Antileishmanial Anthracene Endoperoxides: Efficacy In Vitro,Mechanisms and Structure-Activity Relationships

Leishmaniasis is a vector-borne disease caused by protozoal Leishmania parasites. Previous studies have shown that endoperoxides (EP) can selectively kill Leishmania in host cells. Therefore, we studied in this work a set of new anthracene-derived EP (AcEP) together with their non-endoperoxidic analogs in model systems of Leishmania tarentolae promastigotes (LtP) and J774 macrophages for their antileishmanial activity and selectivity. The mechanism of effective compounds was explored by studying their reaction with iron (II) in chemical systems and in Leishmania. The correlation of structural parameters with activity demonstrated that in this compound set, active compounds had a LogP_OW larger than 3.5 and a polar surface area smaller than 100 Ų. The most effective compounds (IC₅₀ in LtP < 2 µM) with the highest selectivity (SI > 30) were pyridyl-/tert-butyl-substituted AcEP. Interestingly, also their analogs demonstrated activity and selectivity. In mechanistic studies, it was shown that EP were activated by iron in chemical systems and in LtP due to their EP group. However, the molecular structure beyond the EP group significantly contributed to their differential mitochondrial inhibition in Leishmania. The identified compound pairs are a good starting point for subsequent experiments in pathogenic Leishmania in vitro and in animal models.     

Comparison of the photoelectrochemical oxidation of methanol on rutile TiO2 (001) and (100) single crystal faces studied by intensity modulated photocurrent spectroscopy

The photooxidation of methanol as a model substance for pollutants on rutile TiO(2) (001) and (100) surfaces was investigated using intensity modulated photocurrent spectroscopy (IMPS). The results are analyzed in view of the influence of the surface structure, the methanol concentration and the electrode potential on the rate constants of charge transfer and recombination. The obtained results have been explained with a model combining the theory of IMPS for a bulk semiconductor surface and the nature of the surface-bound intermediates (alternatively mobile or immobile OH˙ radicals). The results indicate that water photooxidation proceeds via mobile OH˙ radicals on both surfaces, while methanol addition gives rise to the involvement of immobile OH˙ radicals on the (100) surface. Detailed analysis in view of the surface structures suggests that the latter observation is due to efficient electron transfer from bridging OH˙ radicals on the (100) surface to methanol, while coupling of two of these radicals occurs in the absence of methanol, making them appear as mobile OH˙ radicals. In the case of the (001) surface, the coupling reaction dominates even in the presence of methanol due to the smaller distance between the bridging OH˙ radicals, leading to more efficient water oxidation, but less efficient methanol photooxidation on this surface.     

Hierarchical self-assembly of aminopyrazole peptides into nanorosettes in water

Self-association of aminopyrazole peptide hybrid 1 leads to stacked nanorosettes. This remarkable, well-ordered structure obeys the laws of nucleic acid self-assembly. In a strictly hierarchical process, formation of aminopyrazole "base" triplets via a hydrogen bond network is accompanied by pi-stacking with a second rosette and final dimerization of two double rosettes to a four-layer superstructure, stabilized by a six-fold half-crown alkylammonium lock. The final complex is soluble in organic as well as in aqueous solution. It was characterized in the solid state by X-ray crystallography, in water by NMR spectroscopy, and in silico by quantum chemical shift calculation. All these methods provide strong evidence for the same hexameric complex geometry. Its structural features bear striking similarity to nucleic acid architectures and their peptidic counterparts, especially alanyl-PNA. The whole self-assembly process is highly solvent- and temperature-dependent and occurs with a high degree of cooperativity--no intermediates are observed. Formation and dissociation of the nanorosette, however, are kinetically slow. The limitation to a hexameric aggregate can be explained by six sterically demanding valine residues, whose replacement by alanines may result in formation of infinite fibers.     

Magnetic Signatures of Hydroxyl- and Water-Terminated Neutral and Tetra-Anionic Mn12-Acetate

We investigate the energetics and magnetic signatures of the parent molecular magnet Mn₁₂-Acetate [Mn₁₂O₁₂(COOR)₁₆(H₂O)₄] and a chemically decomposed version of this structure, in which the four water molecules are converted to hydroxyl groups and hydrogen molecules. We determine electron addition and water decomposition energetics for this water-containing molecule using density-functional methods and include the recent Fermi-Löwdin-Orbital self-interaction correction. We find that it only costs 0.32 eV to add four electrons to the parent molecule. Furthermore, due to the strong Coulomb attractions between hydroxyl anions and the Mn cations, the energy cost for breaking the four coordinating water molecules into four coordinating hydroxyls and two hydrogen molecules is decreased in the tetra-anionic structure relative to the neutral structure. We calculate magnetic anisotropy barriers for the neutral molecule and the dehydrogenated tetra-anion and show that large changes in the magnetic anisotropy arise the strong attraction between the hydroxyl anions and four of the crown Mn cations. We suggest that the large changes in magnetic signals associated with the [Mn₁₂O₁₂(COOR)₁₆(HOH)₄] to [Mn₁₂O₁₂(COOR)₁₆(OH⁻)₄ + 2H₂] decomposition could provide a nondestructive spectroscopic method for learning about water decomposition mechanisms in a class of realizable model catalytic systems that have been synthesized recently. © 2019 Wiley Periodicals, Inc.     

Wet Conversion of Methane and Carbon Dioxide in a DBD Reactor

The influence of water on the plasma assisted conversion of methane and carbon dioxide in a dielectric barrier discharge (DBD) plug flow reactor was studied. The plasma at atmospheric pressure was ignited by a power supply at a frequency of 13.56?MHz. Product formation was studied at a power range between 35 and 70?W. The concentrations of the three gases were altered and diluted with helium to 3?%. FTIR spectroscopy and mass spectroscopy were applied to analyze the inlet and the product streams. The main product of this process are hydrogen, carbon monoxide and ethane. Ethene, ethine, methanol and formaldehyde are generated beside the main products in this DBD in lower concentrations. The conversion of methane, the ratio of the synthesis gas components (n(H₂):n(CO)), and the yield of oxygenated hydrocarbons and hydrogen increases by adding water. The total consumed energy reaches lower values for small amounts of water. Additional water does not influence the generated amount of C2 hydrocarbons and of CO, but decreases the carbon dioxide conversion.     

N-methylpiperazinocarbonyl-2',3'-BcNA and 4'-C-(N-methylpiperazino)methyl-DNA: introduction of basic functionalities facing the major groove and the minor groove of a DNA:DNA duplex

Piperazino-functionalized 2',3'-BcNA and 4'-C-hydroxymethyl-DNA are appropriate molecular architectures for the introduction of basic functionalities facing the major groove and the minor groove of nucleic acid duplexes, respectively. 4'-C-(N-Methylpiperazino)methyl-DNA monomers induce significantly increased thermal stability of a DNA:DNA duplex.     

Gas chromatographic determination of aromatic amines in water samples after solid-phase extraction and derivatization with iodine: I. Derivatization

A new method for the selective determination of aromatic amines is presented, which is based on the solid-phase extraction at pH 9 and subsequent derivatization of the analytes to the corresponding iodobenzenes. These can selectively and sensitively be determined with gas chromatography and electron-capture detection. Separation of at least 30 compounds in a single chromatographic run in 30 min is possible. With this method, 56 aromatic amines were investigated, and only in six cases no derivatives were obtained. Limits of quantitation were between 0.5 and 8 μg l⁻¹, but may still be lowered with higher sample volumes or different injection techniques. The application to water samples revealed the suitability for the investigation of ground, leachate and wastewater.     

Synthesis and properties of crosslinked polyvinylformamide and polyvinylamine hydrogels in conjunction with silica particles

Polyvinylamine hydrogels with silica particles encapsulated (PVAm/silica) were produced by a two‐step synthesis. In the first step, polyvinylformamide/silica (PVFA/silica) hybrids were synthesized from vinylformamide (VFA) and 1,3‐divinylimidazolidin‐2‐one (1,3‐bisvinylethyleneurea, BVU), as the crosslinker, by radical copolymerization in silica/water suspensions using different compositions of VFA/BVU. The target product PVAm/silica was obtained by acidic hydrolysis of the PVFA/silica hydrogels in a second step. The chemical structures of both hydrogels, PVFA/silica and PVAm/silica, respectively, were revealed by solid‐state ¹³C(¹H) cross‐polarity/magic‐angle spinning NMR spectroscopy. Both hydrogels swelled significantly in water. The swelling capacity of the two systems was characterized by the correlation length ξ (or hydrodynamic blob size) of the network meshes with small‐angle neutron scattering experiments. ξ is significantly larger for PVAm/silica than for PVFA/silica, which corresponds to the observed higher swelling capacity of this polyelectrolyte material. Furthermore, the swelling behavior of the hybrid hydrogels was quantitatively described in terms of free swell capacity, centrifuge‐retention capacity, adsorption against pressure, and free swell rate as compared with values of the corresponding copolymer hydrogels. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3144–3152, 2002     

Electronic Finetuning of 8-Methoxy Psoralens by Palladium-Catalyzed Coupling: Acidochromicity and Solvatochromicity

Differently 5-substituted 8-methoxypsoralens can be synthesized by an efficient synthetic route with various cross-coupling methodologies, such as Suzuki, Sonogashira and Heck reaction. Compared to previously synthesized psoralens, thereby promising daylight absorbing compounds as potentially active agents against certain skin diseases can be readily accessed. Extensive investigations of all synthesized psoralen derivatives reveal fluorescence in the solid state as well as several distinctly emissive derivatives in solution. Donor-substituted psoralens exhibit remarkable photophysical properties, such as high fluorescence quantum yields and pronounced emission solvatochromicity and acidochromicity, which were scrutinized by Lippert–Mataga and Stern–Volmer plots. The results indicate that the compounds exceed the limit of visible light, a significant factor for potential applications as an active agent. In addition, (TD)DFT calculations were performed to elucidate the underlying electronic structure and to assign experimentally obtained data.     

Tuning Aqueous Supramolecular Polymerization by an Acid-Responsive Conformational Switch

Besides their widespread use in coordination chemistry, 2,2’-bipyridines are known for their ability to undergo cis–trans conformational changes in response to metal ions and acids, which has been primarily investigated at the molecular level. However, the exploitation of such conformational switching in self-assembly has remained unexplored. In this work, the use of 2,2’-bipyridines as acid-responsive conformational switches to tune supramolecular polymerization processes has been demonstrated. To achieve this goal, we have designed a bipyridine-based linear bolaamphiphile, 1 , that forms ordered supramolecular polymers in aqueous media through cooperative aromatic and hydrophobic interactions. Interestingly, addition of acid (TFA) induces the monoprotonation of the 2,2’-bipyridine moiety, leading to a switch in the molecular conformation from a linear (trans) to a V-shaped (cis) state. This increase in molecular distortion along with electrostatic repulsions of the positively charged bipyridine-H⁺ units attenuate the aggregation tendency and induce a transformation from long fibers to shorter thinner fibers. Our findings may contribute to opening up new directions in molecular switches and stimuli-responsive supramolecular materials.