Antitumour Organometallics. III. In Vivo Activity of Diphenylantimony(III) and Diorganotin(IV) Dithiophosphorus Derivatives Against P388 Leukemia

Diphenylantimony(III) and diorganotin(IV) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PR'(2) (R' = Ph, OPr-i) and R(2)Sn(S(2)PR'(2))(2) (R = n-Bu, Ph, R' = Ph; R = Ph, R' = OPr-i), have been screened against P388 leukemia in mice. All the compounds showed marginal activity towards this tumor system, some of them increasing the life span of the animals with more than 20%. The best results were obtained with (di-iso-propylphosphorodithioato)diphenylantimony(III) which exhibited a T/C value of 136%, at a dose of 5 mg/kg, administered on days 1,2 and 3 after tumor transplantation.     

Cytotoxic Activities of O-Cholesteryl-O-Phenyl-N-Phenylphosphoramidate and Its Organometallic Tin(lV) Derivatives

O-Cholesteryl-O-phenyl-N-phenylphosphoramidate (1) and four organotin (lV) derivatives of the ambidentate O-cholesteryl-O -phenyl phosphorothioate ligand formulated as Me(3) SnOSPR'R"(2), Ph(3)SnOSPR'R"(3), O(CH(2)CH(2)S)(2)Sn(n-Bu)OSPR'R"(4), S(CH(2)CH(2)S)(2)Sn(n-Bu)OSPR'R"(5), (R' = O-phenyl; R"= O-cholesteryl) were subjected to cytotoxicity screening against KB (nasopharingel carcinoma), OVCAR-5 (ovarium carcinoma) and SQC-1 UlSO (squamous cell cervix carcinoma) cell cultures. The results of the bioassay showed that these compounds possess potent antitumor activities against the studied human carcinoma cell lines.     

Bond strengths of toluenes, anilines, and phenols: to hammett or not

The Hammett equation correlates the effects of Y on many different chemical properties of YC(6)H(4)ZX families of compounds. One of the most surprising is that the Z-X bond dissociation enthalpy (BDE), a homolytic property, can be correlated for some 4-YC(6)H(4)ZX families with electrophilic substituent constants, sigma(p)(+)(Y), which were largely derived from the rates of the heterolytic S(N)1 solvolyses of para-substituted cumyl chlorides. Although there is no Hammett correlation of the C-X BDEs in 4-YC(6)H(4)CH(2)X (X = H, halide, OPh) families, there are good correlations of N-X BDEs with sigma(p)(+)(Y) in 4-YC(6)H(4)NHX (X = H, CH(3), OH, F) and excellent correlations of O-X BDEs with sigma(p)(+)(Y) in 4-YC(6)H(4)OX (X = H, CH(3), CH(2)Ph) families. The reasons for this varied behavior are discussed.     

苯基-二[(三甲基硅基)亚甲基]锡芳香酸酯合成及杀螨活性

合成了两个含硅混合三烃基锡芳香酸酯：苯基-二【（三甲基硅基）亚甲基】锡苯甲酸酯、苯基-二【（三甲基硅基）亚甲基】锡对硝基苯甲酸酯，利用IR、^1H NMR、^13C NMR和元素分析表征了其结构，并进行杀螨活性测定，发现这两个化合物在200mg／L时杀螨率均超过96％，具有较强的杀螨活性。     

Some New Organoantimony(V) Compounds

A series of antimony(V) compounds containing bifunctional ligands has been prepared. These compounds are of the structure (C₆H₅)₃ Sb (OOCR)₂ and (R = P ? C₆H₄OH₅ o-C₆X₄COOMe and cis-CX=CX where X = H, Cl and Br). These are the first antimony(V) compounds which contain functional reactive end groups.     

Aspirin analogues as dual cyclooxygenase-2/5-lipoxygenase inhibitors: synthesis, nitric oxide release, molecular modeling, and biological evaluation as anti-inflammatory agents

Analogues of aspirin were synthesized through an efficient one-step reaction in which the carboxyl group was replaced by an ethyl ester, and/or the acetoxy group was replaced by an N-substituted sulfonamide (SO(2)NHOR(2):R(2) =H, Me, CH(2)Ph) pharmacophore. These analogues were designed for evaluation as dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors. In vitro COX-1/COX-2 isozyme inhibition studies identified compounds 11 (CO(2) H, SO(2)NHOH), 12 (CO(2)H, SO(2)NHOCH(2)Ph), and 16 (CO(2)Et, SO(2)NHOH) as highly potent and selective COX-2 inhibitors (IC(50) range: 0.07-0.7 μM), which exhibited appreciable in vivo anti-inflammatory activity (ED(50) range: 23.1-31.4 mg kg(-1)). Moreover, compounds 11 (IC(50) =0.2 μM) and 16 (IC(50) =0.3 μM), with a sulfohydroxamic acid (SO(2)NHOH) moiety showed potent 5-LOX inhibitory activity. Furthermore, the SO(2)NHOH moiety present in compounds 11 and 16 was found to be a good nitric oxide (NO) donor upon incubation in phosphate buffer at pH 7.4. Molecular docking studies in the active binding site of COX-2 and 5-LOX provided complementary theoretical support for the experimental biological structure-activity data acquired.     

Antibacterial and Antifungal Activity of Zinc(II) Carboxylates With/Without N-Donor Organic Ligands

The antibacterial and antifungal activity of zinc(II) carboxylates with composition Zn(RCOO)(2)*nH(2)O(R =H-, CH(3) (-), CH(3)CH(2)CH(2) (-), (CH(3))(2)CH-, XCH(2) (-), X=Cl, Br, I, n=0 or 2), [ZnX(2)(Nia(+)CH(2)COO(-))(2)](Nia=nicotinamide, X=Cl, Br, I) and [Zn(XCH(2)COO)(2)(Caf)(2)]*2H(2)O (Car=caffeine, X=Cl, Br) is studied against bacterial strains Staphylococcus aureus, Escherichia coli and yeast Candida albicans. The structural types are assigned to the prepared compounds and the influence of (i) carboxylate chain length, (ii) substitution of hydrogen atom of carboxylate by halogen and (iii) presence of N-donor organic ligands on the biological activity is discussed.     

Toxicity of Certain Penta-Coordinated Organotin(IV) and Tetra-Coordinated Tin(II) Complexes of Heterocyclic beta-Diketones Against the Larvae of Aedes Aegypti (Liston)

Some organotin(IV) and tin(II) complexes of composition R(3)Sn[R'COC:CON(C(6)H(5))N:CCH(3)] (where R=C(4)H(9), R'=CH(3), C(3)H(5), p-ClC(6)H(4); R=C(6)H(5), R'=C(6)H(5) and p-ClC(6)H(4)) and Sn[p-ClC(6)H(4)COC:CON(C(6)H(5))N:CCH(3)](2) were screened for their toxicity against Aedes aegypti larvae. Organotin(IV) complexes were more active than tin(II) complexes.     

三烃基锡锂试剂R3SnLi制备方法的改进

以含金属钠1.2%的高分散锂钠合金粉未代替普通的金属锂,高收率地制备了三烃基锡锂R_3SnLi(R=Me,(?)-Bu,Ph)的四氢呋喃溶液。     

Spectral Studies and Bactericidal, Fungicidal, Insecticidal and Parasitological Activities of Organotin(IV) Complexes of Thio Schiff Bases Having no Donor Atoms

Twelve new organotin(IV) complexes of the type RnSnLm [where n = 3, m = 1, R = CH₃ or C₆H₅; n = 2, m = 2, R = C₆H₅ or C₄H₉ ; L = anion of Schiff bases derived from the condensation of 2-amino-5-(o-anisyl)-l,3,4-thiadiazole with salicylaldehyde (HL-1), 2- hydroxynaphthaldehyde (HL-2) and 2-hydroxyacetophenone (HL-3)] have been synthesized and characterized by elemental analysis, molar conductances, electronic, infrared, far-infrared, ¹H NMR and ¹¹⁹Sn Mössbauer spectral studies. Thermal studies of two complexes, viz., Ph₃Sn (L-1) and Ph₂Sn(L-2)₂ have been carried out in the temperature range 25-1000∘C using TG, DTG and DTA techniques. All these complexes decompose gradually with the formation of SnO₂ as an end product. In vitro antimicrobial activity of the Schiff bases and their complexes has also been determined against Streptococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus Penicillin resistance (2500 units), Candida albicans, Cryptococcus neoformans, Sporotrichum schenckii, Trichophyton mentagrophytes and Aspergillus fumigatus. The Schiff bases (HL-1), (HL-2) and the organotin(IV) compounds have also been tested against various important herbicidal, fungicidal, insecticidal species and also for parasitological activity against freeliving nematode.     

Homolytic cleavage and aggregation processes in cyclopentadienylchromium chemistry

The reactivity of the cyclopentadienylchromium tricarbonyl dimer [CpCr(CO)3]2 (Cp = C5H5, 1) toward several classes of organo-P-, -S- and -N-compounds will be described. The organic substrates include the following: (i) bis(diphenylthiophosphinyl)disulfane, R2P(S)SSP(S)R2; (ii) bis(thiophosphoryl)disulfane, (RO)2P(S)SSP(S)(OR)2; (iii) tetraalkylthiuram disulfides, R2NC(S)SSC(S)NR2; (iv) tetraalkyldiphosphine disulfides, R2P(S)P(S)R2; (v) dibenzothiazolyl disulfide, (C6H4NSC)2; and (vi) Lawesson's reagent, (CH3OC6H4)2P2S4. The primary products, namely, the complexes CpCr(CO)2(SPR2), CpCr(CO)2)(S2CNR2), CpCr(CO)2(SCSN(C6H4)), and CpCr(CO)2(SPC6H4OCH3), containing the thiophosphinito, dithiocarbamate, 2-mercaptobenzothiazole, and dithiophosphorane ligands, respectively, arise from facile cleavage of the S-S, P-P, and P-S bonds in the organic substrates. Further treatment of these complexes with 1 under thermal activation results in cleavage of C-X (X = N, S), P-S, and Cr-E (E = C, N, P, S) bonds, accompanied by C-C and P-P bond formation in some cases, generating a variety of organometallic compounds belonging to the phosphido, phosphinidene, thiocarbenoid, dithiooxamide, aminocarbyne, aminoalkenylacyl, and cuboidal types.     

Synthesis and Antioxidant Activity Evaluation of New Compounds from Hydrazinecarbothioamide and 1,2,4-Triazole Class Containing Diarylsulfone and 2,4-Difluorophenyl Moieties

In the present investigation, new hydrazinecarbothioamides 4–6 were synthesized by reaction of 4-(4-X-phenylsulfonyl)benzoic acids hydrazides (X= H, Cl, Br) 1–3 with 2,4-difluorophenyl isothiocyanate and further these were treated with sodium hydroxide to obtain 1,2,4-triazole-3-thione derivatives 7–9. The reaction of 7–9 with α-halogenated ketones, in basic media, afforded new S-alkylated derivatives 10–15. The structures of the synthesized compounds have been established on the basis of ¹H-NMR, ¹³C-NMR, IR, mass spectral studies and elemental analysis. The antioxidant activity of all compounds has been screened. Hydrazinecarbothioamides 4–6 showed excellent antioxidant activity and 1,2,4-triazole-3-thiones 7–9 showed good antioxidant activity using the DPPH method.     

三苄基锡炔基膦酸酯的合成及波谱分析

合成了6个新的三苄基锡炔基瞵酸酯[(PhCH2)3Sn]2O2P(O)C≡CR(R=n-C5H11,n-C6H13,n-C7H15,Ph,CH2OCH3,CH2OC2H5),对产物进行了红外光谱及核磁共振氢谱分析。     

Insecticidal Effects of Organotin(IV) Compounds on Plutella Xylostella (L.) Larvae. II. Inhibitory Potencies Against Acetylcholinesterase and Evidence for Synergism in Tests With Bacillus Thuringiensis(BER.) and Malathion

Features of pesticide synergism and acetylcholinesterase (AChE) inhibition (in vitro) were studied using a selected range of organotin compounds against the early 4th instar larvae of a highly resistant strain of the diamondback moth (DBM), Plutella xylostella, a major universal pest of cruciferous vegetables.Fourteen triorganotin compounds were evaluated for their ability to enhance the toxicity of the microbial insecticide, Bacillus thuringiensis (BT) and of the commercial insecticide, Malathion to Plutella xylostella larvae. Supplemental synergism was observed with triphenyl- and tricyclopentyltin hydroxides in combinations with Bacillus thuringiensis. Increased synergism was observed with an increase in the number of cyclopentyl groups on tin in the mixed series, Cyp(n) Ph(3-n) SnX, where X = OH, and 1-(1,2,4-triazolyl). The combination of (p-chlorophenyl)diphenyltin N,N-dimethyldithiocarbamate at LD(10) and LD(25) concentrations with sublethal concentrations of Malathion as well as of tricyclohexyltin methanesulphonate at the 0.01% (w/v) concentration with Malathion exerted strong synergistic effects (supplemental synergism) with toxicity index (T.I) values of 7.2, 19.8 and 10.1, respectively.Studies on the in vitro inhibition of acetylcholinesterase prepared from the DBM larvae showed that while most of the triorganotin Compounds tested were without effect on the enzyme, compounds containing the thiocarbamylacetate or the dithiocarbamylacetate moieties demonstrated appreciable levels of inhibition, being comparable in efficacy to commercial grades of Malathion and Methomyl.     

三苯基锡(Ⅳ)四氢吡咯荒酸酯的合成、表征、性质及晶体结构

用三苯基氯化锡和四氢吡咯荒酸钠反应 ,合成了三苯基锡 ( )四氢吡咯荒酸酯。通过元素分析、红外光谱和氢核磁共振谱对其结构进行了表征。用 X-射线单晶衍射测定了该化合物的晶体结构。结果表明 ,化合物中锡原子呈五配位畸变三角双锥构型     

离子液体催化2-氯噻吩氯甲基化反应研究

以2-氯噻吩、多聚甲醛为原料,以离子液体[C2mim]Br、[C3mim]Br、[C4mim]Br、[C5mim]Br、[C6mim]Br、[C7mim]Br、[C8mim]Br、[C12mim]Br、[Bmim]PF6、[Bmim]BF4、[Bmim]C4F9SO3和[Bmim]Cl为催化剂进行氯甲基化反应,得到产物2-氯-3-氯甲基噻吩。研究表明,离子液体可以促进2-氯噻吩的氯甲基化反应,具有相转移催化剂的效果,并且以[C4mim]Br和[C8mim]Br的催化效果为佳。反应最佳条件为:离子液体[C8mim]Br摩尔分数为5%(相对于2-氯噻吩),温度40℃,反应时间8h,产物产率可达92.1%。     

NMR-study of the stereochemistry and dynamic behaviour of thioacrylamides

Several model thioacrylamides, Me₂N CH = C(R) C(S) NMe₂ (R = H, Ph — 2a, b ) and (p)MeO C₆H₄ NH CHC(R) C(S) NMe₂ (R = H, Ph — 3a, b ) have been synthesized. The ¹H-n.m.r. spectra have been taken for discussing the E/Z-isomerism of the thioacrylamides and the assignment further strengthened by an added LIS-study. The 2-unsubstituted compounds have been found to exist exclusively in preferred configurations/conformations: 2a — E(s-cis); 3a — Z(s-cis); the 2-phenylsubstituted analogs are of divergent behaviour: in 2b the C(S) NMe₂ moiety is found to be twisted out of the common plane, and 3b prefers the flat s-trans conformations (E(s-trans) ⇌ Z(s-trans)). The compounds show restricted rotations about C¹, N- and C³, N-partial double bonds. The corresponding rotational barriers, determined as ΔG-values by dynamic n.m.r. spectroscopy, are discussed with respect to (i) the resonance branch at C¹, (ii) the influence of substituents, and (iii) the effect of steric hindrance in the thioacrylamide moiety generally.     

Ethylene polymerisation by Ni–diphosphine azine complexes

The properties of [NiX(PR₂CH₂C(Bu^t)?NN?C(Bu^t)CH₂PR₂)]⁺ complexes (where X = Br, and R = cyclohexyl (Cy), isopropyl (Prⁱ), tert‐butyl (Bu^t), phenyl (Ph); X = Cl or I, and R = cyclohexyl) as catalysts for the polymerisation of ethylene were evaluated with or without the co‐catalysts methylaluminoxane (MAO), diethylaluminium chloride, trimethylaluminium or tri(isobutyl)aluminium. Their efficiency depends on the characteristics of the halogen (X) and the R group of the diphosphine azine ligand. Bromide (X) strongly enhances the catalytic properties of the complexes within the R order Cy > Prⁱ > Ph > Bu^t. Temperature, co‐catalyst ratio (Al/Ni) and complex concentration also influence the catalytic activity. The best results were obtained with [NiBr{PCy₂CH₂C(Bu^t)?NN?C(Bu^t)CH₂PCy₂}]Br activated by MAO (A = 25.8 kg (mol Ni)^?1 bar^?1 h^?1). The polymers were characterised using NMR and differential scanning calorimetry as branched polyethylenes, the number of branches increasing with the temperature of polymerisation. The molecular weights of the polymers were estimated using NMR. A proposal for the catalyst active precursor is made on the basis of experimental data and molecular orbital calculations. Copyright © 2007 Society of Chemical Industry     

In vitro antitumour activity of some triorganophosphinegold(i) thionucleobases

A series of phosphinegold(I) thionucleobase analogues, [R(3)PAu(SR(x))] (R = Et, Ph or chexyl; HSR(1) = 2-mercaptobenzoic acid, HSR(2) = 2-thiouracil, HSR(3) = 6-mercaptopurine and HSR(4) = 6-thioguanine) have been examined for their in vitro cytotoxicity in L1210 murine leukemia cells in culture. The range of ID(50) values (continuous 48 h exposure) for the complexes is 0.041 - 0.131 muM. The complexes with SR(3) and SR(3) are generally the most active; however, there is no clear trend associated with the phosphine ligands.     

Surface decorated platinum carbonyl clusters

Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt(13)(CO)(12){Cd(5)(μ-Br)(5)Br(2)(dmf)(3)}(2)](2-) (1), [Pt(19)(CO)(17){Cd(5)(μ-Br)(5)Br(3)(Me(2)CO)(2)}{Cd(5)(μ-Br)(5)Br(Me(2)CO)(4)}](2-) (2), [H(2)Pt(26)(CO)(20)(CdBr)(12)](8-) (3) and [H(4)Pt(26)(CO)(20)(CdBr)(12)(PtBr)(x)](6-) (4) (x = 0-2), have been obtained from the reactions between [Pt(3n)(CO)(6n)](2-) (n = 2-6) and CdBr(2)·H(2)O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt(26)Cd(12) metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters.