A GPC Method for Analysis of Low Molecular Weight Drugs

Abstract

Gel permeation chromatography has been shown as a versatile method for the analysis of low molecular weight drugs. Aspirin and its hydrolysis product, salicylic acid, which differ in a molecular weight of 42 units have been efficiently separated by a retention time difference of 3.25 minutes. Qualitative idea of other impurities is also obtained.     

Viscosity Molecular Weight Determination of Polyadenylic Acid

Abstract

In this study viscosity measurements of polyadenylic acid (PolyA) in aqueous solution were carried out under different conditions. In the absence of any additives, the polymer degraded during flow through the capillary of a viscometer or when standing still. Degradation during the former was more severe. The degradation of polyadenylic acid can be prevented by addition of an electrolyte such as KCl to increase the ionic strength. However, in this case the deviation from linearity was still considerable at most ionic strength values. The best fit to the Huggins and Kraemer equations was obtained using a Tris–EDTA buffer solution with a final pH of 7.65. Estimation from intrinsic viscosity and weight-average molecular weight values gave k and α as 2.04 × 10^?5 and 0.89 from the equation η = kM ^α. The difference between Huggins (k ₁) and Kraemer (k ₁′) constants was close to 0.50 for all measurements.     

A Study of the Molecular Weight Distribution of Poly(Amino Acid)s Synthesized by Diphenyl Phosphoryl Azide

Abstract

Direct polycondensations of β-benzyl-l-aspartate (Asp.Bz) and β-benzyl-l-glutamate (Glu.Bz) were carried out in the presence of diphenyl phosphoryl azide (DPPA) as a condensation agent and triethyl amine (TEA). Poly(amino acid)s were obtained by this convenient approach whose structure was confirmed by IR and ¹H-NMR spectroscopy. The effects of the monomer concentration, the polymerization time and temperature, the ratios [DPPA]/[monomer] and [TEA]/[monomer], and the solvent used on the molecular weight distribution of the polymer were studied. When the monomer concentrations were higher than 0.2 g/mL, poly(Asp.Bz) with a bimodal molecular weight distribution was obtained (M_w of 37,000 and M_w/M_n of 1.68). The polycondensations carried out in THF or in bulk provided the highest molecular weight (M_w ? 40,000). Several other amino acids were also polymerized by DPPA.     

Enzymatic Synthesis of Phosphoric Monoesters with Alkaline Phosphatase in Reverse Hydrolysis Conditions

Abstract

Title compounds were synthesized on a preparative scale using alkaline phosphatase, orthophosphoric monoester phosphohydrolase E.C. 3.1.3.1, in reverse hydrolysis conditions. Optimization for one of the 25 Fhosphoryl acceptors hvestfgated (glycerol) shovs that up to 55% synthesis yield can be obtained using a large excess of substrate, conditions in which the enzymatic activity remains high. From the results obtained with different phosphoryl group donors, phosphate, pyrophosphate and polyphosphates and with enzymes of different sources, it comes up that the best results are obtained with pyrophosphate and with the weakly purified calf intestine alkaline phosphatase. The extent of enzymatic hydrolysis of the donor can be reduced owing to the existence of two different pH optima for the two reactions, phosphorylation and hydrolysis. The synthesis can be also performed using inert co-solvents which allow to reduce the amount of acceptor used, as long as Zn⁺⁺ is added to the reaction medium. The results are discussed in terms of the catalytic mechanism of alkaline phosphatase.     

Synthesis and Characterization of Poly(ether ether ketone)s with (2,5‐dihydroxy)phenyl Side Group

A new monomer, (2,5‐dimethoxy)phenylhydroquinone (DMPH), was prepared in a two‐step synthetic procedure. One aromatic poly(ether ether ketone)s with 2,5‐dimethoxy phenyl side group (DMP‐PEEK) was synthesized via an aromatic nucleophilic substitution reaction with 4,4′‐difluorobenzophenone (DFB). Poly(ether ether ketone)s with 2,5‐dihydroxy phenyl side group (DHP‐PEEK) was obtained via hydrolysis of methoxy group on the DMP‐PEEK. Both of the high molecular weight polymers could be obtained despite the steric effect of the bulky pendant groups. The two polymers have good solubility at room temperature.     

Malonaldehyde Synthesis

Abstract

Pure malonaldehyde is obtained by organic synthesis. In the first step, malonaldehyde sodium salt is obtained by 1,1,3,3-tetramethoxypropane acidic hydrolysis and purified by recrystallization in methanol/ether. In the second step, malonaldehyde is synthesized by reaction between malonaldehyde sodium salt and gaseous hydrochloric acid dissolved in ether at ? 40 °C. Finally, malonaldehyde is purified by pumping at temperatures less than 0 °C and extracted by sublimation.     

Molecular Weight Distributions and Monodisperse Intrinsic Viscosity-Molecular Weight Equation of Silicone Elastomer

Abstract

The experimental curves of Gel Permeation Chromatography of methyl vinylsilicone elastomer polymerized by a basic catalyst and containing a small amount vinyl groups are given.

They are in consistent with the theoretical curves calculted from logarithmic-normal distribution function. Thereby, the molecular weight distribution of the samples determined belong to the logarithmic-normal distribution. With GPC, [η] and 〈M〉_n of the polydispersed sample the monodispersed [η]-M relationship of the methyl vinyl silicone elastomer was established.

This relation agrees with the monodispersed [η]-M relation established by Qian Ren-yuan, et al.⁽¹⁾     

Studies on Simultaneous Molecular Weight and Spreading Calibration in Steric Exclusion Liquid Chromatography

Abstract

Two improved methods of molecular weight calibration are described where simultaneously parameters of a symmetrical spreading function are obtained through the use of polymolecular molecular weight standards and of average retention volumes. In the first method a linear molecular weight calibration is assumed and the second method is based on a universal molecular weight calibration curve obtained with narrow MWD polystyrene standards.

The proposed methods have been tested using two polymolecular polystyrene standards confirming good convergence of the applied iteration procedures and giving very promising results.     

Olefin Polymerizations and Copolymerizations with Aluminum Alkyl-Cocatalyst Systems. V. The Molecular Weight and Molecular Weight Distribution of Polystyrene

Abstract

The polymerization of styrene with the cationic initiator system AlR₂Cl/RCl was investigated further. Earlier conclusions [1] were corroborated and expanded by an analysis of the number and weight average molecular weights. Alkyl halides with low (high) R?Cl bond dissociation energies are efficient (poor) coinitiators of the polymerization of styrene. In the presence of efficient RCl coinitiators, the molecular weights strongly decrease and the molecular weight distributions strongly increase with increasing conversions (Fig. 1). With poor cointiators, only low conversions are obtained even in the presence of large amounts of AlEt₂Cl. The data are discussed in terms of a previously proposed mechanism [1].     

Generalized Universal Molecular Weight Calibration Parameter in GPC

Abstract

In this report we show by experimental and theoretical investigations that the commonly used GPC universal calibration parameter, the intrinsic viscosity multiplied by the weight average molecular weight ([η] M^w) is incorrect. The error which can arise by using [η] M to calculate the molecular weight across the GPC chromatogram for nonuniformly branched polymers [poly(vinyl acetate) and low density polyethylene] and copolymers with compositional drift, could be very large. We also show conclusively that the number average molecular weight M_n is the correct average to use for the universal calibration parameter. We therefore recommend that our general universal Calibration parameter [η] M_n be used for calculating the molecular weight across the chromatogram for all polymer systems (linear and branched homopolymers, copolymers with or without compositional drift and for polymer blends).     

Universal Calibration and Molecular Weight Averages in Gel Permeation Chromatography Illustrated by Cellulose Nitrate and Poly(oxypropylene)

Abstract

The nature of the averaging process in the analysis of gel permeation chromatograms was examined for cases where the molecules in the detector cell of the apparatus were of different molecular weight and of the same molecular weight. When the molecules have the same molecular weight, the hydrodynamic volume (1), [?]M, averaged across a chromatogram was found to become KM^a+1 for any molecular weight average at the elution volume corresponding to that average. [η] is intrinsic viscosity, M is molecular weight, and K and a are the appropriate Mark-Houwink constants. Thus when size separation is by molecular weight, the universal GPC calibration functions include KM_n ^a+1 where M_n is the number average molecular weight.

Cellulose nitrate and poly(oxypropylene) were analyzed using three sets of columns and two GPC instruments. KM_n ^a+1, KM_w ^a+1, and [η]M_w were found to represent the hydrodynamic volume since these functions fell on the universal calibration plot for nearly nono-disperse polystyrene standards. The function [η]M_n was displaced from the polystyrene universal calibration plot by factor which equaled M_w/M_n. The slopes and intercepts of the universal calibration plots were found to be completely consistent with the slopes and intercepts of the molecular weight calibration plots showing that the Mark-Houwink constants were correct. Intrinsic viscosity - molecular weight relations were presented for 12.0–12.6%N cellulose nitrate and for low molecular weight poly(oxypropylene), the latter relation being a correction of that of Sholtan and Lie (18).     

Synthesis of New Pyrimidine,Quinazoline and Diazatricyclo Derivatives by Multicomponent Reaction and Evaluation of Their Biological Activity

Abstract

A series of new pyrimidine and quinazoline derivatives was synthesized by a Biginelli-like reaction of urea/thiourea, aldehyde, and ketone in the presence of hydrochloric acid as a catalyst. In a similar way, some novel diazatricyclo derivatives were obtained via a Biginelli-like reaction followed by an intramolecular Michael-type addition. The yields of products were reasonable after recrystallization from ethanol. All newly synthesized compounds were characterized using IR and NMR (¹H and ¹³C) spectroscopy and elemental analysis. The antibacterial activity of these compounds was investigated against Staphylococcus aureus (RTCC, 1885), and Escherichia Coli (ATCC, 35922).

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis,Spectroscopic Studies,and Antifungal Activity of Tris(O-Alkyl or O-Aryltrithiophosphato) Aluminum(III)

Abstract

Aluminum(III) derivatives of O-alkyl or O-aryl trithiophosphate of the type Al[S₂P(SH)OR]₃ (R = Me, Et, Prⁱ, Buⁱ, Ph, CH₂Ph) have been synthesized. The products were obtained as white powdery solids. The monomers are soluble in common organic solvents and were characterized by elemental analyses, molecular weight determinations, and IR and (¹H, ²⁷Al, and ³¹P) NMR spectroscopic studies, which are consistent with six coordinated aluminum and bidentate behavior of the trithiophosphate moiety. The products also exhibit antifungal effectiveness against powdery mildew disease.     

The Effect of Molecular Weight on the Thermal Properties of Polystyrene-Based Sidechain Liquid-Crystalline Polymers

Abstract

Sidechain liquid-crystalline polymers were prepared by the derivatization of three poly(4-hydroxystyrene) fractions of different molecular weights (M_w = 1.0 × 10⁴, 2.2 × 10⁴ and 3.0 × 10⁴). 4-Cyanoazobenzene and 4-cyanobiphenyl were incorporated as mesogenic groups with ether-linked methylene spacers of varying length. The polymers all exhibited a smectic A phase, with the exception of the propyl member of the cyanobiphenyl series for which no liquid-crystalline behavior was observed. For short spacers the thermal properties were insensitive to molecular weight changes in the backbone, whereas small but consistent differences in the transition temperatures and entropies were observed as the number of methylene groups in the spacer increased.     

微波辐射下5-取代-2-硫代海因衍生物的合成

微波辐射下, 由硫氰酸铵与α-氨基酸通过两步反应合成了11种5-取代-2-硫代海因衍生物, 并用¹H NMR, IR和元素分析确证了中间产物和终产物的结构. 对比常规加热方法, 微波辐射具有反应时间短(4 min), 每步反应产率高(85%～93%)的优点. 同时对合成化合物2h的反应历程进行了讨论.     

THE SYNTHESIS OF DISODIUM O-n-ALKYLTHIOPHOSPHATES

Abstract

The disodium O-alkylthiophosphates were synthesized by reaction of PSCl₃ with the corresponding alcohols to the O-alkylphosphorodichloridothioates (1), which were hydrolyzed in aqueous triethylamin–sodium acetate solution.¹ The O-alkylthiophosphates (2) were isolated as barium salts and converted to the disodium salts by Na₂SO₄.

Because the barium salts of O-ethyl- and O-n-propyl-thiophosphate were soluble in water, the corresponding dichlorido compounds were hydrolyzed directly to the disodium salts in aqueous sodium hydroxide plus dioxane according to Gray and Hamer.²

Further purification was achieved by column chromatography on Sephadex LH20 using water as an eluant. Pure products, which were not contaminated by either inorganic thiophosphate or O-alkylphosphates, were thus obtained.     

Synthesis and characterization of biodegradable poly(L-aspartic acid-co-PEG)

The melt polycondensation reaction of the prepolymer prepared from N-(benzyloxycarbonyl)-L -aspartic acid anhydride (N-CBz-L -aspartic acid anhydride) and low molecular weight poly(ethylene glycol) (PEG) using titanium isopropoxide (TIP) as a catalyst produced the new biodegradable poly(L -aspartic acid-co-PEG). This new copolymer had pendant amine functional groups along the polymer backbone chain. The optimal reaction conditions for the preparation of the prepolymer were obtained by using a 0.12 mol % of p-toluenesulfonic acid with PEG 200 for 48 h. The weight-average molecular weight of the prepolymer increased from 1,290 to 31,700 upon melt polycondensation for 6 h at 130°C under vacuum using 0.5 wt % TIP as a catalyst. The synthesized monomer, prepolymer, and copolymer were characterized by FTIR, ¹H- and ¹³C-NMR, and UV spectrophotometers. Thermal properties of the prepolymer and the protected copolymer were measured by DSC. The glass transition temperature (T_g) of the prepolymer shifted to a significantly higher temperature with increasing molecular weight via melt polycondensation reaction, and no melting temperature was observed. The in vitro hydrolytic degradation of these poly(L -aspartic acid-co-PEG) was measured in terms of molecular weight loss at different times and pHs at 37°C. This pH-dependent molecular weight loss was due to a simple hydrolysis of the backbone ester linkages and was characterized by more rapid rates of hydrolysis at an alkaline pH. These new biodegradable poly(L -aspartic acid-co-PEG)s may have potential applications in the biomedical field. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2949–2959, 1998     

Application of Capillary Zone Electrophoresis for the Analysis of Low Molecular Weight Organic Acids in Environmental Samples

Abstract

The applicability of a recently developed capillary zone electrophoretic (CZE) method for the determination of low molecular weight (LMW) organic acids in water was tested on five types of environmental samples (rainwater, water extract from peat, and soil water from two polluted sites). A full baseline resolved separation of fourteen commonly found LMW carboxylic acids in natural waters (malonic, oxalic, fumaric, maleic, formic, succinic, tartaric, glutaric, adipic, acetic, propionic, butyric, valeric and citric acids), was achieved within eight minutes. The limits of detection (2 X noise) were in the ranges 90–200 μg/l and 0.5 – 5 μg/l for hydrodynamic and electrokinetic injection, respectively. Two different CZE systems, a Waters Quanta 4000 and a Hewlett Packard HP ^3DCE system, were used and their performance compared.     

Determination of the Molecular Weight of Extracellular Ribonuclease Isoenzymes from Aspergillus Niger in Crude Extracts by Thin Layer Gel Filtration and Polyacrylamide Gel Electrophoresis

Abstract

The extracellular ribonucleases from Asperqillus niger culture medium were fractionated according to their molecular weight by thin layer gel filtration through Sephadex G100 superfine and the enzyme activity was detected by a standard staining technique on a replica print paper. Another replica paper was laid onto the top of a polyacrylamide gel and the absorbed proteins were separated by electrophoresis. By comparing the electrophoretic pattern with that of a control not subjected to gel filtration, the molecular weight of each isoenzyme in the crude extract could be determined. Gel electrophoresis however, is only used to establish the correspondence between the original electrophoretic pattern of the isoenzymes in the crude preparation and that detected on the replica print paper taken after the thin layer gel filtration run. There was good agreement between the values obtained for the crude and purified enzymes.     

Reversible Addition–Fragmentation Chain‐Transfer Polymerization of Octadecyl Acrylate

Abstract

Polymerization of octadecyl acrylate (ODA) was carried out in benzene solution using the 2‐cyanoprop‐2‐yl dithiobenzoate (CPDB) as the reversible addition–fragmentation chain‐transfer (RAFT) agent and AIBN as the initiator. The results show the obtained polymer with controlled molecular weight and low PDI value. The relationships between both of the ln([M ₀]/[M]) vs. reaction time and molecular weight vs. conversion showed a straight line. The block copolymer of ODA and styrene (PODA‐b‐PSt) obtained using poly(octadecyl acrylate) (PODA) as a macro‐RAFT agent. The polymers were characterized by ¹H NMR, DSC, and gel permeation chromatograph (GPC). The effect of molar ratio [CPDB]:[AIBN] and reaction temperature on polymerization was investigated.