The crystal structures of five 1,4-dihydro-2,3-quinoxalinediones, antagonists of the NMDA modulatory glycine binding site on the excitary amino acid (EAA) receptor complex, have been determined: (I) 6,7-dinitro-l,4-dihydro-2,3-quinoxalinedione (DNQX); (II) 5,7-dinitro-1,4-dihydro-2,3-quinoxalinedione (MNQX); (III) 6-nitro-1,4-dihydro-2,3-quinoxalinedione hydrate; (IV) 6,7-dichloro-l,4-dihydro-2,3-quinoxalinedione; (V) 5,7-dichloro-1,4-dihydro-2,3-quinoxalinedione dimethylformamide. The crystal structure of the most active compound (II) contains a unique intramolecular N--H...O(NO2) hydrogen bond, which may be important for activity, as semiempirical calculations show that this bond is stable over a wide range of dihedral angles between the planes of the molecule and of the nitro group. In the other compounds the intermolecular hydrogen bonds connect molecules into three-dimensional networks. In compounds (I), (III) and (IV) headto-tail :r-stacking is found between molecules connected by a center of symmetry. The geometries of the hydrogen-bonded --NH--C--O fragments show evidence of zr-cooperativity or resonance-assisted hydrogen bonding. Graph-set analysis of the hydrogenbond patterns of quinoxalinedione derivatives shows a tendency to form two types of hydrogen-bonding motifs: a centrosymmetric dimeric ring and an infinite chain. Even though this pattern may be modified by the presence of additional hydrogen-bond acceptors and/or donors, as well as by solvent molecules, general similarities have been found. Comparison of all quinoxalinedione structures suggests that the hydrogen-bonding pattern necessary for the biological activity at the glycine binding site contains one donor and two acceptors.
The crystal structures of three tricyclic quinoxalinedione derivatives, 6-bromo-l,8-ethano-4-hydro-2,3-quinoxalinedione (I), 6-methyl-l,8-ethano-4-hydro-2,3-quinoxalinedione hydrate (2), and 6-styryl-l,8-ethano-4-hydro-2,3-quinoxalinedione (3), are reported. For 1 and 2, the space groups are P2,ln with the unit cell parameters for 1: a = 7.4003(5) A, b = 8.5799(5) A, c = 14.3127(9) A, P = 90.639(6)", and for 2: a = 7.0590(2) A, b = 10.7483(3) A, c = 13.9509(7) A, P = 103.290(3)". For 3, the space group is P2,lc, with a = 19.3683(10) A, b = 8.0962(16) A, c = 19.5801(16) A, P =114.028(6)". Compound 3 crystallizes with two molecules in the asymmetric part of the unit cell; in one of them the styryl group is disordered. The geometries of the 1,s-ethano-4-hydro-2,3-quinoxalinedione fragments are similar in all observations, with the differences mainly caused by the different nature of the substituents in the 6-position. Hydrogen bonds connect the molecules into three-dimensional networks. Head-to-tail .ir-stacking between molecules connected by a center of symmetry determines the packing modes in 1 and 2 but there is no .irstacking in the crystal structure of 3. The crystal structures of the three quinoxaline derivative ligands for the glycine receptor suggest a mode of recognition that involves an N-H-.receptor hydrogen bond, a three-centre hydrogen bond to the neighboring carbonyl groups on the ligand, and .ir-stacking between ligand and receptor. This mode is consistent with the geometric constraints of the current binding site model but places greater emphasis on hydrogen-bond interactions.MACIEJ KUBICKI, TERESA W. KINDOPP, MARIO V. CAPPARELLI et PENELOPE W. CODDING. Can. J. Chem. 72,2028 (1994.On a dCterminC les structures cristallines de trois dCrivts tricycliques de la quinoxalinedione, la 6-bromo-1,s-Cthano-4-hydro-2,3-quinoxalinedione (I), l'hydrate de la 6-mCthyl-l,8-Cthano-4-hydro-2,3-quinoxalinedione (2) et la 6-styryl-1,s-Cthano-4-hydro-2,3-quinoxalinedione (3). 114,038(6)". Le composC 3 cristallise avec deux moltcules de solvant dans la partie asymitrique du motif de la maille dans un desquels le groupe styryle est dksordonnC. Les gComCtries des fragments 1,8-tthano-4-hydro-2,3-quinoxalinedione sont semblables dans tous les composCs examinks; les differences sont principalement causees par la nature differente des substituants en position 6. Des atomes d'hydrogkne relient les moltcules dans des rkseaux tridimensionnels. Un entassement .ir t&te-?-queue entre les molCcules relikes par un centre de symetrie determine les modes d'empilement dans les composCs 1 et 2; toutefois, il n'y a pas d'entassernent .ir dans la structure cristalline du composC 3. Les structures cristallines des trois coordinats dCrivCs de la quinoxaline pour le rCcepteur glycine suggkre un mode de reconnaissance qui implique une liaison hydrogkne N-H.-recepteur, une liaison 2 trois centres hydrogbnes avec les groupes carbonyles voisins sur le coordinat et l'empilement .ir entre le ligand et le rCcepteur. Ce mode est en accord avec les ...
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