Bis(α-hydroxycycloalkyl)phosphine Oxides Obtained from White Phosphorus via Phosphine Oxide H<inf>3</inf>PO: Synthesis, Molecular Structure, Coordination Properties and Biological Activity

Abstract

© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. Reaction of the electrochemically in situ from elemental white phosphorus generated phosphine oxide H3PO in a single electrochemical cell, supplied with lead cathode and aluminium anode, with cyclic ketones (cyclopentanone and cyclohexanone) results in formation of secondary phosphine oxides (bis(α-hydroxycyclopentyl)phosphine oxide 2 a, isolated yield 15 %, and bis(α-hydroxycyclohexyl)phosphine oxide 2 b, isolated yield 12 %) with two α-hydroxycycloalkyl substituents at the phosphorus atom. Bis(α-hydroxycyclopentyl)phosphine oxide reacts with [PdCl2(COD)] (COD=1,5-cyclooctadiene) to give a new palladium complex trans-[PdCl2{P(OH)(cyclo-C5H8-1-OH)2}2] (3 a, isolated yield 11 %) bearing phosphinous acid as a ligand formed via tautomerization of the phosphine oxide. Finally, the cytotoxicity of the synthesized secondary phosphine oxides on tumor and healthy human cell lines was studied. It was found that at a concentration of 10−6–10−4 M, phosphine oxides 2 a,b exhibit similar IC50 values for the M-Hela cell line (ca. 50 mM), but are non-toxic for MCF-7 cells. For human alveolar adenocarcinoma cells (A-549), only 2 a is active (ca. 35 mM), while 2 b is not toxic.