A Bivalent Inhibitor of Prostate Specific Membrane Antigen Radiolabeled with Copper‐64 with High Tumor Uptake and Retention

Molecules containing lysine‐ureido‐glutamate functional groups bind to the active site of prostate specific membrane antigen, which is overexpressed in prostate cancer. To prepare copper radiopharmaceuticals for the diagnosis and therapy of prostate cancer, macrobicyclic sarcophagine ligands tethered to either one or two lysine‐ureido‐glutamate functional groups through an appropriate linker have been prepared. Sarcophagine ligands can be readily radiolabeled with positron‐emitting copper‐64 at room temperature. The bivalent agent, in which two targeting groups are tethered to a single copper complex, dramatically outperforms the monomeric agent with respect to tumor uptake and retention. The high tumor uptake, low background, and prolonged tumor retention, even at 24 hours post injection, suggest the bivalent agent is a promising diagnostic for prostate cancer and could be used for prospective dosimetry for therapy with a copper‐67 variant.     

Finite Homogeneous 3-Graphs

By “3-graph” we mean a pair (V, E) such that E ? [V]³. We show that the only non-trivial finite 3-graphs homogeneous in the sense of Fraïssé are those associated with the projective planes over GF(2) and GF(3), and with the projective lines over GF(5) and GF(9). To exclude other possibilities we use the classification of doubly transitive finite permutation groups.     

Transfer and propagation reactions in free-radical copolymerization

The contribution of entropic factors to the penultimate unit effect in free-radical copolymerizations is discussed and exemplified. In addition, significant penultimate unit effects on radical selectivity in transfer reactions are demonstrated and are shown to have a significant polar component. Further, ring-opening copolymerization studies are presented and describe surprising results that seem to originate from strong solvent effects in copolymerization. These results could not have been predicted with current knowledge, prior to the experiment. The present contribution demonstrates in detail that radical reactions are highly complex and there are significant dangers and drawbacks in employing simplified kinetic models when in search of fundamental understanding.     

Advances in Transition Metal Seleno- and Tellurocarbonyl Chemistry

In contrast to the ubiquity of transition-metal carbonyl, and (to a lesser extent) thiocarbonyl complexes, transition-metal complexes of carbon monoselenide L_nMCSe and monotelluride L_nMCTe remain scarce. The last few years, however, have seen notable steps towards expanding this chemistry, specifically with regards to new systematic studies on homologous sets of chalcocarbonyl complexes L_nMCE (E=O, S, Se, Te), the first reports of new bi- and polynuclear CSe and CTe bridging complexes and a confluence with metal carbido chemistry. Herein the properties, syntheses and reactions of these rare but fundamentally intriguing compounds are discussed.     

Characterization of a tricationic trigonal bipyramidal iron(IV) cyanide complex, with a very high reduction potential, and its iron(II) and iron(III) congeners

Currently, there are only a handful of synthetic S = 2 oxoiron(IV) complexes. These serve as models for the high-spin (S = 2) oxoiron(IV) species that have been postulated, and confirmed in several cases, as key intermediates in the catalytic cycles of a variety of nonheme oxygen activating enzymes. The trigonal bipyramidal complex [Fe(IV)(O)(TMG(3)tren)](2+) (1) was both the first S = 2 oxoiron(IV) model complex to be generated in high yield and the first to be crystallographically characterized. In this study, we demonstrate that the TMG(3)tren ligand is also capable of supporting a tricationic cyanoiron(IV) unit, [Fe(IV)(CN)(TMG(3)tren)](3+) (4). This complex was generated by electrolytic oxidation of the high-spin (S = 2) iron(II) complex [Fe(II)(CN)(TMG(3)tren)](+) (2), via the S = 5/2 complex [Fe(III)(CN)(TMG(3)tren)](2+) (3), the progress of which was conveniently monitored by using UV-vis spectroscopy to follow the growth of bathochromically shifting ligand-to-metal charge transfer (LMCT) bands. A combination of X-ray absorption spectroscopy (XAS), Mo?ssbauer and NMR spectroscopies was used to establish that 4 has a S = 0 iron(IV) center. Consistent with its diamagnetic iron(IV) ground state, extended X-ray absorption fine structure (EXAFS) analysis of 4 indicated a significant contraction of the iron-donor atom bond lengths, relative to those of the crystallographically characterized complexes 2 and 3. Notably, 4 has an Fe(IV/III) reduction potential of ～1.4 V vs Fc(+/o), the highest value yet observed for a monoiron complex. The relatively high stability of 4 (t(1/2) in CD(3)CN solution containing 0.1 M KPF(6) at 25 °C ≈ 15 min), as reflected by its high-yield accumulation via slow bulk electrolysis and amenability to (13)C NMR at -40 °C, highlights the ability of the sterically protecting, highly basic peralkylguanidyl donors of the TMG(3)tren ligand to support highly charged high-valent complexes.     

Preparation of molecularly imprinted polymers for the selective recognition of the bioactive polyphenol, (E)-resveratrol

(E)-Resveratrol imprinted polymers have been rationally designed with the aid of molecular modelling and NMR spectroscopic titration techniques to determine the optimal ratio of the template to functional monomer for polymer formation. Based on this approach, (E)-resveratrol imprinted polymers were prepared via non-covalent self-assembly with the functional monomer 4-vinylpyridine (4VP) in a 1:3 molar ratio. Polymerisation in the presence of a cross-linker resulted in rigid block copolymers that had selective capacities towards (E)-resveratrol (e.g. 14 μmol/g) when compared to the non-imprinted reference polymer. The selectivity of these MIPs was also examined using several structurally related polyphenolic compounds to determine the influence of polyphenolic hydroxyl number and position on binding and molecular recognition.