Cyclopalladation of N-phenyl-4-ferrocenylmethylpyrazoles: Crystal structure of [Pd{κ-C,N-C6H4-1-[(3,5-Me2-C3N2)-CH2-(η-C5H4)Fe(η-C5H5)]}Cl(PPh3)] · CH2Cl2

The synthesis and characterization of pyrazole derivatives of general formula [C₆H₄-4-R-1-{(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)}] [R = OMe (1a) or H (1b)] with a ferrocenylmethyl substituent are described.The study of the reactivity of compounds 1 with palladium(II) acetate has allowed the isolation of complexes (μ-AcO)₂[Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}]₂ (2) [R = OMe (2a) or H (2b)] that contain a bidentate [C(sp², phenyl), N]⁻ ligand and a central “Pd(μ-AcO)₂Pd” unit.Furthermore, treatment of 2 with LiCl produced complexes (μ-Cl)₂[Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}]₂ (3) [R = OMe (3a) or H (3b)] that arise from the replacement of the acetato ligands by the Cl⁻.Compounds 2 and 3 also react with PPh₃ giving the monomeric complexes [Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}X(PPh₃)] {X⁻ = AcO⁻ and R = OMe (5a) or H (5b) or X⁻ = Cl⁻ and R = OMe (6a) or H (6b)}, where the phosphine is in a cis-arrangement to the metallated carbon atom. Treatment of 3 with thallium(I) acetylacetonate produced [Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}(acac)] (7) [R = OMe (7a) or H (7b)]. Electrochemical studies of the free ligands and the cyclopalladated complexes are also reported. The dimeric complexes 3 also react with MeO₂C-CC-CO₂Me (in a 1:4 molar ratio) giving [Pd{(MeO₂C-CC-CO₂Me)₂C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}Cl] (8) [R = OMe (8a) or H (8b)], which arise from the bis(insertion) of the alkyne into the σ{Pd-C(sp², phenyl)} bond of 3.     

DFT Mechanistic Study on Diene Metathesis Catalyzed by Ru‐Based Grubbs–Hoveyda‐Type Carbenes: The Key Role of π‐Electron Density Delocalization in the Hoveyda Ligand

The catalytic activity and catalyst recovery of two heterogenized ruthenium‐based precatalysts ( H and NO₂(4) ) in diene ring‐closing metathesis have been studied by means of density functional calculations at the B3LYP level of theory. For comparison and rationalization of the key factors that lead to higher activities and higher catalyst recoveries, four other Grubbs–Hoveyda complexes have also been investigated. The full catalytic cycle (catalyst formation, propagation, and precatalyst regeneration) has been considered. DFT calculations suggest that either for the homogeneous and heterogenized systems the activity of the catalysts mainly depends on the ability of the precursor to generate the propagating carbene. This ability does not correlate with the traditionally identified key factor, the Ru???O interaction strength. In contrast, precatalysts with lower alkoxy‐dissociation energy barriers and lower stabilities compared with the propagating carbene also present larger C1? C2 bond length (i.e., lower π character of the C? C bond that exists between the metal–carbene (Ru?C) and the phenyl ring of the Hoveyda ligand). Catalyst recovery, regardless of whether a release–return mechanism occurs or not, is also mainly determined by the π delocalization. Therefore, future Grubbs–Hoveyda‐type catalyst development should be based on fine‐tuning the π‐electron density of the phenyl moiety, with the subsequent effect on the metalloaromaticity of the ruthenafurane ring, rather than considering the modification of the Ru???O interaction.     

Formation of Pegylated polyurethane and Lysine-coated polyurea nanoparticles obtained from O/W nano-emulsions

The present work describes the formation of Pegylated polyurethane and Lysine-coated polyurea nanoparticles obtained from O/W nano-emulsions via an interfacial polycondensation process in the aqueous solution/polysorbate 80/diisocyanate/medium chain triglyceride systems. The initial nano-emulsions were prepared using the phase inversion composition (PIC) method. Dynamic light scattering studies revealed the changes in the particle size occurring during the process of nanoparticle formation. Well-defined polymeric nanoparticles with a small particle diameter (below 80 nm) and low polydispersity index were obtained using a highly hydrophilic component (polyethylene glycol or lysine) and an aliphatic diisocyante monomer. FT-IR and AFM studies showed that the polymeric matrix of nanoparticles was built by copolymers derived from reaction between the diisocyanate and the hydroxyl groups of both nonionic surfactant and the highly hydrophilic component. Pegylated-polyurethane and lysine-coated polyurea nanoparticles designed in this study are promising tools for future applications in biomedical sciences.     

Regioselective cyclomanganation of Schiff bases. An unexpected effect of chloro substituents

In this paper we describe the synthesis of new metallacycles by the cyclomanganation reaction of benzyl-benzylidene-amines by using [MnMe(CO)₅] as metallating agent. These ligands can undergo metallation on different aromatic carbon atoms but no important differences have been found in the regioselectivity of the process, that can be related to the electronic effect of the substituents, and in all the cases studied the endo-cyclomanganated complexes of para-substituted imines have been obtained. The corresponding exo-metallacycles were obtained by reaction of [MnMe(CO)₅] on the imine 2,6-Cl₂C₆H₃CHNCH₂Ph and 2,4,6-Me₃C₆H₂CHNCH₂Ph, derived from 2,6-dichlorobenzaldehyde and 2,4,6-trimethylbenzaldehyde, respectively.The results described suggest that the mechanism of the cyclomanganation is similar to that of cyclopalladation and it can be proposed that cyclomanganation takes place by the formation of a four-centered transition state, involving the C-H and Mn-C_acetyl bonds, in the acetyl coordination complex formed in the first step of the reaction.     

Easy access to diastereomerically pure platinacycles

The synthesis of the first examples of diastereomerically pure platinacycles having simultaneously a chiral carbon and a sigma[Pt-C(sp(2), ferrocene)] bond is described.     

Direct, two-step synthetic pathway to novel dibenzo[a,c]phenanthridines

Novel dibenzo[a,c]phenanthridines are prepared regioselectively by the application of a straightforward synthetic pathway, starting from new 3,4-diaryl- and 3,4-dihydro-3,4-diarylisoquinolines prepared via Ritter-type heterocyclization and the more classical two-step reductive amination/Bischler-Napieralski cyclization of triarylethanones, respectively. A comparative study of nonphenolic oxidative coupling methodologies provides a highly efficient procedure, based on the hypervalent iodine reagent phenyliodine(III) bis(trifluoroacetate) (PIFA), to accomplish the final coupling step.     

Simultaneous determination of difloxacin and its primary metabolite sarafloxacin in rabbit plasma

Summary An HPLC method with fluorescence detection is presented for the analysis of difloxacin (DIF) and sarafloxacin (SAR) in rabbit plasma using norfloxacin (NOR) as internal standard (Figure 1). Plasma sample preparations were carried out by adding phosphate buffer (pH 7.4, 0.1 M), followed by extraction with trichloromethane. Fluoroquinolones were separated on a reversed-phase column using an aqueous phosphate solution-acetonitrile (82:18) mobile phase. The concentrations of NOR, SAR and DIF eluting off the column, with retention times of 2.16, 5.60 and 6.20, respectively, were monitored by fluorescence detection atλ _ex 338 andλ _em 425 nm. The quantitation limit was 12 ng mL⁻¹ for SAR and DIF. Standard curves were linearly related to concentration in the range from 1 to 1500 ng mL⁻¹. Recovery was determined as 76% and 70% for SAR and DIF, respectively. Inter-and intraassay coefficients of variation were less than 6% for all compounds.     

Determination of grepafloxacin in plasma samples by HPLC: Application to clinical pharmacokinetic studies

Summary A sensitive HPLC assay for the determination of grepafloxacin (GRE) in biological samples is described. Sample preparations were carried out by adding phosphate buffer (pH 7.4, 0.1M), followed by extraction with trichloromethane. GRE and the internal standard, enrofloxacin (ENR), were separated on a reversed-phase column using an aqueous phosphate solution-acetonitrile (78∶22) mobile phase. The concentrations of ENR and GRE eluting of the column with retention times of 2.55, and 4.90 min, respectively were monitored by fluorescence atλ _ex 338 andλ _em 425 nm. The method was shown to be linear from 5 to 4000 ng mL⁻¹. The detection and quantitation limits were 5 and 10 ng mL⁻¹, respectively. Mean recovery was determined as 90%. Inter- and intra-assay precisions were 3.0% and 3.5% respectively. The method was applied to the determination of GRE in plasma samples collected during clinical pharmacokinetic studies.