Binding site optimisation for artificial enzymes by diffusion NMR of small molecules

A binding site optimisation protocol for the design of artificial enzymes based on "small molecule-small molecule" binding studies by diffusion NMR is presented. Since the reaction chosen was the hydrolysis of ester 1 ([4-(4-carboxy-1-oxobutyl)-aminobenzyl]-phenethyl ester), an analogous phosphonate ester 2 ([4-(4-carboxy-1-oxobutyl)-aminobenzyl]-phosphonic phenethyl ester) was selected as a suitable transition state analogue (TSA). The key objective of the NMR studies was to find a unit with functional groups capable of binding to the acidic sites of the TSA. Nine dipeptides, mainly with basic and hydroxyl groups, were used and their affinity to the TSA was studied by measuring the change in the diffusion coefficient, D(pep), upon binding by pulse field gradient NMR. The value of D(pep) at 298 K in D(2)O at pD 5, 7 and 10 was measured both in free solution, and mixtures containing one dipeptide and the TSA. As both components are low molecular weight species with M < 500, a TSA-to-dipeptide ratio of 10:1 was used to detect significant changes in D(pep). The results revealed that dipeptides with basic residues show higher affinity to the TSA than those with hydroxyl or aliphatic side chains in aqueous solutions. The dipeptide showing the most significant relative change in D(pep) was H-Arg-Arg-OH, and the binding constant was estimated to be 86 L M(-1) by measuring D(pep) at varying concentrations of the TSA. In addition, binding of the TSA to a new water-soluble polymer with a polyallylamine backbone and randomly distributed Arg-Arg binding sites was examined, and the binding constant was estimated to be > or =1500 L M(-1). As confirmed by further catalytic activity tests, polymers containing Arg-Arg as a binding site are capable of significant rate accelerations in the hydrolysis of ester 1.     

Iridium mediated methyl and phenyl C-H activation of 2-(arylazo)phenols. Synthesis, structure, and spectral and electrochemical properties of some organoiridium complexes

Reaction of 2-(2′,6′-dimethylphenylazo)-4-methylphenol with [Ir(PPh₃)₃Cl] in refluxing ethanol in the presence of a base (NEt₃) affords an organoiridium complex 5, where the 2-(2′,6′-dimethylphenylazo)-4-methylphenol is coordinated to iridium, via C-H activation of a methyl group, as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride are also coordinated to the metal center. A similar reaction carried out in toluene affords complex 5 along with a similar complex 7, where a chloride is coordinated to iridium instead of the hydride. Reaction of 2-(2′-methylphenylazo)-4-methylphenol with [Ir(PPh₃)₃Cl] in refluxing ethanol in the presence of a base (NEt₃) affords an organoiridium complex 12, where the 2-(2′-methylphenylazo)-4-methylphenol is coordinated to iridium, via C-H activation at the ortho position of the phenyl group in the 2′-methylphenylazo fragment, as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride are also coordinated to the metal center. A similar reaction carried out in toluene affords a complex 12 along with a similar complex 13, where a chloride is coordinated to iridium instead of the hydride. Structures of complexes 5, 12 and 13 have been determined by X-ray crystallography. In all these complexes, the two triphenylphosphines are trans. All these complexes show intense MLCT transitions in the visible region. Cyclic voltammetry on all the complexes shows an Ir(III)-Ir(IV) oxidation within 0.60-0.73 V vs. SCE, followed by an oxidation of the coordinated 2-(arylazo)phenolate ligand within 1.08-1.39 V vs. SCE. A reduction of the coordinated 2-(arylazo)phenolate ligand is observed within −1.10 to −1.26 V vs. SCE.     

均匀棒状过氧化氢合碳酸钠制备及非等温热分解动力学

本文制备了均匀棒状过氧化氢合碳酸钠，化学分析确定其组成为Na₂CO₃·1.5H₂O₂，用DTA-TG-DTG技术并辅以X-ray分析研究了它在静态空气、流动氧气和流动氮气气氛中的非等温热分解过程及动力学。     

Enantioselectivity of 6-O-alkyldimethylsilyl-2,3-di-O-methyl-β-cyclodextrins as chiral stationary phases in capillary GC

Summary Clenbuterol has been determined in urine by solidphase extraction on a C₁₈ cartridge, diazotization of the eluate with nitrite, coupling of the diazonium ion with 1-(naphthyl)ethylenediamine, and separation of the azo dye formed by HPLC with a C₁₈ column and a micellar mobile phase containing 0.1 M sodium dodecyl sulphate, 12%n-butanol and 0.05 M citrate buffer, pH 3. Recoveries higher than 90% were obtained by mixing the samples with a 20% 0.2 M NaOH before extraction. Limits of detection of 51 and 6.7 ng L⁻¹ were obtained with spectrophotometric and thermal lens spectrometric detection, respectively; respective repeatabilities were 3.1% (5 μg mL⁻¹) and 5.6% (0.16 μg mL⁻¹).     

Conformational Studies on Polytripeptides as a Model of Collagen

To study the role of glycine residues in stabilizing the collagen triple helix, the glycine residues in the polytripeptide (Pro-Ala-Gly)_n were partially replaced by alanine. The proline content was kept constant. The stability of the helical conformation of these polypeptides was studied by IR- and X-ray measurements in the solid state and by ORD, CD and viscometry in solution. The renaturation was followed as a function of time. All the polytripeptides studied, with the exception of (-Pro-Ala-Ala-)_n attained the polyproline II conformation. However the stability decreased with increasing alanine content. Obviously the molecules of (-Pro-Ala-Gly-) are highly associated by intermolecular hydrogen bonds and one may therefore suppose that a triple-stranded helix aggregation occurs. The results of the refolding process show that the stability of the helices seems to also affect the refolding rate in terms of the optical rotation, Two transitions appeared: the first one is responsible for a rapid reversible change in conformation and the second one for a further slow and irreversible change in the hydrodynamic shape. The latter seems to be due to the partial helical nature, leading to higher chain mobility.     

Reaction of 4,4′-dimethyldiphenyl ether with phosphorus trichloride in the presence of anhydrous aluminum chloride

The reaction of 4,4-dimethyldiphenyl ether with phosphorus trichloride in the presence of anhydrous aluminum chloride was studied. This reaction affords 2,8-dimethyl-10H-10⁵-phenoxaphosphine 10-oxide as virtually the only product. In air, the latter in an alkaline solution is quantitatively transformed into 10-hydroxy-2,8-dimethyl-10H-10⁵-phenoxaphosphine 10-oxide.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2762–2765, December, 2004.     

Synthesis and inhibitory activity of alkyl(hydroxyaryl)amines

The reaction of ω-(4-hydroxyaryl)haloalkanes with various nitrogen-containing agents afforded primary, secondary, and tertiary amino derivatives of 2,6-dialkylphenols. For the compounds synthesized, the reaction rate constants with peroxide radicals were measured for cumene and methyl oleate oxidation. The total inhibitory activity in the model reactions of thermal autooxidation of lard and hexadecane was studied. The rate constants of alkyl(hydroxylaryl)amines are the same as those of the corresponding alkylphenols, whereas the total inhibitory activity of some alkyl(hydroxylaryl)amines exceeds substantially that for alkylphenols. Dedicated to the memory of Academician N. N. Vorozhtsov on the 100th anniversary of his birth. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1107–1112, June, 2007.     

Stereoselective synthesis of (−)-microcarpalide

A highly convergent and efficient synthesis of (−)-microcarpalide, a 10-membered lactone displaying remarkable microfilament disrupting activity is described. Ring-closing metathesis and Sharpless asymmetric dihydroxylations are the key steps. Our strategy highlights the application of novel hydroxy lactone precursors for the stereoselective synthesis of (−)-microcarpalide.     

An Analytical Study of Molecular Transport in a Zeolite Crystallite Bed

Analytical solutions of the diffusion equations to obtain the diffusant concentrations in the macro- and micropores which constitute the pore system of a zeolite bed are presented. The parameter which determines the influence of each pore type on the evolution of the adsorbate/adsorbant system towards the equilibrium state is described. Examples are given to illustrate a qualitative and quantitative study based on the curves obtained from these equations.     

Darstellung und Kristallstruktur von [P(C6H5)4][2,9-{N,N′-(2-NH?(C5H4N))}B10H8]

Synthesis and Crystal Structure of [P(C₆H₅)₄][2,9-{N,N′-(2-NH? (C₅H₄N))}B₁₀H₈] [N(C₄H₉)₄]₂[B₁₀H₁₀] reacts with 2-aminopyridine forming a product mixture from which [2,9-{N,N′-(2-NH? (C₅H₄N))}B₁₀H₈]^? can be isolated by ion exchange chromatography on diethylaminoethyl(DEAE) cellulose. The crystal structure of [P(C₆H₅)₄][2,9-{N,N′-(2-NH? (C₅H₄N))}B₁₀H₈] (triclinic, space group P1 , a = 10.1103(9), b = 11.5665(9), c = 14.877(2) Å, α = 102.600(8), β = 107.567(8) und γ = 96.487(7)°, Z = 2) reveals the bonding of 2-NH₂-(C₅H₄N) via both N atoms to vicinal B atoms of the two square planes of the B₁₀ cluster (B2? N1 = 1,541(7) und B9? N2 = 1.505(7) Å) forming a five-membered ring.