A novel synthesis of N-methyl asparagine,arginine, histidine,and tryptophan

[reaction: see text] N-Methyl amino acid residues in peptides modify several pharmacologically useful parameters, but synthesis of alkylated peptides is hampered by unavailability of N-methylated monomers. The syntheses of four N-methyl amino acids with basic side chains are presented. The side chains of these basic amino acids needed to be specially protected or constructed. This completes the set of 20 common L-amino acid N-methyl derivatives prepared via 5-oxazolidinone intermediates by our group.     

Peak symmetry as a measure of column performance in high-performance liquid chromatography

Summary During a column-packing method development study, 114 reverse phase and 40 silica gel columns were packed. A relationship between peak symmetry and column efficiency was observed which was found to be useful when evaluating column performance.     

Conflict-free routing of multi-stop warehouse trucks

Optimization Letters - The recent interest in greater vehicular autonomy for factory and warehouse automation has stimulated research in conflict-free routing: a challenging network routing problem...     

Thermal fragmentation of 2-chloropentylphosphonic salts in the solid state. Counter-ion effects on reactivity and selectivity

The monoanion of 2-chloropentylphosphonic acid was thermally decomposed in the solid state, and the products of the fragmentation were identified and quantitatively determined. The reaction can involve either the elimination of HCl or the Cl ion and the metaphosphate (HPO₃), and it was found that the nature of the counter ion affects strongly the selectivity of the fragmentation. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8: 421–428, 1997     

Activation of α-keto acid-dependent dioxygenases: application of an {FeNO}7/{FeO2}8 methodology for characterizing the initial steps of O2 activation

The α-keto acid-dependent dioxygenases are a major subgroup within the O(2)-activating mononuclear nonheme iron enzymes. For these enzymes, the resting ferrous, the substrate plus cofactor-bound ferrous, and the Fe(IV)═O states of the reaction have been well studied. The initial O(2)-binding and activation steps are experimentally inaccessible and thus are not well understood. In this study, NO is used as an O(2) analogue to probe the effects of α-keto acid binding in 4-hydroxyphenylpyruvate dioxygenase (HPPD). A combination of EPR, UV-vis absorption, magnetic circular dichroism (MCD), and variable-temperature, variable-field (VTVH) MCD spectroscopies in conjunction with computational models is used to explore the HPPD-NO and HPPD-HPP-NO complexes. New spectroscopic features are present in the α-keto acid bound {FeNO}(7) site that reflect the strong donor interaction of the α-keto acid with the Fe. This promotes the transfer of charge from the Fe to NO. The calculations are extended to the O(2) reaction coordinate where the strong donation associated with the bound α-keto acid promotes formation of a new, S = 1 bridged Fe(IV)-peroxy species. These studies provide insight into the effects of a strong donor ligand on O(2) binding and activation by Fe(II) in the α-keto acid-dependent dioxygenases and are likely relevant to other subgroups of the O(2) activating nonheme ferrous enzymes.     

Tire Cord Application of High-Modulus Fibers Derived from Polyamide-Hydrazides

Recent developments in tire design have focused interest on new combinations of properties for fibers to be used in tire cords. Different fiber properties are of importance depending on whether the end use is in bias design, breaker belts, or radial design. X-500 class fibers of polyamide-hydrazides can be produced with a range of property combinations. The textile-like fiber with good tenacity, extensibility, and modulus similar to presently used organic fibers has advantages of greater dimensional stability and heat resistance. The high modulus variant shows better flex life, abrasion resistance, and water resistance than glass. X-500 class fibers can be made stronger and stiffer than glass or steel—when compared in textile units. Data, presented show typical prototype X-500 tire cord properties in the greige and the heat-treated form. Experimental tires were made using a polyamide-hydrazide X-500 fiber in the belts of radial and bias constructions. Nylon 66 and polyester were used in the carcasses. Tread-wear data showed equivalent performance of the polyamide-hydrazide X-500 belts when compared to glass, and they were less prone to belt separation failures.     

The relationship between 19F and 13C substituent chemical shifts and electron densities. 2—p-phenylacetyl fluorides

The ¹⁹F substituent chemical shifts (SCS) of a series of para-phenylacetyl fluorides (X? Ph? CH₂? COF) are reported and compared with the related benzoyl fluoride series (X? Ph? COF). A dual substituent parameter analysis of the results for the new series shows that both inductive and resonance effects are reduced by one third when compared with the benzoyl fluorides. ¹³C shifts for the side chain carbonyl were also measured and found to follow a reversed trend in substituent effects, consistent with a pi polarization mechanism. SCS values for the fluorine and its adjacent carbon are not directly related. Ab initio (STO-3G) calculations of the carbon and fluorine electron density for this series have been compared with the appropriate SCS values. From the electron densities and the observation that the fluorine SCS values follow a normal direction, whilst those for electron densities and the observation that the fluorine SCS values follow a normal direction, whilst those for the adjacent carbon are reversed, it is concluded that fluorine SCS values (and Δqπ values) result from polarization of the C? F pi bond and do not merely monitor changes in electron density of the adjacent carbon.     

Isolation,tentative identification,and synthesis studies of the volatile components of the hairpencil secretion of the monarch butterfly

The major volatile components of the hairpencil secretion of the male monarch butterfly have been identified as benzyl caproate and either 1, 5, 5, 9-tetramethyl-10-oxabicyclo[4.4.0]-3- decen-2-one(1), or 2, 2, 6, 8-tetramethyl-7-oxabicyclo[4.4.0]-4-decen-3-one(2). One sequence designed to synthesize 1 yielded two isomeric products of structure 1 whose spectra are very similar to each other but distinctly different from those of the natural product; this sequence also yielded a tricyclic ketal (9). A second sequence gave two epimeric spiro compounds (12) and a third sequence gave a [4.3.0] ring system (14).     

The relationship between 19F substituent chemical shifts and electron densities: meta- and para-substituted benzoyl fluorides

The ¹⁹F substituent chemical shifts (SCS) of meta- and para-benzoyl fluorides are found to correlate well with substituent parameters using the dual substituent parameter (DSP) equation, indicating that they reflect electronic perturbations induced by the substituent. The direction of the SCS values is such that donating substituents cause upfield shifts whilst acceptors cause downfield shifts. STO-3G calculations indicate that substituents induce only very small changes in π-electron density about the fluorine atom, but that these changes correlate reasonably well with the observed SCS values. For the para series, the slope of the relationship between δq and ¹⁹F SCS is 5000 ppm/electron, indicating the great sensitivity of the flourine atom to small changes in electron density.     

Effect of atomic charge,solvation, entropy,and ligand protonation state on MM-PB(GB)SA binding energies of HIV protease

The molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) and MM-generalized-Born surface area (MM-GBSA) approaches are commonly used in molecular modeling and drug design. Four critical aspects of these approaches have been investigated for their effect on calculated binding energies: (1) the atomic partial charge method used to parameterize the ligand force field, (2) the method used to calculate the solvation free energy, (3) inclusion of entropy estimates, and (4) the protonation state of the ligand. HIV protease has been used as a test case with six structurally different inhibitors covering a broad range of binding strength to assess the effect of these four parameters. Atomic charge methods are demonstrated to effect both the molecular dynamics (MD) simulation and MM-PB(GB)SA binding energy calculation, with a greater effect on the MD simulation. Coefficients of determination and Spearman rank coefficients were used to quantify the performance of the MM-PB(GB)SA methods relative to the experimental data. In general, better performance was achieved using (i) atomic charge models that produced smaller mean absolute atomic charges (Gasteiger, HF/STO-3G and B3LYP/cc-pVTZ), (ii) the MM-GBSA approach over MM-PBSA, while (iii) inclusion of entropy had a slightly positive effect on correlations with experiment. Accurate representation of the ligand protonation state was found to be important. It is demonstrated that these approaches can distinguish ligands according to binding strength, underlining the usefulness of these approaches in computer-aided drug design. © 2012 Wiley Periodicals, Inc.