Dual initiator approach

Table 12.1 Initiators and monomer used in dual initiator approach to block copolymers. CL caprolactone 4MCL 4-methyl caprolactone MMA methyl methacrylate CMA glycidyl methacrylate FOMA perfluorooctyl methacrylate 10-HA 10-hydroxydecanoic acid.

In the second dual photo/thermal initiation strategy, the approach described above is augmented by the inclusion of a thermal initiator. Upon illumination, active centers produced by fragmentation of the photoinitiator start the polymerization reaction. The heat evolved from the exothermic photopolymerization elevates the temperature of the system and results in the production of additional active sites by the thermal initiator. This dual initiating strategy provides both the cure on demand (temporal control) afforded by photopolymerization, and the completeness of cure provided by the thermal initiator. 

Apart from ATRP, the concept of dual initiation was also applied to other (controlled) polymerization techniques. Nitroxide-mediated living free radical polymerization (LFRP) is one example reported by van As et al. and has the advantage that no further metal catalyst is required [43], Employing initiator NMP-1, a PCL macroinitiator was obtained and subsequent polymerization of styrene produced a block copolymer (Scheme 4). With this system, it was for the first time possible to successfully conduct a one-pot chemoenzymatic cascade polymerization from a mixture containing NMP-1, CL, and styrene. Since the activation temperature of NMP is around 100 °C, no radical polymerization will occur at the reaction temperature of the enzymatic ROP. The two reactions could thus be thermally separated by first carrying out the enzymatic polymerization at low temperature and then raising the temperature to around 100 °C to initiate the NMP. Moreover, it was shown that this approach is compatible with the stereoselective polymerization of 4-MeCL for the synthesis of chiral block copolymers. 

Figure 12.4 Dual or bifunctional initiator approach to block copolymers combining an enzymatic with a non-enzymatic chemical polymerization.

The bifunctional initiator approach using reversible addition fragmentation chain-transfer polymerization (RAFT) as the free-radical controlling mechanism was soon to follow and block copolymers of styrene and caprolactone ensued [58]. In this case, a trithiocarbonate species having a terminal primary hydroxyl group provided the dual initiation (Figure 13.3). The resultant polymer was terminated with a trithiocarbonate reduction of the trithiocarbonate to a thiol allows synthesis of a-hydroxyl-co-thiol polymers which are of particular interest in biopolymer applications. 

Transformation of free radical polymerization to cationic polymerization is also possible and has been applied to all controlled radical polymerizations, namely, ATRP, NMP, and RAFT (Table 5). The most representative example of this approach is summarized in Scheme 56. A dual initiator containing active sites for both CROP and ATRP is employed first in ATRP generating a macro initiator for the cationic polymer-ization. In this case, PSt macroinitiator was synthesized via ATRP of St initiated by 2-hydroxylethyl 2 -bromobutyrate and consequently utilized in cationic ring polymerization of 1,3-dioxepane (DOP). The AB-type diblock copolymers (PSt-Z -PDOP) that resulted, with narrow polydispersity, indicated that the polymerizations were controlled. 

Elimination of imreacted monomers can be accomplished by two approaches using dual initiators to enhance conversion of monomers to product (293,294)... 

The dual-mechanism approach of McCaig and co-workers described above was able to describe the oxygen permeability decay in bisphenol. A benzophenone-dicarboxylic acid (BPA-BnzDCA) films of varying thickness remarkably well. This data is illustrated in Figure 35. All films, regardless of thickness, experience an initial sharp decline in permeability. This drop is due to the lattice-contraction mechanism, which is independent of sample dimension. Only in the thin films where the half-thickness i was less than 2.5 /u,m was a contribution from the free-volume diffusion mechanism observed. 

The basic element of SL simulation is its dual-grid approach. The traditional static (Eulerian) grid is used to specify petrophysical properties, well locations and rates, and initial conditions, and to solve for the spatial pressure distributions using an implicit pressure exphcit saturation (IMPES) formulation. The dynamic (Lagrangian) grid represented by the SLs, on the other hand, is used to solve the hyperbohc equations that govern the transport of chemical species. 

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 23 3-25 US Food and Drug Administration (2007) Challenge and opportunity on the critical path to new medical products, http //www.fda.gov/oc/initiatives/ criticalpath/whitepaper/html, Cited 6 February 2007 White JD (2003) A dual wavelength optical fluorescence analyser, WO/2003/ 048744... 

At low 7t, the denominator simplifies to unity in each case and both models are linear in n. For sufficiently high n, the parenthesis in the denominator approaches Ketv, the initial rate for the dual-site model then approaches zero, and that of the single-site model approaches a constant value. Thus the plot of the experimental data will indicate that the dual-site model is preferable if a maximum exists in the data, or that the single-site model is preferable if a horizontal high-pressure asymptote exists. Hence, for the data of Franckaerts and Froment (FI) shown in Fig. 2, the dual-site model is preferred over the single-site model. 

The tightly regulated pathway specifying aromatic amino acid biosynthesis within the plastid compartment implies maintenance of an amino acid pool to mediate regulation. Thus, we have concluded that loss to the cytoplasm of aromatic amino acids synthesized in the chloroplast compartment is unlikely (13). Yet a source of aromatic amino acids is needed in the cytosol to support protein synthesis. Furthermore, since the enzyme systems of the general phenylpropanoid pathway and its specialized branches of secondary metabolism are located in the cytosol (17), aromatic amino acids (especially L-phenylalanine) are also required in the cytosol as initial substrates for secondary metabolism. The simplest possibility would be that a second, complete pathway of aromatic amino acid biosynthesis exists in the cytosol. Ample precedent has been established for duplicate, major biochemical pathways (glycolysis and oxidative pentose phosphate cycle) of higher plants that are separated from one another in the plastid and cytosolic compartments (18). Evidence to support the hypothesis for a cytosolic pathway (1,13) and the various approaches underway to prove or disprove the dual-pathway hypothesis are summarized in this paper. 

With a supply route estabhshed (route 2) and supplies of radafaxine available to fund the initial development activities, focus switched to discovering a more efficient synthesis. Environmental considerations were a key consideration, and a dual program of work was initiated to address these concerns. One approach was to investigate the feasibihty of identifying a Dynamic Resolution to avoid the losses associated with the undesired (R,R)-enantiomer, discussed above, while, in parallel, the viability of employing continuous chromatography to separate the enantiomers was examined. 

---