Structural requirements for active intestinal transport. The nature of the carrier–sugar bonding at C-2 and the ring oxygen of the sugar

Several weakly transported sugars were tested for transport by the Na⁺-dependent sugar carrier with slices of everted hamster intestinal tissue. Sugars were assumed to be transported by this carrier if the accumulation was diminished in the absence of Na⁺ and in the presence of the competitive inhibitor 1,5-anhydro-d-glucitol. The extent of accumulation was correlated with the number of hydroxyl groups in the d-gluco configuration if the ring oxygen was placed in the normal d-glucose position. 5-Thio-d-glucose, with a sulphur atom in the ring, was transported at about the same rate as d-glucose and had a similar K_i for d-galactose transport, but myoinositol was poorly accumulated. It is suggested that there is no hydrogen bonding at the ring oxygen atom, but that the oxygen atom is found at this position as a result of steric constraints. No sugar without a hydroxyl group in the d-gluco position at C-2 of the sugar, including d-mannose, 2-deoxy-d-glucose, 2-chloro-2-deoxy-d-glucose and 2-deoxy-2-fluoro-d-glucose, was transported by the Na⁺-dependent carrier, but these sugars and l-fucose weakly and competitively inhibit the Na⁺-dependent accumulation of l-glucose into slices of everted hamster intestinal tissue. It is concluded that the bond between the carrier and C-2 of the sugar may be covalent, and a possible mechanism for active intestinal transport is proposed.     

The Ramberg-Bäcklund reaction for the synthesis of C-glycosides, C-linked-disaccharides and related compounds

The discovery of the Ramberg-B?cklund procedure for preparing exo-glycals from S-glycoside dioxides, developed independently in (Old) York and New York, is reviewed. The methodology is successful with glucose, galactose, mannose, xylose, fucose, ribose, altrose, 2-deoxy-arabino-hexose (2-deoxy-glucose) and daunosamine derivatives, and has been used to prepare di-, tri- and tetra-substituted exo-glycals. More recent developments, such as one-pot variants, and protecting group-free procedures, are also covered. Synthetic applications of the exo-glycals, for example, to prepare beta-glycosidase inhibitors, spirocyclic glucose derivatives, beta-C-glycosides, C-glycosyl porphyrin glycoconjugates and C-glycosyl amino acids, are also discussed. Finally, applications of the Ramberg-B?cklund process for the synthesis of known and novel C-glycosides, and in natural product synthesis, are reviewed.     

Unravelling the interface of Co–Pi/Ag/Fe2O3 and Ni–Pi/Ag/Fe2O3 heterostructures for enhanced solar water splitting

Recently, a new type of haematite-based (a-Fe₂O₃) photoanode has achieved a considerable catalytic performance through simply depositing Ag and cobalt phosphate (Co–Pi) nanoparticles (NPs) onto haematite nanosheets. However, there is no detailed mechanism study on the reason for high-performance catalysis. In view of this, we conduct first-principles calculations and our results indicate that there is a further accumulation of positive charge on Ag NPs on the heterogeneous interfaces with the addition of Co–Pi NPs than that of haematite modified only by Ag NPs. Also, there is a slight increase of the adsorption energy of water molecules.     

The role of spin in biological processes: O2, NO,nucleobases, nucleosides,nucleotides and Watson–Crick base pairs

The experimental electron affinities of adenine, guanine, cytosine, thymine and uracil have been determined from reduction potentials and negative ion photoelectron spectra. Updated values for purine, pyrimidine and other nitrogen heterocyclics, which have not been measured in the gas phase, are presented. The electron affinity of Watson–Crick guanine–cytosine is estimated empirically. The experimental values are consistent with quantum mechanical semi-empirical multiconfiguration configuration interaction calculations. The bulk hydration energies of the nucleobase anions, 2.34 eV, determined from the experimental data and sequential anion hydration energy difference of about 0.20(5) eV suggest that 10–15 water molecules complete the hydration shell. The electron affinities for the formation of doublet and quartet anions of the nucleobases, nucleosides, nucleotides and Watson–Crick base pairs are calculated. We postulate that low-lying quartet anion states and their spin distribution can and will participate in electron conduction, radiation damage, oxidation damage and repair, strand breakage and protein synthesis.     

The biogenesis of [Fe–S] clusters: the role of the unorthodox ABC ATPase,SufC, and the wider implications for understanding iron metabolism

Abstract

Oxidative stress is the hallmark of various chronic inflammatory lung diseases. Increased concentrations of reactive oxygen species (ROS) in the lungs of such patients are reflected by elevated concentrations of oxidative stress markers in the breath, airways, lung tissue and blood. Traditionally, the measurement of these biomarkers has involved invasive procedures to procure the samples or to examine the affected compartments, to the patient's discomfort. As a consequence, there is a need for less or non-invasive approaches to measure oxidative stress. The collection of exhaled breath condensate (EBC) has recently emerged as a non-invasive sampling method for real-time analysis and evaluation of oxidative stress biomarkers in the lower respiratory tract airways. The biomarkers of oxidative stress such as H₂O₂, F₂-isoprostanes, malondialdehyde, 4-hydroxy-2-nonenal, antioxidants, glutathione and nitrosative stress such as nitrate/nitrite and nitrosated species have been successfully measured in EBC. The reproducibility, sensitivity and specificity of the methodologies used in the measurements of EBC oxidative stress biomarkers are discussed. Oxidative stress biomarkers also have been measured for various antioxidants in disease prognosis. EBC is currently used as a research and diagnostic tool in free radical research, yielding information on redox disturbance and the degree and type of inflammation in the lung. It is expected that EBC can be exploited to detect specific levels of biomarkers and monitor disease severity in response to appropriate prescribed therapy/treatment.     

Neural mechanisms of mother–infant bonding and pair bonding: Similarities,differences, and broader implications

This article is part of a Special Issue “Parental Care”.Mother–infant bonding is a characteristic of virtually all mammals. The maternal neural system may have provided the scaffold upon which other types of social bonds in mammals have been built. For example, most mammals exhibit a polygamous mating system, but monogamy and pair bonding between mating partners occur in ~ 5% of mammalian species. In mammals, it is plausible that the neural mechanisms that promote mother–infant bonding have been modified by natural selection to establish the capacity to develop a selective bond with a mate during the evolution of monogamous mating strategies. Here we compare the details of the neural mechanisms that promote mother–infant bonding in rats and other mammals with those that underpin pair bond formation in the monogamous prairie vole. Although details remain to be resolved, remarkable similarities and a few differences between the mechanisms underlying these two types of bond formation are revealed. For example, amygdala and nucleus accumbens–ventral pallidum (NA–VP) circuits are involved in both types of bond formation, and dopamine and oxytocin actions within NA appear to promote the synaptic plasticity that allows either infant or mating partner stimuli to persistently activate NA–VP attraction circuits, leading to an enduring social attraction and bonding. Further, although the medial preoptic area is essential for maternal behavior, its role in pair bonding remains to be determined. Our review concludes by examining the broader implications of this comparative analysis, and evidence is provided that the maternal care system may have also provided the basic neural foundation for other types of strong social relationships, beyond pair bonding, in mammals, including humans.     

Hydrogen bonding to the cysteine ligand of superoxide reductase: acid–base control of the reaction intermediates

Superoxide reductase (SOR) is a non-heme iron metalloenzyme that detoxifies superoxide radical in microorganisms. Its active site consists of an unusual non-heme Fe²⁺ center in a [His₄Cys₁] square pyramidal pentacoordination, with the axial cysteine ligand proposed to be an essential feature in catalysis. Two NH peptide groups from isoleucine 118 and histidine 119 establish hydrogen bonds involving the sulfur ligand (Desulfoarculus baarsii SOR numbering). To investigate the catalytic role of these hydrogen bonds, the isoleucine 118 residue of the SOR from Desulfoarculus baarsii was mutated into alanine, aspartate, or serine residues. Resonance Raman spectroscopy showed that the mutations specifically induced an increase of the strength of the Fe³⁺–S(Cys) and S–C_β(Cys) bonds as well as a change in conformation of the cysteinyl side chain, which was associated with the alteration of the NH hydrogen bonding involving the sulfur ligand. The effects of the isoleucine mutations on the reactivity of SOR with O₂ ^?? were investigated by pulse radiolysis. These studies showed that the mutations induced a specific increase of the pK _a of the first reaction intermediate, recently proposed to be an Fe²⁺–O₂ ^?? species. These data were supported by density functional theory calculations conducted on three models of the Fe²⁺–O₂ ^?? intermediate, with one, two, or no hydrogen bonds involving the sulfur ligand. Our results demonstrated that the hydrogen bonds between the NH (peptide) and the cysteine ligand tightly control the rate of protonation of the Fe²⁺–O₂ ^?? reaction intermediate to form an Fe³⁺–OOH species.     

The rate of the deoxygenation reaction limits myoglobin- and hemoglobin-facilitated O₂ diffusion in cells

A mathematical model describing facilitation of O(2) diffusion by the diffusion of myoglobin and hemoglobin is presented. The equations are solved numerically by a finite-difference method for the conditions as they prevail in cardiac and skeletal muscle and in red cells without major simplifications. It is demonstrated that, in the range of intracellular diffusion distances, the degree of facilitation is limited by the rate of the chemical reaction between myglobin or hemoglobin and O(2). The results are presented in the form of relationships between the degree of facilitation and the length of the diffusion path on the basis of the known kinetics of the oxygenation-deoxygenation reactions. It is concluded that the limitation by reaction kinetics reduces the maximally possible facilitated oxygen diffusion in cardiomyoctes by ～50% and in skeletal muscle fibers by ～ 20%. For human red blood cells, a reduction of facilitated O(2) diffusion by 36% is obtained in agreement with previous reports. This indicates that, especially in cardiomyocytes and red cells, chemical equilibrium between myoglobin or hemoglobin and O(2) is far from being established, an assumption that previously has often been made. Although the "O(2) transport function" of myoglobin in cardiac muscle cells thus is severely limited by the chemical reaction kinetics, and to a lesser extent also in skeletal muscle, it is noteworthy that the speed of release of O(2) from MbO(2), the "storage function," is not limited by the reaction kinetics under physiological conditions.     

The mechanism of the periodate–thiobarbituric acid reaction of sialic acids

1. The chromogen formation from N-acetylneuraminic acid in the periodate-thiobarbituric acid reaction was investigated. Measurement of periodate consumption showed an uptake of approx. 3moles/mole of substrate in neutral as well as in strongly acidic solution. Therefore the chromogen beta-formylpyruvic acid is not a direct product of the periodate oxidation; it is presumed to be formed from the true oxidation product, a hexos-5-uluronic acid, by aldol splitting during the reaction in hot acidic solution with thiobarbituric acid. 2. Methyl (methyl beta-l-threo-hexos-4-enepyranosid)uronate, an analogue of the pre-chromogen, has been shown to yield with thiobarbituric acid in acidic solution a pigment exhibiting an identical absorption spectrum and showing the same behaviour on paper chromatography as the pigment obtained from N-acetylneuraminic acid in the periodate-thiobarbituric acid assay. 3. The substitution at C-2 of methoxyneuraminic acid does not inhibit the periodate-thiobarbituric acid reaction. In neutral solution methoxyneuraminic acid is oxidized by periodate to a substance that reacts readily with thiobarbituric acid in acidic solution. When periodate oxidation is attempted in acidic solution, protonation of the amino group protects this group against oxidation, rendering methoxyneuraminic acid negative in the assay systems of Warren (1959a,b) and Aminoff (1959, 1961).     

Recommendations for the investigation of animal models of Prader–Willi syndrome

Prader–Willi syndrome (PWS) occurs in about 1 in 15,000 individuals and is a contiguous gene disorder causing developmental disability, hyperphagia usually with obesity, and behavioral problems, including an increased incidence of psychiatric illness. The genomic imprinting that regulates allele-specific expression of PWS candidate genes, the fact that multiple genes are typically inactivated, and the presence of many genes that produce functional RNAs rather than proteins has complicated the identification of the underlying genetic pathophysiology of PWS. Over 30 genetically modified mouse strains that have been developed and characterized have been instrumental in elucidating the genetic and epigenetic mechanisms for the regulation of PWS genes and in discovering their physiological functions. In 2011, a PWS Animal Models Working Group (AMWG) was established to generate discussions and facilitate exchange of ideas regarding the best use of PWS animal models. Here, we summarize the goals of the AMWG, describe current animal models of PWS, and make recommendations for strategies to maximize the utility of animal models and for the development and use of new animal models of PWS.     

The kinetics and mechanism of the reaction of 2′-deoxy-5′-guanosinemonophosphoric acid and the diaqua form of cis-platin

2′-Deoxy-5′-guanosinemonosphoric acid (B) reacts with cis-[Pt(NH₃)₂(OH₂)₂]²⁺ in two steps to form the cis-[Pt(NH₃)₂B₂]^y+ ion. In the first step 2′-d-5′- GMPH₂ reacts some ten times faster than 5′-GMPH₂ does. Rate constants, ΔH^#, ΔS^# and ΔV^# are very similar for the two bases in the second reaction. It is proposed that the product in the first step contains no water and is cis-[Pt(NH₃)₂B]^x+ in which the nucleobase is bidentate bonding through both N(7) of guanine and an oxygen atom of the phosphate group.     

The adenosine diphosphate–adenosine triphosphate-exchange reaction of cerebral microsomes and its relation to the sodium ion-stimulated adenosine-triphosphatase reaction

Microsomes from guinea-pig cerebral cortex contain a system capable of exchanging ADP with ATP at rates of about 20mumoles/mg. of protein/hr. The ADP-ATP-exchange reaction requires Mg(2+) for activity. The reaction is not stimulated by Na(+) or K(+) and is not inhibited by ouabain, in contrast with the Na(+)-plus-K(+)-stimulated adenosine triphosphatase. The pH optimum also differs from that of the adenosine triphosphatase. The ADP-ATP-exchange reaction is stimulated two- to three-fold by non-ionic, anionic and cationic detergents, even when these agents are inhibiting the adenosine-triphosphatase reaction. This reaction may represent a component of the Na(+)-plus-K(+)-stimulated adenosine-triphosphatase reaction but is more likely to be due to other enzyme systems present in microsomal subfractions.     

The interplay of O-H?O hydrogen bonding in the generation of three new supramolecular complexes of Cu, Ni and Co: Syntheses, characterization and structural aspects

Three new coordination complexes, [Cu(L¹)(H₂O)] (1), [Ni(L²)₂]·CH₃CN (2) and [Co(HL³)(L³)] (3) [where H₂L¹, N,N′-bis(3-methoxysalicylidenimino)-1,3-diamino-propane; HL², 2-((E)-(1,3-dihydroxy-2-methylpropan-2-ylimino)methyl)phenol; H₂L³, 2-((E)-(2-hydroxyethylimino)methyl)-4-bromophenol] have been synthesized and systematically characterized by elemental analyses, FT-IR, electronic spectroscopy, cyclic voltammetry and thermogravimetric analyses. Single crystal X-ray diffraction studies confirm that the metal center in complex 1 has distorted square-pyramidal geometry while it is distorted octahedral in the other two complexes. In all the complexes O-H?O hydrogen bondings assemble the molecular units leading to ordered supramolecular architectures. While both complexes 1 and 2 form infinite one-dimensional arrays through the self organisation of hydrogen bonded ring motifs, complex 3 is a unique star-shaped cyclic hexamer generated through intermolecular hydrogen bonding.     

FeS2 nanosheets–luminol–O2 chemiluminescence method for determination of venlafaxine hydrochloride,imipramine hydrochloride,and cefazolin sodium

This study introduces a novel chemiluminescence (CL) approach utilizing FeS₂ nanosheets (NSs) catalyzed luminol–O₂ CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS₂ NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 × 10⁻⁷ to 1.00 × 10⁻³ mol L⁻¹, 1.00 × 10⁻⁷ to 1.00 × 10⁻⁴ mol L⁻¹, and 4.00 × 10⁻⁶ to 2.00 × 10⁻⁴ mol L⁻¹ with detection limits (3σ) of 3.54 × 10⁻⁷, 1.08 × 10⁻⁸, and 2.63 × 10⁻⁶ mol L⁻¹ for VFX, IPM, and CEF, respectively. This study synthesized FeS₂ NSs using a facile hydrothermal approach, and then the synthesized FeS₂ NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated.     

Theoretical studies on the structures,intra- and inter-molecular hydrogen bonding interactions in HNF and HNF–H2O clusters in the gaseous,aqueous and solid phases

Hydrazimium nitroformate ([N₂H₅]⁺[C(NO₂)₃]^? , HNF) is an ionic oxidiser used in solid propellants. Its properties are easily affected by H₂O because of its hygroscopicity. In this article, density functional theory (DFT) and molecular dynamics (MD) were employed to study the isolated HNF molecule and the HNF–H₂O cluster in gas phase and in the aqueous solution. Three stable conformations were obtained for HNF in the gas phase and in the aqueous solution, respectively, and each conformation can form several different HNF–H₂O clusters. Irrespective of whether it is in gas phase or in solution, intramolecular hydrogen bond interactions and other interactions (e.g. the binding energy, the dispersion energy, the second-order perturbation energy and the energy gap between frontier orbitals) of HNF are weaker in the clusters than in the isolated state. The initial decomposition energy of the cluster is lower than that of the isolated HNF molecule in both gaseous and aqueous phases, while the dissociation processes are the same. Molecular dynamic simulations showed that the clustered H₂O elongates and weakens the C–NO₂ bond in the solid HNF–H₂O cluster compared with that in the solid HNF. H₂O reduces and weakens intramolecular N–HΛO bonds too, and O–HΛN is the dominant intermolecular hydrogen bond between HNF and H₂O.     

Time and noise: the stable surroundings of reaction experiments, 1860–1890

The ‘Reaction experiment with Hipp chronoscope’ is one of the classical experiments of modern psychology. This paper investigates the technological contexts of this experiment. It argues that the development of time measurement and communication in other areas of science and technology (astronomy, the clock industry) were decisive for shaping the material culture of experimental in psychology. The chronoscope was constructed by Matthäus Hipp (1813–1893) in the late 1840s. In 1861, Adolphe Hirsch (1830–1901) introduced the chronoscope for measuring the ‘physiological time’ of astronomical observers. Hirsch’s observatory at Neuchâtel (Switzerland) served to control the quality of clocks produced in the nearby Jura mountains. Hipp provided the observatory with a telegraphic system that sent time signals to the centers of clock production. Time telegraphy constituted the stable surroundings of the reaction time experiments carried out by both astronomers and psychologists. This technology permitted precise measurements of short time intervals and offered to Hirsch, as well as to Wilhelm Wundt (1832–1920), a useful metaphor for conceptualizing their respective ‘epistemic objects’. But time telegraphy also limited the possibilities of the experimental work conducted within its framework. In particular, noise from outside and inside the research sites at Neuchâtel, Leipzig and elsewhere disturbed the precise communication of time.