摘要
Evidence is presented to indicate that the bisulfite ion (HSO 3−) adds across the C-9 carbonyl group of dinoprostone (prostaglandin E2) and across the Δ10,11-bond of prostaglandin A2. At room temperature, the apparent equilibrium constant, determined by phase solubility analysis, circular dichroism, UV spectroscopy and partitioning, for the formation of the bisulfite adduct of dinoprostone is about 7.5 M−1 at neutral pH. From this result and a free energy relationship reported in the literature for the thermodynamics of nucleophilic addition to carbonyl groups, it is concluded that the chemical reactivity of the C-9 carbonyl group of dinoprostone is not high enough to improve aqueous stability through reversible one-step nucleophilic reactions. However, from a series of kinetic experiments, it is concluded that the equilibrium is extremely favorable for the formation of the bisulfite adduct of prostaglandin A2 over pH 4-8 at room temperature. The second-order rate constant for the attack of sulfite ion (SO32−) to prostaglandin A2 is 1.75 sec−1 M−1.
摘要译文
提供证据表明，亚硫酸氢盐离子（HSO 3）可以跨越Dinoprostone（前列腺素E 2）的C-9羰基并跨越Δsup 10添加，11 / sup前列腺素A 2。在室温下，通过相溶度分析，圆二色性，紫外光谱和分配测定的表观平衡常数，因为在中性pH下二氢石榴石的亚硫酸氢盐加合物的形成约为7.5M sup -1。从该结果和文献中报道的亲核加成到羰基的热力学的自由能关系，得出结论，二硝基石的C-9羰基的化学反应性不足以通过可逆的一步亲核反应改善水的稳定性。然而，从一系列动力学实验可以得出结论，平衡对于在室温下在pH 4-8下形成前列腺素A 2的亚硫酸氢盐加合物非常有利。亚硫酸根离子（SO 3 sup 2 - / sup）对前列腺素A 2的二次速率常数为1.75秒/ sup M sup -1 。
M. J. Cho[*]; W. C. Krueger and T. O. Oesterling;. Nucleophilic addition of bisulfite ion to prostaglandins E2 and A2: Implication in aqueous stability[J]. Journal of Pharmaceutical Sciences, 1977,66(2): 149-154