Antimicrobial activity of stable hemiaminals against Porphyromonas gingivalis.

Porphyromonas gingivalis is a major etiologic agent and a key pathogen responsible for the development and progression of chronic periodontitis. Controlling the number of periodontal pathogens is one of the primary actions for maintaining oral health; therefore, active compounds with a capacity to exert antimicrobial activity have received considerable attention as they may represent potential new therapeutic agents for the treatment of chronic periodontitis. Heterocyclic compounds possessing 1,2,4- or 1,2,3-triazoles are known for several biological activities, including antibacterial properties. Among them are stable hemiaminals which can be obtained in reaction between nitrobenzaldehyde derivatives and 4-amino-1,2,4-triazole or 4-amino-3,5-dimethyl-1,2,4-triazole. In this study, we selected two relatively stable hemiaminals: (2,4-dinitrophenyl)(4H-1,2,4-triazole-4-ylamino)methanol (24DNTAM) and (2,4-dinitrophenyl)(4H-3,5-dimethyl-1,2,4-triazole-4-ylamino)methanol (24DNDMTAM). Both compounds showed promising anti-P. gingivalis activity, higher against ATCC 33277 strain as compared to A7436 strain. The lowest hemiaminal concentration inhibiting visible planktonic bacterial growth under high-iron/heme conditions was ∼0.06 mg/ml, and the lowest hemiaminal concentration showing killing of bacteria was ∼0.25 mg/ml. Antimicrobial activity was also observed against P. gingivalis grown on blood agar plates. Slightly higher antimicrobial activity of both compounds was observed when P. gingivalis was grown in co-cultures with epithelial HeLa cells under low-iron/heme conditions, which mimic those occurring in vivo. 24DNTAM was more effective against P. gingivalis, but exhibited higher cytotoxic activity against epithelial and red blood cells, as compared with 24DNDMTAM. We conclude that both hemiaminals might originate a novel group of biologically important molecules.

A Study on the Condensation Reaction of 4-Amino-3,5-dimethyl-1,2,4-triazole with Benzaldehydes: Structure and Spectroscopic Properties of Some New Stable Hemiaminals.

Studies on the stable hemiaminals and Schiff bases formation in the reaction of substituted benzaldehydes with primary 3,5-dimethyl-1,2,4-triazole 4-amine were carried out under neutral conditions. These products were investigated by IR, Raman, MS, ¹H- and (13)C-NMR spectra as well as by X-ray crystallography. The effect of reaction conditions: temperature, polarity of the solvents utilized, substrate concentration and the ortho and para benzaldehyde substituents on the yield of products was also examined.

Stable Hemiaminals: 2-Aminopyrimidine Derivatives.

Stable hemiaminals can be obtained in the one-pot reaction between 2-aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents on the phenyl ring and pyrimidine ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess a tetrahedral carbon atom constituting a stereogenic centre. As the result of crystallisation in centrosymmetric space groups both enantiomers are present in the crystal structure.

Stable hemiaminals with a cyano group and a triazole ring.

Under neutral conditions the reactions between 4-amino-1,2,4-triazole and cyano-substituted benzaldehyde derivatives yield stable hemiaminals. Addition of small amounts of acid catalyst promotes further step of dehydration resulting in formation of Schiff bases. Four new hemiaminals and the corresponding imines have been obtained. The molecular stability of the hemiaminal intermediates results from both the 1,2,4-triazole moiety and electron withdrawing substituents on the phenyl ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess stereogenic centres on carbon and nitrogen atoms. The chirality of these centres is strongly correlated with the conformation of the molecules due to heteroatom hyperconjugation effects.

The impact of isomers of hemiaminal-1,2,4-triazole conjugates differently substituted in the phenyl ring and their Cu2+ complexes on the catalytic activity of the antigenomic delta ribozyme.

The ability of four stable hemiaminals differently substituted in the phenyl ring and their complexes with Cu(2+) ions to inhibit catalytic cleavage of the antigenomic delta ribozyme was compared. The hemiaminals were novel chiral derivatives of 1,2,4-triazole [i.e. (2,4-dinitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2,4-dnbald), (2-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2-nbald), (3-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (3-nbald) and (4-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (4-nbald)]. The complexes of nbalds with Cu(2+) were characterized using UV and EPR methods and additionally, the formation of 2,4-dnbald-Cu(2+) complex with CuL(2) stoichiometry was confirmed by mass spectrometry. The data suggest that there are two ways in which nbalds and their Cu(2+) complexes can influence catalytic cleavage of antigenomic delta ribozyme. The coordinated Cu(2+) ions may play the role of new cationic ligands increasing the affinity of the complexes to the ribozyme. Such situation occurs in the case of 2- and 2,4-nbald. Their Cu(2+) complexes decrease ribozyme cleavage rates twice more efficiently than uncomplexed compounds. Moreover, the Cu(2+) complexes displace the catalytic divalent metal ions from their strong binding sites located in the ribozyme J4/2 region as shown by the Pb(2+)-induced cleavage approach. On the other hand, 3- and 4-nbald inhibit catalysis more strongly as compared to 2-nbald and 2,4-dnbald but the ribozyme cleavage rates are changed only slightly upon Cu(2+) complexation. The mechanism of ribozyme inhibition by interfering with the formation of a correct ribozyme tertiary structure seems to operate in this case.

Diorganotin complexes of a thiosemicarbazone, synthesis: properties, x-ray crystal structure, and antiproliferative activity of diorganotin complexes.

The synthesis and spectral characterization of novel diorganotin complexes with 3-hydroxypyridine-2-carbaldehyde thiosemicarbazone, H(2)L(1), [SnMe(2)(L)] (2), [SnBu(2)(L)] (3), and [SnPh(2)(L)] (4) are reported. The single-crystal X-ray structure of complex [SnPh(2)(L)(DMSO)] (5) shows that the ligand is doubly deprotonated and is coordinated as tridentate ligand. The six coordination number is completed by two carbon atoms of phenyl groups. There are two similar monomers 5a (Sn1) and 5b (Sn51) in the asymmetric unit. The monomers 5a and 5b are linked through intermolecular hydrogen bonds of N-H-O and C-H-S type. C-H --> pi, intermolecular interactions, intra- and intermolecular hydrogen bonds stabilize this structure and leads to aggregation and a supramolecular assembly. The IR and NMR ((1)H, (13)C and (119)Sn) spectroscopic data of the complexes are reported. The in vitro cytotoxic activity has been evaluated against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T-24 (bladder cancer cell line), A-549 (nonsmall cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). Compounds 1, 3, and 4 were found active against all four cell lines. Selectivity was observed for complexes 3 and 4 which were found especially active against MCF-7 and T-24 cancer cell lines.

Organotin Compound Derived from 3-Hydroxy-2-formylpyridine Semicarbazone: Synthesis, Crystal Structure, and Antiproliferative Activity.

The novel diphenyltin(IV) compound [Ph(2)(HyFoSc)Sn] (2), where H(2)HyFoSc (1) is 3-hydroxy-2-formylpyridine semicarbazone, was prepared and characterized by vibrational and NMR ((1)H, (13)C) spectroscopy. The structure of [Ph(2)(HyFoSc)Sn] was confirmed by single-crystal X-ray crystallography. The doubly deprotonated ligand is coordinated to the tin atom through the enolic-oxygen, the azomethine-nitrogen, and phenolic-oxygen, and so acts as an anionic tridentate ligand with the ONO donors. Two carbon atoms complete the fivefold coordination at the tin(IV) center. Intermolecular hydrogen bonding, C-H --> pi, and pi --> pi interactions combine to stabilize the crystal structure. Compounds 1 and 2 have been evaluated for antiproliferative activity in vitro against the cells of three human tumor cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A549 (nonsmall cell lung carcinoma), and a mouse fibroblast L-929 cancer cell line.

N-fusion approach in construction of contracted carbaporphyrinoids: formation of N-fused telluraporphyrin.

Insertion of PCl(3) into 5,10,15,20-tetraaryl-21-telluraporphyrin leads to a phosphorus complex of N-fused dihydrotelluraporphyrin with an inverted tellurophene ring. Its CNN coordination core places the macrocycle in the family of contracted carbaporphyrinoids. A cycle of direct transformations affords an elegant triangle of three mutually convertible N-fused porphyrinoids, with distinct spectroscopic features: antiaromatic, nonaromatic and aromatic. The nonaromatic species has a dome shaped skeleton which forms in the solid state a ball and socket structure with C(60).

Biotransformations of steroid compounds by Chaetomium sp. KCH 6651.

Biotransformations of steroid compounds: androstenedione, testosterone, progesterone, pregnenolone and DHEA using Chaetomium sp. 1 KCH 6651 strain as a biocatalyst were investigated. The microorganism proved capable of selective hydroxylation of the steroid substrates. Androstenedione was converted to 14alpha-hydroxyandrost-4-en-3,17-dione (in over 75% yield) and 6beta-hydroxyandrost-4-en-3,17-dione (in low yield), while testosterone underwent regioselective hydroxylation at 6beta position. Progesterone was transformed to a single product-6beta,14alpha-dihydroxypregnan-4-en-3,20-dione in high yield, whereas biotransformation of DHEA resulted in the formation of 7alpha-hydroxy derivative, which was subsequently converted to 7alpha-hydroxyandrost-4-en-3,17-dione.

Palladium vacataporphyrin reveals conformational rearrangements involving Hückel and Möbius macrocyclic topologies.

5,10,15,20-Tetraaryl-21-vacataporphyrin (butadieneporphyrin, an annulene-porphyrin hybrid) which contains a vacant space instead of heteroatomic bridge acts as a ligand toward palladium(II). The metal ion of square-planar coordination geometry is firmly held via three pyrrolic nitrogen atoms where the fourth coordination place is occupied by a monodentate ligand or by an annulene part of vacataporphyrin. The macrocycle reveals the unique structural flexibility triggered by coordination of palladium. The structural rearrangements engage the C(20)C(1)C(2)C(3)C(4)C(5) annulene fragment which serves as a linker between two pyrrolic rings of vacataporphyrin albeit the significant ruffling of the tripyrrolic block is also of importance. Two fundamental modes of interactions between the palladium ion and annulene moiety have been recognized. The first one resembles an eta(2)-type interaction and involves the C(2)C(3) unit of the butadiene part. Alternatively the profound conformational adjustments allowed an in-plane coordination through the deprotonated trigonally hybridized C(2) center of butadiene. The coordinated vacataporphyrin acquires Hückel or extremely rare Möbius topologies readily reflected by spectroscopic properties. The palladium vacataporphyrin complexes reveal Hückel aromaticity or Möbius antiaromaticity of [18]annulene applying the butadiene fragment of vacataporphyrin as a topology selector. The properties of specific conformers were determined using (1)H NMR and density functional theory calculations.

X-ray crystal structures, electron paramagnetic resonance, and magnetic studies on strongly antiferromagnetically coupled mixed mu-hydroxide-mu-N(1),N(2)-triazole-bridged one dimensional linear chain copper(II) complexes.

Four new metal-organic polymeric complexes, {[Cu(mu-OH)(mu-ClPhtrz)][(H 2O)(BF 4)]} n ( 1), {[Cu(mu-OH)(mu-BrPhtrz)][(H 2O)(BF 4)]} n ( 2), {[Cu(mu-OH)(mu-ClPhtrz)(H 2O)](NO 3)} n ( 3), and {[Cu(mu-OH)(mu-BrPhtrz)(H 2O)](NO 3)} n ( 4) (ClPhtrz = N-[( E)-(4-chlorophenyl)methylidene]-4 H-1,2,4-triazol-4-amine; BrPhtrz = N-[( E)-(4-bromophenyl)methylidene]-4 H-1,2,4-triazol-4-amine), were synthesized in a reaction of substituted 1,2,4-triazole and various copper(II) salts in water/acetonitrile solutions. The structures of 1- 4 were characterized by single-crystal X-ray diffraction analysis. The Cu(II) ions are linked both by single N (1), N (2)-1,2,4-triazole and hydroxide bridges yielding one dimensional (1D) linear chain polymers. The tetragonally distorted octahedral geometry of copper atoms is completed alternately by two water and two BF 4 (-) anion molecules in 1 and 2 but solely by two water molecules in 3 and 4. Magnetic properties of all complexes were studied by variable temperature magnetic susceptibility measurements. The Cu(II) ions are strongly antiferromagnetically coupled with J = -419(1) cm (-1) ( 1), -412(2) cm (-1) ( 2), -391(3) cm (-1) ( 3), and -608(2) cm (-1) ( 4) (based on the Hamiltonian H = - J[ summation operator S i . S i+ 1]). The nature and the magnitude of the antiferromagnetic exchange were discussed on the basis of complementarity/countercomplementarity of the two competing bridges.

Hydrophobic 'lock and key' recognition of N-4-nitrobenzoylamino acid by strychnine.

During racemic resolution of N-4-nitrobenzoyl-DL-amino acids (alanine, serine and aspartic acid) by a fractional crystallization of strychninium salts, crystals of both diastereomeric salts were grown, and the crystal structures of strychninium N-4-nitrobenzoyl-L-alaninate methanol disolvate (1a), strychninium N-4-nitrobenzoyl-D-alaninate dihydrate (1b), strychninium N-4-nitrobenzoyl-D-serinate dihydrate (2a), strychninium N-4-nitrobenzoyl-L-serinate methanol solvate hydrate (2b), strychninium hydrogen N-4-nitrobenzoyl-L-aspartate 3.75 hydrate (3a) and strychninium hydrogen N-4-nitrobenzoyl-D-aspartate 2.25 hydrate (3b) were determined. The strychninium cations form corrugated layers, which are separated by hydrogen-bonded anions and solvent molecules. Common features of the corrugated layers are deep hydrophobic grooves at their surfaces, which are occupied by the 4-nitrobenzoyl groups of suitable anions. The hydrophobic ;lock and key' recognition of 4-nitrobenzoyl groups of amino acid derivatives in deep grooves of the strychnine self-assembly causes the resulting surface to have more hydrophilic properties, which are more appropriate for interactions in the hydrophilic environments from which strychninium salts were crystallized. In the crystal structure of (2a) and (3a), such hydrophobic ;lock and key' recognition is responsible for the lack of N-H+...O- hydrogen bonds that are usually formed between the protonated tertiary amine N atom of the strychninium cation and the deprotonated carboxyl group of the resolved acid. In the crystal structure of (2a) and (3a), the protonated amine N atom is a donor of hydrogen bonds, while the hydroxyl group of the serine derivative and water molecules are their acceptors. In light of the hydrophobic recognition, chiral discrimination depends on the nature of the hydrogen-bond networks, which involve anions, solvent molecules and the protonated amine N atom of strychninium cations.

Isomorphous crystals of strychninium 4-chlorobenzoate and strychninium 4-nitrobenzoate.

In strychninium 4-chlorobenzoate, C21H23N2O2+.C7H4ClO2-, (I), and strychninium 4-nitrobenzoate, C21H23N2O2+.C7H4NO4-, (II), the strychninium cations form pillars stabilized by C-H...O and C-H...pi hydrogen bonds. Channels between the pillars are occupied by anions linked to one another by C-H...pi hydrogen bonds. The cations and anions are linked by ionic N-H+...O- and C-H...X hydrogen bonds, where X=O, pi and Cl in (I), and O and pi in (II).

Syntheses and molecular structure of some Rh and Ru complexes with the chelating diphenyl (2-pyridyl)phosphine ligand.

The rhodium(III) complex mer,cis-[RhCl3(PPh2py-P,N)(PPh2py-P)] (1) (PPh2py = diphenyl (2-pyridyl)phosphine) has been prepared from RhCl3 x 3H2O and PPh2py and converted to the trans,cis-[RhCl2(PPh2py-P,N)2]PF6 (2) in acetone solution by treatment with Ag+ and PF6(-). Ruthenium(III) and ruthenium(II) compounds with PPh2py, mer,cis-[RuCl3(PPh2py-P,N)(PPh2py-P)] (3) and mer-[RuCl(PPh2py-P,N)2(PPh2py-P)]Cl (5) have been obtained from DMSO precursor complexes. In a chloroform solution, complex (5) isomerizes to fac-[RuCl(PPh2py-P,N)2(PPh2py-P)]Cl (fac-5). All compounds have been characterized by MS, UV-vis, IR, and 1H and 31P{1H} NMR spectroscopy, and the Ru(III) compound has been characterized by EPR spectroscopy as well. The crystal structures of 1, 2, 3, and fac-5 have been determined. In all compounds under investigation, at least one pyridylphosphine acts as a chelate ligand. The 31P chemical shifts for chelating PPh2py-P,N depend on the Ru-P bond lengths.

Chemistry of palladium phosphinite (PPh(2)(OR)) and phosphonite (P(OPh)(2)(OH)) complexes: catalytic activity in methoxycarbonylation and Heck coupling reactions.

The new phosphinite and phosphonite complexes (1-8) are very efficient catalysts for the methoxycarbonylation of iodobenzene and Heck cross-coupling of bromobenzene with butyl acrylate. High catalytic activity of these complexes can be explained by their in situ transformations during the reaction, stimulated by the presence of water, acid (HCl) or base (NEt(3)). Hydrolysis of phosphinite palladium complexes of the form trans-PdCl(2)[PPh(2)(OR)](2) (R = C(6)F(5), 2, (t)Bu 3, or O-menthyl 4) results in the formation of the dimeric complex [mu-ClPd(PPh(2)OH)(PPh(2)O)](2) 5, which is deprotonated by NEt(3), producing a polymeric complex of formula [Pd(P(O)PPh(2))(2)](n) 8. The reverse reaction, protonolysis of 8 with HCl, leads back to 5 and the monomeric complex 5a. The phosphinite complex PdCl(2)[PPh(2)(OBu)](2)1 with a more lipophilic ligand, PPh(2)(OBu), does not undergo hydrolysis under the same conditions. In the reaction of PdCl(2)(cod) with P(OPh)(2)(OH), the new dimer [mu-ClPd(P(OPh)(2)OH)(P(OPh)(2)O)](2) 6 was obtained, whereas reaction of Pd(OAc)(2) with P(OPh)(2)(OH) leads to the polymeric complex [Pd[P(O)(OPh)(2)](2)](n) 7. Protonolysis of 7 with HCl results in the formation of 6.

Similar environments for the ClO4-, HSO4- and H2PO4- anions offered by strychnine self-assemblies.

In strychninium chlorate(VII) monohydrate, C21H23N2O2+.ClO4-.H2O, strychninium hydrogensulfate(VI) dihydrate, C21H23N2O2+.HSO4-.2H2O, and strychninium dihydrogenphosphate(V) dihydrate, C21H23N2O2+.H2PO4-.2H2O, the strychninium cations form bilayer sheets separated by water-anion sheets. The strychnine bilayer sheets in the three compounds are similar to one another. In all three structures, the surfaces of the cation and water-anion sheets exhibit donor-acceptor matching.

Cyclic water pentamers in triclinic crystals of brucinium L-glycerate.

Brucinium L-glycerate 4.75-hydrate, C23H27N2O4+.C3H5O4-.4.75H2O, was obtained by racemic resolution of DL-glyceric acid. This is the first report of triclinic crystals containing brucine. The water and L-glycerate anions form tapes built up of pentamers formed by water and carboxy O atoms, and this appears to be the reason for the low symmetry of the crystal.