Is planarity of pyridin-2-yl- and pyrazin-2-yl-formamide thiosemicarbazones related to their tuberculostatic activity? X-ray structures of two pyrazine-2-carboxamide-N′-carbonothioyl-hydrazones

Crystal structures of two title compounds and several their relatives known earlier reveal conservative and characteristic features, which may be related to their tuberculostatic activity. The molecules are predominantly planar due to conjugation through five successive bonds in the zwitterionic fragment S⁻–C(sp²)–N–NH⁺–C(sp²)–NH₂ and intramolecular hydrogen bonds, which prevent rotation of the adjacent pyrazine (or pyridine) ring. It has been suggested that in spatial sense such planar molecules resemble acridines intercalating with nucleic acids and that similar process may be responsible for tuberculostatic activity of the title pyrazine-2-carboxamide-N′-carbonothioyl-hydrazones.     

Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. II. Crystal structures of 3‐[amino(pyrazin‐2‐yl)methylidene]‐2‐methylcarbazic acid esters

Four compounds showing moderate antituberculostatic activity have been studied to test the hypothesis that the planarity of the 2‐[amino(pyrazin‐2‐yl)methylidene]dithiocarbazate fragment is crucial for activity. N′‐Anilinopyrazine‐2‐carboximidamide, C₁₁H₁₁N₅, D1, and diethyl 2,2′‐[({[amino(pyrazin‐2‐yl)methylidene]hydrazinylidene}methylidene)bis(sulfanediyl)]diacetate, C₁₄H₁₉N₅O₄S₂, B1, maintain planarity due to conjugation and attractive intramolecular hydrogen‐bond contacts, while methyl 3‐[amino(pyrazin‐2‐yl)methylidene]‐2‐methyldithiocarbazate, C₈H₁₁N₅S₂, C1, and benzyl 3‐[amino(pyrazin‐2‐yl)methylidene]‐2‐methyldithiocarbazate, C₁₄H₁₅N₅S₂, C2, are not planar, due to methylation at one of the N atoms of the central N—N bond. The resulting twists of the two molecular halves (parts) of C1 and C2 are indicated by torsion angles of 116.5 (2) and −135.9 (2)°, respectively, compared with values of about 180° in the crystal structures of nonsubstituted compounds. As the methylated derivatives show similar activity against Mycobacterium tuberculosis to that of the nonsubstituted derivatives, maintaining planarity does not seem to be a prerequisite for activity.     

On the Reaction between 1-Aza-1,3-dienes and Push-Pull Olefins of the Acyloxymethylidene-malononitrile Type

 The reaction between push-pull olefins of the acyloxymethylidene-malononitrile type and α, β-unsaturated hydrazones affords selectively 5-alkyl-2-cyano-6-(N′,N′-dimethylhydrazono)-hexa-2,4-dienenitriles. No [4+2]-cycloaddition products were detected. The structure elucidation of the obtained compounds and possible reaction mechanisms are discussed.     

Imidazole-Analogues of 6-Epicastanospermine and of 3,7a-Diepialexine

The chiral bicyclic imidazol derivatives 7 and 8 were obtained from D-glucose derivative 9 by a sequence of selective protection/deprotection and intramolecular S_N2 reactions. Triols 7 and 8 are analogues of 6-epica-stanospermine ( 4 ) and of 3,7a-diepialexine ( 6 ), respectively, and are potential glycosidase inhibitors. However, their anti-HIV activity proved to be only marginal.     

Planarity of <Emphasis Type="Italic">N</Emphasis>′-(amino-2-pyridylmethylene)-hydrazide carbodithioic acid frame and crystal structure of its methyl ester dihydrate

The title compound exists in a dipolar form both in the solvent-free and in the dihydrate crystal. Unit cell dimensions: 23.303(5), 7.3100(10), 15.030(3) Å, β = 101.78(3)^∘; space group C2/c (monoclinic) with Z = 8. The molecule is flat due to extended conjugation in the central N=C(pyr)–N(3)H–N=C–S– fragment and three assisted intramolecular hydrogen bonds, one of them between the pyridine N atom (acceptor) and the N(3)H amine group as a hydrogen bond donor. As a result the molecule adopts an antiperiplanar conformation along the N–N bond and synperiplanar conformation along the neighbouring N–C bonds. Presence of two water molecules results in a very extensive network of intermolecular hydrogen bonds (eight) as compared with the crystal structure of the anhydrous compound.     

Crystal structures of 3-(4-pyridinyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrimidine and its 6-hydroxy derivative

(1): C₁₀H₁₁N₅,M _r=201.23, from water, P ,a=6.913(1),b=8.198(2),c=9.212(2) Å, =72.36(2), =109.03(2) and =88.13(1)^o,D _x=1.436 g/cm³,Z=2. FinalR=0.043 for 1477 observed reflections. (2): C₁₀H₁₁N₅O,M _r=217.23, from methanol/water solution. P2₁/c,a=9.291(2),b=11.263(3),c=10.454(3) Å, and =114.05(1)^o,D _x=1.444, g/cm³,Z=4. FinalR 0.056 for 1587 observed reflections. The data were collected on a diffractometer at room temperature. Structures were solved by direct methods and refined by anisotropic full-matrix least-squares method. In the solid state both molecules have the same conformation and are packed in similar manner. The planarity of the condensed triazole ring and its electrons conjugation with a lone pair at N8 impose C6 sofa conformation of the saturated diazine rings. Hydroxy group in2 is in an energetically unfavorable axial position. Both in1 and2, N8–H ... N34 hydrogen bonds join molecules into infinite chains, and O6–H ... N1 hydrogen bonds in2 span the chains into two-dimensional net. The molecules in hydrogen bonded chains and sheets have the same chirality.     

Electroactive dipyrromethene-Cu(II) self-assembled monolayers: complexation reaction on the surface of gold electrodes

In the work presented, thiol- and COOH-terminated dipyrromethene derivatives have been applied for gold electrode modification. Dipyrromethene deposited onto a solid support, after binding Cu2+, can act as a redox active monolayer. The complexation of Cu(II) ions has been performed on the surface of gold electrodes modified with dipyrromethene. The characterization of dipyrromethene-Cu(II) self-assembled monolayers (SAMs) has been done by cyclic voltammetry (CV), wettability contact angle measurements, and atomic force microscopy (AFM). The new electroactive monolayer could be applied for the immobilization of proteins and ssDNA or for electrochemical anion sensing without redox markers in the solution.     

5,5-Dialkyldipyrromethane as a precursor for the synthesis of calix[4]phyrins and pseudocorroles using MacDonald [2+2] condensations

The reaction of formylated dialkyldipyrromethanes with 5,5-dialkyl or 5-aryldipyrromethanes afforded meso-tetraalkyl or dialkylaryl-calix[4]phyrins, respectively. Templating with Ni(II) was needed to get these compounds in acceptable yields. From these MacDonald condensations, trisubstituted pseudocorroles were also isolated as Ni(II) chelates.