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Linked bis(ketimine) ( 1 ) can be prepared with the reaction of excess 2,4-pentanedione and 4,4′-methylene-bis(2,6-diisopropylaniline) in methanol in the presence of catalytic amount of formic acid. The dialuminum alkyl complexes containing the linked bis(ketiminate) dianionic ligands, [OC(Me)CHC(Me)N(2,6- i Pr 2 C 6 H 2 -4)AlR 2 ] 2 CH 2 ( 2 , R = Me; 3 , R = Et), were prepared by a reaction of 2 equiv AlR 3 with [OC(Me)CHC(Me)NH(2,6- i Pr 2 C 6 H 2 -4)] 2 CH 2 in methylene chloride. Reactions of 2 with 2 and 4 equiv of I 2 gave corresponding aluminum iodo complexes 4 and 5 , respectively. Treatment of 5 with 2 equiv of AgBF 4 , however, gave a diboron complex, [OC(Me)CHC(Me)N(2,6- i Pr 2 C 6 H 2 -4)BF 2 ] 2 CH 2 ( 6 ), in 18% isolated yield. All new complexes have been characterized by 1 H and 13 C NMR spectroscopy and complexes 2 , 3 , and 6 are also confirmed by X-ray diffraction.

The lithiated pyrrolyl ligand, {Li[C 4 H 2 N(CH 2 NMe 2 ) 2 -2,5]} 2 ( 1 ) was synthesized and structurally characterized. Reaction of 1 with YCl 3 in the molar ratio 1:1 in diethyl ether at room temperature afforded a di-yttrium di-lithium tetranuclear complex, {[C 4 H 2 N(CH 2 NMe 2 ) 2 -2,5]YCl 2 (μ-Cl) · Li(OEt 2 ) 2 } 2 ( 2 ) in 87% yield. Compounds 1 and 2 were characterized by NMR spectroscopy and single crystal X-ray crystallography. Compound 1 shows high reactivity for the ring-opening polymerization of e-caprolactone.

The mechanism of N-heterocyclic carbene (NHC) catalyzed transesterification reactions have been studied using density functional theory. Our study shows that the role of NHC is to assist proton transfer from alcohol to the carbonyl oxygen, forming the tetrahedral intermediate, which then decomposes to the acylated product. Our predicted activation energies are in fine agreement with the observed reaction rates. An alternative approach, which uses the tetrahedral intermediate as the transition state mimic, provides satisfactory predictions.

Reactions of the ethylene- and methylene-bridged bis(imidazolium) salts with an equivalent amount of silver oxide in dichloromethane at room temperature produced readily the silver NHC compounds [Ag 2 LBr 2 ]. These compounds are partially soluble in DMF. The X-ray structure determination on 3d (L = 1,1′-dibenzyl-3,3′-ethylenediimidazolin-2,2′-diylidene) reveals the formation of bromide bibridged (Ag 2 LBr 2 ) n chains and a unique supramolecular motif with weak Ag⋯Ag interactions of 3.429 A. Similar to monomeric silver(I) NHC complexes, the silver coordination polymers can also act as carbene transfer reagents for the formation of chelating palladium NHC complexes in excellent yields.

The silver complex of PCNHCP was identified as [Ag3(μ-Cl)(PCNHCP)2]Cl2 (1). Anion exchange of 1 with AgNO3 affords a white compound, which crystallizes into two forms, [Ag3(μ-Cl)(PCNHCP)]2(NO3)2 (2a) and [Ag3(Cl)(NO3)(0.5DMF)(PCNHCP)2]NO3 (2b), from different solvent combinations. Their structural determination reveals interesting structural features, including a short Ag···Ag interaction in both of them. Unlike the common preparation of ruthenium(II) NHC complexes in the literature, a novel silver carbene transfer reaction between 1 and RuCl2(PPh)3 produces fac-[Ru2(μ-Cl)3(PCNHCP)2]Cl (3) in good yield. The nonredox nature of the carbene transfer reaction is different from that of an earlier report and shows that the preparation of divalent ruthenium NHC complexes via silver carbene transfer is a feasible synthetic route. Significantly, complex 3 can also be prepared directly from PCNHCP·HCl and RuCl2(PPh3)3 in the absence of base. Reactions of 3 with CO, phenylacetylene, and pyridine afford mer complexe...

A series of imidzoalium salt, L · HCl, for the potentially bidentate pyrazole/N-heterocyclic carbene was synthesized. Reactions of a 2:1 mixture between L · HCl bearing bulky N-substitution and Ag2O produced Ag(L)Cl, whereas a novel compound with unique stoichiometry AgL2(AgCl)0.5Cl was produced from L · HCl bearing N-methyl group under identical condition. Reactions of L · HCl with PdCl2 produced zwitterionic PdIICl3L · H. Selected structural determinations on L · HCl, Ag(L)Cl, AgL2(AgCl)0.5Cl, and PdIICl3L · H revealed intriguing crystal chemistry in which the less-stable gauche rotamers were obtained exclusively. A preliminary application of the zwitterionic complexes, PdIICl3L · H, in Heck coupling reaction of aryl bromide with n-butyl acrylate shows effective activity.

The reaction of MeC(O)C(H)=C(Me)NHAr (Ar = 2,6-diisopropylphenyl) (1) with excess LiAlH4 in diethyl ether at −78 °C generates [AlH(OCMeCHCMeNAr)2] (2) in 76% yield. The aluminum formate compound [Al(OCMeCHCMeNAr)2(OCOH)] (3) can be isolated from the reaction of 2 with CO2 in 93% yield. Compound 3 is thermally stable and remains unchanged when heated under vacuum at 100 °C for 24 h. Similarly, a solution of 2 in dichloromethane reacts with carbon disulfide or phenyl isocyanate at room temperature to yield the insertion products [Al(OCMeCHCMeNAr)2(SCHS)] (4) and [Al(OCMeCHCMeNAr)2(OCH=NPh)] (5), respectively, in 80% and 92% yield. Reaction of 2 with 1 equiv. of urethane in toluene at refluxing temperature for 1 h yields the aluminum isocyanate compound [Al(OCMeCHCMeNAr)2(NCO)] (6). The molecular structures of compounds 2−6 have been determined by X-ray crystallography. Density functional calculations show that the isomer of compound 2 with an N−N trans arrangement is 3.1 kcal·mol−1 lower in energy than the O−O trans isomer. Inserting CO2 into the Al−H bond of compound 2 results in the formation of the formate compound 3; this reaction is predicted to be exothermic by 29.8 kcal·mol−1. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

A series of imidazolium chlorides as ligand precursors, L · HCl (L = (1-R)-(3-diphenylphosphanylethyl)-imidazol-2-ylidene; R = aryl, benzyl, naphthylmethyl), for the phosphine-functionalized N -heterocyclic carbene (NHC), L, were prepared by a convenient synthetic procedure of reacting 1,2-dichloroethane with appropriate N -substituted imidazoles to give (β-chloroethyl)imidazolium chlorides, which were subsequently reacted with HPPh 2 producing L · HCl in good yield. Palladium complexes of L, PdLCl 2 ( 4 ), were prepared by a one pot reaction of PdCl 2 , sodium acetate, and L · HCl in DMSO. Complexes 4b (R = naphthylmethyl) and 4e (R = m -methoxybenzyl) were characterized by X-ray crystallography. Catalytic studies have shown that the palladium complexes are efficient in Suzuki coupling reactions of aryl bromides with phenylboronic acid.

Treatment of (t-)BuN=TiCl(2)Py(3) with 2 equiv lithium ketiminate compound, Li[OCMeCHCMeN(Ar)] (where Ar = 2,6-diisopropylphenyl), in toluene at room temperature gave (t-)BuN=Ti[OCMeCHCMeN(Ar)](2) (1) in high yield. The reaction of 1 with phenyl isocyanate at room-temperature resulted in imido ligand exchange producing PhN=Ti[OCMeCHCMeN(Ar)](2) (2). Compound 1 decomposed at 90 degrees C to form a terminal titanium oxo compound O=Ti[OCMeCHCMeN(Ar)](2) (3) and (t-)BuNHCMeCHCMeNAr (4). Also, the compound 3 could be obtained by reacting 1 with CO(2) under mild condition. Similarly, while 1 reacts with an excess of carbon disulfide, a novel terminal titanium sulfido compound S=Ti[OCMeCHCMeN(Ar)](2) (5) was formed via a C=S bond breaking reaction. A novel titanium isocyanate compound Ti[OCMeCHCMeN(Ar)](2)(NCO)(OEt) (6) was formed on heating 1 with 1 equiv of urethane, H(2)NCOOEt. Compounds 1-6 have been characterized by (1)H and (13)C NMR spectroscopies. The molecular structures of 1, 3, 5, and 6 were determined by single-crystal X-ray diffraction. A theoretical calculation predicted that the cleavage of the C-S double bonds for carbon disulfide with the Ti=N bond of compound 1 was estimated at ca. 21.8 kcal.mol(-1) exothermic.

Reactions of HfCl4 with 2 and 3 equiv. of Li[C4H3N(CH2NMe2)-2] in toluene afford HfCl2[C4H3N(CH2NMe2)-2]2 (1) and HfCl[C4H3N(CH2NMe2)-2]3 (2), respectively. Transmetallation reaction of 1 with 2 equiv. of MeLi results in a hafnium dimethyl compound HfMe2[C4H3N(CH2NMe2)-2]2 (3). A variable-temperature 1H NMR spectroscopic study shows that the activation energy for the dissociation/association of the NMe2 units of compound 2 in solution is ca. 13.6 kcal/mol. Compounds 1–3 are characterized by NMR spectroscopy and single crystal X-ray diffraction. A polymerization study shows that compounds 1 and 3 exhibit moderate activity toward ethylene in the presence of TIBA and MAO.

Black crystals of C60·μ-O{FeIII(OEP)}2·C6H6 and 2C60·{FeIII(OEPO)}2·4C6H6 suitable for single-crystal X-ray diffraction studies have been obtained by growth from benzene solutions of the appropriate binuclear metalloporphyrin and the fullerene. C60·μ-O{FeIII(OEP)}2·C6H6 crystallizes with two molecules of μ-O{FeIII(OEP)}2, two fully ordered molecules of C60, and two molecules of benzene in the asymmetric unit. Each independent molecule of μ-O{FeIII(OEP)}2 makes close contact with two fullerene molecules. In C60·μ-O{FeIII(OEP)}2·C6H6 the Fe−O−Fe angles (150.18(11)° and 151.89(11)°) are markedly bent with a benzene molecule wedged into the opening between the two porphyrins, whereas in the triclinic and monoclinic polymorphs of μ-O{FeIII(OEP)}2 the Fe−O−Fe angles are more nearly linear (172.16(17)° and 176.2(2)°, respectively). The structure of 2C60·{FeIII(OEPO)}2·4C6H6 consists of a centrosymmetric {FeIII(OEPO)}2 molecule in which the two macrocycles are connected to one another through axial coordination o...

The trimetallic nitride template (TNT) approach has been successfully utilized to prepare the new endohedral Lu 3 N@C 8 0 . Well-ordered crystals of Lu 3 N@C 8 0 .5 (o-xylene) and Sc 3 N@C 8 0 . 5 (o-xylene) form upon cooling of o-xylene solutions of these endohedrals and they are isomorphous. Although the positions of the fullerene cage (which is fully ordered and located at a crystallographic center of symmetry) and the o-xylene molecules are nearly identical in these two structures, the positioning of the metal ions in the two crystals differ in significant ways. However, the expected difference in sizes of lutetium and scandium does not affect the dimensions of the C 8 0 cage. Nevertheless, the positions of the metal atoms do produce a slight outward dislocation of the immediately adjacent carbon atoms.

In this mini-review, we present a summary of our recent work in the field of palladium-catalyzed cross-coupling reactions, with emphasis on the use of nucleophilic N-heterocyclic carbenes (NHC) as ancillary ligand. The palladium-mediated coupling reactions investigated include the Suzuki–Miyaura, Kumada–Tamao–Corriu, Heck, Sonogashira, Stille, Hiyama and aryl amination reactions.

Pyridinimine-modified Pd(II) complexes of general formulae (N-N′)Pd(Y)2 catalyze the methoxycarbonylation of styrene to give dimethyl phenylsuccinate as the largely major product [N-N′ = py-2-C(R)N(2,6-R′C6H3), R = H, Me; R′ = Me, i-Pr; 6-Mepy-2-C(H)N[2,6-(i-Pr)2C6H3]; py-2-C(H)N(C6H5); Y = acetate, trifluoroacetate]. The influence of various catalytic parameters on the overall conversion of styrene to carbonylated products and on the product selectivity has been studied by systematically varying the type of palladium initiator, the concentrations of organic oxidant (1,4-benzoquinone) and protic acid (p-toluenesulfonic acid), and the CO pressure. By an appropriate choice of the structure of the pyridinimine ligand and of the reaction parameters, turn-over numbers as high as 96 and selectivities in dimethyl phenylsuccinate as high as 98% were obtained. In particular, the overall conversion of styrene is controlled by the steric properties of the alkyl substituents on the imine aryl group, while the nature of the substituent (H or Me) on the imine carbon influences the selectivity. The addition of 2 equivalents of TsOH to the catalytic mixtures generally increased the styrene conversion but lowered the selectivity in dimethyl phenylsuccinate due to greater production of methyl 3,6-diphenyl-4-oxohexanoate. Further additions of TsOH (up to 6 equivalents) resulted in better selectivities and lower conversions for all precursors.

An effective organocatalytic system based on an amido-functionalized imidazolium salt allows the synthesis of biaryls from arylhalides and benzene.

In an extended phase I/II study we evaluated 36 prostate cancer patients with local recurrence after radiotherapy who received single or repeated cycles of replication-deficient adenoviral vector (ADV)-mediated herpes simplex virus-thymidine kinase (HSV-tk) plus ganciclovir (GCV) in situ gene therapy with respect to serum PSA levels, alterations in immune cells, and numbers of apoptotic cells in needle biopsies. An initial cycle of HSV-tk plus GCV gene therapy caused a significant prolongation of the mean serum PSA-doubling time (PSADT) from 15.9 to 42.5 months (p = 0.0271) and in 28 of the injected patients (77.8%) there was a mean PSA reduction (PSAR) of 28%. It took a mean of 8.5 months for the PSA to return to the initial PSA (TR-PSA) value. A repeated cycle of gene therapy failed to significantly extend PSADT but did result in significant increases in PSAR (29.4%) and TR-PSA (10.5 months). Moderately increased serum adenovirus antibody titers were generally observed 2 weeks after initial vector injection. Also at this time there was a statistically significant increase in the mean percent of CD8(+) T cells positive for the HLA-DR marker of activation in peripheral blood (p = 0.0088). Studies using prostate biopsies obtained at the same time point demonstrated that vector DNA was detectable by PCR in most samples yet all patients remained positive for prostate cancer in at least one biopsy core. Further analysis demonstrated a correlation between the level of CD8(+) cells and the number of apoptotic cells in biopsies containing cancer cells (p = 0.042). We conclude that repeated cycles of in situ HSV-tk plus GCV gene therapy can be administered to prostate cancer patients who failed radiotherapy and have a localized recurrence. Biological responses to this experimental therapy including increases in PSADT, PSAR, and TR-PSA, and activated CD8(+) T cells present in the peripheral blood, were demonstrated. Interestingly, the density of CD8(+) cells in posttreatment biopsies correlated with the number of apoptotic cells.

The synthesis and characterization by X-ray crystallography of the complexes [Ir(cod)(py)(L)]PF6 (L = IMes, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (2); L = IPr, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (3); L = ICy, 1,3-bis(cyclohexyl)imidazol-2-ylidene (4)) are reported. Complexes 2−4 have been employed as catalysts for transfer hydrogenation reactions from 2-propanol to a number of unsaturated substrates and their activity compared with that of the related cationic iridium(I) species [Ir(cod)(py)(SIMes)]PF6 (1), [Ir(cod)(py)(PCy3)]PF6 (5), and complexes formed in situ from [Ir(cod)(py)2]PF6 and diazabutadienes (RNCHCHNR, DAB-R; R = cyclohexyl, DAB-Cy; R = 2,4,6-trimethylphenyl, DAB-Mes; R = adamantyl, DAB-Ad; R = 2,4,6-trimethoxyphenyl, DAB-trimethoxyphenyl). All complexes tested were found to be active catalysts for transfer hydrogenation of ketones, with complex 4 displaying the highest activity. Complex 4 also exhibits moderate activity toward simple olefins and an aromatic nitro co...

We previously demonstrated significant therapeutic activities associated with adenoviral vector-mediated Herpes Simplex Virus/thymidine kinase (AdHSV-tk) with ganciclovir (GCV) in situ gene therapy in the RM-1 orthotopic mouse prostate cancer model and interleukin-12 (AdmIL-12) in situ gene therapy in the RM-9 orthotopic mouse prostate model for prostate cancer. In both protocols, local cytotoxicity and activities against pre-established lung metastases were demonstrated. To test whether combined AdHSV-tk+GCV+IL-12 gene therapy would lead to enhanced therapeutic effects when compared to either treatment alone, we used RM-9 mouse prostate cancer cells in both orthotopic and pre-established lung metastases models of prostate cancer. Combined treatment with a single injection of optimal doses of AdHSV-tk+GCV or AdmIL-12 led to significantly increased suppression of orthotopic tumor growth. IL-12 gene therapy alone was more effective than AdHSV-tk+GCV in suppressing spontaneous lymph node metastases and pre-established lung metastases but combination gene therapy did not result in additional anti-metastatic activities. Combination gene therapy also did not achieve significantly better animal survival compared to AdHSV-tk+GCV or AdmIL-12 alone. Analysis of localized antitumor activities demonstrated that AdHSV-tk+GCV therapy induced higher levels of necrosis compared to AdmIL-12 or combination therapy. However, both treatments alone and combination therapy produced similar increases in apoptotic index. To address the possible mechanisms of locally co-operative cytotoxic activities, we analyzed the systemic natural killer (NK) response and the numbers of tumor-infiltrating immune cells using quantitative immunohistochemical analysis. AdHSV-tk+GCV therapy alone led to detectable increases in iNOS-positive cells, CD4+and CD8+T-cells and moderately increased numbers of F4/80 (macrophage selective)-positive cells within treated tumors. In contrast, AdmIL-12 elicited a highly robust pattern of tumor infiltration for all four of these immune cells that was in general mimicked by combination therapy. Further analysis of the accumulation of transforming growth factor-beta1 (TGF-beta1) immunohistochemical staining demonstrated that AdHSV-tk+GCV treatment, but not AdmIL-12 treatment, produced cancer cell-associated increases in this cytokine relative to control Ad-beta-gal injections. Interestingly, local injection with AdHSV-tk+GCV induced significant splenocyte-derived NK cell cytolytic activities with maximal response 7 days following treatment, whereas AdmIL-12 injection produced significantly higher NK activity with maximal response 2 days following injection. The combined treatment produced a higher systemic NK response over the 14-day treatment period. Depletion of NK cells in vivo demonstrated that this immunocyte subpopulation was responsible for early locally cytotoxic activities induced by AdHSV-tk+GCV but not AdmIL-12 and that NK activities were largely responsible for activities against pre-established metastases generated by both gene therapy protocols. Prostate Cancer and Prostatic Diseases (2001) 4, 44-55

The new cationic iridium carbene complex [Ir(cod)(py)(SIMes)]PF6 (2) has been synthesized by reaction of [Ir(cod)(py)2]PF6 with SIMes. Complex 2 is an active hydrogenation catalyst capable of hydrogenating simple olefins at room temperature and atmospheric pressure of hydrogen.

Using an exchange reaction involving one PCy3 ligand in HRu(CO)Cl(PCy3)2 (1) for one IMes, a ruthenium−hydride complex HRu(CO)Cl(PCy3)(IMes) (2) has been prepared. Complex 2 is an active catalyst in the hydrogenation of alkenes. A TON of 24 000 h-1 has been obtained at 100 °C under 4 atm of hydrogen. Addition of HBF4·OEt2 as cocatalyst enhanced the catalytic activity.

The optically pure 2,6-bis(imino)pyridyl ligands (R)-2,6-bis{1-[α-methylbenzylimine]ethyl}pyridine [(R)-2,6-py(NCHMePh)2] and (S)-2,6-bis{1-(1-naphthyl)ethylimine]ethyl}pyridine [(S)-2,6-py(NCHMeNaph)2] have been prepared by condensation of 2,6-diacetylpyridine with (R)-(+)-α-methylbenzylamine and (S)-(−)-1-(1-naphthyl)ethylamine, respectively. These two ligands and others bearing different substituents on the imine nitrogen atoms (i.e., c-C6H11, C6H5, 2,6-Me2Ph) form, in combination with ruthenium(II) fragments, efficient catalysts for the cyclopropanation of styrene with ethyl diazoacetate (EDA). The catalyst precursors have the general formula RuCl2(PPh3){2,6-py(NR)2} (R = Cy,1; Ph, 6; CHMeNaph, 7; CHMePh, 8). It is generally found that the catalytic activity increases with the size of the substituents on the imine nitrogen atoms. Consistently, the solvento complex RuCl2{2,6-py(N(2,6-Me2Ph2)2}·CH2Cl2 is the most efficient in the series. Best results in terms of activity, diastereoselectivity, and enant...

Treatment of RhCl(ttp*) (ttp*=( S , S )-PhP(CH 2 CHMeCH 2 PPh 2 ) 2 ) with NaBH 4 produced Rh(BH 4 )(ttp*). The reaction of RuCl 2 (ttp*) with NaBH 4 produced RuH(BH 4 )(ttp*). The complexes RhCl(ttp*), RuCl 2 (ttp*), Rh(BH 4 )(ttp*), and RuH(BH 4 )(ttp*) were found to be catalytically active for the hydrogenation of α-acetamidocinnamic acid.

The hydroformylation of 1-hexene with syngas (40 bar of 1:1 CO/H2) in the presence of the catalyst precursor RhH(CO)(PPh3)3 has been studied by high-pressure NMR spectroscopy in a 10 mm sapphire tube equipped with a Ti-alloy valve. Except for RhH(CO)2(PPh3)2, no direct observation of labile intermediates involved in the catalytic cycle has been detected; however as many as four rhodium resting states have been seen, and some factors controlling their formation/interconversion/inhibition have been identified. The information gathered from this in situ investigation is particularly relevant to a better understanding of the inhibiting action of the CO pressure as well as the positive action of PPh3 addition.

The effects of the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) on prostate cancer metastasis in vivo were evaluated in the mouse prostate reconstitution (MPR) model. MPRs were produced by infection of either heterozygous (+/−) or nullizygous (−/−) p53-mutant fetal prostatic epithelial cells with the recombinant retrovirus Zipras/myc 9. Previous studies have documented that loss of p53 function potentiates metastasis in this model system. MPRs were grafted into homozygous (+/+) p53 male mice, fed a 4-HPR containing diet or a control diet and maintained until the status of tumor progression dictated sacrifice. Under these experimental conditions, treatment with 4-HPR did not have a significant effect on primary tumor wet weight for either p53 +/− or p53 −/− MPRs. For, p53 +/− MPRs the animals fed the 4-HPR diet had a slight improvement in survival and a significant reduction in the number of mesenteric metastases (P=0.0477, t-test). Notably, in p53 +/− MPRs the incidence of metastasis to lumbar spine and sternum was 92% in the control animals compared to 54% in the 4-HPR treated animals (P=0.035, χ2-test). In p53 −/− MPRs there was a trend toward a reduction in the number of soft tissue metastases to lung and liver in the 4-HPR group relative to the control diet group and a statistically significant reduction in the incidence of metastasis to bone was demonstrated in that 50% of control animals versus 30% of 4-HPR treated p53 −/− animals harbored bone metastases (P=0

In this work are described the syntheses of several new dppp-like ligands (dppp =1,3-bis(diphenylphosphino)propane) bearing different substituents on the carbon backbone and of their palladium(II) complexes with acetate or trifluoroacetate coligands (L). The complexes exhibit the general formula Pd(P−P)(L)2 and have been employed as catalyst precursors for the copolymerization of ethene and carbon monoxide in MeOH under experimental conditions that are comparable to those reported in the relevant literature and patents for dppp-based Pd(II) copolymerization catalysts. It has been found that the introduction of alkyl substituents in the 2-position of the carbon backbone of dppp does not significantly improve the performance of the corresponding catalyst precursors (highest productivity value 6.2 kg of copolymer (g of Pd h)-1 vs 5.4 kg of copolymer (g of Pd h)-1 for Pd(dppp)(L)2). In contrast, the productivity increases remarkably when methyl groups are introduced in both 1-positions of the diphosphine liga...

The water-soluble diphosphine (NaO3S(C6H4)CH2)2C(CH2PPh2)2 (Na2DPPPDS) was employed to prepare the bis-trifluoroacetate Pd(II) complex Pd(Na2DPPPDS)(CO2CF3)2·2THF (1). The catalytic performance of ...

Various five-coordinate ruthenium(II) complexes of the general formula RuCl2L, where L is a chiral triphosphine ligand, have been tested as catalyst precursors for the cyclopropanation of styrene u...

Interleukin-12 (IL-12) can elicit potent antitumoral effects that involve the recruitment of specific immune effector cells. We investigated the efficacy of a single injection of a recombinant adenovirus expressing murine IL-12 (AdmIL-12) directly into orthotopic mouse prostate carcinomas generated from a poorly immunogenic cell line (RM-9) derived from the mouse prostate reconstitution system. Significant growth suppression (> 50% reduction of tumor weight) and increased mean survival time (23.4 to 28.9 days) were observed compared with controls. Suppression of pre-established lung metastases was also observed following the injection of AdmIL-12 into the orthotopic tumor. Cytolytic natural killer cell activity was markedly enhanced 1-2 days after virus injection. Immunohistochemical analysis showed significantly elevated intratumoral infiltration of CD4+ and CD8+ T cells 7 days after virus injection. However, splenocyte-derived cytotoxic T lymphocytes were not detected during the 14 days following treatment. Increased numbers of nitric oxide synthase-positive macrophages were seen in the AdmIL-12 treated group 7 days following injection. Systemic inhibition of natural killer cells with antiasialo-GM1 serum led to increased numbers of lung metastases in AdmIL-12-treated orthotopic tumors but did not affect local tumor growth. In this model system the antitumor effects of a single injection of adenovirus-mediated IL-12 appears to be based to a large extent on the activation of nitric oxide synthase in macrophages and possibly T cell activities, whereas the relatively early cytolytic activity of natural killer cells are largely but not exclusively responsible for the antimetastatic effects.

Several bis-chelated palladium(II) complexes, [Pd(P-P)(N-N)x](PF6)2, containing binary combinations of diphosphine and dinitrogen ligands have been prepared and characterized. The diphosphine ligands comprise 1,3-bis(diphenylphosphino)propane (dppp), meso-2,4-bis(diphenylphosphino)pentane (meso-bdpp), rac-2,4-bis(diphenylphosphino)pentane (rac-bdpp) and 2,2′-bis(diphenylphosphinoethyl)pentane (Etdppp), while the dinitrogen ligands are either 2,2′-bipyridine (bipy; x=1) or 1,8-naphthyridine (napy; x=2). The structure of [Pd(meso-bdpp)(N,N′-bipy)](PF6)2·CH2Cl2 has been determined by an X-ray structural analysis. All the Pd(II) complexes have been tested as catalyst precursors for the copolymerization of carbon monoxide and ethene in methanol solution in either autoclaves or high-pressure sapphire NMR tubes. The combination of meso-bdpp and bipy at palladium, in conjuction with both 1,4-benzoquinone and p-toluenesulfonic acid, has shown the best catalytic performance. The different catalytic activities exhibited by the stereoisomers [Pd(meso-bdpp)(N,N′-bipy)]- (PF6)2 and [Pd(rac-bdpp)(N,N′-bipy)](PF6)2 has been interpreted in terms of the different spatial distribution of the phenyl rings around the metal center determined by the conformation of the six-membered metallaring.

A 3D supramolecular metal-organic host could be realized in solid in which the water assembly as a whole acted as a building block of the 3D framework with rectangular channels where guest molecules reside, adding a new dimension to water cluster research where the role of water has been shifted from its usual behavior of guest to that of a host. The crystal structure of the compound, {[Cu(mal) 2 ](picH) 2 ·5H 2 O} n , 1 [mal = malonate dianion, picH = protonated 2-amino-4-picoline], synthesized from purely aqueous media, shows that the Cu(II)-malonate 2D coordination polymeric sheets are locked together by the water assembly that lines up perpendicular to the Cu(II)-malonate sheets constituting a 3D infinite supramolecular host where within the channels protonated 2-amino-4-picoline auxiliary ligands are accommodated. A spirocyclic tetrameric water chain having a dimeric crown on it describes the composition of the water assembly that runs down the c-axis.

C21H26AuClN2, orthorhombic, Pbca (no. 61), a = 8.7507(1) Å, b = 15.8341(2) Å, c = 29.9642(4) Å, V = 4151.8 Å3, Z = 8, Rgt(F) = 0.0204, wRref(F2) = 0.0403, T = 150 K.

Reactions of RuCl(PPh3)(PCP) (PCP = 2,6-(PPh2CH2)2C6H3) with PhC⋮CH and HC⋮CC(OH)Ph2 gave the unusual coupling products RuCl(PPh3)(η4-PhCHC-2,6-(PPh2CH2)2C6H3) and RuCl(PPh3)(η4-Ph2C(OH)CHC-2,6-(PPh2CH2)2C6H3), respectively. Dehydration was observed in the coupling reactions of RuCl(PPh3)(PCP) with HC⋮CC(OH)PhMe and HC⋮C-cyclo-C6H10(OH). Thus, the coupling products RuCl(PPh3)(η4-CH2CPhCHC-2,6-(PPh2CH2)2C6H3) and RuCl(PPh3)(η4-cyclo-C6H9-CHC-2,6-(PPh2CH2)2C6H3) were obtained from the reactions of RuCl(PPh3)(PCP) with HC⋮CC(OH)PhMe and HC⋮C-cyclo-C6H10(OH), respectively. Treatment of [Ru(PMe3)2(PCP)]BF4 with PhC⋮CH produced [Ru(PMe3)2(η4-PhCHC-2,6-(PPh2CH2)2C6H3)]BF4.

A series of ruthenium complexes with the orthometallated ligand [2,6-(Ph2PCH2)2C6H3]− (PCP) was synthesized. Reaction of RuCl2(PPh3)3 with 1,3-(Ph2PCH2)2C6H4 produced the coordinatively unsaturated complex RuCl(PPh3)(PCP), which was characterized by X-ray crystallography. Treatment of RuCl(PPh3)(PCP) with 4-phenylpyridine (pyph) yielded RuCl(pyph)(PPh3)(PCP). Treatment of RuCl(PPh3)(PCP) with PMe3 and CO generated RuCl(PMe3)2(PCP) and RuCl(CO)2(PCP) respectively. Reactions of RuCl(PPh3)(PCP) with NaH in THF and NaBH4 in methanol gave RuH(PPh3)(PCP) and RuH(CO)(PPh3)(PCP) respectively. The hydride complex RuH(PMe3)2(PCP) was prepared by the reaction of RuCl(PMe3)2(PCP) with NaBH4.

Different benzoic acids containing electron-drawing groups can be converted into the corresponding coumarines or phtalides via the simple title reaction.

A wide range of heteroaromatic biaryls, required in organic and drug synthesis, can be prepared and the coupling proceeds with high regioselectivity.

In the presence of carbene complex PAL, the acids (I) and (IV) undergo decarboxylative coupling with aryl bromides as a new and regioselective access to heteroaromatic biaryls like (III) and (V).

Different amounts of AuCl4− (i.e. 3.0, 0.5 and 0.1 wt% of Au) were supported onto the anion-exchange resin Dowex Marathon MSA in its chloride form. A successive rapid reduction of the latter anchored Au-compound with NaBH4 combined with anion exchange reactions (i.e. replacement of chloride by acetate or carbonate) gave resin-stabilized Au-nanoparticles (NPs) of comparable size and size distribution. A screening of the catalytic performance of the obtained heterogenous catalysts in the aerobic oxidation reaction of selected diols to lactones in toluene revealed the carbonate form of the resin bearing 0.1 wt% of Au to be the most active catalytic system. The aerobic oxidation of aliphatic diols led to the formation of the corresponding dicarboxylic acid as side-product, which deactivates the catalyst. By washing the deactivated catalyst after each cycle with a solution of Na2CO3 in water restored the initial catalyst performance for at least four consecutive catalytic cycles.

A novel cyclometalation pathway to form CC-type palladacycles is reported. Unlike common donor-assisted cyclometalation, the NH(CO) auxiliary group undergoes a deprotonation step to form a palladalactam intermediate. The coordinating nitrogen atom functions as an intramolecular base promoting selective C–H bond cleavage. Without the NH proton, the ortho-N-phenyl C–H is activated instead.

In the title compound, C(24)H(28)N(4)O(2) (2+)·2Br(-)·2H(2)O, the diimid-azo-lium cation is located on an inversion center. The imidazole and the benzene rings make a dihedral angle of 68.08 (04)°. In the crystal, O-H⋯Br, C-H⋯O and C-H⋯Br hydrogen bonds link the diimidazolium cations, the bromide anions and the water mol-ecules into a two-dimensional network.

The ligand combination of semirigid 2,6-bis(imidazole-1-yl)pyridine (2,6-bip) and rigid benzenecarboxylate allow the isolation of three new zinc coordination polymers. Hydrothermal synthesis between Zn(NO3)2 3 6H2O, 2,6- bip, and terephthalic acid under basic condition affords [Zn(1,4-bdc)(2,6-bip) 3 2 H2O]n (1) (1,4-bdc =1,4-benzenedicarboxylate), which shows an undulating 2D (4,4)-network with 2-fold interpenetration. Contrastingly, solvothermal synthesis with identical starting materials in DMF, yields [Zn(1,4-bdc)(2,6-bip) 3DMF]n (2), which exhibits noninterpenetrating 2D (4,4)-network. Thus 1 and 2 are pseudosupramolecular isomeric pair, illustrating the strong effect of guest solvents in controlling the entanglement. A similar hydrothermal reaction to 1 but using 1,3,5- benzenetricarboxylic acid instead yields [Zn2(?OH)(1,3,5-btc)(2,6-bip) 3H2O]n (3) (btc = benzenetricarboxylate), which exhibits a (3,4,6)-connected 3D framework with an unprecedented {5.6.7}2{52.6.7.82}2{54.62.73.84.92} topology. Compound 1 and 2 show reversible solvent incorporation properties.

A new phosphine−imidazolium salt, L·HBr (1, L = (1-ethylenediphenylphosphino-3-(mesityl))imidazol-2-ylidene), has been prepared. A combination of 0.5 mol % of Pd(dba)2 and 0.5 mol % of L·HBr in the presence of 2 equiv of Cs2CO3 as base has proven to be highly efficient in the Heck coupling reactions of aryl bromides (from electron-deficient to electron-rich aryl bromides) with n-butyl acrylate.

In this mini-review, we present a summary of our recent work in the field of palladium-catalyzed cross-coupling reactions, with emphasis on the use of nucleophilic N-heterocyclic carbenes (NHC) as ancillary ligand. The palladium-mediated coupling reactions investigated include the Suzuki–Miyaura, Kumada–Tamao–Corriu, Heck, Sonogashira, Stille, Hiyama and aryl amination reactions.

In the title complex, [Ni(C(14)H(12)N(3)O)(2)], the Ni(II) atom lies at the centre of a distorted octahedron formed by two tridentate hydrazone ligands. Inter-molecular hydrogen bonds of the type C-H⋯X (X = N, O) link the complexes into a two-dimensional network.

We have generated mutant mice that do not express pp59fyn, a nonreceptor protein tyrosine kinase related to pp60src, by homologous recombination in embryonic stem cells. fyn- mice did not display an overt phenotype. Because fyn is associated with the T cell receptor (TCR), thymocyte and T cell signaling was analyzed in the mutant background. Cross-linking of TCR-CD3 in thymocytes led to markedly reduced calcium fluxes and abrogated proliferation, whereas mature splenic T cells retained largely normal proliferation despite depressed calcium movements and IL-2 production. Similarly, proliferation induced by Thy-1 cross-linking was reduced in thymocytes but not in splenic T cells. fyn- thymocytes were impaired at a late stage of maturation and showed limited clonal deletion to the Mls-1a self-super-antigen but not to staphylococcal enterotoxin A. These results implicate fyn as a critical component in TCR signaling in thymocytes and, potentially, in the process that determines T cell repertoire in the adult mouse.

A combination of palladium acetate and the imidazolium salt IPr.HCl (1, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) has proven to be highly efficient in the cross coupling reactions of aryl bromides and electron-deficient aryl chlorides with phenyltrimethoxysilane or vinyltrimethoxysilane. The catalytic performance of this system was found to be comparable to that of systems using PCy(3) and P(o-tol)(3).

The title complex, [Fe(2)(C(2)H(5)OS)(2)(NO)(4)], lies on a crystallographic inversion center. The Fe-Fe distance is characteristic of a metal-metal bond. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link complex mol-ecules into a two-dimensional network.

Two compounds, namely, [TTPH(2)](Cl)(2) x 4 H(2)O (1) and [TTPH(2)](Br)(2) x 4 H(2)O (2), (TTP = 4'-p-tolyl-2,2':6',2''-terpyridine) were synthesized from purely aqueous media and characterized by physical techniques. In the solid-state structures of these compounds, interesting supramolecular assemblies are observed. In 1, an unusual staircase-like architecture of the tape of edge-shared planar water hexamer is of importance, where the chloride ions are at the two edges of the tape. In 2, the polymeric nature of the water-bromide assembly is of interest, where discrete open-cube water octamers are doubly bridged by bromide ions. Semiempirical and DFT calculations confirm that the nature of the anion indeed affects the topology of the water-halide assemblies. We conclude that the protonated [TTPH(2)](2+) species can act as appropriate receptors for halide ions, which in turn act as a matrix for the formation of polymeric 1D water-halide assemblies.

A new imidazolinium ligand precursor [L 2 H]Cl (2) was prepared in 86 % yield. Compared with its imidazolium counterpart, [L 1 H]Cl (1), 2 is very sensitive to moisture and can undergo ring-opening reactions very readily. Palladium complexes with the ring-opened products from imidazolinium salts were isolated and characterized by X-ray crystallography. Theoretical studies confirmed that the imidazolinium salt has a higher propensity for the ring-opening reaction than the imidazolium counterpart. New mixed phosphine/carbene palladium complexes, cis-[PdCl 2 (L)(PR 3 )] (L=L 1 and L 2 ; R= Ph, Cy), were successfully prepared. These complexes are highly robust as revealed by variable-temperature NMR spectroscopic studies and thermal gravimetric analysis. The structural and electronic properties of the new complexes on varying the carbene group (imidazol-2-ylidene group (unsaturated carbene) vs. imidazolin-2-ylidene (saturated carbene)) and the phosphine group (PPh 3 vs. PCy 3 ) were studied in detail by X-ray crystallography, X-ray photoelectron spectroscopy, and theoretical calculations. The catalytic study reveals that cis-[PdCl 2 (L 2 )-(PCy 3 )] is a competent Pd II precatalyst for Suzuki coupling reactions, in which unreactive aryl chlorides can be applied as substrates.