title: A revisited structure for nitrosoprodenafil from NMR, mass spectrometry, X-ray and hydrolysis data.
abstract: The sildenafil analogue adulterant previously identified as a nitroso derivative (nitrosoprodenafil) in a dietary supplement (DS) marketed to increase sexual performance and sold in Europe in the early 2010s is the same as that found in the same type of DS available in Japan whose structure was established as a nitro derivative (mutaprodenafil or nitroprodenafil). Indeed, the compound isolated from the Man Power DS has identical UV, IR, NMR and MS spectroscopic characteristics and hydrolysis behavior than nitrosoprode-nafil. By revisiting its NMR assignments and MS and MS/MS data interpretation, it is demonstrated that the compound is actually a nitrothioimidazole-methisosildenafil hybrid, i.e. nitroprodenafil, whose structure is unequivocally confirmed by X-ray crystallography and synthesis experiments. Because the product is converted to methisosildenafil by hydrolysis, it is named nitropromethisosildenafil.
authors.affiliation: Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, Université de Toulouse, 118 route de Narbonne, 31062 Toulouse cedex, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Martino
authors.affiliation: Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, Université de Toulouse, 118 route de Narbonne, 31062 Toulouse cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Menendez
authors.affiliation: Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, Université de Toulouse, 118 route de Narbonne, 31062 Toulouse cedex, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Balayssac
authors.affiliation: Service Commun de Spectrométrie de Masse, ICT, Université Paul Sabatier, Université de Toulouse, 31062 Toulouse cedex, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Martins-Froment
authors.affiliation: Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, Université de Toulouse, 118 route de Narbonne, 31062 Toulouse cedex, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Lherbet
authors.affiliation: Equipe MAPES, Laboratoire IMRCP (UMR CNRS 5623), Université Paul Sabatier, Université de Toulouse, 118 route de Narbonne, 31062 Toulouse cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Couderc
authors.affiliation: Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, Université de Toulouse, 118 route de Narbonne, 31062 Toulouse cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gilard
authors.affiliation: Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, Université de Toulouse, 118 route de Narbonne, 31062 Toulouse cedex, France. Electronic address: martino@chimie.ups-tlse.fr.
authors.forename: Myriam
authors.initials: M
authors.lastname: Malet-Martino
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods; D019587:Dietary Supplements / Q000032:analysis*; D004340:Drug Contamination; D006801:Humans; D006868:Hydrolysis; D007093:Imidazoles / Q000032:analysis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D058986:Phosphodiesterase 5 Inhibitors / Q000032:analysis* / Q000737:chemistry; D010879:Piperazines / Q000032:analysis / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; C520362:methisosildenafil; C573109:mutaprodenafil
keywords: Mass spectrometry; NMR; Nitropromethisosildenafil; Nitrosoprodenafil; X-ray crystallography