G.s Harbison | University of Nebraska Lincoln (original) (raw)
Papers by G.s Harbison
![Research paper thumbnail of 15N chemical shift and 15N-13C dipolar tensors for the peptide bond in [1-13C]glycyl[15N]glycine hydrochloride monohydrate](https://attachments.academia-assets.com/43913518/thumbnails/1.jpg)
](Journal of Magnetic Resonance (1969), 1984
Solid state i5N NMR is a technique which is increasingly being applied to the investigation of pr... more Solid state i5N NMR is a technique which is increasingly being applied to the investigation of proteins and other biopolymers. It is of particular importance in systems for which solution NMR spectra cannot be obtained. For example, one recent study of c-['5N]lysyl-bacteriorhodopsin (I) used magic angle sample spinning to detect a single nitrogen-containing residue in a specifically labeled protein of effective molecular weight -70,000, and gave definitive information on both the protonation state and the hydrogen bonding of the bacteriorhodopsin Schiff base. Another virtue of solid state NMR is its ability to provide spatial information which would be averaged out in solution by rotational tumbling of the molecule. For example, Cross et al. (2, 3) have used an "N-labeled bacteriophage which spontaneously orients in the magnetic field to infer orientations of tryptophan and peptide groups with respect to the field axis, and thus relative to the axis of orientation.
Chemical Physics Letters, 1987
Biochemistry, 1984
Page 1. 2662 Biochemistry 1984, 23, 2662-2667 nosine and two cytidine residues is GC:GC is more s... more Page 1. 2662 Biochemistry 1984, 23, 2662-2667 nosine and two cytidine residues is GC:GC is more stable than GG:CC which is more stable than CG:CG. (2) The greater stability of a GC:GC core over a CG:CG core can be outweighed ...
Inorganic Chemistry, 1993
ABSTRACT Nitrogen-15 chemical shift measurements carried out under NO at 1 atm and pH greater-tha... more ABSTRACT Nitrogen-15 chemical shift measurements carried out under NO at 1 atm and pH greater-than-or-equal-to 2.2 yield the value DELTA(deltaN-15) = -30.4 ppm for the total protonation shielding of NO2-(aq). Measurements at higher acidity levels reflect the increasing significance of NO+ and confirm the presence of two N-15 resonances, one sharp and one broadened, in the region around 45% D2SO4. Assignment of the sharp peak to NO+ is confirmed by solid-state NMR of NOBF4. Broadening in the other suggests that exchange between HNO2 and some form of acidium ion (e.g. H2NO2+) precedes NO+ release, but no NOE is detected in 42.4% D2SO4 and it is inferred that no proton-to-nitrogen connnectivity occurs in this species. Nitrogen- 1 5 chemical shifts and chemical shift anisotropies have been obtained in the solid state at natural isotopic abundance for the nitrosonium and nitronium ions in their respective tetrafluoroboride salts.
Solid state nuclear magnetic resonance, 2000
The low order moments for chemical shift and second-order quadrupolar powder patterns have been c... more The low order moments for chemical shift and second-order quadrupolar powder patterns have been calculated as functions of the anisotropy and asymmetry parameter of the governing interaction, and the expressions inverted to give these parameters as a function of the moments. Theoretical simulations and experimental experience show that moment analysis in most cases equals and in some cases exceeds the accuracy of direct inspection as a method of obtaining NMR parameters. We illustrate the efficacy of the method applied to 31P chemical shift spectra of nucleic acids, and 39K second-order patterns of series of potassium salts.
Solid State Communications, 2000
Isotopes in Environmental and Health Studies, 2006
The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP) crystallises in a tric... more The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP) crystallises in a triclinic space group. If the same complex is synthesized from deuterated pentachlorophenol, it crystallizes in an entirely different monoclinic polymorph. Using solid-state NMR of samples synthesized with a full range of deuteration levels, crystallized from solution or the melt, and in the presence or absence of seeds, we have confirmed that the isotopomers indeed have different thermodynamically stable crystal structures. The roots of this phenomenon of isotopomeric polymorphism apparently lie in the differences in hydrogen bonding between the polymorphs. The triclinic form has a relatively short hydrogen bond. High-field solid-state NMR shows both the 1H chemical shift and the 2H electric quadrupole coupling of the hydrogen involved in the bond to be strongly temperature-dependent, indicating a low-lying excited state of the hydrogen bond longitudinal vibration. Inelastic neutron scattering of isotopomers of 4MPPCP has allowed us to identify the three orthogonal vibrational modes of the hydrogen in the hydrogen bond, at 29.7, 145, and 205 meV (240, 1168, and 1651 cm(-1)). The longitudinal mode is the lowest in energy, and it indicates a slightly asymmetric low-barrier double-well potential. Intrinsic to such potentials is a very small difference in zero-point energies (ZPEs) between the protonated and deuterated forms. As a contrast, the monoclinic form has a comparatively normal hydrogen bond, in which the proton and deuteron ZPEs should be different by approximately 500 cm(-1). A scenario can be envisaged where the triclinic protonated form is lower in energy than the monoclinic protonated form, but the triclinic deuterated form is higher in energy than the monoclinic deuterated form. This evidently accounts for the difference in relative stabilities of the two forms upon isotope substitution.
Journal of Combinatorial Chemistry, 2008
Many of today's drug discovery programs utilize high-throughput screening methods that rely on qu... more 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 1 H 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.
Journal of Magnetic Resonance (1969), 1984
Solid state i5N NMR is a technique which is increasingly being applied to the investigation of pr... more Solid state i5N NMR is a technique which is increasingly being applied to the investigation of proteins and other biopolymers. It is of particular importance in systems for which solution NMR spectra cannot be obtained. For example, one recent study of c-['5N]lysyl-bacteriorhodopsin (I) used magic angle sample spinning to detect a single nitrogen-containing residue in a specifically labeled protein of effective molecular weight -70,000, and gave definitive information on both the protonation state and the hydrogen bonding of the bacteriorhodopsin Schiff base. Another virtue of solid state NMR is its ability to provide spatial information which would be averaged out in solution by rotational tumbling of the molecule. For example, Cross et al. (2, 3) have used an "N-labeled bacteriophage which spontaneously orients in the magnetic field to infer orientations of tryptophan and peptide groups with respect to the field axis, and thus relative to the axis of orientation.
Chemical Physics Letters, 1987
Biochemistry, 1984
Page 1. 2662 Biochemistry 1984, 23, 2662-2667 nosine and two cytidine residues is GC:GC is more s... more Page 1. 2662 Biochemistry 1984, 23, 2662-2667 nosine and two cytidine residues is GC:GC is more stable than GG:CC which is more stable than CG:CG. (2) The greater stability of a GC:GC core over a CG:CG core can be outweighed ...
Inorganic Chemistry, 1993
ABSTRACT Nitrogen-15 chemical shift measurements carried out under NO at 1 atm and pH greater-tha... more ABSTRACT Nitrogen-15 chemical shift measurements carried out under NO at 1 atm and pH greater-than-or-equal-to 2.2 yield the value DELTA(deltaN-15) = -30.4 ppm for the total protonation shielding of NO2-(aq). Measurements at higher acidity levels reflect the increasing significance of NO+ and confirm the presence of two N-15 resonances, one sharp and one broadened, in the region around 45% D2SO4. Assignment of the sharp peak to NO+ is confirmed by solid-state NMR of NOBF4. Broadening in the other suggests that exchange between HNO2 and some form of acidium ion (e.g. H2NO2+) precedes NO+ release, but no NOE is detected in 42.4% D2SO4 and it is inferred that no proton-to-nitrogen connnectivity occurs in this species. Nitrogen- 1 5 chemical shifts and chemical shift anisotropies have been obtained in the solid state at natural isotopic abundance for the nitrosonium and nitronium ions in their respective tetrafluoroboride salts.
Solid state nuclear magnetic resonance, 2000
The low order moments for chemical shift and second-order quadrupolar powder patterns have been c... more The low order moments for chemical shift and second-order quadrupolar powder patterns have been calculated as functions of the anisotropy and asymmetry parameter of the governing interaction, and the expressions inverted to give these parameters as a function of the moments. Theoretical simulations and experimental experience show that moment analysis in most cases equals and in some cases exceeds the accuracy of direct inspection as a method of obtaining NMR parameters. We illustrate the efficacy of the method applied to 31P chemical shift spectra of nucleic acids, and 39K second-order patterns of series of potassium salts.
Solid State Communications, 2000
Isotopes in Environmental and Health Studies, 2006
The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP) crystallises in a tric... more The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP) crystallises in a triclinic space group. If the same complex is synthesized from deuterated pentachlorophenol, it crystallizes in an entirely different monoclinic polymorph. Using solid-state NMR of samples synthesized with a full range of deuteration levels, crystallized from solution or the melt, and in the presence or absence of seeds, we have confirmed that the isotopomers indeed have different thermodynamically stable crystal structures. The roots of this phenomenon of isotopomeric polymorphism apparently lie in the differences in hydrogen bonding between the polymorphs. The triclinic form has a relatively short hydrogen bond. High-field solid-state NMR shows both the 1H chemical shift and the 2H electric quadrupole coupling of the hydrogen involved in the bond to be strongly temperature-dependent, indicating a low-lying excited state of the hydrogen bond longitudinal vibration. Inelastic neutron scattering of isotopomers of 4MPPCP has allowed us to identify the three orthogonal vibrational modes of the hydrogen in the hydrogen bond, at 29.7, 145, and 205 meV (240, 1168, and 1651 cm(-1)). The longitudinal mode is the lowest in energy, and it indicates a slightly asymmetric low-barrier double-well potential. Intrinsic to such potentials is a very small difference in zero-point energies (ZPEs) between the protonated and deuterated forms. As a contrast, the monoclinic form has a comparatively normal hydrogen bond, in which the proton and deuteron ZPEs should be different by approximately 500 cm(-1). A scenario can be envisaged where the triclinic protonated form is lower in energy than the monoclinic protonated form, but the triclinic deuterated form is higher in energy than the monoclinic deuterated form. This evidently accounts for the difference in relative stabilities of the two forms upon isotope substitution.
Journal of Combinatorial Chemistry, 2008
Many of today's drug discovery programs utilize high-throughput screening methods that rely on qu... more 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 1 H 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.