Biomedical subjects

Timofei Privalov

Publications and source records attributed to Timofei Privalov.

9 recordsLinked to original sources

PubMed2006

Mechanistic study of hydrogen transfer to imines from a hydroxycyclopentadienyl ruthenium hydride. Experimental support for a mechanism involving coordination of imine to ruthenium prior to hydrogen transfer.

Reaction of [2,3,4,5-Ph(4)(eta(5)-C(4)COH)Ru(CO)(2)H] (2) with different imines afforded ruthenium amine complexes at low temperatures. At higher temperatures in the presence of 2, the complexes decomposed to give [Ru(2)(CO)(4)(mu-H)(C(4)Ph(4)COHOCC(4)Ph(4))] (1) and free amine. Electron-rich imines gave ruthenium amine complexes with 2 at a lower temperature than did electron-deficient imines. The negligible deuterium isotope effect (k(RuHOH)/k(RuDOD) = 1.05) observed in the reaction of 2 with N-phenyl[1-(4-methoxyphenyl)ethylidene]amine (12) shows that neither hydride (RuH) nor proton (OH) is transferred to the imine in the rate-determining step. In the dehydrogenation of N-phenyl-1-phenylethylamine (4) to the corresponding imine 8 by [2,3,4,5-Ph(4)(eta(4)-C(4)CO)Ru(CO)(2)] (A), the kinetic isotope effects observed support a stepwise hydrogen transfer where the isotope effect for C-H cleavage (k(CHNH)/k(CDNH) = 3.24) is equal to the combined (C-H, N-H) isotope effect (k(CHNH)/k(CDND) = 3.26). Hydrogenation of N-methyl(1-phenylethylidene)amine (14) by 2 in the presence of the external amine trap N-methyl-1-(4-methoxyphenyl)ethylamine (16) afforded 90-100% of complex [2,3,4,5-Ph(4)(eta(4)-C(4)CO)]Ru(CO)(2)NH(CH(3))(CHPhCH(3)) (15), which is the complex between ruthenium and the amine newly generated from the imine. At -80 degrees C the reaction of hydride 2 with 4-BnNH-C(6)H(9)=NPh (18), with an internal amine trap, only afforded [2,3,4,5-Ph(4)(eta(4)-C(4)CO)](CO)(2)RuNH(Ph)(C(6)H(10)-4-NHBn) (19), where the ruthenium binds to the amine originating from the imine, showing that neither complex A nor the diamine is formed. Above -8 degrees C complex 19 rearranged to the thermodynamically more stable [Ph(4)(eta(4)-C(4)CO)](CO)(2)RuNH(Bn)(C(6)H(10)-4-NHPh) (20). These results are consistent with an inner sphere mechanism in which the substrate coordinates to ruthenium prior to hydrogen transfer and are difficult to explain with the outer sphere pathway previously proposed.

Journal Article↗

PubMed2006

The importance of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide-catalyzed enantioselective transfer hydrogenation of ketones.

We studied the role of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide-catalyzed enantioselective transfer hydrogenation of ketones with isopropanol. Lithium salts were shown to increase the enantioselectivity of the reaction when iPrONa or iPrOK was used as the base. Similar transfer-hydrogenation systems that employ chiral amino alcohol or monotosylated diamine ligands are not affected by the addition of lithium salts. These observations have led us to propose that an alternative reaction mechanism operates in pseudo-dipeptide-based systems, in which the alkali cation is an important player in the ligand-assisted hydrogen-transfer step. DFT calculations of the proposed transition-state (TS) models involving different cations (Li+, Na+, and K+) confirm a considerable loosening of the TS with larger cations. This loosening may be responsible for the fewer interactions between the substrate and the catalytic complex, leading to lower enantiodifferentiation. This mechanistic hypothesis has found additional experimental support; the low ee obtained with [BnNMe3]OH (a large cation) as base can be dramatically improved by introducing lithium cations into the system. Also, the complexation of Na+, K+, and Li+ cations by the addition of [15]crown-5 and [18]crown-6 ethers and cryptand 2.1.1 (which selectively bind to these cations and, thus, increase their bulkiness), respectively, to the reaction mixture led to a significant drop in the enantioselectivity of the reaction. The lithium effect has proved useful for enhancing the reduction of different aromatic and heteroaromatic ketones.

Alkalies↗

PubMed2006

A computational study of oxidation of ruthenium porphyrins via ORu(IV) and ORu(VI)O species.

An unrestricted density functional theory (UDFT) was applied to study the oxidation of ruthenium porphyrins, [RuP], via an interaction with molecular oxygen. The important role of dimeric [RuP] complexes, i.e. [RuP]-O2-[RuP], in the oxidation mechanism and particular in the cleavage of O-O bond of molecular oxygen has been studied. Geometries and relative Gibbs free energies of the intermediate Ru-complexes, i.e. dimeric oxo-Ru-porphyrins and O2Ru(II)-(or O2- Ru(III))-, ORu(IV)- and ORu(VI)O-porphyrins, were evaluated along the proposed reaction pathway. The detailed thermodynamic data of the oxidation reaction [Ru(II)P] --> O[Ru(IV)P] --> O[Ru(VI)P]O and important aspects of the vibrational spectra of an oxo-[RuP] has been presented.

Computer Simulation↗

PubMed2005

Conformational preferences and enantiodiscrimination of phosphino-4-(1-hydroxyalkyl)oxazoline-metal-olefin complexes resulting from an OH-metal hydrogen bond.

[reaction: see text] Phosphinooxazolines carrying (1-hydroxy-1-phenyl)methyl and (1-methoxy-1-phenyl)methyl substituents in the 4 position of the oxazoline ring exhibit contrasting behavior in Pd- and Ir-catalyzed allylic alkylations. Whereas catalysts with the methoxy-containing ligand generally provide products with high ee's, use of catalysts prepared from the hydroxy-containing ligand results in products with low ee's or even racemates. DFT calculations suggest the presence of a hydrogen bond with Pd(0) as the proton acceptor in the hydroxy-containing olefin-Pd(0) complexes, which induces a conformational change in the ligand, leading to different stereoselectivity.

Alkenes↗

PubMed2005

Using mechanistic and computational studies to explain ligand effects in the palladium-catalyzed aerobic oxidation of alcohols.

The experimental and computational mechanistic details of the Pd(OAc)(2)/TEA-catalyzed aerobic alcohol oxidation system are disclosed. Measurement of various kinetic isotope effects and the activation parameters as well as rate law derivation support rate-limiting deprotonation of the palladium-coordinated alcohol. Rate-limiting deprotonation of the alcohol is contrary to the majority of related kinetic studies for Pd-catalyzed aerobic oxidation of alcohols, which propose rate-limiting beta-hydride elimination. This difference in the rate-limiting step is supported by the computational model, which predicts the activation energy for deprotonation is 3 kcal/mol higher than the activation energy for beta-hydride elimination. The computational features of the similar Pd(OAc)(2)/pyridine system were also elucidated. Details of the study illustrate that the use of TEA results in an active catalyst that has only one ligand bound to the Pd, resulting in a significant lowering of the activation energy for beta-hydride elimination and, therefore, a catalyst that is active at room temperature.

Aerobiosis↗

PubMed2005

Electron transfer in neptunyl(VI)-neptunyl(V) complexes in solution.

The rates and mechanisms of the electron self-exchange between Np(V) and Np(VI) in solution have been studied with quantum chemical methods and compared with previous results for the U(V)-U(VI) pair. Both outer-sphere and inner-sphere mechanisms have been investigated, the former for the aqua ions, the latter for binuclear complexes containing hydroxide, fluoride, and carbonate as bridging ligand. Solvent effects were calculated using the Marcus equation for the outer-sphere reactions and using a nonequilibrium PCM method for the inner-sphere reactions. The nonequilibrium PCM appeared to overestimate the solvent effect for the outer-sphere reactions. The calculated rate constant for the self-exchange reaction NpO2(+)(aq) + NpO2(2+)(aq) right harpoon over left harpoon NpO2(2+)(aq) + NpO2(+)(aq), at 25 degrees C is k = 67 M(-1) s(-1), in fair agreement with the observed rates 0.0063-15 M(-1) s(-1). The differences between the Np(V)-Np(VI) and the U(V)-U(VI) pairs are minor.

Journal Article↗

PubMed2005

Spin-orbit effects in electron transfer in neptunyl(VI)-neptunyl(V) complexes in solution.

The spin-orbit effects were investigated on the complexes involved in the electron self-exchange between Np(V) and Np(VI) in both the outer-sphere and inner-sphere mechanisms, the latter for binuclear complexes containing hydroxide, fluoride, and carbonate as bridging ligands. Results obtained with the variation-perturbation and the multireference single excitation spin-orbit CI calculations are compared. Both effects due to different relaxations of spinors within a multiplet (spin-orbit relaxation) and scalar (electrostatic) relaxation effects in the excited states are accounted for in the latter scheme. The results show that the scalar (electrostatic) relaxation is well described by the single-excitation spin-orbit CI, and that spin-orbit relaxation effects are small in the Np complexes, as in the lighter d-transition elements but in contrast to the main group elements.

Journal Article↗

PubMed2004

Electron transfer in uranyl(VI)-uranyl(V) complexes in solution.

The rates and mechanisms of the electron self-exchange between U(V) and U(VI) in solution have been studied with quantum chemical methods. Both outer-sphere and inner-sphere mechanisms have been investigated; the former for the aqua ions, the latter for binuclear complexes containing hydroxide, fluoride, and carbonate as bridging ligand. The calculated rate constant for the self-exchange reaction UO(2)(+)(aq) + UO(2)(2+)(aq) <=>UO(2)(2+)(aq) + UO(2)(+)(aq), at 25 degrees C, is k = 26 M(-1) s(-1). The lower limit of the rate of electron transfer in the inner-sphere complexes is estimated to be in the range 2 x 10(4) to 4 x 10(6) M(-1) s(-1), indicating that the rate for the overall exchange reaction may be determined by the rate of formation and dissociation of the binuclear complex. The activation energy for the outer-sphere model calculated from the Marcus model is nearly the same as that obtained by a direct calculation of the precursor- and transition-state energy. A simple model with one water ligand is shown to recover 60% of the reorganization energy. This finding is important because it indicates the possibility to carry out theoretical studies of electron-transfer reactions involving M(3+) and M(4+) actinide species that have eight or nine water ligands in the first coordination sphere.

Journal Article↗

PubMed2004

The mechanism of water exchange in AmO2(H2O)5(2+) and in the isoelectronic UO2(H2O)5(+) and NpO2(H2O)5(2+) complexes as studied by quantum chemical methods.

The water exchange mechanism for AmO2(H2O)52+ and the isoelectronic UO2(H2O)5+ and NpO2(H2O)52+ ions has been investigated using quantum chemical methods and compared to previous findings in the uranyl(VI) system (Vallet, V. et al. J. Am. Chem. Soc. 2001, 123, 11999). There are substantial and predictable changes in the geometry and preferred exchange pathways between uranyl(V) and the different actinyl(VI) complexes. The smaller charge on the uranyl(V) center makes the dissociative pathway more favorable than the associative/interchange pathways in the actinyl(VI) systems.

Journal Article↗