Nitrodiphenyl Ether Research Articles

Degradation of diphenyl ether herbicides by the lignin-degrading basidiomycete Coriolus versicolor.

Under ligninolytic conditions, the white-rot basidiomycete Coriolus versicolor metabolized chloronitrofen (2, 4, 6-trichloro-4'-nitrodiphenyl ether; CNP) and nitrofen (2, 4-dichloro-4'-nitrodiphenyl ether, NIP), which constitute the largest class of commercially produced diphenyl ether herbicides. The pathway of CNP degradation was elucidated by the identification of fungal metabolites upon addition of CNP and its metabolic intermediates. The metabolic pathway was initially branched to form four metabolites--2, 4, 6-trichloro-3-hydroxy-4'-nitrodiphenyl ether, 2, 4-dichloro-6-hydroxy-4'-nitrodiphenyl ether, NIP, and 2, 4, 6-trichloro-4'-aminodiphenyl ether--indicating the involvement of hydroxylation, oxidative dechlorination, reductive dechlorination, and nitro-reduction. Of these reactions, hydroxylation was relatively major compared to the others. Extracellular ligninolytic enzymes such as lignin peroxidase, manganese peroxidase and laccase did not catalyze the oxidation of either CNP or NIP. Piperonyl butoxide, an inhibitor of cytochrome P450, suppressed fungal oxidation of CNP and NIP to their hydroxylated products. The inhibition resulted in increasing the amount of reductively dechlorinated and nitro-reduced products. These observations strongly suggest that basidiomycetes may possess a mechanism for a strict substrate recognition system and a corresponding metabolic response system to effectively degrade environmentally persistent aromatic compounds.

Application of Tri-n-octylphosphine Oxide as an Ionophorefor a Vanadyl Ion-Selective Membrane Electrode

We found that tri-n-octylphosphine oxide (TOPO) acts as an excellent ionophore for vanadyl ion (VO2+). An electrode constructed using this ionophore and 2-fluoro-2′-nitrodiphenyl ether as a solvent mediator in a poly(vinyl chloride) membrane matrix exhibited a near-Nernstian response to VO2+ in the concentration range of 1×10−5–1×10−2 M with a slope of 29.5 mV per concentration decade in a solution containing 0.1 M Na2SO4. The limit of detection was 1×10−6 M. The electrode showed high selectivity for VO2+ over other cations including uranyl ion (UO22+). Other phosphine oxides such as triphenylphosphine oxide and tribenzylphosphine oxide, as well as phosphonate and phosphate analogs responded weakly to VO2+, indicating that the TOPO with the strong basicity of the P=O group was especially useful for constructing a VO2+-selective electrode.

Nitrofen-induced congenital malformations of the heart and great vessels in rats: An animal model

Background: Nitrofen (2,4-dichloro-4′-nitrodiphenyl ether), a diapheny ether herbicide, is known to induce in rat fetuses a variety of congenital cardiovascular anomalies, together with diaphragmatic hernia and hydronephrosis. The purpose of the current study was to produce congenital cardiovascular anomalies in rat fetuses by oral nitrofen administration at the indicated doses and days of gestation, and to determine the characterstics of resulting nitrofen-induced cardiovascular anomalies. Methods: All the observed fetuses were removed from pregnant Sprague-Dawley rats killed on the 21st day of gestation. They were preserved in 10% formalin, and dissection for examination was carried out under a dissecting microscope. Results: The following results were based on dissecting microscopic findings of 482 offspring: (1) The 11th day of gestation was the most sensitive for nitrofen induction of congenital cardiovascular anomalies. The incidence of these was dose related. (2) Ventricular septal defect was the most common single cardiovascular anomaly, representing more than half of all such irregularities. The next most common were aortic arch anomalies and tetralogy of Fallot. (3) Cardiac anomalies derived from infundibular maldevelopment such as tetralogy of Fallot and pulmonary atresia with ventricular septal defect were observed only in the group treated with nitrofen on the 11th gestational day. (4) Aortic arch anomalies were very frequent; the great majority were anomalous right subclavian artery with left aortic arch. Conclusion: This animal model is suitable for further embryological investigation of the development of congenital cardiovascular anomalies.

Maternal and developmental toxicity of halogenated 4′‐nitrodiphenyl ethers in mice

In an ongoing effort to delineate structure-activity relationships in the developmental toxicity of diphenyl ethers, we evaluated the maternal and developmental toxicity of 10 diphenyl ethers related to the herbicide nitrofen. All possible trichlorophenyl 4′-nitrophenyl ethers were evaluated, as were the 2,4-difluorophenyl and 2,4-dibromophenyl 4′-nitrophenyl ethers. We also evaluated bifenox and chlomethoxyfen, which are 2,4-dichlorophenyl congeners with meta-substituents on the 4′-nitrophenyl ring. Nitrofen (2,4-dichlorophenyl 4′-nitrophenyl ether) was included for comparison. Identity of the halogen affected the postnatal (but not prenatal) mortality induced by 2,4-dihalogenated 4′-nitrophenyl ethers. The presence of 3′-substituents on the 4′-nitrophenyl ring reduced both pre- and postnatal toxicity of 2,4-dichlorinated congeners. Among chlorinated 4′-nitrophenyl congeners without meta-substituents on the nitrophenyl ring, the position of chlorine substituents strongly affected the congener's potential for inducing prenatal vs. postnatal syndromes. All congeners increased liver to body weight ratios in unmated females, but such increases were not well-correlated with either prenatal or postnatal embryotoxicity. Teratology 59:69–80, 1999. © 1999 Wiley-Liss, Inc.

Determination of free disopyramide in blood serum in situ using a disopyramide-sensitive membrane electrode

Free disopyramide levels in blood serum, the monitoring of which is especially effective for antiarrhythmic therapy, were determined in situ using a disopyramide-sensitive membrane electrode. Sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate was incorporated as the ion-exchanger and 2-fluoro-2′-nitrodiphenyl ether as the solvent mediator in a poly(vinyl chloride) membrane matrix to form the electrode. The lower limit of the detection for free disopyramide in serum was 0.8 μM. The free disopyramide concentrations measured by the ion-selective electrode agreed well with those determined by an established fluorescence polarization immunoassay that requires an additional ultrafiltration procedure to remove disopyramide bound to serum protein.

Potentiometric determination of alkaline phosphatase in blood serum using a hordenine‐sensitive membrane electrode

AbstractA hordenine‐sensitive membrane electrode was constructed and applied for the determination of alkaline phosphatase (ALP) in blood serum. The method is based on the detection of hordenine formed by the enzymatic reaction of 4‐O‐phosphonohordenine (hordenine phosphate) with ALP. The hordenine electrode was constructed by incorporating sodium tetrakis[3,5‐bis(2‐methoxyhexafluoro‐2‐propyl)phenyl]borate as an ion‐exchanger and 2‐fluoro‐2′‐nitrodiphenyl ether as a solvent mediator in a poly(vinyl chloride) membrane matrix. This is the first attempt to apply an ion‐selective electrode for the assay of serum ALP. The results were compared with those obtained by colorimetry using phenyl phosphate as a substrate.

A New Bretylium-Selective Electrode for Monitoring the Drug in Blood Serum

Abstract We determined serum bretylium levels using a bretylium-selective electrode, constructed by incorporating sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate as an ion-exchanger and 2-fluoro-2′-nitrodiphenyl ether as a solvent mediator in a poly(vinyl chloride) membrane matrix. The detection limit was 0.4 μM and the sensitivity completely covered the bretylium concentration range (2-12 μM) required for antiarrhythmic therapy. The results correlated well with those obtained by conventional gas chromatographic analysis. The potentiometric procedure is simple, rapid, economical and, thus, useful for therapeutic drug monitoring in a clinical setting.

Protoporphyrinogen oxidase: high affinity tetrahydrophthalimide radioligand for the inhibitor/herbicide-binding site in mouse liver mitochondria.

Protoporphyrinogen oxidase (protox), the last common enzyme in heme and chlorophyll biosynthesis, is the target of several classes of herbicides acting as inhibitors in both plants and mammals. N-(4-Chloro-2-fluoro-5-(propargyloxy)phenyl)-3,4,5,6-tetrahydro phthalimide (a potent protox inhibitor referred to as THP) was synthesized as a candidate radioligand ([3H]-THP) by selective catalytic reduction of 3,6-dihydrophthalic anhydride (DHPA) with tritium gas followed by condensation in 45% yield with 4-chloro-2-fluoro-5-(propargyloxy)aniline. Insertion of tritium at the 3 and 6 carbons of DHPA as well as the expected 4 and 5 carbons resulted in high specific activity [3H]THP (92 Ci/mmol). This radioligand undergoes rapid, specific, saturable, and reversible binding to the inhibitor/herbicide binding site of the protox component of cholate-solubilized mouse liver mitochondria with an apparent Kd of 0.41 nM and Bmax of 0.40 pmol/mg of protein. In the standard assay, mouse preparation (150 micrograms of protein) and [3H]THP (0.5 nM) are incubated in 500 microL of phosphate buffer at pH 7.2 for 15 min at 25 degrees C followed by addition of ammonium sulfate and filtration with glass fiber filters. The potencies of five nitrodiphenyl ethers and two other herbicides as inhibitors of [3H]THP binding correlate well with those for inhibition of protox activity (r2 = 0.97, n = 7), thus validating the binding assay as relevant to enzyme inhibition. It is also suitable to determine in vivo block as illustrated by an approximately 50% decrease in [3H]THP binding in liver mitochondria from mice treated ip with oxyfluorfen at 4 mg/kg. This is the first report of a binding assay for protox in mammals. The high affinity and specific activity of [3H]THP facilitate quantitation of protox and therefore research on a sensitive inhibition site for porphyrin biosynthesis.

Determination of Drug Substances Using Ion-Selective Electrodes.

The use of ion-selective electrodes for the determination of drug substances is reviewed. Although the primary emphasis is placed on drugs in the field of forensic chemistry, for example, paraquat, methamphetamine, amphetamine, and cocaine, other clinically important drugs such as procainamide, bretylium, disopyramide, and salicylate, as well as serotonin, a biogenic amine, are also discussed. Sensor membranes of these ion-selective electrodes can be prepared by incorporating a lipophilic ion-exchanger (or neutral carrier) and an appropriate membrane solvent in a poly (vinyl chloride) membrane matrix. In many cases, the combination of the ion-exchanger, sodium tetrakis [3, 5-bis (2-methoxyhexafluoro-2-propyl) phenyl] borate and the membrane solvent, 2-fluoro-2'-nitrodiphenyl ether afforded the most sensitive sensor membrane for drugs. In some cases, the choice of membrane solvent was important and tris (2-ethylhexyl) phosphate, tricresyl phosphate, and tetrakis (2-ethylhexyl) pyromellitate became excellent membrane solvents for making sensor membranes responding to serotonin, methamphetamine and cocaine, respectively. Neutral carriers may be useful to make highly selective electrodes to specific drugs, but have not been studied in detail. We discussed here amphetamine-selective and salicylate-selective electrodes using the neutral carriers, dicyclohexano-18-crown-6 and heptyl-4-trifluoroacetylbenzoate, respectively, as typical examples.

Synthesis and QSAR of Herbicidal 3-Pyrazolyl α,α,α-Trifluorotolyl Ethers

Pyrazole nitrophenyl ethers (PPEs) were recently identified as a novel class of chemistry exerting herbicidal effects by inhibition of protoporphyrinogen IX oxidase. This area of chemistry has been extended to include herbicidal pyrazolyl fluorotolyl ethers. In these compounds, a trifluoromethyl group substitutes for the 4‘-nitro group found in the original herbicides and in “classical” nitrodiphenyl ether hebicides. Fluoroanisole pyrazole ethers, in which a trifluoromethoxy group replaces the nitro group of diphenyl ether herbicides, are also described. The shift from 4‘-nitro to 4‘-trifluoromethyl substitution, which is conservative in terms of electrostatics, produced a novel class of herbicide with substantial pre-emergent activity on narrowleaf weed species. Quantitative structure/activity relationships obtained with respect to substitution on the pyrazole ring and at the 3‘-position of the fluorotolyl moiety can be summarized effectively by comparative molecular field analysis. In general, 5-methanesulfonyl fluorotoluidide ethers were found to be most active. Keywords: Herbicide; protoporphyrinogen oxidase; structure/activity; QSAR; pyrazole phenyl ether; comparative molecular field analysis; CoMFA

Genotoxicity of potential metabolites of nitroscanate — an antischistosomal drug

The potential metabolites of nitroscanate(4-isothiocyanato-4′-nitrodiphenyl ether) such as 4-amino-4′-nitrodiphenyl ether (ANDE), 4-acetamido -4″-nitrodiphenyl ether (AcNDE), 4-acetamido-4′-nitrosodiphenyl ether (4-N = 0), 4-acetamido-4′- hydroxylaminodiphenyl ether (4-NHOH), 4-acetamido-4′-acetohydroxamicdiphenyl ether [4-N(OH)AC], 4-acetamido-4′-for-mohydroxamicdiphenyl ether [4-N(OH)CHO] and 4-acetamido-4′-acetylaceto-hydroxamicdiphenyl ether [4-N(OAc)Ac] were synthesized and investigated in the standard Salmonella mutagenicity test using TA98, TA98NR, TA98/1,8-DNP 6, TA100 and TA100NR as indicator strains, in the presence and absence of hepatic S9. The relative order of activity among nitro and its reduction products, 4-N =0 and 4-NHOH in TA98 and TA100 was 4-N - 0 > 4-NHOH > AcNDE. In nitroreductase deficient strain TA98NR, AcNDE was inactive, but expressed a slight activity in TA100NR while 4-N =0 and 4-NHOH showed a large increase in specific activity in both the strains. In O-acetyltransferase deficient strain TA98/1,8-DNP 6, AcNDE was inactive, while 4-N = 0 and 4-NHOH showed a sharp fall inactivity. The hydroxylamine derived products with an activity order 4-N(OAc)Ac > 4-N(OH)CHO > 4-N(OH)Ac in both TA98 and TA100, showed 3–6 times increase in the specific activity for the latter two compounds in the presence of S9 mix, which was inhibited in the presence of paraoxan, indicating N-deacylation as an important metabolic activation pathway. Except the 4-NO in TA100, the observed mutagenicity of nitroscante (NSC) was higher than those of potential metabolites and the nor-isothiocyanato derivative 4′-nitrodiphenyl ether, thereby showing that -NCS function has a potentiating effect on the mutagenicity of this drug.

EMF response of neutral-carrier based ion-sensitive field effect transistors with membranes free of ionic sites

Response characteristics of field effect transistors covered by membranes containing neutral carriers and an organic liquid but neither a polymer nor ionic sites were determined. The commercially available 2-nitrophenyl octyl ether and dioctyl sebacate, both frequently used plasticizers for poly(vinyl chloride) ISE membranes, had impurity concentrations large enough to lead to small emf responses. Upon removal of these impurities by HPLC, no emf responses were detectable any more, which seems to be due to a negligibly small permselective uptake of primary ions into the membrane and not the high impedance of the membrane bulk. The use of membranes of the more polar nitrobenzene and 2-fluoro-2′-nitrodiphenyl ether resulted in small but transient emf responses. The absence of ionic sites led however to the failure of permselectivity and resulted in co-extraction even of the highly hydrophilic chloride ions. Liquid membranes containing neutral carriers but no ionic sites are thus not only unsuitable for ISEs due to their high impedance, but also because it is very likely that either the failure of permselectivity occurs or the concentration of primary ions permselectivity entering the membrane is too small to determine the phase boundary potential.

Mutagenicity of nitroscanate, an antischistosomal drug

Nitroscanate (NSC) was found to be a direct acting mutagen in the Ames Salmonella tester strains TA100 and TA98 and this activity increased further in the presence of rat liver S9 mix. It was inactive in TA98NR and TA100NR, and weakly active in TA98/1,8-DNP 6. A substantial fall in drug induced mutagenicity by pentachlorophenol, an inhibitor of acetyltransferase, in TA98, TA100 and YG1024 suggests the initial bioconversion of a nitro group to hydroxylamine and its further activation to the ultimate N-acetoxyarylamine. The refrigerated DMSO solution of the drug in the plate incorporation assay and freshly prepared solutions using the pre-incubation procedure indicated a fall in mutagenicity owing to the conversion of NSC to N, N′-bis-4-( p-nitrophenoxy)phenyl thiourea (NFPT). The drastic reduction in mutagenicity in the presence of 4-amino-4′-nitrodiphenyl ether (ANDE) and 4-aminodiphenyl ether (ADE) was also attributed to the conversion of NSC to the corresponding thiourea, a non-mutagen. The negligible mutagenicity of ANDE and its absence in ADE and 4-isothiocyanate diphenyl ether (ITDE) suggests that the mutagenicity of NSC is due to the nitro group, and the -NCS function is responsible for enhanced mutagenicity over nor-isothiocyanate 4-nitrodiphenyl ether (NDE).

Potentiometric discrimination of organic amines by liquid membrane electrodes based on a long alkyl chain derivative of ?-cyclodextrin

A long alkyl chain derivative of β-cyclodextrin (6A,6B,6C,6D,6E,6F,6G-hepta-S-dodecyl-6A, 6B,6C,6D,6E,6F,6G-heptathio-β-cyclodextrin tetradecaacetate) was examined as a new type of sensory element of an ion-selective electrode for organic amines. Poly(vinyl chloride) (PVC) matrix liquid membrane electrodes based on this host were prepared by using several membrane solvents, among which 2-fluoro-2′-nitrodiphenyl ether (FNDPE) was found to be by far most effective for potentiometric responses by the cyclodextrin host. Guest-induced potential changes were examined at pH 5.0 for several groups of protonated organic amine guests having different types of nonpolar moieties. The magnitude of the guest-induced potential change was in the order of 2-phenylethylamine > 1-adamantanamine > benzylamine > cyclohexanamine > dopamine. Potentiometric discrimination was also observed for the positional isomers of di- and trimethoxybenzylamines, though the discrimination between the isomers of monomethoxybenzylamines was negligible. These potentiometric selectivities were quite different from those for a liquid membrane electrode containing no particular sensory element. No appreciable effect was observed by addition of potassium tetrakis(p-chlorophenyl)borate as a fixed anionic site. Such a characteristic feature of this cyclodextrin-based liquid membrane electrode was explained in terms of the availability of an inclusion complex between the cyclodextrin host and each guest in a geometry that would be stable at the membrane surface.

Potentiometric method for the determination of adenosine-5′-triphosphate

A potentiometric method for the determination of adenosine-5′-triphosphate (ATP) concentrations using a choline-sensitive membrane electrode and choline kinase enzyme is described. The choline electrode was constructed from a poly(vinyl chloride)-based membrane containing sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate as an ion exchanger and 2-fluoro-2′-nitrodiphenyl ether as a membrane solvent. Choline reacted quantitatively with ATP to produce the electrode-insensitive choline phosphate and, therefore, the concentration of ATP could be determined by the measurement of choline consumed by the enzymatic reaction. ATP down to 10 μM could be detected. This method was used successfully to determine the intracellular ATP content of human red blood cells.

Photoreactions of Nitrodiphenyl Ethers

Photoreactions of Nitrodiphenyl Ethers

Mode of Action Studies on a Chiral Diphenyl Ether Peroxidizing Herbicide

The nitrodiphenyl ether herbicide 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitroacetophenone oxime-O-(acetic acid, methyl ester) (DPEI) induced an abnormal accumulation of protoporphyrin IX in darkness in the green alga Chlamydomonas reinhardtii, as determined by high-performance liquid chromatography and spectrofluorimetry. It also inhibited the increase in cell density of the alga in light-grown cultures with an I(50) (concentration required to decrease cell density increase to 50% of the noninhibited control value) of 0.16 mum. The relative ability of four peroxidizing diphenyl ether herbicides to cause tetrapyrrole accumulation in C. reinhardtii correlated qualitatively with their ability to inhibit the increase in cell density in light-grown cultures. The purified S(-) enantiomer of the optically active phthalide DPE 5-[2-chloro-4-(trifluoromethyl)phenoxy]-3-methylphthalide (DPEIII), which has greater herbicidal activity than the R(+) isomer, induces a 4- to 5-fold greater tetrapyrrole accumulation than the R(+) isomer. The I(50) for inhibition of increase in cell density in light-grown cultures of C. reinhardtii by the S(-) isomer (0.019 mum) is less than 25% of that for the R(+) isomer. DPEIII inhibits protoporphyrinogen IX oxidase activity in pea (Pisum sativum) etioplast lysates, with the S(-) enantiomer showing considerably greater potency than the R(+) isomer and the racemic mixture showing a potency intermediate between the two. The results indicate that the site at which DPEs inhibit protoporphyrinogen IX oxidase shows chiral discrimination and provide further evidence for the link between inhibition of this enzyme, protoporphyrin IX accumulation, and the phytotoxicity of DPE herbicides.

Construction of a Paraquat-Sensitive Membrane Electrode and Its Application to Forensic Chemistry.

A paraquat-sensitive electrode was constructed by use of a poly (vinyl chloride)-based membrane containing sodium tetrakis [3, 5-bis (trifluoromethyl) phenyl] borate as an ion exchanger and 2-fluoro-2'-nitrodiphenyl ether as a membrane solvent. The minimum detection limit of paraquat was 5×10-7M. The calibration slope of the electrode in linear region was 28 mV/decade. The selectivity coefficients against Na+, K+, Mg2+ and Ca2+ were less than 10-4, and substantially, these inorganic ions did not interfere with the response to paraquat. This electrode was utilized for a criminal investigation. Paraquat added intentionally to drinks such as juice, cola and milk in cases of murder can speedily be measured by the paraquat-sensitive electrode without separating the herbicide from assay mixtures. By using the present electrode, we could estimate paraquat down to 5×10-5M contained in juice. This sensitivity was sufficient enough for the detection of paraquat used in a crime : when the lethal dose of paraquat (2.4 g/a man of 60 kg) was mixed with juice (250 ml), the concentration became about 40 mM. The electrode was also applied to a clinical analysis, and paraquat in the serum could successfully be detected down to 2μM.

Study of the Mode of Action of Some Nitrodiphenyl Ethers

Nitrosoderivatives of the nitrodiphenyl ether herbicides (nitrofen, bifenox) have been studied. UV irradiation in different organic solvents gives degradation products. In buffered aqueous media, in the presence of chloroplasts and spin traps such as DMPO, hydroxy and peroxy radicals have been characterized. In organic media and in the presence of spin traps such as DMPO, PBN, 4-POBN, solvent radicals (.CHCl2, .CCl3, .CH2 [symbol: see text]) have been formed. Nitro-derivatives have been studied under UV irradiation and in the presence of tetramethylethylene (TME), alkenylhydroxylamines are formed which autoxidize in nitroxide radicals. The formation of the stable nitroxide radical occurs in the dark process after continuous irradiation. The intensity of the signal decreases strongly when a new irradiation is applied. Radical species, with analogous ESR spectral characteristics are formed on reaction with nitrodiphenyl ethers and fatty acids. The reactivity of these herbicides in micellar media (SDS, Brij 35, and CTAB) has been investigated. The kinetics of formation of the ESR signal corresponding to the photoreduction of the nitrodiphenyl ether in the presence of TME behave differently in a micellar environment as compared to solution. The intensity of the formation of the nitroxide increases under irradiation and decreases in the dark; the rotational correlation time tau c has been determined for each type of micelle. Synthetic nitrosodiphenyl ether made by the reduction of nitrodiphenyl ether using hydrogen gas and PtO2 as a catalyst gives the corresponding amine, which is oxidized with meta-chloroperbenzoic acid (m.CPBA). The nitrosodiphenyl ether in the presence of soja azolectin liposome containing a fluorescent probe has been analysed.(ABSTRACT TRUNCATED AT 250 WORDS)

Review—mechanism of action of herbicidal and fungicidal compounds on cell membranes

AbstractThe eukaryotic cell membrane is thought to consist of a mobile bilayer of phospholipid, sometimes intercalated with sterols, in which peripheral and transmembrane proteins are embedded. This provides a model whereby the mode of action of many fungicidal and herbicidal compounds can be rationalised and understood. Some compounds, such as the polyene antibiotics, steroidal saponins and certain phytoalexins, induce membrane malfunction by direct insertion, often complexing with vital components. Others, such as paraquat and the nitrodiphenyl ether herbicides, cause membrane damage by inducing lipid peroxidations. Furthermore, there are many compounds, including the sterol‐biosynthesis‐inhibiting fungicides and the aryloxyphenoxypropionate and cyclohexanedione herbicides, which interfere with the biosynthesis of membrane components. Because membrane structure is fundamentally similar in eukaryotes, it is important to discover the reasons for any differential toxicity displayed by these compounds and, if necessary, to find ways of optimising desirable patterns of selectivity.