title: An innovative method for the non-destructive identification of photodegradation products in solid state: 1H-14N NMR-NQR and DFT/QTAIM study of photodegradation of nifedipine (anti-hypertensive) to nitrosonifedipine (potential anti-oxidative).
abstract: Stability of the antihypertensive drug nifedipine (NIF) has been studied experimentally in solid state by (1)H-(14)N NMR-NQR double resonance (NQDR) and theoretically by the Density Functional Theory (DFT). Photodegradation of NIF to its metabolite in vivo nitrosonifedipine, NO-NIF (antioxidative agent) upon long term daylight exposure was detected and the changes in the molecular structure of NIF were analysed. The photoconversion of NIF to NO-NIF in solid was found to be accompanied with the electron density redistribution at nitrogen sites (NH to N and NO(2) to NO) and proved to be successfully detected with identification of photoproducts by (1)H-(14)N NQDR and DFT methods. The increase in the e(2)qQ/h and η describing EFG tendency towards non-spherical symmetry was significantly greater upon the reduction of NO(2) site than upon hydrogen abstraction from NH site. The level of sensitivity of detection of the photodegradation product was about 1% of the original sample. The Quantum Theory of Atoms in Molecules (QTAIM) analysis has been found useful in predicting photoreactive sites in the molecules and finding the explanation of differences in reactivity between parent NIF and its photoproduct NO-NIF. Using NIF as a model, this study demonstrates the suitability of NQDR supported by DFT for non-destructive determination of the photodegradation products in solid state.
authors.affiliation: Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland. Jolanta.Latosinska@amu.edu.pl
authors.forename: J N
authors.initials: JN
authors.lastname: Latosińska
authors.forename: M
authors.initials: M
authors.lastname: Latosińska
authors.forename: J
authors.initials: J
authors.lastname: Seliger
authors.forename: V
authors.initials: V
authors.lastname: Zagar
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry* / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D006859:Hydrogen / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D009584:Nitrogen / Q000737:chemistry; D009603:Nitroso Compounds / Q000737:chemistry* / Q000378:metabolism; D010782:Photolysis; D011789:Quantum Theory
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D009603:Nitroso Compounds; C539379:nitrosonifedipine; D006859:Hydrogen; D009543:Nifedipine; D009584:Nitrogen