The PAW/GIPAW approach for computing NMR parameters: a new dimension added to NMR study of solids.

Proteins exhibit structural fluctuations over decades of time scales. From the picosecond side chain motions to aggregates that form over the course of minutes, characterizing protein structure over these vast lengths of time is important to understanding their function. In the past 15 years, two-dimensional infrared spectroscopy (2D IR) has been established as a versatile tool that can uniquely probe proteins structures on many time scales. In this review, we present some of the basic principles behind 2D IR and show how they have, and can, impact the field of protein biophysics. We highlight experiments in which 2D IR spectroscopy has provided structural and dynamical data that would be difficult to obtain with more standard structural biology techniques. We also highlight technological developments in 2D IR that continue to expand the scope of scientific problems that can be accessed in the biomedical sciences.

Watching Proteins Wiggle: Mapping Structures with Two-Dimensional Infrared Spectroscopy

Potassium channels are responsible for the selective permeation of K+ ions across cell membranes. K+ ions permeate in single file through the selectivity filter, a narrow pore lined by backbone carbonyls that compose four K+ binding sites. Here, we report on the two-dimensional infrared (2D IR) spectra of a semisynthetic KcsA channel with site-specific heavy (13C18O) isotope labels in the selectivity filter. The ultrafast time resolution of 2D IR spectroscopy provides an instantaneous snapshot of the multi-ion configurations and structural distributions that occur spontaneously in the filter. Two elongated features are resolved, revealing the statistical weighting of two structural conformations. The spectra are reproduced by molecular dynamics simulations of structures with water separating two K+ ions in the binding sites, ruling out configurations with ions occupying adjacent sites.

https://science.sciencemag.org/content/sci/353/6303/1040.full.pdf

Instantaneous ion configurations in the K+ ion channel selectivity filter revealed by 2D IR spectroscopy.

Residue-Specific Structural Kinetics of Proteins through the Union of Isotope Labeling, Mid-IR Pulse Shaping, and Coherent 2D IR Spectroscopy

Hydrogels prepared from self-assembling peptides are promising materials for medical applications, and using both l- and d-peptide isomers in a gel’s formulation provides an intuitive way to control the proteolytic degradation of an implanted material. In the course of developing gels for delivery applications, we discovered that a racemic mixture of the mirror-image β-hairpin peptides, named MAX1 and DMAX1, provides a fibrillar hydrogel that is four times more rigid than gels formed by either peptide alone—a puzzling observation. Herein, we use transmission electron microscopy, small angle neutron scattering, solid state NMR, diffusing wave, infrared, and fluorescence spectroscopies, and modeling to determine the molecular basis for the increased mechanical rigidity of the racemic gel. We find that enantiomeric peptides coassemble in an alternating fashion along the fibril long axis, forming an extended heterochiral pleat-like β-sheet, a structure predicted by Pauling and Corey in 1953. Hydrogen bonding ...

Molecular, Local, and Network-Level Basis for the Enhanced Stiffness of Hydrogel Networks Formed from Coassembled Racemic Peptides: Predictions from Pauling and Corey.

Multiple-Turnover Isotopic Labeling of Fmoc- and Boc-Protected Amino Acids with Oxygen Isotopes

The reactions of 5-benzylidene-3-phenylrhodanine (2; rhodanine = 2-thioxo-1,3-thiazolidin-4-one) with diazomethane (7a) and phenyldiazomethane (7b) occurred chemoselectively at the exocyclic C=C
bond to give the spirocyclopropane derivatives 9 and, in the case of 7a, also the C-methylated products 8 (Scheme 1). In contrast, diphenyldiazomethane (7c) reacted exclusively with the C=S group leading to the 2-(diphenylmethylidene)-1,3-thiazolidine 11 via [2+3] cycloaddition and a two-fold extrusion reaction. Treatment of 8 or 9b with an excess of 7a in refluxing CH2Cl2 and in THF at room temperature in the presence of [Rh2(OAc)4], respectively, led to the 1,3-thiazolidine-2,4-diones 15 and 20,
respectively, i.e., the products of the hydrolysis of the intermediate thiocarbonyl ylide. On the other hand, the reactions with 7b and 7c in boiling toluene yielded the corresponding 2-methylidene derivatives 16, 21a, and 21b. Finally, the reaction of 11 with 7a occurred exclusively at the electron-poor C=C bond, which is conjugated with the C=O group. In addition to the spirocyclopropane 23, the C-methylated 22 was formed as a minor product. The structures of the products (Z)-8, 9a, 9b, 11, and 23 were established
by X-ray crystallography.

Chemoselectivity of the Reactions of Diazomethanes with 5-Benzylidene-3-phenylrhodanine

Reactions of three different thiocarbonyl S-methylides, generated from thiobenzophenone (2), 2,2,4,4-tetramethyl-3-thioxocyclobutanone (3), and adamantanethione (8), respectively, and diazomethane, with 5-benzylidene-3-phenylrhodanine (12) were carried out. The aromatic thiocarbonyl ylide 1a adds chemoselectively to the C,C-double bond, but the spirocyclic 1,3-dithiolane 18, i.e. the [2+3]-cycloadduct with the C=S group of 12,was also formed as a minor product. In the cases of the aliphatic thiocarbonyl ylides 6 and 20, the [2+3]-cycloaddition occurred at the exocyclic C,C-double bond exclusively to give the spirocyclic tetrahydrothiophene derivatives 23 and 21, respectively. A smooth acid-catalyzed decomposition of 18 yielded the 2-diphenylmethylidene derivative 19. The formation of product 24, which was obtained in the reaction of the sterically congested ylide 6 with 12, is explained by a 1,4-H-shift in an intermediate zwitterionic adduct. The structures of the tetrahydrothiophenes 17, 21 and 23, as well as that of 24, were established by X-ray crystallography.

https://www.zora.uzh.ch/id/eprint/54086/1/pj-2006-08-1363_16sey_Kopie.pdf

Chemoselectivity of the [2+3]-Cycloaddition of Thiocarbonyl Ylides with 5-Benzylidene-3-phenylrhodanine

Metal-free hemiporphyrazine (HpH2) is a notoriously insoluble material possessing interesting photophysical properties. Here we report the synthesis, structure, and photophysical properties of an o...

/pdf/excitonic-luminescence-of-hemiporphyrazines-306ftjj76b.pdf

Martin S. Seyfried

Papers

Multiple-Turnover Isotopic Labeling of Fmoc- and Boc-Protected Amino Acids with Oxygen Isotopes

Chemoselectivity of the Reactions of Diazomethanes with 5-Benzylidene-3-phenylrhodanine

Chemoselectivity of the [2+3]-Cycloaddition of Thiocarbonyl Ylides with 5-Benzylidene-3-phenylrhodanine

Excitonic luminescence of hemiporphyrazines.

Molecular design and synthesis of a planar telomestatin analogue