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The article presents as an introduction a short review on the problem of membranous nephropathy. A patient suffering from membranous nephropathy that is resistant to traditional therapy with glucocorticoids and cyclophosphane, as well as cyclosporine, was selected as a clinical case. The use of rituximab at a dose of 375 mg/m2 twice with a difference of one week led to the development of remission in the patient, normalization of clinical and laboratory parameters. No side effects of rituximab were detected.

Three extracts were obtained from the aerial parts of meadowsweet ( Filipendula ulmaria (L.) Maxim.) using water, 40% ethanol, and 70% ethanol as extractants. Comparative assessment of their effect on the development of Lewis lung carcinoma (LLC) in C57Bl/6 line mice showed that, in isolated introduction, development of the metastatic process was inhibited by the extracts prepared in water and 70% ethanol, without influence on the growth of the tumor node. A comparative assessment of the effect of extracts on the antitumor effect of cyclophosphane (CPh) on the primary tumor node showed no changes in effectiveness of the cytostatic agent. When included in the treatment regimen of mice using extracts at a dose of 25 and 50 μg/kg, a significant increase in the antimetastatic action of CPh was detected under the influence of aqueous extract with metastasis inhibition index IMI = 75 and 98%, respectively, and with 70% ethanol extract (IMI = 95 and 96%). The effect of 40% ethanol extract on development of the tumor process in mice with LLC and the effectiveness of CPh therapy were not found.

Objective: to evaluate the dynamics of T-cell recovery after exposure to cyclophosphamide (CP). CP was injected at a dose of 125 mg/kg, followed by killing of mice on days 0, 10, 20, 30, 60 and determination of the subpopulation composition by flow cytometry. It was shown that thymocytes are more vulnerable to the action of the CP than spleen lymphocytes. Cell restoration in the thymus begins earlier with delayed recovery of spleen lymphocytes. Due to CP, there is an increase in the conversion of the naive T-cells into central memory T-cells with a relative accumulation of the latter.

The effect of the 20 coded amino acids was investigated on the development of the processes of the proliferation in the organotypic tissue culture of rat skin. The amino acids lysine, arginine and glutamine acid at 0,05 ng/ml concentration stimulated the cellular proliferation in the growth zone of explants by 29-30%. The mustard-like agent cyclophosphane at 1 mg/ml concentration inhibited the cellular proliferation. The delay of this inhibiting effect of cyclophosphane was observed by the combined action of stimulating amino acids with the cyclophosphane. Thus, the amino acids with the charge radicals can be protectors of the cellular proliferation by the toxic effect of the cyclophosphane on the skin. This effect can be used for the treatment of the mustard injury of skin and for the delay of the adverse effect of cytostatic in oncology (1 figure, 1 table, bibliography: 28 refs).

По мере своего роста злокачественные новообразования оказывают выраженное токсическое воздействие на работу всех органов и тканей организма, способствуя развитию разнообразной сопутствующей патологии, изменяя тактику лечения и ухудшая прогноз заболевания. Дополнительным фактором, усиливающим степень тяжести сопутствующей патологии или провоцирующим обострение хронических заболеваний, являются проводимые лечебные процедуры, в том числе, цитостатическая терапия. Это определяет актуальность комплексной оценки лекарственных препаратов, применяющихся в онкологии, в отношении влияния и на опухолевый процесс, и на работу систем жизнеобеспечения организма. Цель исследования: комплексный анализ влияния на развитие экспериментальной опухоли и состояние системы крови потенциального противоопухолевого средства меглюмина акридонацетата, в том числе, на фоне цитостатической терапии. Материалы и методы. Исследование проведено на 256 самцах мышей линии BALB/c. В качестве модели опухолевого процесса использовали аденокарциному толстой кишки (АКАТОЛ). Экспериментальную химиотерапию проводили на 2е и 5е сутки после трансплантации опухоли препаратом циклофосфан в дозе 175 мг/кг массы тела. Меглюмина акридонацетат применяли ежедневно в дозе 100 мг/кг на протяжении 5 суток после трансплантации АКАТОЛ. Оценивали динамику роста опухоли и её метастатическую активность. Осуществляли общий клинический анализ крови. Результаты. Циклофосфан оказал выраженное ингибирующее действие на рост первичного опухолевого узла АКАТОЛ и процесс распространения новообразования в организме животного. При этом наблюдалось сильное гемотоксическое действие цитостатической терапии, имеющее временный, краткосрочный характер. Включение в экспериментальную схему лечения меглюмина акридонацетата потенциировало терапевтические эффекты циклофосфана и в значительной степени нивелировало его токсическое действие в отношении системы крови. На фоне монотерапиии новообразования меглюмина акридонацетатом наблюдалось выраженное ингибирование метастазирования АКАТОЛ и увеличение продукции форменных элементов крови. Выводы. Включение меглюмина акридонацетата в схему терапии циклофосфаном экспериментальной модели колоректального рака усиливает эффективность цитостатика и улучшает профиль его безопасности в отношении влияния на состояние системы крови. Монотерапия новообразования меглюмина акридонацетатом показала умеренный терапевтический эффект в отношении роста опухолевого узла и клинически значимый эффект в отношении ингибирования интенсивности метастазирования опухоли., Growing malignant tumors exert a pronounced toxic effect on all organs and tissues. Thereby, they contribute to various concomitant pathology, change the treatment tactics, and aggravate prognosis for the disease. The treatment itself, specifically a cytotoxic therapy, may also worsen the associated pathology and provoke exacerbation of chronic conditions. These factors determine a need for complex assessment of the drugs used in oncology, both regarding their effect on the neoplasm and side effects on functioning of vital organ systems. Aim: Complex evaluation of the effect of a candidate antitumor drug, meglumine acridonacetate, on experimental tumor growth and the blood system, including the effect on the background of cytostatic therapy. Material and methods. The study was performed on 256 male BALB/c mice. Colon adenocarcinoma (CAC) was used as an experimental model of tumor growth. The experimental chemotherapy with cyclophosphane (175 mg/kg) was administered on days 2 and 5 of tumor implantation. Meglumine acridonacetate (100 mg/kg) was administered daily for 5 days after the CAC implantation. The studied parameters included the tumor growth rate and metastatic activity. Clinical blood tests were also performed. Results. Cyclophosphane exerted a pronounced inhibitory effect on the growth of CAC primary node and tumor dissemination. The cytotostatic therapy produced a severe but brief hemotoxic effect. Addition of meglumine acridonacetate to the experimental treatment plan potentiated the therapeutic effect of cyclophosphane and considerably compensated for its hemotoxic effect. The monotherapy with meglumine acridonacetate significantly inhibited CAC metastasis and stimulated hematopoiesis. Conclusion: Supplementation of the cyclophosphane treatment plan with meglumine acridonacetate enhanced the cytostatic efficacy and improved its safety with respect of the blood system. The meglumine acridonacetate monotherapy exerted a moderate therapeutic effect on tumor growth and a clinically significant inhibitory effect on tumor metastasis., №2 (2019)

The capacity of the bone marrow-derived myelopeptide-1 (MP-1) to affect in vivo and in vitro the functional activity of phagocytes of intact mice and mice treated with a cytostatic agent (cyclophosphane) has been studied. It was found that MP-1 produces a correcting effect on the functional activity of bone marrow and peripheral blood phagocytes. An optimal scheme of the injection of MP-1 to mice with the cyclophosphane-induced immunodeficiency was developed, which provides a maximum immunocorrecting action. MP-1 had the most pronounced effect on the quantitative characteristics and the functional activity of phagocytes of different localization when introduced prior to the cytostatic; under these conditions, the pep tide affects peripheral blood neutrophils. The results obtained enable one to consider MP-1 as a preparation protecting the peripheral blood phagocytes from the damaging action of cyclophosphane.

The efficacy of the combination treatment of P388 leukemia with cisplatin (cPt) and the platinum(IV) nitroxyl complex BC118 [e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bis(acetato)-b,c-dichloroplatinum(iv)] applied in low doses was found to be synergistically increased. Thus, the use of 1/10 of their LD50 cured 100% of animals. The monotherapy with these drugs used in the same doses and at the same schedules showed moderate efficacy, and no animals survived. A synergistic increase in the toxicity was not observed. The rate of the development of resistance decreases in the series cPt+BC118, cPt, and BC118. Strains resistant to cPt+BC118 and BC118 are highly sensitive to doxorubicin, etoposide, and cyclophosphane.

Experiments on animals with transplanted tumors (Lewis lung carcinoma and carcinosarcoma Walker-256) showed that combination treatment with cyclophosphane and its homeopathically potentiated forms increases antiblastic activity of the preparation.

The applicability of alkaline comet assay to studying the organ specificity of the genotoxic effects of drugs has been estimated using cells from four organs of mice (the liver, lungs, spleen, and brain). It has been found that cyclophosphamide damages DNA in all the four organs; and dioxidine, in all organs except the brain. It is concluded that this method can be used for studying the organ specificity of the DNA-damaging effects of various substances.

Bei der Umsetzung von Triorganylcyclotriphosphanen mit Ubergangsmetallkomplexen entstehen ein- und mehrkernige Verbindungen, in denen die Cyclophosphane in unterschiedlicher Form – teils unter Erhalt ihrer Ringstruktur, teils unter Ringoffnung – an das Metall binden. Durch weitere Ligandabspaltung kann man zu groseren Aggregaten gelangen. Abhangig von den Reaktionsbedingungen konnten folgende Verbindungen charakterisiert werden:[(PPh3)2Pt(PtBu)3] (1), [(PPh3)2Pd(PtBu)2] (2), [(CO)4Cr{(PiPr)3}2] (3), [RhCl(PPh3)(PtBu)3] (4), [(NiCO)6(μ2-CO)3{(PtBu)2}2] (5) und [(CpFeCO)2(μ-CO)(μ-PHtBu)]+ · [FeCl3(thf)]– (6). Die Strukturen von 1–6 wurden mit Hilfe der Einkristall-Rontgenstrukturanalyse aufgeklart (1: Raumgruppe P21/n (Nr. 14), Z = 4, a = 1279,6(3) pm, b = 1733,1(4) pm, c = 2079,1(4) pm, β = 90,20(3)°; 2: Raumgruppe P21/c (Nr. 14), Z = 4, a = 1053,3(2) pm, b = 2085,2(4) pm, c = 1855,7(4) pm, β = 98,77(3)°; 3: Raumgruppe P 1 (Nr. 2), Z = 2, a = 1022,6(2) pm, b = 1026,4(2) pm, c = 1706,0(3) pm, α = 82,36(3)°, β = 86,10(3)°, γ = 64,40(3)°; 4: Raumgruppe P 1 (Nr. 2), Z = 2, a = 980,2(2) pm, b = 1309,5(3) pm, c = 1573,4(3) pm, α = 99,09(3)°, β = 99,46(3)°, γ = 111,87(3)°; 5: Raumgruppe P21/c (Nr. 14), Z = 4, a = 1804,0(5) pm, b = 2261,2(6) pm, c = 1830,1(7) pm, β = 96,99(3)°; 6: Raumgruppe P21/c (Nr. 14), Z = 4, a = 943,2(3) pm, b = 2510,6(7) pm, c = 1325,1(6) pm, β = 98,21(3)°). New Research of Reaction Behaviour of Triorganylcyclotriphosphines. The Crystal Structures of [(PPh3)2Pt(PtBu)3], [(PPh3)2Pd(PtBu)2], [(CO)4Cr{(PiPr)3}2], [RhCl(PPh3)(PtBu)3], [(NiCO)6(μ2-CO)3{(PtBu)2}2], and [(CpFeCO)2(μ-CO)(μ-PHtBu)]+ · [FeCl3(thf)]– By the reaction of triorganylcyclotriphosphines with transition metal complexes single- and polynuclear compounds are formed, in which the cyclophosphines are bonded in different ways to the metal, the ring either preserving structure or under going ring opening. Depending on the reaction conditions the following compounds can be characterized: [(PPh3)2Pt(PtBu)3] (1), [(PPh3)2Pd(PtBu)2] (2), [(CO)4Cr{(PiPr)3}2] (3), [RhCl(PPh3)(PtBu)3] (4), [(NiCO)6(μ2-CO)3{(PtBu)2}2] (5) and [(CpFeCO)2(μ-CO)(μ-PHtBu)]+ · [FeCl3(thf)]– (6). The structures of 1–6 were obtained by X-ray single crystal structure analysis (1: space group P21/n (No. 14), Z = 4, a = 1279.6(3) pm, b = 1733.1(4) pm, c = 2079.1(4) pm, β = 90.20(3)°; 2: space group P21/c (No. 14), Z = 4, a = 1053.3(2) pm, b = 2085.2(4) pm, c = 1855.7(4) pm, β = 98.77(3)°; 3: space group P 1 (No. 2), Z = 2, a = 1022.6(2) pm, b = 1026.4(2) pm, c = 1706.0(3) pm, α = 82.36(3)°, β = 86.10(3)°, γ = 64.40(3)°; 4: space group P 1 (No. 2), Z = 2, a = 980.2(2) pm, b = 1309.5(3) pm, c = 1573.4(3) pm, α = 99.09(3)°, β = 99.46(3)°, γ= 111.87(3)°; 5: space group P21/c (No. 14), Z = 4, a = 1804.0(5) pm, b = 2261.2(6) pm, c = 1830.1(7) pm, β = 96.99(3)°; 6: space group P21/c (No. 14), Z = 4, a = 943.2(3) pm, b = 2510.6(7) pm, c = 1325.1(6) pm, β = 98.21(3)°).

Quantitative and qualitative composition of hemopoietic tissue and the intensity of proliferation and differentiation of committed hemopoietic precursors are studied in mice treated with adriamycin, cyclophosphane, or 5-fluorouracil. It is shown that intense maturation of colony-forming units results in rapid regeneration of hemopoiesis even under conditions of reduced proliferation of these cells, whereas inhibition of their differentiation suppresses restoration of bone marrow cellularity despite intense proliferation of hemopoietic precursors.

tBu2PPP(Br)tBu21 reagiert mit PR3 [R3 Et3, tBu3, Ph3, (NMe2)3, (NEt2)3, (NEt2)2Me, Me2SiMe3] nach tBu2PPP(Br)tBu2 + PR3 tBu2PPPR3 + tBu2PBr Wahrend 1 oberhalb −30°C unter Bildung von tBu2PBr und der Cyclophosphane (tBu2P)3P3, (tBu2P)4P4 zerfallt, unterbleibt die Kondensation des intermediar auftretenden tBu2PP zu den Cyclophosphanen in Anwesenheit von PR3 aufgrund der Addition des Phosphans. Die Chlorphosphane tBu2PCl, tBuPhPCl, (Et2N)2PCl und Ph2PCl sowie (CF3)2PBr reagieren weitgehend entsprechend Gl. (1) unter Bildung von tBu2PPPtBu2Cl, tBu2PPPtBuPhCl, tBu2PPP(NEt2)2Cl, tBu2PPP(NEt2)2Br. Reactions of tBu2PPP(Br)tBu2 with Phosphanes A Route to Variously Substituted Phosphinophosphinidene-phosphoranes tBu2PPP(Br)tBu21 reacts with PR3 [R3 = Et3, tBu3, Ph3, (NMe2)3, (NEt2)3, (NEt2)2Me, Me2SiMe3] according to tBu2PPP(Br)tBu2 + PR3 tBu2PPPR3 + tBu2PBr While 1 decomposes above −30°C yielding tBu2PBr and the cyclophosphanes (tBu2P)3P3 and (tBu2P)4P4, there is no condensation to give any cyclophosphanes from the intermediately formed tBu2PP in the presence of PR3. The chlorophosphanes tBu2PCl, tBuPPhCl, (Et2N)2PCl and Ph2PCl as well as (CF3)2PBr react quite analogously to the above equation yielding tBu2PPP(Cl)tBu2, tBu2PPPtBuPhCl, tBu2PPP(NEt2)2Cl and tBu2PPP(NEt2)2Br.

Es wird uber die Bildung von tBu2PP = P · (R)tBu2a und (tBu2P)2PR b, R = Me, Et, nPr, iPr, nBu, PhCH2, CH2CH = CH2, CF3 bei Umsetzungen von Li(THF)2 · [η2-(tBu2P)2P] 2 mit MeCl, MeI, EtCl, EtBr, nPrCl, nPrBr, iPrCl, nBuBr, PhCH2Cl, ClCH2CH = CH2 und CF3Br berichtet. Neben den ylidischen Verbindungen a bilden sich die entsprechenden Triphosphane (tBu2P)2PR b, wobei in THF-Losung die Bildung von a, in Pentan-Losung die von b begunstigt ist. Mit ClCH2CH2 = CH2 bildet sich nur b, mit CF3Br dagegen die Ylide tBu2PP = P(Br)tBu2 und tBu2PPP(CF3)tBu2, aber kein Phosphan b. Das Verhaltnis zwischen a und b wird auch durch die Reaktionstemperatur beeinflust. So bildet 2 mit EtBr in THF bei −70°C die Produkte tBu2PP = P(Et)tBu24a und (tBu2P)2PEt 4 b im Verhaltnis 4:3, bei 20°C 1:1; in Pentan bei −70°C 4a:4b = 1:1, bei 20°C 1:2. 2reagiert nicht mit tBuCl und H2C = CHCl. Die Verbindungen a zersetzen sich bei UV-Bestrahlung oder beim Erwarmen unter Bildung von tBu2PR und der Cyclophosphane (tBu2P)nPn. The Phosphinophosphinidene-phosphoranes tBu2PP = P(R)tBu2 from Li(THF)2[η2-(tBu2P)2P] and Alkyl Halides We report the formation of tBu2PP = P(R)tBu2a and (tBu2)2PR b (with R = Me, Et, nPr, iPr, nBu, PhCH2, H2C = CHCH2 and CF3) reactions of Li(THF)2[η2-(tBu2P)2P] 2 with MeCl, MeI, EtCl, EtBr, nPrCl, nPrBr, iPrCl, nBuBr, PhCH2Cl, H2C = CHCH2Cl or CF3Br. In THF solutions the ylidic compounds a predominate, whereas in pentane the corresponding triphosphanes b are preferrably formed. With ClCH2CH = CH2 only b is produced; CF3Br however yields both tBu2PP = P(Br)tBu2 and tBu2PP = P(CF3)tBu2, but no b. The ratio of a:b is influenced by the reaction temperature, too. The compounds tBu2PP = P(Et)tBu24a and (tBu2P)2PEt 4 b, e. g., are produced in a ratio of 4:3 at −70°C in THF, and 1:1 at 20°C; whereas 1:1 is obtained at −70°C in pentane, and 1:2 at 20°C. Neither tBuCl nor H2C = CHCl react with 2. The compounds a decompose thermally or under UV irradiation forming tBu2PR and the cyclophosphanes (tBu2P)nPn.

The reaction of the cyclophosphane (EtP)5 with the activated triosmium cluster [Os3(µ-H)2(CO)10] at 80 °C gave [Os3(µ-H)(CO)8(µ-η3-P5Et5H)]1 and [Os3(CO)10{1,3-(PEt)5}]2. The compound (PhP)5 reacted with [Os3(µ-H)2(CO)10] at room temperature to give [Os3(µ-H)(CO)8(µ-η3-P5Ph5H)]3. Treatment of (EtP)5 with [Os3(CO)10(NCMe)2] at room temperature afforded [Os3(CO)10{1,2-(PEt)5}]4, while the reaction at 80 °C yielded only 2. All the reaction products have been characterized by elemental analysis and IR, 1H and 31P NMR spectroscopy. The solid-state structures of compounds 1, 2 and 4 established by single-crystal X-ray diffraction showed that the phosphorus ring in 1 has undergone one P–P bond cleavage while those in 2 and 4 are intact. The solution structure of 3 has been fully characterized by two-dimensional 31P NMR spectroscopy.

Dei Bildung von (tBu)2PP = P(Br)tBu21 aus [(tBu)2P]2PLi und BrH2CCH2Br wird eingeleitet durch den Lithium-Brom-Austausch und ist bedingt durch die anschliesende Br-wanderung vom sekundaren P-Atom im [(tBu)2P]2PBr 6 zum primaren P-Atom in 1 Entsprechend bildet sich (tBu)2PP = P(CI)tBu22 bei de Synthese von [(tBu)2P]2PC1 7 aus PC13 und Lip(tBu)2. Der Reaktionsablauf it unabhangig von den Halogensubstituenten, wird aber entscheidend beeinflust durch die tBu-Gruppen. So bildet (tBu)2PP(Li)P(SiMe3)2 mit BrH2CCH2Br das (tBu)2PP(br)P(SiMe3)2, das aber ebenso wie (tBu)2PP(CI)P(SiMe3)2 keine Umlagerung zm Phosphanyliden-Phosphoran eingeht. Der Ein1Us der F3C-Gruppe auf die Umlagerung war nicht zu untersuchen, da [(F3C)2P]2PSIMe3 auch mit BuLi nicht in das lithiierte Derivat zu uberfuhren ist. 1 und 2 zeigen charakteristische Reaktionen in Abhangigkeit von der Temperatur. Wahrend 1 bei +20°C uber das Reaktiv (tBu)2PP die Cyclophosphane P3[P(tBu)2]4 bildet, Kristallisiert aus den Losungen von 1 (z. B. Toluol) bei −20°C [(tBu)2P]2PP[P(tBu)2]2. Die Umsetzungen von 1 mit tBuLi fuhren zu (tBu)2PP(H)tBu220 und (tBu)2PP(H)P(tBu)214. Dei Reaktion wird durch die Umlithiierung zwischen 1 und tBuLi zu tBuBr und (tBu)2PPP(Li)tBu221 eingeleitet, der unter LiBr-Abspaltung und Isobuten-Eliminierung die Bildung von 20 folgt, das zu 14 umlagert. 21 wird durch Reaktion von 1 mit nBuLi fasbar [Ausblieben der Buten-Eliminierung], das mit Me3SiCl zu (tBu)2PP(SiMe3)P(tBu)223 abreagiert. Hauptprodukt der Umsetzung ist [(tBu)2P]2P-nBu 22. Formation and Reaction of the Phosphanylidene-phosphorane (tBu)2PP = PX(tBu)2 (X = Br, Cl) The formation of (tBu)2PP = P(Br)tBu21 from [(tBu)2P]2PLi and BrH2CCH2Br begins with an exchange of Li against Br and is then determined by the migration of Br from the secondary P atom in [(tBu)2P]2PBr 6 to the primary P in 1. Similarly, (tBu)2PP = PC1(tBu)22 is obtained starting from PCl3 and LiP(tBu)2. The formation of Phospanylidene—phosporane is not influenced by the choice o the halogene substituent, but the presence of the tBu groups is strongly required. (tBu)2PP(Li)P(SiMe3)2 e. g., yields (tBu)2PP(br)P(SiMe3)2 with BrH2CCH2Br; however neither this nor (tBu)2PP(Cl)P(SiMe3)2 do rearrange to a Phosphanylidene-phosphorane. The F3C substituent could be neglected in this investigation as [(F3C)2P]2PSiMe3 cannot be lithiated by means of BuLi. Compounds 1 and 2 display a charateristic temperature dependent behavior. While 1 at +20°C decomposes via the reactive intermediate (tBu)2PP to from the cyclophosphanes P3[P(tBu)2]4, it gives crystals of [(tBu)2P]2Pp[P(tBu)2]2 at −20°C (from a solution in toluene). Reacting 1 with tBuLi produces (tBu)2PP = P(H)tBu220 and (tBu)2PP(H)P(tBu)214. Initially, a transmetallation yield tBuBr and (tBu)2 PP=Pli(tBu)221,then LiBr and isobutene are eliminated and 20 is formed which can rearrange to produce 14. Without the elimination of isobutene, 1 react with nBuLi to give 21 witch can be trapped with Me3SiCl as (tBu)2PP(tBu)223. The main product in in this reaction is however [(tBu)2P]2PnBu 22.

The effects of various energy metabolism modifiers and their combinations on cyclophosphane toxicity are examined in the fresh-water crustaceaDaphnia magna. The role of acute energy deficiency in the development of paralyzing effect of cyclophosphane is demonstrated. Transporting forms of succinic acid and combinations of carbonic acids with NAD exhibit high protective activity, while glucose reduces protective activity of NAD and sensitizing activity of amino acids.

Es werden alle Reaktionsprodukte der Umsetzung von [tBu2P]2PLi 1 und 1,2-Dibromethan 2 aufgeklart. Aus 1 und 2 bilden sich bereits bei −70°C tBu2PPP(Br)tBu23 (Hauptprodukt) und [tBu2P]2PBr 4. Nur bei einem Uberschus an 1 entsteht auch [(tBu)2P]2PP · [P(tBu)2]25. In einer reinen Losung von 3 (Toluol, −70°C) bilden sich um −30°C 4, um 20°C tBu2PBr und die Cyclophosphane P4[P(tBu)2]4, P3[P(tBu)2]3. 5 entsteht nicht aus 3, sondern immer als Nebenprodukt der Umsetzung von 1 mit 4. Das Ylid 3 bildet mit 1 ebenfalls Verbindung 5. [(tBu)2P]2PP[P(tBu)2]2 from LiP[P(tBu)2]2 and 1,2-Dibromomethane. Pyrolysis of tBu2PPP(Br)tBu2 All products of the reaction of [tBu2P]2PLi 1 with 1,2-dibromoethane 2 were investigated. Already at −70°C tBu2PPP(Br)tBu23 as main product and [tBu2P]2PBr 4 are formed. Only with an excess of 1 also [tBu2P]PP[P(tBu)2]25 is obtained. Warming of a pure solution of 3 in toluene from −70°C to −30°C leads to 4, and at 20°C tBu2PBr and the cyclophosphanes P4[P(tBu)2]4 and P3[P(tBu)2]3 are observed. 5 does not result from 3, it's rather a byproduct from the reaction of 1 with 4. Also the ylide 3 and 1 yields 5.

A case of Kaposi's sarcoma development in a pt with Wegener's granulomatosis during immunosupres- sive treatment with cyclophosphane and prednisolone.

Reaction of the cyclopolyphosphane (PhP)5 with [Ru3(CO)12] in p-xylene at 135 °C for 19 h afforded the new clusters [Ru4(CO)10(µ3-(PPh)2){µ4-(PPh)2}]1 and [Ru4(CO)8(µ-PHPh)2(µ4-PPh)}µ4-(PPh)2}]2. Treatment of (PhP)5 with the activated triruthenium cluster [Ru3(CO)10(NCMe)2] at room temperature overnight gave [Ru3(CO)10{(PhP)5}]3. The structures of the three clusters have been established by single-crystal X-ray analysis. In 1 the four ruthenium atoms have a skew, chain structure while in 2 the four ruthenium atoms adopt a rectangular geometry. Novel phosphido or phosphinidene groups are present in both clusters. In the case of 3 the cyclophosphane (PhP)5 remains intact and acts as a bidentate ligand, occupying the equatorial sites of the ruthenium triangular plane, through the two P atoms in the 1,3 positions.

Phenylcyclophosphane werden durch Tetrachlorkohlenstoff zum Chlor-trichlormethyl-phosphin 2a, Tetracyclohexylcyclotetraphosphan zum Diphosphan 3 abgebaut. Methyl-und Athylcyclophosphane bilden mit Tetrachlorkohlenstoff die monoquartaren Salze 4c bzw. 4d. Daneben entstehen die Spaltprodukte 5 bzw. 2d und 6. Durch die Einwirkung von Aminen auf Cyclophosphane und Tetrachlorkohlenstoff werden die Tris(amino)-phosphoniumsalze 7a,/–j und das Chlormethylphosphoniumchlorid 8a erhalten. Alle Phosphoniumchloride werden als Per-chlorate isoliert und charakterisiert. The Reaction of Cyclophosphanes with Carbon Tetrachloride and Amines The cleavage of phenylcyclophosphanes with carbon tetrachloride leads to the chloro-trichloromethyl-phosphine 2a; tetracyclohexycyclotetraphosphine decomposes in the same manner to the diphosphane 3. Methyl-and ethylcyclophosphanes give with carbon tetrachloride the monoquaternary salts 4c and 4d. The cleavage products 5, 2d and 6 are also formed. The tris-(amino)-phosphonium salts 7a–j and the chloromethylphosphonium chloride 8a are obtained by reaction of amines with cyclophosphanes and carbon tetrachloride. All phosphonium chlorides are isolated and charakterized as perchlorates.

Die Reaktionen von π-C5H5(CO)3MH (M = Cr, Mo, W) 1a–c mit den symmetrischen Diphosphanen (Ph2P)2, [Ph(CN)P]2 und [(CN)2P]2 laufen ebenso wie die mit dem Cyclophosphan (PPh)5 unter Spaltung der PP-Bindung ab. Die Reaktivitat nimmt in den Reihen ab. Die Tendenz zur Bildung zweikerniger Komplexe spiegelt die Basizitat der metallierten Phosphane π-C5H5(CO)3MPRR′ wider und steigt in der Folge P(CN)2 < P(CN)Ph ≪ P(Ph)H < PPh2 an. Iodhaltige Diphosphane [Ph(I)PP(I)Ph und P2I4] reagieren mit 1a–c unter Reduktion und Bildung von π-C5H5(CO)3MI und instabilen Iodo-diphosphanen. Keine PP-Bindungsspaltung tritt bei der Umsetzung der silylsubstituierten Diphosphane [Ph(Me3Si)P]2 und [(Me3Si)2P]2 mit 1a–c auf; bevorzugte Reaktion ist hier unter Bildung von π-C5H5(CO)3MSiMe3 die PSi-Bindungs-spaltung. Perfluoromethyl Element Ligands. XXXII. Reactions of the Metal Hydrides π-C5H5(CO)3MH (M = Cr, Mo, W) with Diphosphanes [Ph2−nYnP]2 (Y = I, CN, SiMe3; n = 2, 1, 0) The reactions of π-C5H5(CO)3MH (M = Cr, Mo, W) (1a–c) with the symmetric diphosphanes (Ph2P)2, [Ph(CN)P]2, [(CN)2P]2, and the cyclophosphane (PPh)5, respectively, occur under cleavage of the PP bond. The reactivity decreases in the series The tendency to form binuclear complexes reflects the basicity of the metallated phosphanes π-C5H5(CO)3MPRR′ and increases in the order P(CN)2 < P(CN)Ph ≪ P(Ph)H < PPh2. Iodine containing diphosphanes [Ph(I)PP(I)Ph and P2I4] undergo redox reactions with 1a–c, yielding π-C5H5(CO)3MI and unstable iodo-diphosphanes. No PP bond cleavage occurs in the reaction of the silyl substituted diphosphanes [Ph(SiMe3)P]2 and [(Me3Si)2P]2 with 1a–c, but PSi bond fission is the preferred reaction giving π-C5H5(CO)3MSiMe3.

Activation of extramedullar hemopoiesis in the liver together with an appreciable elevation of the alpha-fetoprotein (alpha-FP) level in the blood were observed in CBA, C3H/HeJ, DD, C57BL/6 and CC57BR/Mv mice after a single injection of cyclophosphane in a dose of 200 mg/kg bw. The alpha-FP concentration reached maximum days 2-4 after cyclophosphane administration, amounting of 290-560 ng/ml which surpasses 2-5-fold the basal level of the protein. In mice with an earlier serum alpha-FP elevation (CBA, C3H/HeJ and DD), the liver hemopoiesis also started earlier than in those with a delayed alpha-FP maximum (C57BL/6 and CC57BR/Mv).

Lithiumorganyls RLi (R = Me, Bu, Ph) add to (PhP)5 in successive degradation and disproportionation equilibria depending on the ratio of the reactants. At -70 °C (R = Me) disproportionation is blocked and (PhP)4R- and (PhP)3R- can be detected. With excess RLi m onophosphides PhPR- are formed. CpNa with the help of a crown ether degrades (PhP)5 or substitutes cyanide from PhPCN- to give an equilibrium mixture of (PhP)nCp- anions, which stabilize by proton shifts: In case of n = 1 and 2 a shift from the Cp unit to the terminal phosphorus results in the formation of the phenylphosphino- and diphenyldiphosphino-cyclopentadienide anion, in case of n = 3 two proton shifts within the Cp unit result in a cyclopenteno-l,2,3-triphospholene allylic anion.

Die Reaktion von K(tBu)P–P(tBu)K mit Isocyanid-dichloriden fuhrt zu den ersten Diphosphiraniminen (tBuP)2CNR. Daneben entstehen die Cyclophosphane (tBuP)n (n=3,4) und die entsprechenden zwei konfigurationsisomeren 1,3-Diphosphetan-2,4-diimine. N-Arylsubstituierte Diphosphiranimine mit einem voluminosen Substituenten in ortho-Position zur Iminofunktion, wie (tBuP)2CN(2,4-tBu2C6H3) (1) und (tBuP)2CN(2-tBuC6H4) (2), sind bei Raumtemperatur bestandig und konnten in reiner Form isoliert werden. Die Darstellung der Isocyanid-dichloride 2,4-tBu2C6H3NCCl2 und 2-tBuC6H4NCCl2 wird beschrieben. The reaction of K(tBu)P–P(tBu)K with isocyanide dichlorides yields the first diphosphiranimines (tBuP)2CNR. Besides, the cyclophosphanes (tBuP)n (n=3,4) and the two configurational isomers of the corresponding 1,3-diphosphetane-2,4-diimines are formed. N-Aryl-substituted diphosphiranimines with one bulky substituent in ortho-position to the imino function, such as (tBuP)2CN(2,4-tBu2C6H3) (1) and (tBuP)2CN(2-tBuC6H4) (2), are stable at room temperature and could be isolated in the pure state. The preparation of the isocyanide dichlorides 2,4-tBu2C6H3NCCl2 and 2-tBuC6H4NCCl2 is described.

The experiments were conducted on 186 Wistar rats with an average weight of 140 g. We used CP produced by the Saransk Medical Preparations Factory. The maximum tolerable dose of CP in the case of a single intraperitoneal injection is i00 mg/kg for rats. Considering that the drug exhibits a highly cummulative toxic effect, and on the basis of the literature data [i], to produce the maximum toxic effect CP was injected in 25 mg/kg doses intraperitoneally for four days (total dose i00 mg/kg). The toxicity of CP was assessed according to changes in the following parameters: body weight, relative weight of the spleen (RWS the ratio of the weight of the spleen in milligrams to the body weight in grams), number of lymphocytes, and lifetime of the animals, over a month after administration of the drug. The influence of CP on the intensity of antitularemic immunity was determined according to antibody formation by the agglutination reaction, which is extremely specific in tularemia.

Hexachlorcyclohexaphosphan (1) und Hexabromcyclohexaphosphan (2) werden bei der partiellen Enthalogenierung von Phosphor(III)-chlorid bzw. Phosphor(III)-bromid mit Magnesium oder Lithiumhydrid in polaren Solventien gebildet. Sie sind als erste perhalogenierte Cyclophosphane nur in verdunnter Losung bei tiefer Temperatur bestandig und konnten massenspektrometrisch und 31P-NMR-spektroskopisch charakterisiert werden. Wie das schon bekannte Hexaphenylcyclohexaphosphan, aber im Unterschied zur „Stammverbindung” P6H6, enthalten 1 und 2 ein Phosphor-Sechsringgerust, das offenbar durch elektronegative Substituenten stabilisiert wird. Contributions to the Chemistry of Phosphorus, 1881). – Halogen-Substituted Cyclohexaphosphanes: Formation and Properties of (PCl)6 and (PBr)6 Hexachlorocyclohexaphosphane (1) and hexabromocyclohexaphosphane (2) are formed in the partial dehalogenation of phosphorus trichloride and phosphorus tribromide, respectively, by magnesium or lithium hydride in polar solvents. As the first perhalogenated cyclophosphanes they are only stable in diluted solutions at low temperature and could be characterized by means of mass spectrometry and 31P nuclear magnetic resonance. Like the known hexaphenylcyclohexaphosphane, but in contrast to the „parent compound” P6H6, 1 and 2 have a six-membered phosphorus ring skeleton, which is obviously stabilized by electronegative substituents.

Restoration of granulomonocytopoiesis in CBA mice treated with maximum tolerated doses of adriamycin or cyclophosphane is strongly dependent on the maturation of precursor cells. Accelerated maturation is provided by the binding of the microenvironment cells to stem precursor cells. Restoration of erythroid precursors damaged by cytostatics is slower in the absence of such a binding.