Bis(α‐hydroxycycloalkyl)phosphine Oxides Obtained from White Phosphorus via Phosphine Oxide H₃PO: Synthesis, Molecular Structure, Coordination Properties and Biological Activity

Abstract

This contribution is dedicated to Prof. Manfred Scheer on the occasion of his 65th birthday.Reaction of the electrochemically in situ from elemental white phosphorus generated phosphine oxide H 3 PO 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 [PdCl 2 (COD)] (COD = 1,5-cyclooctadiene) to give a new palladium complex trans-[PdCl 2 {P(OH)(cyclo-C 5 H 8 -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 À 6 -10 À 4 M, phosphine oxides 2 a,b exhibit similar IC 50 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.[a] Dr.

A Study on the Biological Activity of Optically Pure Aziridine Phosphines and Phosphine Oxides

“…Our comprehensive evaluation of all nine derivatives revealed that the phosphine oxide derivatives (5-8) exhibit enhanced activity against the tested cancer cells in comparison to the aziridine phosphines (1-4) (Table 1). This is consistent with the literature reports indicating that the presence of bulky substituents on the phosphorus atom enhances biological activity [18,22,23]. It was also confirmed that aziridine should have a protected amino group to exhibit cancer cell viability inhibition, indicated by a lack of compound 9 activity, and Carraminana et al observed a similar effect [19].…”

Increasing Anticancer Activity with Phosphine Ligation in Zwitterionic Half-Sandwich Iridium(III), Rhodium(III), and Ruthenium(II) Complexes

“…In the last few years, organometallic anticancer complexes bearing phosphine-containing chelating ligand have become a new approach to adjust the chemical and biological properties. − A typical example is RAPTA family (e.g., RAPTA-C; Scheme , V ) containing 1,3,5-triaza-7-phosphatricyclo[3.3.1.1. ]­decane ligand and Ru–arene complexes, , which has been at an advanced preclinical trial .…”

Synthesis of Pd-NNP Phosphoryl Mononuclear and Phosphinous Acid-Phosphoryl-Bridged Dinuclear Complexes and Ambient Light-Promoted Oxygenation of Benzyl Ligands

“…Thus, taking advantage of these stable structures as pseudo-bidentate ligands, several catalytic reactions have been developed. ,,,,,,,,− In contrast, monodentate PA or phosphoryl ligand-coordinated complexes without the formation of quasi-chelate structures are relatively rare. Bulky SPO preligands tend to afford PA complexes, ,,− although these preligands can also furnish quasi-chelate structures. ,, Bidentate NP­(O)H preligands also form quasi-chelate structures. , Phosphoryl complexes without intramolecular hydrogen bonding were formed as transient intermediates in transition metal-catalyzed reactions using SPOs as substrates. , Structurally defined Au 11 clusters with monodentate phosphoryl ligands were also reported . To utilize the cooperative effects of the PA ligand (or phosphoryl ligand) and the transition metal in catalysis, such as oxygenation shown in Scheme , SPO preligands that do not form strong intramolecular hydrogen bonding are required.…”