Synthesis, Dynamics, and DFT Studies of Rhenium Dicarbonyl PNN Pincer Complexes in Three Different Oxidation States

The synthesis and characterization of Re^I and Re^II dicarbonyl halides <b>1</b> and <b>2</b> and the Re^III dicarbonyl dihalide <b>3</b> supported by a PNN pincer ligand are described. Complex <b>1</b> (<b>1a</b>, X = Br; <b>1b</b>, X = Cl) was synthesized by refluxing the PNN ligand with Re­(CO)₅X (X = Br, Cl) in toluene. One-electron oxidation of <b>1</b> by [(4-BrC₆H₄)₃N]­[SbCl₆] gave <b>2</b>, which when oxidized by PhIO afforded <b>3</b>. X-ray and IR analysis of <b>1</b>–<b>3</b> revealed a systematic increase of <i>Re</i>–<i>C</i>(O) and decrease of <i>C</i><i>O</i> bond lengths and increase in the corresponding CO stretching frequency. All of these results are consistent with weakening in the <i>Re</i>–<i>C</i>(O) bond from <b>1</b> to <b>3</b> upon increasing the oxidation state from +1 in <b>1</b> to +3 in <b>3</b>, with <b>2</b> being in between. The heptacoordinate complex <b>3</b> exhibited temperature-dependent fluxional behavior, caused by the pseudorotation of the rhenium center. This phenomenon was observed by NMR and supported computationally by density functional theory (DFT) calculations

Progress in 13C and 1H solid-state nuclear magnetic resonance for paramagnetic systems under very fast magic angle spinning.

High-resolution solid-state NMR (SSNMR) of paramagnetic systems has been largely unexplored because of various technical difficulties due to large hyperfine shifts, which have limited the success of previous studies through depressed sensitivity/resolution and lack of suitable assignment methods. Our group recently introduced an approach using "very fast" magic angle spinning (VFMAS) for SSNMR of paramagnetic systems, which opened an avenue toward routine analyses of small paramagnetic systems by (13)C and (1)H SSNMR [Y. Ishii et al., J. Am. Chem. Soc. 125, 3438 (2003); N. P. Wickramasinghe et al., ibid. 127, 5796 (2005)]. In this review, we discuss our recent progress in establishing this approach, which offers solutions to a series of problems associated with large hyperfine shifts. First, we demonstrate that MAS at a spinning speed of 20 kHz or higher greatly improves sensitivity and resolution in both (1)H and (13)C SSNMR for paramagnetic systems such as Cu(II)(DL-alanine)(2)H(2)O (Cu(DL-Ala)(2)) and Mn(acac)(3), for which the spectral dispersions due to (1)H hyperfine shifts reach 200 and 700 ppm, respectively. Then, we introduce polarization transfer methods from (1)H spins to (13)C spins with high-power cross polarization and dipolar insensitive nuclei enhanced by polarization transfer (INEPT) in order to attain further sensitivity enhancement and to correlate (1)H and (13)C spins in two-dimensional (2D) SSNMR for the paramagnetic systems. Comparison of (13)C VFMAS SSNMR spectra with (13)C solution NMR spectra revealed superior sensitivity in SSNMR for Cu(DL-Ala)(2), Cu(Gly)(2), and V(acac)(3). We discuss signal assignment methods using one-dimensional (1D) (13)C SSNMR (13)C-(1)H rotational echo double resonance (REDOR) and dipolar INEPT methods and 2D (13)C(1)H correlation SSNMR under VFMAS, which yield reliable assignments of (1)H and (13)C resonances for Cu(Ala-Thr). Based on the excellent sensitivity/resolution and signal assignments attained in the VFMAS approach, we discuss methods of elucidating multiple distance constraints in unlabeled paramagnetic systems by combing simple measurements of (13)C T(1) values and anisotropic hyperfine shifts. Comparison of experimental (13)C hyperfine shifts and ab initio calculated shifts for alpha- and beta-forms of Cu(8-quinolinol)(2) demonstrates that (13)C hyperfine shifts are parameters exceptionally sensitive to small structural difference between the two polymorphs. Finally, we discuss sensitivity enhancement with paramagnetic ion doping in (13)C SSNMR of nonparamagnetic proteins in microcrystals. Fast recycling with exceptionally short recycle delays matched to short (1)H T(1) of approximately 60 ms in the presence of Cu(II) doping accelerated 1D (13)C SSNMR for ubiquitin and lysozyme by a factor of 7.3-8.4 under fast MAS at a spinning speed of 40 kHz. It is likely that the VFMAS approach and use of paramagnetic interactions are applicable to a variety of paramagnetic systems and nonparamagnetic biomolecules

Synthesis and Quantitative Analysis of Plasma-Targeted Metabolites of Catechin and Epicatechin

Grape seed polyphenolic extract (GSPE) rich in the flavan-3-ols (+)-catechin and (−)-epicatechin beneficially modulates Alzheimer’s Disease phenotypes in animal models. The parent molecules in the extract are converted to a series of methylated and glucuronidated derivatives. To fully characterize these metabolites and establish a robust quantitative assay of their levels in biological fluids, we have implemented a partial synthetic approach utilizing chemical methylation followed by enzymatic glucuronidation. Liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to assign unequivocal structures to the compounds. An analytical method using solid-phase extraction and LC-MS/MS in selective reaction monitoring mode (SRM) was validated for their quantitation in plasma. These studies provide a basis for improvements in future work on the bioavailability, metabolism, and mechanism of action of metabolites derived from dietary flavan-3-ols in a range of interventions