Two-dimensional nuclear magnetic resonance correlation spectroscopy at zero field

Three methods for two-dimensional correlation nuclear magnetic resonance spectroscopy at zero field are discussed. All three involve coherence transfer via longitudinal polarization, double quantum coherence, or both in parallel. The double quantum pulse sequences exploit the spinor property of spin states. These sequences have been applied to connected Δm=1 transitions, as well as for the indirect detection of forbidden or nearly forbidden Δm.1 transitions

Methylene-Only Subspectra in \u3csup\u3e13\u3c/sup\u3eC CPMAS Using a New Double Quantum Filtering Sequence

Methodology for the assignment of 13C CPMAS spectra is still in its infancy. Previous methods of CPMAS spectral editing have utilized differences in the strength of the 13C–1H dipolar interaction or the rate and spin thermodynamics of crosspolarization from protons to carbon, to differentiate between quaternary, tertiary, and methylene carbons. We introduce a different approach, which is based on the fact that double-quantum coherence develops between the protons of a methylene group considerably faster than between most other proton spin pairs in an organic solid. We generate this coherence, filter it, convert it back to single quantum, and then crosspolarize selectively to carbon, followed by a short period of reversed crosspolarization to null out unwanted coherence generated from longer distance spin pairs. The sequence has been named DQCP. While the signal-to-noise of this method is poorer than ordinary CP, it is comparable to previous methods for generating methylene-only spectra, and the technique is straightforward and easy to implement

Estimating Protein-Ligand Binding Affinity using High- Throughput Screening by NMR

Many of today’s drug discovery programs utilize high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or linewidth to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR-based screens that use 1D 1H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA

Estimating Protein-Ligand Binding Affinity using High- Throughput Screening by NMR

Many of today’s drug discovery programs utilize high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or linewidth to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR-based screens that use 1D 1H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA

Slow turning reveals enormous quadrupolar interactions (STREAQI)

We introduce a new solid-state NMR method, which uses very slow sample rotation to visualize NMR spectra whose width exceeds feasible spectrometer bandwidths. It is based on the idea that if we reorient a tensor by a known angle about a known axis, the shifts in the NMR frequencies observed across the spectral width allow us to reconstruct the entire tensor. Called STREAQI (Slow Turning Reveals Enormous Anisotropic Quadrupolar Interactions), this method allows us to probe NMR nuclei that are intractable to current methods. To prove the concept and demonstrate its promise we have implemented the method for several 79Br containing samples with quadrupolar coupling constants in the range of 10–50 MHz

Calculation of \u3csup\u3e13\u3c/sup\u3eC Chemical Shifts in RNA Nucleosides: Structure-\u3csup\u3e13\u3c/sup\u3eC Chemical Shift Relationships

Isotropic 13C chemical shifts of the ribose sugar in model RNA nucleosides are calculated using SCF and DFT-GIAO ab initio methods for different combinations of ribose sugar pucker, exocyclic torsion angle, and glycosidic torsion angle. Idealized conformations were obtained using structures that were fully optimized by ab initio DFT methods starting with averaged parameters from a collection of crystallographic data. Solid-state coordinates of accurate crystal or neutron diffraction structures were also examined directly without optimization. The resulting 13C chemical shifts for the two sets of calculations are then compared. The GIAO-DFT method overestimates the shifts by an average of 5 ppm while the GIAOSCF underestimates the shifts by the same amount. However, in the majority of cases the errors appear to be systematic, as the slope of a plot of calculated vs experimental shifts is very close to unity, with minimal scatter. The values of the 13C NMR shifts of the ribose sugar are therefore sufficiently precise to allow for statistical separation of sugar puckering modes and exocyclic torsion angle conformers, based on the canonical equation model formulated in a previous paper

The \u3csup\u3e14\u3c/sup\u3eN quadrupole coupling in hexamethylene triperoxide diamine (HMTD)

Using high-field NMR, we have determined the magnitude of the nuclear quadrupole interaction in hexamethylene triperoxide diamine (HMTD), the explosive allegedly used in the London bombings of July 2005. The experimental quadrupolar coupling constant, 5.334 MHz, is in good agreement with quantum chemical calculations. The predicted single zero-field transition frequency should lie in a relatively empty part of the 14N nuclear quadrupole resonance (NQR) spectrum; the spin relaxation rate is reasonably fast