Site-to-site peptide transport on a molecular platform using a small-molecule robotic arm

Peptides attached to a cysteine hydrazide ‘transporter module’ are transported selectively in either direction between two chemically similar sites on a molecular platform, enabled by the discovery of new operating methods for a molecular transporter that functions through ratcheting. Substrate repositioning is achieved using a small-molecule robotic arm controlled by a protonation-mediated rotary switch and attachment/release dynamic covalent chemistry. A polar solvent mixtures were found to favour Z to E isomerization of the doubly-protonated switch, transporting cargo in one direction (arbitrarily defined as ‘forward’) in up to 85% yield, while polar solvent mixtures were unexpectedly found to favour E to Z isomerization enabling transport in the reverse (‘backward’) direction in >98% yield. Transport of the substrates proceeded in a matter of hours (compared to 6 days even for simple cargoes with the original system) without the peptides at any time dissociating from the machine nor exchanging with others in the bulk. Under the new operating conditions, key intermediates of the switch are sufficiently stabilized within the macrocycle formed between switch, arm, substrate and platform that they can be identified and structurally characterized by ¹H NMR. The size of the peptide cargo has no significant effect on the rate or efficiency of transport in either direction. The new operating conditions allow detailed physical organic chemistry of the ratcheted transport mechanism to be uncovered, improve efficiency, and enable the transport of more complex cargoes than was previously possible.

Peptides are transported in either direction between chemically similar sites on a molecular platform, substrate repositioning is achieved using a cysteine hydrazide transporter module and a small-molecule robotic arm controlled by a rotary switch.     

Synthesis of O,O Ethane Bridged Bis-copper(II) Macrocycles. Selective Enzyme Model for Catecholase Activity

New mononuclear and dinuclear complexes [3-hydroxyethyl-1,3,5,8,11pentaazacyclotridecane]copper(II) (1)/nickel(II) (2) perchlorate and O,O ethane bridged bis-copper(II) (3)/nickel(II) (4) macrocycles have been synthesized and characterized by various spectroscopic techniques, viz. i.r., n.m.r., e.p.r., u.v.–vis. and conductance measurements. Spectral data and conductance measurements reveal that all the complexes are consistent with square-planar geometry and are ionic in nature. The catalytic activity of the dinuclear Cu(II) complex (3) in the presence of pyrocatechol was determined spectrometrically by monitoring the increase of the o-benzoquinone characteristic absorption band at 25,000 cm⁻¹ with respect to time in DMF saturated with molecular oxygen. The kinetic parameters V_max (2.8×10⁻³ M s⁻¹) and K_M (1.4×10⁻³ mm) have been determined by Michaelis–Menten method. Electrochemistry of the dinuclear Cu(II) complex has been studied in the presence of molecular oxygen with pyrocatechol and without pyrocatechol at a scan rate of 0.1 V s⁻¹ by cyclic voltammetry. On addition of pyrocatechol, complex shows a shift in E_pc, E_pa and E_1/2 values indicating the oxidation of substrate (pyrocatechol).     

On the structure of nonarchimedean exponential fields I

Given an ordered fieldK, we compute the natural valuation and skeleton of the ordered multiplicative group (K ^>0, ·, 1, <) in terms of those of the ordered additive group (K,+,0,<). We use this computation to provide necessary and sufficient conditions on the value groupv(K) and residue field , for theL -equivalence of the above mentioned groups. We then apply the results to exponential fields, and describev(K) in that case. Finally, ifK is countable or a power series field, we derive necessary and sufficient conditions onv(K) and forK to be exponential. In the countable case, we get a structure theorem forv(K).This paper represents some results of the author's doctoral thesisThis paper was written while the author was supported by a research grant from the University of Heidelberg     

New asymmetric N2S2 macrocycles,their metal chelates and the photokinetics of DNA-complex interaction

New asymmetric ligands have been synthesized by condensing o-phenylene diamine with CS₂ and PhCHO/MeCHO, and their complexes with Mn^II, Co^II, Ni^II, Cu^II and Zn^II were prepared and characterized by elemental analyses, conductivity measurements, i.r., u.v.–vis., e.p.r. and n.m.r. spectra. The transition metals in the complexes show square planar geometry and are ionic. Photokinetic studies of the DNA-metal complexes [C₁₀H₁₀S₄N₂Cu](NO₃)₂ and [C₁₀H₁₀S₄N₂Ni](NO₃)₂ were carried out and the rate constants k_{(DNA-complex)} were calculated. The results indicate that DNA reacts with the metal complex in two steps. DNA first undergoes structural degradation and is then completely hydrolysed as indicated by spectral changes consistent with earlier results. The asymmetric N₂S₂ macrocyclic metal complexes show a strong propensity for DNA inhibition and can be used as an intercalating binding model.     

Interaction of a new cobalt(II) complex of five-coordinated chiral porphyrin with calf thymus DNA

A new template-directed chiral porphyrin [(TPP)Co(Trp)], where TPP = tetraphenylporphyrin and Trp = 1-tryptophan, was prepared and characterized by various physico-chemical methods. Interaction of [(TPP)Co(Trp)] with calf thymus DNA was studied by u.v.–vis. spectroscopy and cyclic voltammetry. The complex [(TPP)Co(Trp)], after interaction with calf thymus DNA, shows a shift in the absorption spectrum and a large hypochromicity, indicating an intercalating binding mode. This observation was further confirmed by the electrochemical behavior of [(TPP)Co(Trp)] before and after interaction with calf thymus DNA. The complex experiences a negative shift in E _1/2 and a decrease in E _p. The ratio of cathodic to anodic peak currents i _pc/i _pa was 1 for [(TPP)Co(Trp)] while for DNA bound complex i _pc/i _pa 1, suggesting that the calf thymus DNA moiety is bound strongly to the complex [(TPP)Co(Trp)]. Kinetic studies of the DNA-porphyrin complex reveal a psuedo-first order rate law as the plot of k _obs versus calf thymus DNA is linear passing through the origin.     

Combined application of INAA and PIXE for studying the regional aerosol composition in Southern Africa

As part of the SAFARI-92 biomass buming experiment, aerosol collections were carried out with several size-fractionating sampling devices at a number of sites in Southern Africa. One of the samplers used at all ground-based sites was a stacked filter unit (SFU). The SFU samples were analyzed by both INAA and PIXE analysis. The present paper gives an intercomparison of the analytical results obtained in order to assess the accuracy and to check the quality assurance of the analytical procedures. Twenty-one common elements were determined by both INAA and PIXE. Concentrations of 13 elements (i.e., Na, Mg, Al, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Zn and Br) were generally measured with sufficient precision in both techniques for performing the intercomparison. The INAA and PIXE data were compared in terms of PIXE/INAA concentration ratios on a sample by sample basis for the coarse and fine size fraction separately. the atmospheric concentrations for K, Mn and Fe agreed within 5–10%, the agreement between the data for the other common elements was typically better than 15%. Possible explanations for lower than 1.0 ratios for Cl, Br and Na are presented. The common elements were classified into groups according to their detectability and sensitivity in each technique.     

A sequential injection spectrophotometric method for the determination of penicillamine in pharmaceutical products by complexation with iron(III) in acidic media

A simple, robust and sensitive sequential injection spectrophotometric method for the assay of penicillamine (PA) in pharmaceutical formulations is developed. The method was based on the complex formation when PA is reacted with iron(III) solution in hydrochloric acid media. The deep blue colored PA-iron(III) complex produced is monitored at a maximum wavelength of 600 nm. A five level orthogonal array design coupled to genetic algorithm was employed to obtain the optimum experimental conditions for the determination of PA using peak absorbance as the measure of the system's performance criterion. A linear dynamic range for the determination of PA of 25-300 ppm was obtained with a sampling frequency of 50 h⁻¹ and a relative standard deviation of less than 0.98%. The method was successfully applied to the determination of PA in pharmaceutical formulations.     

Ketalizations of aryl ω-(2-imidazolyl)alkyl ketones by glycerol and 3-mercapto-1,2-propanediol. synthesis and characterization of cis- and trans-{2-aryl-2-[ω-(2-imidazolyl)alkyl](1,3-dioxolan-4-yl and 1,3-oxathiolan-5-yl)}methanols

Aryl 2-[(2-imidazolyl)ethyl or 3-(2-imidazolyl)propyl]ketones were ketalized by glycerol or 3-mercapto-1,2-propanediol in boiling benzene in the presence of 4-toluenesulfonic acid to provide the title compounds. The aryl substituents are 4-chloro-, 4-bromo-, 4-fluoro-, or 2,4-dichlorophenyl. While aryl (2-imidazolyl)methyl ketones condensed with glycerol to form cis- and trans-{2-aryl-2-[(2-imidazolyl)methyl]-4-(hydroxymethyl)}-1,3-dioxolanes, related condensations with 3-mercapto-1,2-propanediol, under similar, or even more stringent reaction conditions, produced no 1,3-oxathiolane analogs, with the starting ketones being recovered. Separation and structure determination of these racemic cis and trans isomeric products are described. The structure of these stereoisomers was established by means of ¹H and ¹³C nmr correlation and nOe experiments. Selective methylation of the N-unsubstituted 2-imidazolyl alcohols with one equivalent sodium hydride and methyl iodide provided the corresponding N-methyl alcohols in excellent yields. With excess benzoyl chloride, N-unsubstituted 2-imidazolyl alcohols were initially converted to O, N-dibenzoates from which the N-benzoyl group was easily cleaved by ammonium hydroxide in ethanol to provide benzoate esters.     

Synthesis of 1-[3-methyl-2(3H)-benzazolon-5- or 6-yl]-4-{4-[cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methyleneoxyphenyl}piperazines

Reactions of 3-methyl-6-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzoxazolone, 3-methyl-6-[4-(4-hydroxy-phenyl)-1-piperazinyl]-2(3H)-benzothiazolone and 1,3-dimethyl-5-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzimidazolone with cis-{[2-(2,4-dichlorophenyl) -2-(1H-imidazol-1-ylmethyl)]-1,3-dioxolan-4-yl}methyl meth-anesulfonate in the presence of sodium hydride furnish the title compounds.     

Silica iodide catalyzed,ultrasound-promoted,one-pot four-component synthesis of novel 1,4,5,6-tetrahydropyridine-3-carboxylate derivatives

Silica iodide catalyzed, competent synthesis of 15 novel substituted-1,4,5,6-tetrahydropyridine-3-carboxylate derivatives was achieved by a one-pot four-component cyclocondensation of Meldrum's acid, aryl aldehydes, aromatic amines and ethyl acetoacetate under ultrasonic irradiation. In comparison to the conventional methods, our protocol is convenient, eco-friendly and offers several benefits such as: mild conditions, high yields, shorter reaction time and ease in product isolation.