Monday, August 27, 2007

Hiyam's Journal Update

J. Am. Chem. Soc.,

Characterization of Polymorphs and Solid-State Reactions for Paramagnetic Systems by 13C Solid-State NMR and ab Initio Calculations
Medhat A. Shaibat, Leah B. Casabianca, Nalinda P. Wickramasinghe, Stephen Guggenheim, Angel C. de Dios, and Yoshitaka Ishii*

Despite its importance in drug and material science, spectroscopic characterization of polymorphs or supramolecular structures of paramagnetic systems often poses challenges, particularly for noncrystalline solids. This work demonstrates that 13C solid-state NMR (SSNMR) of paramagnetic systems under very fast magic angle spinning (VFMAS) (spinning speed of 20 kHz or higher) provides exceptionally sensitive means to probe small structural difference among polymorphs of paramagnetic complexes in noncrystalline solids, including drugs and materials containing paramagnetic metal ions. 13C VFMAS SSNMR experiments and corresponding ab initio shift calculations for Cu(II)(8-quilinolinol)2, anticancer agents, show that - and -forms of this compound can be easily distinguished by notable difference in paramagnetic relaxation times and hyperfine shifts. It is also shown that applications of the present technique allow for quantitative and chemical characterization of solid-state reactions for Cu(8-quilinolinol)2 and Cu(imidazole)2 in a noninvasive manner.

J. Am. Chem. Soc.

Residual Dipolar Couplings by Off-Magic-Angle Spinning in Solid-State Nuclear Magnetic Resonance Spectroscopy

Giuseppe Pileio, Ying Guo, Tran N. Pham, John M. Griffin, Malcolm H. Levitt,* and Steven P. Brown*

A solid-state NMR analogue of the solution-state residual dipolar coupling effect is demonstrated. A small misset of the spinning axis by less than 0.5 changes the modulation frequency of spin-echoes, allowing the estimation of internuclear dipole-dipole couplings and hence internuclear distances.

J. Am. Chem. Soc.,

Phosphate-Mediated Arginine Insertion into Lipid Membranes and Pore Formation by a Cationic Membrane Peptide from Solid-State NMR
Ming Tang, Alan J. Waring, and Mei Hong*

The insertion of charged amino acid residues into the hydrophobic part of lipid bilayers is energetically unfavorable yet found in many cationic membrane peptides and protein domains. To understand the mechanism of this translocation, we measured the 13C-31P distances for an Arg-rich -hairpin antimicrobial peptide, PG-1, in the lipid membrane using solid-state NMR. Four residues, including two Arg's, scattered through the peptide were chosen for the distance measurements. Surprisingly, all residues show short distances to the lipid 31P: 4.0-6.5 Å in anionic POPE/POPG membranes and 6.5-8.0 Å in zwitterionic POPC membranes. The shortest distance of 4.0 Å, found for a guanidinium C at the -turn, suggests N-H···O-P hydrogen bond formation. Torsion angle measurements of the two Arg's quantitatively confirm that the peptide adopts a -hairpin conformation in the lipid bilayer, and gel-phase 1H spin diffusion from water to the peptide indicates that PG-1 remains transmembrane in the gel phase of the membrane. For this transmembrane -hairpin peptide to have short 13C-31P distances for multiple residues in the molecule, some phosphate groups must be embedded in the hydrophobic part of the membrane, with the local 31P plane parallel to the -strand. This provides direct evidence for toroidal pores, where some lipid molecules change their orientation to merge the two monolayers. We propose that the driving force for this toroidal pore formation is guanidinium-phosphate complexation, where the cationic Arg residues drag the anionic phosphate groups along as they insert into the hydrophobic part of the membrane. This phosphate-mediated translocation of guanidinium ions may underlie the activity of other Arg-rich antimocrobial peptides and may be common among cationic membrane proteins.

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