Unsymmetrical zinc azaphthalocyanines,peripherally substituted with thiophen-2-yl and 2-functionalized phenoxy groups

Four targeted octasubstituted zinc azaphthalocyanines (ZnAzaPc), substituted with thiophen-2-yl groups and ortho-substituted phenoxy groups, were obtained by cyclotetramerization of 5-aryloxy-6-(thiophen-2-yl)pyrazine-2,3-dicarbonitriles. Thiophen-2-yl substituents are known to extend the macrocyclic conjugation, and thereby cause red-shifted UV–Vis Q-bands. Peripheral phenoxy groups with bulky ortho substituents are expected to suppress aggregation and thereby improve solubility of these compounds. The reagent Zn(quinoline)₂Cl₂ was used for one-step syntheses of these ZnAzaPc. Four tetrasubstituted ZnAzaPc, with phenoxy, (2-isopropyloxy)phenoxy, (2-isopropyl)phenoxy or (2-tert-butyl)phenoxy substituents, were obtained as controls from 5-aryloxypyrazine-2,3-dicarbonitriles. The tetra- and octa-substituted ZnAzaPc, 5 and 6, were obtained in 30–50% yields after purification by chromatography on silica. UV–Vis Q-bands with high molar extinction coefficients (100 000–160 000), were observed at 635 nm for compounds 5, and at 660–665 nm for 6. Grass-green solutions were obtained of compounds 6 in most organic solvents, whereas the less soluble compounds 5 gave blue-green solutions. 2D NMR methods were applied in analyses of DMSO-d₆ solutions of ZnAzaPc 5 and 6. Broad and partly overlapping ¹H NMR signals for some of the compounds indicate some aggregation as well as presence of two or more structural isomers. Molecular ions of ZnAzaPc 5 and 6 were determined by mass spectrometry (MALDI-TOF).     

Ultrafast photodynamics of furan

Ultrafast photodynamics of furan has been studied by time-resolved photoelectron imaging (TRPEI) spectroscopy with an unprecedented time resolution of 22 fs. The simulation of the time-dependent photoelectron kinetic energy distribution (PKED) has been performed with ab initio nonadiabatic dynamics "on the fly" in the frame of time-dependent density functional theory. Based on the agreement between experimental and theoretical time-dependent photoelectron signal intensity as well as on PKED, precise time scales of ultrafast internal conversion from S(2) over S(1) to the ground state S(0) of furan have been revealed for the first time. Upon initial excitation of the S(2) state which has π-π* character, a nonadiabatic transition to the S(1) state occurs within 10 fs. Subsequent dynamics invokes the excitation of the C-O stretching and C-O-C out of plane vibrations which lead to the internal conversion to the ground state after 60 fs. Thus, we demonstrate that the TRPEI combined with high level nonadiabatic dynamics calculations provide fundamental insight into ultrafast photodynamics of chemically and biologically relevant chromophores.     

Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots

Kaletra® (Abott Laboratories) is a co-formulated medication used in the treatment of HIV-1-infected children, and it contains the two antiretroviral protease inhibitor drugs lopinavir and ritonavir. We validated two new ultrafast and high-throughput mass spectrometric assays to be used for therapeutic drug monitoring of lopinavir and ritonavir concentrations in whole blood and in plasma from HIV-1-infected children. Whole blood was blotted onto dried blood spot (DBS) collecting cards, and plasma was collected simultaneously. DBS collecting cards were extracted by an acetonitrile/water mixture while plasma samples were deproteinized with acetone. Drug concentrations were determined by matrix-assisted laser desorption/ionization-triple quadrupole tandem mass spectrometry (MALDI-QqQ-MS/MS). The application of DBS made it possible to measure lopinavir and ritonavir in whole blood in therapeutically relevant concentrations. The MALDI-QqQ-MS/MS plasma assay was successfully cross-validated with a commonly used high-performance liquid chromatography (HPLC)–ultraviolet (UV) assay for the therapeutic drug monitoring (TDM) of HIV-1-infected patients, and it showed comparable performance characteristics. Observed DBS concentrations showed as well, a good correlation between plasma concentrations obtained by MALDI-QqQ-MS/MS and those obtained by the HPLC-UV assay. Application of DBS for TDM proved to be a good alternative to the normally used plasma screening. Moreover, collection of DBS requires small amounts of whole blood which can be easily performed especially in (very) young children where collection of large whole blood amounts is often not possible. DBS is perfectly suited for TDM of HIV-1-infected children; but nevertheless, DBS can also easily be applied for TDM of patients in areas with limited or no laboratory facilities.     

Assessment of cardiac iron by MRI susceptometry and R2* in patients with thalassemia

A magnetic resonance imaging cardiac magnetic susceptometry (MRI-CS) technique for assessing cardiac tissue iron concentration based on phase mapping was developed. Normal control subjects (n=9) and thalassemia patients (n=13) receiving long-term blood transfusion therapy underwent MRI-CS and MRI measurements of the cardiac relaxation rate R2*. Using MRI-CS, subepicardium and subendocardium iron concentrations were quantified exploiting the hemosiderin/ferritin iron specific magnetic susceptibility. The average of subepicardium and subendocardium iron concentrations and R2* of the septum were found to be strongly correlated (r=0.96, P<.0001), and linear regression analysis yielded CIC (μg Fe/g_{wet tissue})=(6.4±0.4)·R2* _septum (s⁻¹) − (120±40). The results demonstrated that septal R2* indeed measures cardiac iron level.     

Three-dimensional T1, T2 and proton density mapping with inversion recovery balanced SSFP

By combining a balanced steady-state free precession (bSSFP) readout with an initial inversion pulse, all three contrast parameters, T₁, T₂ and proton density (M₀), may be rapidly calculated from the signal progression in time. However, here it is shown that this technique is quite sensitive to variation in the applied transmit RF (B₁) field, leading to pronounced errors in calculated values. Two-dimensional (2D) acquisitions are taxed to accurately quantify the relaxation, as the short RF pulses required by SSFP's rapid TR contain a broad spectrum of excitation angles. A 3D excitation using a large diameter excitation coil was able to correctly quantify the parameters. While the extreme B₁ sensitivity was previously problematic and has precluded use of IR-bSSFP for relaxometry, in this work these obstacles were significantly reduced, allowing the rapid quantification of T₁, T₂ and M₀. The results may further be used to simulate image contrast from common sequences, such as a T₁-weighted or fluid-attenuated inversion recovery (FLAIR) examination.     

Origins of life and biochemistry under high-pressure conditions

Life on Earth can be traced back to as far as 3.8 billion years (Ga) ago. The catastrophic meteoritic bombardment ended between 4.2 and 3.9 Ga ago. Therefore, if life emerged, and we know it did, it must have emerged from nothingness in less than 400 million years. The most recent scenarios of Earth accretion predict some very unstable physico-chemical conditions at the surface of Earth, which, in such a short time period, would impede the emergence of life from a proto-biotic soup. A possible alternative would be that life originated in the depth of the proto-ocean of the Hadean Earth, under high hydrostatic pressure. The large body of water would filter harmful radiation and buffer physico-chemical variations, and therefore would provide a more stable radiation-free environment for pre-biotic chemistry. After a short introduction to Earth history, the current tutorial review presents biological and physico-chemical arguments in support of high-pressure origin for life on Earth.     

Reactivity of the CHBr2+ dication toward molecular hydrogen

Structural aspects as well as the stability and reactivity of the CHBr(2+) dication are studied both experimentally and theoretically. Translational energy distributions of the CHBr(+) products from charge transfer between CHBr(2+) and Kr indicate that the dication exists in two isomeric forms, H-C-Br(2+) and C-Br-H(2+). In the reaction of CHBr(2+) with H(2), the dominant channel corresponds to proton transfer leading to CBr(+) + H(3)(+). Other reaction channels involve the formation of the intermediates CH(3)Br(2+) and CH(2)BrH(2+), respectively. Both of the latter dications can either lose a proton to form CH(2)Br(+) or undergo a spin-isomerization followed by cleavage of the C-Br bond. The proposed mechanisms are supported by DFT calculations and deuterium labeling experiments.     

Thermodynamic scaling of the viscosity of van der Waals, H-bonded, and ionic liquids

Viscosities eta and their temperature T and volume V dependences are reported for seven molecular liquids and polymers. In combination with literature viscosity data for five other liquids, we show that the superpositioning of relaxation times for various glass-forming materials when expressed as a function of TV(gamma), where the exponent gamma is a material constant, can be extended to the viscosity. The latter is usually measured to higher temperatures than the corresponding relaxation times, demonstrating the validity of the thermodynamic scaling throughout the supercooled and higher T regimes. The value of gamma for a given liquid principally reflects the magnitude of the intermolecular forces (e.g., steepness of the repulsive potential); thus, we find decreasing gamma in going from van der Waals fluids to ionic liquids. For some strongly H-bonded materials, such as low molecular weight polypropylene glycol and water, the superpositioning fails, due to the nontrivial change of chemical structure (degree of H bonding) with thermodynamic conditions.