Applications to Molecular Recognition

Another example described in Section 9.5.3 reports the synthesis and screening of a synthetic receptor library aimed at transition metal binding. Other similar examples have been reported recently. Burger and Clark Still (211) prepared ionophoric, cyclen-based libraries decorated by amino acid units and screened them for their ability to complex copper and cobalt ions Malin et al. (212) identified novel hexapeptidic technetium-binding sequences from the screening of cellulose-bound libraries and 

Shibata et al. (213) prepared and screened an SP oligopeptide library for its ability to complex cobalt ions, isolating several high-binding sequences. 

Finally, libraries aimed to chiral resolution of racemates will be covered here in particular, the use of chiral stationary phases (CSPs) has recently been reported for the identification of materials to be used for chiral separation of racemates by HPLC. The group of Frechet reported the selection of two macroporous poly methacrylate-supported 4-aryl-1,4-dihydropyrimidines (DHPs) as CSPs for the separation of amino acid, anti-inflammatory drugs, and DHP racemates from an 140-member discrete DHP library (214,215) as well as a deconvolutive approach for the identification of the best selector phase from a 36-member pool library of macroporous polymethacrylate-grafted amino acid anilides (216,217). Welch and co-workers (218,219) reported the selection of the best CSP for the separation of a racemic amino acid amide from a 50-member discrete dipeptide iV-3,5-dinitrobenzoyl amide hbrary and the follow-up, focused 71-member library (220). Wang and Li (221) reported the synthesis and the Circular Dichroism- (CD) based screening of a 16-member library of CSPs for the HPLC resolution of a leucine ester. Welch et al. recentiy reviewed the field of combinatorial libraries for the discovery of novel CSPs (222). Dyer et al. (223) reported an automated synthetic and screening procedure based on Differential Scanning Calorimetry (DSC) for the selection of chiral diastereomeric salts to resolve racemic mixtures by crystallization. Clark Still rejxrrted another example which is discussed in detail in Section 9.5.4. 

2 An Example Ligand and Receptor Libraries Based on Guanidinium Tweezer Receptors 

The C-exposed library L35c was screened for its binding affinity for the guanidinium-based, fluorescent tweezer receptor 9.135 (225), whose structure is reported in Fig. 9.50. The dansylated chains should have assured the fluorescent detection of beads containing ligand tripeptidic sequences, and a series of control experiments ruled out the possibility of significant, nonspecific interaction of the beads with the receptor or with the biological assay constituents. The assay conditions were carefully optimized, and around 7000 beads (seven library equivalents, complete representation of the library individuals) were incubated with 9.135. 

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Fuzzy set theory and fuzzy logic and its application to molecular recognition are explained in Chapter IX, Section 1.5 in the Handbook. 

Classification of macrocyclic compounds containing tetrathiafulvalene moieties, synthetic methods, the latest advances in research on electrochemical properties and applications to molecular recognition and development trends in research on such macrocyclic compounds were outlined and reviewed <2007MI1220>. 

Rein R. On physical properties and interactions of polyatomic molecules with applications to molecular recognition in biology. Adv Quantum Chem 1973 7 335-396. 

N. Gresh, /. Chim. Phys. Phys. Chim. Biol., 94(7-8), 1365-1416 (1997). Inter- and Intramolecular Interactions. Inception and Refinements of the SIBFA, Molecular Mechanics (SMM) Procedure, A Separable, Polarizable Methodology Grounded on Ab Initio SCF/MP2 Computations. Examples of Applications to Molecular Recognition Problems. 

A selection of the most successful CSPs, chiral particles and chiral additive techniques used for analytical and preparative enantioseparation by LC is discussed in the following sections with respect to molecular recognition and experimental application. As additional sources of background information recent books and review articles2-16, which contain numerous relevant references and examine the most important aspects of the field of liquid chromatographic enantioseparation, should be consulted. 

Application of molecular recognition principles allows the design of small molecules able to interact with biological systems for use, e.g. as anticancer drugs. 

Izatt, N.E., Bruening, R.L., Krakowiak, K.E. and Izatt, S.R. (2000) Contributions of Professor Reed M. Izatt to molecular recognition technology from laboratory to commercial application, Ind. Eng. Chem. Res. 39, 3405-3411. 

Toda, F. (1989) Studies of Host-Guest Chemistry. -Fundamentals and Applications of Molecular Recognition and their Development to New Organic Solid State Chemistry-, J. Syn. Org. Chem., Jpn. 47, 1118-1131. 

It is also important to establish that the chemistry of molecular bioprobes is not a sub-discipline of molecular recognition [i.e. host-guest chemistry [4] (Fig. 7.1) in which a guest molecule binds in an artificial receptor site (the host ) which through selective interactions provides the recognition effect] rather, it is an application of molecular recognition. 

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