Pavel N. Gaponik

1,5-Diamino-1H-1,2,3,4-tetrazolium picrate: X-ray molecular and crystal structures and ab initio MO calculations

The crystal and molecular structures of 1,5-diamino-1H-1,2,3,4-tetrazolium picrate (DATP) were determined by X-ray diffraction analysis. The tetrazolium cation in DATP has a structure with protonated N4 atom of the ring. Two amino groups in the cation are found to be rather different. The 5-amino group lies in the plane of the tetrazole ring and valence angles around the N atom are close to 1208, which indicates sp 2 hybridization of atomic orbital of the nitrogen atom. In contrast, valence angles around the N atom of the 1-amino group are close to tetrahedral angle, which suggests sp 3 hybridization. The exocyclic C– N bond in the cation is substantially shorter than that in 1,5-diaminotetrazole. The obtained results indicate a conjugation between the p-system of the tetrazole ring and the 5-amino group. The results of ab initio calculations of electronic structure and relative stability for various tautomeric forms of protonated 1,5-diaminotetrazole using MP2/6-31G* and B3LYP/6-31G* levels of theory are in a good agreement with X-ray data and show that there are differences in s-electron overlap populations for the C– N bonds in the cation in DATP, while p-electrons are delocalized. q 2003 Elsevier Science B.V. All rights reserved.

Synthesis, characterization, and biological evaluation of new tetrazole-based platinum(II) and palladium(II) chlorido complexes--potent cisplatin analogues and their trans isomers.

Two series of tetrazole-containing platinum(II) and palladium(II) chlorido complexes, trans-[ML(2)Cl(2)] (M=Pt, Pd) and cis-[PtL(2)Cl(2)]·nH(2)O (n=0, 1), where L is 1- or 2-substituted 5-aminotetrazole, have been synthesized and thoroughly characterized. Configuration of platinum(II) complexes obtained from the reaction of 5-aminotetrazoles with K(2)PtCl(4) has been found to vary depending on the nature of tetrazole derivatives and reaction conditions. According to in vitro cytotoxic evaluation, only platinum complexes display noticeable antiproliferative effect, and their cytotoxicity depends strongly on their geometry and hydrophobicity of the carrier ligands. The most promising complexes are cis-[Pt(1-apt)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O, where 1-apt is 5-amino-1-phenyltetrazole and 2-abt is 5-amino-2-tert-butyltetrazole. In comparison with cisplatin, they show comparable cytotoxic potency against cisplatin-sensitive human cancer cell lines, cis-[Pt(2-abt)(2)Cl(2)]·H(2)O performing substantially higher activity against cisplatin-resistant cell lines. Cell cycle studies in H1299 cell line indicated that cis-[Pt(2-abt)(2)Cl(2)]·H(2)O induced apoptosis launched from G2 accumulations. The DNA interaction with cis-[Pt(1-apt)(2)Cl(2)]·H(2)O was followed by UV spectroscopy, circular dichroism, hydrodynamic and electrophoretic mobility studies. Both cis-[Pt(1-apt)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O complexes appeared to be significantly less toxic than cisplatin in mice, while only compound cis-[Pt(1-apt)(2)Cl(2)]·H(2)O displayed noticeable efficacy in vivo.

Synthesis, Properties, and Structure of Tetrazoles: Certain Achievements and Prospects

The review generalizes and systematizes the results of research on the synthesis and properties of tetrazole derivatives obtained in the Belarusian State University within the last decade. The main attention is fixed on important directions in the tetrazole synthesis: the acid-catalyzed N-alkylation, the reactions of primary amines with triethyl orthoformate and sodium azide followed by the heterocyclization of imidoyl azides, and on the transformation of the obtained 1-aryltetrazoles into 1-aryl-5-aminotetrazoles. The results of quantum-chemical and X-ray investigations as well as aspects of the practical application of tetrazoles are reviewed.

Two derivatives of 5-aminotetrazole: 5-amino-1-phenyltetrazole and 5-amino-1-(1-naphthyl)tetrazole

In the molecules of 5-amino-1-phenyltetrazole, C(7)H(7)N(5), (I), and 5-amino-1-(1-naphthyl)tetrazole, C(11)H(9)N(5), (II), the tetrazole rings and aryl fragments are not coplanar; corresponding dihedral angles are 50.58 (5) and 45.19 (7) degrees for the two independent molecules of (I), and 64.14 (5) degrees for (II). Intermolecular N-H.N hydrogen bonds between the amino groups and tetrazole N atoms are primarily responsible for formation of two-dimensional networks extending parallel to the bc plane in both compounds. The presence of the amino group has a distinct effect on the geometry of the tetrazole rings in each case.

Synthesis of New Functionally Substituted 1-R-tetrazoles and Their 5-Amino Derivatives

It has been shown that amino derivatives of sulfanilamide, and also some functionally substituted primary arylamines and cycloalkylamines, undergo heterocyclization with triethyl orthoformate and sodium azide with the formation of 1-monosubstituted tetrazoles. Primary amines of the azole series, 5-aminotetrazole, 5-amino-1-methyltetrazole, 4-amino-1,2,4-triazole, and also less basic arylamines (4-fluoro-3-nitroaniline, 2,6-dibromo-4-nitroaniline) did not react. An efficient method of introducing an amino group into position C(5) of the tetrazole ring of 1-aryltetrazoles is proposed, based on alkaline decomposition of the tetrazole ring and heterocyclization of the resulting N-arylcyanamides on interaction with ammonium azide generated in situ.

Selective synthesis of binuclear N-substituted tetrazoles and tetrazolium salts

The selective alkylation of mononuclear tetrazoles by 2,5-dimethyl-2,5-hexanediol and of N-unsubstituted binuclear tetrazoles by tert-butyl alcohol was realized in perchloric and sulfuric acids. A series of previously unknown N-substituted binuclear tetrazoles and tetrazolium salts were synthesized. Data from X-ray crystallographic analysis of 2,5-dimethyl-2,5-di(5-phenyl-2-tetrazolyl)hexane are presented.

Synthesis and properties of phenylenebis-1H-tetrazoles

Heterocyclization of m- and p-phenylenediamines with orthoformic ester and sodium azide has given phenylenebis-1H-tetrazoles. Under these conditions, o-phenylenediamine gives benzimidazole. o-, m-, and p-Phenylenebis-1H-tetrazoles were also obtained from the nitroanilines via the intermediate nitro- and aminophenyltetrazoles. The reactions of the bistetrazoles examined were basic hydrolysis, aminomethylation, and complex formation with copper salts.

catena-Poly­[[bis­[μ-1,2-bis(1-methyl­tetrazol-5-yl)­ethane-κ2N4:N4′]bis[chloro­copper(II)]]-di-μ-chloro]

In the title compound, [Cu 2 Cl 4 (C 6 H 10 N 8 ) 2 ] n , the ligand has C 2 symmetry, and the Cu and Cl atoms lie on a mirror plane. The coordination polyhedron of the Cu atom is a distorted square pyramid, with the basal positions occupied by two N atoms from two different ligands [Cu-N = 2.0407 (18) A] and by the two Cl atoms [Cu-Cl = 2.2705 (8) and 2.2499 (9) A], and the apical position occupied by a Cl atom [Cu-Cl=2.8154(9) A] that belongs to the basal plane of a neighbouring Cu atom. The [CuCl 2 (C 6 H 10 N 8 )] 2 units form infinite chains extending along the a axis via the Cl atoms. Intermolecular C-H...Cl contacts [C...Cl = 3.484 (2) A] are also present in the chains. The chains are linked together by intermolecular C-H...N interactions [C...N = 3.314 (3) A].

Synthesis and structure of 1-tert-butyl-3-R-tetrazolium salts

An effective method was developed for the synthesis of 1,3-disubstituted tetrazolium salts by the quaternization of 2-monosubstituted tetrazoles, including functionally substituted compounds, with tert-butanol in 72% perchloric acid. An X-ray diffraction investigation of examples of this series of salts - 1-tert-butyl-3-(1-methylvinyl)- and 1,3-di-tert-butyltetrazolium perchlorates - was carried out.

Copper(II) chloride and bromide complexes with 2-methyl-2H-tetrazol-5-amine: an X-ray powder diffraction study.

The complex catena-poly[[dibromidocopper(II)]-bis(mu-2-methyl-2H-tetrazol-5-amine)-kappa(2)N(4):N(5);kappa(2)N(5):N(4)], [CuBr(2)(C(2)H(5)N(5))(2)](n), (I), and the isotypic chloride complex catena-poly[[dichloridocopper(II)]-bis(mu-2-methyl-2H-tetrazol-5-amine)-kappa(2)N(4):N(5);kappa(2)N(5):N(4)], [CuCl(2)(C(2)H(5)N(5))(2)](n), (II), were investigated by X-ray powder diffraction at room temperature. The crystal structure of (I) was solved by direct methods, while the Rietveld refinement of (II) started from the atomic coordinates of (I). In both structures, the Cu atoms lie on inversion centres, adopting a distorted octahedral coordination of two halogen atoms, two tetrazole N atoms and two 5-amine group N atoms. Rather long Cu-N(amine) bonds allow consideration of the amine group as semi-coordinated. The compounds are one-dimensional coordination polymers, formed as a result of 2-methyl-2H-tetrazol-5-amine ligands bridging via a tetrazole N atom and the amine N atom. In the polymeric chains, adjacent Cu atoms are connected by two such bridges.