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.

2-tert-Butyl-5-(2-pyridyl)-2H-tetrazole as a chelating ligand in the direct synthesis of novel Cu(II) and heterobimetallic Cu(II)/Mn(II) complexes.

For the first time, a representative of the 2,5-disubstituted tetrazoles, namely, 2-tert-butyl-5-(2-pyridyl)-2H-tetrazole (L), has been found to participate in oxidative dissolution of copper powder in homometalic systems Cu0­L­NH4X­DMSO (X = Cl, SCN, ClO4) and heterobimetallic ones Cu0­Mn(OAc)2­L­NH4OAc­Solv (Solv = DMSO, DMF), providing the formation of molecular homometallic complexes [CuL2Cl2] (1), [CuL2(SCN)2] (2), and [CuL2(H2O)](ClO4)2 (3), heterobimetallic complex [Cu2MnL2(OAc)6] (4) from DMF solution and its mixture with complex [Cu2MnL2(OAc)6]·2DMSO (5) from DMSO solution. Free ligand L and complexes 1­4 were characterized by elemental analysis, IR spectroscopy, thermal and X-ray single crystal analyses, whereas complex 5 was characterized by X-ray analysis only. Compounds 1­3 are mononuclear complexes, with chelating coordination mode of L via the tetrazole ring N4 and pyridine ring N7 atoms. Heterobimetallic complexes 4 and 5 possess trinuclear structures, with a linear Cu­Mn­Cu arrangement of the metal atoms, linked by the acetate anions; each copper(II) atom is decorated by a chelating unit of L via the tetrazole ring N1 and pyridine ring N7 atoms in complex 4, and via the N4, N7 atoms in complex 5. Temperature-dependent magnetic susceptibility measurements of complex 4 revealed a weak antiferromagnetic coupling between the paramagnetic copper(II) and manganese(II) ions (J = −2.5 cm(−1), g(Cu) = 2.25 and g(Mn) = 2.01), with magnetic exchange through the acetato bridges.

An X-ray powder diffraction study of cis-dichloridobis(2-methyl-2H-tetrazol-5-amine-κN(4))platinum(II), a tetrazole-containing analogue of cisplatin.

The structure of the title compound, cis-[PtCl(2)(C(2)H(5)N(5))(2)], was analysed using in-house X-ray powder diffraction data at room temperature. The structure was solved by direct methods and refined using Rietveld analysis. A slightly distorted square-planar coordination geometry is formed around the Pt atom by two Cl atoms and two ring N atoms of the 2-methyl-2H-tetrazol-5-amine ligands, which are in a cis configuration. The planes of the tetrazole rings are inclined at 79.7 (7) and 73.8 (6)° with respect to the coordination plane, with their substituents oriented in such a way that the complex as a whole has approximate C(2) symmetry. Intermolecular N-H···Cl hydrogen bonds mediate the formation of a three-dimensional supramolecular network.

CdTe nanocrystals capped with a tetrazolyl analogue of thioglycolic acid: aqueous synthesis, characterization, and metal-assisted assembly.

A novel ligand, 5-mercaptomethyltetrazole, is applied to the direct colloidal synthesis of highly luminescent (quantum yield of up to 60%) water-soluble CdTe nanocrystals. In the synthesis the 5-mercaptomethyltetrazole behaves analogously to the widely used thioglycolic acid, providing the additional advantage of solubility of the resulting nanocrystals in methanol. Moreover, the 5-mercaptomethyltetrazole-capped nanocrystals possess the unique ability to reversibly form fine 3D networks (hydrogels) upon the addition of metal salts.

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.

A tetrazol-5-yl analogue of glycine, 5-ammoniomethyl-1H-tetrazolide, and its copper(II) complex.

A nonclassical tetrazole isostere of glycine, viz. zwitterionic 5-ammoniomethyl-1H-tetrazolide, C(2)H(5)N(5), (I), crystallizes in the chiral P3(1) space group, similar to gamma-glycine. The crystal packing of (I) is determined by a set of classical hydrogen bonds, forming a three-dimensional network that is practically the same as that in gamma-glycine. The Cu(II) complex of (I), poly[[bis(mu(2)-5-aminomethyl-1H-tetrazolido-kappa(3)N(1),N(5):N(4))copper(II)] dihydrate], {[Cu(C(2)H(4)N(5))(2)].2H(2)O}(n), (II), is a layered coordination polymer formed as a result of tetrazole ring bridges. The Cu(II) cations lie on inversion centres, are surrounded by four anions and adopt elongated octahedral coordination. Water molecules are located in the interlayer space and connect the layers into a three-dimensional network via a system of hydrogen bonds.

trans-Dichloridotetrakis-[1-(2-hydroxy-ethyl)-1H-tetrazole-κN]cobalt(II).

The title cobalt(II) complex, [CoCl(2)(C(3)H(6)N(4)O)(4)], was obtained from metallic cobalt by direct synthesis. There are two Co atoms in the asymmetric unit, each lying on an inversion centre and adopting a distorted octa-hedral coordination. Classical and non-classical hydrogen bonds are responsible for formation of a three-dimensional polymeric network in the crystal.

catena-Poly[cobalt(II)-di-µ-chlorido-κCl:Cl-µ-1,5-dimethyl-1H-tetra-zole-κN:N]: an X-ray powder investigation.

The asymmetric unit of the title compound, [CoCl(2)(C(3)H(6)N(4))](n), contains two Co atoms, both lying on inversion centres, two Cl atoms and one 1,5-dimethyl-tetra-zole ligand. The coordination polyhedra of both Co atoms adopt flattened octa-hedral geometry, with two N atoms from two ligands in axial positions and four Cl atoms in equatorial sites. Neighbouring Co atoms are linked together via two bridging Cl atoms and one tetra-zole ring to form polymeric chains running along the a axis.

Two derivatives of 1,5-disubstituted tetrazoles: 1-(4-nitrophenyl)-1H-tetrazol-5-amine and {(E)-[1-(4-ethoxyphenyl)-1H-tetrazol-5-yl]iminomethyl}dimethylamine.

The geometric features of 1-(4-nitrophenyl)-1H-tetrazol-5-amine, C(7)H(6)N(6)O(2), correspond to the presence of the essential interaction of the 5-amino group lone pair with the pi system of the tetrazole ring. Intermolecular N-H...N and N-H...O hydrogen bonds result in the formation of infinite chains running along the [110] direction and involve centrosymmetric ring structures with motifs R(2)(2)(8) and R(2)(2)(20). Molecules of {(E)-[1-(4-ethoxyphenyl)-1H-tetrazol-5-yl]iminomethyl}dimethylamine, C(12)H(16)N(6)O, are essentially flattened, which facilitates the formation of a conjugated system spanning the whole molecule. Conjugation in the azomethine N=C-N fragment results in practically the same length for the formal double and single bonds.

catena-Poly[[bis-[1-(2-hydroxy-ethyl)-1H-tetra-zole-κN]copper(II)]-di-µ-chlorido]: a powder study.

The crystal structure of the title polymeric complex, [CuCl(2)(C(3)H(6)N(4)O)(2)](n), was obtained by the Rietveld refinement from laboratory X-ray powder diffraction data collected at room temperature. The unique Cu(II) ion lies on an inversion center and is in a slightly distorted octa-hedral coordination environment. In the hydroxy-ethyl group, all H atoms, the O atom and its attached C atom are disordered over two positions; the site occupancy factors are ca 0.6 and 0.4. The OH group is involved in an intra-molecular O-H⋯N hydrogen bond.

An X-ray powder investigation of catena-poly[copper(II)-di-mu-chloro-kappa41:2Cl-mu-1,5-dimethyl-1H-tetrazole-kappa2N3:N4].

The crystal structure of the polymeric title complex, [CuCl2(C3H6N4)]n, has been solved from laboratory X-ray powder diffraction data collected at room temperature. The structural model obtained was refined with the Rietveld method using geometric soft restraints. There are two Cu atoms, two Cl atoms and one 1,5-dimethyltetrazole ligand in the asymmetric unit. Both Cu atoms lie on inversion centres and adopt essentially elongated octahedral coordination. Within the octahedra, the elongated axial positions are occupied by Cl atoms, while two Cl and two N atoms (N3 and N4 of the tetrazole ring) are in equatorial sites. Each Cl atom forms an asymmetric bridge between neighbouring Cu atoms, which are also bridged via the N3-N4 bond of the tetrazole ring. These bridges result in the formation of polymeric chains, running along the a axis, with weak C-H...Cl hydrogen bonds crosslinking the chains.

Bis(1-methyl-1H-tetrazol-5-yl)diazene and two its copper(I) chloride complexes poly[[[mu-1,2-bis(1-methyl-1H-tetrazol-5-yl)diazene-kappa4N',N4:N,N4']dicopper(I)]-di-mu-chloro] and catena-poly[[chlorocopper(I)]-mu-1,2-bis(1-methyl-1H-tetrazol-5-yl)diazene-kappa4N',N4:N,N4'].

While bis(1-methyl-1H-tetrazol-5-yl)diazene, C4H6N10, (I), has no crystallographically imposed symmetry, in the two title chlorocopper(I) complexes, [Cu2Cl2(C4H6N10)]n, (II), and [CuCl(C4H6N10)]n, (III), the organic ligands lie across centres of inversion; in (III), the Cu and Cl atoms additionally lie about a twofold rotation axis in the space group P2/c. Complex (II) forms a two-dimensional coordination polymer containing tetrahedrally coordinated Cu(I) atoms, and complex (III) forms a one-dimensional coordination polymer containing five-coordinate square-pyramidal Cu(I) atoms.

Coordination polymers formed by bridging 2-substituted tetrazole ligands: poly[[dichlorocopper(II)]-di-mu2-2-propyl-2H-tetrazole-kappa2N1:N4] and poly[[dichlorocopper(II)]-di-mu2-2-allyl-2H-tetrazole-kappa2N1:N4].

Two polymeric complexes, [CuCl2L2]n, where L is 2-propyltetrazole (C4H8N4) or 2-allyltetrazole (C4H6N4), are the first coordination polymers of 2-substituted tetrazoles in which only the tetrazole rings bridge neighbouring Cu atoms. In both complexes, the Cu atoms lie on inversion centres and are six-coordinated in tetragonally distorted octahedral geometries, CuCl2N4, with two N1 tetrazole ring atoms in the axial positions and two Cl atoms and two N4 tetrazole ring atoms in the equatorial sites. The Cl atoms do not participate in the polymeric layer formation.

Bis[1,3-bis(2-methyltetrazol-5-yl-kappaN4)triazenido-kappaN2]nickel(II).

The title compound, [Ni(BMTT)2], where BMTT is 1,3-bis(2-methyltetrazol-5-yl)triazenide (C4H6N11), presents a molecular complex with tridentate ligands. The tridentate mode of the ligand is realised through the central N atom of the triazene group and two N atoms of the two tetrazole rings. The [Ni(BMTT)2] molecule is the meridional isomer, with crystallographic 4 symmetry in space group P4(2)/n. The nickel centre has a distorted octahedral environment, with two axial Ni-N bonds of 2.041 (2) A and four equatorial Ni-N bonds of 2.0739 (14) A. The molecules are linked together by van der Waals interactions only.

1-phenyl-5-(piperidinomethyl)-1H-tetrazole.

In the molecule of the title 1,5-disubstituted tetrazole, C(13)H(17)N(5), the tetrazole and benzene rings are not coplanar, having a dihedral angle of 42.96 (5) degrees between them. The piperidine fragment adopts a chair conformation, and there is a non-classical intramolecular contact between the benzene H atom and the piperidine N atom. Intermolecular C-H...pi interactions involving the piperidine C-H groups and the benzene rings are responsible for the formation of two-dimensional networks, extending parallel to the ab plane. These networks are linked together into a three-dimensional polymeric structure via pi-pi stacking interactions between the tetrazole rings of two adjacent molecules.

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.

Non-linear optical crystals of 2,2,3-trimethyl-3-(1H-1,2,3,4-tetrazol-5-yl)butanenitrile.

The title compound, C(8)H(13)N(5), is a novel functionally substituted 5-alkyltetrazole. The substituent on the tetrazole C atom is symmetrical, with intrinsic symmetry close to m. There is intermolecular N-H.N hydrogen bonding between adjacent tetrazole rings, which is responsible for the formation of one-dimensional polymeric chains running along the c axis. The polycrystalline compound exhibits frequency doubling for incident light (lambda = 1064 nm) from a YAG:Nd pulsed laser.

The layered structure of poly[[di-mu-chloro-bis[chloro(2-ethyltetrazole-kappaN(4))copper(II)]]-di-mu-2-ethyltetrazole-kappa(2)N(1):N(4)].

In the polymeric title complex, [CuCl(2)(C(3)H(6)N(4))(2)](n), there are two ligands in the asymmetric unit. The Cu atom adopts an elongated octahedral geometry, with two 2-ethyltetrazole ligands [Cu-N = 2.0037 (16) and 2.0136 (16) A] and two Cl atoms [Cu-Cl = 2.2595 (6) and 2.2796 (6) A] in equatorial positions. A Cl atom and a symmetry-related 2-ethyltetrazole molecule [Cu-Cl = 2.8845 (8) A and Cu-N = 2.851 (2) A] lie in the axial positions of the octahedron. One of the two 2-ethyltetrazole ligands of the asymmetric unit exhibits bidentate binding to two Cu atoms through two N atoms of the tetrazole ring, whereas the other ligand is coordinated in a monodentate fashion via one tetrazole N atom. The Cu-atom octahedra form dimer entities by sharing edges with equatorial and axial Cl atoms. The dimers are linked together through the 2-ethyltetrazole ligands to form one-dimensional polymeric zigzag chains extending along the b axis. The chains are connected into infinite layers parallel to the (10-1) plane via the 2-ethyltetrazole ligands.