Nitrogen Atoms N3 Research Articles

Silver(I) and gold(III) complexes with miconazole: The influence of the metal ion on the antimicrobial activity of the coordinated azole

To develop a new antimicrobial agent, we used the clinically approved antifungal azole, miconazole (mcz), as a ligand for the synthesis of silver(I) and gold(III) complexes. The new complexes [Ag(NO3-O)(mcz-N)2] (1) and [AuCl3(mcz-N)] (2) were synthesized and characterized by 1H NMR, IR and UV–Vis spectroscopy and mass spectrometry, while the crystal structure of 1 was determined by single-crystal X-ray diffraction analysis. From the results obtained, it can be concluded that in both complexes, mcz is monodentately coordinated to the silver(I) and gold(III) ions through the imidazole nitrogen atom N3. In the solid state, complex 1 contains two mcz ligands and monodentately coordinated nitrate in the third position, while in the case of 2 gold(III) ion is coordinated by one mcz and three chlorido ligands, resulting in the expected square-planar arrangement around the metal center. DFT and TDDFT calculations were employed to elucidate the electronic structures and thermodynamic stability of the synthesized complexes in solution to complement the experimental findings. The coordination of mcz to silver(I) and gold(III) ions leads to an enhancement of its activity against Gram-negative Escherichia coli and Pseudomonas aeruginosa strains, while against the panel of Staphylococcus aureus and Candida species, only 2 shows improved activity compared to mcz. Both complexes 1 and 2 were tested in vitro for their antimycobacterial activity against the strain Mycobacterium tuberculosis H37Rv and showed good growth inhibition with minimum inhibitory concentration (MIC) values of 3.12 and 8.69 μM, respectively, with complex 1 being twice effective as mcz (MIC = 7.50 μM). Complex 2 significantly reduced the production of pyocyanin, a virulence factor in P. aeruginosa controlled by quorum sensing, while this effect was not observed for 1.

Single crystal-to-single crystal transformation - from two distinct to three distinct spin crossover centers in 2D coordination polymer [Fe(bbtr)3](CF3SO3)2.

1,4-Di(1,2,3-triazol-1-yl)butane (bbtr) forms a two-dimensional (2D) coordination polymer (1) in a reaction with iron(II) triflate. In the crystal lattice there are two crystallographically unique iron(II) ions surrounded octahedrally by a 1,2,3-triazole ring coordinated through nitrogen atoms N3. Single crystal X-ray diffraction studies revealed that spin crossover for each crystallographically independent iron(II) ion proceeds at a different temperature (T1/2(Fe1) = 201 K; T1/2(Fe2) = 216 K), while the magnetic measurements showed that there is one step, complete thermally induced spin crossover (T1/2 = 205 K). Complex 1 undergoes, with time, single crystal-to-single crystal transformation (SCSC) to the converted system (1c) from the R3̄ to the P63 space group, accompanied by significant changes in the lattice parameter c (a shortening of approximately one-third) and consequently unit cell volume. Structural transformation is associated with rebuilding of the polymeric layer as well as the anion network, which is reflected in the results of Mössbauer studies. In the polymorphic system (1c) there are three crystallographically independent iron(II) ions. The temperature dependence results for magnetic susceptibility indicated complete, one-step spin crossover very similar to that of 1; however, single-crystal X-ray diffraction studies of 1c revealed that spin crossover for each crystallographically independent iron(II) ion occurs in a different manner, revealing three elementary stages (T1/2(Fe1) = 200 K; T1/2(Fe2) = 212 K, T1/2(Fe3) = 214 K).

Synthesis and Antiviral Properties of 1-Substituted 3-[ω-(4-Oxoquinazolin-4(3H)-yl)alkyl]uracil Derivatives.

A series of uracil derivatives containing a 4-oxoquinazoline fragment bound to the nitrogen atom N3 of the pyrimidine ring by a short methylene bridge was synthesized to search for new antiviral agents. Some compounds in this series are shown to exhibit high inhibitory activity against human cytomegalovirus and the varicella zoster virus in a HEL cell culture.

Spectroscopic investigations and molecular docking study of 3-(1H-imidazol-1-yl)-1-phenylpropan-1-one, a potential precursor to bioactive agents

The optimized molecular structure, vibrational wavenumbers, corresponding vibrational assignments of 3-(1H-imidazol-1-yl)-1-phenylpropan-1-one have been investigated theoretically and experimentally. The calculated geometrical parameters of the title compound are in agreement with the reported XRD data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Molecular electrostatic potential was performed by the DFT method and from the MEP plot, it is evident that the negative charge covers the carbonyl group and the nitrogen atom N3 of the imidazole ring and the positive region is over the remaining portions of the molecule. The first and second hyperpolarizabilities are calculated and the first hyperpolarizability of the title compound is 16.99 times that of standard NLO material urea and the title compound and its derivatives are good object for further studies in nonlinear optics. The docked ligand title compound forms a stable complex with plasmodium falciparum and gives a binding affinity value of −5.5 kcal/mol and the preliminary results suggest that the compound might exhibit antimalarial activity against plasmodium falciparum.

Exploration of Excited State Deactivation Pathways of Adenine Monohydrates.

Binding of a single water molecule has a dramatic effect on the excited state lifetime of adenine. Here we report a joint nonadiabatic dynamics and reaction paths study aimed at understanding the sub-100 fs lifetime of adenine in the monohydrates. Our nonadiabatic dynamics simulations, performed using the ADC(2) electronic structure method, show a shortening of the excited state lifetime in the monohydrates with respect to bare adenine. However, the computed lifetimes were found to be significantly longer that the observed one. By comparing the reaction pathways of several excited state deactivation processes in adenine and adenine monohydrates, we show that electron-driven proton transfer from water to nitrogen atom N3 of the adenine ring may be the process responsible for the observed ultrafast decay. The inaccessibility of the electron-driven proton transfer pathway to trajectory-based nonadiabatic dynamics simulation is discussed.

Synthesis, crystal structure and complexation behaviour of a thiacalix[4]arene bearing 1,2,3-triazole groups

The structure and complexation behaviour of 1,3-alternate-1,2,3-triazole based on thiacalix[4]arene,1,3-alternate-1 and 2 have been determined by means of X-ray analysis, fluorescence and 1H NMR spectroscopy. The X-ray results suggested that the nitrogen atom N3 on triazole ring can act as hydrogen bond acceptors in the self-assembly of a supramolecular structure. The fluorescence spectra changes indicated that the thiacalix[4]arene bearing 1,2,3-triazole groups were highly selective for Ag+ in comparison with other tested metal ions by enhancement of the monomer emission of pyrene. The 1H NMR results suggested that Ag+ can be strongly bonded by the triazole groups with the cooperation of the ionophoric cavity formed by the two inverted benzene rings and the sulfur atoms of the thiacalix[4]arene.

Platinum(IV) coordination compounds containing 5-methyl-1,2,4-triazolo[1,5- a]pyrimidin-7(4 H)-one as nonleaving ligand. Molecular and cytotoxicity in vitro characterization

Novel platinum(IV) coordination compounds with 5-methyl-1,2,4-triazolo[1,5- a]pyrimidin-7(4 H)-one (HmtpO): cis– trans-[PtCl 2(OH) 2(NH 3)(HmtpO)] ( 1), cis– trans-[PtCl 5(HmtpO)][(CH 3) 2NH 2] ( 2) have been prepared and structurally characterized by spectroscopic methods ( 1H, IR and X-ray crystallography ( 2)). The X-ray results indicate that the local geometry around the platinum(IV) centre approximates a typical octahedral arrangement with nitrogen atom N3 of the HmtpO and three chloride atoms in equatorial positions. The remaining two axial positions are occupied by two chlorides. The preliminary assessment of antitumor properties of ( 1) was performed as an in vitro antiproliferative activity against HL-60 human acute promyelocytic leukemia and HCV29T bladder cancer. The cis– trans-[PtCl 2(OH) 2(NH 3)(HmtpO)] ( 1) exhibits higher cytotoxic activity against HL-60 (IC 50 = 6.4 μM) than cisplatin.

Retention Behavior of Purine-Like Compounds on Titania and the Effect of Organic Modifiers Content in the Mobile Phase

The retention behavior of purine and purine-like compounds on titania was investigated in order to elucidate the strong retention of purine on titania. It was verified that, as expected, the strong retention stemmed from the formation of a chelate ring using the two nitrogen atoms N3 and N9 with titania. Purine has two possible tautometric forms because of proton tautomerism between N7 and N9. Hence, the lone pair of either of the two nitrogen atoms could be located immediately in an sp2 orbital. Therefore, it was found that the lone pairs of N3 and N9 must be located in an sp2 orbital, and the location is essential to forming the chelate with titania. Moreover, the effect of the presence of methanol and acetonitrile in the mobile phase on retention was also investigated. The retention strength increased with their content, but the tendency of this increase was different for the two organic solvents. It was concluded that the difference stems from the differing degrees of strength of the ligands, which includes the analytes and the solvents, as a result of competing with each other. Water and methanol acted as ligands strong enough to compete with the analytes, but acetonitrile did not, probably because it lacks hydroxy groups, which have a strong affinity for titania.

Studies of an Important Residue Involved in the Proton Transfer in the M. HhaI Catalytic Mechanism

The DNA methyltransferase M. HhaI catalyzes transfer of methyl group from SAM to the cytosine base which has been flipped out of DNA duplex into the enzyme active site. Transient protonation of the cytosine ring at the endocyclic nitrogen atom N3 mediated by Glu119 residue has been proposed to facilitates nucleophilic attack on the target base. Replacement of Glu119 into Ala result in the enzyme total loss of catalytic function, and binding affinity for the cognate DNA is decreased about 103 fold . Interestingly when the Glu119 residue is replaced by the Asp, we found the catalytic activity for this mutant protein is only decreased 10 fold in comparison to the WT M. HhaI enzyme. However, the binding affinity for the cognate DNA is decreased around 103 fold, similar to the E119A mutant. Currently, our group is trying to determine the E119A M. HhaI ternary structure and to help us to understand the total loss in enzyme function upon mutation to a shorter side chain. On the other hand, hope that the E119D M. HhaI ternary structure can support Glu119 as a proton donor, and also show why the side chain shorter by only one carbon atom causes the catalytic function to decrease around 10 fold. Moreover, because the residue Glu119 locating in a motif which is highly conserved in the DNA methyltransferases, these results provide insights into catalytic mechanisms for the entire class of enzymes.

Crystal structure of sodium 4-azido-1,2,3-triazolide monohydrate, Na(N3C2HN3) · H2O

C2H3N6NaO, monoclinic, P121/m1 (no. 11), a = 3.6146(8) A, b = 7.146(1) A, c = 11.258(2) A, = 92.02(1)°, V = 290.6 A, Z = 2, Rgt(F) = 0.042, wRref(F) = 0.110, T = 233 K. Source of material The sodium salt of 4-azido-1,2,3-triazole [1,2] was obtained as a hydrate by refluxing perfluoroallylbenzene [CA-registry no. 67899-41-6] with an excess of sodium azide in moist acetone. Crystals of this unexpected product were collected in low yield after filtration and evaporization of the solvent. This compound is certainly an energetic material, but no hazard assessment has been conducted so far. Experimental details Thin plate with thickness of 0.01 mm and its small X-ray scattering power led to a reduced number of observed reflections and a low Ngt/Nparam ratio. Hydrogen atom at C1 (or C1A) could not be found from Fourier difference map because of the overlying with N3 from the disordered azido group. Therefore, it was calculated geometrically. The water hydrogen atom (with O1 in a special position) was found and refined with an isotropic displacement parameter and an O—H bond restraint of 0.85 A. Discussion The title compound crystallizes centrosymmetrically with a positional disorder of the azido group N3-N4-N5 by a mirror plane through the atoms O1, Na1, N1 and N5. The nitrogen atoms N3 and N4 in general positions were refined with an occupancy of 0.5. In the figure the disordered azido group at C1A and the disordered hydrogen atom at C1 were omitted for clarity. The azido group is not linear with an N3–N4–N5 angle of 172.5° (maybe an indication that the nitrogen atom N5 lies not exactly on the mirror plane), and it is tilted slightly out of the ring plane. Hydrogen bridges are observed between the water molecule and the azido group with d(O1–H···N3 ) = 2.009 A. The sodium ion has a distorted octahedral coordination by four nitrogen atoms from different azolide rings and two oxygen atoms from water molecules with distances between 2.347 A – 2.721 A and deviations from the right angle of ±10°. By the coordination of the sodium ion a monolayer is formed and the azido groups penetrate into the adjacent layers which are stacked along the c axis. Z. Kristallogr. NCS 220 (2005) 575-576 575 © by Oldenbourg Wissenschaftsverlag, Munchen Na(1) 2e 1.2529(4) −1⁄4 0.5939(1) 0.040(1) 0.034(1) 0.038(1) 0 −0.0074(7) 0 O(1) 2e 0.7817(9) −1⁄4 0.7321(3) 0.049(2) 0.064(3) 0.039(2) 0 −0.005(2) 0 N(1) 2e 0.7784(9) −1⁄4 0.4267(3) 0.040(2) 0.035(2) 0.034(2) 0 −0.002(2) 0 Table 3. Atomic coordinates and displacement parameters (in A). Atom Site Occ. x y z U11 U22 U33 U12 U13 U23 Crystal: colorless plate, size 0.01 × 0.25 × 0.35 mm Wavelength: Mo K radiation (0.71073 A) : 2.00 cm−1 Diffractometer, scan mode: Nonius KappaCCD, / 2 max: 43.94° N(hkl)measured, N(hkl)unique: 1328, 392 Criterion for Iobs, N(hkl)gt: Iobs > 2 (Iobs), 342 N(param)refined: 66 Programs: SHELXS-97 [3], SHELXL-97 [4] Table 1. Data collection and handling. H(1O) 4f 0.76(1) −0.162(5) 0.782(3) 0.10(2) H(1) 4f 0.5 0.4769 −0.0796 0.1971 0.048 Table 2. Atomic coordinates and displacement parameters (in A). Atom Site Occ. x y z Uiso _____________ * Correspondence author (e-mail: herwig.schottenberger@uibk.ac.at) N2 C1 N3 N4 N5

SYNTHESIS, STRUCTURE, AND CONFORMATION OF ANTI-TUMOR AGENTS IN THE SOLID AND SOLUTION STATES: HYDROXYL DERIVATIVES OF FTORAFUR

ABSTRACT The pyrimidine antimetabolite Ftorafur [FT; 5-fluoro-1-(tetrahydro-2-furyl)uracil] has shown significant antitumor activity in several adenocarcinomas with a spectrum of activity similar to, but less toxic than, 5-fluorouracil (5-FU). It is considered as a prodrug that acts as a depot form of 5-FU, and hence the two drugs exhibit a similar spectrum ofchemotherapeutic activity. Ftorafur is metabolized in animals and humans when hydroxyl groups are introduced into the tetrahydrofuran moiety. These metabolites are also thought to be as active as ftorafur but less toxic than 5-FU. Hydroxyl derivatives: 2′-hydroxyftorafur (III), 3′-hydroxyftorafur (IV) and 2′,3′-dihydroxyftorafur (II) were synthesized and X-ray and NMR studies of these hydroxyl derivatives were undertaken in our laboratories to study the structural and conformational features of Ftorafur and its metabolites in the solid and solution states. X-ray crystallographic investigations were carried out with data collected on a CAD-4 diffractometer. The structures were solved and refined using the SDP crystallographic package of Enraf-Nonius on PDP 11/34 and Microvax computers. All of the compounds studied had the base in the anti conformation. The glycosidic torsion angles varied from −20 to 60 degrees. There is an inverse correlation between the glycosyl bond distances and the χ angle. Molecules with a lower χ angle have a larger bond distance and vice versa. The sugar rings show a wide variation of conformations ranging from C2′-endo through C3′-endo to C4′-exo. The crystal structures are stabilized by hydrogen bonds involving the base nitrogen atom N3 and the hydroxyl oxygen atoms of the sugar rings as donors and the keto oxygens O2 and O4 of the base and the hydroxyl oxygen atoms O2′ and O3′ as acceptors. The NMR studies were carried out on Brüker 400 and 600 MHz instruments. Simulated proton spectra were obtained through Laocoon, and pseudorotational parameters were solved by Pseurot. Presence of syn or anti forms was demonstrated with the use of NOE experiments. The glycosyl conformations in solution vary more widely than in the solid state. The conformations of the sugar molecules are in agreement with the values obtained in the solid state. The studies of the structure and conformation in the solid and solution states give a model for the Ftorafur molecule that could be used in structure, function and biological activity correlation studies.

Die Kristallstrukturen von (1,5-Ditolylpentaazadienido)(triphenylphosphan)gold(I) und 1,5-Ditolyl-3-methylpentaazadien / The Crystal Structures of (1,5-Ditolylpentaazadienido)(triphenylphosphane)gold(I) and 1,5-Ditolyl-3-methylpentaazadien

PPh3Au(tolN5tol) is obtained by the reaction of PPh3Au+ClO4 - with Tl(tolN5tol). It crystallizes in the monoclinic space group P21/c with the lattice parameters a = 1548.8(5), b = 1070.7(2), c = 1779.1(3) pm, β = 90.33(2)°, Z = 4. In the monomeric complex the gold atom is nearly linearcoordinated by the phosphorus atom of the PPh3 group and nitrogen atom N3 of the pentaazadienido ligand ( N3 - Au - P 178.4°). tolNN(NCH3)NNtol crystallizes in the orthorhombic space group Pccn with the lattice constants a = 2426.7(9), b = 469.3(2), c = 1195.3(4) pm. The unit cell contains four molecules, located on twofold axes. Due to the isolobality of the CH3 and the PPh3Au group, the two structures are closely related. Both contain the typical planar zig-zag chain of five nitrogen atoms with located double bonds N1-N2 and N4 - N5 (from 119.8 to 126.6 pm) and shortened single bonds N2 - N3 and N3 - N4 (132.7 to 140.0 pm).

Studies on metal complexes of isocytosine derivative: The crystal structure of zinc(II) complex of 2-hydrazino-4-hydroxy-6-methylpyrimidine.

The crystal structure of the copper (II) complex of 2-hydrazino-4-hydroxy-6-methylpyrimidine (LH) has been determined from three-dimensional X-ray diffractometer data by heavy atom Fourier methods. Crystals of [Cu (LH)2 (H2O)] Cl2·2H2O are triclinic with unit cell dimensions a=10.020 (2), b=14.384 (2), c=7.205 (1) A, α=104.63 (2)°, β=111.04 (1)°, γ=84.93 (2)°, space group P 1, and Z=2. Block-diagonal least-squares refinement using 3126 independent reflections yielded an R value of 0.062. There are two mirror-image complex molecules in a unit cell. Each copper (II) complex has five coordinated bonds and assumes a distorted square pyramid structure. The two ligand molecules, (LH)2 are trans coordinated to the copper (II) ion through nitrogen atoms N3 of the pyrimidine rings and also through the amino nitrogen atoms of the hydrazino groups. In each copper (II) complex, the one apical coordination site is occupied by the water oxygen atom. The hydroxyl group at C4 of the pyrimidine ring takes the keto form, since the hydrogen atom of the hydroxyl group transfers to N1 of the ring. The chloride ions are not directly hydrogen bonded to the N1 atoms of the pyrimidine bases, but are bound to the apical water oxygen atoms. The pyrimidine rings in the crystals are not stacked in parallel but are inclined at an angle of 18.9 or 18.8°.

On the molecular embrace of bleomycin with helical DNA

The active centre model of bleomycin, proposed in our recent paper, has developed in such a way as to reveal the precise physical structure of the bleomycin molecule as a whole and to clarify the mode of binding interaction of this antibiotic molecule with the helically arranged DNA. The thorough model building researches have shown that the three strong hydrogen bonds are formed between the bleomycin molecule and the double helical DNA. The partial intercalation of a thiazole ring in the former molecule into the neighbouring bases on one strand of DNA also contributes to the binding of bleomycin with DNA. These interactions, together with the previously predicted one ionic interaction, establish many points of fixation of the bleomycin molecule with DNA and constitute the origin of the specific selectivity of this molecule with the helical DNA as the partner of molecular embrace. The concept of partial intercalation, introduced in the above-mentioned paper, has also been developed so as to elucidate the essential feature of electronic interaction between the thiazole ring moiety of the bleomycin molecule and the thymine base of DNA, in contact with one thiazole ring. This electronic interaction can be expressed as the intermolecular electron transfer from the 2pπ-orbital of the ring nitrogen atoms N3 in the thymine base to the 3dπ- and/or 4s-orbital(s) of sulphur atom contained in the thiazole ring. As a result of this electron transfer, the release of thymine base is plainly explained. The liberation of a thymine base from DNA results in the restabilization of the double helical DNA with which the bleomycin molecule is still linked. This finding has given the resolution of the existing most puzzling experimental results. Then as a consequence of this resolution, the correctness of our active centre model of the bleomycin molecule is verified with sufficient confidence.

Electronic structure of thymine.

The electronic structures of the ground and low-lying excited states of thymine and the anions 1-HT− and 3-HT−, derived by removing a proton from nitrogen atom N3 and N1, respectively, have been described by all-electron all-integral LCAO–SCF calculations using Gaussian basis functions. In accord with experiment, we find the carbonyl bonds weakened in the anions relative to thymine because of a decrease in their overlap charge densities. On the other hand, our calculations and interpretation of the observed optical and ESR spectra suggest that both for T and 1-HT− the lowest singlet and triplet π → π* states are very similar and localized in the region of the ethylenic bond of thymine.