GTP Monomers

Acrylates polymerize two orders of magnitude faster than methacrylates by anion catalyzed GTP however, the polymerization dies at about 10,000 MW. During the anion catalyzed polymerization of acrylates the silyl ketene acetal end groups migrate to internal positions. These ketene acetals are too hindered to act as initiators for branch formation [9]. 

The living polymerization of acrylates by GTP does proceed under Lewis acid catalysis [14]. ZnCl2 or ZnBr2 are effective but require concentrations of catalyst at a level of 10% based on monomer. R2A1C1 works at lower levels. However, HgCl2 activated by TMS iodide is the best Lewis acid system and 

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After ligand binding, the a subunit releases GDP and binds GTP. The GTP-liganded trimer dissociates into a monomers and B-y dimers. The a-GTP monomer then hydrolyzes GTP to GDP, enabling reassodation of the trimer and termination of the signal. These trimer G proteins are responsible for the effects of ligand binding to the receptor. The nature of the protein constituents of the trimeric G protein determines whether there is activation of adenylate cyclase or phospholipase C or inhibition of these enzymes. This determines whether there is an increase of cAMP-dependent protein kinase A activity, an elevation of intracellular Ca, or an inhibition of cell responses. 

GTP is a safe operation. A runaway polymerization can be quickly quenched with a protonic solvent. Since the group transfer polymerization goes to completion, no unwanted toxic monomer remains the silicone group on the living end after hydroxylation is removed as inactive siloxane. The living polymer in GTP is costlier than traditional polymerization techniques because of the stringent reaction conditions and requirements for pure and dry monomers and solvents. It can be used in fabrication of silicon chips, coating of optical fibers, etc. 

The role of silyl groups in condensation polymerization is different from that in GTP. The use of silylated monomers in condensation polymerization was studied first by Klebe [90-92] in 1964. N-trimethylsilyl-substi-... 

These TMS-carbamate-mediated NCA polymerizations resemble to some extent the group-transfer polymerization (GTP) of acrylic monomers initiated by organo-silicon compounds [40]. Unlike GTPs that typically require Lewis acid activators or nucelophilic catalysts to facilitate the polymerization [41], TMS-carbamate-mediated NCA polymerizations do not appear to require any additional catalysts or activators. However, it is still unclear whether the TMS transfer proceeds through an anionic process as in GTP [41] or through a concerted process as illustrated in Scheme 14. 

ABC, ACB, and BAC triblock terpolymers, where A is PMMA, B is PDMAEMA, and C is poly[hexa(ethylene glycol)methacrylate], PHEGMA, were synthesized via GTP and sequential monomer addition [89]. The polymerizations were conducted in THF using MTS and TBABB as the initiator... 

G-proteins are a family of guanine nucleotide-binding proteins and represent an initial stage of signal transduction. Many G-proteins are trimers and mediate a wide range of responses to hormonal action, which are discussed in Chapter 12. However, G-proteins involved in cell proliferation are monomers. The significant property of aU G-proteins is that they are active (and transmit a signal) when GTP is bound but are inactive when GDP is bound. 

The mechanisms for nucleophilic GTP and electrophilic GTP are not the same. Electrophilic GTP proceeds by an associative or concerted mechanism that does not involve anionic propagating centers. Initiation involves a concerted addition of methyl trimethylsilyl dimethyl ketene acetal to monomer to form species XXV. The overall effect is to transfer... 

Coupling of GTP living polymers with halide-terminating agents to form star polymers has been achieved [Hertler, 1996 Webster and Sogah, 1989]. Star polymers are also synthesized by using polyfunctional initiators or by copolymerization with dimethacrylate monomers. 

Figure 7-33 Stereoscopic ribbon diagram of the tubulin dimer with a-tubulin with bound GTP at the top and P-tubulin with bound GDP at the bottom. The p-tubulin subunit also contains a bound molecule of taxotere (see Box 7-D) which is labeled TAX. This model is based upon electron crystallography of zinc-induced tubulin sheets at 0.37-nm resolution and is thought to approximate closely the packing of the tubulin monomers in microtubules.315 The arrow at the left points toward the plus end of the microtubule. Courtesy of Kenneth H. Downing.

Scheffers, D.J., de Wit,J. G., den Blaauwen, T., and Driessen, A.J. (2002). GTP hydrolysis of cell division protein FtsZ Evidence that the active site is formed by the association of monomers. Biochemistry 41, 521-529. 

Based on evidence available at the time, the DuPont workers proposed that the trimethylsilyl group was transferring to monomer as it was adding to the polymer chain ends and thus named the new procedure Group Transfer Polymerization (GTP). Based on all the evidence now available this mechanism is almost certainly wrong but the name should remain since it is firmly imbedded in the chemical literature. 

As shown in Scheme 1, GTP converts methacrylate monomer to a polymer with one end group corresponding to the R on the initiator and the other end a trimethylsilyl ketene acetal. If the initiator contains a vinyl group not reactive to GTP, a macromonomer results [8]. The silyl ketene acetal end can be used to initiate another monomer, for example butyl methacrylate, to give... 

By far the best monomers for GTP are the methacrylates. Glycidyl methacrylate and other substituted members of the family can be used to make highly functional block polymers. If the monomer contains active hydrogen, for example, hydroxyethyl methacrylate or methacrylic acid, GTP does not proceed. These functions can, however, be masked by trimethylsilyl groups [9] (Scheme 5). 

In a process related to GTP, aldehydes initiate the polymerization of silyl vinyl ethers and silyl diene ethers. Here the silyl group is present in the monomer and transfers to the aldehyde ended chains regenerating aldehyde ends [17] (Scheme 8). A Lewis acid catalyst is required. terf-Butyldimethylsilyl works best as a transfer group for vinyl ether while trimethylsilyl is suitable for diene ethers [18]. Even though aldol GTP provides a route to polyvinyl alcohol segments in the subsequent block polymer synthesis, the projected cost of the monomers discouraged further research aimed at commercialization. 

Lewis acid catalysts were discussed in the acrylic monomer section. They are used at about 10% concentration vs monomer. Although no significant research has been done with them, other than looking for new ones, they most likely work by activating the monomers. Type Y zeolites catalyze GTP at about 25% concentration vs initiator. Conversions are quantitative and... 

In a study that in itself almost lays to rest the associative mechanism for GTP, Quirk generated an ester enolate by addition of TBA 9-methylfluo-renide to MMA and used it as a catalyst for GTP of MMA initiated by MTS at 50 °C. The conversion was quantitative, the MWD was in the 1.2 range, and the molecular weight was controlled by the ratio of MTS to monomer [6]. In similar experiments without the MTS, conversions of only 14-52% were obtained, the MWD was broad and molecular weight control was lost. 

In the absence of monomer, GTP catalysts are destroyed by the initiator. A one to one molar mixture of bifluoride and MTS, for example produces methyl isobuterate, trimethylsilylfluoride, trimethylsilylmethoxide, methyl 2,2,4-trimethyl-3-oxopentanoate, and other oligomers [19, 26]. Seebach has shown that ester enolates generate ketenes at room temperature [27] (Scheme 16). These reactions support the dissociative mechanism wherein... 

An example of an inhibitor being consumed is seen in the initiation of GTP with TMS cyanide catalyzed by TBA CN . Here the polymerization does not begin until all of the TMS cyanide has added to the MMA (Scheme 17). Hertler studied the system by NMR and showed that Me3SiCN complexes with the cyanide catalyst to the extent that polymerization will not take place [28] until the complex is gone. This complexation will certainly take place however, the cyanide catalyst should continue to add to monomer until it is also gone leaving the polymer enolate complex (Scheme 17a), which then initiates polymerization. 

Certain monomers provide evidence relating to the GTP mechanism problem. Ober has shown that [3-(methacryloxy)propyl]pentamethyldisiloxane, (Scheme 23a) polymerizes very slowly under GTP conditions (100 h). Molecular weight control and MWD, however, were excellent [44]. A dissociative mechanism can explain this unusual property. The tethered siloxane group is stabilizing the enolate ends by forming a cyclic complex (Scheme 23). No mention has been made of a similar stabilizing effect for 2-trimethylsily-loxyethyl methacrylate (Scheme 23b). 

The fact that trimethylsilyl methacrylate is a sluggish monomer under GTP conditions [45, 46] also bodes well for a dissociative mechanism. The excess silyl carboxy groups are silylating enolate chain ends Thus lowering the rate of polymerization and changing the nature of the carboxylate catalyst (Scheme 23c). 

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