Imidazo[1,5-g][1,4]diazepines, TIBO analogues lacking the phenyl ring: synthesis and evaluation as anti-HIV agents.

The imidazo[1,5-g][1,4]diazepine derivatives 7a and 7b, analogues of TIBO lacking the aromatic ring, were prepared as part of a research program to find compounds displaying antiviral activity against HIV-2 and resistant strains of HIV-1. Condensation of N-trityl and N-tosyl 4-(2-chloroethyl)-imidazole with the appropriate amino alcohols gave compounds 10a-c and 16a-e. The hydroxyl group in these intermediates was activated toward closure of the [1,4]diazepine ring by either conversion to the corresponding chloro derivative, or by N → O transfer of the tosyl group. However, only cyclization to compounds 13a and 13b proved efficient. These products were converted to the target molecules 7 by reaction of their C-2 anion with S₈. In vitro evaluation of compounds 7a,b and 13,a,b in cell culture (CEM SS/HIV-1-LAI and CEM SS/HIV 1 nevirapine resistant cells) revealed that only 13b displayed minimal activity.     

Simultaneous Triple Radiation Mössbauer Spectroscopy (STRMS)

The setup for Simultaneous Triple Radiation Mössbauer Spectroscopy (STRMS) is described. The arrangement allows an independent and simultaneous recording of conversion electron Mössbauer spectra (CEMS) and of conversion X-ray Mössbauer spectra (CXMS), both in backscattering geometry, and-in addition-of γ-ray absorption spectra in transmission (TMS). Due to the different escape or penetration ranges of the three radiations involved, the spectra give information on phases, depth and orientation. From a practical point of view the counter for γ-rays, X-rays and electrons must be separated and shielded to minimize the mutual perturbation.     

Prodrugs of HIV protease inhibitors-saquinavir, indinavir and nelfinavir-derived from diglycerides or amino acids: synthesis, stability and anti-HIV activity

With the aim of improving the pharmacological properties of current protease inhibitors (PIs), the synthesis of various acyl and carbamate amino acid- or diglyceride-containing prodrugs derived from saquinavir, indinavir and nelfinavir, their in vitro stability with respect to hydrolysis and their anti-HIV activity in CEM-SS and MT4 cells have been investigated. l-Leucine (Leu) and l-phenylalanine (Phe) were connected through their carboxyl to the PIs while l-tyrosine (Tyr) was conjugated through its aromatic hydroxyl via various spacer units. Hydrolysis of the prodrug with liberation of the active free drug was crucial for antiviral activity. The Leu- and Phe-PI prodrugs released the active free drug very rapidly (half-lives of hydrolysis in buffer at 37 degree C of 3-4 h). The Tyr-PI conjugates with a -C(O)(CH(2))(4)- linker exhibited half-lives in the 40-70 h range and antiviral activities in the 21-325 nM range (from 2 to 22 nM for the free PIs). The chemically very stable carbamate "peptidomimetic" Tyr-PI prodrugs (no hydrolysis detected after 7 days in buffer) displayed a very low anti-HIV activity or were even inactive (EC(50) from 2300 nM to >10 microM). A very low antiviral activity was measured for the diglyceride-substituted saquinavir and for all of the disubstituted indinavir and nelfinavir prodrugs. All these prodrugs probably released the active parent PI too slowly under the antiviral assay conditions. These results combined with those from transepithelial transport studies (Rouquayrol et al., Pharm. Res., 2002, 19, 1704-1712) indicate that conjugation of amino acids (through their carboxyl) to the PIs constitutes a most appealing alternative which could improve the intestinal absorption of the PIs and reduce their recognition by efflux carriers.     

Hydrogen desorption in Zr3Fe H5.5

Hydrogen desorption during heat treatments of (crystalline) Zr₃FeH_5.5 was studied by Mössbauer spectroscopy (MS), X-ray (powder) diffraction (XRD) and thermal gravimetry (TG). In case of sufficiently slow heating rate all hydrogen effuses below 650°K and no phase segregation occurs. At higher temperatures retained hydrogen induce phase separation into Fe₂Zr (or more likely Fe₂ZrH_x) and zirconium hydride. The existence of a highly disordered f.c. tetragonal ternary hydride phase was also detected both by XRD (a_o=4.76 Å, c=4.96 Å) and MS .     

Working group report: Heavy-ion physics and quark-gluon plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of quark-gluon plasma believed to have created in heavy-ion collisions and in early Universe are reported.     

Carbon and nitrogen in steel

The phase composition at the surface of plasma nitrocarborized carbon steel was measured in backscattering geometry. The hyperfine parameters of the various iron sites in cementite, γ′-iron nitride and ε-carbonitride reflect the variation of composition with distance from the sample surface in a similar way as in the fractional areas of the respective phases. This revised version was published online in August 2006 with corrections to the Cover Date.     

Intermetallic phases of the Hf−Fe system

An assessment of the phases present in the Hf?Fe system agress well with the phase diagram and yields parameters in general agreement with previous Mössbauer studies. The Hf₂Fe phase exhibits a quadrupole split spectrum whereas the HfFe₂ compound shows magnetic hyperfine splitting.