Lactides structures

FIGURE 11.7 Possible lactide structures. The dark color represents an 1-lactic acid residue. The light color represents a d-Iactic acid residue. 

Kulinski, Z. and Piorkowska, E. 2005. Crystallization, structure and properties of plasticized poly(L-lactide). Polymer 46 10290-10300. 

Pego AP, Siebum SB, Luyn MJAV, et al. Preparation of degradable porous structures based on 1,3-trimethylene carbonate and D,L-lactide(co)polymers for heart tissue engineering. Tissue Eng, 2003, 9, 981 994. 

Rate of hydration of the polymeric materials has been shown to be an important consideration in regard to drug release. Gilding and Reed (24) demonstrated that water uptake increases as the glycolide ratio in the copolymer increases. The extent of block or random structure in the copolymer can also affect the rate of hydration and the rate of degradation (25). Careful control of the polymerization conditions is required in order to afford reproducible drug release behavior in a finished product. Kissel (26) showed drastic differences in water uptake between various homopolymers and copolymers of caprolactone, lactide, and glycolide. 

Occasionally in the synthesis of the copolymers, insoluble material is produced. This results from polymer containing blocks of polyglycolide rather than the desired random structure. Obviously, such compositions would have considerable effect on the performance of controlled release formulations utilizing those polymers. This problem is particularly evident when one is seeking to utilize the 50 50 glycolide/lactide copolymer as a biodegradable excipient. However, with carefully controlled polymerization conditions, useful 50 50 polymer is readily produced. 

Classical or conventional pharmaceutical agents in combination with lactide/glycolide polymers have been widely studied since about 1973. In general, these compounds are bioactive agents usually produced by synthetic chemistry, with molecular weights of less than a few hundred and relatively stable structures. Examples include steroid hormones, antibiotics, narcotic antagonists, anticancer agents, and anesthetics. 

The process proceeds through the reaction of pairs of functional groups which combine to yield the urethane interunit linkage. From the standpoint of both the mechanism and the structure type produced, inclusion of this example with the condensation class clearly is desirable. Later in this chapter other examples will be cited of polymers formed by processes which must be regarded as addition polymerizations, but which possess within the polymer chain recurrent functional groups susceptible to hydrolysis. This situation arises most frequently where a cyclic compound consisting of one or more structural units may be converted to a polymer which is nominally identical with one obtained by intermolecular condensation of a bifunctional monomer e.g., lactide may be converted to a linear polymer... 

Even more complex structures have been described. For example, chirality of blocks may lead to other morphologies. A polystyrene-fc-poly-(L-lactide) diblock copolymer, PS-fr-PLLA, constituting both achiral and chiral blocks was reported to form an array of hexagonally packed PLLA nanohelices with a left-handed helical sense in the bulk state (Fig. 3). The structure was found... 

For applications in ring-opening catalysis of chiral lactides, pyrazolylborates have been suitably modified to yield chiral zinc complexes. An example of such a chiral pre-catalyst is the highly sterically encumbered tris(indazolyl)bo-rate methylzinc complex 107, introduced by Chisholm et al., whose C -symmetric structure is shown in Figure 53.165... 

So far, many studies have focused on the development and application of aliphatic polyesters such as PLA [1-3], PGA [41,42], and PCL [43,44], Figure 2 shows the structures of their monomers lactides (LAs), glycolide (GA), e-caprolactone (CL), and some typical comonomers. 

Our Form II has two uncommon features. In the first place it contains two hydroxyl groups attached to the same carbon but we have that in chloral hydrate. In the second place there is an ethylene oxide oxygen linkage. This might be called an alpha lactone with the water not split off. This formation of a ring structure is believed to account for the reversal of the sign of rotation. It is well known that the formation of the lactide from lactic acid, while not a lactone formation in the same... 

Meanwhile Ethicon (and others) developed alternative absorbable surgical sutures, based, for example, on copolymers of polyglycolide with poly-L-lactide or poly(trimethylene carbonate), and on polydioxanone, and on poly(e-oxycaproate), and also on copolymers of these with polyglycolide or with each other. These different structures made it possible to provide fibres with different rates of absorption, with different degrees of stiffness or flexibility, and for use in monofilaments, braided multifilaments, and other yam structures, as required for different surgical operations. 

H. Tsuji, Y. Kawashima, H. Takikawa, S. Tanaka, Poly(L-lactide)/nano-structured carbon composites Conductivity, thermal properties, crystallization, and biodegradation., Polymer, vol. 48, pp. 4213-4225, 2007. 

Structurally very close to the N,N,O-tridentate ketiminate systems, magnesium complexes bearing bis-amido-oxazolinate complexes 44a-e were used in the PLA preparation from L-lactide in the presence of benzyl alcohol. The low reactivity of 44d, e is due to the presence of a pendant functionality engaging the metal center, and the steric bulk of the phenyl group hindering the coordination of benzyl alcohol or of a monomer to the metal center, contributing to a diminution of the propagation [69]. 

Hybrid scorpionate/cyclopentadienyl-Mg (63) and -Zn (64,65) complexes were structurally characterized and reported to catalyze the formation of PLAs with medium molecular weights and narrow polydispersities [85]. Among them, the magnesium complex 63 is much more active than the others, giving a polymerization of L-lactide in toluene at 90 °C with 97% conversion in 2.5 h. However, it takes 30 h for zinc complexes 64 and 65 to reach similar results under the same conditions. Some representative structures of magnesium and zinc complexes are summarized in Table 2 as they display closely related ROP activity of lactide, and often stmcrnrally similar ligand systems are employed to construct these initiators. 

It has been found that magnesium complexes supported with bidentate p-diketiminate are more active in the ROP of l- and rac-lactide than their structurally analogous zinc complexes. Faster rate of polymerization of magnesium complexes were such that an almost complete conversion (97%) occurred in 1 min at 20 °C for a p-diketiminate magnesium complex [(BDI-l)Mg(0 Pr)]2 31 (O Pr = isopropoxide) whereas the zinc analog needed 33 min for a similar conversion at the same temperature [64] (Table 3, entry 1). Similarly a higher... 

In a more recent report, a novel dinuclear N,N,0-donor Schiff base-calcium complex [(DAIP)2Ca]2 where DAIP = 2-[2(-dimethylamino-ethylimino)methyl] phenol 76 (Fig. 12) was shown to initiate ROP of L-lactide in a controlled fashion in the presence of benzyl alcohol giving a 96% conversion within 30-60 min at room temperature, yielding polymers with high molecular weight and low PDIs [89]. Taking into account the dimeric molecular structures of hexa- and hepta-coordinated Ca" in the solid state and the kinetic results gained from this study (first order dependency on [LA] a first order dependency on [BnOH] with d[LA]/ df = prop[LA] [BnOH] and a p op constant of 1.95 s ), a coordinatio-... 

More recently reported was a bridged bis(amidinate)-isopropoxy ytterbium complex 85 (Fig. 14), which displayed excellent polymerization activity in conjunction with a good control of the polymerization of L-lactide with a linear increases of polymer molecular weights (M ) with [M]o/[I]o [103]. It was also evidenced that 85 was even more active in the polymerization of lactide than its structural analog with bridging phenoxide group, as an isopropoxide is intrinsically more nucleophilic than a phenoxide. 

The selective S3mthesis of tri- and dichlorotitanium complexes 140-142 bearing chiral tridentate Schiff base ligands derived from (lf ,25)-( )-l-aminoindanol (Fig. 20) has been recently reported. X-ray structural studies of these complexes revealed a mononuclear feature with an octahedral coordination sphere at the metal center, and a meridional occupation of the Schiff base. Surprisingly, though these complexes lack the typical ROP-initiating units such as aUcoxides or amides, they are effective catalysts for the controlled ROP of L-lactide, as evidenced by the linearity of the molecular weight versus [l-LA] [Ti] ratio as well as the narrow PDIs (1.17-1.33) [127]. 

Spassky and coworkers discovered a remarkable stereocontrol of an enantiomerically pure A1 complex (7 )-161a for the ROP of rac-lactide resulting in a tapered stereoblock PLA microstructure with high melting point =187 °C) (Fig. 26) [160]. Structurally analogous, racemic salen-Al complex 162 resulted in highly isotactic PLA [161]. Feijen s enantiopure chiral complex (RJ )-163 (Fig. 26) exhibited an excellent reverse stereocontrol by preferential polymerization of L-lactide over D-lactide monomer (Kss/Krr = 14) that resulted in PLA with... 

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