Comparison of the protonation of isophosphoramide mustard and phosphoramide mustard.
Comparison of the protonation of isophosphoramide mustard and phosphoramide mustard.
复制标题
异磷酰胺芥子气和磷酰胺芥子气的质子化比较。
DOI：
10.1021/jm00012a017
复制
发表时间：
1995
影响因子：
7.3
通讯作者：
Gamcsik,MP
中科院分区：
文献类型：
--
作者：
Millis,KK;Colvin,ME;Shulman-Roskes,EM;Ludeman,SM;Colvin,OM;Gamcsik,MP
The alkylating agent isophosphoramide mustard (IPM) spontaneously forms a relatively stable aziridine derivative which can be directly observed using NMR spectroscopy. Theprotonations of IPM and itsaziridine were probed using, 31P, 15N, and 170 NMR spectroscopy. The positions of the 31P, 15N, and 170 resonances of IPM between pH 2 and 10 each exhibit a single monobasic titration curve with the same pK& of 4.31±0.02. On the basis of a comparison with other compounds and our earlier work with phosphoramide mustard, the NMR results for IPM indicate that protonation occurs at nitrogen and not oxygen. Over this same pH range, each of the, 31P, and 15N resonances of IPM-aziridine also show a single monobasic titration with a pKa of 5.30±0.09. Themagnitude of the change in chemical shifts suggests that the protonation of the IPM-aziridine occurs at the ring nitrogen. Theoretical gas-phase calculations of PM, IPM, and IPM-aziridine suggest O-protonation to be more likely; however, aqueous phase calculations predict the N-protonated forms to be most stable. Furthermore, for PM and IPM-aziridine, which contain nonequivalent nitrogens, the theoretical calculations and experimental data both agree as to which nitrogen undergoes protonation. These results suggest that the IPM-aziridine remains unprotonated under physiological conditions and may, in part, explain the lower alkylating activity of IPM as compared to PM.
