Complex Molecular Architectures

Hyperbranched molecules can be prepared using condensation polymerization methods and ABj-type molecules typified by the hydroxydiacids. However, a self-condensing nnimolecular initiator, such as 

Use of a multifimctional core, e.g., (9) has been used to prepare star-shaped molecules by applying a RAFT process with styrene and acrylate monomers. 

FIGURE 5.5 Schematic representation of the growth of the poly(r-butyl acrylate) star by the arm-first approach. (From Matyjaszewski, K., Polym. Int., 52, 1559, 2003. With permission 

This approach involves growth of the side arms outward from the core molecule, but an alternative is to prepare monofunctional living chains that are then coupled with a multifunctional core molecule. Other core molecules can be used that are modified inorganic structures, such as cyclotetrasiloxanes (10) and cyclotriphos-phazenes. These can be used as the initiating core for ATR polymerization of styrene or acrylate chains to form four- or six-armed star molecules. 

Multiarm polymers (11) can be prepared that still have the reactive functional groups (Z) close to the core. As these are still active, they can be used as sites to initiate the growth of more arms by adding either the same monomer used to prepare (11) or a second monomer to prodnce mikto-arm star polymers, in which the arms have different chemical structures. Thus, an active ended poly(t-butyl acrylate), prepared by ATRP, can be coupled with divinyl benzene to form a multiann star polymer. This structure can be converted to a mikto-arm star polymer by reacting the living ends still present with n-butyl acrylate, and so propagate poly(n-butyl acrylate) chains from the core outward. 

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Baxter, P. N. W. Metalion directed assembly of complex molecular architectures and nanostructures. In Comprehensive Supramolecular Chemistry Sauvage, J.-P. Hosseini M. W., Eds. Pergamon Oxford, UK, 1996 Vol. 9, pp 165-211. 

The increasing current interest in processes that are able to generate complex molecular architectures in one pot has stimulated the development of domino-like procedures that create three bonds in one synthetic operation, with considerable advantages in terms of synthetic efficiency and environmental friendliness. This section describes some examples of the application of these concepts to the preparation of quinolizidine compounds. 

The utility of these N-H addition reactions for the construction of complex molecular architectures was nicely illustrated in the behavior of 46 towards... 

Many other oligomeric enzymes and other complex assemblies of more than one kind of protein subunit are known. For example, the 2-oxoacid dehydrogenases are huge 2000- to 4000-kDa complexes containing three different proteins with different enzymatic activities in a cubic array (Fig. 15-14). The filaments of striated muscle (Chapter 19), antibodies and complement of blood (Chapter 31), and the tailed bacteriophages (Box 7-C ) all have complex molecular architectures. 

However, functional groups, other than a trimethylsilyl group, were not used and complex molecular architectures were not addressed. The regioselectivity for many terminal alkynes is only moderate (R1 = Ph, R2 = H 44 45 = 65 35), whereas the regioselectivity for trimethylsilylacetylene is excellent (R1 = SiMe3, R2 = H 44 45 = 5 95). 

Catalytic formation of carbon-carbon bonds is a powerful tool for construction of complex molecular architectures, and has been developed extensively for applications in organic synthesis. Three main classes of carbon-carbon bond forming reactions have been studied in sc C02 carbonylation (with particular attention paid to the hydroformylation of a-olefins), palladium-catalyzed coupling reactions involving aromatic halides, and olefin metathesis. 

Modern concepts in polymer chemistry are based on complex molecular architectures. In this way, some new functions such as self-organisation, adaptability and self-healing can be realised in synthetic materials of different dimensions and complexity. Colloidal polymer networks (nano- or microgels) are unique 3-D polymer structures with tuneable properties and enormous application potential. 

After Buchi confirmed this finding in the 19S0s, numerous other investigators immediately recognized the rapidity with which complex molecular architectures could be constructed by this reaction. Cookson irradiated the Diels-Alder adduct (3) of cyclopentadiene and benzoquinone to produce the caged diketone (4) (equation 2) while Eaton utilized a photochemical cycloaddition of diene (5) in a synthesis of the platonic solid cubane (6) (equation 3). ... 

The complex molecular architecture of proteins and enzymes leads to more subtle aggregation properties than those of synthetic copolymers. In particular, the chirality of these biological molecules offers an extra degree of freedom to the self-assembly process. This is discussed in more detail in the next section for now we neglect the effect of chirality. 

Apart from the significant clinical potential of 1 and its restricted natural supply, the attraction of laulimalide (1) as a synthetic target originates from its unique and complex molecular architecture. Specifically, its 16,17-epoxide is liable to nucleophilic attack from the 20-hydroxy group to form the more stable but biologically less active tetrahydrofuran isomer 2, and the 2,3-c/5-enoate moiety readily undergoes /Z-isomerization. To date, in addition to an impressive number of 15 approaches to key fragments, as many as ten total syntheses of 1 have been completed. 

Earner, L. Barner-Kowollik, C. Davis, T.P. Stenzel, M.H. Complex molecular architecture polymers via RAFT. Aust. J. Chem. 2004,57 (1), 19-24. 

One of the most fascinating products containing multiple components is a combination of the natural product reserpine, hydralazine hydrochloride, and hydrochlorothiazide. This drug product is available in tablet form and contains 0.1 mg of reserpine USP, 25 mg of hydralazine hydrochloride, and 15 mg of hydrochlorothiazide (Fig. 6). Reserpine is an indole alkaloid derived from the dried root of Rauwolfia serpentina and is well known for its complex molecular architecture, the challenges faced during its total synthesis, and its profound effect on the central nervous system as an antihypertensive. Hydralazine is also an antihypertensive and hydrochlorothiazide has diuretic properties. The combination of these three very different molecular structures brings diversity to the analytical testing required. 

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