Can glycans unveil the origin of glycoprotein hormones? - human chorionic gonadotrophin as an example -

Doping with (glyco)protein hormones represent an extremely challenging, analytical problem as nearly all are constitutively present at low concentrations that fluctuate according to circadian or alternative periodical, or external stimuli. Thus the mere concentration in a biological sample is only resolutive when this surpasses extreme values. As the vast majority of these molecules are produced by recombinant DNA technology it is believed that the exogenous molecules could bear the signature of the host cell. In particular, these could comprise structural differences originated from co or post-translational differences. In this study we have employed both proteomics and glycomics strategies to compare recombinant and urinary human chorionic gonadotrophin in order to evaluate this hypothesis. As anticipated the recombinant hormone could be shown to contain N-glycolyl neuraminic acid, a sialic acid that cannot be produced by humans. Furthermore, differences were observed in the overall glycosylation, in particular the presence of abundant hybrid-type glycans that were much less pronounced in the recombinant species. These differences were determined to occur predominantly in the alpha-subunit for which antidoping strategies focussed on these elements could be used for both chorionic gonadotrophin and lutrophin as they share the same alpha-subunit.     

Fast electron density methods in the life sciences--a routine application in the future?

The understanding of mutual recognition of biologically interacting systems on an atomic scale is of paramount importance in the life sciences. Electron density distributions that can be obtained from a high resolution X-ray diffraction experiment can provide--in addition to steric information--electronic properties of the species involved in these interactions. In recent years experimental ED methods have seen several favourable developments towards successful application in the life sciences. Experimental and methodological advances have made possible on the one hand high-speed X-ray diffraction experiments, and have allowed on the other hand the quantitative derivation of bonding, non-bonding and atomic electronic properties. This has made the investigation of a large number of molecules possible, and moreover, molecules with 200 or more atoms can be subject of experimental ED studies, as has been demonstrated by the example of vitamin B12. Supported by the experimentally verified transferability concept of submolecular electronic properties, a key issue in Bader's The Quantum Theory of Atoms in Molecules, activities have emerged to establish databases for the additive generation of electron densities of macromolecules from submolecular building blocks. It follows that the major aims of any experimental electron density work in the life sciences, namely the generation of electronic information for a series of molecules in a reasonable time and the study of biological macromolecules (proteins, polynucleotides), are within reach in the near future.     

Can deuterium stable isotope values be used to assign the geographic origin of an auxiliary hoverfly in south‐western France?

Deuterium δD isotopic analysis is increasingly being used to trace wildlife movement, and undoubtedly has much to offer in this respect, but questions still remain as to the feasibility and practicality of the method in ecology. Here we report our attempt to determine the geographic origin of an auxiliary hoverfly, Episyrphus balteatus, in south-western France. We used quantile regression to calculate the minimum separation distance, based on the International Atomic Energy Agency/World Meteorological Organization (IAEA/WMO) data, at which two insects could be said to originate from different latitudes with a given degree of confidence. We collected larvae in spring 2007 and 2009 to obtain the δD signal of indigenous hoverflies and we trapped adults during one complete year (from Dec. 2006 to Nov. 2007). The smallest separation distance calculated was about 1400 km in western Europe. Our results revealed greater variability in δD of adults in autumn than in spring. From this we infer an autumnal migration. Because of the presence of mountains and the Mediterranean Sea, the δD gradient in precipitation in western Europe is less clear than on the American continent, where it has been used successfully to infer geographical origins of animals under certain conditions. Despite the complications encountered in Europe, the minimum separation distance model proved a useful first step to obtain a first range of possible origins of E. balteatus and the application of the model to other arthropod species in Europe warrants investigation.     

Microwave-assisted reaction of peptide formation by amino acid with phosphate:Exploration of the most possible channels for the origin of life

The formation of peptides and then protein by small abiological molecules clusters such as amino acid is a key stage in the origin of life[1]. More and more ex- perimental results showed that phosphate plays an important role in the formation of biomolecules in prebiotic chemical evolution. The principal reservoirs of biochemical energy are phosphates (such as ATP). The peculiar role of phosphates in contemporary life might suggest its essential role in prebiotic energy conversion, syntheses …     

Can the DFT-D method describe the full range of noncovalent interactions found in large biomolecules?

The DFT-D method is shown to yield interaction energies between biologically important groups to an accuracy comparable to that obtained using state-of-the-art ab initio methods.     

Can we predict the conformational preference of amides?

To what extent, if any, is the conformation of secondary amides revealed by theory? This question has now been addressed by computational methods using calculations at the B3LYP/6-31G level of theory and (1)H NMR spectroscopy. Both gas-phase and solvent studies predict a Z-anti conformation to be the lowest in energy for an evaluated series of acetamides. Moreover, Z-anti conformations may also be inferred from the chemical shifts of the N-CH alpha protons determined by NMR spectroscopy. Thus, a proton situated anti to the N-H proton consistently appears approximately 0.8 ppm further downfield than a proton situated gauche to the N-H proton. This finding, which could only be derived by using the DFT calculations of conformational preference as a guide to interpret the NMR data, might prove to be useful as a simple and convenient methodology for establishing amide conformation experimentally.     

The origin of obsidian in the valley of Maltrata, Veracruz México

Five archaeological sites have been selected for a study of the precedence of obsidian from the Valley of Maltrata, Veracruz, Mexico: Teteles de la Ermita and Barriales de las Besanas (pre-Classic, 1,500 B.P. 100 A.P.), Rincón de Aquila (pre-Classic and Classic, 1,500 B.P.–650 A.P.), Tepeyacatitla (Classic, 100–650 A.P. and Rincón Brujo (post-Classic 900/1,000–1,521 A.P.). For this investigation, 51 artifacts were analyzed by neutron activation analysis. The statistic analysis of the chemical compositions allowed us to identify the places of origin of the obsidian sources: Sierra de Pachuca, Pico de Orizaba, Zaragoza-Oyameles, Otumba and Paredón. Based on these results it can be affirmed that the settlements of the valley of Maltrata actively participated in the interregional trade routes of obsidian from the pre-Classic period to the post-Classic period, and maintained relations with the Olmec, Teotihuacan, Cantona and Mexica cultures, among others.     

Can the theory of gradient liquid chromatography be useful in solving practical problems?

Advances in the theory of gradient liquid chromatography and their practical impacts are reviewed. Theoretical models describing retention in reversed-phase, normal-phase and ion-exchange modes are compared. Main attention is focused on practically useful models described by two- or three-parameter equations fitting the experimental data in the range of mobile phase composition utilized for sample migration during gradient elution. The applications of theory for gradient method development, optimization and transfer are addressed. The origins and possibilities for overcoming possible pitfalls are discussed, including the effects of the instrumental dwell volume, uptake of mobile phase components on the column and size of the sample molecules. Special attention is focused on gradient separations of large molecules.     

Chemical evolution of biomolecule building blocks. Can thermodynamics explain the accumulation of glycine in the prebiotic ocean?

It has always been a question of considerable scientific interest why amino acids (and other biomolecule building blocks) formed and accumulated in the prebiotic ocean. In this study, we suggest an answer to this question for the simplest amino acid, glycine. We have shown for the first time that classical equilibrium thermodynamics can explain the most likely selection of glycine (and the derivative of its dipeptide) in aqueous media, although glycine is not the lowest free energy structure among all (404) possible constitutional isomers. Species preceding glycine in the free energy order are either supramolecular complexes of small molecules or such molecules likely to dissociate and thus get back to the gas phase. Then, 2-hydroxyacetamide condensates yielding a thermodynamically favored derivative of glycine dipeptide providing an alternative way for peptide formation. It is remarkable that a simple equilibrium thermodynamic model can explain the accumulation of glycine and provide a reason for the importance of water in the formation process.     

Applications of cellular automata: attractors and fractals in analytical chemistry?

A cellular automaton is a discrete dynamic system of simple construction, yet capable of exhibiting complex self-organizing behavior. A cellular automaton can be used to model differential systems by assuming that time and space are quantized, and that the dependent variable takes on a finite set of possible values. Cellular-automaton behavior falls into four distinct universality classes, analogous to (1) limit points, (2) limit cycles, (3) chaotic attractors (fractals), and (4) 'universal computers'. The behavior of members of each of these four classes is explored in the context of digital spectral filtering. The utility of class 2 behavior in experimental data analysis is demonstrated with a laboratory example.     

Can the presence of chemically inert species modify the face selectivity in asymmetric induction by cyclodextrins?

Reduction of-cyclodextrin (-CD) aromatic ketone (acetophenone and acetonaphthones) inclusion compounds were carried out in the presence of a large number of chemically inert species as potential co-guests. In several cases, it was observed that stoichiometric molar ratios of these compounds to ketone significantly modify the chiral induction yielding the inverted alcohol enantiomer and increasing the face selectivity. The results were found to depend strongly on the respective structure and shape of both the ketone and the additive, and on the molar ratio of-CD:ketone:third compound. These observations suggest the formation of a three-component inclusion complex in which the geometry of binding of the substrate and its mobility are changed with respect to the binary system.     

Can the ebselen derivatives catalyze the isomerization of peroxynitrite to nitrate?

The reaction of ebselen and its derivatives (1-7) with peroxynitrite anion (ONOO(-); PN) has been studied in gas phase and in aqueous, dichloromethane, benzene, and cyclohexane solutions using B3LYP/6-311+G(d,p)//B3LYP/6-311G(d,p) and PCM-B3LYP/6-311+G(d,p)//B3LYP/6-311G(d,p) approaches, respectively. It was shown that the reaction of 2 (R=H) with PN proceeds via 2 + PN --> 2-PN --> 2-TS1 (O-O activation) --> 2-O(NO(2)(-)()) --> 2-SeO + NO(2)(-) pathway with a rate-determining barrier of 25.3 (14.8) kcal/mol at the NO(2)(-) dissociation step (numbers presented without parentheses are enthalpies, and those in parentheses are Gibbs free energies). The NO(3)(-) formation process, starting from the complex 2-O(NO(2)(-)()), requires by (7.9) kcal/mol more energy than the NO(2)(-) dissociation process and is unlikely to compete with the latter. Thus, in the gas phase, the peroxynitrite --> nitrate isomerization catalyzed by complex 2 is unlikely to occur. It is shown that the NO(3)(-) formation process is slightly more favorably than the NO(2)(-) dissociation process for complex 4, with a strongest electron-withdrawing ligand R=CF(3). Therefore, complex 4 (as well as complex 6 with R=OH) is predicted to be a good catalyst for peroxynitrite <--> nitrite isomerization in the gas phase. Solvent effects (a) change the rate-determining step of the reaction 2 + PN from NO(2)(-) dissociation in the gas phase to O-O activation, which occurs with barriers of (13.9), (8.4), (8.4), and (8.2) kcal/mol in water, dichloromethane, benzene, and cyclohexane, respectively, and (b) significantly reduce the NO(2)(-) dissociation energy, while only slightly destabilizing the NO(3)(-) formation barrier, and make the peroxynitrite <--> nitrate isomerization process practically impossible, even for complex 4.     

On the origin of non-Markovian kinetics of light-induced magneto-structural relaxation in “breathing” crystals

Russian Chemical Bulletin - Traditional mean-field theory of light-induced magneto-structural relaxation in spin-crossover compounds provides a qualitatively correct explanation for the...     

Can radical cations of the constituents of nucleic acids be formed in the gas phase using ternary transition metal complexes?

Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) of ternary transition metal complexes of [M(L(3))(N)](2+) (where M = copper(II) or platinum(II); L(3) = diethylenetriamine (dien) or 2,2':6',2'-terpyridine (tpy); N = the nucleobases: adenine, guanine, thymine and cytosine; the nucleosides: 2'deoxyadenosine, 2'deoxyguanosine, 2'deoxythymine, 2'deoxycytidine; the nucleotides: 2'deoxyadenosine 5'-monophosphate, 2'deoxyguanosine 5'-monophosphate, 2'deoxythymine 5'-monophosphate, 2'deoxycytidine 5'-monophosphate) was examined as a means of forming radical cations of the constituents of nucleic acids in the gas phase. In general, sufficient quantities of the ternary complexes [M(L(3))(N)](2+) could be formed for MS/MS studies by subjecting methanolic solutions of mixtures of a metal salt [M(L(3))X(2)] (where M = Cu(II) or Pt(II); L(3) = dien or tpy; X = Cl or NO(3)) and N to ESI. The only exceptions were thymine and its derivatives, which failed to form sufficient abundances of [M(L(3))(N)](2+) ions when: (a) M = Pt(II) and L(3) = dien or tpy; (b) M = Cu(II) and L(3) = dien. In some instances higher oligomeric complexes were formed; e.g., [Pt(tpy)(dG)(n)](2+) (n = 1-13). Each of the ternary complexes [M(L(3))(N)](2+) was mass-selected and then subjected to collision-induced dissociation (CID) in a quadrupole ion trap. The types of fragmentation reactions observed for these complexes depend on the nature of all three components (metal, auxiliary ligand and nucleic acid constituent) and can be classified into: (i) a redox reaction which results in the formation of the radical cation of the nucleic acid constituent, N(+.); (ii) loss of the nucleic acid constituent in its protonated form; and (iii) fragmentation of the nucleic acid constituent. Only the copper complexes yielded radical cations of the nucleic acid constituent, with [Cu(tpy)(N)](2+) being the preferred complex due to suppression, in this case, of the loss of the nucleobase in its protonated form. The yields of the radical cations of the nucleobases from the copper complexes follow the order of their ionization potentials (IPs): G (lowest IP) > A > C > T (highest IP). Sufficient yields of the radical cations of each of the nucleobases allowed their CID reactions (in MS(3) experiments) to be compared to their even-electron counterparts.     

Is vanadium a more versatile target in the activity of primordial life forms than hitherto anticipated?

The two predominant forms of vanadium occurring in the geo-, aqua- and biosphere, soluble vanadate(V) and insoluble oxovanadium(IV) (vanadyl), are subject to bacterial activity and transformation. Bacteria belonging to genera such as Shewanella, Pseudomonas and Geobacter can use vanadate as a primary electron acceptor in dissimilation or respiration, an important issue in the context of biomineralisation and soil detoxification. Azotobacter, which can employ vanadium as an essential element in nitrogen fixation, secretes a vanadophore which enables the uptake of vanadium(V). Siderophores secreted by other bacteria competitively (to ferric iron) take up vanadyl and thus interfere with iron supply, resulting in bacteriostasis. The halo-alkaliphilic Thioalkalivibrio nitratireducens possibly uses vanadium as a constituent of an alternative, molybdopterin-free nitrate reductase. Marine macro-algae can generate a variety of halogenated organic compounds by use of vanadate-dependent haloperoxidases, and a molecular vanadium compound, amavadin, from Amanita mushrooms has turned out to be an efficient catalyst in oxidation reactions. The present account is a focused and critical review of the current knowledge of the interplay of bacteria and other primitive forms of life (cyanobacteria, algae, fungi and lichens) with vanadium, with the aim to provide perspectives for applications and further investigations.