Non-covalent template

It was not only for the basic scientific knowledge but also for the new challenges in the synthesis and the beauty of the final structures that nearly half a century ago, chemists started to investigate intertwined macrocyclic supramolecules such as rotaxanes and catenanes [4], Earlier, when the syntheses of such structures were at their infancy, the routes to such systems were troublesome. The statistical methods [5] proved to be low-yield processes. Multistep procedures [6] involving a covalent junction which is formed between two parts that are needed to stay together until the structure is complete were not convenient as well. The use of non-covalent templates thus provided a more straightforward and high-yield approach to the problem. 

Conventionally, MlPs are obtained by bulk co-polymerization from a mixture consisting of a functional monomer, cross-linker, chiral template, and a porogenic solvent mixture. Nowadays, imprinting via non-covalent template binding is preferred over the covalent mode and involves three major steps (see Fig. 9.9). (i) Functional monomers (e.g. methacrylic acid, MAA) and a cross-linker (e.g. ethyleneglycol dimethacrylate, EDMA) assemble around the enantiomeric print molecule, e.g. (S)-phenylalanine anilide (1), driven by non-covalent intermolecular interactions, e.g. ionic interactions, hydrogen bonding, dipole-dipole interaction. Tr-rt-interaction. (ii) By thermally or photochemi-... 

Woolfson and Mahmoud have classified the routes to preparation of decorated self-assembling peptide materials [53] as (1) co-assembly, where the functional part is already attached to a self-assembling component prior to assembly, and (2) postassembly, where a non-functionahsed self-assembled structure is modified by covalent or non-covalent means. This discussion adheres to this classification. A third route, beyond the scope of this review, is the use of structured peptides as templates for inorganic materials. Section 4.1 discusses functionalised self-assemblies formed from co-assembly-type approaches, while post-assembly modifications of self-assembled structures are considered in Sect. 4.2. 

The most convenient way of categorizing the classes of cathepsin inhibitors is based on the nature of the electrophilic warhead that interacts with the sulfhydryl group of the active site cysteine residue. Since a large portion of the binding energy of a cysteine protease inhibitor comes from the covalent interaction with this thiol, the properties of the resulting molecules are largely derived from the electrophile. In broad terms, these inhibitors can be broken down into ketone and nitrile-based reversible covalent inhibitors, or the more recent non-covalent inhibitors based on an aminoaniline template. 

Vogtle has developed this approach further and employed a series of anionic templates to prepare rotaxanes (instead of the neutral template in the above reaction) [65-67]. In this approach a phenolate, thiophenolate or sulfonamide anion is non-covalently bound to the tetralactam macrocycle (46) forming a host-guest complex via hydrogen bonding (see Scheme 21). 

Few examples of covalent and non-covalent DCLs have been reported over the past few years, with only a small number of them making use of hydrogen-bonding templates. One of such examples is the barbiturate receptor 73 reported by... 

Fig. 1. Concept of molecular imprinting - the non-covalent approach. 1. Self-assembly of template with functional monomers. 2. Polymerization in the presence of a cross-linker. 3. Extraction of the template from the imprinted polymer network. 4. Selective recognition of the template molecule...

Two different techniques have been developed for MIP production, namely the covalent and the non-covalent approaches. The covalent way is based on the chemical derivatization of the template with molecules containing polymerizable groups using reversible covalent bonds. Different chemical reactions can be ap-... 

Commonly, new non-covalent MIPs are designed using a generic approach where the functional groups on the binding monomers are chosen according to their complementarity with the chemical groups of the template. In order to... 

Most MIPs show a heterogeneous distribution of binding sites and can be considered as polyclonal in their nature. In non-covalent imprinting, the amorphous material contains binding sites which are not identical because they may have different cross-linking density or accessibility. Moreover, the monomer (M) and the template molecule (A) may form complexes of different stoichiometry (MnA) in the pre-polymerization mixture [5]... 

In theory, the use of stoichiometric non-covalent or covalent imprinting yields a homogeneous binding site population ( monoclonality ) after template removal from the material [24]. 

Generally, two different procedures have been adopted for preparation of MIPs. They involve either covalent or non-covalent complex formation of a template and complementary monomers with apt functional groups. [19]. Co-polymerization of this complex with a cross-linking monomer in a porogenic solvent solution, followed by removal of the template, results in formation of the porous polymer material with recognition sites complementary in size and shape to molecules of the target compound that can next be determined as an analyte. 

Both of these MIP preparation procedures have their advantages and limitations [20, 21]. For instance, the size of the analyte molecule is not a discriminating criterion in covalent imprinting since the template selectively determines the interaction sites. In contrast, non-covalent imprinting has the advantage of being simpler since an additional synthetic step is not required to introduce the template into the polymer matrix. Moreover, removal of the template via extraction with the suitable solvent solution is simple and mostly complete for the non-covalent imprinting. 

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