Modeling the Structure of Crystalline Alamethicin and Its NMR Chemical Shift Tensors

Alamethicin (ALM) is an antimicrobial peptide that is frequently employed in studies of the mechanism of action of pore-forming molecules. Advanced techniques of solid-state NMR spectroscopy (SSNMR) are important in these studies, as they are capable of describing the alignment of helical peptides, such as ALM, in lipid bilayers. Here, it is demonstrated how an analysis of the SSNMR measurements can benefit from fully periodic calculations, which employ the plane-wave density-functional theory (PW DFT) of the solid-phase geometry and related spectral parameters of ALM. The PW DFT calculations are used to obtain the structure of desolvated crystalline ALM and predict the NMR chemical shift tensors (CSTs) of its nuclei. A variation in the CSTs of the amidic nitrogens and carbonyl carbons along the ALM backbone is evaluated and included in simulations of the orientation-dependent anisotropic 15N and 13C chemical shift components. In this way, the influence of the site-specific structural effects on the experimentally determined orientation of ALM is shown in models of cell membranes.

Isolation and characterization of a covalent CeIV-Aryl complex with an anomalous 13C chemical shift

The synthesis of bona fide organometallic CeIV complexes is a formidable challenge given the typically oxidizing properties of the CeIV cation and reducing tendencies of carbanions. Herein, we report a pair of compounds comprising a CeIV − Caryl bond [Li(THF)4][CeIV(κ2-ortho-oxa)(MBP)2] (3-THF) and [Li(DME)3][CeIV(κ2-ortho-oxa)(MBP)2] (3-DME), ortho-oxa = dihydro-dimethyl-2-[4-(trifluoromethyl)phenyl]-oxazolide, MBP2– = 2,2′-methylenebis(6-tert-butyl-4-methylphenolate), which exhibit CeIV − Caryl bond lengths of 2.571(7) – 2.5806(19) Å and strongly-deshielded, CeIV − Cipso13C{1H} NMR resonances at 255.6 ppm. Computational analyses reveal the Ce contribution to the CeIV − Caryl bond of 3-THF is ~12%, indicating appreciable metal-ligand covalency. Computations also reproduce the characteristic 13C{1H} resonance, and show a strong influence from spin-orbit coupling (SOC) effects on the chemical shift. The results demonstrate that SOC-driven deshielding is present for CeIV − Cipso13C{1H} resonances and not just for diamagnetic actinide compounds.

Curcinomarcoide, a Novel Limonoid From Trichilia hirta (Meliaceae)—Complete 1H and 13C Chemical Shift Assignments

A novel limonoid named curcinomarcoide (1) was isolated from Trichilia hirta and characterized on the basis of its nuclear magnetic resonance and mass spectrometry spectral data and comparison with literature data.

Determining isoleucine side-chain rotamer-sampling in proteins from 13C chemical shift

A framework is presented to derive the conformational sampling of isoleucine side chains from nuclear magnetic resonance 13C chemical shifts.

NMR Crystallography of the Polymorphs of Metergoline

Two polymorphs of the drug compound metergoline (C25H29N3O2) were investigated in detail by solid-state NMR measurements. The results have been analysed by an advanced procedure, which uses experimental input together with the results of quantum chemical calculations that were performed for molecular crystals. In this way, it was possible to assign the total of 40 1H–13C correlation pairs in a highly complex system, namely, in the dynamically disordered polymorph with two independent molecules in the unit cell of a large volume of 4234 Å3. For the simpler polymorph, which exhibits only small-amplitude motions and has just one molecule in the unit cell with a volume of 529.0 Å3, the values of the principal elements of the 13C chemical shift tensors were measured. Additionally, for this polymorph, a set of crystal structure predictions were generated, and the {13C, 1H} isotropic and 13C anisotropic chemical shielding data were computed while using the gauge-including projector augmented-wave approach combined with the “revised Perdew-Burke-Ernzerhof“ exchange-correlation functional (GIPAW-RPBE). The experimental and theoretical results were combined in an application of the newly developed strategy to polymorph discrimination. This research thus opens up new routes towards more accurate characterization of the polymorphism of drug formulations.