Beaded polyethylene glycol-based resins

Details Beaded polyethylene glycol-based resins Beaded polyethylene glycol-based resins

2001-07-09

2003-11-04

Harlan, Robert D. (Department: 1713)

Synthetic resins or natural rubbers -- part of the class 520 ser

Synthetic resins

Polymers from only ethylenic monomers or processes of...

C526S317100, C526S318000, C526S320000, C526S332000, C526S930000, C526S936000

Reexamination Certificate

active

06642334

ABSTRACT:

FIELD OF THE INVENTION
The invention relates to beaded polyethylene glycol-based resins prepared in silicone oil using a polymeric surfactant containing a pentaalkyldisiloxane group. The invention also relates to the pentaalkyldisiloxane containing surfactant.
BACKGROUND OF THE INVENTION
The recent renaissance of solid phase organic chemistry for synthesis of various molecules has created an increasing demand for new solid supports. Traditionally, polystyrene-divinylbenzene (PS-DVB) has been used as a support for solid phase chemistry because of its high thermal stability, chemical inertness, and mechanical robustness. However, the limited swelling of PS-DVB supports in polar media can limit reagent accessibility and prevent chemical applications in which complete solvation of the polymer matrix is essential for reactivity. For example, the poor swelling of conventional PS-DVB in polar solvents such as an aqueous buffer results in limited diffusion of reagents and low yields for reactions performed in these media. Although increased swelling in polar solvents can be achieved by grafting polyethylene glycol (PEG) to chloromethylated PS-DVB, the resulting PEG-grafted PS-DVB supports such as TentaGel™ (Rapp Polymere GmbH; Tübingen, Germany) and ArgoGel™ (Argonault Technologies; San Carlos, Calif.) have limitations for use in aqueous solvents and for enzymatic chemistry.
Several PEG-based resins have been developed recently that exhibit high swelling volumes in both nonpolar solvents and water. These resins include, for example, polyoxyethylene-polyoxypropylene (POEPOP), SPOCC (Superior Polymer for Organic Combinatorial Chemistry, a polymer formed by cationic polymerization of a mixture of mono- and bis-oxetanylated PEG macromonomers), and polyoxyethylene-polystyrene (POEPS). These resins have been successfully used for solid phase organic reactions in both aqueous and organic media. The PEG-based supports thus exhibit several advantages for application in solid-phase organic chemistry, solid-phase enzymatic reactions, and on-bead screening assays.
The PEG-based resins typically have been prepared by bulk polymerization. To obtain the appropriate particle size, the resins have been mechanically ground and sieved. However, the grinding process is labor intensive and tends to generate irregular particles as well as a considerable quantity of fines that have to be removed by sedimentation. Because irregular and fragile particles have limited use for applications such as on-bead screening assays, attempts have been made to prepare uniform beads of PEG-based resins.
Inverse suspension polymerization methods for producing beads from acrylic monomers are well established and can produce a higher yield of particles possessing uniform shape and size. For example, POEPS resin was prepared in beaded form by inverse suspension polymerization using water to generate stable emulsion droplets in a mixture of carbon tetrachloride and heptane. Water is, however, incompatible with the cationic and anionic ring-opening polymerization methods to prepare SPOCC and POEPOP polymers, respectively. In order to circumvent the problems of using dispersants that interfere with the cationic and anionic reactions, an entirely new suspension polymerization technique was developed based on the reaction of emulsions of the PEG macromonomers in silicone oil. Silicone oil is generally immiscible with organic compounds and can serve as an inert phase for suspension polymerization. Suspension polymerization in silicone oil has worked well on a one to two gram scale with short PEG monomers such as PEG 194 and PEG 400 chains. However, aggregation occurred when the process was scaled up or when longer PEG-monomers such as PEG 900 and PEG 1500 were used. As used herein, the number following the term “PEG” refers to the average molecular weight of the PEG polymer.
Improved methods are needed for preparing beads of PEG-based resins.
SUMMARY OF THE INVENTION
The invention relates to the synthesis of beaded polyethylene glycol-based resins in silicone oil in the presence of a polymeric surfactant containing a pentaalkyldisiloxane group.
One aspect of the invention provides a pentaalkyldisiloxane containing polymeric surfactant. The surfactant is the copolymerization product of n moles of an alkoxypolyoxyalkylenyl acrylate and m moles of a pentaalkyldisiloxane containing acrylate, wherein the molar ratio m:n ranges from about 1:100 to about 1:0.01. In some embodiments of the invention, the molar ratio m:n ranges from about 1:20 to about 1:4.
Another aspect of the invention provides a method for forming beaded resins by polymerization of macromolecules having a three, four, or five membered ring attached to one or both ends of a polyoxyalkylene. Polymerization of the macromonomers proceeds through an anionic or cationic ring opening reaction as the macromonomers are suspended in silicone oil in the presence of a pentaalkyldisiloxane containing polymeric surfactant.
The resins of the invention can be used, for example, as a support for solid phase organic synthesis, as a chromatographic resin, as a resin for solid phase MAS-NMR spectroscopy, and as a carrier for drug molecules, various reagents, or scavengers.


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