Joanna Skalik

High Cytotoxic Activity of Phosphonium Salts and Their Complementary Selectivity towards HeLa and K562 Cancer Cells: Identification of Tri-n-butyl-n-hexadecylphosphonium bromide as a Highly Potent Anti-HeLa Phosphonium Salt.

Quaternary ammonium and phosphonium salts have been screened for their toxic effect on HeLa and K562 cancer cell lines, as well as on normal HUVEC cells. Tri-n-butyl-n-hexadecylphosphonium bromide, the first phosphonium salt with a halogen anion tested against HeLa cells, was 12 times more potent (IC50 <5 μm after 24 and 48 h) than the clinically used reference compound cisplatin and 17 times more potent than tri-n-hexyltetradecylphosphonium bis(trifluoromethylsulfonyl)imide, which, to the best of our knowledge, is the first phosphonium salt to be evaluated in HeLa cells. However, it was inactive against K562 cells (24 and 48 h). According to a caspase-3/7 assay, its toxicity has not been connected with the induction of apoptosis. In contrast, triphenylalkylphosphonium iodides with shorter C1–5 alkyl chains were inactive against HeLa cells but very active against K562 cells (IC50=6–10 μm after 48 h). Phosphonium cations with halide counterions proved to be more potent than those with (CF3SO2)2N− as the anion, as in the anticancer agent NSC 747251, or other anions in molecules with similar alkyl chain lengths. On the other hand, a series of ammonium salts containing a short methylthiomethyl or methoxymethyl side chain revealed low cytotoxicity (IC50 >500 μm after 24 and 48 h) against both HeLa and K562 cancer cell lines as well as normal HUVEC cells, showing that the nontoxic N+CH2YMe (Y=S, O) structural motif in ammonium salts could be suitable for further optimization and development, especially in transfection experiments.

Recent studies of the synthesis, functionalization, optoelectronic properties and applications of dibenzophospholes

The first dibenzophospholes were described in the 1950s, but only recently have they gained greater importance, due to their use in organic electronics and the possibility of designing new π-conjugated, optoelectronic materials that incorporate these heterocycles. Our comprehensive review covering a period of 15 years (2001–2016), includes methods of synthesis of these compounds, methods for their functionalization, a description of their optoelectronic properties and their first use in optoelectronic devices. The review represents the current state of knowledge in this field and shows the great potential of simple and functionalized dibenzophospholes. The work described in this review suggests that dibenzophospholes should also be investigated more intensively as single materials, as well as in structural combinations with other π-extended conjugated aromatic and heteroaromatic systems containing phosphorus, nitrogen, silicon or sulfur atoms.

Use of isomeric, aromatic dialdehydes in the synthesis of photoactive, positional isomers of higher analogs of o-bromo(hetero)acenaldehydes

Synthesis of the pairs of positional isomers of the title compounds is based on utilization of two isomeric o,o-dibromo dialdehydes and a selective ortho-metallation/Friedel–Crafts cyclization sequence of the corresponding diacetals. Photophysical and electrochemical properties of the new group of fluorescent and photoresistant compounds have also been performed.

Quinquevalent phosphorus acids

This chapter shows the most important achievements in the area compounds containing three P–O bonds (phosphates), two P–O and one P–C bonds (phosphonates) as well as one P–O and two P–C bonds (phosphinates) in addition to the phosphoryl group P=O. Each of the main sections has been divided in the same way, covering synthesis, reactions and biological aspects. In all three sections, there has been good coverage of the traditional subjects like new reagents, new methods of synthesis, total syntheses, stereocontrolled syntheses proceeding with good diastereoselectivities and enantioselectivities. Practical aspects of phosphorus chemistry has been realized by analysis of biological and medicinal applications of active compounds.In this year, a subsection concerning use of chiral phosphoric acids as catalysts in various chemical reactions, introduced in 2009 for the first time, has been maintained and expanded with new categories due to further, rapid progress in this area. In the subsection: reactions of phosphoric acids and their derivatives, total syntheses of valuable, biologically active compounds have been presented in the literature of the review period too.

Ammonium haloacetates – An alternative to glyphosate?

This study shows the design, synthesis and evaluation of eco(phyto)toxic and herbicidal activities of quaternary ammonium salts (QASs), derived from haloacetic acids, in context of the search for safer alternatives to the commonly used herbicide, N-(phosphonomethyl)glycine (glyphosate). The structure of the investigated QASs refers to the heteroatom sequence in the anion of glyphosate in which the (P-C)-N nitrogen atom was replaced by one or more halogens (F, Cl). The ecotoxicity of the synthesized QASs was tested against luminescent marine bacteria Vibrio fischeri (Microtox® test) and the crustaceans Heterocypris incongruens (Ostracodtoxkit F™). The phytotoxic effect of QASs was also studied with respect to spring barley (Hordeum vulgare) and common radish (Raphanus sativus L. radicula Pers.), whereas herbicidal activity was investigated in relation to popular weeds species gallant soldier (Galinsoga parviflora Cav.) and common sorrel (Rumex acetosa L.). The results showed that toxicity of the synthesized QASs depends on a number of halo-substituents, especially for bioluminescent bacteria Vibrio fischeri for which EC50 values were those varying the most. Phytotoxicity tests proved that the investigated QASs had a similar high, toxic effect both on monocotyledonous and dicotyledonous plants with exception of DIPA - DCA. Moreover, their herbicidal activity against common sorrel was comparable to glyphosate.

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

We present a successful deoxygenation reaction of ortho-1,3-dithianylaryl(aryl)methanols which enables a selective removal of the secondary hydroxy group in presence of the 1,3-dithianyl moiety under reductive conditions. This reaction proceeds well with ZnI2/Na(CN)BH3 in dichloroethane or benzene for both unsubstituted and substituted aryls (by electron-rich groups). This is leading to formyl-protected diarylmethanes with potential application in the synthesis of new pharmaceuticals and optoelectronic materials. This synthetic approach gives an access to a wide variety of functionalized ortho-1,3-dithianylaryl(aryl)methanes in 26–95% yields and is recommended for the substrates containing sulfur atoms, for which transition metal-induced reactions fail.

Synthesis of Polycyclic (Hetero)Aromatic Hydrocarbons via the Friedel–Crafts/Bradsher Cyclization

This review covers the literature on synthesis of polycyclic aromatic hydrocarbons via the Friedel–Crafts/Bradsher cyclization, published in the period of 1987–2016. Syntheses of partly and fully fused (hetero)aromatic systems with 5- or 6-membered rings formed upon the cyclization and containing C, O, S, N ring (hetero)atoms are reported in this work. All described aromatic systems have been formed in reactions using aromatic aldehydes and their derivatives as carbonyl reagents.

Chapter 7:Quinquevalent phosphorus acids

This chapter shows some of the most important achievements in the area of organophosphorus compounds containing three P–O bonds (phosphates), two P–O and one P–C bonds (phosphonates) as well as one P–O and two P–C bonds (phosphinates), in addition to the phosphoryl group P=O. Each of the main sections has been divided in the same way, covering synthesis, reactions and biological aspects. The chiral phosphoric acids have been applied successfully, mainly as catalysts, to afford high chemical yields and excellent stereoselectivities in various organic reactions.