Synthesis, crystal structure and properties of two acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide) complexes: bis(5-acetamidato- 1,3,4-thiadiazole-2-sulfonamide- O)bis( 1,2-ethanediamine)copper(II) and bis(5-acetamidato-1,3,4-thiadiazole-2-sulfonamide- N)bis(1,3- propanediamine)copper(II); an unusually weak ambidentate anionic ligand

Abstract

The diverse coordination chemistry exhibited by acetazolamide (H 2acm), a potent inhibitor of the carbonic anhydrase metalloenzyme, is highlighted in two new copper(II) complexes of this ligand: [Cu(Hacm) 2(en) 2] ( I) and [Cu(Hacm) 2(tn) 2] ( II). The synthesis, crystal structure and spectroscopic properties of both compounds are reported in this paper. The structures of both compounds consist of discrete units of [Cu(Hacm) 2(en) 2] ( I) and [Cu(Hacm) 2(tn) 2] ( II), respectively, interacting through van der Waals contacts and hydrogen bonds only. Hacm, however, binds differently in each compound. In both cases, the Cu(II) ions, lying on the symmetry centers, show an elongated octahedral geometry with the four 1,2-ethanediamine or 1,3-propanediamine N atoms in an approximately square coplanar arrangement (Cu-N distances of 2.00 and 2.01 Å for I; 2.04 and 2.05 Å for II); two sulfonamido O atoms in I and two thiadiazole N atoms in II, from two trans Hacm ligands, complete the distorted octahedron at the longer distance of 2.65 and 2.46 Å, respectively. Although the ligand is deprotonated at the acetamido group, in neither case is the interaction with the copper produced via the donor atoms of that group. Furthermore, in I, unexpectedly, in spite of its four potentially chelating N atoms, and in spite of the deprotonation of the acetamido group, acetazolamide acts as a monodentate ligand coordinating through one of the O atoms of the sulfonamido moiety. This behavior is completely different from that observed in II and in all acetazolamide complexes described up to now, and it must be related to hydrogen bonding and to the copper(II) Jahn-Teller effect. Stabilization of the negative charge at the deprotonated group takes place through ‘pairing’ of the Hacm ions in the packing system. These results further emphasize the many coordinating possibilities of the ligand, which could be of relevance to a proper understanding of the mechanism of inhibition in the enzyme. Crystallographic data: [Cu(C 4N 4S 2O 3H 5) 2(C 2N 2H 8) 2] ( I) (MW=626.2) crystallizes in the triclinic space group P 1 , Z=1, with the cell dimensions a=8.196(7), b=9.094(4), c=9.352(3) Å, α=84.51(3), β=74.83(6), γ=63.57(5)° and V=602 Å 3, D calc=1.73 Mg m −3; the final agreement values were R=0.0335 and R w=0.0427 for 3947 independent significant reflections. [Cu(C 4N 4S 2O 3H 5) 2(C 3N 2H 10) 2] ( II) (MW=654.3) crystallizes in the monoclinic space group P2 1/ n, Z=2, with the cell dimensions a=9.336(3), b=10.232(1), c=14.138(3) Å, β=103.80(2) and V=1312 Å 3, D calc=1.66 Mg m −3; the final agreement values were R=0.0327 and R w=0.0405 for 1932 independent significant reflections. The structures were solved by using the copper coordinates (at the inversion center) for repeated Fourier calculations (AUTOFOUR, SHELXS-86). Ligand field and EPR spectra for both complexes are in agreement with the tetragonal Cu(II)N 4O 2 ( I) and Cu(II)N 4N 2′ ( II) chromophores, respectively.