Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

Translational and rotational invariance requisites for density functional derivatives

Translational and rotational invariance of functionals lead to hierarchies of equations between successive derivatives. These hierarchies allow alternating series expansions of some density functionals in terms of functional derivatives and charge density. Translational and rotational invariance also give rise to integrodifferential equations that link derivatives of all orders. From the minimal properties of the kinetic energy functional T_s[ρ] and the functional F[ρ] = min_Ψ→ρ <Ψ|T + V_ee|Ψ>, it follows that $int dˆ3 r dˆ3 rˆprimef({bold r}) {delˆ2 T―s[rho]}over{delrho({bold r})delrho({bold rˆprime})}f({bold rˆprime}) geq 0hspace{1cm}hbox{and}hspace{1cm}int dˆ3 r dˆ3 rˆprimef({bold r}) {delˆ2 F[rho]}over{delrho({bold r})delrho({bold rˆprime})}f({bold rˆprime}) geq 0$ for all ∫ d³ r d³ f′ f(r) = 0. This property combined with constraints on functionals due to translational invariance lead to inequalities satisfied by first derivatives of selected density functionals. © 1997 John Wiley & Sons, Inc.     

Improving the Performance of a Continuous Process for the Production of Ethanol from Starch

In a previous work, a continuous simultaneous saccharification and fermentation process to produce ethanol from cassava starch was studied, using a set of fixed-bed reactors. The biocatalyst consisted of glucoamylase immobilized in silica particles and co-immobilized with S. cerevisiae in pectin gel. Using 3.8 U mL^?1 _reactor and 0.05 g_{wet yeast} mL^?1 _reactor at start-up, starch hydrolysis was the rate-limiting step. Maximum ethanol productivity was 5.8 g_ethanol L^?1 h^?1, with 94.0% conversion of total reducing sugars (TRS) and 83.0% of the ethanol theoretical yield. In this work, the molar mass of the substrate and the biocatalyst particle size were reduced in an attempt to improve the bioreactor performance. The diameters of silica and pectin gel particles were reduced from 100 μm and 3–4 mm, respectively, to 60 μm and 1–1.5 mm, and the degree of substrate prehydrolysis by α-amylase was increased. The bioreactor performance was assessed for different loads of immobilized glucoamylase (2.1, 2.8, and 3.8 U mL^?1 _reactor), for the same initial cell concentration (0.05 g_{wet yeast.}mL^?1 _reactor). Feeding with 154.0 g L^?1 of TRS and using 3.8 U mL^?1 _reactor, fermentation became the rate-limiting step. Productivity reached 11.7 g L^?1 h^?1, with 97.0% of TRS conversion and 92.0% of the ethanol theoretical yield. The reactor was operated during 275 h without any indication of destabilization.     

Synthesis of (±)-1,2,3-triazolo-3′-deoxy-4′-hydroxymethyl carbanucleosides via ‘click’ cycloaddition

The synthesis of 1,2,3-triazolo-3′-deoxy-4′-hydroxymethyl carbanucleosides with different reaction conditions and diverse modulations on the heterocycle residues was developed. Heterocycle moieties were efficiently introduced on the pseudo-sugar either via nucleophilic substitution or via 1,3-dipolar Huisgen cycloaddition. With this latter approach, 1,4-disubstituted and 1,4,5-trisubstituted-(±)-[1,2,3]-triazolo-3′-deoxy-4′-hydroxymethyl carbanucleosides were prepared from the corresponding azido-carbocycle and various terminal or internal alkynes. Antiviral activities and cellular toxicities of the final compounds were evaluated as smallpox inhibitors. Unfortunately, at concentrations up to 100 mM, none of them inhibited production of vaccinia virus (Lister strain) or cowpox virus (Brighton strain) in vero cells.     

Ab initio study of phonon dispersion and thermodynamic properties of pure and doped pyrites

Pyrites (FeS₂) are solid minerals that are found abundantly in Nigeria and are easy to prepare in laboratories. In this work, FeS₂ is studied extensively in its pure state as well as when iron is substitutionally doped with zinc and calcium at concentrations of 0, 0.25, 0.5, 0.75 and 1. Using density functional theory, the eectronic, dynamic and thermodynamic properties were calculated. The results revealed that the lattice parameters and bulk modulus increases with increasing concentration and the obtained values are in agreement with available experimental and theoretical values. Though pyrite, when doped with zinc, obeys Vegard’s law, doping with calcium revealed pronounced deviation from this law. The calculated band structures showed that FeS₂ has an indirect band gap whose size decreases after introducing zinc while doping with calcium increases the band gap. The phonon dispersion of the end members FeS₂ and ZnS₂ indicate that the systems are dynamically stable while CaS₂ is dynamically unstate. Also, the thermodynamic properties of the pure and doped pyrites were calculated and the ranges of temperature at which the lattice and electronic degrees of freedom contribute to the specific heat capacity are presented.     

Structural Insights and Docking Analysis of Adamantane-Linked 1,2,4-Triazole Derivatives as Potential 11β-HSD1 Inhibitors

The solid-state structural analysis and docking studies of three adamantane-linked 1,2,4-triazole derivatives are presented. Crystal structure analyses revealed that compound 2 crystallizes in the triclinic P-1 space group, while compounds 1 and 3 crystallize in the same monoclinic P2₁/c space group. Since the only difference between them is the para substitution on the aryl group, the electronic nature of these NO₂ and halogen groups seems to have no influence over the formation of the solid. However, a probable correlation with the size of the groups is not discarded due to the similar intermolecular disposition between the NO₂/Cl substituted molecules. Despite the similarities, CE-B3LYP energy model calculations show that pairwise interaction energies vary between them, and therefore the total packing energy is affected. HOMO-LUMO calculated energies show that the NO₂ group influences the reactivity properties characterizing the molecule as soft and with the best disposition to accept electrons. Further, in silico studies predicted that the compounds might be able to inhibit the 11β-HSD1 enzyme, which is implicated in obesity and diabetes. Self- and cross-docking experiments revealed that a number of non-native 11β-HSD1 inhibitors were able to accurately dock within the 11β-HSD1 X-ray structure 4C7J. The molecular docking of the adamantane-linked 1,2,4-triazoles have similar predicted binding affinity scores compared to the 4C7J native ligand 4YQ. However, they were unable to form interactions with key active site residues. Based on these docking results, a series of potentially improved compounds were designed using computer aided drug design tools. The docking results of the new compounds showed similar predicted 11β-HSD1 binding affinity scores as well as interactions to a known potent 11β-HSD1 inhibitor.     

Shelf-Life Stability of Ready-to-Use Green Rooibos Iced Tea Powder—Assessment of Physical,Chemical, and Sensory Properties

Green rooibos extract (GRE), shown to improve hyperglycemia and HDL/LDL blood cholesterol, has potential as a nutraceutical beverage ingredient. The main bioactive compound of the extract is aspalathin, a C-glucosyl dihydrochalcone. The study aimed to determine the effect of common iced tea ingredients (citric acid, ascorbic acid, and xylitol) on the stability of GRE, microencapsulated with inulin for production of a powdered beverage. The stability of the powder mixtures stored in semi-permeable (5 months) and impermeable (12 months) single-serve packaging at 30 °C and 40 °C/65% relative humidity was assessed. More pronounced clumping and darkening of the powders, in combination with higher first order reaction rate constants for dihydrochalcone degradation, indicated the negative effect of higher storage temperature and an increase in moisture content when stored in the semi-permeable packaging. These changes were further increased by the addition of crystalline ingredients, especially citric acid monohydrate. The sensory profile of the powders (reconstituted to beverage strength iced tea solutions) changed with storage from a predominant green-vegetal aroma to a fruity-sweet aroma, especially when stored at 40 °C/65% RH in the semi-permeable packaging. The change in the sensory profile of the powder mixtures could be attributed to a decrease in volatile compounds such as 2-hexenal, (Z)-2-heptenal, (E)-2-octenal, (E)-2-nonenal, (E,Z)-2,6-nonadienal and (E)-2-decenal associated with “green-like” aromas, rather than an increase in fruity and sweet aroma-impact compounds. Green rooibos extract powders would require storage at temperatures ≤ 30 °C and protection against moisture uptake to be chemically and physically shelf-stable and maintain their sensory profiles.     

Applying min–max <Emphasis Type="Italic">k</Emphasis> postmen problems to the routing of security guards

The most essential and alluring characteristic of a security estate is the estate's ability to provide 24-h security to its residents, of which the continual patrolling of roads and paths is vital. The objective of this paper is to address the lack of sufficient patrol route design procedures by presenting a tabu search algorithm capable of generating multiple patrol routes for an estate's security guards. The paper shows that the problem of designing these routes can be modelled as an Arc Routing Problem, specifically as min–max k postmen problems. The algorithm is illustrated with a real problem instance from an estate in Gauteng, South Africa. The patrol routes generated by the algorithm provide a significant improvement in the even patrolling of the road network, and a more balanced work distribution among guards. The algorithm is also tested on several benchmark problems from literature.