Studies on the Synthesis and Properties of Temperature Responsive and Biodegradable Hydrogels

Novel linear poly(NIPA‐co‐CL) copolymers have been synthesized by radical copolymerization of N‐isopropylacrylamide (NIPA) and 2‐methylene‐1,3‐dioxepane (MDO). The structure of copolymers was confirmed by ¹H NMR and IR spectroscopy. Cross‐linked poly(NIPA‐co‐CL) hydrogels have also been prepared in toluene using N,N′‐methylenebisacrylamide as cross‐linking agent. The hydrogels thus obtained exhibit good temperature response and are biodegradable in the presence of proteinase K.

Temperature influence on the enzymatic degradation by proteinase K of poly(NIPA‐co‐CL) hydrogel (G‐60).     

Purification and characterization of recombinant pyrrolidone carboxyl peptidase of Bacillus subtilis.

Bacillus subtilis pyrrolidone carboxyl peptidase (Pcp) overexpressed in Escherichia coli was purified to homogeneity in less than 12 h using ammonium sulphate precipitation and hydrophobic interaction chromatography. The enzyme, which removes amino-terminal L-pyroglutamic acid from peptides, appears to be a tetramer of 25,200 molecular mass subunits. The protein cross-reacted with polyclonal antibodies raised against Pcp from Streptococcus pyogenes. The overexpressed enzyme exhibits an absolute substrate specificity towards N-terminal pyroglutamyl residues with a Michaelis constant of 1.04 mM for L-pyroglutamyl-beta-naphthylamide. The enzyme could be used for the removal of pyroglutamyl residues that block amino termini of proteins and peptides before performing Edman sequential degradation.     

Target-templated de novo design of macrocyclic d-/l-peptides: discovery of drug-like inhibitors of PD-1

Peptides are a rapidly growing class of therapeutics with various advantages over traditional small molecules, especially for targeting difficult protein–protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing bioactive cyclic topologies that go beyond natural l-amino acids. Here, we report a generalizable framework that exploits the computational power of Rosetta, in terms of large-scale backbone sampling, side-chain composition and energy scoring, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we developed two new inhibitors (PD-i3 and PD-i6) of programmed cell death 1 (PD-1), a key immune checkpoint in oncology. A comprehensive biophysical evaluation was performed to assess their binding to PD-1 as well as their blocking effect on the endogenous PD-1/PD-L1 interaction. Finally, NMR elucidation of their in-solution structures confirmed our de novo design approach.

In silico design of heterochiral cyclic peptides that bind to a specific surface patch on the target protein (PD-1, in this case) and disrupt protein–protein interactions.     

Three New Neolignans from the Aril of Myristica fragrans

Three new neolignans, named 1‐deoxycarinatone ( 1 ), isodihydrocarinatidin ( 2 ), and isolicarin A ( 3 ), together with the known neolignan (+)‐dehydrodiisoeugenol ( 4 ), were isolated from mace (the aril of Myristica fragrans Houtt .). Their structures were elucidated as 2‐[(1S)‐2‐(4‐hydroxy‐3‐methoxyphenyl)‐1‐methylethyl]‐6‐methoxy‐4‐(prop‐2‐enyl)phenol ( 1 ), 4‐[(2R,3R)‐2,3‐dihydro‐7‐methoxy‐3‐methyl‐5‐(prop‐2‐enyl)benzofuran‐2‐yl]‐2‐methoxyphenol ( 2 ), and 4‐{(2S,3R)‐2,3‐dihydro‐7‐methoxy‐3‐methyl‐5‐[(1E)‐prop‐1‐enyl]benzofuran‐2‐yl}‐2‐methoxyphenol ( 3 ) on the basis of spectroscopic data.     

Oxidative Methyl Esterification of Primary Alcohols with Iodine‐Mediated Poly[4‐(Diacetoxyiodo)Styrene]

An operationally simple oxidative methyl esterification of primary alcohols in good yields using an iodine‐mediated poly[4‐(diacetoxyiodo)styrene] in methanol at room temperature is described. The polymeric reagent can be regenerated and reused as an environmentally benign reagent.     

Synthesis of well‐designed polymers carrying saccharide moieties via RAFT miniemulsion polymerization

Two hydrophobic vinyl saccharide monomers based on D ‐glucose and D ‐fructose were polymerized by employing the reversible addition‐fragmentation transfer (RAFT) miniemulsion polymerization technique to prepare well‐designed glycopolymers. Three dithiobenzoate‐RAFT agents [S?C(Ph)S? R], 1‐phenylethyl dithiobenzoate (PED), 2‐phenylprop‐2‐yl dithiobenzoate (PPD), and 2‐cyanoprop‐2‐yl dithiobenzoate (CPD), were used to control the growth of polymer chains. The best results were obtained in the presence of the PPD‐RAFT agent and the formed polymers have polydispersity index's (PDI) lower than 1.15. Under adequate miniemulsion polymerization conditions, a glycopolymer with PDI of 1.1 and molecular weight of 5 × 10⁴ g/mol has been successfully synthesized in a short reaction time of 100 min. Furthermore, some block copolymers containing saccharide segment with butyl or methyl methacrylate were prepared. Copyright © 2007 John Wiley & Sons, Ltd.     

Theoretical study of 3d‐metal mononitrides using DFT method

3d‐Metal mononitrides are studied using the density functional theory method. The lowest spin state for these dimers is obtained using the B3LYP hybrid functional with the 6‐311+G* basis set. The equilibrium geometries, vibrational frequencies, binding energies, Mulliken, and natural orbital population analysis charges, natural orbital electronic configuration, electron affinity, and ionization potential are obtained. Mulliken as well as natural orbital population analysis charges indicate that for all dimers, in cations most of the positive charge localized on the transition metal atom where in anions most of the negative charge localized on nitrogen atom. The binding energies for 3d‐metal mononitrides are higher than those for monocarbides and monoxides. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

呋喃西林水溶液在光和热作用下的稳定性

The influence of both light and heat on the stability of nitrofurazone aqueous solution was studied. Results show that in either heating experiments or the exposure to light at high temperatures, the degradation rate obeyed zero-order kinetics. The total rate constant ktotal caused by both light and heat can be divided into two parts: ktotal =kdark klight, where kdark and klight are the degradation rate constants caused by heat and light, respectively. The klight can be expressed as klight=Alight*exp(-Ea,light/RT)*E, where E is the illuminance of light, and Alight and Ea,light both are experimental constants. The values of these kinetic parameters were determined based on the experiments in the dark and upon exposure to three different light sources. Results show that the values of Alight and Ea, light varied with the light source. To save time, labor, and drugs, exponential heating experiments were employed and compared with the isothermal experiments. Results indicated that kinetic parameters obtained by exponential heating experiments are comparable to those obtained by isothermal experiments either in the dark or upon exposure to light.     

Synthesis of Carboxylated Monodisperse Latexes and Their Self-Organization in Thin Films

The capability of carboxylated latexes of poly(methyl methacrylate) and copolymers of styrene with glycidyl methacrylate or methacrylic acid for self-organization in thin films was studied in relation to the compositions of the dispersion medium and polymer and to the latex particle size.__________Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 1, 2005, pp. 161–167.Original Russian Text Copyright © 2005 by Men’shikova, Shabsel’s, Evseeva, Shevchenko, Bilibin.     

Theoretical study of the electronic spectrum of binuclear gold(I) complexes

The electronic structure and the spectroscopic properties of [Au₂(CS₃)₂]^?2, [Au₂(pym‐2‐S)₂] (pym = pyrimidethiolate), [Au₂(dpm)₂]⁺² (dpm = bis(diphosphino)methane) were studied using density functional theory (DFT) at the B3LYP level. The absorption spectrum of these binuclear gold(I) complexes was calculated by single excitation time‐dependent (TD) method. All complexes showed a ¹(5dσ* → 6pσ) transition associated with a metal–metal charge transfer, which is strongly interrelated with the gold–gold distance. Furthermore, we have calculated the frequency of the gold–gold vibration (ν_Au2) on the above complexes. The values obtained are theoretically in agreement with experimental range. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005