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Soluble and polymer-bound palladium and platinum complexes of ferrocene derivativesHan, Nam Fong January 1986 (has links)
The preparation, characterization, and catalytic properties of some soluble and polymer-bound palladium and platinum complexes of ferrocene derivatives are described. Special emphasis has been placed on studies of the mixed "hard-soft" ligands such as PPFA and ISOPFA. [Formula Omitted]
The soluble complexes (L-L)MC1₂ (L-L = BPPF, PPFA, ISOPFA, BPPFA; M = Pd, Pt) and [(L-L)PdS₂][C10₄]₂ (L-L = BPPF, PPFA; S = DMF, py) have been characterized by microanalyses, NMR and IR spectroscopic techniques.
The cationic palladium(II) complex [(L-L)PdS₂][C10₄]₂ (L-L = PPFA, S = DMF) is an effective catalyst precursor for the hydrogenation of simple olefins at 30°C and 1 atm pressure. The rate of styrene hydrogenation
depends on the substrate concentration, catalyst concentration and the solvent. The results are consistent with a homogeneous catalytic system. Platinum(II) complexes (L-L)PtCl₂ (L-L = (S,R)-PPFA, (S,R)-ISOPFA) are effective catalyst precursors for the hydrosilylation of aromatic ketones with Ph₂SiH₂. The complexes with mixed "hard-soft" ligands are better catalyst precursors than those with di(tertiary phosphine) ligands. Under the same conditions the hydrosilylation of ferrocenyl ketones results in further reduction and affords mainly the alkylferrocene products. The stable carbonium ion FcC⁺HCH₃ (Fc = Fe-(C₅H₅)(C₅H₄)-) is reduced by Ph₂SiH₂ to FcCH₂CH₃ in a thermal reaction which is catalyzed by the complex (PPFA)PtCl₂. The reaction of Ph₂SiH₂ with (L-L)PtCl₂ (L-L = PPFA, ISOPFA) yields a stable platinum(IV) hydride, which eliminates Ph₂SiHCl in solution to afford (L-L)PtHCl. The mechanistic implications of these observations are discussed.
Polymers functionalized with ferrocene and ferrocene derivatives
have been prepared. Mossbauer spectroscopic techniques and microanalyses
are used to characterize these polymers and their palladium and platinum
complexes. In a number of cases these results are confirmed by the cross-polarization/magic-angle spinning ¹³C NMR spectroscopic technique.
The palladium(II) and platinum(II) derivatives of the ferrocenyl-amine and -phosphine containing polymers are effective catalysts for the hydrogenation and hydrosilylation of olefins. All the catalysts can be easily separated from the reaction mixture and can be recycled with no loss of activity. The pronounced effect of the attached ligand in the palladium based polymers indicates that free metal is not involved.
However, in the case of platinum based catalysts, it is likely that reduction to platinum metal takes place. / Science, Faculty of / Chemistry, Department of / Graduate
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Synthesis Of 1,2,3,5-tetrasubstituted Pyrrole Derivatives Via 5-exo-dig Type Cyclization And Stereoselective Functionalisation Of Ferrocene DerivativesKayalar, Metin 01 January 2005 (has links) (PDF)
ABSTRACT
SYNTHESIS OF 1,2,3,5-TETRASUBSTITUTED PYRROLE DERIVATIVES VIA 5-EXO-DIG TYPE CYCLIZATION AND STEREOSELECTIVE FUNCTIONALISATION OF FERROCENE DERIVATIVES
Metin Kayalar
M.S., Department of Chemistry
Supervisor: Prof. Dr. Ayhan S. Demir
January 2005, 102 pages
A convenient and new method for the synthesis of 1,2,3,5-tetrasubstituted pyrrole derivatives starting from 1,3,-dicarbonyl compounds through acid catalyzed cyclization reaction is described. Alkylation of 1,3-dicarbonyl compound with propargyl bromide followed by one step cyclization with the introduction of primary amines in the presence of catalytic amount of triflouroacetic acid (TFA) affords the corresponding pyrrole derivatives in high yields.
The investigations on the studies of developing a new method for catalytic and stereoselective functionalisation of ferrocene derivatives were summarized. Functionalisation studies were carried out in three main strategy the first one of which is carboxylation, second one is arylation and the last one is oxidative cross-coupling with & / #945 / , & / #946 / -unsaturated carbonyl compounds.
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Novel Redox Responsive Cationic Lipids, Lipopolymers, Glycolipids And Phospholipid-Cationic Lipid Mixtures : Syntheses, Aggregation And Gene Transfection PropertiesGuru Raja, V January 2014 (has links) (PDF)
The thesis entitled “Novel Redox Responsive Cationic Lipids, Lipopolymers,
Glycolipids and Phospholipid-Cationic Lipid Mixtures: Syntheses, Aggregation and Gene Transfection Properties” elucidates the design, synthesis, aggregation and gene transfection properties of novel cholesterol based cationic lipids with ferrocene as the redox moiety, polyethylenimine based ferrocenylated lipopolymers and cholesterol based non-ionic glycolipids. The thesis also discusses the cationic phospholipid-cationic lipid mixtures as superior gene transfection agents. The work has been divided into six chapters.
Chapter 1. Introduction
Part A. Various Cholesterol based Systems for Applications as Biomaterials
Liposomes composed of cationic lipids have become popular gene delivery vehicles. A great deal of research is being pursued to make efficient vectors by varying their molecular architecture. Cholesterol being ubiquitous component in most of the animal cell membranes is increasingly being used as a hydrophobic segment of synthetic cationic lipids. In this chapter we describe various cholesterol based cationic lipids and focus on the effect of modifying various structural segments like linker and the headgroup of the cationic lipids on gene transfection efficiency with a special emphasis on the importance of ether linkage between cholesteryl backbone and the polar headgroup. Interaction of cationic cholesteryl lipids with dipalmitylphosphatidycholine membranes is also discussed here. Apart from cholesterol being an attractive scaffold in
the drug/gene delivery vehicles, certain cholesteryl derivatives have also been shown to be attractive room temperature liquid-crystalline materials.
Part B. Diverse Applications of Ferrocene Derivatives
This chapter gives a brief overview of ferrocene chemistry followed by description of major applications of ferrocenyl derivatives in a variety of fields like catalysis, materials chemistry, electrochemical sensors, medicinal chemistry etc. We discuss the use of ferrocene as an electrochemical and redox active switch to achieve control over supramolecular aggregation. It also reviews ferrocene based amphiphiles including surfactants, lipids and polymers with an emphasis on the role of ferrocene over aggregate formation and their utilization in biological applications.
Chapter 2: Optimization of Redox Active Alkyl-Ferrocene Modified Polyethylenimines for Efficacious Gene Delivery in Serum
1a-c, n = 6, P8-C6-F1, P8-C6-F2, P8-C6-F3
2a-c, n = 11, P8-C11-F1 P8-C11-F2, P8-C11-F3
% ferrocene grafting, F1 = 15%, F2 = 25% and F3 = 50%
Figure 1. Structure of the alkyl-ferrocene modified 800 Da Branched Polyethylenimine.
In this chapter we present six new lipopolymers based on low molecular weight polyethylenimines (BPEI 800 Da) which are hydrophobically modified using ferrocene
terminated alkyl tails of variable lengths. The effects of degree of grafting, spacer length and redox state of ferrocene in the lipopolymer on the self assembly properties were investigated in detail by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and zeta potential measurements. The assemblies displayed a redox induced increase in the size of the aggregates. The coliposomes comprising of the lipopolymer and a helper lipid 1,2-Dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) showed excellent gene delivery capability in serum containing environment in two cancer cell lines (HeLa, U251 cells). Optimized formulations showed remarkably higher transfection activity than BPEI 25 KDa and even better than commercial Lipofectamine 2000 as evidenced from luciferase activity and EGFP expression analysis. Oxidation of ferrocene in lipopolymers led to reduced levels of gene transfection which was also followed by cellular internalization of fluorescently labeled pDNA using confocal microscopy. Cytotoxicity assay revealed no obvious toxicity for the lipopolyplexes in the range of optimized transfection levels. Overall, we have exploited the redox activity of ferrocene in PEI based polymeric gene carriers for trenchant control over gene transfection potential.
RLU/mg protein HeLa Cells
Figure 2. Maximum transfection efficacies of optimized redox lipopolymer/DOPE formulations by (A) Luciferase Assay and (B) Flow cytometry (GFP expression).
Chapter 3. Membranes derived from Redox-active Cholesterol based Cationic Lipids and their Interactions with DNA and Phospholipid Membranes
Figure 3. Molecular structures of the electroactive cholesterol based monomeric and gemini lipids.
This chapter describes the synthesis and aggregation properties of two series of redox-active ferrocene containing monomeric and gemini cationic lipids with cholesterol as a hydrophobic domain. These cationic lipids are modified at their headgroup region using ferrocene terminated alkyl chains of differing length. All the four cationic lipids formed stable suspensions in water. Aggregation behavior of these cationic lipids in aqueous suspensions in their unoxidized and oxidized state was studied using TEM, DLS, zeta potential measurements and XRD studies. Cationic lipids with ferrocene in natural, reduced state were found form bigger sized vesicles which upon oxidation became smaller aggregates with increased zeta potential. XRD results indicate the existence of nice lamellar arrangements of the lipid bilayers. Thermotropic phase transition behavior of DPPC membranes incorporated with cationic ferrocene lipids was also studied using differential scanning calorimetry. Finally, we assayed pDNA (plasmid DNA) binding ability of all the four cationic lipids using ethidium bromide intercalation assay where all the cationic lipid formulations showed excellent DNA binding capability. In the experiments involving SDS-induced release of DNA, we observed that redox-active monomeric lipids (3a-b) were found to be more efficient in facilitating the release of DNA from the liposome-DNA complex in the presence of negatively charged SDS micelles than their gemini counterparts (4a-b).
Chapter 4. Redox-responsive Gene Delivery by Ferrocene containing Cationic Cholesteryl Lipids in Serum
This chapter describes the transfection efficacy of redox-active monomeric and gemini cationic lipids with cholesterol backbone. The transfection efficiency of all the lipids could be tuned by changing the oxidation state of the ferrocene moiety. Gene transfection capability was assayed in terms of EGFP expression using pEGFP-C3 plasmid DNA in three cancer cell lines of different origin, namely Caco-2, HEK293T and HeLa in the presence of serum.
Figure 4. Effect of oxidation state of ferrocene on maximum transfection efficacies of monomeric and gemini lipids in three different cell lines (Caco-2, HEK 293T and HeLa).
Cationic liposomal formulations with ferrocene in its reduced state were observed to be potent transfectants reaching the EGFP expression levels even better than
commercial lipofectamine 2000 in the presence of serum as evidenced by flow cytometry. EGFP expression was further substantiated using fluorescence microscopy studies. All liposomal formulations containing oxidized ferrocene displayed diminished levels of gene expression and interestingly, these results were consistent for each formulation in all the three cell lines. Assessment of EGFP expression mediated by both reduced and oxidized ferrocene containing formulations was also undertaken following cellular internalization of labelled pDNA using confocal microscopy and flow cytometry. Lipoplexes derived from different liposomal formulations with reduced and oxidized ferrocene were characterised using TEM, AFM, zeta potential and DLS measurements. Overall, we demonstrate here controlled gene transfection levels using redox driven, transfection efficient cationic monomeric and gemini lipids.
Chapter 5: Synthesis of ‘Click Chemistry’ Mediated Glycolipids: Their
Aggregation Properties and Interaction with DPPC Membranes
This chapter describes the synthesis and aggregation properties of cholesterol based glycolipids along with their interaction with a model phosphatidylcholine membranes. Three series of non-ionic glycolipids with hydrophobic cholesterol backbone and various monosaccharide and disaccharide sugars as the hydrophilic polar domain have been synthesized. These were conjugated to the cholesteryl backbone via oligooxyethylene spacers of different lengths (n = 1, 3 and 4) using Cu (I) catalyzed Huisgen [3+2] cycloaddition, which is popularly known as „Click Chemistry‟. All the synthetic glycolipids (5a-d, 6a-d and 7a-d) formed vesicular aggregates in aqueous medium as confirmed by TEM and DLS. XRD studies with the cast films of lipids revealed that the bilayer width increased with increase in the length of oligoethylene spacer unit that has been incorporated between the hydrophobic and hydrophilic domains. Also, within the same series containing a particular oligoethylene unit, bilayer widths were found to be more for the lipids containing disaccharides as their headgroup than monosaccharides.
Figure 5. Molecular structures of various cholesterol-based glycolipids. Calorimetry studies of the coaggregates containing naturally occurring 1, 2-dipalmitoylphosphatidylcholine (DPPC) and various mol-% of each of the glycolipids revealed that more than 30 mol-% of glycolipids are required to completely abolish the phase transition of DPPC membranes. These results were further supported by fluorescence anisotropy measurements of the co-aggregates using 1, 6-diphenylhexatriene (DPH) as a probe. Fluorescence anisotropy of the neat vesicles revealed that 9a and 9c were more rigid than DPPC vesicles in the solid-like gel phase, while the glycolipids with longer oxyethylene spacers (n = 3 and 4) were less rigid than the DPPC vesicles.
Chapter 6. Hydrophobic Moiety Decides the Synergistic Increase in Transfection
Efficiency in Cationic Phospholipid/Cationic Lipid mixtures
This chapter describes the effect of inclusion of cationic lipid/cationic gemini lipids into the membranes of a cationic phospholipid on the gene delivery efficiency across HeLa and HEK293T cell lines. Although all the three cationic lipids have the same quaternary ammonium moiety as their headgroup, they differ from each other in terms of their hydrophobic moiety and in the number of cationic headgroups. Chol-N is a cholesterol based monocationic lipid, while 2C14-N and 2C14N-5-N2C14N are monomeric and gemini cationic lipids respectively with pseudoglycerol backbone consisting of tetradecyl (n-C14H29) chains. Each of the three cationic lipids under the current investigation, namely, Chol-N, 2C14-N and 2C14N-5-N2C14N were added in different ratios to EtDMoPC and the resultant mixed membranes were studied for the biophysical characterization and gene delivery efficacies.
Figure 6. Molecular structures of cationic lipids used in this study.
All the formulations were characterized using dynamic light scattering and zeta potential measurements to obtain their hydrodynamic diameters and surface charge properties respectively. Their DNA binding ability was also studied by measuring changes in zeta potential and gel electrophoresis of the lipoplexes formed by the coliposomal formulations and pDNA at different Lipid/DNA weight ratios. The gene delivery efficacies of various formulations were studied in terms of EGFP expression using pEGFP-C3 plasmid DNA in two different cell lines, namely HeLa and HEK293T. In the absence of serum we found that the formulation (EtDMoPC+2C14N-5-N2C14N) showed better transfection efficiency than the individual lipids. However, in the case of others, i.e., (EtDMoPC+Chol-N) and (EtDMoPC+2C14-N) formulations, there was a slight decrease in transfection efficiency compared to the individual lipids. In the presence of serum, the formulations (EtDMoPC+2C14-N) and (EtDMoPC+2C14N-5-N2C14N) showed significantly higher transfection efficacies compared to their individual lipids. Fusion assay using labelled cationic lipid formulations and unlabelled anionic liposomes revealed that lipoplexes prepared from EtDMoPC+ 2C14-N and EtDMoPC+ 2C14N-5-N2C14 exhibited much higher fusogenicity as compared to the lipoplexes prepared using EtDMoPC+Chol-N as well as the individual lipids. Thus, the liposome formulations which showed better transfection activity fused more readily with the anionic liposomes than did the formulations with poorer activity. Overall, we found that the hydrophobic domain of the cationic lipid/cationic gemini lipid that is added to cationic phospholipid has an important role on the transfection efficiency of the mixed formulations. Additionally the cytotoxicity studies revealed that each of these formulations was not significantly toxic making them viable for applications in vivo.
(For structural formula pl see the abstract pdf file)
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