G. Hänggi

The geometry of the neutral, protonated or coordinated purine derivatives hypoxanthine, xanthine, allopurinol and alloxanthine: quantum chemical and X-ray crystallographic studies

Abstract The structures of neutral, protonated and coordinated purine derivatives were calculated by semiempirical and ab initio geometry optimizations using MIDI or 6-31G ∗∗ basis sets. The predicted geometries agree well with the available crystallographic data and allow a systematic interpretation of the structural changes resulting from tautomerization, protonation or coordination. Protonation at a nitrogen atom induces alterations in the range 0.050-0.080 A of the CN and CC bond lengths of the pyrimidine or pyrazole ring. The corresponding CNC angles are increased by about 4° upon protonation in the oxopurines hypoxanthine and xanthine and in the pyrazolopyrimidines allopurinol and alloxanthine; the adjacent angles are reduced by approximately 3–4°°. The 1H,9H ⇌ 1H,7H tautomerization of neutral oxopurines results in changes in the respective CNC angles of approximately ±l° only. The pyrazolopyrimidines,, in contrast, show alterations of both neighboring bonding angles of the five-membered ring by about ± 6–8° upon 1 H,9H⇌1H,8H tautomerization. In contrast to the effects of protonation, the influence of metal coordination is very small, but still significant. Monodentate coordination at the pyrimidine ring of neutral hypoxanthine induces about 50% of the shifts effected by tautomerization and about 20% only of those resulting from protonation. Allopurinol, monodentately coordinating through N(8), shows structural changes of the pyrazole moiety up to a maximum of about 30% of those associated with an attachment of a hydrogen atom. The molecular electrostatic potential has been calculated for the optimized geometries of the free ligands at the ab initio level, using the MIDI basis set. Metal coordination of purine derivatives is discussed in terms of contour diagrams of the electrostatic potential in the molecular plane. Partial atomic charges have been fitted to the electrostatic potential and compared with charges derived according to various other methods.

Thermal degradation and crystallographic data of metal complexes of oxopurines and thiopurines

Abstract The thermal behaviour of metal compounds of the naturally occurring oxopurines hypoxanthine, xanthine and uric acid and of the synthetic pyrazolopyrimidines allopurinol and alloxanthine as well as of the thiopurine 6-mercaptopurine has been investigated using thermogravimetric and X-ray crystallographic techniques. The thermogravimetric data confirm the structural characteristics of the metal complexes. The degradation of hydrated complexes occurs in two steps with a dehydration reaction followed by complete decomposition to the corresponding metal oxides. Anhydrous compounds are decomposed in one step overall reactions. The temperature range of dehydrations of the hydrated complexes strongly depends on the binding mode of the water molecules. The reaction rate of the final decompositions of these complexes seems to be influenced by the respective metal ions. Copper and iron complexes show a sharp increase in the reaction rate in respect of the complexes of cobalt and nickel, whereas zinc, cadmium and manganese compounds are slowly decomposed over a wide temperature range.

Characterization and crystal structure of (xanthine +)2[ZnCl4]

Abstract The reaction of the oxopurine base xanthine with zinc chloride in diluted hydrochloric acid has resulted in the formation of single crystals of the composition (xanthine+)2[ZnCl4]. Crystal data: orthorhombic, space group Pmn21 a=19.701(6), b=6.583(1), c=6.610(2) A, V=857.3(7) A3, Z=2, R=0.042 using 1129 observed reflections with I ⩾ 3σ(I). (Xanthine+)2[ZnCl4] contains isolated [ZnCl4]2− tetrahedra and non-coordinating xanthinium cations, which are linked to the anions via strong NH···Cl hydrogen bonds with donor-acceptor distances in the range 3.202(6)-3.434(6) A. The discrete xanthinium cations are interconnected by hydrogen bonding contacts of the type NH···O with N···O distances of 2.782(7) and 2.948(7) A. A detailed analysis of the alterations of the ring geometry of xanthine upon protonation is given.

Interaction of metal ions with the antihyperuricemic drug allopurinol (H2L): synthesis and crystal structure of dimeric [Zn2(µ-HL)2Cl2(H2O)2]

The complex ZnII(HL)Cl(H2O)(H2L = allopurinol = 1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one) has been crystallized from aqueous solution. Crystal data: triclinic, space group P1–(no. 2), a= 7.052(2), b= 7.726(2), c= 8.341(4)A, α= 69.78(3), β= 87.75(3), γ= 68.27(3)° and Z= 2. The complex exhibits a new centrosymmetric dimeric structure of the type [Zn2(µ-HL)2Cl2(H2O)2]. Two zinc ions with an intramolecular metal-to-metal distance of 3.713(2)A are bridged by two N(8)–N(9)-chelating anionic allopurinol ligands. The dimeric complex units are stabilized by an extended network of hydrogen bonding contacts. The co-ordinating allopurinol rings are stacked with a mean spacing distance of 3.39 A. A review of the co-ordinating properties of neutral, anionic and cationic allopurinol including recent crystallographic data is given.

Cd(alloxanthine)2(NO3)2(H2O)2

The title complex, diaquadinitratobis{[1H]pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione-N 1 }cadmium(II), was prepared as part of a study of the coordinating properties of the xanthine oxidase inhibiting molecule, alloxanthine. [Cd(NO 3 ) 2 (C 5 H 4 N 4 O 2 ) 2 ] contains monomeric centrosymmetric units with the Cd ion octahedrally coordinated by two NO 3 groups, two H 2 O molecules and by two alloxanthine ligands. Alloxanthine coordinates monodentately though the pyrazole N atom N(9). The H atoms of the neutral alloxanthine molecule are bonded to the other atoms N(1), N(3) and N(8)