Horseradish Peroxidase as a Catalyst for Atom Transfer Radical Polymerization

The hemoprotein horseradish peroxidase (HRP) catalyzes the polymerization of N‐isopropylacrylamide with an alkyl bromide initiator under conditions of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) in the absence of any peroxide. This is a novel activity of HRP, which we propose to name ATRPase activity. Bromine‐terminated polymers with polydispersity indices (PDIs) as low as 1.44 are obtained. The polymerization follows first order kinetics, but the evolution of molecular weight and the PDI upon increasing conversion deviate from the results expected for an ATRP mechanism. Conversion, and PDI depend on the pH and on the concentration of the reducing agent, sodium ascorbate. HRP is stable during the polymerization and does not unfold or form conjugates.

     

Rational design of inhibitors against LpxA protein of Acinetobacter baumannii using a virtual screening method

BackgroundAcinetobacter baumannii is a highly antimicrobial resistant nosocomial pathogen. Resistance to currently used antibiotics has limited effective drugs against this bacterium. This study aimed to propose a rational inhibitor design against the LpxA protein of A. baumannii using a virtual screening method based on a similar structure of ligands.MethodsIn this study, we targeted LpxA protein, which is involved in the early stage of LPS biosynthesis. In the next step, we used Peptide920 and 1,2- Ethanediol as templates to find similar compounds using Drugbank and Zinc15 webservers, respectively. Subsequently, molecular dynamics (MD) simulations were carried out for LpxA protein and two complexes of ZINC895081 and Macrolactam-1 which represented the highest binding affinity and best conformation. Finally, ADMET properties, water solubility and drug-likeness of the desired compounds were evaluated using SwissADME and DruLiTo softwares.ResultsAccording to considered criteria, Drugbank suggested 5 compunds including Ilomastat, Macrolactam-1, Macrolactam-2, Macimorelin, and Oglufanide. On the other hand, Zinc15 webserver suggested 4 compunds including ZINC895048, ZINC895081, ZINC901061 and ZINC1531008. The result of the HDOCK server and Molegro virtual docker (MVD) showed that Macrolactam-1 and ZINC895081 (Citrate) had the highest docking score. In addition, MD simulations showed that ZINC895081 and Macrolactam-1 ligands have the stable binding to the LpxA protein. According to Lipinski's rule, these two compounds are non-carcinogenic, non-toxic and promising inhibitors against LpxA of A. baumannii.ConclusionIt seems that Macrolactam-1 and ZINC895081 (Citrate) are two valuable promising inhibitors against the LpxA protein of A. baumannii. Further in vitro and in vivo experiments are needed to confirm the capabilities of these proposed compounds against A. baumannii.     

Synthesis of methylene- and difluoromethylenephosphonate analogues of uridine-4-phosphate and 3-deazauridine-4-phosphate

Cytidine triphosphate synthetase (CTPS) catalyzes the formation of cytidine triphosphate from glutamine, uridine-5'-triphosphate (UTP), and adenosine-5'-triphosphate. Inhibitors of CTPS are of interest because of their potential as therapeutic agents. One approach to potent enzyme inhibitors is to use analogues of high energy intermediates formed during the reaction. The CTPS reaction proceeds via the high energy intermediate UTP-4-phosphate (UTP-4-P). Four novel analogues of uridine-4-phosphate (U-4-P) and 3-deazauridine-4-phosphate (3-deazaU-4-P) were synthesized in which the labile phosphate ester oxygen was replaced with a methylene and difluoromethylene group. The methylene analogue of U-4-P, compound 1, was prepared by a reaction of the sodium salt of tert-butyl diethylphosphonoacetate with protected, 4-O-activated uridine followed by acetate deprotection and decarboxylation. It was found that this compound undergoes relatively facile dephosphonylation presumably via a metaphosphate intermediate. The difluoromethylene derivative, compound 2, was prepared by electrophilic fluorination of protected 1. This compound was stable and did not undergo dephosphonylation. Synthesis of the methylene analogue of 3-deazaU-4-P, compound 3, was achieved by ribosylation of protected 4-(phosphonomethyl)-2-hydroxypyridine. Electrophilic fluorination was also employed in the preparation of protected 4-(phosphonodifluoromethyl)-2-hydroxypyridine which was used as the key building block in the synthesis of difluoro derivative 4. These compounds represent the first examples of a nucleoside in which the base has been chemically modified with a methylene or difluormethylenephosphonate group.     

An unsymmetrical approach to the synthesis of bismethylene triphosphate analogues

A protected, unsymmetrical bismethylene triphosphate analogue was prepared by sequential Michaelis-Arbuzov reactions on ethyl bis(halomethyl)phosphinates. This species was monodeprotected at one of the terminal phosphonate groups in high yield. The resulting monodeprotected compound was used to achieve the first syntheses of the bismethylene triphosphate analogues of UTP and CTP.     

Investigation of kinetic and mechanism of triphenylphosphine addition to para‐naphthoquinone

This work reports the results of a kinetic and mechanistic investigations of the addition reaction of triphenylphosphine to para‐naphtoquinone in 1,2‐dichloromethane as solvent. The order of reaction with respect to the reactants was determined using initial rate method, and the rate constant was obtained on the basis of pseudo‐first‐order method. Variable time method using Uv–Vis spectrophotometry (at 400 nm) was utilized for monitoring this addition reaction, for which the following Arrhenius equation was obtained: The resulting activation parameters E_a, ΔH^#, ΔG^#, and ΔS^# at 300 K were 13.63, 14.42, 18.75 kcal mol^?1, and ?14.54 cal mol^?1K^?1, respectively. The results suggest that the reaction is first order with respect to both triphenylphosphine and para‐naphthoquinone. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 427–433, 2005     

Dynamical analysis and anti-oscillation-based adaptive control of the FO arch MEMS with optimality

Nonlinear Dynamics - This paper mainly investigates dynamical analysis and anti-oscillation-based adaptive control issues of the fractional-order (FO) arch microelectromechanical system (MEMS) with...     

Regio- and stereoselective synthesis of functionalized oxazolidin-2-ones from the reaction of α-epoxyketones with urea

A regio- and stereoselective synthesis of functionalized 4,5-disubstituted oxazolidin-2-ones is reported with moderate to good yields from the reaction of α-epoxyketones with urea in the presence of p-toluenesulfonic acid as the catalyst. Correspondence: Farzad Nikpour, Department of Chemistry, Faculty of Sciences, University of Kurdistan, P.O. Box 66315-416, Sanandaj, Iran.     

Asymptotically optimal blind estimation of multichannel images.

Optimal estimation of a two-dimensional (2-D) multichannel signal ideally decorrelates the data in both channel and space and weights the resulting coefficients according to their SNR. Many scenarios exist where the required second-order signal and noise statistics are not known in which the decorrelation is difficult or expensive to calculate. An asymptotically optimal estimation scheme proposed here uses a 2-D discrete wavelet transform to approximately decorrelate the signal in space and the discrete Fourier transform to decorrelate between channels. The coefficient weighting is replaced with a wavelet-domain thresholding operation to result in an efficient estimation scheme for both stationary and nonstationary signals. In contrast to optimal estimation, this new scheme does not require second-order signal statistics, making it well suited to many applications. In addition to providing vastly improved visual quality, the new estimator typically yields signal-to-noise ratio gains 12 dB or higher for hyperspectral imagery and functional magnetic resonance images.