Synthesis and Characterization of N‐methylenephenyl Phosphonic Chitosan

Chitosan is a natural based polymer obtained by alkaline deacetylation of chitin, exhibiting excellent properties such as non‐toxicity, biocompatibility and biodegradability. N‐Methylenephenyl phosphonic chitosan (NMPPC) is synthesized from chitosan by reacting with phenyl phosphonic acid using formaldehyde. The NMPPC was characterized by FTIR, ³¹P‐NMR, X‐ray diffraction, scanning electron microscopy, thermogravimeteric analysis and solubility studies. A significant decrease of molecular weight was observed in the NMPPC. The TGA studies suggested that NMPPC has less thermal stability than chitosan. The X‐ray diffraction analysis showed that NMPPC was amorphous in nature. The solubility property of the polymer was improved after the incorporation of a phenyl phosphonic group.     

Molecular Dynamics Simulation of Interaction between Calcite Crystal and Phosphonic Acid Molecules

The interactions between calcite crystal and seven kinds of phosphonic acids, nitrilotris(methylphosphonic acid) (NTMP), nitrilo‐methyl‐bis(methylphosphonic acid) (NMBMP), N,N‐glycine‐bis(methylphosphonic acid) (GBMP), 1‐ hydroxy‐1,1‐ethylenebis(phosphonic acid) (HEBP), 1‐amino‐1,1‐ethylenebis(phosphonic acid) (AEBP), 1,2‐ethylenediamine‐N,N,N′,N′‐tetrakis(methylphosphonic acid) (EDATMP), and 1,6‐hexylenediamine‐N,N,N′,N′‐tetrakis‐ (methylphosphonic acid) (HDATMP) have been simulated by a molecular dynamics method. The results showed that the binding energy of each scale inhibitor with the (1l?0) (1l?0) face of calcite crystal was higher than that with (104) face, which has been approved by the analysis of pair correlation functions. The sequence of scale inhibition efficiencies for phosphonic acids against calcite scale is as follows: EDATMP>HDATMP>HEBP>NTMP>GBMP>HEBP>NMBMP, and the growth inhibition on the (1l?0) face of calcite was at the leading status. Phosphonic acids deformed during the binding process, and electrovalent bonds formed between the phosphoryl oxygen atoms in phosphonic acids and the calcium ions on calcite crystal.     

Synthesis and Characterization of Novel Quaternary Ammonium RAFT Agents

Synthesis of three new cationic thio compounds suitable to control free‐radical polymerization according to the reversible addition fragmentation chain transfer (RAFT) process (reversible addition fragmentation transfer) is presented. Among them, two bear a quaternary ammonium group in the R group [i.e., N,N‐dimethyl‐N‐(4‐(((phenylcarbonothionyl)thio)methyl)benzyl)ethanammonium bromide and N‐(4‐((((dodecylthio) carbonothioyl)thio)methyl)benzyl)‐N,N‐dimethylethanammonium bromide, a dithioester and a trithiocarbonate, respectively]. The synthesis of a trithiocarbonate bearing an ammonium group in the Z group [i.e., 2‐((11‐((benzylthio)carbonothioyl)thio)undecanoyl)oxy)‐N,N,N‐trimethylammonium iodide] is also presented. Another three thio compounds, namely 1,4‐phenylenebis(methylene)dibenzenecarbodithioate, didodecyl‐1,4‐phenylenebis(methylene)bistrithiocarbonate, and 11‐(((benzylthio)carbonothioyl)thio)undecanoic acid, identified as other potentially interesting mono‐or difunctional RAFT agents, which were obtained as side products or intermediates, were isolated and fully characterized.     

Versatile Use of Chitosan and Hyaluronan in Medicine

Chitosan is industrially acquired by the alkaline N-deacetylation of chitin. Chitin belongs to the β-N-acetyl-glucosamine polymers, providing structure, contrary to α-polymers, which provide food and energy. Another β-polymer providing structure is hyaluronan. A lot of studies have been performed on chitosan to explore its industrial use. Since chitosan is biodegradable, non-toxic, bacteriostatic, and fungistatic, it has numerous applications in medicine. Hyaluronan, one of the major structural components of the extracellular matrix in vertebrate tissues, is broadly exploited in medicine as well. This review summarizes the main areas where these two biopolymers have an impact. The reviewed areas mostly cover most medical applications, along with non-medical applications, such as cosmetics.     

Glucose-lowering A ivity of Amino Acid- phosphonic Acid Oxovanadium Complexes and Its Interaction with DNA

Vanadium has well-documented lowering glucose properties both in vitro and in vivo. The design of new oxovanadium（IV） coordination compounds, intended for use as insulin-enhancing agents in the treatment of diabetes mellitus, can potentially benefit from a synergistic approach, in which the whole complex has more than an additive effect from its component parts. Biological testing with oxovanadium（IV） organic phosphonic acid, for insulin-enhancing potential included acute administration, by oral gavage in streptozotocin （STZ） diabetic rats. The complexes of oxovanadium（IV） amino acid-N-phosphonic acid exhibit higher lowering glucose activity in vivo. The interaction of the complexes of oxovanadium（IV） amino acid-N-phosphonic acid with DNA was investigated by agarose gel electrophoresis. The results indicated that these complexes have strong interaction with DNA.     

Chemical Modification and some Aligned Composites of Chitosan in a Filament State

The mono‐filaments (> 10 m in length) of chitosan and the blends of chitosan‐collagen, chitin‐collagen and chitin‐silk fibroin were wet‐spun. The mono‐filaments were chemically N‐modified with each of n‐fatty acid anhydrides, intra‐molecular carboxylic anhydrides, fragrant aldehydes and transition metal ions. The mono‐filament was aligned on a straight line with the mono‐filament of silk fibroin or poly(ethylene terephthalate) (PET), and a bundle of one to three mono‐filaments was coated with a medium of sericin (Se), chitosan or N‐acylchitosan to give rise to novel silk‐mimic filament composites. The filaments coated with a medium of sericin exhibited 26–27 denier for the titer, 2.46–3.36 gf · denier^?1 for the tenacity and 11.8–25.0% for the elongation. The apparent density (denier · μm^?1 in the filament diameter) of the filament composites was about 3–4 times higher than that of the mono‐filaments. Portion of fragrant aldehydes in Schiff's base was slowly hydrolyzed at room temperature by contacting with atmospheric moisture in the open air, and released from the fragrant filaments and composites. The filament composites coated with a chitosan medium were thrombogenic, and those coated with N‐acylchitosans were antithrombogenic.

An illustrated model for a silk‐mimic filament composite, N₀(N₂I‐FI).     

Studies of Co(II), Ni(II), Cu(II) and Cd(II) chelates with different phosphonic acids

Co(II), Ni(II), Cu(II) and Cd(II) chelates with 1-aminoethylidenediphosphonic acid (AEDP, H₄L¹), α-amino benzylidene diphosphonic acid (ABDP, H₄L²), 1-amino-2-carboxyethane-1,1-diphosphonic acid (ACEDP, H₅L³), 1,3-diaminopropane-1,1,3,3-tetraphosphonicacid (DAPTP, H₈L⁴), ethylenediamine-N,N′-bis(dimethylmethylene phosphonic)acid (EDBDMPO, H₄L⁵), O-phenylenediamine-N,N′-bis(dimethyl methylene phosphonic)acid (PDBDMPO, H₄L⁶), diethylene triamine-N,N,N′,N′,N″N″-penta(methylene phosphonic)acid (DETAPMPO, H₁₀L⁷) and diethylene triamine-N,N″-bis(dimethyl methylene phosphonic)acid (DETBDMPO, H₄L⁸) have been synthesised and were characterised by elemental and thermal analyses as well as by IR, UV–VIS, EPR and magnetic measurements. The first stage in the thermal decomposition process of these complexes shows the presence of water of hydration, the second denotes the removal of the coordinated water molecules. After the loss of water molecules, the organic part starts decomposing. The final decomposition product has been found to be the respective MO·P₂O₅. The data of the investigated complexes suggest octahedral geometry with respect to Co(II) and Ni(II) and tetragonally distorted octahedral geometry with respect to Cu(II). Antiferromagnetism has been inferred from magnetic moment data. Infrared spectral studies have been carried out to determine coordination sites.     

A Simple and Convenient Strategy for the Synthesis of Novel Ten,Twelve, and Fourteen‐membered Phosphorus Macrocyclic Compounds

Synthesis of the title compounds 4(a – i) was accomplished through a two‐step process. The synthetic route involves the cyclization of equimolar quantities of 2,2′‐methylene(methyl)bis(4,6‐di‐tert‐butyl‐phenol) ( 1 ) with tris‐(2‐chloro‐ethyl) phosphite ( 2a ), tris‐(2‐bromo‐ethyl) phosphine ( 2b ), and tris‐bromo methyl phosphine ( 2c ) in the presence of sodium hydride in dry tetrahydrofuran at 45–50°C. They were further converted to the corresponding oxides, sulfides, and selenides under N₂ atmosphere by reacting them with hydrogen peroxide, sulfur, and selenium, respectively ( 4a – c , 4d – f, and 4g – i ). But the compounds 6a , b were prepared by the direct cyclocondensation of equimolar quantities of 1 with (2‐chloro‐ethyl)‐phosphonic acid dibromomethyl ester ( 5a ) and (2‐chloro‐ethyl)‐phosphonic acid bis(2‐bromo‐ethyl) ester ( 5b ) in the presence of sodium hydride in dry tetrahydrofuran at 45–50°C in moderate yields. All the newly synthesized compounds 4 ( a – i ) and 6 ( a – b ) exhibited moderate in vitro antibacterial and antifungal activities.     

Studies on N-methylene phosphonic chitosan

N-methylene phosphonic (NMPC) chitosan was studied by several techniques to determine their properties in aqueous solution and its capacity to emulsify edible oils. The phosphonic groups are all equivalent and their ionization constants were estimated (pK _a1=6.45 and pK _a2=11.75). The chitosan derivative in pure water starts to aggregate at 0.09% w/v, and the aggregates’ structure at 0.5% w/v. Unlike pure chitosan, NMPC chitosan is strongly surface active. Its hydrophile-lipophile balance (HLB) value was estimated in 37, very similar to that of chitosan. As a consequence, it favors the formation of oil in water (o/w) emulsions with scarce water/oil/water (w/o/w) droplets.     

Regioselective synthesis and biological activity of oxidized chitosan derivatives

Oxidized chitosan derivatives with various degrees of oxidation (DS, 0.1–1.0) were prepared by the treatment of chitosan with CrO₃/aq HClO₄ or by the oxidation of ­3‐O‐ and N‐protected chitosan with 30% aq H₂O₂/Na₂WO₄ followed by 3‐O‐ and N‐deprotection. The oxidized products were then N‐acetylated with Ac₂O in order to improve their water‐solubility. Although the oxidized chitosan derivative of DS 0.28 and the degree of N‐acetylation of chitosan (DA) 38% was insoluble in the pH 3–8 region, that of DS 0.26 and DA 76% was soluble in the neutral pH range. The newly‐prepared acetylated and oxidized chitosan derivatives were found to suppress the chemiluminescence response of inflammatory cells such as canine polymorphonuclear cells (PMNs). Analysis by the surface plasmon resonance method revealed that the bind and release behavior of PMNs to acetylated oxidized chitosan derivatives was similar to that against carboxymethylated chitosan derivatives. The amount of water‐soluble chitosan derivative bound to cytokine IL‐8 was found to be affected by the structural and electronic features of the chitosan substituents in the chitosan chain. Copyright © 2003 John Wiley & Sons, Ltd.     

Heterogeneous chloroacetylation of chitosan powder in the presence of sodium bicarbonate

Because of the importance of the chloroacetyl group to carbohydrate synthesis, the objective of this work is to disclose a method that has been found useful for the heterogeneous chloroacetylation of chitosan powder in which sodium bicarbonate is used as the base for the neutralization of the acid byproduct. A series of reactions were conducted to determine the more optimal conditions under which to perform acylation. The three varied aspects of the reaction were the acylating reagent (chloroacetyl chloride and chloroacetic anhydride), the solvent (methylene chloride and N,N‐dimethylformamide), and the temperature (0 or 44 °C). According to Fourier transform infrared (FTIR), the chitosan powder being refluxed in methylene chloride in the presence of chloroacetic anhydride constituted the best conditions. By incorporating these conditions and increasing the amount of the base, we obtained a chloroacetylated chitosan powder that, characterized by FTIR, solid‐state cross‐polarity/magic‐angle spinning ¹³C NMR, and elemental analysis, had degrees of N‐ and O‐chloroacetylation of 0.32 and 0.15, respectively. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 4174–4181, 2001     

Effective methylation of phosphonic acids related to chemical warfare agents mediated by trimethyloxonium tetrafluoroborate for their qualitative detection and identification by gas chromatography-mass spectrometry

The effective methylation of phosphonic acids related to chemical warfare agents (CWAs) employing trimethyloxonium tetrafluoroborate (TMO·BF₄) for their qualitative detection and identification by gas chromatography-mass spectrometry (GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be conveniently carried out at ambient temperature, thus providing a safer alternative to the universally employed diazomethane-based methylation protocols. Optimization of the methylation parameters led us to conclude that methylene chloride was the ideal solvent to carry out the derivatization, and that even though methylated products can be observed surfacing after only 1 h, additional time was not found to be detrimental but beneficial to the process particularly when dealing with analytes at low concentrations (∼10 μg mL⁻¹). Due to its insolubility in methylene chloride, TMO·BF₄ conveniently settles to the bottom during the reaction and does not produce additional interfering by-products that may further complicate the GC-MS analysis. The method was demonstrated to successfully methylate a variety of Schedule 2 phosphonic acids, including their half esters, resulting in derivatives that were readily detected and identified using the instrument's spectral library. Most importantly, the method was shown to simultaneously methylate a mixture of the organophosphorus-based nerve agent hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 μg mL⁻¹ concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O3) featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW) Proficiency Test. In addition, the protocol was found to effectively methylate N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid that are products arising from the oxidative degradation of the V-series agents VR and VX respectively. The work described herein represents the first report on the use of TMO·BF₄ as a viable, stable and safe agent for the methylation of phosphonic acids and their half esters and within the context of an OPCW Proficiency Test sample analysis.     

Synthesis and Antimicrobial Activity of Some Novel Hydrazide,Pyrazole, Triazine,Isoxazole, and Pyrimidine Derivatives

In continuation of our efforts to find a new class of antimicrobial agents, a series of pyrazole, 1,2,4‐triazine, isoxazole, pyrimidine, and other related products containing a hydrazide moiety were prepared via the reaction of 2‐cyano‐N‐((2‐methoxynaphthalen‐1‐yl)methylene) acetohydrazide ( 1 ) with appropriate chemical reagents. These compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration against most of test organisms was performed. Among the tested compounds 4 , 5 , 6 , and 16 displayed excellent antimicrobial activity. All the synthesized products were confirmed by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral data.     

Effect of chemical structure on the properties of some hydrogels prepared by using gamma radiation polymerization

Several hydrogels were prepared using radiolytic polymerization of aqueous solutions of acrylamide or acrylamide containing appropriate comonomer such as acrylic acid, maleic acid, itaconic acid, and maleic anhydride. The hydrogels have been prepared at an irradiation dose of 30 kGy. The effects of the chemical structure of the monomer(s) and crosslinking agents on the yield of homopolymer(s) or copolymers have been studied. These crosslinking agents include N, N′‐methylene dimethacrylate (MDA) and N, N′‐methylene bisallyamide (MBA). The hydrogels obtained were characterized using swelling technique, thermal and spectroscopic analysis. The results obtained showed that the prepared samples are able to reject sodium ions and are not able to recover the Basic Blue Dye from their aqueous solution. © 2005 John Wiley & Sons, Ltd.     

Ligand‐Free,Cu‐ and Fe‐Catalyzed Selective Ring‐Opening Arylations of Benzoxazoles with Aryl Iodides

Cu‐ or Fe‐based catalyst systems have been reported to selectively catalyze the N,N‐diarylation or N‐monoarylation of benzoxazoles ring‐opening with aryl iodides in the absence of additional added ligand in polyethylene glycol under an inert atmosphere. Two types of coupling products (triphenylamines and diphenylamines) have been examined and the reaction routes can be simply controlled by changing the metal salts (Cu or Fe) as catalyst. A range of substrates have been investigated for the diverse reactions, and the corresponding arylation products were achieved in good to high yields. This selective, low‐cost, and environmentally friendly protocol displays great potential for replacing existing methodologies as well as extending the synthetic applications of benzoxazoles.     

Studies on Lyotropic Liquid‐Crystalline N‐Alkyl Chitosans in Formic Acid

A series of derivatives of chitosan – N‐alkyl(methyl, ethyl, propyl and butyl) chitosans – were synthesized from completely deacetylated chitosan. The degree of substitution (from 0.15 to 0.81) of the N‐ethyl chitosan were obtained by controlling the molar ratio of the reactants. All the products showed lyotropic liquid‐crystalline properties regardless of the length of the side chains and the degree of substitution. The critical concentration (C*) of the samples were measured by both microscopy and refractometry. C* seemed not to vary with the degree of substitution (ds) in the case of a given subsitituent chain, but rose dramatically depending on the length of the substituent group as this was varied from methyl to butyl. The results were explained according to Flory's classical theory as well as experimental of X‐ray diffraction measurements.     

Chiral stationary phases based on chitosan bis(4‐methylphenylcarbamate)‐(alkoxyformamide)

Highly N‐deacetylated chitosan was chosen as a natural chiral origin for the synthesis of the selectors of chiral stationary phases. Therefore, chitosan was firstly acylated by various alkyl chloroformates yielding chitosan alkoxyformamides, and then these resulting products were further derivatized with 4‐methylphenyl isocyanate to afford chitosan bis(4‐methylphenylcarbamate)‐(alkoxyformamide). A series of chiral stationary phases was prepared by coating these derivatives on 3‐aminopropyl silica gel. The content of the derivatives on the chiral stationary phases was nearly 20% by weight. The chiral stationary phases prepared from chitosan bis(4‐methylphenylcarbamate)‐(ethoxyformamide) and chitosan bis(4‐methylphenylcarbamate)‐(isopropoxyformamide) comparatively showed better enantioseparation capability than those prepared from chitosan bis(4‐methylphenylcarbamate)‐(n‐pentoxyformamide) and chitosan bis(4‐methylphenylcarbamate)‐(benzoxyformamide). The tolerance against organic solvents of the chiral stationary phase of chitosan bis(4‐methylphenylcarbamate)‐(ethoxyformamide) was investigated, and the results revealed that this phase can work in 100% ethyl acetate and 100% chloroform mobile phases. Because as‐synthesized chiral selectors did not dissolve in many common organic solvents, the corresponding chiral stationary phases can be utilized in a wider range of mobile phases in comparison with conventional coating type chiral stationary phases of cellulose and amylose derivatives.     

Kinetics and mechanism of gas‐phase pyrolysis of N‐aryl‐3‐oxobutanamide ketoanilides,their 2‐arylhydrazono derivatives,and related compounds

Rates and products of reaction and Arrhenius activation parameters were determined for the gas‐phase thermolysis of 14 substrates of the title compounds using sealed pyrex reactor tubes and HPLC/UV‐VIS to monitor substrate pyrolysis. The 14 compounds under study are N‐phenyl‐3‐oxo‐ ( 1 ), N‐(p‐chlorophenyl)‐3‐oxo‐ ( 2 ), N‐(p‐methylphenyl)‐3‐oxo‐ ( 3 ), and N‐(p‐methoxyphenyl)‐3‐oxobutanamide ( 4 ), in addition to (i) four substrates ( 5–8 ) obtained by the replacement of the pairs of methylene hydrogens at the 2‐position of compounds ( 1–4 ), each pair by a phenylhydrazono group; (ii) three arylhydrazono derivatives ( 9–11 ) in which Cl, CH₃, or OCH₃ groups are substituted at the para position of the phenylhydrazono moiety of compound 5 ; (iii) 3‐oxobutanamide (acetoacetamide, 12 ), N‐phenyl‐3‐oxo‐3‐phenylpropanamide ( 13 ), and N,N′‐diphenylpropanediamide ( 14 ). The reactions were conducted over 374–546 K temperature range, and the values of the Arrhenius log A(s^?1) and E_a(kJ mol^?1) of these reactions were, respectively, 12.0 ± 2.0 and 119.2 ± 17.0 for the ketoanilides ( 1–4, 12–14 ), and 13.0 ± 0.7 and 157.5 ± 8.6 for the arylhyrazono compounds ( 5–11 ). Kinetically, the arylhydrazono derivatives were found to be ca. 1.4 × 10³ to 5.7 × 10³ times less reactive than the parent ketoanilides. A mechanism is proposed to account for reaction products and to rationalize molecular reactivities. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 39: 82–91, 2007     

Cloning and Expression of Chitinase A from Serratia Marcescens for Large‐Scale Preparation of N,N‐Diacetyl Chitobiose

The gene of Serratia marcescens chitinase A (chiA) was cloned by PCR. The complete gene was constructed into a pRSET vector and expressed in Escherichia coli. The recombinant enzyme was purified to > 90% homogeneity by hydrophobic interaction chromatography followed by ion‐exchange separation. Measured with an electrospray‐ionization mass spectrometer, the molecular mass of the protein was 58,607 Da, consistent with a theoretical calculation of the deduced protein without the signal peptide. The recombinant enzyme was characterized and tested for the preparation of chitobiose. In general, the recombinant Chtinase A exhibited an exo‐type catalytic activity toward colloidal chitin and released both N‐acetylglucosamine and N,N‐diacetyl chitobiose as products. After extensive testing, we produced N,N‐diacetyl chitobiose as the predominant product when the enzymatic reaction was performed in sodium acetate buffer at pH 5.5; under such conditions, an enzymatic process is established for the production of the disaccharide on a 100‐g scale.