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PubMed2002

Study on the concentration effects in size exclusion chromatography VII. A quantitative verification for the model theory of concentration and molecular mass dependences of hydrodynamic volumes for polydisperse polymers.

A model theory of concentration effects for polydisperse polymers was proposed in 1988. It is successful in relating the concentration of the injected solution to the effective hydrodynamic volumes of peak, the retention volumes of peak and the polydispersity index (Dc = (Vhcw)/(Vhcn) of hydro-dynamic volume distribution for polydisperse polymers at a given concentration. The dependence of the concentration of injected polymer solution on the effective hydrodynamic volumes, the retention volumes of peak and the polydispersity index of hydrodynamic volume distribution for narrow disperse and polydisperse polystyrene, poly(dodecyl methacrylate), poly(tridecyl methacrylate) and poly(methyl methacrylate) in tetrahydrofuran solvent were studied. The proposed theory was verified by these experimental data. Results show that the proposed theory can predict the concentration effects in GPC for polydisperse polymers quantitatively and can provide a theoretical foundation for the two methods of calibrating the universal calibration curves with polydisperse polymers and of determining the second virial coefficients (A2) of polymers. It is found that the determined values of A2 for narrow disperse and polydisperse polymers by the proposed method are in agreement with those obtained by the LALLS method, and the two universal calibration curves with narrow disperse and polydisperse polymers are in excellent agreement.

Calibration↗

PubMed2003

Blends of enteric and GIT-insoluble polymers used for film coating: physicochemical characterization and drug release patterns.

THE OBJECTIVES OF THIS STUDY WERE: (i). to use blends of gastrointestinal tract (GIT)-insoluble and enteric polymers (ethyl cellulose and Eudragit L) as coating materials for multiparticulate controlled release dosage forms; (ii). to investigate the effects of the polymer blend ratio and coating level on the resulting drug release patterns; and (iii). to explain the observed phenomena based on the physicochemical properties of the systems. Propranolol HCl-loaded pellets were coated in a fluidized bed coater with organic polymer solutions; thin, drug-containing and drug-free, polymeric films were prepared using a casting knife. In vitro drug release, water uptake and dry weight loss studies were performed in 0.1 M HCl and phosphate buffer pH 7.4, respectively. The apparent drug diffusion coefficients within the polymeric systems were determined using different experimental and theoretical techniques (side-by-side diffusion cells, in vitro drug release from thin films; exact and approximate solutions of Fick's second law of diffusion). A broad range of drug release patterns from coated pellets could be achieved by varying the GIT-insoluble:enteric polymer blend ratio. With increasing relative amounts of Eudragit L, the release rates in both media significantly increased. The increase at low pH could be attributed to an increase in water uptake, as observed with thin films. Interestingly, only partial Eudragit L leaching occurred in phosphate buffer pH 7.4 even at high enteric polymer contents, indicating that the GIT-insoluble polymer effectively hindered the dissolution of the entrapped Eudragit L. At high pH, both polymer leaching and polymer swelling contributed to the control of drug release. The determined apparent drug diffusion coefficients take the two effects adequately into account.

Cellulose↗

PubMedDate not supplied

Hydrophobically driven attachments of synthetic polymers onto surfaces of biological interest: lipid bilayers and globular proteins.

This paper gives a brief overview of the consequences of associations between amphiphilic water-soluble polymers and small colloidal particles of biological interest: proteins and vesicles. Typical structures of water-soluble synthetic polymers containing hydrophobic groups are presented. The segregation between polar and apolar units in these polymers induces self-organisation in micro-domains despite the lack of specific primary structure. In the presence of other amphiphilic particles like proteins and vesicles, mixed assemblies are formed. Examples of polymer associations with vesicles or globular proteins, mainly focused on the acrylic derivatives, bring out common features in these mixtures. When the size of the polymer is of the same order of magnitude as that of the particle, adsorption of polymer chains creates a protective layer around each individual particle. Depending on the hydrophobicity of the partners, the association can stabilise the dispersion of unmodified particles or induce structural changes (membrane disruption, leakage). When small particles are added to solutions of long polymers, multimolecular complexation occurs. In this case, the size of the resulting aggregates depends on the concentrations. It goes from the size of one polymer molecule up to formally infinity as revealed by gelation. The identification of non-specific association modes between biological nanoparticles and macromolecules might be revealed by the general behaviour of these synthetic mixed systems.

Acrylic Resins↗

PubMed2000

Polymer displacement/shielding in protein chromatography.

An overview of different applications of polymer interactions with ion-exchange and dye-affinity chromatographic matrices is presented here. The strength of interaction between the ligand and the polymer plays a crucial role in deciding the mode of chromatographic application. Charged, non-ionic and thermosensitive polymers such as poly(ethylene imine), poly(N-vinyl pyrrolidone) and poly(vinyl caprolactam) respectively, show different degrees of interaction with the dye molecules in dye ligand chromatography. Polymers, with their ability of multipoint and hence strong attachment to the chromatographic matrices, were used as efficient displacers in displacement chromatography. The polymer displacement resulted in better recoveries and sharper elution profiles than traditional salt elutions. The globule-coil transition of the thermosensitive reversible soluble-insoluble polymer, poly(vinyl caprolactam), can be exploited in dye-affinity columns for the temperature induced displacement of the bound protein. In another situation, prior to the column chromatography of crude protein extract, polymers formed complexes with the dye matrix and "shielded" the column. The polymer shielding decreased the nonspecific interactions without affecting the specific interactions of the target protein to the dye matrix.

Chromatography↗

PubMed2001

Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers.

Microspheres were prepared from poly(L-lactic acid) polymers having molecular weights between 500 and 50k g/mol. The polymers were synthesized using two initiator molecules, L-lactic acid oligomer (PLLA-LA) or stearyl alcohol (PLLA-SA). For both PLLA-LA and PLLA-SA polymers, glass (Tg) and melting (Tm) transition temperatures and enthalpy of melting all increased as the polymer molecular weight increased. PLLA-SA showed the greatest change in Tg (-13 to 54 degrees C) as molecular weight increased from 500 to 10k x g/mol, compared to 25 to 55 degrees C for PLLA-LA polymers. Changes in Tm and enthalpy of melting with increasing molecular weight were similar for both PLLA-LA and PLLA-SA. Paclitaxel release from 30% paclitaxel loaded microspheres in the size range of 50-90 microm was affected by these changes in polymer properties as molecular weight increased. As the molecular weight increased from 2k to 50k x g/mol the amount of drug released from microspheres over 14 days decreased from 76 to 11% of the initial drug load. The release profiles were consistent with a diffusion controlled mechanism provided a two-compartment model was employed. According to this model, the total amount of 'available' drug (compartment 1) was released by diffusion in 14 days while the remainder (compartment 2) was confined within the polymeric matrix and could not diffuse out at a measurable rate. Following the in vitro release study, microsphere made from 2k-10k g/mol polymers showed significant signs of disintegration whereas 50k x g/mol polymer microspheres remained intact.

Antineoplastic Agents, Phytogenic↗

PubMed1990

New concepts in the prevention of polymer-associated foreign body infections.

Polymer-associated foreign body infections, especially those caused by coagulase negative staphylococci, have become a problem of increasing importance in modern medicine. Therapy of such infections is often difficult and requires in many cases the removal of a catheter or an implant. On the basis of polymer material modification alternative strategies for the prevention of foreign body infections are presented. By use of high energy radiation or glow discharge techniques polymers can be modified so that new chemical groups with potential antiadhesive or antimicrobial activities can be introduced to the polymer (surface). Another approach is the coupling or incorporation of antimicrobial agents (e.g. antibiotics) to or into polymers. Such polymer-antibiotic systems are obviously not able to prevent initial bacterial adhesion to the polymer material but can effectively eliminate already adherent bacteria from the polymer surface.

Anti-Bacterial Agents↗

PubMed2000

Polymer and microsphere blending to alter the release of a peptide from PLGA microspheres.

The objective of this study was to evaluate the effect of polymer and microsphere blending in achieving both a sufficient initial release and a desired continuous release of a peptide from poly(D, L-lactide-co-glycolide) microspheres. Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a solvent-extraction/evaporation process and were characterized for their drug load, bulk density, size distribution, surface area, surface morphology, in vitro drug release, and in vivo efficacy. Combining PLGA polymers that varied in their molecular weights in various ratios yielded microspheres with varied drug release profiles commensurate with the hydration tendencies of the polymers. Increasing the component of lower molecular weight 50:50 hydrophilic PLGA polymer, 8.6 kDa increased the initial drug release. A similar microsphere formulation prepared instead with blending microspheres from individual polymers showed a similar increase. In an animal model, microspheres obtained from polymer or microsphere blends attained a faster onset of testosterone suppression as compared to microspheres from higher molecular weight 50:50 hydrophilic PLGA polymer, 28.3 kDa, alone. These studies illustrated the feasibility of blending polymers or microspheres of varied characteristics in achieving modified drug release. In particular the increased initial release of the peptide could help avoid the therapeutic lag phase usually observed with microencapsulated macromolecules.

Animals↗

PubMed2003

Evaluation of pH-dependent membrane-disruptive properties of poly(acrylic acid) derived polymers.

Anionic pH-sensitive membrane-disruptive polymers have evolved as a new class of bioactive excipients for the cytosolic delivery of therapeutic macromolecules. A large variety of anionic copolymers and analogues of poly(acrylic acid) (PA) was investigated and compared to a cationic PA copolymer. The pH-responsive membrane-disruptive properties were characterized by employing three in vitro models, such as pH dependent shift of pyrene fluorescence, liposome leakage and lysis of red blood cells. The pH-dependent increase of polarity and membrane disruption in the different model systems was in good agreement for all tested PA polymers. The efficacy of polymer-induced membrane disruption was concentration-dependent and significantly affected by the composition of the membrane. The sensitivity of relatively complex membranes of mammalian cells can be ranked between plain diphosphatidylcholine (DPPC) liposomal membranes and the more rigid cholesterol-containing DPPC membranes. Among the various studied PA polymers, medium and low molecular poly(ethacrylic acid) (PEA) and poly(propacrylic acid) (PPA) were identified as displaying significant pH-dependent disruptive activity. Relative to the disruptive cationic PA polymer (PDMAEM) the ranking is PEA < PPA < PDMAEM. The fine tuning of the pH-responsive hydrophilic-hydrophobic balance is likely to be responsible for the superior effect of PEA and PPA compared to other anionic PA polymers. This thorough investigation of a large variety of different anionic PA polymers and the comparison with an efficient, although rather toxic cationic PA polymer provides a good assessment for further therapeutic applications.

Acrylic Resins↗

PubMed1998

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for polymer analysis: solvent effect in sample preparation.

The success of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry for the characterization of polymer structures and for the determination of average molecular weights and distributions depends on the use of a proper sample/matrix preparation protocol. This work examines the effect of solvents, particularly solvent mixtures, used to prepare polymer, matrix, and cationization reagent solutions, on MALDI analysis. It is shown that the use of solvent mixtures consisting of polymer solvent does not have a significant effect on the molecular weight determination of polystyrene 7000 and poly(methyl methacrylate) 3750. However, solvent mixtures containing a polymer nonsolvent can affect the signal reproducibility and cause errors in average weight measurement. This solvent effect was further investigated by using confocal laser fluorescence microscopy in conjunction with the use of a fluorescein-labeled polystyrene. It is demonstrated that sample morphology and polymer distribution on the probe can be greatly influenced by the type of solvents used. For sample preparation in MALDI analysis of polymers, it is important to select a solvent system that will allow matrix crystallization to take place prior to polymer precipitation. The use of an excess amount of any polymer nonsolvent should be avoided.

Algorithms↗

PubMed2003

Protein binding to polymer brush, based on ion-exchange, hydrophobic, and affinity interactions.

The major limitations associated with conventional packed bed chromatography for protein separation and purification can be overcome by using adsorptive microporous membranes as chromatographic media. Microporous membranes have advantages as support matrices in comparison to conventional bead supports because they are not compressible and they eliminate diffusion limitations. As a result, higher throughput and shorter processing times are possible using these membrane systems. In this paper, we review the current state of development in the area of attaching functionalized polymer brushes onto a microporous membrane to form a novel chromatographic medium for protein separation and purification. The functionalized polymer brushes were appended onto the pore surface of a microporous hollow-fiber membrane uniformly across the membrane thickness by radiation-induced graft polymerization and subsequent chemical modifications. We review various applications of this adsorptive membrane chromatography by focusing on polymer brushes bearing ion-exchange, hydrophobic and affinity groups. Proteins were captured in multilayers by the ion-exchange group-containing polymer brushes due to the formation of a three-dimensional space for protein binding via the electrostatic repulsion of the polymer brushes. In contrast, proteins were captured in a monolayer at most by the polymer brushes containing hydrophobic or affinity ligands. By permeating a protein solution through the pores rimmed by the polymer brushes, an ideal capturing rate of the proteins with a negligible diffusional mass-transfer resistance was achieved by the functionalized polymer brushes, based on ion-exchange, hydrophobic, and affinity interactions.

Chromatography, Affinity↗

PubMedDate not supplied

Mechanistic investigation of smart polymer-protein conjugates.

Many affinity separation and diagnostic applications rely upon both capture and release steps. There is thus a need for methods to enhance the reversibility of biomolecular interactions. We have previously demonstrated that stimuli-responsive polymers can be used to gate biomolecular reactions when conjugated near the active site of proteins. Here we have used a new smart polymer, N,N-dimethyl acrylamide-co-4-phenylazophenylacrylate that has allowed a mechanistic investigation of the smart polymer switches. This polymer was conjugated via a vinyl sulfone terminus to cysteine residues of genetically engineered streptavidin mutant E116C, where the polymer is conjugated close to the biotin-binding site, and streptavidin mutant S139C, where the conjugation site is distant. The biotin binding switching activity was strongly dependent on conjugation position, as the E116C conjugate displayed a large thermal response while the S139C conjugate displayed only small effects. Kinetic measurements of biotin release demonstrated that the off-rate of biotin was unperturbed and that the thermally triggered release of biotin with the E116C conjugate was due to the blocking the reassociation of biotin. The addition of free polymer to purified E116C conjugates was also shown to increase the blocking and release properties of the switch. This effect was site dependent, suggesting that the conjugated polymers were directing a physical aggregation near the binding site that effectively enhanced the switching activity. These investigations provide mechanistic insight that can be utilized to design better molecular switches for a variety of stimuli-responsive polymer-protein conjugates.

Acrylates↗

PubMedDate not supplied

Photoswitching of ligand association with a photoresponsive polymer-protein conjugate.

Light-regulated molecular switches that reversibly control biomolecular function could provide new opportunities for controlling activity in diagnostics, affinity separations, bioprocessing, therapeutics, and bioelectronics applications. Here we show that site-specific conjugation of light-responsive polymers near the biotin-binding pocket of streptavidin provides control of ligand binding affinity in response to UV and visible light irradiation. Two different light-responsive polymers were utilized that display opposite photoresponsive solubility changes under UV or visible (vis) light irradiation in aqueous solutions. At 40 degrees C, the N,N-dimethylacrylamide (DMA)-co-4-phenylazophenyl acrylate (AZAA) copolymer (DMAA) was soluble under UV irradiation and precipitated under visible light, while the DMA-co-N-4-phenylazophenyl acrylamide (AZAAm) copolymer (DMAAm) was soluble under visible irradiation and precipitated under UV light. Both polymers were synthesized with a vinyl sulfone terminus and conjugated to the Glu116Cys (E116C) streptavidin mutant via thiol coupling. The DMAA-streptavidin conjugate bound biotin efficiently when the polymer was in the soluble state under UV irradiation, but under visible irradiation, the polymer collapsed and blocked free biotin association. Furthermore, if biotin was allowed to bind when the polymer was in the soluble state under UV irradiation, then when the polymer was collapsed by visible light, the streptavidin released the bound biotin. The DMAAm-streptavidin conjugate showed the opposite response, with association of biotin allowed under visible light irradiation and blocked under UV irradiation. The photoresponses of the streptavidin conjugates thus correspond to the original photoresponsive phase transition properties of the polymer switches triggered by the cis-trans isomerization of the diazo chromophores.

Acrylates↗

PubMedDate not supplied

New class of polymers for the delivery of macromolecular therapeutics.

Cationic polymers show promise for the in vitro and in vivo delivery of macromolecular therapeutics. Known cationic polymers, e.g., poly(L)lysine (PLL) and polyethylenimine (PEI), have been employed in native and modified forms for the delivery of plasmid DNA (pDNA) and reveal varying levels of toxicity. Here, we report the preparation of a new class of cationic polymers that are specifically designed to deliver macromolecular therapeutics. Linear, cationic, beta-cyclodextrin (beta-CD)-containing polymers (CD-polymers) are synthesized by copolymerizing difunctionalized beta-CD monomers (AA) with other difunctionalized comonomers (BB) such that an AABBAABB product is formed. The beta-CD polymers are able to bind approximately 5 kbp pDNA above polymer to DNA (+/-) charge ratios of 1.5, compact the bound pDNA into particles of approximately 100-150 nm in size at charge ratios above 5+/-, and transfect cultured cells at charge ratios above 10+/-. In vitro transfections with the new beta-CD-polymers are comparable to the best results obtained in our hands with PEI and Lipofectamine. Some cell line-dependent toxicities are observed for serum-free transfections; however, no toxicity is revealed at charge ratios as high as 70+/- in transfections conducted in 10% serum. Single IV and IP doses as high as 200 mg/kg in mice showed no mortalities.

Animals↗

PubMed1996

Interactions of 2-methoxyestradiol, an endogenous mammalian metabolite, with unpolymerized tubulin and with tubulin polymers.

2-Methoxyestradiol (2ME) is an endogenous mammalian catabolite of estradiol with antimitotic activity. Although it is a competitive inhibitor of the binding of colchicine to tubulin, it has unusual effects on glutamate-induced tubulin polymerization. Polymer that was little changed in morphology assembled at a reduced rate and was relatively cold stable. We have now examined interactions of [4-3H]-2ME with unpolymerized tubulin and polymer. The [3H]2ME binds avidly to tubulin even on ice, and it is readily displaced by other colchicine site drugs. An association rate constant on ice of 1.9 x 10(2) M-1s-1 was obtained. Scatchard analysis indicated a single class of binding site and an association equilibrium constant of 5.7 x 10(5) M-1. These values lead to a calculated dissociation rate constant of 3.3 x 10(-4) s-1. In glutamate-induced tubulin assembly, a reaction that requires GTP and leads to the formation of sheets of parallel protofilaments, increasing amounts of [3H]2ME were incorporated into polymer, reaching near-stoichiometry with tubulin at 100 microM 2ME. Equivalent binding of [3H]2ME occurred when the drug was added to preformed polymer, but binding of [3H]2ME to polymer was not readily inhibited by colchicine site drugs. Significant amounts of [3H]2ME were also incorporated into microtubule polymer formed with microtubule-associated proteins, glycerol, or 4-morpholineethanesulfonate buffer, but the stoichiometry was substantially lower than that in the sheet polymer induced by either glutamate or 1,4-piperazineethanesulfonate buffer. The structural differences between the microtubule and sheet polymers leading to these differences in apparent affinity for 2ME are unknown, but presumably interaction of the estrogen metabolite with cellular microtubules has functional significance related to the antimitotic properties of the compound.

2-Methoxyestradiol↗

PubMed2001

Gamma-irradiation stability of saturated and unsaturated aliphatic polyanhydrides--ricinoleic acid based polymers.

The effect of terminal sterilization by gamma-irradiation on several ricinoleic acid based polyanhydrides was investigated. The following polymers were used: poly(ricinoleic acid maleate) [P(RAM)], poly(ricinoleic acid succinate) [P(RAS)], poly(hydroxy stearic acid succinate) [P(HSAS)], poly(hydroxy stearic acid maleate) [P(HSAM)], and their copolymers with sebacic acid. The polymers were irradiated with an absorbed dose of 2.5 or 10 Mrad by means of a 60Co source under dry ice or at room temperature. No differences were found between samples irradiated under dry ice and at room temperature. Polymers prepared from monomers containing maleate residues, which contain double bonds adjusted to the anhydride linkage along the polymer chain, decreased in molecular weight, became insoluble, and showed fast hydrolytic degradation. For example, p(RAM), p(HSAM), and their copolymers with sebacic acid decreased in Mw from about 10,000 to about 2000, and from about 30,000 to about 5000, respectively, while polymers based on RAS and HSAS remained stable. This phenomenon was explained by an anhydride interchange-self-depolymerization process of the unsaturated anhydride bonds induced by gamma-irradiation. This explanation was supported by the depolymerization of another class of polymers having an anhydride bond between two double bonds, fumaric acid anhydride polymers. The anhydride bond that lies between two double bonds was found to be more sensitive to gamma-irradiation. This anhydride bond may be cleaved to form two radicals that further react with aliphatic anhydride bonds along the polymer chain to form inter- and/or intracyclization products.

Anhydrides↗

PubMedDate not supplied

Polymer development for enhanced delivery of phenol in a solid-liquid two-phase partitioning bioreactor.

Two-Phase Partitioning Bioreactors (TPPBs) have traditionally been used to partition toxic concentrations of xenobiotics from a cell-containing aqueous phase by means of an immiscible organic solvent and to deliver these substrates back to the cells on the basis of metabolic demand and the maintenance of thermodynamic equilibrium between the phases. A limitation of TPPBs, which use organic liquid solvents, is the possibility that the solvent can be bioavailable, and this has therefore limited organic liquid TPPBs to the use of pure strains of microbes. Solid polymer beads have recently been introduced as a replacement for liquid organic solvents, offering similar absorption properties but with the capability to be used with mixed microbial populations. The present work was aimed at identifying a polymer with a greater capacity for and more rapid uptake and release of phenol for use as the second phase in a mixed culture TPPB. Polarity and hydrogen bonding capabilities between polymer and phenol were considered in the screening and selection process of candidate polymers. Hytrel (a copolymer of poly(butylene terephthalate) and butylene ether glycol terephthalate) polymer beads, offered improved capacity (19 mg phenol/g polymer at a fixed initial phenol concentration of 2000 mg/L) and a greater diffusivity (1.54 x 10(-7) cm2/s) when compared to the capacity and diffusivity of previously used EVA (ethylene vinyl acetate) beads (12.4 mg phenol/g polymer and 3.73 x 10(-9) cm2/s, respectively). Hytrel polymer beads were then used in a TPPB for the investigation of various substrate feeding strategies (fed-batch, bead replacement, and concentrated spikes of phenol), with rapid and complete phenol degradation shown in all cases.

Absorption↗

PubMedDate not supplied

Analysis of surface microtopography of biodegradable polymer matrices using confocal reflection microscopy.

Currently, synthetic degradable polymers are frequently employed as culture substrates prior to cell transplantation and as implantable scaffolds for cellular infiltration during soft and hard tissue repair. The surface microstructure of matrices based on such polymers may be important in controlling cellular anchorage, spreading, and growth on the external surface, as well as infiltration into the voids of porous polymer scaffolds. While the chemistry, bulk structure, and mechanical properties of such polymers have been extensively studied, the surface microstructure has not yet been systematically examined, particularly following polymer degradation. In this study, we present the first account of the use of confocal laser-scanning reflection microscopy (CLSM) to visualize and quantitate the microtopography of the surface of porous matrices of poly(lactic acid)/poly(glycolic acid) (PLAGA) copolymers following polymer degradation. Utilizing this technique, we report that the surface morphology of PLAGA matrices changes significantly upon degradation, with increased local clustering of textured regions. Our quantitative analysis suggests that polymer degradation results in a lower spatially-averaged surface roughness, with significant cyclical variations observed at later time points. The computed surface correlation function was observed to increase upon degradation, confirming the results from our morphological studies. Finally, we demonstrate the efficacy of CLSM to concomitantly image both the polymer surface and locally attached cells, in real time.

Carcinoma, Hepatocellular↗

PubMed2002

Preparation of new microgel polymers and their application as supports in organic synthesis.

A series of soluble microgel polymers have been synthesized using solution-phase polymerization reactions. In a systematic manner, several variables such as monomer concentration, cross-linker content, reaction solvent and reaction time were examined, and this provided an optimal polymer with both solubility and precipitation characteristics suitable for synthetic applications. Thus, a chemically functionalized microgel polymer was synthesized, and the utility of this polymer in the synthesis of a small array of oxazole compounds has been demonstrated. The advantage of the microgel polymers produced was that they exhibited solution viscosities lower than those of conventional linear polymers even at higher concentrations, and this was found to be beneficial for their precipitation properties. Compounds prepared using the described microgel polymer supports were obtained in similar yields and purity when compared with insoluble resins, and more importantly, the soluble polymer bound intermediates could be analyzed at each step using standard NMR techniques.

Catalysis↗