 0.02 at. pct for Eu to 10.5 at. pct for Sc. The stoichiometries of the silver-rich compounds and some of their crystal structures were determined. The silver-rich compounds found in this study are: RAg₅(La, Ce, Pr, Eu, and Yb), RAg₄(Lu and Sc), R₁₄Ag_5l(La to Sm, Gd to Er, Yb, and Y) and TmAg₃. The silver/silver-rich compound eutectic temperatures were also determined. Analysis of these data indicates that several factors in addition to the Hume-Rothery criteria influence the formation and extent of solid solutions. These include the mutual adjustment of size and electronegativity of the solvent and solute if the pure metal size differences are less than a critical value of 22 to 25 pct, the composition of the first solvent-rich compound, and the lattice rigidity of the solvent. Formerly Research Helper, Institute for Atomic Research, is in the U.S. Armed Forces.     

The Effects of Prodrug Size and a Carbonyl Linker on l-Type Amino Acid Transporter 1-Targeted Cellular and Brain Uptake

The l -type amino acid transporter 1 (LAT1, SLC7A5) imports dietary amino acids and amino acid drugs (e. g., l -DOPA) into the brain, and plays a role in cancer metabolism. Though there have been numerous reports of LAT1-targeted amino acid-drug conjugates (prodrugs), identifying the structural determinants to enhance substrate activity has been challenging. In this work, we investigated the position and orientation of a carbonyl group in linking hydrophobic moieties including the anti-inflammatory drug ketoprofen to l -tyrosine and l -phenylalanine. We found that esters of meta-carboxyl l -phenylalanine had better LAT1 transport rates than the corresponding acylated l -tyrosine analogues. However, as the size of the hydrophobic moiety increased, we observed a decrease in LAT1 transport rate with a concomitant increase in potency of inhibition. Our results have important implications for designing amino acid prodrugs that target LAT1 at the blood-brain barrier or on cancer cells.