Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections.
We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the nitrogen collision cross-section (Ω(N(2))) range of 124.5-254.3 Å(2) and the helium collision cross-section (Ω(He)) range of 63.0-178.8 Å(2). Ab...
| Autors principals: | , , , , , |
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| Format: | Journal article |
| Idioma: | English |
| Publicat: |
2012
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| _version_ | 1826305781371240448 |
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| author | Campuzano, I Bush, M Robinson, C Beaumont, C Richardson, K Kim, H Kim, H |
| author_facet | Campuzano, I Bush, M Robinson, C Beaumont, C Richardson, K Kim, H Kim, H |
| author_sort | Campuzano, I |
| collection | OXFORD |
| description | We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the nitrogen collision cross-section (Ω(N(2))) range of 124.5-254.3 Å(2) and the helium collision cross-section (Ω(He)) range of 63.0-178.8 Å(2). Absolute Ω(N(2)) and Ω(He) values for the drug-like calibrants and two diastereomers were measured using a drift-tube instrument with radio frequency (RF) ion confinement. T-wave drift-times for the protonated diastereomers betamethasone and dexamethasone are reproducibly different. Calibration of these drift-times yields T-wave Ω(N(2)) values of 189.4 and 190.4 Å(2), respectively. These results demonstrate the ability of T-wave IM spectrometry to differentiate diastereomers differing in Ω(N(2)) value by only 1 Å(2), even though the resolution of these IM experiments were ∼40 (Ω/ΔΩ). Demonstrated through density functional theory optimized geometries and ionic electrostatic surface potential analysis, the small but measurable mobility difference between the two diastereomers is mainly due to short-range van der Waals interactions with the neutral buffer gas and not long-range charge-induced dipole interactions. The experimental RF-confining drift-tube and T-wave Ω(N(2)) values were also evaluated using a nitrogen based trajectory method, optimized for T-wave operating temperature and pressures, incorporating additional scaling factors to the Lennard-Jones potentials. Experimental Ω(He) values were also compared to the original and optimized helium based trajectory methods. |
| first_indexed | 2024-03-07T06:38:03Z |
| format | Journal article |
| id | oxford-uuid:f856822e-ff6f-4e57-b0df-ebbd3fd9c1aa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:38:03Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:f856822e-ff6f-4e57-b0df-ebbd3fd9c1aa2022-03-27T12:49:25ZStructural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f856822e-ff6f-4e57-b0df-ebbd3fd9c1aaEnglishSymplectic Elements at Oxford2012Campuzano, IBush, MRobinson, CBeaumont, CRichardson, KKim, HKim, HWe present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the nitrogen collision cross-section (Ω(N(2))) range of 124.5-254.3 Å(2) and the helium collision cross-section (Ω(He)) range of 63.0-178.8 Å(2). Absolute Ω(N(2)) and Ω(He) values for the drug-like calibrants and two diastereomers were measured using a drift-tube instrument with radio frequency (RF) ion confinement. T-wave drift-times for the protonated diastereomers betamethasone and dexamethasone are reproducibly different. Calibration of these drift-times yields T-wave Ω(N(2)) values of 189.4 and 190.4 Å(2), respectively. These results demonstrate the ability of T-wave IM spectrometry to differentiate diastereomers differing in Ω(N(2)) value by only 1 Å(2), even though the resolution of these IM experiments were ∼40 (Ω/ΔΩ). Demonstrated through density functional theory optimized geometries and ionic electrostatic surface potential analysis, the small but measurable mobility difference between the two diastereomers is mainly due to short-range van der Waals interactions with the neutral buffer gas and not long-range charge-induced dipole interactions. The experimental RF-confining drift-tube and T-wave Ω(N(2)) values were also evaluated using a nitrogen based trajectory method, optimized for T-wave operating temperature and pressures, incorporating additional scaling factors to the Lennard-Jones potentials. Experimental Ω(He) values were also compared to the original and optimized helium based trajectory methods. |
| spellingShingle | Campuzano, I Bush, M Robinson, C Beaumont, C Richardson, K Kim, H Kim, H Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. |
| title | Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. |
| title_full | Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. |
| title_fullStr | Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. |
| title_full_unstemmed | Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. |
| title_short | Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. |
| title_sort | structural characterization of drug like compounds by ion mobility mass spectrometry comparison of theoretical and experimentally derived nitrogen collision cross sections |
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