Radiation chemistry of solid-state carbohydrates using EMR

We review our research of the past decade towards identification of radiation-induced radicals in solid state sugars and sugar phosphates. Detailed models of the radical structures are obtained by combining EPR and ENDOR experiments with DFT calculations of g and proton HF tensors, with agreement in their anisotropy serving as most important criterion. Symmetry-related and Schonland ambiguities, which may hamper such identification, are reviewed. Thermally induced transformations of initial radiation damage into more stable radicals can also be monitored in the EPR (and ENDOR) experiments and in principle provide information on stable radical formation mechanisms. Thermal annealing experi-ments reveal, however, that radical recombination and/or diamagnetic radiation damage is also quite important. Analysis strategies are illustrated with research on sucrose. Results on dipotassium glucose-1-phosphate and trehalose dihydrate, fructose and sorbose are also briefly discussed. Our study demonstrates that radiation damage is strongly regio-selective and that certain general principles govern the stable radical formation

Effects of Terminal Dimethylation and Metal Coordination of Proline-2-formylpyridine Thiosemicarbazone Hybrids on Lipophilicity, Antiproliferative Activity, and hR2 RNR Inhibition

The nickel­(II), copper­(II), and zinc­(II) complexes of the proline-thiosemicarbazone hybrids 3-methyl-(<i>S</i>)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone (l-Pro-FTSC or (<i>S</i>)-H₂L¹) and 3-methyl-(<i>R</i>)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone (d-Pro-FTSC or (<i>R</i>)-H₂L¹), as well as 3-methyl-(<i>S</i>)-pyrrolidine-2-carboxylate-2-formylpyridine 4,4-dimethyl-thiosemicarbazone (dm-l-Pro-FTSC or (<i>S</i>)-H₂L²), namely, [Ni­(l-Pro-FTSC–2H)]₂ (<b>1</b>), [Ni­(d-Pro-FTSC–2H)]₂ (<b>2</b>), [Ni­(dm-l-Pro-FTSC–2H)]₂ (<b>3</b>), [Cu­(dm-l-Pro-FTSC–2H)] (<b>6</b>), [Zn­(l-Pro-FTSC–2H)] (<b>7</b>), and [Zn­(d-Pro-FTSC–2H)] (<b>8</b>), in addition to two previously reported, [Cu­(l-Pro-FTSC–2H)] (<b>4</b>), [Cu­(d-Pro-FTSC–2H)] (<b>5</b>), were synthesized and characterized by elemental analysis, one- and two-dimensional ¹H and ¹³C NMR spectroscopy, circular dichroism, UV–vis, and electrospray ionization mass spectrometry. Compounds <b>1</b>–<b>3</b>, <b>6</b>, and <b>7</b> were also studied by single-crystal X-ray diffraction. Magnetic properties and solid-state high-field electron paramagnetic resonance spectra of <b>2</b> over the range of 50–420 GHz were investigated. The complex formation processes of l-Pro-FTSC with nickel­(II) and zinc­(II) were studied in aqueous solution due to the excellent water solubility of the complexes via pH potentiometry, UV–vis, and ¹H NMR spectroscopy. The results of the antiproliferative activity <i>in vitro</i> showed that dimethylation improves the cytotoxicity and hR2 RNR inhibition. Therefore, introduction of more lipophilic groups into thiosemicarbazone-proline backbone becomes an option for the synthesis of more efficient cytotoxic agents of this family of compounds

Electronic Structural Flexibility of Heterobimetallic Mn/Fe Cofactors: R2lox and R2c Proteins

The electronic structure of the Mn/Fe cofactor identified in a new class of oxidases (R2lox) described by Andersson and Högbom [<i>Proc. Natl. Acad. Sci. U.S.A.</i> <b>2009</b>, 106, 5633] is reported. The R2lox protein is homologous to the small subunit of class Ic ribonucleotide reductase (R2c) but has a completely different in vivo function. Using multifrequency EPR and related pulse techniques, it is shown that the cofactor of R2lox represents an antiferromagnetically coupled Mn^III/Fe^III dimer linked by a μ-hydroxo/bis-μ-carboxylato bridging network. The Mn^III ion is coordinated by a single water ligand. The R2lox cofactor is photoactive, converting into a second form (R2lox_Photo) upon visible illumination at cryogenic temperatures (77 K) that completely decays upon warming. This second, unstable form of the cofactor more closely resembles the Mn^III/Fe^III cofactor seen in R2c. It is shown that the two forms of the R2lox cofactor differ primarily in terms of the local site geometry and electronic state of the Mn^III ion, as best evidenced by a reorientation of its unique ⁵⁵Mn hyperfine axis. Analysis of the metal hyperfine tensors in combination with density functional theory (DFT) calculations suggests that this change is triggered by deprotonation of the μ-hydroxo bridge. These results have important consequences for the mixed-metal R2c cofactor and the divergent chemistry R2lox and R2c perform