XAFS Study of Gadolinium and Samarium Bisporphyrinate Complexes

The comparative X-ray absorption spectroscopy study of gadolinium and samarium bisporphyrinate complexes represented by the formulas GdIIIH(oep)(tpp), GdIII(oep)2, GdIIIH(tpp)2 and SmIIIH(oep)(tpp), SmIII(oep)2, SmIIIH(tpp)2 is reported. The XAFS spectra are recorded on the LURE-DCI storage ring (Orsay, France) in transmission mode on the microcrystalline samples at the Gd and Sm L3 edges. The local environment for Ln3+ ions has been reconstructed applying one-shell and two-shell XAFS analysis procedures. The protonated and nonprotonated bisporphyrinate complexes present different XAFS features. After our analysis on the title derivatives, the gadolinium ion (at 80 K) is found to be bonded:  (i) to eight nitrogen atoms at R(Gd−N) 2.50 Å, for GdIII(oep)2 [Debye−Waller (DW) factor 0.004 Å2]; (ii) to seven nitrogen atoms at R(Gd−N) 2.49 Å, for GdIIIH(oep)(tpp) [DW factor 0.005 Å2] and one nitrogen at long distance; and (iii) to six nitrogen atoms at R(Gd−N) 2.50 Å [DW factor 0.006 Å2] and two nitrogen atoms at long distance for GdIIIH(tpp)2. A similar coordination sphere has been detected for the corresponding Sm derivatives. So, the samarium ion (at room temperature) is bonded:  (i) to eight nitrogen atoms at R(Sm−N) 2.53 Å, for SmIII(oep)2 [DW factor 0.006 Å2]; (ii) to seven nitrogen atoms at R(Sm−N) 2.53 Å, for SmIIIH(oep)(tpp) [DW factor 0.006 Å2] and one nitrogen at long distance; and (iii) to six nitrogen atoms at R(Sm−N) 2.50 Å, for SmIIIH(tpp)2 [DW factor 0.006 Å2] and two nitrogen atoms at long distance. As far as concerns LnIII(oep)2 complexes, the increase of Ln−N distance in the series Gd3+ 3+ < Sm3+ reflects an increase in the ionic radii, which are in good agreement with previously published XRD data on EuIII(oep)2. Moreover, the protonated LnIIIH(oep)(tpp) and LnIIIH(tpp)2 complexes possess systematically shorter distances of about 0.02 Å between the XAFS and XRD data. This difference is attributed to the asymmetry of the distribution concerning Ln−N distances

Virtual Screening Discovery of New Acetylcholinesterase Inhibitors Issued from CERMN Chemical Library

In our quest to find new inhibitors able to inhibit acetylcholinesterase (AChE) and, at the same time, to protect neurons from beta amyloid toxicity, i.e., inhibitors interacting with the catalytic anionic subsite as well as with the peripherical anionic site of AChE, a virtual screening of the Centre d’Etudes et de Recherche sur le Médicament de Normandie (CERMN) chemical library was carried out. Two complementary approaches were applied, i.e., a ligand- and a structure-based screening. Each screening led to the selection of different compounds, but only two were present in both screening results. In vitro tests on AChE showed that one of those compounds presented a very good inhibition activity, of the same order as Donepezil. This result shows the real complementary of both methods for the discovery of new ligands