Fr Francium

An efficient method for the synthesis of β-hydroxy and β-amino ketones from allylic alcohols catalyzed by Ru(η⁵-C₅Ph₅)(CO)₂Cl is described. The influence of the stereoelectronic properties of the catalyst on the reaction outcome has been studied. Optimization of the reaction conditions supressed the formation of undesired side products such as saturated ketones, benzyl alcohols, and α,β-unsaturated ketones. Several aromatic and aliphatic allylic alcohols have been reacted with a large variety of aldehydes or imines to produce β-hydroxy ketones or β-amino ketones, respectively, in yields up to 99 %. Based on experimental data, a mechanism via ruthenium alkoxides and ruthenium aldoxides is proposed. In addition, a C-bound ruthenium enolate has been characterized.

β-Hydroxy and β-amino ketones are synthesized from allylic alcohols and aldehydes or imines, respectively. The coupling reaction is catalyzed by Ru(η⁵-C₅Ph₅)(CO)₂Cl. Mechanistic investigations support a mechanism via ruthenium alkoxide intermediates.

The previous mechanistic studies of the Rh-mediated polymerization of carbenes suggests the involvement of organometallic compounds that have been derived from Rh(diene) species that contain a five-membered chelate ring of the type Rh{κ²-C,O-[–CH(COOR)–CH(Pol)–C(OR)=O–]} (Pol = polymer chain), which are characterized by the coordination of the β-ester group of the growing polymer chain to the metal. Herein we present our efforts to characterize the possibly related Rh^I(cod){κ²-C,O-[–CH(COOR)–CHR′–C(OR)=O–]} (cod = 1,5-cyclooctadiene) species. These structures can be generated by means of olefin exchange with an allyl complex and with the concomitant release of the corresponding 1,3-diene, which is derived from the allyl ligand. The product is unstable and further reacts by means of a bimolecular C–H activation process to form a related dinuclear complex [(cod)Rh(μ-{–CH(COOR)–CH–C(OR)=O–})₂Rh(cod)], in which the carbon dianion of the dimethyl or diethyl succinate bridges two Rh(cod) moieties. The complex was synthesized in an independent way and was structurally characterized. We investigated the importance of these complexes in carbene polymerization.

Rhodium chelate complexes where the β-ester group of the growing polymer chain is involved in backbonding to the metal are the predicted intermediates in the polymerization of the diazoesters. The Rh^I(cod) species of this type proved to be unstable and reacted by means of C–H activation to form dinuclear complexes. The implications for catalysis in the carbene polymerization reactions were investigated.

A simulating interaction: The P-glycoprotein (P-gp) ligand 13 displays high P-gp interacting activity (EC₅₀=2.90 μM) and selectivity in tumor cell lines. Here, this promising compound was further evaluated ex vivo in an everted gut sac assay and found to behave as a P-gp stimulator, making this agent a potential lead for the development of new therapeutics to treat Alzheimer′s disease.

The neuromodulatory peptide neurotensin has been described to functionally interact with dopaminergic pathways of the human brain. We employed radioligand binding studies to investigate the physical interaction between co-expressed dopamine D_2L or D₃ and neurotensin NTS₁ or NTS₂ receptors. Substantial cross-inhibitory effects of both receptor subtypes NTS₁ and NTS₂ on the agonist binding of D_2L or D₃ were detected in the presence of neurotensin. To identify ligand-specific modulation and subtype-dependent differences, the novel dopamine receptor agonists 5 and 6 bearing the 7-OH-DPAT pharmacophore were synthesized. Exceptional ligand specificity was observed for D₃–NTS₂ co-expression, which gave a 20-fold decrease in affinity for biphenylcarboxamide 5 in the presence of neurotensin. Comparing the binding properties of dopaminergic compounds in the presence of neurotensin, dopamine receptor subtype-selective profiles of the cross-inhibitory effect of neurotensin were observed.

Select the right pair: Radioligand binding studies of the physical interaction between co-expressed dopamine D_2L or D₃ and neurotensin NTS₁ or NTS₂ receptors indicate substantial cross-inhibitory effects of both NTS₁ and NTS₂ receptor subtypes on the agonist binding of D_2L or D₃ in the presence of neurotensin (NT). D₃–NTS₂ co-expression gave a 20-fold decrease in affinity for biphenylcarboxamide 5 in the presence of NT.

The oxidative addition of HF at trans-[Ir(Ar^F)(η²-C₂H₄)(PiPr₃)₂] (1a: Ar^F = 4-C₅NF₄; 1b: Ar^F = 2-C₆H₃F₂) affords the fluorido complexes trans-[Ir(Ar^F)(F)(H)(PiPr₃)₂] (2a: Ar^F = 4-C₅NF₄; 2b: Ar^F = 2-C₆H₃F₂). The hydrido fluorido complex 2a is also accessible by means of the reaction of the hydroxido complex trans-[Ir(4-C₅NF₄)(H)(OH)(PiPr₃)₂] (3a) with Et₃N·3HF. Both compounds 2a and 2b react with CO to give the carbonyl complexes trans-[Ir(4-C₅NF₄)(F)(H)(CO)(PiPr₃)₂] (4a: Ar^F = 4-C₅NF₄; 4b: Ar^F = 2-C₆H₃F₂). In the presence of traces of water, a slow reaction of 2a with CO₂ yields the hydrogencarbonato complex trans-[Ir(4-C₅NF₄)(H)(κ²-(O,O)-O₂COH)(PiPr₃)₂] (5a). Upon using 2a or 2b as fluorinating agent, Ph₃SiH could be converted into Ph₃SiF and CH₃C(O)Cl into CH₃C(O)F.

The oxidative addition of HF at trans-[Ir(4-C₅NF₄)(η²-C₂H₄)(PiPr₃)₂] affords the fluorido complex trans-[Ir(4-C₅NF₄)(F)(H)(PiPr₃)₂], which exhibits a square-pyramidal configuration. The latter reacts with acetyl chloride to yield acetyl fluoride and trans-[Ir(4-C₅NF₄)(Cl)(H)(PiPr₃)₂].

Paramagnetic lanthanide(III) complexes stable in aqueous solutions have gained increasing interest in the recent years due to their importance as contrast agents in magnetic resonance imaging (MRI). Lanthanide(III) complexes with macrocyclic ligands derived from 1,4,7,10-tetraazacyclododecane (cyclen) are widely used for the design of MRI probes because of their high thermodynamic stability and kinetic inertness. The rational design of more efficient contrast agents requires a better understanding of the structure and dynamics of these systems in solution. This contribution reviews the work of the author and his collaborators on the solution structure and dynamics of lanthanide(III) complexes with different cyclen-based ligands and closely related systems. DFT calculations provide molecular geometries and relative energies of the different stereoisomers of these complexes in good agreement with the experimental data. The conformational analysis performed with the aid of density functional theory (DFT) calculations was validated with the investigation of the Yb^III-induced ¹H NMR paramagnetic shifts, which encode information on the position of the observed NMR nuclei with respect to the Ln^III ion. Additionally, DFT calculations provide a better understanding of the dynamic processes responsible for the interconversion between the square-antiprismatic (SAP) and twisted-square-antiprismatic (TSAP) isomers of these complexes in solution, which might proceed through the inversion of the cyclen unit or the rotation of the pendant arms. The activation barriers obtained from theoretical calculations show a good agreement with the experimental values obtained from variable-temperature NMR spectroscopy. The work presented in this paper shows that DFT calculations in combination with NMR spectroscopy provide detailed information on the structure and dynamics of lanthanide(III) complexes at the molecular level and represent a powerful tool for the characterization of lanthanide(III) complexes relevant to the field of MRI contrast agents.

We present a short overview of the potential of DFT and paramagnetic NMR spectroscopy to explore the solution structure and dynamics of Ln^III complexes with cyclen-based ligands, providing information at the molecular level on the factors that affect the relative populations of square-antiprismatic (SAP) and twisted-square-antiprismatic (TSAP) isomers, as well as their interconversion mechanisms.

By using cost-efficient density functional theory accounting for dispersion in combination with an implicit solvent model, for the first time it has been possible to reproduce activation Gibbs free energies for phosphane dissociation from the Grubbs ruthenium olefin metathesis precatalysts in solution with good accuracy (mean unsigned error compared to experiment <2.5 kcal mol^–1). The barrier is calculated to be in the range 17.8–25.7 kcal mol^–1 for a set of nine catalysts, and is found to be located at intermediate Ru–P distances (ca. 4 Å). The agreement with the experimental activation parameters is gratifying and suggests that the calculations may give insight into these reactions and, in particular, offer resolution as to the individual components of the barriers. The forward (dissociation) barriers are much higher than the corresponding reaction free energies and the reverse reaction, phosphane binding, is associated with a significant barrier (13.2–15.6 kcal mol^–1). The latter barrier mainly arises from loss of entropy and solute–solvent dispersion interactions for the two fragments prior to Ru–P bond formation. Moreover, the fact that the barrier to phosphane binding is so significant means that the reaction free energy of phosphane dissociation cannot be taken to be identical or similar to the forward barrier, as has occasionally been assumed in earlier studies.

A DFT model validated against Ru–P bond energies from gas-phase MS experiments on Grubbs olefin metathesis catalysts also offers, in conjunction with an implicit solvent model, high accuracy for the corresponding dissociation barriers in solution. The accurate description is used to extrapolate information about the different components of the barriers.

Reaction of cis-Ru(κ²-OAc)₂(PPh₃)₂ with two-electron donor ligands L results in the formation of complexes trans-[Ru(κ¹-OAc)(κ²-OAc)L(PPh₃)₂] (L = CO, NO⁺, CNtBu). Vinylidene complexes (L = C=CHR) may be prepared from the corresponding reaction with terminal alkynes HC≡CR, and species containing hydroxyvinylidene ligands (L = C=CHCR¹R²{OH}) may be prepared from related reactions with propargyl alcohols HC≡CCR¹R²{OH}. Treatment of cis-Ru(κ²-OAc)₂(PPh₃)₂ with ω-alkynols HC≡C(CH₂)_nOH (n = 2–4) results in the formation of oxacyclocarbene complexes [L = CCH₂(CH₂)_nO]. An analysis of the spectroscopic data and the structural metrics (as determined by X-ray crystallography) of this series of complexes allows for the relative donor/acceptor properties of the ligand L to be evaluated. This comparison indicates that the vinylidene ligand behaves in a similar fashion to the isocyanide ligand.

The complex cis-[Ru(κ²-OAc)₂(PPh₃)₂] acts as a precursor for the formation of the complexes trans-[Ru(κ¹-OAc)(κ²-OAc)L(PPh₃)₂] where L is a two-electron donor, σ-donor/π-acceptor ligand. The structural and spectroscopic data of these species provide insight into the relative electron demand of the ligands L.

We report a cyano-bridged V–Nb bimetal assembly,K_0.59V^II_1.59V^III_0.41[Nb^IV(CN)₈]·(SO₄)_0.50·6.9H₂O, exhibiting ferrimagnetism with a high Curie temperature (T_C) of 210 K, which is the highest T_C value among those of octacyano-bridged bimetal assemblies. Such a high T_C value originates from the high coordination number of octacyanoniobate and the strong superexchange interaction between V^II (S = 3/2) and Nb^IV (S = 1/2) through the CN groups.

We prepared a V–Nb octacyano-bridged bimetal assembly, K_0.59V^II_1.59V^III_0.41[Nb^IV(CN)₈]·(SO₄)_0.50·6.9H₂O, with a high Curie temperature (T_C) of 210 K, which is the highest T_C among those of other octacyanometalate-based compounds. The high coordination number of octacyanoniobate and the strong superexchange interaction between V^II (S = 3/2) and Nb^IV (S = 1/2) through the CN groups are the reasons for such a high value.

Treatment of an arene–ruthenium dichloride dimer with thiols RSH to lead to cationic trithiolato complexes of the type [(arene)₂Ru₂(SR)₃]⁺ was shown to proceed through the neutral thiolato complexes [(arene)₂Ru₂(SR)₂Cl₂], which have been isolated and characterized for arene = p-MeC₆H₄iPr and R = CH₂Ph (1), CH₂CH₂Ph (2), CH₂C₆H₄-p-tBu (3), and C₆H₁₁ (4). The single-crystal X-ray structure analysis of the p-tert-butylbenzyl derivative 3 reveals that the two ruthenium atoms are bridged by the two thiolato ligands without a metal–metal bond. The neutral dithiolato complexes[(arene)₂Ru₂(SR)₂Cl₂] (1–3) are intermediates in the formation of the cationic trithiolato complexes [(arene)₂Ru₂(SR)₃]⁺ (5–7). Of the new [(arene)₂Ru₂(SR)₂Cl₂] complexes, derivative 2 is highly cytotoxic against human ovarian cancer cells, with IC₅₀ values of 0.20 μM for the A2780 cell line and 0.31 for the cisplatin-resistant cell line A2780cisR.

Treatment of p-cymene–ruthenium dichloride dimer with aliphatic thiols to give cationic trithiolato–diruthenium complexes was shown to proceed through the intermediacy of the corresponding neutral dithiolato complexes.