SUMMARYLong-distance communication between leaves and roots are key to properly regulate the uptake of trace metals from the soil. The molecular basis of this shoot-to-root signaling is currently unknown. In this manuscript, we describe the role of OPT3 in the shoot-to-root signaling of the iron status in Arabidopsis. We also show that reduced expression of OPT3 induces an over-accumulation of the toxic metal cadmium, but not other metals, in seeds.

pH (low) insertion peptides (pHLIP peptides) target acidic extracellular environments in vivo due to pH-dependent cellular membrane insertion. Two variants (Var3 and Var7) and wild-type (WT) pHLIP peptides have shown promise for in vivo imaging of breast cancer. Two positron emitting radionuclides (64Cu and 18F) were used to label the NOTA- and NO2A-derivatized Var3, Var7, and WT peptides for in vivo biodistribution studies in 4T1 orthotopic tumor-bearing BALB/c mice. All of the constructs were radiolabeled with 64Cu or [18F]-AlF in good yield. The in vivo biodistribution of the 12 constructs in 4T1 orthotopic allografted female BALB/c mice indicated that NO2A-cysVar3, radiolabeled with either 18F (4T1 uptake; 8.9 ± 1.7%ID/g at 4 h p.i.) or 64Cu (4T1 uptake; 8.2 ± 0.9%ID/g at 4 h p.i. and 19.2 ± 1.8% ID/g at 24 h p.i.), shows the most promise for clinical translation. Additional studies to investigate other tumor models (melanoma, prostate, and brain tumor models) indicated the universality of tumor targeting of these tracers. From this study, future clinical translation will focus on 18F- or 64Cu-labeled NO2A-cysVar3.

Nucelophilic substitution at selenium is examined using the B3LYP and MP2 methods. Various nucleophiles (HS -, CH 3 S -, HSe -, and CH 3 Se -) and substrates (R 1 SSeR 2 and R 1 SeSeR 2 with R 1 and R 2 ) H or Me) are used to model substitution at selenium in diselenides and selenosulfides. In all cases, the mechanism is additionelimination. A stable hypercoordinate selenium intermediate lies in a well that is 8-14 kcal mol -1 deep. Nucleophilic attack at selenium is both kinetically and thermodynamically more favorable than at sulfur.

Microsolvation of the neutral, zwitterion, and unconventional zwitterion (formed by the proton transfer from the thiol to the amine group) was performed using PBE1PBE/6-311+G(d,p) calculations. A large sampling of the configurations of the clusters involving one to six water molecules was created by analogy to glycine clusters and through analysis of hydrogen-bonding trends. Clusters of the neutral tautomer are lowest in energy with the inclusion up to five water molecules. With six water molecules the neutral and zwitterion are nearly isoenergetic. The unconventional zwitterion, while a stable structure when at least one water molecule is associated with it, remains energetically noncompetitive with the other two tautomers regardless of the degree of microsolvation.

Summary Radiometals play an important role in diagnostic and therapeutic radiopharmaceuticals. This field of radiochemistry is multidisciplinary, involving radiometal production, separation of the radiometal from its target, chelate design for complexing the radiometal in a biologically stable environment, specific targeting of the radiometal to its in vivo site, and nuclear imaging and/or radiotherapy applications of the resultant radiopharmaceutical. The critical importance of inorganic chemistry in the design and application of radiometal-containing imaging and therapy agents is described from a historical perspective to future directions.