Robert A. Gossage

Recent Findings in Cyclometallation of meta-Substituted Aryl Ligands by Platinum Group Metal Complexes by Caryl–R Bond Activation (R=H, CR3, SiR3)

Cyclometallation of aryl ligands with two donor substituents in the meta-positions occurs by Caryl - R bond activation and is facilitated by intramolec- ular coordination of these donor substituents. This procedure has been used for the preparation of a variety of platinum group metal organometallic complexes with interesting catalytic and electronic properties. Some recent findings are detailed.

Resveratrol analog trans 3,4,5,4′-tetramethoxystilbene (DMU-212) mediates anti-tumor effects via mechanism different from that of resveratrol

PurposeResveratrol is a well-known chemopreventive and chemotherapeutic agent. Among all of the resveratrol analogs synthesized, 3,4,5,4′-tetramethoxystilbene (DMU-212) shows high activity and selectivity against various cancer cell types. The objective of this study is to investigate why DMU-212 has higher anti-tumor activity than resveratrol.MethodsThe effects of DMU-212 and resveratrol on cell viability, cell cycle, Stat3 activation, and microtubule dynamic were investigated and compared using MTT assay, cell cycle analysis, Western blot, tubulin polymerization assay, respectively, in MDA-MB-435 and MCF-7 human breast cancer cells.ResultsCompared to resveratrol, DMU-212 exerted a significantly higher growth inhibition in both cell lines. Further studies demonstrated that DMU-212 acted via different mechanisms from resveratrol. First, DMU-212 induced predominantly G2/M arrest whereas resveratrol induced G0/G1 arrest in both cell lines. Correlating with these findings, resveratrol induced more dramatic changes in the expression of Cyclin D1 compared to DMU-212. Second, DMU-212 induced apoptosis and reduced the expression of multiple anti-apoptotic proteins more appreciably than resveratrol. Third, while both agents inhibited Stat3 phosphorylation, treatments of DMU-212 but not resveratrol led to a significant increase in tubulin polymerization. The higher sensitivity to DMU-122 in MDA-MB-435 correlated with the more prominent effects seen in these parameters in this cell line, as compared to MCF7.ConclusionCompared to resveratrol, the novel stilbene derivative, DMU-212, had higher anti-tumor effects, which are likely owing to its modulation of multiple cellular targets.

Novel tridentate diamino organomanganese(II) complexes as homogeneous catalysts in manganese(II):copper(I) catalyzed carbon-carbon bond forming reactions

The new, paramagnetic arylmanganese(II) complex Li[MnCl2(NCN)] (2, NCN [C6H3(CH2NMe2)2-2,6]) has been obtained in high yield from the reaction of MnCl2 and [Li(NCN)]2 in a 2:1 molar ratio. In THF solution, 2 is likely an ionic species [Li(THF)n] [MnCl2(NCN)] (molecular weight determination and conductivity measurements), while magnetic measurements indicate that a high spin d 5 manganese(II) center is present. Subsequent reaction of 2 with RLi afforded [MnR(NCN)] (R Me (3a), n-Bu (3b)). Complex 2, using CuCl as a co-catalyst, is an effective catalyst system for cross-coupling of Grignard reagents with alkyl bromides and the 1,4-addition of organomagnesium halides to a,b-unsaturated ketones. No further additives or co-solvents are necessary. For both reactions a dramatic decrease in reaction times is observed when compared to standard manganese:copper systems. Alkyl bromides with unsaturated or heteroatom functionalities can be cross-coupled. Also, excellent reactivity towards normally unreactive b,b-disubstituted ketones has been observed in the 1,4-addition reaction.

Synthesis and catalytic application of amino acid based dendritic macromolecules

The use of amino acid based dendrimers as molecular scaffolds for the attachment of catalytically active organometallic Ni “pincer” complexes, via a urea functionality, is described; the dendrimer catalysts have comparable activity to their mononuclear (NCN)NiX analogues.

The Effect of the Trimethylsilyl Group on Electrophilic Cyclopalladation; A Study of Caryl–Si versus Caryl–H Selective Bond Activation with 2,6‐(Me2NCH2)2C6H3R (R=H or SiMe3)

The site selectivity of electro- philic palladation has been studied by using two bis(aminomethyl)-substituted benzenes 1,3-(Me2NCH2)2C6H4 (6) and 2,6-(Me2NCH2)2C6H3(SiMe3 )( 7) and Li2(PdCl4) or Pd(OAc)2 in solution in MeOH or CH2Cl2. The major product of direct palladation of 6 in both solvents is the polymeric cyclopalladated organo- metallic complex (1,5-{PdCl}2-2,4-(Me2- NCH2)2C6H2)n, which was characterized as its dinuclear pyridine derivative (1,5- {PdCl(C5H5N)}2-2,4-(Me2NCH2)2C6H2) (9). The effect of the trimethylsilyl group present at the 1-position in 7 leads to inversion of the site selectivity in comparison to that observed for 6, and to activation of the C - Si bond when MeOH is used as solvent; the major product of this direct palladation is the known monomeric cyclopalladated complex ({PdCl}2,6-(Me2NCH2)2C6H3) (8). However, using CH2Cl2 instead of MeOH in the palladation reaction of 7 leads to the major product arising from C - H rather than C - Si bond activation.

The privileged pincer-metal platform : coordination chemistry & applications

Synthesis, Structure and Chemical Reactivity of Rare Earth Pincer Complexes.- Pincer-like cyclic systems for unraveling fundamental transition metal redox processes.- Pincer complexes of lithium, sodium, magnesium and copper: a discussion of solution and solid-state aggregated structure and reactivity.- Organometallic complexes with pincer ligands for hydrogen generation and hydrogen storage.- Tethered Pincer Complexes for Green Catalysis.- The Privileged Pincer-Metal Platform: Coordination Chemistry & Applications.

Ortho-bis(amino)arylnickel(II) halide complexes containing perfluoroalkyl chains as model catalyst precursors for use in fluorous biphase systems

Abstract A novel synthetic procedure is presented to modify 1,3-bis[(dimethylamino)methyl]benzene to accommodate perfluoro alkyl chains. These ligands are then converted into nickel- and platinum-chloride organometallic derivatives, which can serve as model compounds for use in homogeneous catalysis. A nickel complex is shown to be an active catalyst for the 1 : 1 addition of CCl4 to methylmethacrylate (Kharasch addition reaction) in dichloromethane but lacks sufficient solubility for use under fluorous biphase conditions. The structure in the solid state of this fluorous Ni species, which is a rare example of a structurally characterised perfluoro organometallic compound, was elucidated by single crystal X-ray diffraction.

Mixed Metal Acetylides: The PtII Aryl Acetylide “[PtC6H2(CH2NMe2)22,6‐(C≡C)‐4]” as a Connective Fragment

Using Me3SiCC{Pt}Cl (1; Me3SiCC{Pt} = [Pt(C6H2{CH2NMe2}2-2,6-{CCSiMe3}-4]+) a series of platinum monoacetylides of the type XCC{Pt}CCR [X = SiMe3: 2, R = Ph; 3, R = (5-C5H4)Fe(5-C5H5) (abbreviated as Fc); 4, R = C6H4CN-4; 5, R = C6H4(CCSnMe3)-4; X = H: 7, R = Ph; 8, R = Fc; 9, R = C6H4CN-4] have been prepared. Studies directed towards the coordinative properties of the C2 unit of 1 have been carried out and heterotrimetallic [-(Me3SiCC{Pt}Cl][Co2(CO)6] (10) could be synthesised. The successful attachment of 1 to a Ph3PAu unit leads to linear Ph3PAuCC{Pt}Cl (11). Treatment of 11 with FcCCSnMe3 produces the heterotrimetallic rigid-rod shaped complex Ph3PAuCC{Pt}CCFc (13). Cyclic voltammetric studies carried out on these Ph3PAu-capped molecules show that the attachment of an organometallic entity on either side of the CC{Pt} fragment leads to a facilitation of the PtII/PtIV oxidation.

New “bucky-ligands”. Potentially monoanionic terdentate diamino aryl pincer ligands anchored to C60

Abstract Two new methanofullerenes have been prepared by the reaction of C 60 with diazo substituted, potentially monoanionic, terdentate diamino aryl ligands, yielding a mixture of the open valence [5,6]- and closed valence [6,6]-isomers. Single isomers of the pure [6,6]-methanofullerenes were obtained by heating these mixtures in toluene solution.

Synthesis of a New Multidentate Phosphane Ligand C6H2(CH2PPh2)4-1,2,4,5 − X-ray Structure of a Dinuclear Ruthenium(II)-Bridged Complex: [{RuCl2(PPh3)}2{C6H2(CH2PPh2)4-1,2,4,5-P,P′,P′′,P′′′}]

The tetrakis(phosphane oxide) C6H2{CH2P(O)Ph2}4-1,2,4,5 (5), has been prepared in high yield from the Arbuzov reaction of C6H2(CH2Br)4-1,2,4,5 (4), with excess (7 equiv.) of Ph2POEt. Subsequent reduction of 5 with HSiCl3 (12 equiv.) in C6H4Cl2-1,2 afforded the new tetraphosphane C6H2(CH2PPh2)4-1,2,4,5 (6), in high yield. The reaction of 6 with [RuCl2(PPh3)4] in CH2Cl2 afforded the green dinuclear ruthenium(II) coordination complex [{RuCl2(PPh3)}2{C6H2- (CH2PPh2)4-1,2,4,5-P,P′,P′′,P′′′}]·0.5 CH2Cl2 (8), in 39% isolated yield. The solid-state molecular geometry of 8, determined by X-ray analysis, shows that the tetraphosphane is ortho-P,P′-chelated to each of the two [RuIICl2(PPh3)] units.