Synthesis and reactivity of di(silylamido)cyclopentadienyl titanium and zirconium complexes

We present in this account the synthesis and recent developments of a new class of group 4 metal complexes with the tridentate di(silylamido)cyclopentadienyl ligand. These doubly silyl-bridged group 4 metal amido chelates are receiving increasing interest as they are efficient catalysts for ethene polymerization when activated with MAO despite generating 14-electron d0 cationic species free of the alkyl group required for the first insertion reaction in the polymerization process.Programa Juan de la Cierva (Ministerio de Educación y Ciencia

Cis- and trans-titanium complexes with doubly silyl-bridged dicyclopentadienyl ligands: molecular structure of [(TiCl)2 (μ-0) {(SiMe2)2(η5-C5H3)2}]2 (μ-O)2

The reaction of TiCl4 with Li2[(SiMe2)2(η5-C5H3)2] in toluene at room temperature afforded a mixture of cis- and trans-[(TiCl3)2{(SiMe2)2(η5-C5H3)2}] in a molar ratio of Full-size image (<1 K) after recrystallization. The complex trans-[(TiCl3)2{(SiMe2)2(η5-C5H3)2}] was hydrolyzed immediately by the addition of water to THF solutions to give trans-[(TiCl2)2(μ-O){(SiMe2)2(η5-C5H3)2}] as a solid insoluble in all organic solvents, whereas hydrolysis of cis-[(TiCl3)2{(SiMe2)2(η5-C5H3)2}] under different conditions led to the dinuclear μ-oxo complex cis-[(TiCl2)2)(μ-O){(SiMe2)2(η5-C5H3)2}] and two oxo complexes of the same stoichiometry [(TiCl)2(μ-O){(SiMe2)2(η5-C5H3)2}]2(μ-O)2 as crystalline solids. Alkylation of cis- and trans-[(TiCl3)2{(SiMe2)2(η5-C5H3)2}] with MgCIMe led respectively to the partially alkylated cis-[(TiMe2Cl)2{(SiMe2)2(η5-C5H3)2}] and the totally alkylated trans-[(TiMe3)2{(SiMe2)2(η5-C5H3)2}] compounds. The crystal and molecular structure of the tetranuclear oxo complex [(TiCl)2(μ-O){(SiMe2)2(η5-C5H3)2}]2(μ-O)2 was determined by X-ray diffraction.Universidad de Alcal

Evidence of fluoride transfer from the anion of\ud [Zr{C5H3[SiMe2(η1-NtBu)]2}]+[RB(C6F5)3]_\ud complexes to the zirconocenium cation

In summary, we have found experimental evidence to support a reaction pathway involving direct fluoride migration\ud to the zirconium cation without previous transfer of C6F5.\ud It is noteworthy that the opening of the silyl–amido bridge was not observed in the course of these activations. Experiments with other donor ligands are in progress to investigate the conditions under which the ion pairs 1 and 2 may follow different decomposition routes and the possible mechanisms of these reactions.Financial support by the Spanish MEC (project MAT2004-02614)\ud and DGUI/CM (program S/0505/PPQ-0328) is acknowleged

A new type of doubly silylamido-bridged\ud cyclopentadienyl group 4 metal complexes

Doubly bridged di(silyl-η-amido)cyclopentadienyltitanium and -zirconium complexes and their related cations as the [(PhCH 2)B(C 6F 5) 3] - salts have been isolated (see structure of the Ti derivative). The neutral benzylzirconium complex was a very efficient catalyst in the presence of methylaluminoxane for producing high molecular weight polyethylene and ethylene-1-hexene copolymer

Neutral and Cationic [Bis(η1-amidosilyl)-η5-cyclopentadienyl]titanium and -zirconium complexes: synthesis, X-ray molecular structures and DFT calculations

Treatment of LiNHtBu with THF solutions of C5H4(SiMe2Cl)2 gave C5H4(SiMe2NHtBu)2 (1). Deprotonation of 1 with M(NMe2)4 (M = Ti, Zr) under different conditions provided the monocyclopentadienyl complexes [M{η5-C5H3- [SiMe2(NHtBu)]2}(NMe2)3] [M = Ti (2), Zr (3)] and the single (η-amidosilyl)cyclopentadienyl compounds [M{η5-C5H3[SiMe2(NHtBu)][SiMe2(η1-NtBu)]}(NMe2)2] [M = Ti (4), Zr (5)]. The related dibenzyl compounds [M{η5-C5H3[SiMe2- (NHtBu)][SiMe2(η1-NtBu)]}(CH2Ph)2] [M = Ti (6), Zr (7)] resulted from treatment of 1 with M(CH2C6H5)4 (M = Ti, Zr). Further deprotonation of the amido complexes 4 and 5 and the benzyl complexes 6 and 7 by heating in toluene solution gave the bis(η-amidosilyl)cyclopentadienyl complexes [M{η5-C5H3[SiMe2(η1-NtBu)]2}(NMe2)] [M = Ti (8), Zr (9)] and [M{η5-C5H3[SiMe2(η1-NtBu)]2}(CH2Ph)] [M = Ti (10), Zr (11)], respectively. Treatment of the monobenzyl complexes 10 and 11 with B(C6F5)3 yielded the cationic compounds [M{η5-C5H3[SiMe2(η1-NtBu)]2}]+ as [(CH2Ph)B(C6F5)3] − [M = Ti (12), Zr (13)] salts. All new compounds were characterized by NMR spectroscopy, and the crystal structures of 10 and 13 were studied by diffraction methods. DFT calculations for the neutral and cationic species are described and provide an explanation for the unusual η1 coordination of a phenyl ring to a group-4 metal cationThe authors acknowledge the MCyT (project MAT2001-1309) for\ud financial support and the EC (project COST-D12/0016/98). J. C.\ud acknowledges CAM for a fellowship

Allylsilylcyclopentadienyl Group 4 metal complexes: synthesis, structure and reactivity

(Allyldimethyl)silyl-substituted cyclopentadiene C5H5SiMe2(CH2CH /CH2) (1) and indene C9H7 /1-SiMe2(CH2CH /CH2) (2)\ud were synthesized by reaction of SiMe2(CH2CH /CH2)Cl with NaC5H5 or LiC9H7, respectively. Metallation of 1 with n-BuLi and\ud TlOEt gave the corresponding lithium 3 and thallium 5 salts. The disilylcylopentadienes C5H4 /1-SiMe3 /1-SiMe2(CH2CH /CH2) (6)\ud and C5H4 /1,1-[SiMe2(CH2CH /CH2)]2 (7) were prepared by reaction of 3 with the corresponding chlorosilanes. Compound 7\ud reacted with TiCl4 to give the monocyclopentadienyl compound [Ti{h5\ud -C5H4SiMe2(CH2CH /CH2)}Cl3] (8), while 5 was used to\ud prepare the titanocenes [Ti(h5\ud -Cp){h5\ud -C5H4SiMe2(CH2CH /CH2)}Cl2] (Cp /C5H4SiMe2(CH2CH /CH2) 9, C5H5 10, C5Me5 11) by\ud reaction with the appropriate TiCpCl3 derivative. The related dicyclopentadienyl [Zr{h5\ud -C5H4SiMe2(CH2CH /CH2)}2Cl2] (12),\ud [Zr(h5\ud -C5H5){h5\ud -C5H4SiMe2(CH2CH /CH2)}Cl2] (13), and indenyl [Zr(h5\ud -C5H5){h5\ud -C9H6SiMe2(CH2CH /CH2)}Cl2] (14) zirconium\ud derivatives were isolated by reaction of ZrCl4 and Zr(h5\ud -C5H5)Cl3 /DME with the lithium salts 3 and 4, respectively.\ud Alkylation of the metallocene complexes using MeLi, MgMeCl, Mg(CH2Ph)Cl and Mg(CH2Ph)2(THF)2 afforded the monomethyl\ud titanium [Ti(h5\ud -C5H5){h5\ud -C5H4SiMe2(CH2CH /CH2)}ClMe] (15) and the dialkyl cyclopentadienyl [M(h5\ud -C5H5){h5\ud -C5H4SiMe2\ud (CH2CH /CH2)}R2] (R /Me, M /Ti 16, Zr 18; R /CH2Ph, M /Ti 20, Zr 22), [Zr{h5\ud -C5H4SiMe2(CH2CH /CH2)}2R2] (R /Me\ud 17, CH2Ph 21) and indenyl derivatives [Zr(h5\ud -C5H5){h5\ud -C9H6SiMe2(CH2CH /CH2)}R2] (R /Me 19, CH2Ph 23). The molecular\ud structure of 11 was studied by X-ray diffraction methods. The reactions of the dialkyl derivatives with B(C6F5)3 were monitored by\ud NMR spectroscopy at variable temperature. The catalytic activity of the dichloro zirconium complexes in the presence of\ud methylalumoxane (MAO) for ethylene polymerization was determined.Financial support of our work by MCyT (Project\ud MAT2001-1309) is gratefully acknowledged. G.H., G.M\ud and J.C are grateful to to the Alexander von HumboldtStiftung,\ud MEC and CAM for fellowships

Carbon dioxide activation assisted by a bis(chlorodimethylsilyl)cyclopentadienyl titanium compound

A great deal of interest has focused on the role of metal ions\ud as the active centers in the fixation of CO2 and its transformation. Activation of CO2 by hydroxo and oxo metal complexes to afford metal hydrogencarbonato and carbonato\ud species, respectively, is related to the function of the carbonic\ud anhydrase metalloenzyme, which catalyzes the physiologically\ud important hydration of CO2 to hydrogencarbonate

Carbosilane dendritic nanostructures, highly versatile platforms for pharmaceutical applications

Dendrimers are multifunctional molecules with well-defined size and structure due to the step-by-step synthetic procedures required in their preparation. Dendritic constructs based on carbosilane scaffolds present carbon-carbon and carbon-silicon bonds, which results in stable, lipophilic, inert, and flexible structures. These properties are highly appreciated in different areas, including the pharmaceutical field, as they can increase the interaction with cell membranes and improve the therapeutic action. This article summarizes the most recent advances in the pharmaceutical applications of carbosilane dendritic molecules, from therapeutics to diagnostics and prevention tools. Dendrimers decorated with cationic, anionic, or other moieties, including metallodendrimers; supramolecular assemblies; dendronized nanoparticles and surfaces; as well as dendritic networks like hydrogels are described. The collected examples confirm the potential of carbosilane dendrimers and dendritic materials as antiviral or antibacterial agents; in therapy against cancer, neurodegenerative disease, or oxidative stress; or many other biomedical applications.This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Nanomedicine for Infectious DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseMinisterio de Economía y CompetitividadComunidad de MadridJunta de Comunidades de Castilla-La ManchaUniversidad de Alcal

Alteration of the HIF-1alfa/VEGF Signalling Pathway and Disruption of the Cell Cycle by Second Generation Carbosilan Dendrimers

Current therapies against prostate cancer (PCa) disease, such as surgery, radiotherapy, or in last term chemical castration by androgen deprivation, have led to significant reduction of the incidence of PCa throughout the world. Worse prognosis found in those patients which exhibit castration resistance, relapsing into the disease with e v e n greater aggressiveness. Hypoxia cancer cell adaption has been observed to be closely connected to fatal prognostic tumor features. Therefore, hypoxia adaptive mechanisms of cancer cells have attracted large interest as a relev a n t biological target for treatment-resistant patients. Dendrimer s have been established as a promising nanotechnological tool owing to their beneficial physicochemical features such as multivalency and monodispersity. Herein, we have completed a thorough study to better understand the effect wit h i n the cel l of the already published ruthenium(II)-N-heterocyclic carbene metallodendrimer (G2Ru) that was able to drastically reduce HIF-1 alpha stabilization and exhibited antiproliferative capabi l i t y against androgen-sensitive (LNCaP) and androgen-resistant prostate cancer cells (LNFLU) in vitro. G2Ru, as well as its cationic imidazol i u m precursor (G2P), displayed scaven g i n g properties against intracellula r and externa l l y stimulated ROS levels, which would presumably hinder the stabilization of HIF-1 alpha by prolyl hydroxylase (PHD) inhibition. Furthermore, these dendrimers have shown considerably beneficial properties against tumor progression capabi l i t y in terms of apoptosis, cell cycle, CSCs expression, and epithelial phenotype promotion. Taken all together, in this study we could demonstrate the extraordinary anticancer properties of NHC-based carbosilane dendrimers against androgen-resistant prostate cancer cells in vitroInstituto de Salud Carlos IIIComunidad de MadridFundación Tatiana Pérez de Guzmán el BuenoUniversidad de AlcaláMinisterio de Economía, Industria y Competitivida

Removing lead from water with carboxylate dendrimers and magnetic nanoparticles modified with carboxylate dendrimers

Contamination of water with heavy metals as lead (Pb2+) is a relevant problematic issue. In this work, we have tested diferent types of dendritic materials for lead removal from water and further recovery. The systems employed are magnetic nanoparticles (MNP) modifed with monocarboxylate and dendritic carboxylate ligands, and they are compared to pristine MNP and carbosilane dendrimers. They are all efective at removing Pb2+, but the key variations are in their recyclability. The usage of a fltering membrane was required for dendrimers, which was signifcantly degraded by the acidic media. In terms of MNP, those that were covered by dendritic molecules were clearly less damaged in acidic media. Finally, isotherm analysis revealed that Pb2+ interacts diferently with unmodifed and modifed MNP.Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER¿BBN)Ministerio de Ciencia e InnovaciónComunidad de MadridUniversidad de Alcal