Proliferous polymerization

Proliferous Polymerization. Eady attempts to polymerize VP anionicaHy resulted in proliferous or "popcorn" polymerization (48). This was found to be a special form of free-radical addition polymerization, and not an example of anionic polymerization, as originally thought. VP contains a relatively acidic proton alpha to the pyrroHdinone carbonyl. In the presence of strong base such as sodium hydroxide, VP forms cross-linkers in situ probably by the following mechanism ... 

If chain transfer of the radical center to a previously formed polymer molecule is followed ultimately by termination through coupling with another similarly transferred center, the net result of these two processes is the combination of a pair of previously independent polymer molecules. T. G. Fox (private communication of results as yet unpublished) has suggested this mechanism as one which may give rise to network structures in the polymerization of monovinyl compounds. His preliminary analysis of kinetic data indicates that proliferous polymerization of methyl acrylate may be triggered by networks thus generated. 

A composition of vinyl acetate, ethylene dimethacrylate, benzil (a UV sensitizer), and finely ground vinyl acetate-ethylene dimethacrylate popcorn copolymer on exposure to radiation at 365 mn gave rise to a proliferating polymerization which continued after the source of radiation had been turned off. It has been postulated that in this case most of the growing radicals are formed by chain scission during polymerization [182]. 

Briefly summarized, the observations of Breitenbach and Kauffmann [2] are these. In a polymerization system, such as that of acrylic acid, which is characterized by the formation of a polymer that is insoluble in its pure monomer, if the monomer cannot penetrate the polymer coil, no proliferating polymerization is possible. If, however, a solvent for the polymer, e.g, water, is present, there are concentration ranges in which the monomer can penetrate the polymer coil, and popcorn polymers form. Under the experimental conditions [polymerization of acrylic acid containing 35 X 10" moles of 2,2 -azobis(isobutyronitrile) per mole of acrylic acid at 40°C along with some water], compositions containing 96.6wt. o or more of acrylic acid exhibit no tendency to popcorn polymer formation. Systems containing between approximately 86 /o and 96<7o of acrylic acid proliferate only after polymerization times of 15-50 hr. At concentrations of 50-80% of acrylic acid, popcorn polymers form very rapidly (1.5-4 hr). At about 35% of acrylic acid the appearance of popcorn polymers occurs only after approximately 17 hr of polymerization. Unfortunately the behavior of 25-30% solutions of acrylic acid in water was not reported upon. This happens to be the concentration range usually recommended for practical polymer solution preparation. 

Although the compounds were isolated in quantities of only a few milligrams per kilogram of cmde plant leaves, extensive work on a variety of animal tumor systems led to eventual clinical use of these bases, first alone and later in conjunction with other materials, in the treatment of Hodgkin s disease and acute lymphoblastic leukemia. Their main effect appears to be binding tightly to tubuHn, the basic component of microtubules found in eukaryotic cells, thus interfering with its polymerization and hence the formation of microtubules required for tumor proliferation (82). 

Antipyrimidine antimetabolite inhibits DNA polymerase with inhibition of DNA strand elongation and replication activated in tumor cells in triphosphate form competes with conversion of cytidine to deoxycytidine nucleotides, further blocking polymerization of DNA leads to production of short DNS strands cell-cycle specific (S phase) acts only on proliferating cells. 

Microtubules have a key role in mitosis and cell-proliferation. They are dynamic assemblies of heterodimers of a and f3 tubullin. In the cell-reproduction cascade tubulin polymerizes fast and subsequently depolymerizes. Tubulin dimers are unusual guanyl nucleotide binding (G) proteins, which bind GTP reversibly at a site in the (3-tubulin. GTP irreversibly hydrolyzes to GDP during polymerization. 

Studies on the cationic polymerization of cyclic ethers, cyclic formals, lactones and other heterocyclic compounds have proliferated so greatly in the last few years that a detailed review of the evidence concerning participation of oxonium and analogous ions in these reactions cannot be given here. Suffice it to say that there is firm evidence for a few, and circumstantial evidence for many such systems, that the reactive species are indeed ions and there appears to be no evidence to the contrary. A few systems will be discussed in sub-sections 3.2 and 4.4. 

Vinblastine, vincristine, and structurally related analogs inhibit microtubule polymerization by 50% at concentrations in the range 0.1-1 xM, and the process of tubulin addition to preformed microtubules, at steady state, is comparably sensitive to inhibition by these agents (5). As shown in Table I, the differences in values for inhibition of steady-state tubulin addition by vinblastine, vincristine, vindesine, and vinepidine were relatively small, but the pattern of activity in the tubulin addition system did not parallel that observed when the compounds were evaluated for effects on the proliferation of B16 melanoma cells in vitro. Vinepidine was more than twice as potent as vinblastine as an inhibitor of steady-state tubulin addition but nearly 10-fold less potent than vinblastine as an inhibitor of cell growth (i). 

A two-dimensional micropatterned tissue can be easily obtained by utihz-ing the inherent differences in cell adhesiveness between different micropatterned photografted regions. This was attained by photoiniferter graft polymerization with a projection mask placed on an iniferter-derivatized surface. Since protein adsorption and cell adhesion are markedly suppressed on nonionic graft polymers, such as polyDMAm, any anchorage-dependent cells such as endothelial cell adhere and proliferate only on nonirradiated surfaces, resulting in the formation of a two-dimensional patterned tissue or cellular sheet (Fig. 24). 

The MTT assay was initially developed as a quantitative assay for cell survival and proliferation, not as an in vitro assay for chemosensitivity testing. Further study was required to ascertain if the method accurately predicted the in vivo antitumor activities of anticancer agents. Shimoyama et al. [189] studied the predictability of the MTT assay with respect to a clonogenic assay (Sect. 4.1.1.3.) and showed excellent reproducibility and a close correlation to the in vivo predictability rate of the clonogenic assay. Another study [190] also showed that the MTT assay closely approximated (90%) the clinical activity of anticancer agents. Many authors have since utilized the MTT assay to determine the efficacy of polymeric anticancer drug conjugates. 

---