Tetrazole Group Research Articles

A three-dimensional cadmium(II) coordination polymer with unequal homochiral double-stranded concentric helical chains.

A homochiral helical three-dimensional coordination polymer, poly[[(μ2-acetato-κ(3)O,O':O)(hydroxido-κO)(μ4-5-nicotinamido-1H-1,2,3,4-tetrazol-1-ido-κ(5)N(1),O:N(2):N(4):N(5))(μ3-5-nicotinamido-1H-1,2,3,4-tetrazol-1-ido-κ(4)N(1),O:N(2):N(4):N(5))dicadmium(II)] 0.75-hydrate], {[Cd2(C7H5N6O)2(CH3COO)(OH)]·0.75H2O}n, was synthesized by the reaction of cadmium acetate, N-(1H-tetrazol-5-yl)isonicotinamide (H-NTIA), ethanol and H2O under hydrothermal conditions. The asymmetric unit contains two crystallographically independent Cd(II) cations, two deprotonated 5-nicotinamido-1H-1,2,3,4-tetrazol-1-ide (NTIA(-)) ligands, one acetate anion, one hydroxide anion and three independent partially occupied water sites. The two Cd(II) cations, with six-coordinated octahedral and seven-coordinated pentagonal bipyramidal geometries are located on general sites. The tetrazole group of one symmetry-independent NTIA(-) ligand links one of the independent Cd(II) cations into 61 helical chains, while the other NTIA(-) ligand links the other independent Cd(II) cations into similar but unequal 61 helical chains. These chains, with a pitch of 24.937 (5) Å, intertwine into a double-stranded helix. Each of the double-stranded 61 helices is further connected to six adjacent helical chains through an acetate μ2-O atom and the tetrazole group of the NTIA(-) ligand into a three-dimensional framework. The helical channel is occupied by the isonicotinamide groups of NTIA(-) ligands and two helices are connected to each other through the pyridine N and carbonyl O atoms of isonicotinamide groups. In addition, N-H···O and O-H···N hydrogen bonds exist in the complex.

λ-Orthogonal pericyclic macromolecular photoligation.

A photochemical strategy enabling λ-orthogonal reactions is introduced to construct macromolecular architectures and to encode variable functional groups with site-selective precision into a single molecule by the choice of wavelength. λ-Orthogonal pericyclic reactions proceed independently of one another by the selection of functional groups that absorb light of specific wavelengths. The power of the new concept is shown by a one-pot reaction of equimolar quantities of maleimide with two polymers carrying different maleimide-reactive endgroups, that is, a photoactive diene (photoenol) and a nitrile imine (tetrazole). Under selective irradiation at λ=310-350 nm, any maleimide (or activated ene) end-capped compound reacts exclusively with the photoenol functional polymer. After complete conversion of the photoenol, subsequent irradiation at λ=270-310 nm activates the reaction of the tetrazole group with functional enes. The versatility of the approach is shown by λ-orthogonal click reactions of complex maleimides, functional enes, and polymers to the central polymer scaffold.

Computer-aided virtual screening of Telmisartan analogues as possible CDK cell cycle inhibitors

Cyclin dependent kinases (CDKs) act as potential therapeutic targets in cancer disease and automated docking was performed on a set of 144 Telmisartan analogues containing imidazole rings which are reported as angiotensin II receptor antagonists. Molecular docking analysis of CDKs 2, 4 and 5 resulted in better binding affinities within the active site region of each CDK. Compounds 122 and 121 are selective towards CDK2 and CDK4 inhibitions, whereas compounds 131, 133 and 134 were found to be selective towards CDK4 and CDK5 inhibitions. Compound 27 was found to be highly selective towards CDK2 with binding affinity of −201.547 kcal/mol when compared with dock scores of CDK4 and CDK5 (−195.687 and −170.421 kcal/mol). On the basis of geometric orientation of docked poses within active sites of CDKs, it was observed that the presence of triazole and tetrazole groups on these compounds is responsible for better inhibitory activities.

Influence of N-donor sites in 5-(x-pyridyl)-1H-tetrazole ligands (x = 2, 4) on assembly of polyoxometalate-based compounds modified by multinuclear metal clusters and infinite chains

Through tuning the N-donor site of the pyridyl group in 5-(x-pyridyl)-1H-tetrazole ligands (x = 2, 4), four new Keggin-based compounds, [Cu7(2-ptz)8(OH)2(H2O)2(HPMoVI10MoV2O40)]·4H2O (1), [Cu5(2-ptz)6(HPMoVI10MoV2O40)(H2O)4]·4H2O (2), [Ag6(4-ptz)4(H2SiMo12O40)] (3) and [Ag5(4-ptz)4(H2PMo12O40)]·5H2O (4) (2-ptzH = 5-(2-pyridyl)-1H-tetrazole, 4-ptzH = 5-(4-pyridyl)-1H-tetrazole), were successfully synthesized under hydrothermal conditions and structurally characterized. Compound 1 possesses two kinds of CuII subunits: penta-nuclear clusters and mono-nuclear subunits, which connect with each other to form a one dimensional (1D) stair-like metal–organic chain. The adjacent 1D stair-like chains are further linked by tetradentate Keggin anions to construct a 2D layer. In compound 2, the tetra-nuclear CuII clusters and mono-nuclear CuII subunits construct a 2D metal–organic layer, which is further linked by bidentate Keggin anions to build a 3D framework. In compound 3, the 4-ptz ligand links AgI ions with tetrazole groups to form 1D infinite Ag–ptz chains, which are extended by the pyridyl group of 4-ptz and the tetrazole groups of other 4-ptz molecules to construct a 2D layer. The adjacent 2D layers are further linked by 6-connected Keggin anions to build a 3D framework. In compound 4, the 4-ptz ligands are linked by AgI ions to form 1D infinite Ag–ptz belts. The Keggin anions are linked by AgI ions to construct another infinite inorganic chain, in which each Keggin anion provides six oxygen atoms to coordinate with the AgI ions from adjacent Ag–ptz belts to construct a 2D layer. The roles of the ptz ligands with different N-donor sites in the construction of multinuclear clusters and 1D chains are discussed. The electrochemical and photocatalytic properties of the title compounds were investigated as well.

Conformational Studies of [11Ψ12(CN4)]ScyII and [15Ψ16(CN4)]ScyII? Two Scyliorhinin II Analogues by means of 2D NMR Spectroscopy and Theoretical Methods

A conformational analysis of two analogues of scyliorhinin II [11Ψ12(CN4])]ScyII and [15Ψ16(CN4)]ScyII was performed in DMSO-d6. 2D NMR techniques and restrained molecular dynamics were applied. Our previous studies had shown Scyliorhinin II adopts three cis peptide bonds in DMSO-d6 solution. Moreover, in its two analogues [Aib16] ScyII and [Sar16]ScyII, we also found cis peptide bond geometries. Taking above into consideration, we decided to perform extensive conformational studies of restrained ScyII analogues. To do so, we introduced tetrazole groups into either of peptides studied. These peptides were synthesized by the solid-phase method using the Fmoc chemistry. In the case of two analogues, the following spectra were recorded: TOCSY, NOESY, ROESY, DQF-COSY and set of temperature ones. To obtain final structures, we performed restrained molecular dynamics simulations carried out using CHARMM force field as implemented in XPLOR 3.11 programm. Our calculations resulted in two ensembles of 10 conformations each. Comparing the obtained structures, we found that introduction of a 1,5-substituted tetrazole ring influences the three dimensional structure both locally and globally.

Tetrazole substituted polymers for high temperature polymer electrolyte fuel cells

Tetrazole (TZ) has lower basicity than imidazole and may not be fully protonated by phosphoric acid. DFT calculations suggest that the basicity of TZ groups can be increased by introducing a 2,6-dioxy-phenyl-group in position 5.

Utilization of a ligand containing 2,2'-bipyridyl and tetrazolate groups to construct a 2D Co(II) coordination polymer: spin canting and metamagnetism.

The use of anions of 6,6'-bis(1H-tetrazol-5-yl)-2,2'-bipyridine (H2btzbp) as chelating ligands in preparing a coordination polymer is described. The synthesis, X-ray crystal structure and magnetic properties of a new Co(II) coordination polymer, [Co(btzbp)]n (1), are reported. The in situ [2 + 3] cycloaddition reaction of 6,6'-dicyano-2,2'-bipyridine with sodium azide in the presence of Co(ClO4)2 under hydrothermal conditions afforded compound 1. Structural characterization revealed that 1 features a distorted two-dimensional (2D) grid layer generated by both tetrazolate and 2,2'-bipyridyl bridges of the btzbp(2-) ligand. Variable temperature and field magnetic susceptibility measurements indicate that compound 1 exhibits spin canting with T(N) = 4.0 K and metamagnetism with H(c) = 300 G.

Two Coordination Polymers Constructed from 5‐(4‐Pyridyl)‐1H‐tetrazole Ligands with Different Organic Carboxylates: Structure and Luminescence Properties

AbstractTwo coordination polymers (CPs), namely, [Cu(Hptz)2(Hhba)2]n (1) [Hptz = 5‐(4‐pyridyl)‐1H‐tetrazole, H2hba = 2‐hydroxybenzoic acid] and [Zn3(ptz)2(hpa)2]n (2) (H2hpa = 2‐hydroxy‐2‐phenylacetic acid), were synthesized by solvothermal reactions. Both complexes were characterized by elemental analysis, infrared spectroscopy, powder X‐ray diffraction, thermogravimetric analysis, and single‐crystal X‐ray diffraction analysis. Compound 1 exhibits a 2D (4,4) network, where each layer connects to four adjacent layers to construct a 3D supramolecular framework. Compound 2 has a 3D framework structure composed of 1D SUBs, which are formed by both carboxyl and tetrazole groups. The complexes represent two rare examples of CPs constructed from Hptz and organic carboxyl acid ligands. Complex 2 exhibits intense, red‐shifted emissions in the visible region at room temperature.

Reassessment of the Unique Mode of Binding between Angiotensin II Type 1 Receptor and Their Blockers

While the molecular structures of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are very similar, they are also slightly different. Although each ARB has been shown to exhibit a unique mode of binding to AT1 receptor, different positions of the AT1 receptor have been analyzed and computational modeling has been performed using different crystal structures for the receptor as a template and different kinds of software. Therefore, we systematically analyzed the critical positions of the AT1 receptor, Tyr113, Tyr184, Lys199, His256 and Gln257 using a mutagenesis study, and subsequently performed computational modeling of the binding of ARBs to AT1 receptor using CXCR4 receptor as a new template and a single version of software. The interactions between Tyr113 in the AT1 receptor and the hydroxyl group of olmesartan, between Lys199 and carboxyl or tetrazole groups, and between His256 or Gln257 and the tetrazole group were studied. The common structure, a tetrazole group, of most ARBs similarly bind to Lys199, His256 and Gln257 of AT1 receptor. Lys199 in the AT1 receptor binds to the carboxyl group of EXP3174, candesartan and azilsartan, whereas oxygen in the amidecarbonyl group of valsartan may bind to Lys199. The benzimidazole portion of telmisartan may bind to a lipophilic pocket that includes Tyr113. On the other hand, the n-butyl group of irbesartan may bind to Tyr113. In conclusion, we confirmed that the slightly different structures of ARBs may be critical for binding to AT1 receptor and for the formation of unique modes of binding.

5-[(1R,2R,4R)-2-Methoxy-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]-1H-tetrazole

The title compound, C12H20N4O, undergoes a phase transition on cooling. The room-temperature structure is tetra­gonal (P43212, Z′ = 1), with the meth­oxy­bornyl group being extremely disordered. Below 213 K the structure is ortho­rhom­bic (P212121, Z′ = 2), with ordered mol­ecules. The two independent mol­ecules (A and B) have very similar conformations; significant differences only occur for the torsion angles about the Cborn­yl—Ctetra­zole bonds. The independent mol­ecules are approximately related by the pseudo-symmetry relation: xB = −1/4 + yA, yB = 3/4 - xA and zB = 1/4 + zA. In the crystal, mol­ecules are connected by N—H⋯N hydrogen bonds between the tetra­zole groups, forming a pseudo-43 helix parallel to the c-axis direction. The crystal studied was a merohedral twin with a refined twin fraction value of 0.231 (2).

Rational design, efficient syntheses and biological evaluation of N,N′-symmetrically bis-substituted butylimidazole analogs as a new class of potent Angiotensin II receptor blockers

A series of symmetrically bis-substituted imidazole analogs bearing at the N-1 and N-3 two biphenyl moieties ortho substituted either with tetrazole or carboxylate functional groups was designed based on docking studies and utilizing for the first time an extra hydrophobic binding cleft of AT1 receptor. The synthesized analogs were evaluated for their in vitro antagonistic activities (pA2 values) and binding affinities (–logIC50 values) to the Angiotensin II AT1 receptor. Among them, the potassium (–logIC50 = 9.04) and the sodium (–logIC50 = 8.54) salts of 4-butyl-N,N′-bis{[2′-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}imidazolium bromide (12a and 12b, respectively) as well as its free acid 11 (–logIC50 = 9.46) and the 4-butyl-2-hydroxymethyl-N,N′-bis{[2′-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}imidazolium bromide (14) (–logIC50 = 8.37, pA2 = 8.58) showed high binding affinity to the AT1 receptor and high antagonistic activity (potency). The potency was similar or even superior to that of Losartan (–logIC50 = 8.25, pA2 = 8.25). On the contrary, 2-butyl-N,N′-bis{[2′-[2H-tetrazol-5-yl)]biphenyl-4-yl]methyl}imidazolium bromide (27) (–logIC50 = 5.77) and 2-butyl-4-chloro-5-hydroxymethyl-N,N′-bis{[2′-[2H-tetrazol-5-yl)]biphenyl-4-yl]methyl}imidazolium bromide (30) (–logIC50 = 6.38) displayed very low binding affinity indicating that the orientation of the n-butyl group is of primary importance. Docking studies of the representative highly active 12b clearly showed that this molecule has an extra hydrophobic binding feature compared to prototype drug Losartan and it fits to the extra hydrophobic cavity. These results may contribute to the discovery and development of a new class of biologically active molecules through bis-alkylation of the imidazole ring by a convenient and cost effective synthetic strategy.

Selective antitumour activity and ERα molecular docking studies of newly synthesizedd-homo fused steroidal tetrazoles

Here we report a convenient “click” synthesis for D-homo fused steroidal tetrazoles 11–14 from androstane and estratriene 16,17-seco-16-nitrile-17-mesyloxy derivatives 5–8, via intramolecular 1,3-dipolar cycloaddition from in situ generated 16,17-seco-17-azido-16-nitriles 5a–8a. Products were validated by 1H/13C-NMR, IR, HRMS, and structurally characterized by X-ray crystallography and computational methods. Compounds were evaluated as potential anti-proliferative agents against a panel of human cancer cell lines. D-Homo fused steroidal tetrazoles 13 and 14 appear to have specific, selective anti-proliferative effects against estrogen receptor positive (ER+) breast adenocarcinoma cells, which correlate with binding energies calculated from molecular docking to the estrogen receptor α-ligand binding domain (ERα-LBD). Moreover, molecular docking suggests that D-ring fused steroidal tetrazoles 13 and 14 could bind to ERα-LBD in a manner similar to known anti-estrogenic compounds. Addition of a D-homo fused tetrazole group appears to structurally mimic the hydrogen bonding potential of β-estradiol, suggesting their general utility in designing novel steroidal tetrazole derivatives as anti-estrogens or inhibitors of steroidogenic enzymes.

Efficient copper-catalyzed domino synthesis of tetrazoloisoquinolines

A novel and efficient copper-catalyzed method for the synthesis of tetrazolo[5,1-a]isoquinolines has been developed. The protocol uses readily available substituted 5-(2-halophenyl)-1H-tetrazoles and alkynes as the starting materials and inexpensive copper(I) iodide as the catalyst. The domino reaction underwent sequential copper-catalyzed Sonogashira cross-coupling and intramolecular addition of the NH from a tetrazole group to an internal alkyne.

Comparative study of the AT1 receptor prodrug antagonist candesartan cilexetil with other sartans on the interactions with membrane bilayers

Drug–membrane interactions of the candesartan cilexetil (TCV-116) have been studied on molecular basis by applying various complementary biophysical techniques namely differential scanning calorimetry (DSC), Raman spectroscopy, small and wide angle X-ray scattering (SAXS and WAXS), solution 1H and 13C nuclear magnetic resonance (NMR) and solid state 13C and 31P (NMR) spectroscopies. In addition, 31P cross polarization (CP) NMR broadline fitting methodology in combination with ab initio computations has been applied. Finally molecular dynamics (MD) was applied to find the low energy conformation and position of candesartan cilexetil in the bilayers. Thus, the experimental results complemented with in silico MD results provided information on the localization, orientation, and dynamic properties of TCV-116 in the lipidic environment. The effects of this prodrug have been compared with other AT1 receptor antagonists hitherto studied. The prodrug TCV-116 as other sartans has been found to be accommodated in the polar/apolar interface of the bilayer. In particular, it anchors in the mesophase region of the lipid bilayers with the tetrazole group oriented toward the polar headgroup spanning from water interface toward the mesophase and upper segment of the hydrophobic region. In spite of their localization identity, their thermal and dynamic effects are distinct pointing out that each sartan has its own fingerprint of action in the membrane bilayer, which is determined by the parameters derived from the above mentioned biophysical techniques.

Polymers of intrinsic microporosity (PIMs) substituted with methyl tetrazole

A polymer of intrinsic microporosity (PIM-1) containing nitrile groups was reacted by [2 + 3] cycloaddition reaction to give a polymer substituted with tetrazole groups (TZ-PIM), and then was further methylated to give a new PIM substituted with methyl tetrazole groups (MTZ-PIM). In contrast to TZ-PIMs, the MTZ-PIMs had distinctly improved solubility characteristics, enabling a more detailed investigation of the degree of conversion for the cycloaddition reaction and the structures of TZ-PIMs, which showed the presence of two kinds of tetrazole rings. Compared with PIM-1, the MTZ-PIM showed higher gas permselectivity with a corresponding decrease in gas permeability for pure gas pairs such as O2/N2 and CO2/N2, and for mixed gases, such as CO2/N2. Data for selectivity coupled with high gas permeability is close to the Robeson 2008 upper-bound performance limit for the O2/N2 and CO2/N2 pure gas pairs, and exceeds the upper-bound for the CO2/N2 mixed gas pair.

Synthesis of some novel amino and thiotetrazole purine derivatives and investigation of their antimicrobial activity and DNA interactions

A series of amino and thiotetrazole purine derivatives introduced with different alkyl groups in position 9 was synthesized. The structures of the synthesized compounds were characterized using spectroscopic methods. All the synthesized compounds were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against yeast strains. The effect of the compounds on pBR322 plasmid DNA was studied by gel electrophoretic mobility measurements. The results of antimicrobial activity show that attachment of tetrazole group to purine bases results in disappearance of antimicrobial activity The results of the plasmid DNA interaction and the restriction studies suggest that while aminotetrazole purine derivatives cause DNA damages, thiotetrazole purine derivatives are believed to form a range of interstrand GG adducts with duplex DNA that induce global changes in the DNA conformation.

One- and two-dimensional coordination polymers of substituted tetrazoles with cadmium(II)

The reactions of Cd(NO3)2·4H2O with derivatized tetrazolate ligands yielded a series of coordination polymers of the Cd(II)/iminetetrazolate/anion/solvent family. [Cd(4-Hpyrtet)2(OH)2] (1) (4-Hpyrtet=4-pyridinetetrazole) is two-dimensional with the ligand in the protonated form with the tetrazole N3 site as the protonation location. The Co(II) and Cu(II) analogous [M(4-pyrtet)2(H2O)2] (M=Co (2), Cu (3)) are structurally similar to 1, but with the aqua ligands projecting to the intralamellar voids rather than into the interlamellar domains, as observed for the hydroxy groups of 1. The 2-pyridyltetrazolate derivative [CdCl(2-pyrtet)(DMF)] (4) is one-dimensional with chloride and DMF ligands projecting from a {Cd(2-pyrtet)}nn+ ribbon. Compound 5, [Cd4Cl6(prytet)2(DMF)4], (prytet=pyrazinetetrazolate) is two-dimensional and exhibits {Cd4Cl6} secondary building units linked through tetrazolate groups and pyrazine units into the network structure. The azide derivative, [Cd3(N3)4(4-pyrtet)2(H2O)2 (6), is a “pillared” layer three-dimensional framework with {Cd3(N3)4(tetrazolate)2(H2O)2}n layers through the 4-pyrtet ligands.

A Novel Zinc(II)‐Organic Coordination Framework Involving in situ Tetrazole Ligand Synthesis: Crystal Structure and Luminescent Properties

AbstractThe compound [Zn(5‐(2‐M)ET)2]n (1) [5‐(2‐M)ET = 5‐(2‐methoxyl)ethyltetrazole] was obtained by reaction of ZnSO4, sodium azide, and 3‐methoxyl propionitrile via an in situ [2+3] cycloaddition under hydrothermal conditions. It was characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis, and single‐crystal X‐ray diffraction. Compound 1 is a 3D coordination framework with diamond‐like topology that is built up by infinite helical chains, which are interconnected by tetrazole groups.

Magnesium(II), Calcium(II), and Barium(II) Coordination Compounds Constructed by 1H‐Tetrazolate‐5‐acetic Acid Ligand

AbstractReactions of H2tza (H2tza = 1H‐tetrazolate‐5‐acetic acid) with Mg(NO3)2·6H2O, Ca(NO3)2·4H2O, or Ba(NO3)2 with the presence of KOH under hydrothermal conditions, produced three new coordination compounds, [M(tza)(H2O)2] (M = Mg (1), Ca (2), Ba (3)). These compounds were structurally characterized by elemental analysis, IR spectroscopy, and single‐crystal X‐ray diffraction. Compounds 1 and 3 display 2D structures, whereas 2 reveals a 1D structure with bridging tza ligand molecules as linkers. Furthermore, the luminescence properties of 1–3 at room temperature in the solid state were also investigated. The results show that the nature of metal ions play an important role in governing the molecular frameworks of 1–3, and the strong coordinate abilities of carboxylate and tetrazolate group, endow tza with abundant coordination modes.

Three-dimensional networks based on trinuclear motifs with tricomponent azide-carboxylate-tetrazolate cobridges: synthesis, structure and magnetic properties

Two 3D coordination polymers of Mn(II) with azide and bifunctional zwitterionic ligands bearing both carboxylate and tetrazolate groups, 1-(carboxylatomethyl)-3-(5-tetrazolato)pyridinium (L(1)) and 1-(carboxylatoethyl)-4-(5-tetrazolato)pyridinium (L(2)), were synthesized, and structurally and magnetically characterized. They are formulated as [Mn(3)(L(1))(2)(N(3))(4)(H(2)O)(2)](n)·4nH(2)O (1) and [Mn(3)(L(2))(2)(N(3))(4)(H(2)O)(3)](n)·3.5nH(2)O (2). In both compounds, octahedral Mn(II) ions are linked by the mixed (μ(2)-EO-N(3))(μ(2)-syn,syn-COO)(μ(2)-N(2),N(3)-CN(4)) (CN(4) = tetrazolate and EO = end-on) triple bridges to give anionic linear trinuclear motifs. The motifs are connected through EE-N(3) (EE = end-to-end) bridges to give layers and chains in 1 and 2, respectively, and the cationic pyridinium spacers serve to interlink the layers or chains into three-dimensional frameworks with the α-Po and CdSO(4)-type topology, respectively. Magnetic studies demonstrated that the magnetic interactions within and between the trinuclear motifs, through the tricomponent and EE-N(3) bridges, respectively, are both antiferromagnetic in both compounds.