Organophosphorus compounds. VI.—Structure and activity of certain 4-(diethoxyphosphinothiomethyl) 4H 1,3,4-oxadiazoline-5-thiones,of certain 4-diethoxyphosphinothioylthiomethyl-thiazoles,and related compounds

Contact activity of 4-diethoxyphosphinothioylthiomethyl-4H-1,3,4-oxadiazoline-5-thiones is affected by the nature of the 2-substituent. Alkyl substitution gives high activity against Aphis fabae, Tetranychus telarius and Plutella maculipennis (Curtis), but not against Musca domestica; p-nitrophenyl substitution gives high activity, and p-chlorophenyl substitution lower activity against all of these organisms. Replacement of oxygen of the heterocycle by sulphur reduces acaricidal activity, and replacement by N-methyl increases toxicity to insects and mammals. The compounds lack systemic activity. 4-Diethoxyphosphinothioylthiomethyl-2-phenylthiazole, whether substituted or not in the heterocycle or on the phenyl ring with a nitro-group, lacks activity. 3-Diethoxyphosphinothioylthiomethyl-5-methyloxazolid-2,4-dione has good activity. The structures of the compounds were tentatively assigned on the basis of infra-red and p.m.r. spectra.     

Structures and pesticidal activities of derivatives of dinitrophenols. XI. Effects of substitution of dinitrophenols with C3 to C13 alpha-branched alkyl groups and of esterification on the eradication of cucumber mildew

The eradication of cucumber mildew caused by Sphaerotheca fuliginea (Schlecht. ex Fr.) Poll. with 2-(C₄ to C₁₃ α-branched alkyl)-4,6-dinitrophenols and 4-(C₄ to C₁₃ α-branched alkyl)-2,6-dinitrophenols was examined. 2-(C₈ to C₁₃ α-Branched alkyl)-4,6-dinitrophenols were highly active, but O-methylation produced compounds with no activity. 4-(C₇ to C₁₀ and several C₁₁ to C₁₃ α-branched alkyl)-2,6-dinitro-phenols gave a significant degree of eradication. 2-(C₆ to C₁₃ α-Branched alkyl)-4,6-dinitrophenols were significantly more active than their 4-alkyl-2,6-dinitrophenol analogues. Esterification of C₄ to C₇ α-branched alkyl dinitrophenols to methyl- or ethyl- carbonates or crotonates gave compounds with enhanced activity. Generally, the methyl- or ethyl- carbonates or 2-C₈-alkyl-4,6-dinitrophenols were as active as the parent phenols, but the higher alkyl carbonates or crotonates had lower activity. Esterification of 2-(C₉ to C₁₃ α-branched alkyl)-4,6-dinitrophenols to ethyl carbonates and crotonates gave compounds with reduced activity.     

Structures and pesticidal activities of derivatives of dinitrophenols. IX. Effects of substitution of dinitrophenols with C4 to C13 alpha-branched alkyl groups and of esterification on the eradication of apple mildew

The eradication of apple mildew caused by Podosphaera leucotricha (Ell. and Everh.) Salm. with 2-(C₄ to C₁₃ α-branched alkyl)-4,6-dinitrophenols and 4-(C₄ to C₁₃ α-branched alkyl)-2,6-dinitrophenols was examined. 4-(1-Ethylbutyl)- and most 4-(C₇ to C₁₂ α-branched alkyl)-2,6-dinitrophenols were significantly more active than their 2-alkyl-4,6-dinitrophenol analogues. Compounds containing 4-C₁₃ alkyls did not show significant activity. Activity generally increased as the α-alkyl branch lengthened. Methyl carbonates did not show lower activity than the parent phenols, but esterification of 4-(C₁₂ or C₁₃ α-branched alkyl)-2,6-dinitrophenols to ethyl carbonates or crotonates gave compounds with reduced activity. Methyl-, ethyl- or isopropyl-carbonates and crotonates of 4-(1-ethylhexyl)-2,6-dinitrophenol had much higher activity than the corresponding esters of the 4-(1-methylheptyl) isomer or of 2-(1-ethyl-hexyl)-4,6-dinitrophenol. Compounds containing long ester chains (C₇ or C₈) had less activity than 4-(1-ethylhexyl)-2,6-dinitrophenol. O-Methylation produced compounds with less activity than the parent 4-(1-ethylhexyl)- and 4-(1-propyl-pentyl)-2,6-dinitrophenols.     

Exploring the Effects of Glycosylation and Etherification of the Side Chains of the Anticancer Drug Mitoxantrone

Herein we report the synthesis and biological evaluation of symmetric and asymmetric analogues of the DNA intercalating drug mitoxantrone (MTX) in which the side chains of the parent drug were modified through glycosylation or methyl etherification. Several analogues with glycosylated side chains exhibited higher DNA affinity than the parent MTX. The most potent in vitro cytotoxicity was observed for MTX analogue 8 (1,4‐dimethoxy‐5,8‐bis[2‐(2‐methoxyethylamino)ethylamino]anthracene‐9,10‐dione) with methoxy ether containing side chains. Treatment of melanoma‐bearing mice with MTX or analogue 8 decreased the intraperitoneal tumor burden relative to untreated mice; the effect of 8 was less pronounced than that of MTX. In vitro metabolism assays of MTX with rabbit liver S9 fraction gave rise to several metabolites; almost no metabolites were detected for MTX analogue 8 . The results presented indicate that derivatization of the MTX side chain primary hydroxy groups may result in a significant improvement in DNA affinity and lower susceptibility to the formation of potentially toxic metabolites.     

Deviation of Fiber Tracts in the Vicinity of Brain Lesions: Evaluation by Diffusion Tensor Imaging

Diffusion Tensor Imaging (DTI) is used to characterize the diffusion properties of deviated white matter caused by brain tumors. DTI was recently shown to be very helpful in delineating white matter both within brain lesions and surrounding them. Displacement of white matter fibers may be one of the consequences of tumor growth adjacent to white matter. The combination of white matter mapping with DTI and gray matter mapping using functional MRI, in some cases, facilitated assessment of the relation between the shifted cortical areas and the corresponding white matter tracts. We found that the fractional anisotropy extracted from DTI is increased by 38% in areas of non-edematous shifted white matter fibers. By contrast, trace apparent diffusion coefficient (ADC) values in those areas were found to be similar to contralateral side and normal control values. Analysis of the three diffusion tensor eigenvalues revealed that the increase in the fractional anisotropy is a result of two processes. The first is the increase in the diffusion parallel to the fibers—λ₁ (by 18%), and the second is the decrease in the diffusion perpendicular to fibers—λ₃ (by 34%) as compared with the contralateral side. These opposing changes cause an increase in the diffusion anisotropy but no change in the trace ADC. It is suggested that the pressure caused by the tumor may lead to an increase in white matter fiber tension, thus causing an increase in λ₁. On the other hand, the same pressure causes increased fiber density per unit area, leading to a higher degree of restricted diffusion in the extracellular space and, hence, a reduction in λ₃.     

Studies in fungitoxicity. V. Fungicidal activity of certain dithiocarbamates

Forty-nine derivatives of dimethyldithiocarbamic acid: dimethyldithiocarbamoylamides, N-(dimethyl- dithiocarbamoylalkyl)-amides, -acid esters and -ethers and related compounds were synthesised and tested for fungitoxicity. Of the amides, only those compounds that readily split off the dimethyl-dithiocarbamate ion, detected by a brown colour with copper acetate, had high activity against Venturia inaequalis. Of six ethylenebis-S-alkanamidoalkyl dithiocarbamates, all of which readily yielded the ethylenebisdithiocarbamate ion, only those with a trichloromethyl substituent had high activity. Of the other new condensation products of N-(l,2,2,2-tetrachloroethyl)amides with various nucleophiles, only the 8-oxinate was highly active.     

Structures and pesticidal activities of derivatives of dinitrophenols. X. Effects of substitution od dinitrophenols with C3 to C13 alpha-branched alkyl groups and of esterification on the eradication of barley mildew

The studies of the eradication of barley mildew due to Erysiphe graminis Mérat with alkyldinitrophenols reported earlier¹ were continued. The degree of eradication was highest with 4-(C₉ α-branched alkyl)-2,6-dinitrophenols. 4-Alkyl-2,6-dinitrophenols containing a heptyl or higher alkyl branch were significantly less active, and compounds containing the C₁₂ or C₁₃ alkyls were not active since the most compact of the C₁₂ α-branched alkyls is 1-pentylheptyl. 2-(1-Methylheptyl)- and 2-(1-propylpentyl)-4,6-dinitrophenols had high activity, but their esters showed reduced activity. Esterification of 4-(α-branched alkyl)-2,6-dinitrophenols to methyl carbonates did not affect the activity shown by the compounds, but when certain 4-C₁₀ and C₁₁ alkyl-2,6-dinitrophenols were esterified to ethyl carbonates the activity of the products was reduced. Also activity was diminished by conversion of some 4-C₉ and C₁₀ alkyl-2,6-dinitrophenols to crotonates. Whereas the methyl- and ethyl- carbonates of 4-(1-ethylhexyl)-2,6-dinitrophenol gave consistently high degrees of eradication of barley mildew, the performance of the crotonate of this phenol was not consistent. Lower aliphatic esters of the active C₈-alkyl phenols were themselves active. Esterification of 4-(1-ethylhexyl)-2,6-dinitrophenol to the benzoate, isopropyl carbonate or S-methyl thiolocarbonate gave compounds with substantially reduced activity. 2-t-Butyl-4,6-dinitrophenyl or 4-t-butyl- or t-octyl-2,6-dinitrophenyl esters gave little or no significant eradication.     

Studies in fungitoxicity. VII.—Fungicidal activity of certain ethylenes and heterocyclic compounds substituted with the 2,4-dinitrophenylthio- group

Certain ethylenes and heterocyclic compounds substituted with the 2,4-dinitrophenylthio- group were synthesised and tested for activity against Venturia inaequalis, Botrytis cinerea, Fusarium bulbigenum and Cercospora melonis. 1-Alkylthio-1-(2,4-dinitrophenylthio)-2-cyano-2-(ethoxycarbonyl or cyano) ethylenes in which the Ph-S bond is not shielded by the alkyl substituent from attack, perhaps by nucleophilic cell constituents, were found to be active against Venturia. 3,5-Di(methyl- or ethyl-thio)-4-cyanoisothiazoles were also active against Venturia. 2-Substituted-5-(2,4-dinitrophenylthio)-1,3,4-oxadiazoles had no or low fungicidal activity, and of several 2-(2,4-dinitrophenylthio) heterocyclic compounds that were tested 2-(2,4-dinitrophenylthio)-benzothiazole and -benzoxazole had good activity against Venturia. The infra-red and proton magnetic resonance spectra of several compounds were examined.     

Surfaces with Adjustable Features—Effective and Durable Materials for Water Desalination

Materials based on PVDF with desirable and controllable features were successfully developed. The chemistry and roughness were adjusted to produce membranes with improved transport and separation properties. Membranes were activated using the novel piranha approach to generate OH-rich surfaces, and finally furnished with epoxy and long-alkyl moieties via stable covalent attachment. The comprehensive materials characterization provided a broad spectrum of data, including morphology, textural, thermal properties, and wettability features. The defined materials were tested in the air-gap membrane distillation process for desalination, and improvement compared with pristine PVDF was observed. An outstanding behavior was found for the PVDF sample equipped with long-alkyl chains. The generated membrane showed an enhancement in the transport of 58–62% compared to pristine. A relatively high contact angle of 148° was achieved with a 560 nm roughness, producing a highly hydrophobic material. On the other hand, it was possible to tone the hydrophobicity and significantly reduce adhesion work. All materials were highly stable during the long-lasting separation process and were characterized by excellent effectiveness in water desalination.     

Organophosphorus compounds. III.—Structure and activity of certain OO-dialkyl S-(N-alkoxycarbonylcarbamoylmethyl) phosphorothiolothionates

Several dialkyl S-(N-alkoxycarbonylcarbamoylmethyl) phosphorothiolothionates and related compounds were synthesised and tested for contact (2 days) and systemic (2 days) activity by root-uptake against Aphis fabae and Tetranychus telarius. The activity was more affected by increase in the length of the alkyl chain in the phosphate part than by increase in the carbamate part of the compounds. Substitution by a methyl group on the carbon of the S-methyl reduced activity, whereas substitution by a methyl group on the nitrogen atom broadened the spectrum of activity.