1.Scope and Mechanistic Analysis for Chemoselective Hydrogenolysis of Carbonyl Compounds Catalyzed by a Cationic Ruthenium Hydride Complex with a Tunable Phenol Ligand.
Kalutharage N1, Yi CS1. J Am Chem Soc. 2015 Sep 2;137(34):11105-14. doi: 10.1021/jacs.5b06097. Epub 2015 Aug 25.
A cationic ruthenium hydride complex, [(C6H6)(PCy3)(CO)RuH](+)BF4(-) (1), with a phenol ligand was found to exhibit high catalytic activity for the hydrogenolysis of carbonyl compounds to yield the corresponding aliphatic products. The catalytic method showed exceptionally high chemoselectivity toward the carbonyl reduction over alkene hydrogenation. Kinetic and spectroscopic studies revealed a strong electronic influence of the phenol ligand on the catalyst activity. The Hammett plot of the hydrogenolysis of 4-methoxyacetophenone displayed two opposite linear slopes for the catalytic system 1/p-X-C6H4OH (ρ = -3.3 for X = OMe, t-Bu, Et, and Me; ρ = +1.5 for X = F, Cl, and CF3). A normal deuterium isotope effect was observed for the hydrogenolysis reaction catalyzed by 1/p-X-C6H4OH with an electron-releasing group (kH/kD = 1.7-2.5; X = OMe, Et), whereas an inverse isotope effect was measured for 1/p-X-C6H4OH with an electron-withdrawing group (kH/kD = 0.
2.Reaction mechanism in crystalline solids: kinetics and conformational dynamics of the Norrish type II biradicals from α-adamantyl-p-methoxyacetophenone.
Kuzmanich G1, Vogelsberg CS, Maverick EF, Netto-Ferreira JC, Scaiano JC, Garcia-Garibay MA. J Am Chem Soc. 2012 Jan 18;134(2):1115-23. doi: 10.1021/ja2090004. Epub 2011 Dec 29.
In an effort to determine the details of the solid-state reaction mechanism and diastereoselectivity in the Norrish type II and Yang cyclization of crystalline α-adamantyl-p-methoxyacetophenone, we determined its solid-state quantum yields and transient kinetics using nanocrystalline suspensions. The transient spectroscopy measurements were complemented with solid-state NMR spectroscopy spin-lattice relaxation experiments using isotopically labeled samples and with the analysis of variable-temperature anisotropic displacement parameters from single-crystal X-ray diffraction to determine the rate of interconversion of biradical conformers by rotation of the globular adamantyl group. Our experimental findings include a solid-state quantum yield for reaction that is 3 times greater than that in solution, a Norrish type II hydrogen-transfer reaction that is about 8 times faster in crystals than in solution, and a biradical decay that occurs on the same time scale as conformational exchange, which helps to explain the diastereoselectivity observed in the solid state.
3.Spectrophotometric, voltammetric and cytotoxicity studies of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone and its N(4)-substituted derivatives: a combined experimental-computational study.
Akgemci EG1, Saf AO2, Tasdemir HU3, Türkkan E4, Bingol H5, Turan SO6, Akkiprik M7. Spectrochim Acta A Mol Biomol Spectrosc. 2015 Feb 5;136 Pt B:719-25. doi: 10.1016/j.saa.2014.09.087. Epub 2014 Sep 30.
In this study, 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) and its novel N(4) substituted derivatives were synthesized and characterized by different techniques. The optical band gap of the compounds and the energy of HOMO were experimentally examined by UV-vis spectra and cyclic voltammetry measurements, respectively. Furthermore, the conformational spaces of the compounds were scanned with molecular mechanics method. The geometry optimization, HOMO and LUMO energies, the energy gap of the HOMO-LUMO, dipole moment of the compounds were theoretically calculated by the density functional theory B3LYP/6-311++G(d,p) level. The minimal electronic excitation energy and maximum wavelength calculations of the compounds were also performed by TD-DFT//B3LYP/6-311++G(d,p) level of theory. Theoretically calculated values were compared with the related experimental values. The combined results exhibit that all compounds have good electron-donor properties which affect anti-proliferative activity.
4.An improved method for specific and quantitative determination of the clopidogrel active metabolite isomers in human plasma.
Tuffal G1, Roy S, Lavisse M, Brasseur D, Schofield J, Delesque Touchard N, Savi P, Bremond N, Rouchon MC, Hurbin F, Sultan E. Thromb Haemost. 2011 Apr;105(4):696-705. doi: 10.1160/TH10-09-0582. Epub 2011 Feb 8.
Pharmacokinetic analyses of clopidogrel are hampered by the existence of multiple active metabolite isomers (H1 to H4) and their instability in blood. We sought to retest the pharmacodynamic activities of the four individual active metabolite isomers in vitro, with the ultimate aim of determining the isomers responsible for clopidogrel activity in vivo. In vitro activity was evaluated by measuring binding of [³³P]-2-methylthio-ADP on P2Y₁₂-expressing Chinese hamster ovary (CHO) cells and human platelets in platelet-rich plasma (PRP). A stereoselective method that used reverse-phase ultra high-performance liquid chromatography (UHPLC) and tandem mass spectrometry (MS) was developed to measure individual concentrations of the stable 3'-methoxyacetophenone (MP) derivatives of H1-H4. The new method was used to analyze plasma samples from clopidogrel-treated subjects enrolled in a phase I clinical trial. In vitro binding assays confirmed the previously observed biological activity of H4 (IC₅₀: CHO-P2Y₁₂: 0.