H-abstraction is more efficient than cis-trans isomerization in (4-methylcyclohexylidene) fluoromethane. An ab initio molecular dynamics study

Non-adiabatic molecular dynamics simulations have been performed in the fluoro-olefin (4-methylcyclohexylidene) fluoromethane (4MCF) using multiconfigurational CASSCF (complete active space self-consistent field) on-the-fly calculations. As an olefin containing a C[double bond, length as m-dash]C double bond, 4MCF is expected to undergo cis-trans isomerization after light irradiation. However, ab initio molecular dynamics shows that a preferential dissociation of atomic hydrogen is taking place after population transfer to the bright ππ* state. This state is strongly mixed with πσ* states allowing dissociation in the electronic excited state before deactivation to the ground state occurs. A minor amount of trajectories experiences F-dissociation, followed by pyramidalization at the sp(2) carbons and CHF dissociation. In contrast, the amount of trajectories undergoing torsion around the double bond, and therefore cis-trans isomerization, is marginal. The H-abstraction reaction is ultrafast, taking place in less than 60 fs.     

Transformations of diphenylphosphinothioic acid tertiary amides mediated by directed ortho metallation

ortho-Lithiation of N,N-diisopropyl-P,P-diphenylphosphinothioic amide using n-BuLi in the presence of TMEDA in diethyl ether followed by electrophilic trapping is described as an efficient method for the synthesis of ortho-functionalised derivatives in high yields. The structural modification of the phosphinothioic amide includes C-X (X = P, S, Si, Sn, I) and C-C bond forming reactions with a large variety of electrophiles. Additional applications based on functional group transformations are also reported. They include imine formation, desulfurization and Suzuki cross-coupling reactions on selected compounds.     

Synthesis, 5-hydroxytryptamine1A receptor affinity and docking studies of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives

A series of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives (12a-h) was synthesized and evaluated for binding affinity at the human 5-hydroxytryptamine(1A) receptor (5-HT(1A)R) compounds (12b) and (12h) showed the highest 5-HT(1A) receptor affinity (IC(50)=15 nM). Molecular docking studies with all the compounds in a homology model of 5-HT(1A) showed that the main interaction anchoring the ligand in the receptor was a charge-reinforced bond between the protonated nitrogen atom (N-4) of the piperazine ring and Aspartate(3.32).     

A non-adiabatic quantum-classical dynamics study of the intramolecular excited state hydrogen transfer in ortho-nitrobenzaldehyde

Ab initio surface-hopping dynamics calculations have been performed to simulate the intramolecular excited state hydrogen transfer dynamics of ortho-nitrobenzaldehyde (o-NBA) in the gas phase from the electronic S(1) excited state. Upon UV excitation, the hydrogen is transferred from the aldehyde substituent to the nitro group, generating o-nitrosobenzoic acid through a ketene intermediate. The semiclassical propagations show that the deactivation from the S(1) is ultrafast, in agreement with the experimental measurements, which detect the ketene in less than 400 fs. The trajectories show that the deactivation mechanism involves two different conical intersections. The first one, a planar configuration with the hydrogen partially transferred, is responsible for the branching between the formation of a biradical intermediate and the regeneration of the starting material. The conversion of the biradical to the ketene corresponds to the passage through a second intersection region in which the ketene group is formed.     

Conformational flexibility of a synthetic glycosylaminoglycan bound to a fibroblast growth factor. FGF-1 recognizes both the (1)C(4) and (2)S(O) conformations of a bioactive heparin-like hexasaccharide

The first direct NMR determination of the conformation of a conformationally flexible heparin-like hexasaccharide bound to a key receptor, FGF-1, is described. The determination has been based on the use of a 13C-labeled protein and a regular 12C sugar. FGF-1 recognizes several conformations of the iduronic moieties of the hexasaccharide. Therefore, this case is different than that described for the controversial recognition of heparin-like saccharides by AT-III, which seems to recognize just one conformation of the iduronic acid residues.     

Effect of dielectric medium on angiotensin converting enzyme inhibitors binding to Zn<Superscript>2+</Superscript>

The Becke3LYP density functional was used to study structural and thermodynamic parameters of bivalent zinc cation complexes with selected substrates and ACE inhibitors (H₂O/OH⁻, neutral forms of captopril, zofenoprilat, omapatrilat, CH₃CONHCH₃, and N-terminal anions of captopril, zofenoprilat, omapatrilat, enalaprilat, perindoprilat, trandolaprilat, and fosinoprilat). The combination of DFT and the conductor-like polarizable continuum model (CPCM) were employed to compute the Gibbs interaction energies (ΔG) between Zn²⁺ and the selected ACE inhibitors for dielectric media with ɛ = 5 (to simulate the protein environment) and for water media (ɛ = 78.39) for comparison purposes. The results show that ΔG is sensitive to the dielectric constant of the environment and that lower dielectric medium favors the binding of inhibitors to the zinc cation.     

Visible Light-Gated Organocatalysis Using a RuII-Photocage

The light-gated organocatalysis via the release of 4-N,N-dimethylaminopyridine (DMAP) by irradiation of the [Ru(bpy)₂(DMAP)₂]²⁺ complex with visible light was investigated. As model reaction the acetylation of benzyl alcohols with acetic anhydride was chosen. The pre-catalyst releases one DMAP molecule on irradiation at wavelengths longer than 455 nm. The photochemical process was characterized by steady-state irradiation and ultrafast transient absorption spectroscopy. The latter enabled the observation of the ³MLCT state and the spectral features of the penta-coordinated intermediate [Ru(bpy)₂(DMAP)]²⁺. The released DMAP catalyzes the acetylation of a wide range of benzyl alcohols with chemical yields of up to 99 %. Control experiments revealed unequivocally that it is the released DMAP which takes the role of the catalyst.     

Study of the capillary electrophoresis profile of intact α-1-acid glycoprotein isoforms as a biomarker of atherothrombosis

α-1-Acid glycoprotein (AGP) is a serum glycoprotein that presents several isoforms. Changes in the isoforms of AGP have been related to different pathological states including cardiovascular diseases (CVDs) such as acute myocardial infarction. However, to our knowledge, the role of variations of AGP isoforms as a potential biomarker of atherothrombosis has not been addressed. In this work, a preliminary study about differences in the capillary zone electrophoresis (CZE) profile of intact (non-hydrolyzed) AGP isoforms between healthy individuals and patients with atherothrombosis, specifically abdominal aortic aneurysm (AAA) and carotid atherosclerosis (CTA), has been performed. Biological samples (plasmas and sera) were analyzed by CZE after immunoaffinity chromatography purification. Up to 13 peaks corresponding to groups of isoforms of intact AGP from plasma samples were detected by CZE-UV. Electrophoretic profiles were aligned, peaks assigned, and linear discriminant analysis (LDA) of percentage of the corrected areas of AGP peaks was employed to discriminate and classify the CZE profiles of AGP samples. LDA enabled to accomplish 92.9% of correct classification of the AGP samples when the three groups of samples were considered. Besides, the LDA model showed high predictive power in the groups healthy vs. sick, healthy vs. AAA, and healthy vs. CTA. The described method was a successful approach to study the potential of AGP isoforms profile as a biomarker of atherothrombosis. To the best of our knowledge this has been the first time that a possible role of the CZE profile of intact AGP isoforms as a biomarker of vascular diseases has been demonstrated.     

Effect of additives on the performance of Dyckerhoff cement,Class G,submitted to simulated hydrothermal curing

Stability of Dyckerhoff cement Class G partially substituted (15 mass%) by metakaolin (MK), silica fume (SF) and ground granulated blast-furnace slag (BFS) was investigated after 7 days of curing under standard and two different autoclaving conditions. Mercury intrusion porosimetry, X-ray diffraction analysis and combined thermogravimetric–differential scanning calorimetry were used to evaluate pore structure development, compressive strength and their dependence on the type of additives in relation to the particular phase composition. Hydrothermal curing led to the formation of α-C₂SH and jaffeite, mostly in the case of referential samples and compositions with addition of slowly reacting BFS. Whilst modest hydrothermal curing (0.6 MPa, 165 °C) favoured formation of α-C₂SH, larger amounts of jaffeite were determined after curing at the highest used pressure and temperature (2.0 MPa, 220 °C). Undesired transformation of primary hydration products was prevented especially by addition of highly reactive and very fine SF. Particular composition attained the best pore structure characteristics and compressive strength after curing at 0.6 MPa and 165 °C. Formation of more stable phases with C/S ratio close to 1 was proved by wollastonite formation during DSC analyses. More severe conditions of curing, however, led to the significant deterioration of microstructure and strength of corresponding sample, probably due to the formation of trabzonite, killalaite and zoisite. Considering the values of hydraulic permeability coefficient and compressive strength, replacement of cement by MK improved significantly the properties of cement when compared with the referential as well as with other blended compositions under the mentioned curing conditions.