title: Aliphatic β-nitroalcohols for therapeutic corneoscleral cross-linking: chemical stability studies using 1H-NMR spectroscopy.
abstract: Recent studies suggest that aliphatic β-nitro alcohols may represent a useful class of compounds for use as in vivo therapeutic corneoscleral cross-linking agents with higher order nitroalcohols (HONAs) showing enhanced efficacy over the mono-nitroalcohols. The current study was undertaken in order to evaluate the chemical stability of these compounds during storage conditions. Two mono-nitroalcohols (2-nitroethanol=2ne and 2-nitro-1-propanol = 2 nprop) and two HONAs, a nitrodiol (2-methyl-2-nitro-1,3-propanediol = MNPD), and a nitrotriol (2-hydroxymethyl-2-nitro-1,3-propanediol = HNPD) were monitored for chemical stability by (1)H-NMR for up to 7 months. Each compound was studied at two concentrations (1% and 10%) either in unbuffered H2O or 0.2 m NaH2 PO4/Na2 HPO4 (pH = 5), and at 0 °C and room temperature (RT) for a total of eight conditions for each compound. The (1)H-NMR spectra for the starting material were compared to subsequent spectra. Under all four of the conditions studied, both the nitrodiol (MNPD) and nitrotriol (HNPD) were stable for the duration of 7 months. 2nprop became unstable under all conditions at 3 months. 2ne was the most unstable of all the compounds tested. HONAs exhibit excellent chemical stability under long-term storage conditions. In contrast, the nitromonols tested are significantly less stable. These findings are relevant to the translation of this technology into clinical use.
authors.affiliation: Department of Chemistry, Columbia University, New York, NY.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Li
authors.forename: Mijung
authors.initials: M
authors.lastname: Kim
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Trokel
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Turro
authors.forename: David C
authors.initials: DC
authors.lastname: Paik
mesh_terms: D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003315:Cornea / Q000187:drug effects*; D006801:Humans; D007640:Keratoconus / Q000628:therapy; D009574:Nitro Compounds / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D012590:Sclera / Q000187:drug effects*
chemical_list: D000438:Alcohols; D009574:Nitro Compounds