C. Doucet

HD 97048: a closer look at the disk

Aims.Large ground-based instruments, like VISIR on the VLT, providing diffraction-limited (~0.3 arcsec) images in the mid-infrared where strong PAH features appear, enable us to see the flaring structure of the disks around Herbig Ae stars. Although progress has been made in modelling the disk with radiative transfer models able to reproduce the spectral energy distribution (SED) of Herbig Ae stars, the constraints brought by images have not been yet fully exploited. We investigate whether these new observational imaging constraints can be accounted for by predictions based on existing models of passive, centrally irradiated hydrostatic disks made to fit the SEDs of the Herbig Ae stars. Methods: The images taken by VISIR in the 8.6 and 11.3 μm aromatic features reveal a large flaring disk around HD 97048 inclined to the line of sight. To analyse the spatial distribution of these data, we use a disk model that includes the most up to date understanding of disk structure and physics around Herbig Ae stars with grains in thermal equilibrium, in addition to transiently-heated PAHs. Results: We compare the observed spatial distribution of the PAH emission feature and the adjacent continuum emission with predictions based on existing full disk models. Both SED and spatial distribution are in very good agreement with the model predictions for common disk parameters. Conclusions: We take the general agreement between observations and predictions as strong support for the physical pictures underlying our flared disk model. Based on observations obtained at VLT (Paranal) with VISIR. Program number 075.C-0540(C).

Coumarinic derivatives as mechanism-based inhibitors of α-chymotrypsin and human leukocyte elastase

Novel coumarinic derivatives were synthesized and tested for their inhibitory potency toward alpha-CT and HLE. Cycloalkyl esters and amides were found to be essentially inactive on both enzymes. On the opposite, aromatic esters strongly inactivated alpha-CT whereas HLE was less efficiently inhibited with dichlorophenyl ester derivatives (kinact/K(I) = 4000 M(-1) s(-1) for 36). Representative examples of amide, ester, thioester and ketone derivatives were prepared in order to evaluate the influence of the link between the coumarinic ring and the phenyl side chain. The irreversible inactivation of alpha-CT by 6-chloromethyl derivatives should be due to alkylation of a histidine residue as suggested by the amino acid analysis of the modified chymotrypsin. Conversely the inhibition of HLE was transient. Intrinsic reactivity of coumarins has been calculated using a model of a nucleophilic reaction between the ligand and the couple methanol-water. From this calculation, it appears that differences in the inhibitory potency expressed by these molecules cannot only be explained by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack.

Inhibition of human leukocyte elastase by functionalized N-aryl-3,3-dihalogenoazetidin-2-ones. Stereospecific synthesis and chiral recognition of dissymmetrically C3-substituted β-lactams

Abstract (3R)- and (3S)-N-(2-chloromethylphenyl)-3-bromo-3-fluoroazetidin-2-ones 2 were synthesized via the separation of diastereoisomeric phenylglycinol derivatives of the starting 2,3-dibromo-2-fluoropropanoic acid. Acidic hydrolysis of the hydroxyamides led to the chiral trihalogenopropanoic acids. Then, an expeditious four step synthesis provided the (3S)- and (3R)-azetidinones 2, both of which behaved as strictly irreversible inhibitors of HLE. The configuration of the bromofluorocarbon was shown to have a significant effect on the partition ratio: kcat/kinact=4.6 and 34.3 for (3S)- and 3R)-2, respectively.

Synthesis and inhibition of human leucocyte elastase by functionalized N-aryl azetidin-2-ones: effect of different substituents on the aromatic ring.

N‐aryl‐3,3‐difluoroazetidin‐2‐ones featured by a latent electrophilic methylene quinoniminium function have been synthesized and evaluated as inhibitors of human leucocyte elastase.