Structural parameters of the Sr 2+ and, for the first time, of the Eu 2+ ions in aqueous solution were determined by the XAFS method. For the Sr 2+ , the use of an improved theoretical approach led to a first shell coordination number of 8.0 (3), a Sr-O distance of 2.600 (3) Å and a Debye-Waller factor of σ 2 ) 0.0126 (5)

Eu(II) complexes are potential candidates for pO(2)-responsive contrast agents in magnetic resonance imaging. In this regard, we have characterized two novel macrocyclic Eu(II) chelates, [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) (H(4)DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, H(4)TETA=1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) in terms of redox and thermodynamic complex stability, proton relaxivity, water exchange, rotation and electron spin relaxation. Additionally, solid-state structures were determined for the Sr(II) analogues. They revealed no inner-sphere water in the TETA and one inner-sphere water molecule in the DOTA complex. This hydration pattern is retained in solution, as the (17)O chemical shifts and (1)H relaxation rates proved for the corresponding Eu(II) compounds. The thermodynamic complex stability, determined from the formal redox potential and by pH potentiometry, of [Eu(II)(DOTA)(H(2)O)](2-) (lg K(Eu(II))=16.75) is the highest among all known Eu(II) complexes, whereas the redox stabilities of both [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) are inferior to that of 18-membered macrocyclic Eu(II) chelates. Variable-temperature (17)O NMR, NMRD and EPR studies yielded the rates of water exchange, rotation and electron spin relaxation. Water exchange on [Eu(II)(DOTA)(H(2)O)](2-) is remarkably fast (k298(ex)=2.5 x 10(9) s(-1)). The near zero activation volume (DeltaV++ =+0.1+/-1.0 cm(3) mol(-1)), determined by variable-pressure (17)O NMR spectroscopy, points to an interchange mechanism. The fast water exchange can be related to the low charge density on Eu(II), to an unexpectedly long M-O(water) distance (2.85 A) and to the consequent interchange mechanism. Electron spin relaxation is considerably slower on [Eu(II)(DOTA)(H(2)O)](2-) than on the linear [Eu(II)(DTPA)(H(2)O)](3-) (H(5)DTPA=diethylenetriaminepentaacetic acid), and this difference is responsible for its 25 percent higher proton relaxivity (r(1)=4.32 mM(-1) s(-1) for [Eu(II)(DOTA)(H(2)O)](2-) versus 3.49 mM(-1) s(-1) for [Eu(II)(DTPA)(H(2)O)](3-); 20 MHz, 298 K).

Structural parameters of the Sr 2+ and, for the first time, of the Eu 2+ ions in nonaqueous solutions were determined by the X-ray absorption fine structure (XAFS) method and compared with those of the aqua ions. For both Eu 2+ and Sr 2+ ions, a decrease in coordination number (N) and metal-to-solvent distances was found along the increasingly solvating MeCN < H 2 O , DMF < DMSO solvent series: for strontium, N ) 8 with [Sr (MeCN)

Tetraarylporphyrins with differently substituted aryl groups attached at the meso positions have, in the past, been obtained through the condensation of pyrrole with a mixture of two different benzaldehydes. 1 We are interested in making meso-(2,6-diaminophenyl)porphyrins that are useful in the synthesis of porphyrin complexes with superstructure functionality on both faces. Our preliminary epoxidation studies using the metalated Mosher's amide derivative (1c, Figure 1) 2 of the parent octaaminoporphyrin (1b) failed for the moment to produce good enantiomeric excesses and a good turnover number. We believe this catalyst with eight Mosher's pickets is too bulky to perform efficient or selective epoxidation. The results reported here provide evidence that placing fewer chiral groups on each face of a porphyrin can generate a more active and more selective metal center. These results are in keeping with those of Jacobsen et al. which indicate that efficient chiral induction can be achieved with one very modest chiral diamine. 3 The sterics of the remaining chiral passage must be tuned so as to maximize both ∆∆G and overall epoxidation. Just enough chiral bulk must be present to destabilize exactly one enantioapproach. It is our belief that the failure of many enantioselective catalysts stems from restriction of both enantioapproaches to the metal center.Our new family of aminoporphyrins provides templates for making less hindered catalysts. The "blank" picket (the p-tert-butyl or pentafluoro-meso-phenyl group) can-not be derivatized. This means catalysts made from these new templates always have at least one unencumbered approach which can serve as a chiral substrate passage to the metal center. We are currently working on strategies to add a variety of chiral substituents to these porphyrin templates.Recently, we reported the synthesis of 5,10,15,20tetrakis(2′,6′-diamino-4′-tert-butylphenyl)porphyrin 1b. 2 This octaaminoporphyrin, which, thanks to p-tert-butyl substituents, is slightly soluble in CH 2 Cl 2 , was obtained by mixing pyrrole and 2,6-dinitro-4-tert-butylbenzaldehyde in the presence of BF 3 ‚OEt 2 followed by oxidation of the porphyrinogen with tetrachlorobenzoquinone.In the present paper, we report the extension of this work to the synthesis of hexaaminoporphyrins 5c and 5d, tetraaminoporphyrins 7c and 7d, and diaminoporphyrin 8d (see Figure 2). These porphyrins were obtained via condensation of pyrrole and a mixture of 2′,6′dinitro-4′-tert-butylbenzaldehyde and an unfunctionalized benzaldehyde in the presence of BF 3 ‚OEt 2 , 4 followed by reduction 5 of the two, four, or six nitro groups to amines. Incorporation of an unfunctionalized benzaldehyde gives rise to a "blank" meso-phenyl picket. Two different blank pickets have been used: porphyrin 5c was made by incorporating a single 4-tert-butyl phenyl "blank" picket into the macrocycle (eq a, Scheme 1) while one, two, and three pentafluorophenyl groups were incorporated into porphyrins 5d, 7d, and 8d, respectively (eq b and Figure 2). Interestingly, ...

Numerous methods are available for use as part of a virtual screening strategy but, as yet, no single method is able to guarantee both a level of confidence comparable to experimental screening and a level of computing efficiency that could drastically cut the costs of early phase drug discovery campaigns. Here, we present VSM-G (virtual screening manager for computational grids), a virtual screening platform that combines several structure-based drug design tools. VSM-G aims to be as user-friendly as possible while retaining enough flexibility to accommodate other in silico techniques as they are developed. In order to illustrate VSM-G concepts, we present a proof-of-concept study of a fast geometrical matching method based on spherical harmonics expansions surfaces. This technique is implemented in VSM-G as the first module of a multiple-step sequence tailored for high-throughput experiments. We show that, using this protocol, notable enrichment of the input molecular database can be achieved against a specific target, here the liver-X nuclear receptor. The benefits, limitations and applicability of the VSM-G approach are discussed. Possible improvements of both the geometrical matching technique and its implementation within VSM-G are suggested.