Template self-association complexes

Fig. 3.2. A schematic representation of the molecular imprinting pre-arrangement phase (corresponding to 2 in Fig. 3.1), here using ()-nicotine as the template and carboxylic acid containing functional monomers. In this case a total of five states of complexation are proposed I, non-complexed template II, weak single point interaction III, strong single point interaction IV, combination of weak and strong interactions V, higher order complexes e.g. monomer interactions with template-template self-association complexes, higher monomer solvation levels.

A similar approach has been adopted by Whitcombe et al. [15], where NMR chemical shift studies allowed the calculation of dissociation constants and a potential means for predicting the binding capacities of MIPs. The NMR characterization of functional monomer-template interactions has also been applied to the study of the interaction of 2,6-bis(acrylamido) pyridine and barbiturates [16], and of 2-aminopyridine and methacrylic acid [17]. Recent NMR work in our laboratory [18] has involved the determination of template-monomer interactions for a nicotine-methacrylic acid system. Significantly, it was shown in this study that template self-association complexes are present in the prepolymerization mixture and that the extent template self-association is dependent both upon solvent and the presence of monomer. 

In biological recognition phenomena, protein-protein interactions are of primary importance. In an attempt to mimic these processes, LaBrenz and Kelly [51] synthesized the peptidic host 64. In this receptor, the dibenzofuran template separates the two peptide units by roughly 10 A and allows for the complexation of a guest peptide (65), as depicted in Fig. 21. The complex first forms a three-stranded, antiparallel /J-sheet that is stabilized by hydrogen bonds, electrostatic interactions, and aromatic-aromatic interactions between the dibenzofuran and the benzamide moieties. This complex can further self associate to form more complex structures. This example shows that structurally defined peptide nanostructures can interfere with biological recognition processes and potentially have therapeutic applications. 

The template polymerization of MAOT in the presence of stereoregular poly-MAOA was never accelerated. A strong tendency to cause self-association of adenine bases observed along the polyMAOA chain32) as well as in poly-VAd17,24) appears to inhibit the complex formation between a growing chain and polyMAOA and may result in a depression of the template effect of the polymerization. 

The actual mechanism of self-association of monomeric protein into amyloid is complex and three mechanisms of stmcture conversion have been proposed (32) In templated assembly, a monomeric native state peptide binds to an existing nucleus. Upon binding, there is a change in the secondary stmcture of the monomer as it is added to the growing chain. Monomer directed conversion involves the presence of a misfolded monomer that templates the stmcture conversion of a native monomer, followed by disassociation and chain formation. The third model is nucleated polymerization, which is the most widely accepted model for the fibril growth. 

A primary indication on how well the monomers have been chosen is to simply see whether they are capable of assisting solubilization of the template in the prepolymerization mixture. A small-scale solubility test may thus be a good way to initially screen the monomers for strong monomer-template interactions. Weak interactions may be revealed by complexation induced spectral changes (in NMR,UVor fluorescence spectra). The complexation induced shifts of the characteristic H-NMR signals of the template upon increasing monomer concentrations are often used to estimate the monomer-template association constants. Prior to this, however, knowledge about the stoichiometry of the monomer-template complexation and the tendency of the monomer and template to self-associate are required.The former can be obtained by means of a so-called Job s plot whereas the latter by a dilution experiment. 

Receptor 15 has been designed for the complexation of barbiturates [ref 17]. The syndiesis was accomplished by Ba -templated macrocyclization of the appropiate dialdehyde and cis-l,2-cyclohexanediamine, followed by reaction with uranyl acetate. NMR experiments in CDCI3 revealed that intramolecular self-complexation takes place and a constant Kg if-ass for this process of IS has been estimated. The association constants of three barbiturates could be determined by NMR titrations in a mixture of CDC13 and DMSO-dg (95 5). The association constants of dimethyl, diethyl, and ethylphenyl barbituric acid are 112, 97, and 45 Imol respectively. It is obvious that a sterically more demanding barbiturate results in a lower association constant. The host 15 is able to transport barbituric... 

As seen in the previous example, DNA-like structures are attractive Unear arrays in which self-assembly can be tuned and associated with the use of metal coordination complexes. A subtle use of coordination metal complexes to tune DNA was reported in which a transition metal complex [Ru(bipy)3] + served as a template for the formation of various architectures, especially wires formed of DNA ladders (Figure 18). ... 

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