INTERACTION OF METAL-IONS WITH ALLOXANTHINE, A MODEL IN XANTHINE-OXIDASE INHIBITION BY THE DRUG ALLOPURINOL - SYNTHESIS AND CHARACTERIZATION OF M(ALLOXANTHINE)(2)(NO3)(2)CENTER-DOT-2H2O (M=CU, CO) AND ZN(ALLOXANTHINE)(2)CL-2

Metal complexes of the xanthine oxidase inhibiting molecule alloxanthi ne (pyrazolo[3,4-d]pyrimidine-2,6-dione) have been synthesized in form of single crystals from aqueous solutions by the reaction of alloxant hine with an excess of the respective metal salts. Crystal data: Cu-II (alloxanthine)(2)(NO3)(2).2H(2)O, a = 6.985(3) Angstrom, b = 7.582(3) Angstrom, c = 9.051(2) Angstrom, alpha = 107.50(3)degrees, beta = 98.4 9(3)degrees, gamma = 103.79(3)degrees, V = 429.6(7) Angstrom(3), Z = 1 , space group P (1) over bar 1; Co-II-(alloxanthine)(2)( NO3)(2).2H(2) O, a = 7.408(3) Angstrom, b = 7.838(2) Angstrom, c = 8.666(1) Angstrom , alpha = 109.72(2)degrees, beta = 101.35(3)degrees, gamma = 104.93(2) degrees, V = 434.8(6) Angstrom(3) Z = 1, space group P (1) over bar; Z n-II(alloxanthine)(2)Cl-2, a = 8.267(3) Angstrom, b = 11.256(2) Angstr om, c = 15.804(4) Angstrom, alpha = beta = gamma = 90 degrees, V = 147 0.6(12) Angstrom(3), Z = 4, space group Pbcn. The structures of all th ree complexes were refined to final R values of 0.030 (Cu), 0.041 (Co) , and 0.049 (Zn). In the metal complexes of the type M(II)(alloxanthin e)(2)(NO3)(2).2H(2)O with M = Cu or Co, the metal ion is situated in t he center of a distorted MN(4)O(2) octahedron including two N(9)-coord inating alloxanthine ligands and two water molecules in the equatorial plane and two nitrate groups at the apical positions. A pronounced (4 + 2) elongation of the octahedral geometry is observed in the copper complex. The hydrogen atoms of the neutral, N(9)-coordinating alloxant hine ligand are bonded to the nitrogen atoms N(1), N(3), and N(8). The structure exhibits relatively strong hydrogen-bonding interactions of the types N-H...O and O-H...O. Two pairs of intramolecular bifurcated N-H...O hydrogen-bonding contacts around the hydrogen atoms H(3) and H(8) reveal the formation of indirect chelates, thus stabilizing the m olecular complex units. In the monomeric zinc complex Zn(alloxanthine) (2)Cl-2, the metal ion exhibits a tetrahedral coordination by two chlo ride ions and two alloxanthine ligands monodentately binding through N (9). The hydrogen atoms of the neutral alloxanthine molecule, which ar e attached at the nitrogen atoms N(1), N(3), and N(8), are involved in hydrogen bonds of the types N-H...O and N-H...Cl. Quantum chemical ca lculations at the ab initio level predict the 1H,3H,8H-tautomer of all oxanthine to be more stable than the 1H,3H,9H-form by about 13 kJ.mol( -1). These findings support those models of the inhibition of xanthine oxidase by alloxanthine, which suggest complexation of the metal cent er by N(9).