Protonation of phosphoramide mustard and other phosphoramides
| Autor: | Colvin Om, I J McLennan, Susan M. Ludeman, Michael E. Colvin, Michael P. Gamcsik, Ellen M. Shulman-Roskes |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Magnetic Resonance Spectroscopy
Titration curve Chemical Phenomena Stereochemistry Protonation Antineoplastic Agents Medicinal chemistry chemistry.chemical_compound Drug Stability Drug Discovery Reactivity (chemistry) Phosphoric Acids Bifunctional Molecular Structure Chemistry Chemistry Physical Monobasic acid Phosphoramides Nuclear magnetic resonance spectroscopy Hydrogen-Ion Concentration Phosphoramide Mustard Amides Molecular Medicine Thermodynamics Phosphoramide Mustards Gases Protons |
| Zdroj: | Journal of medicinal chemistry. 36(23) |
| ISSN: | 0022-2623 |
| Popis: | The chemistry of the bifunctional alkylating agent phosphoramide mustard and model phos phoramides was probed by multinuclear NMR spectroscopy as a function of pH. Between pH 1 and 11, both the 31 P and 15 N resonances for phosphoramide mustard displayed a single monobasic titration curve with a pK a of 4.9. The protonation below pH 4.9 correlates with the loss in reactivity of the mustard. The 17 O NMR spectrum of 17 O-enriched phosphoramide mustard shows little change with pH. The data on the mustard was compared to 15 N and 31 P NMR data on 15 N-enriched phosphoramidic acid, phosphorodiamidic acid, and phosphoric triamide. Contrary to the conclusions of previous studies, our combined 31 P, 15 N, and 17 O NMR results are more consistent with N-protonation of phosphoramide mustard rather than an O-protonation. Theoretical calculations on the phosphoramidic acid, phosphorodiamidic acid, and phosphoric triamide show O-protonation to be more stable in the gas phase. For the latter two compounds, the calculations suggest that N-protonation may be the most stable protonated form in the aqueous phase. These findings influence our understanding of the structure-activity relationships of phosphoramide mustards |
| Databáze: | OpenAIRE |
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