Selective Synthesis of N-Acylnortropane Derivatives in Palladium-Catalysed Aminocarbonylation

The aminocarbonylation of various alkenyl and (hetero)aryl iodides was carried out using tropane-based amines of biological importance, such as 8-azabicyclo[3.2.1]octan-3-one (nortropinone) and 3α-hydroxy-8-azabicyclo[3.2.1]octane (nortropine) as N-nucleophile. Using iodoalkenes, the two nucleophiles were selectively converted to the corresponding amide in the presence of Pd(OAc)₂/2 PPh₃ catalysts. In the presence of several iodo(hetero)arenes, the application of the bidentate Xantphos was necessary to produce the target compounds selectively. The new carboxamides of varied structure, formed in palladium-catalyzed aminocarbonylation reactions, were isolated and fully characterized. In this way, a novel synthetic method has been developed for the producing of N-acylnortropane derivatives of biological importance.     

Experiments on the synthesis of carotenoid glycosides

Isozeaxanthin was treated with trifluoroacetic acid and tetra-O-benzoyl-1-thio-β-d-glucose to afford β,β-carotene-4,4′-bisthioglucoside isomers in good yields. The deprotected compounds are mimetics of naturally occurring thermoxanthins and can show favourable effects against oxidation stress.     

Photoionization,Structures, and Energetics of Na-Doped Formic Acid–Water Clusters

The influence of formic acid on water cluster aggregation has been investigated experimentally by mass spectrometry and tunable UV laser ionization applied to Na-doped clusters formed in the supersonic expansion of water vapors seeded with formic acid (FA) as well as theoretically using high level quantum chemistry methods. The mass spectra of Na−FA(H₂O)_n clusters show an enlarging of mass distribution toward heavier clusters with respect to the Na−(H₂O)_n clusters, suggesting similar mass distribution in neutral clusters and an influence of formic acid in water aggregation. Density functional theory and coupled-cluster type (DLPNO-CCSD(T)) calculations have been used to calculate structures and energetics of neutral and ionized Na−FA(H₂O)_n as well as neutral FA(H₂O)_n. Na-doped clusters are characterized by very stable geometries. The theoretical adiabatic ionization potential values match pretty well the measured appearance energies and the calculated first six electronic excited states show Rydberg-type characters, indicating possible autoionization contributions in the mass spectra. Finally, theoretical calculations on neutral FA(H₂O)_n clusters show the possibility of similarly stable structures in small clusters containing up to n=4–5 water molecules, where FA interacts significantly with waters. This suggests that FA can compete with water molecules in the starting stage of the aggregation process, by forming stable nucleation seed.     

LC-MS Quantitative Determination of Atropine and Scopolamine in the Floral Nectar of Datura Species

The present study aimed at determining selected alkaloid components in the nectar of Datura species, to elucidate whether the alkaloid content of the floral nectar can lead to intoxication. A simple and rapid liquid chromatography coupled with electrospray mass spectrometry analysis was developed for the quantitative determination of atropine and scopolamine, the main toxic alkaloids of the Datura species. This method allowed the direct coupling of an electrospray mass selective detector to the LC system. Under these conditions, atropine and scopolamine were well separated from other components and detected with mass spectrometry (mass selective detector). Simultaneous determination of atropine and scopolamine was performed with gradient elution on an Ascentis Express C₁₈ (Supelco) reversed-phase column based on a new fused core particle design. Liquid chromatography coupled with electrospray mass spectrometry was used in positive ion mode. Atropine and scopolamine produced protonated species at m/z 290 and 304 (which are also the base peaks). Our data confirmed that the alkaloid characteristics for the vegetative and reproductive parts of the Datura plants may also occur in the nectar secreted by the flowers. In Datura species with large flowers and high nectar amounts, the alkaloid content increases proportionately and thus the nectar may be a potential source of intoxication.     

Colourings of the cartesian product of graphs and multiplicative Sidon sets

Let F be a family of connected bipartite graphs, each with at least three vertices. A proper vertex colouring of a graph G with no bichromatic subgraph in F is F-free. The F-free chromatic number χ(G,F) of a graph G is the minimum number of colours in an F-free colouring of G. For appropriate choices of F, several well-known types of colourings fit into this framework, including acyclic colourings, star colourings, and distance-2 colourings. This paper studies F-free colourings of the cartesian product of graphs.     

The case of the weak N-X bond: Ab initio, semi-experimental, and experimental equilibrium structures of XNO (X = H, F, Cl, OH) and FNO2

The equilibrium structures of FNO, ClNO, HONO, and FNO2 have been determined using three different, somewhat complementary methods: a completely experimental, a semi-experimental (where the equilibrium rotational constants are derived from the experimental effective ground-state rotational constants and an ab initio cubic force field), and an ab initio, where geometry optimizations are usually performed at the coupled cluster level of nonrelativistic electronic structure theory using small to very large Gaussian basis sets. For the sake of comparison, the equilibrium structures of HNO and N2O have also been redetermined, confirming and extending earlier results. The semi-experimental method gives structural parameters in good agreement with the reliable experimental results for each compound investigated. Because of inadequate treatment of electron correlation, the single-reference CCSD(T) method gives N-X (X[double bond]F, Cl, OH) bonds that are too strong and associate bond lengths that are significantly too short. The discrepancy increases with increase in the size of the basis set. A much more elaborate treatment of electron correlation at the CCSDTQ level solves this problem and results in increased bond lengths, correctly representing the weakness of the N-X bond in these XNO and XNO2 species. The equilibrium structures determined are accurate to better than 0.001 A and 0.1 degrees .     

Adsorption of the enantiomers of 3-chloro-1-phenyl-propanol on silica-bonded chiral quinidine carbamate

The interactions of 3-chloro-1-phenyl-propanol with a quinidine carbamate-bonded chiral stationary phase under NPLC conditions were studied by measuring the adsorption isotherm data of its enantiomers by frontal analysis, modeling these data with a suitable isotherm model, and comparing the experimental overloaded elution band profiles with those calculated with this isotherm and the equilibrium dispersive model of liquid chromatography. The affinity energy distribution was calculated from the adsorption isotherm data. The results show that the surface of the adsorbent is heterogeneous and exhibits a bimodal adsorption energy distribution. This fact is interpreted in terms of the presence of two different types of adsorption sites on the stationary phase, nonselective and enantioselective sites. Albeit the bi-Langmuir isotherm model successfully accounts for the single-component data corresponding to both enantiomers, the competitive bi-Langmuir isotherm model does not allow an accurate prediction of the overloaded band profiles of the racemic mixture. Thermodynamic data are drawn for explanation. Some aspects of the retention mechanism are discussed in the light of the data obtained.     

Perturbation theory of Phi-value analysis of two-state protein folding: relation between p fold and Phi values

In protein folding, the transition state ensemble is defined as the set of conformations with p(fold)=12, where the p(fold) of a conformation is the probability that starting from this conformation the protein folds before it unfolds. Experimentally, this ensemble is probed by the Phi-value analysis, where Phi is the ratio of the changes in the logarithms of the folding rate and the equilibrium constant when the system is perturbed by a mutation. We show that for a two-state protein the Phi value can be expressed in terms of the perturbation and only the first two eigenfunctions of the evolution operator (e.g., a rate matrix) of the wild-type protein. The first eigenfunction is the equilibrium probability distribution while the second is proportional to p(fold), thus establishing a formal relation between p(fold) and Phi values. In addition to providing insight into the theoretical foundation of the Phi-value analysis, our results may prove practically useful in performing such analyses within the framework of models containing a large number of states.