Berners-Price S J, Norman R E, Sadler P J
Department of Chemistry, Birkbeck College, University of London, United Kingdom.
J Inorg Biochem. 1987 Nov;31(3):197-209. doi: 10.1016/0162-0134(87)80005-3.
The pKas and autoxidation properties of a number of diphosphines which exhibit varying degrees of antitumor and cytotoxic activity were investigated. Titration by HClO4 in CH3NO2 was used to determine pKas of the following diphosphines: R2P(CH2)nPR'2, where for R = R' = Ph, n = 1, 2, and 3 (dppm, dppe, and dppp respectively); for R = R' = Et, n = 2 (depe); for R = Ph, R' = Et, n = 2 (eppe); and for cis and trans Ph2PCH = CHPPh2 (dppey). The difference between the first and second protonation constants decreases as the length of the carbon chain between the two phosphorus centers increases. Unsaturation in the carbon chain lowers pKas. -PEt2 centers are apparently more basic than -PPh2 centers. Apart from electrostatic effects, the protonation of a given phosphine center appears to be independent of the substituents at the second phosphine center. The autoxidation reactions of dppm, dppe, dppp, depe, and cis-dppey were studied in a variety of solvents by 31P NMR spectroscopy. The ethyl-substituted diphosphines were much more rapidly oxidized than the phenyl-substituted, and the pathways of autoxidation differed. Generally, the phenyl-substituted diphosphines gave only mono- and dioxides, while the ethyl-substituted diphosphines additionally gave phosphinites and other oxidation products. The relevance of the autoxidation reactivity and the pKas to the contrasting antitumor activity of these diphosphines is discussed.
对一些具有不同程度抗肿瘤和细胞毒性活性的二膦化合物的pKa值和自氧化性质进行了研究。采用在CH3NO2中用HClO4滴定的方法来测定下列二膦化合物的pKa值：R2P(CH2)nPR'2，其中R = R' = Ph，n = 1、2和3（分别为dppm、dppe和dppp）；R = R' = Et，n = 2（depe）；R = Ph，R' = Et，n = 2（eppe）；以及顺式和反式Ph2PCH = CHPPh2（dppey）。随着两个磷中心之间碳链长度的增加，第一和第二质子化常数之间的差异减小。碳链中的不饱和键会降低pKa值。-PEt2中心显然比-PPh2中心碱性更强。除了静电效应外，给定膦中心的质子化似乎与第二个膦中心的取代基无关。通过31P NMR光谱研究了dppm、dppe、dppp、depe和顺式dppey在多种溶剂中的自氧化反应。乙基取代的二膦化合物比苯基取代的氧化得快得多，且自氧化途径不同。一般来说，苯基取代的二膦化合物只生成单氧化物和二氧化物，而乙基取代的二膦化合物还会生成亚膦酸酯和其他氧化产物。讨论了自氧化反应活性和pKa值与这些二膦化合物截然不同的抗肿瘤活性之间的相关性。
